Laureate Professor Rodney Scott

Laureate Professor Rodney Scott

Laureate Professor

School of Biomedical Sciences and Pharmacy (Medical Genetics)

Mining your genes

Geneticist Professor Rodney Scott and computer scientist Professor Pablo Moscato come from disparate academic backgrounds, but they share a common purpose. The leading researchers are blending their respective knowledge with the aim of making personalised medicine a reality.

Scott and Moscato are co-directors of the University of Newcastle's forward-thinking Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine. As one of only two research sites  in Australia that directly link bioinformatics with clinical research practice, it is at the forefront of the emerging field of developing patient-tailored treatments based on genetic analysis.

Both researchers bring considerable expertise to the collaboration. Scott has been working in the field of hereditary diseases for 20 years, and has attracted global recognition for his genetic research, particularly in the areas of breast and bowel cancers.

Moscato began his influential work in computer science in the late 1980s as a member of the Caltech parallel computing group – supercomputing pioneers based at the California Institute of Technology. While there, he developed in collaboration with another researcher a computer optimisation strategy known as a memetic algorithm, now widely used in computation-based applications in many areas of Science and Technology.

What has drawn them together is the need for more efficient ways of processing and appropriately interpret the mass of genetic research data being collected by medical researchers. Working alongside this is the tantalising prospect of being able to use computer profiling technology to customise treatments for individual patients.

"Since I have been working in genetics there has been an explosion of knowledge and huge advances in the technology that can be used to identify risk factors associated with disease," Scott says.

"Technology allows us to acquire a huge amount of data but a bottleneck is created by the analysis, because there is physically so much data to sift through.

"Bioinformatics is providing a mechanism whereby we can reduce the complexity of research data, manage it and interpret it."

Scott and Moscato first collaborated in 2006 when Moscato applied his statistical and computational skills to analysing data associated with the rare genetic disorder xeroderma pigmentosum, a trigger for childhood skin cancer. Scott was impressed with the results and the University, recognising the potential for this valuable interdisciplinary research, approved the investigators' request to set up the centre.

University medical and bioinformatics researchers have since successfully worked together on the interpretation of genetic data relating not only to cancer but a range of conditions including stroke, multiple sclerosis, macular degeneration, Alzheimer's Disease and lung disease.

"When I came to the University in 2002 there was a lot of strength on the clinical side of medical research but not a lot of work underway in bioinformatics," Moscato says.

"I established the Newcastle Bioinformatics Initiative with the support of the university in 2002. On my lead, and with ARC support, Newcastle has been the only NSW node of the ARC Centre of Excellence in Bioinformatics since 2003.

"Now, in some areas, particularly in supercomputing based approaches to interrogate these datasets, we are clearly leading this research field in Australia."

Moscato is pushing the boundaries of molecular interrogation techniques, looking for ways to provide more sophisticated information, including a forensic analysis of data that seeks to explain, rather than dismiss, even minor statistical anomalies. He has developed a method based on Information Theory to track the progession of cancer and Alzheimer's Disease in the brain.

"It is a unifying theory, the Entropic Hallmark," he says.

"A medical researcher can come to us with data that contains a number of variables and our methods are able to highlight the possibilities," he says. "We seek to open new working hypotheses, rather than just give a straightforward reading of the data."

For example, detailed analysis of data over a number of years by his team has led to the identification of what they believe to be the 'genetic signature' of two new subtypes of breast cancer.  If validated, the research could lead to new approaches to treatment.

The "final quest", Moscato says, is personalising medicine.

"With cancer, for instance, we are moving away from the approach that there is a silver bullet cure," he says.

"There are thousands of drugs that can be used to treat cancers. That presents a huge number of possible combinations for treatment. Only with sophisticated computer analysis can you screen all of the combinations according to a patient's specific gene characteristics."

Scott picks up the theme: "What we are aiming to achieve is user-friendly programs that can be applied at the clinical level; programs that will efficiently and effectively analyse the data and deliver meaningful information describing a person's risk factors and suggesting optimal treatment."

Professor Rodney Scott and Professor Pablo Moscato research in collaboration with the Hunter Medical Research Institute's (HMRI) Information Based Medicine Program. HMRI is a partnership between the University, Hunter New England Local Health District and the community.

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Rodney Scott

Mining your genes

A successful collaboration between Professor Rodney Scott and Pablo Moscato is using medical science and computer analysis to unlock the mysteries of cancer and other diseases.

Read more

Career Summary

Biography

Inherited forms of cancer have been my main interest for around 20 years. The research I have been involved first focused on the identification of genes associated with with inherited forms of colorectal cancer and breast cancer.

The research area proved to be extremely successful as it really set the scene for our current understanding of the genetic basis of malignancy. Since the identification of genetic susceptibilities my research interests have focused on better defining these inherited entities such that more appropriate intervention strategies can be developed. Initially, much emphasis was placed on recognising genotype/phenotype correlations with disease and as such the research I have undertaken has done much to define such relationships.

More recently, the role of modifier genes in disease penetrance has been a major thematic area and data forthcoming from these studies indicates that there are additional disease susceptibilities that are important in assessing individual risk on a genetic background of high risk. This research is now beginning to be translated to the general population as it represents the first tentative move towards determining cancer risk in the general population. With increasing emphasis on disease prevention it is to be expected that this research will continue to flourish.

My research career took off in Switzerland where I consolidated a centre dedicated to the study of inherited predispositions to cancer. During this period of my research career I was heavily involved in the identification of genetic predispositions to breast cancer and bowel cancer and through my activities supervised 4 PhD students who have since had excellent careers in medical research. The research that I am focused on is consistent with two of Australia's national priorities, healthy aging and a healthy start to life.

Research Expertise
Expertise in the genetic basis of disease especially in relation to the development of malignancy.

Teaching Expertise
Expertise in the teaching of medical genetics.

Administrative Expertise
I have been on numerous State and National committees that are involved in ensuring the delivery of genetic services to the public. I have also served on ethics committees and a variety of other administrative committees.

Collaborations
The genetics of bowel cancer, Genetic variation and its relationship to disease, The genetics of breast cancer.


Qualifications

  • Privat Dozent - German equivalent to DSc, University of Basel
  • Bachelor of Science (Honours), University of Western Australia
  • PhD, University of Western Australia

Keywords

  • human
  • Medical
  • Genetics
  • evolution
  • DNA Repair
  • DNA repair
  • Molecular
  • homeostasis
  • Developmental
  • breast cancer
  • family studies
  • modifier genes
  • Cancer Genetics
  • Colorectal cancer
  • genetic epidemiology
  • Gene environment interaction

Languages

  • German (Fluent)

Fields of Research

Code Description Percentage
110399 Clinical Sciences not elsewhere classified 20
111299 Oncology and Carcinogenesis not elsewhere classified 40
060499 Genetics not elsewhere classified 40

Professional Experience

Academic appointment

Dates Title Organisation / Department
1/06/2005 -  Scientific Advisor Cancer Institute NSW
1/06/2005 -  Member gene technology technical advisory committee Gene Technology Regulator, Federal Government
Australia
1/01/2003 -  Chair of the Board of Censors for Molecular Genetics Human Genetics Society of Australasia (HGSA)
Australia
1/01/2002 -  Founding Member International Hereditary Cancer Center
Poland
1/01/2002 - 1/12/2003 Member of the Working Group on Human Gene Patents Australian Health Ministers' Advisory Council (AHMAC)
Australia
1/04/2000 -  Visiting Professor of Cancer Genetics Pomeranian Academy of Medicine
Department of Pathology and Genetics
Poland
1/01/1990 - 1/07/1997 Research Group Leader University Clinics Basel
Department of Research and Teaching
Switzerland

Membership

Dates Title Organisation / Department
Member - Royal College of Pathologists of Australasia Royal College of Pathologists of Australasia
Member of the Management Committee Ramaciotti Centre for Gene Function Analysis
Australia
Secretary - NSWOG (Familial Cancer) Cancer Institute of NSW NSWOG (Familial Cancer) Cancer Institute of NSW
Australia
Member of the DNA Working Party NSW Department of Health
Editor-in-Chief Hereditary Cancer in Clinical Practice
Australia
Member - International Network for Cancer Treatment and Research (INCTR) International Network for Cancer Treatment and Research (INCTR)
Australia
Member of the Genetic Services Advisory Committee NSW Department of Health
Examiner - Royal College of Pathologists of Australasia Royal College of Pathologists of Australasia

Professional appointment

Dates Title Organisation / Department
1/08/1997 -  Director of Genetics Hunter Area Pathology Service
Health
Australia

Awards

Honours

Year Award
2017 Fellow
Royal Society of New South Wales

Professional

Year Award
2011 Fellow of the Faculty of Science
Royal College of Pathologists of Australasia
2005 FRCPath
Royal College of Pathologists, London

Recipient

Year Award
2017 Honorary PhD
Pomeranian Academy of Medicine
2002 Commentary on newly identified genes in breast cancer
The Lancet (Journal)

Research Award

Year Award
2009 Researcher of the Year
Hunter Medical Research Institute (HMRI)
2004 Research Excellence in Cancer Research
Cancer Council NSW
1994 Susanne Huggenberger-Bishoff Stiftung Prize for Cancer Genetics
Huggenberger-Bischoff Stiftung zur Krebsforschung (Huggenberger-Bischoff Foundation for Cancer Research)

Invitations

External Examiner

Year Title / Rationale
2006 Polymorphism analysis in breast cancer
Organisation: Georgian National Science Foundation
2006 Histology of tumours derived from early onset cancer cases
Organisation: Georgian National Science Foundation

External Reviewer - Programs

Year Title / Rationale
2000 Genetic studies on colorectal cancer
Organisation: Canadian Medical Research Council

Participant

Year Title / Rationale
2007 The role of DNA repair genes in cancer
Organisation: Regional Conference on Molecular Medicine From Molecular Mechanisms to Clinical Practice
2007 Molecular epidemiology of colorectal cancer
Organisation: Regional Conference on Molecular Medicine From Molecular Mechanisms to Clinical Practice
2007 The Genetic basis of early familial colorectal cancer
Organisation: Australasian Association of Clinical Biochemists
2006 Future considerations for genetic testing
Organisation: IMPACT and AIDIT meeting
2004 Translation of medical research into clinical practice or From Bench to Bedside
Organisation: The Hunter Medical Research Institute Inaugural Cancer Conference
2003 Molecular Genetics: What is it being used for and where is it taking us
Organisation: . Australian Institute of Medical Science
2002 European inaugural conference on tissue banking 'Cogene'.
Organisation: European Union
2001 Attenuated Familial Adenomatous Polyposis.
Organisation: UICC Familial Cancer Project and International Oncology Conference, Beijing
1996 BRCA1 mutations and early onset breast cancer
Organisation: 3rd European Cancer Center (EUCC) Symposium. Kaiser Augst
1995 Identification of persons eligible for gene therapy: Limitations and expectations
Organisation: 5th. Basler Radio-Oncology Conference, Basel
1993 Hereditary conditions in which a loss of heterozygosity may be important
Organisation: 23rd. Annual Meeting of the European Environmental Mutagen Society, Barcelona. September 1993.

Thesis Examinations

Year Level Discipline Thesis
2017 PHD Health PhD
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Book (3 outputs)

Year Citation Altmetrics Link
2017 BERG AO, BERG JS, BROWN CW, BURKE W, CALONGE BN, CHUNG WK, et al., An evidence framework for genetic testing (2017)

© 2017 by the National Academy of Sciences. All rights reserved. Advances in genetics and genomics are transforming medical practice, resulting in a dramatic growth of genetic tes... [more]

© 2017 by the National Academy of Sciences. All rights reserved. Advances in genetics and genomics are transforming medical practice, resulting in a dramatic growth of genetic testing in the health care system. The rapid development of new technologies, however, has also brought challenges, including the need for rigorous evaluation of the validity and utility of genetic tests, questions regarding the best ways to incorporate them into medical practice, and how to weigh their cost against potential short- and long-term benefits. As the availability of genetic tests increases so do concerns about the achievement of meaningful improvements in clinical outcomes, costs of testing, and the potential for accentuating medical care inequality. Given the rapid pace in the development of genetic tests and new testing technologies, An Evidence Framework for Genetic Testing seeks to advance the development of an adequate evidence base for genetic tests to improve patient care and treatment. Additionally, this report recommends a framework for decision-making regarding the use of genetic tests in clinical care.

DOI 10.17226/24632
Citations Scopus - 2
2014 Percher M, Tohoku, Japan, earthquake and Tsunami of 2011: Survey of port and harbor facilities, northern region (2014)

© 2014 by the American Society of Civil Engineers. All Rights Reserved. Sponsored by the Coasts, Oceans, Ports, and Rivers Institute of ASCE On March 11, 2011, the largest earthqu... [more]

© 2014 by the American Society of Civil Engineers. All Rights Reserved. Sponsored by the Coasts, Oceans, Ports, and Rivers Institute of ASCE On March 11, 2011, the largest earthquake ever recorded in Japan struck off the coast of the Tohoku region. This 9.0 magnitude earthquake induced shaking and tsunamis along more than 2000 km of Japanese coastline and damaged port and harbor facilities from metropolitan Tokyo to the northern extent of Honshu. In May 2011, the ASCE-COPRI Port and Harbor Facilities Field Survey Team worked closely with Japan's Ports and Airports Research Institute to conduct extensive field reconnaissance examining the tsunami and earthquake effects specific to port waterfront structures and ancillary components, such as cargo cranes, conveyance systems, and piping equipment. This investigation focused on the design and construction of these structures with an emphasis on the lessons learned from both failures and successes. Information from on-site observations and interviews with facility owners, eyewitnesses, researchers, and government officials are incorporated into this report. The broad area covered, from Soma to Hachinohe in the northern prefectures of Aomori, Iwate, Miyagi, and Fukushima, facilitated the interpretation of damage patterns across the region affected by the earthquake, with a primary goal of distinguishing port damage due to strong ground shaking from that caused by subsequent and significant tsunami inundation. This report highlights field observations and initiates efforts to develop an extensive collection of geotechnical, structural, coastal, and seismological data. Port engineers, structural engineers, and disaster risk managers will find the field observations helpful in highlighting the most prevalent port vulnerabilities and the recommendations useful in improving the seismic performance of port facilities and protecting the lives of port personnel.

DOI 10.1061/9780784413180
2014 Bridge RO, Clarke MJ, Leon RT, Lui EM, Sheikh TM, White DW, Hajjar JF, Effective length and notional load approaches for assessing frame stability: Implications for american steel design (2014)

© 1997 by the American Society of Civil Engineers. All Rights Reserved. Prepared by the Task Committee on Effective Length of the Technical Committee on Load and Resistance Factor... [more]

© 1997 by the American Society of Civil Engineers. All Rights Reserved. Prepared by the Task Committee on Effective Length of the Technical Committee on Load and Resistance Factor Design of the Technical Division of the Structural Engineering Institute of ASCE. This report examines several contemporary techniques for assessing column stability in the design of steel frame structures. It provides an understanding of the strengths, limitations, and assumptions with respect to column and frame stability made in Load and Resistance Factor Design Specification for Structural Steel Buildings (LRFD), Second Edition (1993), published by the American Institute of Steel Construction (AISC). This report focuses on three techniques for stability design. Two approaches use effective length factors and are specifically outlined in the Commentary of the AISC specifications. The third method involves the use of a notional load approach for stability design (with the use of an effective length factor equal to one for all columns in the frame). Even though notional load approaches are not mentioned in the AISC specifications, this technique is commonly used in some form within several other design standards throughout much of the rest of the world. Examples illustrate the procedures for both common and unusual conditions encountered in practice. This document is applicable to both unbraced and braced frames having either fully restrained or partially restrained connections. In addition, even though most of the discussions pertain equally to either AISC Allowable Stress Design or LRFD practice, all discussions in this report are framed within the context of the more current LRFD specification. A practical introduction to this material is provided through the discussions of the assumptions, advantages, and disadvantages of each of the methods and through step-by-step examples. The more detailed discussions and derivations provide a reference regarding some of the more complex issues involved with design for stability.

DOI 10.1061/9780784402306

Chapter (9 outputs)

Year Citation Altmetrics Link
2017 Gandhi R, Weston M, Talavera M, Brittes GP, Barbosa E, 'Design and operation of the world's first long distance bauxite slurry pipeline', Essential Readings in Light Metals 75-80 (2017)

© 2016 by The Minerals, Metals & Materials Society. Mineracao Bauxita Paragominas (MBP) is the fum long distance slurry pipeline transporting bauxite slurry. Bauxite had dev... [more]

© 2016 by The Minerals, Metals & Materials Society. Mineracao Bauxita Paragominas (MBP) is the fum long distance slurry pipeline transporting bauxite slurry. Bauxite had developed a reputation for being difficult to hydraulically transport using long distance pipelines. This myth has now been proven wrong. The 245- km- long, 13.5 MTPY capacity MBP pipeline was designed and commissioned by PSI for CVRD. The pipeline is located in the State of Para, Brazil. The Miltonia bauxite mine is in a remote location with no other efficient means of transport. The bauxite slurry is delivered to Alunorte Alumina refinery located near Barcarena. This first of its kind pipeline required significant development work in order to assure technical and economic feasibility. This paper describes the technical aspects of design of the pipeline. It also summarizes the operating experience gained during the first year of operation.

DOI 10.1007/978-3-319-48176-0
2017 Young G, Penney S, Anderson J, Badenhorst C, Dawe N, Hesson J, et al., 'Women reflect on becoming an academic: Challenges and supports', The Academic Gateway: Understanding the Journey to Tenure 79-92 (2017)
2015 Riveros C, Vimieiro R, Holliday EG, Oldmeadow C, Wang JJ, Mitchell P, et al., 'Identification of genome-wide SNP-SNP and SNP-clinical Boolean interactions in Age-related Macular Degeneration', Epistasis: Methods and Protocols, Springer, New York 217-255 (2015) [B1]
DOI 10.1007/978-1-4939-2155-3_12
Citations Scopus - 2
Co-authors John Attia, Liz Holliday, Pablo Moscato, Christopher Oldmeadow, Carlos Riveros
2015 Jaworska-Bieniek K, Lener M, Muszynska M, Serrano-Fernández P, Sukiennicki G, Durda K, et al., 'Selenium and Cancer', Selenium : Chemistry, Analysis, Function and Effects, Royal Society of Chemistry, London 377-390 (2015) [B1]
DOI 10.1039/9781782622215-00377
2014 Attia JR, Holliday EG, Ioannidis JPA, Thakkinstian A, McEvoy M, Scott RJ, et al., 'How to use an article about genetic association', Users' Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice 3e, McGraw Hill Professional, USA (2014)
Co-authors Liz Holliday, John Attia
2012 Scott RJ, Reeves S, Talseth-Palmer B, 'The Role of Modifier Genes in Lynch Syndrome', Colorectal Cancer Biology, InTech, Croatia 37-58 (2012)
2012 Scott R, Reeves SG, Talseth-Palmer B, 'The role of modifier genes in Lynch Syndrome', Colorectal Cancer Biology From Genes To Tumor, InTech, Slovenia 37-58 (2012) [B1]
DOI 10.5772/1163
Co-authors Bente Talseth-Palmer
2009 Scott R, Lubinski J, 'Genetic epidemiology studies in hereditary non-polyposis colorectal cancer', Cancer Epidemiology, Humana Press, New York 89-102 (2009) [B1]
DOI 10.1007/978-1-60327-492-0_4
Citations Scopus - 4
2008 Mendes ADS, Scott R, Moscato PA, 'Microarrays - Identifying molecular portraits in prostrate tumors with different gleason patterns', Clinical Bioinformatics, Humana Press, New York 131-151 (2008) [B1]
DOI 10.1007/978-1-60327-148-6
Citations Scopus - 18
Co-authors Alexandre Mendes, Pablo Moscato
Show 6 more chapters

Journal article (893 outputs)

Year Citation Altmetrics Link
2018 Aggarwal S, Black J, Egan BF, Hedrick LJ, Abbinante C, Jamal S, et al., 'Annual survey of judicial developments pertaining to mergers and acquisitions', Business Lawyer, 73 379-424 (2018)
2018 Tsui CK, Boedo JA, Myra JR, Duval B, Labit B, Theiler C, et al., 'Filamentary velocity scaling validation in the TCV tokamak', Physics of Plasmas, 25 (2018)

© 2018 EURATOM. A large database of reciprocating probe data from the edge plasma of TCV (Tokamak à Configuration Variable) is used to test the radial velocity scalings of filamen... [more]

© 2018 EURATOM. A large database of reciprocating probe data from the edge plasma of TCV (Tokamak à Configuration Variable) is used to test the radial velocity scalings of filaments from analytical theory [Myra et al., Phys. Plasmas 13, 112502 (2006)]. The measured velocities are mainly scattered between zero and a maximum velocity which varies as a function of size and collisionality in agreement with the analytical scalings. The scatter is consistent with mechanisms that tend to slow the velocity of individual filaments. While the radial velocities were mainly clustered between 0.5 and 2 km/s, a minority reached outward velocities as high as 5 km/s or inward velocities as high as -4 km/s. Inward moving filaments are only observed in regions of high poloidal velocity shear in discharges with B × ¿B away from the X-point, a new finding. The filaments have diameters clustered between 3 and 11 mm, and normalized sizes â clustered between 0.3 and 1.1, such that most filaments populate the resistive-ballooning regime; therefore, most of the filaments in TCV have radial velocities with little or no dependence on collisionality. Improvements in cross-correlation techniques and conditional averaging techniques are discussed which reduce the sizes determined for the largest filaments, including those larger than the scrape-off layer.

DOI 10.1063/1.5038019
2018 Bialkowska K, Marciniak W, Muszynska M, Baszuk P, Gupta S, Jaworska-Bieniek K, et al., 'Association of zinc level and polymorphism in MMP-7 gene with prostate cancer in Polish population', PLOS ONE, 13 (2018) [C1]
DOI 10.1371/journal.pone.0201065
2018 Kamien B, Ronan A, Poke G, Sinnerbrink I, Baynam G, Ward M, et al., 'A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing', Molecular Syndromology, 9 70-82 (2018) [C1]
DOI 10.1159/000484532
Citations Scopus - 1
Co-authors T Dudding
2018 Lee JJ, Wedow R, Okbay A, Kong E, Maghzian O, Zacher M, et al., 'Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals', Nature Genetics, (2018)

© 2018, The Author(s). Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,2... [more]

© 2018, The Author(s). Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11¿13% of the variance in educational attainment and 7¿10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

DOI 10.1038/s41588-018-0147-3
Co-authors Christopher Oldmeadow, John Attia
2018 Holmes M, Connor T, Oldmeadow C, Pockney PG, Scott RJ, Talseth-Palmer BA, 'CD36 - a plausible modifier of disease phenotype in familial adenomatous polyposis', Hereditary Cancer in Clinical Practice, 16 (2018)

© 2018 The Author(s). Background: Familial adenomatous polyposis (FAP) is a well characterised genetic predisposition to early onset colorectal cancer (CRC) that is characterised ... [more]

© 2018 The Author(s). Background: Familial adenomatous polyposis (FAP) is a well characterised genetic predisposition to early onset colorectal cancer (CRC) that is characterised by polyposis of the colon and rectum. Animal models have consistently suggested the role of modifier genes in determining disease phenotype, yet none have been substantiated in the human population. The mouse homologue of cluster of differentiation 36 (CD36) has been proposed as a modifier of disease in the MIN mouse model of FAP. Methods: Three single nucleotide polymorphisms (SNPs); rs1049673, rs1761667 and rs1984112 in CD36, have been investigated in 275 FAP patients to determine if they were associated with age of polyposis or risk of developing disease. Results: The results revealed a substantially lower age of polyposis diagnosis for patients belonging to the severe FAP group (harbouring adenomatous polyposis coli (APC) variants in the mutation cluster region (MCR)) and high age for patients in the attenuated familial adenomatous polyposis (AFAP) group for SNPs rs1761667 and rs1984112. Conclusions: This study provides evidence for patients belonging to the MCR and AFAP groups harbouring specific genotypes for SNPs in CD36 to initiate screening/treatment for FAP at much earlier (MCR) and much later (AFAP) ages than the norm in today's clinical practice. The findings need to be verified in an independent FAP patient cohort.

DOI 10.1186/s13053-018-0096-y
Co-authors Peter Pockney, Bente Talseth-Palmer, Christopher Oldmeadow
2018 Kelly S, Jahanshad N, Zalesky A, Kochunov P, Agartz I, Alloza C, et al., 'Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.', Molecular psychiatry, 23 1261-1269 (2018) [C1]
DOI 10.1038/mp.2017.170
Citations Scopus - 2Web of Science - 3
Co-authors Ulrich Schall, Frans Henskens, Pat Michie
2018 Fullerton JM, Klauser P, Lenroot RK, Shaw AD, Overs B, Heath A, et al., 'Differential effect of disease-associated ST8S/A2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls', TRANSLATIONAL PSYCHIATRY, 8 (2018) [C1]
DOI 10.1038/s41398-017-0052-z
Citations Scopus - 1
Co-authors Murray Cairns
2018 Debniak T, Scott RJ, Lea RA, Górski B, Masojc B, Cybulski C, et al., 'Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland.', Cancer Res Treat, (2018)
DOI 10.4143/crt.2018.157
2018 Butel-Simoes GI, Spigelman AD, Scott RJ, Vilain RE, 'Low-level parental mosaicism in an apparent de novo case of Peutz¿Jeghers syndrome', Familial Cancer, 1-4 (2018)

© 2018 Springer Nature B.V. We report the case of a female found to have mosaicism for mutation in the STK11 gene, with the mutant allele expressed in her gametes, evident by her ... [more]

© 2018 Springer Nature B.V. We report the case of a female found to have mosaicism for mutation in the STK11 gene, with the mutant allele expressed in her gametes, evident by her affected offspring, and in her gastrointestinal tract demonstrated on an excised polyp analysed for diagnosis. Mosaicism for Peutz¿Jeghers syndrome (PJS) has been reported in a small number of cases previously but a clinical presentation such as this has not previously been described. This finding of mosaicism was several years after initial investigations failed to identify the same STK11 mutation in this woman whose son was diagnosed with PJS at a young age. This case highlights the importance of considering mosaicism as an explanation for apparent de novo cases of PJS syndrome. It also has implications for genetic counselling, predictive testing and cancer screening.

DOI 10.1007/s10689-018-0093-3
2018 Groen K, Lea RA, Maltby VE, Scott RJ, Lechner-Scott J, 'Letter to the editor: blood processing and sample storage have negligible effects on methylation', CLINICAL EPIGENETICS, 10 (2018) [C1]
DOI 10.1186/s13148-018-0455-6
Co-authors Vicki E Maltby, Jeannette Lechner-Scott
2018 Joo JE, Dowty JG, Milne RL, Wong EM, Dugué PA, English D, et al., 'Heritable DNA methylation marks associated with susceptibility to breast cancer /631/67/69 /631/337/176/1988 /692/699/67/1347 /692/308/2056 /45 /45/61 article', Nature Communications, 9 (2018)

© 2018 The Author(s). Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable... [more]

© 2018 The Author(s). Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable methylation marks associated with breast cancer susceptibility by studying 25 Australian multiple-case breast cancer families. Here we report genome-wide DNA methylation measured in 210 peripheral blood DNA samples provided by family members using the Infinium HumanMethylation450. We develop and apply a new statistical method to identify heritable methylation marks based on complex segregation analysis. We estimate carrier probabilities for the 1000 most heritable methylation marks based on family structure, and we use Cox proportional hazards survival analysis to identify 24 methylation marks with corresponding carrier probabilities significantly associated with breast cancer. We replicate an association with breast cancer risk for four of the 24 marks using an independent nested case-control study. Here, we report a novel approach for identifying heritable DNA methylation marks associated with breast cancer risk.

DOI 10.1038/s41467-018-03058-6
Citations Scopus - 1
2018 Ko YA, Jamaluddin MFB, Adebayo M, Bajwa P, Scott RJ, Dharmarajan AM, et al., 'Extracellular matrix (ECM) activates ß-catenin signaling in uterine fibroids', Reproduction, 155 61-71 (2018) [C1]

© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/ß-catenin pathway, lead to the ... [more]

© 2018 Society for Reproduction and Fertility. Recent studies showed that genetic aberrations in the MED12 gene, probably through the canonical WNT/ß-catenin pathway, lead to the pathogenesis of uterine fibroids. However, a comprehensive analysis of the WNT pathway in MED12-mutated and MED12-wildtype fibroids has not been performed. The objective of this study was to determine the status of the WNT pathway in human fibroids. We performed Sanger sequencing to define the MED12 mutational status of fibroids and normal myometrium samples. qPCR arrays were carried out to determine the status of the WNT signaling pathway in MED12-mutated and MED12-wild-type fibroids. Liquid chromatography-mass spectrometry (LC-MS), Western blotting and immunohistochemistry were used to monitor the expression of ß-catenin. We showed that ß-catenin expression was increased in fibroids compared to the adjacent myometrium samples. However, ß-catenin expression showed no correlation with MED12 mutation status. Of all the WNT signaling components, WNT inhibitors showed the greatest differences in expression between fibroids and controls. WIF1, a WNT inhibitor, was identified as the most significantly upregulated gene in fibroids. We cultured primary fibroid cells on hydrogels of known stiffness to decipher the influence of biomechanical cues on ß-catenin expression and revealed increased levels of ß-catenin when cells were cultured on a stiffer surface. In conclusion, our data showed that ß-catenin expression in fibroids occurs independently of MED12 mutations. Biomechanical changes upregulate ß-catenin expression in fibroids, providing an attractive avenue for developing new treatments for this disease.

DOI 10.1530/REP-17-0339
Citations Web of Science - 1
Co-authors Pradeep Tanwar, Muhammad Jamaluddin
2018 van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, et al., 'Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.', Biol Psychiatry, (2018)
DOI 10.1016/j.biopsych.2018.04.023
Co-authors Paul Tooney, Murray Cairns, Pat Michie, Frans Henskens, Carmel Loughland, Ulrich Schall
2018 Del Chiaro M, Besselink MG, Scholten L, Bruno MJ, Cahen DL, Gress TM, et al., 'European evidence-based guidelines on pancreatic cystic neoplasms', Gut, 67 789-804 (2018)

© Article author(s) 2018. All rights reserved. Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative o... [more]

© Article author(s) 2018. All rights reserved. Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter =40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

DOI 10.1136/gutjnl-2018-316027
Citations Scopus - 7
2018 Mikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, et al., 'Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines', Journal of Infection, 76 20-37 (2018)

© 2017 The British Infection Association Objectives Fluoroquinolone (FQ) prophylaxis was recommended in 2005 by European Conference on Infections in Leukemia (ECIL) for patients w... [more]

© 2017 The British Infection Association Objectives Fluoroquinolone (FQ) prophylaxis was recommended in 2005 by European Conference on Infections in Leukemia (ECIL) for patients with prolonged neutropenia. In consideration of a worldwide increase in antibiotic resistance, the issue of FQ prophylaxis during neutropenia was re-evaluated. Methods Literature review of randomised controlled trials (RCT) and observational studies published in years 2006¿2014 was performed. Their results were analysed in meta-analysis. Meta-regression model was applied to evaluate whether the rates of FQ resistance in community and hospital settings influenced the efficacy of FQ prophylaxis. The impact of FQ prophylaxis on colonisation and infection with resistant bacteria was reviewed. Results Two RCTs and 12 observational studies were identified. FQ prophylaxis did not have effect on mortality (pooled OR 1.01, 95%CI 0.73¿1.41), but was associated with lower rate of bloodstream infections (BSI) (pooled OR 0.57, 95%CI 0.43¿0.74) and episodes of fever during neutropenia (pooled OR 0.32, 95%CI 0.20¿0.50). No effect of the background rate of FQ resistance on the efficacy of FQ prophylaxis was observed. In few studies, FQ prophylaxis resulted in an increased colonisation or infection with FQ- or multi-drug resistant strains. Conclusions The possible benefits of FQ prophylaxis on BSI rate, but not on overall mortality, should be weighed against its impact in terms of toxicity and changes in local ecology in single centres.

DOI 10.1016/j.jinf.2017.10.009
Citations Scopus - 4
2018 Schrauben SJ, Hsu JY, Rosas SE, Jaar BG, Zhang X, Deo R, et al., 'CKD Self-management: Phenotypes and Associations With Clinical Outcomes', American Journal of Kidney Diseases, (2018)

© 2018 National Kidney Foundation, Inc. Background: To slow chronic kidney disease (CKD) progression and its complications, patients need to engage in self-management behaviors. T... [more]

© 2018 National Kidney Foundation, Inc. Background: To slow chronic kidney disease (CKD) progression and its complications, patients need to engage in self-management behaviors. The objective of this study was to classify CKD self-management behaviors into phenotypes and assess the association of these phenotypes with clinical outcomes. Study Design: Prospective cohort study. Setting & Participants: Adults with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. 3,939 participants in the CRIC Study recruited between 2003 and 2008 served as the derivation cohort and 1,560 participants recruited between 2013 and 2015 served as the validation cohort. Predictors: CKD self-management behavior phenotypes. Outcomes: CKD progression, atherosclerotic events, heart failure events, death from any cause. Measurements: Latent class analysis stratified by diabetes was used to identify CKD self-management phenotypes based on measures of body mass index, diet, physical activity, blood pressure, smoking status, and hemoglobin A1cconcentration (if diabetic); Cox proportional hazards models. Results: 3 identified phenotypes varied according to the extent of implementation of recommended CKD self-management behaviors: phenotype I characterized study participants with the most recommended behaviors; phenotype II, participants with a mixture of recommended and not recommended behaviors; and phenotype III, participants with minimal recommended behaviors. In multivariable-adjusted models for those with and without diabetes, phenotype III was strongly associated with CKD progression (HRs of 1.82 and 1.49), death (HRs of 1.95 and 4.14), and atherosclerotic events (HRs of 2.54 and 1.90; each P < 0.05). Phenotype II was associated with atherosclerotic events and death among those with and without diabetes. Limitations: No consensus definition of CKD self-management; limited to baseline behavior data. Conclusions: There are potentially 3 CKD self-management behavior phenotypes that distinguish risk for clinical outcomes. These phenotypes may inform the development of studies and guidelines regarding optimal self-management.

DOI 10.1053/j.ajkd.2018.01.047
2018 Habbous S, Arnold J, Begen MA, Boudville N, Cooper M, Dipchand C, et al., 'Duration of Living Kidney Transplant Donor Evaluations: Findings From 2 Multicenter Cohort Studies', American Journal of Kidney Diseases, (2018)

© 2018 The Authors Background: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process ... [more]

© 2018 The Authors Background: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process may help inform future donors and identify opportunities for improvement. Study Design: 1 prospective and 1 retrospective cohort study. Setting & Participants: At 16 Canadian and Australian transplantation centers (prospective cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed the duration of living kidney donor evaluation and explored donor, recipient, and transplantation factors associated with longer evaluation times. Data were obtained from 2 sources: donor medical records using chart abstraction and health care administrative databases. Predictors: Donor and recipient demographics, direct versus paired donation, center-level variables. Outcomes: Duration of living donor evaluation. Results: The median total duration of transplantation evaluation (time from when the candidate started the evaluation until donation) was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the first and last consultation among donors who completed a nephrology, surgery, and psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months, and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2) months. After adjustment, the total duration of transplantation evaluation was longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7] months) and if the recipient was referred later relative to the donor's evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed referral]). Results depended on whether the recipient was receiving dialysis. Limitations: Living donor candidates who did not donate were not included and proxy measures were used for some dates in the donor evaluation process. Conclusions: The duration of kidney transplant donor evaluation is variable and can be lengthy. Better understanding of the reasons for a prolonged evaluation may inform quality improvement initiatives to reduce unnecessary delays.

DOI 10.1053/j.ajkd.2018.01.036
Citations Scopus - 2
2018 Vernetti A, Senju A, Charman T, Johnson MH, Gliga T, Baron-Cohen S, et al., 'Simulating interaction: Using gaze-contingent eye-tracking to measure the reward value of social signals in toddlers with and without autism', Developmental Cognitive Neuroscience, 29 21-29 (2018)

© 2017 The Authors Several accounts have been proposed to explain difficulties with social interaction in autism spectrum disorder (ASD), amongst which atypical social orienting, ... [more]

© 2017 The Authors Several accounts have been proposed to explain difficulties with social interaction in autism spectrum disorder (ASD), amongst which atypical social orienting, decreased social motivation or difficulties with understanding the regularities driving social interaction. This study uses gaze-contingent eye-tracking to tease apart these accounts by measuring reward related behaviours in response to different social videos. Toddlers at high or low familial risk for ASD took part in this study at age 2 and were categorised at age 3 as low risk controls (LR), high-risk with no ASD diagnosis (HR-no ASD), or with a diagnosis of ASD (HR-ASD). When the on-demand social interaction was predictable, all groups, including the HR-ASD group, looked longer and smiled more towards a person greeting them compared to a mechanical Toy (Condition 1) and also smiled more towards a communicative over a non-communicative person (Condition 2). However, all groups, except the HR-ASD group, selectively oriented towards a person addressing the child in different ways over an invariant social interaction (Condition 3). These findings suggest that social interaction is intrinsically rewarding for individuals with ASD, but the extent to which it is sought may be modulated by the specific variability of naturalistic social interaction.

DOI 10.1016/j.dcn.2017.08.004
Citations Scopus - 1
2018 Ranjan C, Paynabar K, Reuter M, Jafari-Khouzani K, 'Longitudinal MRI data analysis in presence of measurement error but absence of replicates', IISE Transactions on Healthcare Systems Engineering, 8 117-130 (2018)

© 2018 ¿IISE¿. Longitudinal data analysis has found immense importance in biomedical fields to assess relationships between an outcome and its explanatory variables over time. How... [more]

© 2018 ¿IISE¿. Longitudinal data analysis has found immense importance in biomedical fields to assess relationships between an outcome and its explanatory variables over time. However, this analysis is unreliable in presence of measurement errors in response data because the errors confound the effect of any signal caused by process changes. This confounding can be easily resolved by estimating and isolating the measurement errors using replicated measurements; i.e., multiple measurements in a small (stationary) time interval. However, in many medical applications, such as in magnetic resonance imaging (MRI), taking replicated measurements is not possible due to cost and/or risk considerations. This makes measurement error estimation and data analysis very challenging. In this article, we propose a novel method for the analysis of unreplicated longitudinal data under the presence of measurement errors. We formulate the problem using mixed-effect regression and develop a new EM-Variogram technique to estimate regression coefficients as well as variance components. The proposed approach decouples the confounded observed variance into the process and measurement system variances, and helps construct precise confidence intervals, leading to a more powerful statistical hypothesis test for the model parameters. We validate the proposed method using simulation and also apply it to a longitudinal MRI data for patients with neurodegenerative diseases. The results show improved statistical power in measuring their hippocampal volume loss, and a quicker degeneration detection. We also demonstrate the robustness of the proposed method with respect to missing values, a common issue in longitudinal data.

DOI 10.1080/24725579.2017.1423419
2018 Aupérin A, 'Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission', Cochrane Database of Systematic Reviews, 2018 (2018)

© 2018 The Cochrane Collaboration. Background: Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized ... [more]

© 2018 The Cochrane Collaboration. Background: Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized trials conducted on patients in complete remission were unable to clarify whether this treatment improves survival. Objectives: This study aims to test whether prophylactic cranial irradiation prolongs survival of patients with small cell lung cancer in complete remission. Search methods: Published and unpublished trials were eligible. Electronic databases (Medline, Cancerlit, Excerpta Medica, Biosis from 1965 to 1998), reference lists of trial publications, review articles and relevant books were used to identify potentially eligible trials. The search was also guided by discussions with investigators and experts, and the examination of meeting proceedings and of the Physician Data Query clinical trial registry. Selection criteria: Randomized trials comparing prophylactic cranial irradiation with no prophylactic cranial irradiation in patients with small cell lung cancer in complete remission. Data collection and analysis: Meta-analysis based on updated individual data. The main endpoint was survival. Main results: Seven trials with a total of 987 participants were included. The relative risk of death in the treatment group compared to the control group was 0.84 (95% confidence interval=0.73 to 0.97, P=0.01), corresponding to a 5.4 percent increase in the 3-year survival rate (from 15.3 percent in the control group to 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased disease-free survival (relative risk=0.75, 95% confidence interval=0.65 to 0.86, P<0.001) and decreased the risk of brain metastases (relative risk=0.46, 95% confidence interval=0.38 to 0.57, P<0.001). Increasing doses of irradiation decreased the risk of brain metastases when four groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed [trend test, P=0.02], but the effect on survival did not differ significantly according to the dose. We found a trend (P=0.01) for a decrease in the brain metastasis risk in favour of earlier administration of cranial irradiation after the initiation of induction treatment. Authors' conclusions: Prophylactic cranial irradiation significantly improves survival and disease-free survival for patients with small cell lung cancer in complete remission. Further clinical trials are needed to confirm the potential greater benefit on brain metastasis rate suggested when cranial irradiation is given earlier or at higher doses.

DOI 10.1002/14651858.CD002805.pub2
2018 Saez L, Langlois J, Legrand K, Quinet MH, Lecomte E, Omorou AY, Briançon S, 'Reach and acceptability of a mobile reminder strategy and facebook group intervention for weight management in less advantaged adolescents: Insights from the PRALIMAP-INÈS trial', Journal of Medical Internet Research, 20 (2018)

© Laura Saez, Johanne Langlois, Karine Legrand, Marie-Hélène Quinet, Edith Lecomte, Abdou Y Omorou, Serge Briançon, PRALIMAP-INÈS Trial Group. Background: Although information and... [more]

© Laura Saez, Johanne Langlois, Karine Legrand, Marie-Hélène Quinet, Edith Lecomte, Abdou Y Omorou, Serge Briançon, PRALIMAP-INÈS Trial Group. Background: Although information and communication technology interventions appear to be a promising means of reducing the health inequality gap in overweight and obesity prevention, research on information and communication technology interventions is lacking outside the Anglo-Saxon world. Objective: The aim of this study was to assess the reach and acceptability of 2 information and communication technology interventions delivered as part of a French nutritional program: an SMS text messaging (short message service, SMS) attendance-reminder for collective sessions strategy and a Facebook challenge group. Methods: This study sample comprised 262 socially less advantaged overweight adolescents aged between 13 and 18 years. The information and communication technology interventions were carried out during the 2013-2014 academic year in 33 French state-run schools. For the SMS attendance-reminder for collective sessions strategy, at the start of the academic year, adolescents were asked to give their mobile number. SMS attendance-reminders were sent shortly before each of the 5 collective sessions. For the Facebook challenge group, adolescents were invited to join a closed Facebook group in which challenges on physical activity and on diet were posted weekly. Process data and 2 sets of face-to-face interviews were also used to interpret participation rates and access to Facebook. Appreciation for both interventions was evaluated by a questionnaire at the end of the academic year. Results: Of the recruited adolescents, 79.0% (207/262) gave their mobile number, reflecting high access to a mobile phone. Giving a number was significantly more likely for girls (odds ratio [OR] 2.1, 95% CI 1.1-3.9; P=.02) and adolescents in a vocational or general high school as opposed to middle school (OR 1.0, 95% CI 0.4-2.7; OR 0.2, 95% CI 0.1-0.5; P<.001). Indicating a mobile number at the start of the year was not significantly associated with participation in collective sessions. Of the adolescents seen at the start-of-year face-to-face interviews, 78.1% (153/196) declared an interest in the Facebook challenge group, which implies having a Facebook account or being able to have access to one. However, only 21 adolescents went through the process of joining the group. Although there was satisfaction with the Facebook group among the participants, the low participation rate in the Facebook group does not allow conclusions to be drawn with confidence. Conclusions: The results are in line with the claim that using information and communication technologies in health programs is unlikely to widen health inequalities. However, in this population of French adolescents, mobile phone strategies seem more adapted to a high school context, and caution should be exercised with a younger audience. Although there is positive appreciation of the SMS attendance-reminders and a Facebook intervention is initially highly appealing to less advantaged adolescents, no evidence of impact could be demonstrated. These results highlight the difficulty in assessing the impact of specific interventions in complex health programs.

DOI 10.2196/mhealth.7657
2018 Painter JN, O'Mara TA, Morris AP, Cheng THT, Gorman M, Martin L, et al., 'Genetic overlap between endometriosis and endometrial cancer: Evidence from cross-disease genetic correlation and GWAS meta-analyses', Cancer Medicine, 5 1978-1987 (2018) [C1]
DOI 10.1002/cam4.1445
Citations Scopus - 1Web of Science - 1
Co-authors John Attia, Liz Holliday, Mark Mcevoy
2018 Revelas M, Thalamuthu A, Oldmeadow C, Evans T-J, Armstrong NJ, Kwok JB, et al., 'Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.', Mech Ageing Dev, 175 24-34 (2018)
DOI 10.1016/j.mad.2018.06.002
Co-authors Christopher Oldmeadow, John Attia
2018 Wu L, Shi W, Long J, Guo X, Michailidou K, Beesley J, et al., 'A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer', Nature Genetics, 50 968-978 (2018)

© 2018 The Author(s). The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes resp... [more]

© 2018 The Author(s). The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10-6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

DOI 10.1038/s41588-018-0132-x
2018 Groen K, Maltby VE, Lea RA, Sanders KA, Fink JL, Scott RJ, et al., 'Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis.', BMC medical genomics, 11 (2018) [C1]
DOI 10.1186/s12920-018-0365-7
Co-authors Jeannette Lechner-Scott, Vicki E Maltby
2018 Iglesias AI, Mishra A, Vitart V, Bykhovskaya Y, Höhn R, Springelkamp H, et al., 'Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases', Nature Communications, 9 (2018) [C1]
DOI 10.1038/s41467-018-03646-6
Co-authors Liz Holliday, John Attia
2018 Xavier MJ, Mitchell LA, McEwan KE, Scott RJ, Aitken RJ, 'Genomic integrity in the male germ line: evidence in support of the disposable soma hypothesis.', Reproduction, 156 269-282 (2018)
DOI 10.1530/REP-18-0202
Co-authors John Aitken
2018 Jamaluddin MFB, Ko YA, Kumar M, Brown Y, Bajwa P, Nagendra PB, et al., 'Proteomic profiling of human uterine fibroids reveals upregulation of the extracellular matrix protein periostin', Endocrinology, 159 1106-1118 (2018) [C1]

Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bu... [more]

Copyright © 2018 Endocrine Society The central characteristic of uterine fibroids is excessive deposition of extracellular matrix (ECM), which contributes to fibroid growth and bulk-type symptoms. Despite this, very little is known about patterns of ECM protein expression in fibroids and whether these are influenced by the most common genetic anomalies, which relate to MED12. We performed extensive genetic and proteomic analyses of clinically annotated fibroids and adjacent normal myometrium to identify the composition and expression patterns of ECM proteins in MED12 mutation-positive and mutation-negative uterine fibroids. Genetic sequencing of tissue samples revealed MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated (.1.5-fold) and downregulated (,0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.

DOI 10.1210/en.2017-03018
Citations Scopus - 1Web of Science - 1
Co-authors Mark Baker, Muhammad Jamaluddin, Hubert Hondermarck, Manishkumar Jhamb, Pradeep Tanwar, Matt Dun
2018 Maltby VE, Lea RA, Ribbons KA, Sanders KA, Kennedy D, Min M, et al., 'DNA methylation changes in CD4+ T cells isolated from multiple sclerosis patients on dimethyl fumarate.', Mult Scler J Exp Transl Clin, 4 2055217318787826 (2018)
DOI 10.1177/2055217318787826
Co-authors Vicki E Maltby, Jeannette Lechner-Scott
2018 Davies G, Lam M, Harris SE, Trampush JW, Luciano M, Hill WD, et al., 'Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.', Nat Commun, 9 2098 (2018)
DOI 10.1038/s41467-018-04362-x
Citations Scopus - 2
Co-authors Christopher Oldmeadow, Peter Schofield, Liz Holliday, John Attia
2018 Ni G, Gratten J, Wray NR, Lee SH, Ripke S, Neale BM, et al., 'Age at first birth in women is genetically associated with increased risk of schizophrenia', Scientific Reports, 8 (2018)

© 2018 The Author(s). Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-a... [more]

© 2018 The Author(s). Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.

DOI 10.1038/s41598-018-28160-z
Co-authors Ulrich Schall, Carmel Loughland, Pat Michie, Frans Henskens
2018 Wyss AB, Sofer T, Lee MK, Terzikhan N, Nguyen JN, Lahousse L, et al., 'Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function', Nature Communications, 9 (2018) [C1]
DOI 10.1038/s41467-018-05369-0
Co-authors John Attia, Christopher Oldmeadow, Mark Mcevoy, Liz Holliday
2017 Pan X, Bowman M, Scott RJ, Fitter J, Smith R, Zakar T, 'Promoter methylation pattern controls corticotropin releasing hormone gene activity in human trophoblasts', PLoS ONE, 12 1-18 (2017) [C1]
DOI 10.1371/journal.pone.0170671
Co-authors Maria Bowman, Roger Smith, John Fitter
2017 Daneshi N, Holliday E, Hancock S, Schneider JJ, Scott RJ, Attia J, Milward EA, 'Prevalence of clinically actionable genotypes and medication exposure of older adults in the community', Pharmacogenomics and Personalized Medicine, 10 17-27 (2017) [C1]

© 2017 Daneshi et al. This study analyzed clinically actionable pharmacogenotypes for clopidogrel, warfarin, statins, thiopurines, and tacrolimus using microarray data for 2121 pa... [more]

© 2017 Daneshi et al. This study analyzed clinically actionable pharmacogenotypes for clopidogrel, warfarin, statins, thiopurines, and tacrolimus using microarray data for 2121 participants (55¿85 years) from the Australian Hunter Community Study (HCS). At least 74% of participants (95% confidence interval [CI]: 72%¿76%) had strong level evidence for at least one medium- or high-risk actionable genotype that would trigger a change in standard therapy under current international recommendations. About 14% of these participants (95% CI: 12%¿16%) were taking medication potentially affected by the genotype in question. Furthermore, ~2.6% of all participants with medication data (95% CI: 1.4%¿3.8%) had a high-risk clinically actionable genotype for a medication to which they were exposed. This represents a considerable number of people at the population level. Although relationships between genotype and health outcomes remain contentious, pharmacogenotyping of multiple variants simultaneously may have considerable potential to improve medication safety and efficacy for older people in the community.

DOI 10.2147/PGPM.S123719
Co-authors John Attia, Liz Milward, Jennifer Schneider, Liz Holliday
2017 Strumidlo A, Skiba S, Scott RJ, Lubinski J, 'The potential role of miRNAs in therapy of breast and ovarian cancers associated with BRCA1 mutation', Hereditary Cancer in Clinical Practice, 15 1-5 (2017) [C1]
DOI 10.1186/s13053-017-0076-7
Citations Scopus - 1Web of Science - 1
2017 Le Hellard S, Wang Y, Witoelar A, Zuber V, Bettella F, Hugdahl K, et al., 'Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment', Schizophrenia Bulletin, 43 654-664 (2017) [C1]
DOI 10.1093/schbul/sbw085
Co-authors Brian Kelly, Pat Michie, Frans Henskens, Carmel Loughland, Paul Tooney, Ulrich Schall, Murray Cairns
2017 Burnard S, Lechner-Scott J, Scott RJ, 'EBV and MS: Major cause, minor contribution or red-herring?', Multiple Sclerosis and Related Disorders, 16 24-30 (2017) [C1]

© 2017 Multiple Sclerosis (MS) is a chronic neurological disease with genetic and environmental risk factors. Epstein Barr-Virus (EBV) has been closely associated with MS but with... [more]

© 2017 Multiple Sclerosis (MS) is a chronic neurological disease with genetic and environmental risk factors. Epstein Barr-Virus (EBV) has been closely associated with MS but with a significant amount of conflicting evidence. Some of the evidence for EBV involvement in MS includes: almost 100% of MS patients showing past EBV infection, an association with Infectious Mononucleosis (acute EBV infection), higher titres of EBV antibodies associated with an increased risk of MS development, and an overall altered immune response to EBV found in peripheral blood and the CNS of MS patients. However, evidence for EBV presence in the CSF and T cell responses to EBV in MS have been particularly conflicting. Several hypotheses have been proposed for direct and indirect EBV involvement in MS such as 1) Molecular Mimicry 2) Mistaken Self 3) Bystander Damage and 4) Autoreactive B cells infected with EBV. More recently, an association between EBV and human endogenous retrovirus in MS has been shown, which may provide an alternative pathogenetic target for MS treatment. However, if EBV is not the major contributor to MS and is instead one of several viral or infectious agents able to elicit a similar altered immune response, MS development may be the result of a failure of viral clearance in general. This review aims to evaluate the evidence for the currently discussed theories of EBV involvement in MS pathogenesis.

DOI 10.1016/j.msard.2017.06.002
Citations Scopus - 2Web of Science - 2
Co-authors Jeannette Lechner-Scott
2017 Hansen MF, Johansen J, Sylvander AE, Bjørnevoll I, Talseth-Palmer BA, Lavik LAS, et al., 'Use of multigene-panel identifies pathogenic variants in several CRC-predisposing genes in patients previously tested for Lynch Syndrome', Clinical Genetics, 92 405-414 (2017) [C1]

© 2017 The Authors. Clinical Genetics published by John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd. Background: Many families with a high burden of colorecta... [more]

© 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Background: Many families with a high burden of colorectal cancer fulfil the clinical criteria for Lynch Syndrome. However, in about half of these families, no germline mutation in the mismatch repair genes known to be associated with this disease can be identified. The aim of this study was to find the genetic cause for the increased colorectal cancer risk in these unsolved cases. Materials and methods: To reach the aim, we designed a gene panel targeting 112 previously known or candidate colorectal cancer susceptibility genes to screen 274 patient samples for mutations. Mutations were validated by Sanger sequencing and, where possible, segregation analysis was performed. Results: We identified 73 interesting variants, of whom 17 were pathogenic and 19 were variants of unknown clinical significance in well-established cancer susceptibility genes. In addition, 37 potentially pathogenic variants in candidate colorectal cancer susceptibility genes were detected. Conclusion: In conclusion, we found a promising DNA variant in more than 25 % of the patients, which shows that gene panel testing is a more effective method to identify germline variants in CRC patients compared to a single gene approach.

DOI 10.1111/cge.12994
Citations Scopus - 3Web of Science - 3
Co-authors Bente Talseth-Palmer
2017 Atkinson RJ, Fulham WR, Michie PT, Ward PB, Todd J, Stain H, et al., 'Electrophysiological, cognitive and clinical profiles of at-risk mental state: The longitudinal Minds in Transition (MinT) study', PLOS ONE, 12 (2017) [C1]
DOI 10.1371/journal.pone.0171657
Citations Scopus - 2Web of Science - 2
Co-authors Juanita Todd, Ulrich Schall, Carmel Loughland, Renate Thienel, Paul Tooney, Pat Michie
2017 Gorski M, Van der Most PJ, Teumer A, Chu AY, Li M, Mijatovic V, et al., '1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function', SCIENTIFIC REPORTS, 7 (2017) [C1]
DOI 10.1038/srep45040
Citations Scopus - 10Web of Science - 11
Co-authors John Attia, Mark Mcevoy, Liz Holliday
2017 Gromowski T, Gapska P, Scott RJ, Kaklewski K, Marciniak W, Durda K, et al., 'Serum 25(OH)D concentration, common variants of the VDR gene and lung cancer occurrence', International Journal of Cancer, 141 336-341 (2017) [C1]
DOI 10.1002/ijc.30740
2017 Cox AJ, Zhang P, Evans TJ, Scott RJ, Cripps AW, West NP, 'Gene expression profiles in whole blood and associations with metabolic dysregulation in obesity', Obesity Research and Clinical Practice, 12 204-213 (2017) [C1]
DOI 10.1016/j.orcp.2017.07.001
2017 Najdawi F, Crook A, Maidens J, McEvoy C, Fellowes A, Pickett J, et al., 'Lessons learnt from implementation of a Lynch syndrome screening program for patients with gynaecological malignancy', Pathology, 49 457-464 (2017) [C1]

© 2017 Despite a trend towards universal testing, best practice to screen patients presenting with gynaecological malignancy for Lynch syndrome (LS) is uncertain. We report our in... [more]

© 2017 Despite a trend towards universal testing, best practice to screen patients presenting with gynaecological malignancy for Lynch syndrome (LS) is uncertain. We report our institutional experience of a co-ordinated gynaecological LS screening program. All patients with endometrial carcinoma or carcinosarcoma, or gynaecological endometrioid or clear cell carcinomas undergo reflex four panel immunohistochemistry (IHC) for MLH1, PMS2, MSH2 and MSH6 followed by cascade somatic hypermethylation analysis of the MLH1 promoter locus for dual MLH1/PMS2 negative tumours. On the basis of these results, genetic counselling and targeted germline mutation testing is then offered to patients considered at high risk of LS. From 1 August 2013 to 31 December 2015, 124 patients were screened (mean age 64.6 years). Thirty-six (29.0%) demonstrated abnormal MMR IHC: 26 (72.2%) showed dual loss of MLH1/PMS2, five (13.9%) dual loss of MSH2/MSH6, three (8.3%) isolated loss of MSH6, and two (5.6%) isolated loss of PMS2. Twenty-five of 26 (96.1%) patients with dual MLH1/PMS2 loss demonstrated MLH1 promoter methylation. Therefore, 11 (8.9%) patients screened were classified as high risk for LS, of whom nine (81.8%) accepted germline mutation testing. Three (2.4% of total screened) were confirmed to have LS, two with germline PMS2 and one with germline MSH2 mutation. Massive parallel sequencing of tumour tissue demonstrated somatic mutations which were concordant with the IHC results in the remainder. Interestingly, the one MLH1/PMS2 IHC negative but not hypermethylated tumour harboured only somatic MLH1 mutations, indicating that universal cascade methylation testing in MLH1/PMS2 IHC negative tumours is very low yield and could be reconsidered in a resource-poor setting. In conclusion, universal screening for LS in patients presenting with gynaecological malignancy using the algorithm described above identified LS in three of 124 (2.4%) of our population. Only three of nine (33.3%) patients considered at high risk for LS by combined IHC and hypermethylation analysis were proven to have LS. Only one of the LS patients was less than 50 years of age and none of these patients would have been identified had more restrictive Amsterdam or Bethesda criteria been applied.

DOI 10.1016/j.pathol.2017.05.004
Citations Scopus - 3Web of Science - 3
2017 Kwon SJ, Lee HS, Park DJ, 'A novel in-situ corrosion monitoring electrode for reinforced concrete structures', Electrochimica Acta, (2017)

© 2017 Elsevier Ltd. In this study, an embeddable in-situ corrosion monitoring electrode based on Ce-doped NiFe2O4was fabricated, and their corrosion performance of the steel reba... [more]

© 2017 Elsevier Ltd. In this study, an embeddable in-situ corrosion monitoring electrode based on Ce-doped NiFe2O4was fabricated, and their corrosion performance of the steel rebar was evaluated in the simulated concrete environment under passive and active conditions. The passive and active environment consists of simulated concrete pore solution (SCPS) without and with 3% NaCl. The corrosion performance of embedded steel rebar in concrete was monitored by exposing the concrete specimens under alternate dry and wet condition in 3% NaCl solution. The corrosion behavior of the steel rebar was studied by using open circuit potential, AC-impedance, and potentiodynamic polarization studies. The relative corrosion performance of the embeddable steel rebar was assessed with fabricated corrosion monitoring electrode (FCME) and compared with the surface mounted electrode (SME) by using saturated calomel electrode (SCE). The results revealed that the FCME could use as an in-situ electrode for assessing the corrosion monitoring of the reinforced concrete structures.

DOI 10.1016/j.electacta.2017.10.088
Citations Scopus - 2
2017 Penzias A, Bendikson K, Butts S, Coutifaris C, Falcone T, Fossum G, et al., 'Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline', Fertility and Sterility, 108 426-441 (2017)

© 2017 American Society for Reproductive Medicine Metformin alone compared with placebo increases the ovulation rate in women with polycystic ovary syndrome (PCOS) but should not ... [more]

© 2017 American Society for Reproductive Medicine Metformin alone compared with placebo increases the ovulation rate in women with polycystic ovary syndrome (PCOS) but should not be used as first-line therapy for anovulation because oral ovulation induction agents such as clomiphene citrate or letrozole alone are much more effective in increasing ovulation, pregnancy, and live-birth rates in women with PCOS. There is fair evidence that metformin alone does not increase rates of miscarriage when stopped at the initiation of pregnancy and insufficient evidence that metformin in combination with other agents used to induce ovulation increases live-birth rates.

DOI 10.1016/j.fertnstert.2017.06.026
Citations Scopus - 2
2017 Penzias A, Bendikson K, Butts S, Coutifaris C, Falcone T, Fossum G, et al., 'Removal of myomas in asymptomatic patients to improve fertility and/or reduce miscarriage rate: a guideline', Fertility and Sterility, 108 416-425 (2017)

© 2017 The purpose of this systematic review is to evaluate if uterine myomas impact the likelihood of pregnancy and pregnancy loss, and if myomectomy influences pregnancy outcome... [more]

© 2017 The purpose of this systematic review is to evaluate if uterine myomas impact the likelihood of pregnancy and pregnancy loss, and if myomectomy influences pregnancy outcomes in asymptomatic women. There is insufficient evidence to conclude that the presence of myomas reduces the likelihood of achieving pregnancy. However, there is fair evidence that myomectomy (open or laparoscopic) for cavity-distorting myomas (intramural or intramural with a submucosal component) improves pregnancy rates and reduces the risk of early pregnancy loss. There is fair evidence that hysteroscopic myomectomy for cavity-distorting myomas improves clinical pregnancy rates but insufficient evidence regarding the impact of this procedure on the likelihood of live birth or early pregnancy loss. In women with asymptomatic cavity-distorting myomas, myomectomy may be considered to optimize pregnancy outcomes.

DOI 10.1016/j.fertnstert.2017.06.034
Citations Scopus - 3
2017 Daar J, Benward J, Collins L, Davis J, Davis O, Francis L, et al., 'Child-rearing ability and the provision of fertility services: an Ethics Committee opinion', Fertility and Sterility, 108 944-947 (2017)

© 2017 American Society for Reproductive Medicine Fertility programs may withhold services from prospective patients on the basis of well-grounded reasons that those patients will... [more]

© 2017 American Society for Reproductive Medicine Fertility programs may withhold services from prospective patients on the basis of well-grounded reasons that those patients will be unable to provide minimally adequate or safe care for offspring. This document was reviewed and updated; this version replaces the previous version of this document, last published July 2013 (Fertil Steril 2013;100:50-53). Earn online CME credit related to this document at www.asrm.org/elearn

DOI 10.1016/j.fertnstert.2017.10.006
Citations Scopus - 1
2017 Wangler MF, Yamamoto S, Chao HT, Posey JE, Westerfield M, Postlethwait J, et al., 'Model organisms facilitate rare disease diagnosis and therapeutic research', Genetics, 207 9-27 (2017)

© 2017 by the Genetics Society of America. Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing an... [more]

© 2017 by the Genetics Society of America. Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functions. Here, we review the current state of research into undiagnosed diseases, highlighting large efforts in North America and internationally, including the Undiagnosed Diseases Network (UDN) (Supplemental Material, File S1) and UDN International (UDNI), the Centers for Mendelian Genomics (CMG), and the Canadian Rare Diseases Models and Mechanisms Network (RDMM). We discuss how merging human genetics with model organism research guides experimental studies to solve these medical mysteries, gain new insights into disease pathogenesis, and uncover new therapeutic strategies.

DOI 10.1534/genetics.117.203067
Citations Scopus - 14
2017 Willoughby MT, Magnus B, Vernon-Feagans L, Blair CB, Cox M, Blair C, et al., 'Developmental Delays in Executive Function from 3 to 5 Years of Age Predict Kindergarten Academic Readiness', Journal of Learning Disabilities, 50 359-372 (2017)

© 2016, © Hammill Institute on Disabilities 2016. Substantial evidence has established that individual differences in executive function (EF) in early childhood are uniquely predi... [more]

© 2016, © Hammill Institute on Disabilities 2016. Substantial evidence has established that individual differences in executive function (EF) in early childhood are uniquely predictive of children¿s academic readiness at school entry. The current study tested whether growth trajectories of EF across the early childhood period could be used to identify a subset of children who were at pronounced risk for academic impairment in kindergarten. Using data that were collected at the age 3, 4, and 5 home assessments in the Family Life Project (N = 1,120), growth mixture models were used to identify 9% of children who exhibited impaired EF performance (i.e., persistently low levels of EF that did not show expected improvements across time). Compared to children who exhibited typical trajectories of EF, the delayed group exhibited substantial impairments in multiple indicators of academic readiness in kindergarten (Cohen¿s ds = 0.9¿2.7; odds ratios = 9.8¿23.8). Although reduced in magnitude following control for a range of socioeconomic and cognitive (general intelligence screener, receptive vocabulary) covariates, moderate-sized group differences remained (Cohen¿s ds = 0.2¿2.4; odds ratios = 3.9¿5.4). Results are discussed with respect to the use of repeated measures of EF as a method of early identification, as well as the resulting translational implications of doing so.

DOI 10.1177/0022219415619754
Citations Scopus - 10
2017 Salinas RR, Echeverría B C, Anamaría U A, Goic G A, Quintana V C, Rojas O A, et al., 'Does therapeutic privilege have a place in modern medicine?', Revista Medica de Chile, 145 1198-1202 (2017)

© 2017, Sociedad Medica de Santiago. All rights reserved. During the last years, bioethical discussion has highlighted the role of the patients¿ autonomy, being informed consent i... [more]

© 2017, Sociedad Medica de Santiago. All rights reserved. During the last years, bioethical discussion has highlighted the role of the patients¿ autonomy, being informed consent its particular expression, about decisions that they should make about their own health. The Hippocratic tradition, the deontological positions of the Geneva Declaration of the World Medical Association and numerous codes of ethics in various countries, require that the physician, above all, should ensure patients¿ health. In this context the discussion on pros and cons for the so-called ¿therapeutic privilege¿ are discussed. The ¿therapeutic privilege¿ refers to the withholding of information by the clinician during the consent process in the belief that disclosure of this information would lead to harm or suffering of the patient. The circumstances and conditions in which this privilege can become valid are discussed. Special reference is made in order to respect multiculturalism and to the possibility of obtaining advice from health care ethics committees. The role of prudence in the doctor-patient relation must be highlighted. Disclosure of information should be subordinated and oriented to the integral well-being of the patient.

DOI 10.4067/s0034-98872017000901198
Citations Scopus - 1
2017 Pennington RT, Banda-R K, Delgado-Salinas A, Dexter KG, Linares-Palomino R, Olivera-Filho A, et al., 'Forest conservation: Humans' handprints - Response', Science, 355 467 (2017)
DOI 10.1126/science.aal2602
2017 Pennington RT, Banda-R K, Delgado-Salinas A, Dexter KG, Galetti L, Linares-Palomino R, et al., 'Forest conservation: Remember Gran Chaco - Response', Science, 355 465-466 (2017)
DOI 10.1126/science.aal5010
2017 Azani N, Babineau M, Bailey CD, Banks H, Barbosa AR, Pinto RB, et al., 'A new subfamily classification of the leguminosae based on a taxonomically comprehensive phylogeny', Taxon, 66 44-77 (2017)

© International Association for Plant Taxonomy (IAPT) 2017. The classification of the legume family proposed here addresses the long-known non-monophyly of the traditionally recog... [more]

© International Association for Plant Taxonomy (IAPT) 2017. The classification of the legume family proposed here addresses the long-known non-monophyly of the traditionally recognised subfamily Caesalpinioideae, by recognising six robustly supported monophyletic subfamilies. This new classification uses as its framework the most comprehensive phylogenetic analyses of legumes to date, based on plastid matK gene sequences, and including near-complete sampling of genera (698 of the currently recognised 765 genera) and ca. 20% (3696) of known species. The matK gene region has been the most widely sequenced across the legumes, and in most legume lineages, this gene region is sufficiently variable to yield well-supported clades. This analysis resolves the same major clades as in other phylogenies of whole plastid and nuclear gene sets (with much sparser taxon sampling). Our analysis improves upon previous studies that have used large phylogenies of the Leguminosae for addressing evolutionary questions, because it maximises generic sampling and provides a phylogenetic tree that is based on a fully curated set of sequences that are vouchered and taxonomically validated. The phylogenetic trees obtained and the underlying data are available to browse and download, facilitating subsequent analyses that require evolutionary trees. Here we propose a new community-endorsed classification of the family that reflects the phylogenetic structure that is consistently resolved and recognises six subfamilies in Leguminosae: a recircumscribed Caesalpinioideae DC., Cercidoideae Legume Phylogeny Working Group (stat. nov.), Detarioideae Burmeist., Dialioideae Legume Phylogeny Working Group (stat. nov.), Duparquetioideae Legume Phylogeny Working Group (stat. nov.), and Papilionoideae DC. The traditionally recognised subfamily Mimosoideae is a distinct clade nested within the recircumscribed Caesalpinioideae and is referred to informally as the mimosoid clade pending a forthcoming formal tribal and/or cladebased classification of the new Caesalpinioideae. We provide a key for subfamily identification, descriptions with diagnostic charactertistics for the subfamilies, figures illustrating their floral and fruit diversity, and lists of genera by subfamily. This new classification of Leguminosae represents a consensus view of the international legume systematics community; it invokes both compromise and practicality of use.

DOI 10.12705/661.3
Citations Scopus - 78
2017 Ally A, Balasundaram M, Carlsen R, Chuah E, Clarke A, Dhalla N, et al., 'Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma', Cell, 169 1327-1341.e23 (2017)

© 2017 Elsevier Inc. Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases ... [more]

© 2017 Elsevier Inc. Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

DOI 10.1016/j.cell.2017.05.046
Citations Scopus - 71
2017 Abeshouse A, Adebamowo C, Adebamowo SN, Akbani R, Akeredolu T, Ally A, et al., 'Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas', Cell, 171 950-965.e28 (2017)

© 2017 The Authors Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 ad... [more]

© 2017 The Authors Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types. Genetic analysis of soft tissue sarcomas shows that they are characterized predominantly by copy-number changes and offers insights into the immune microenviroment to inform clinical trials of checkpoint inhibitors.

DOI 10.1016/j.cell.2017.10.014
Citations Scopus - 18
2017 Aabakken L, Karlsen TH, Albert J, Arvanitakis M, Chazouilleres O, Dumonceau JM, et al., 'Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline', Journal of Hepatology, 66 1265-1281 (2017)

© 2017 European Association for the Study of the Liver, Georg Thieme Verlag KG Stuttgart - New York This guideline is an official statement of the European Society of Gastrointest... [more]

© 2017 European Association for the Study of the Liver, Georg Thieme Verlag KG Stuttgart - New York This guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE) and of the European Association for the Study of the Liver (EASL) on the role of endoscopy in primary sclerosing cholangitis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1. ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic resonance cholangiography (MRC) should be preferred over endoscopic retrograde cholangiopancreatography (ERCP). Moderate quality evidence, strong recommendation. 2. ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is equivocal or contraindicated in patients with persisting clinical suspicion of PSC. The risks of ERCP have to be weighed against the potential benefit with regard to surveillance and treatment recommendations. Low quality evidence, weak recommendation. 6. ESGE/EASL suggest that, in patients with an established diagnosis of PSC, MRC should be considered before therapeutic ERCP. Weak recommendation, low quality evidence. 7. ESGE/EASL suggest performing endoscopic treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies) of suspected significant strictures identified at MRC in PSC patients who present with symptoms likely to improve following endoscopic treatment. Strong recommendation, low quality evidence. 9. ESGE/EASL recommend weighing the anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a case-by-case basis. Strong recommendation, moderate quality evidence. Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation. Strong recommendation, low quality evidence. Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation. Strong recommendation, low quality evidence. 16. ESGE/EASL suggest routine administration of prophylactic antibiotics before ERCP in patients with PSC. Strong recommendation, low quality evidence. 17. EASL/ESGE recommend that cholangiocarcinoma (CCA) should be suspected in any patient with worsening cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant stricture, particularly with an associated enhancing mass lesion. Strong recommendation, moderate quality evidence. 19. ESGE/EASL recommend ductal sampling (brush cytology, endobiliary biopsies) as part of the initial investigation for the diagnosis and staging of suspected CCA in patients with PSC. Strong recommendation, high quality evidence.

DOI 10.1016/j.jhep.2017.02.013
Citations Scopus - 8
2017 Elvira Perales A, Espinosa Díaz A, 'Activity of the constitutional court: List of rulings handed down during the first four-month period of 2017', Revista Espanola de Derecho Constitucional, 110 187-208 (2017)
DOI 10.18042/cepc/redc.110.07
2017 Lainï F, Ruivard M, Loustaud-Ratti V, Bonnet F, Calï s P, Bardou-Jacquet E, et al., 'Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients', Hepatology, 65 465-474 (2017)

� 2016 by the American Association for the Study of Liver Diseases. Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinemia, accounting for a mild incr... [more]

� 2016 by the American Association for the Study of Liver Diseases. Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinemia, accounting for a mild increase of iron stores in insulin-resistant subjects. Iron removal could improve insulin sensitivity. We performed a prospective, randomized, controlled trial (NCT01015525) in nondiabetic DIOS patients with hepatic iron >50 µmol/g at magnetic resonance imaging to compare the metabolic and hepatic outcomes of 1-year maintenance of serum ferritin levels <50 µg/L by bloodletting associated with lifestyle and diet advice (LFDA) to those of LFDA only. Patients were randomly assigned (1:1) with stratification by center (n = 8) and hyperglycemia (>5.6 mmol/L). Sample size was calculated to provide 90% power and a difference in fasting glycemia of 0.25 mmol/L. Analysis was done in an intention-to-treat population. In 2010-2014, 146 patients were randomly assigned to receive venesections with LFDA and 128 to LFDA only. At the end of the study, comparison of iron-depleted patients and controls showed ferritin levels 71 � 48 µg/L after removal of 4.9 � 1.6 L of blood versus 733 � 277 µg/L (P < 0.0001), glycemia 5.44 � 0.7 versus 5.49 � 0.7 mmol/L (P = 0.57), body weight +0.5 � 4.3% versus -0.6 � 3.3% (P = 0.03), homeostasis model of assessment of insulin resistance 3.39 versus 2.40 (P = 0.002), alanine aminotransaminase 33 � 22 versus 37 � 21 IU/L (P = 0.10), aspartate aminotransaminase 27 � 13 versus 27 � 10 IU/L (P = 0.81), gamma-glutamyl transferase 54 � 138 versus 49 � 35 IU/L (P = 0.72), Fatty Liver Index 58.9 � 24.6 versus 61.2 � 22.9 (P = 0.37), and Fibrosis-4 score 1.5 � 0.6 versus 1.30 � 0.6 (P = 0.51). Fatigue occurred in 25.3% of venesected patients versus 2.3% of controls (P < 0.0001). In the subgroup of patients who lost weight, glycemia, homeostasis model of assessment of insulin resistance, serum ferritin, lipid profile, and liver function tests improved irrespective of bloodletting. Conclusion: In DIOS patients, iron depletion by bloodletting does not improve metabolic and hepatic features, is associated with weight gain, and is not as well tolerated as expected; sustained modification of diet and lifestyle habits remains the first therapeutic intervention in DIOS. (Hepatology 2017;65:465-474).

DOI 10.1002/hep.28856
Citations Scopus - 6
2017 Sandoval A, Cofré F, Delpiano L, Izquierdo G, Labraña Y, Reyes A, et al., 'Neonatal infection and universal screening for Streptococcus agalactiae (group B ß-hemolytic Streptococcus) in the pregnant woman. Technical recommendation', Revista Chilena de Infectologia, 34 259-262 (2017)
DOI 10.4067/S0716-10182017000300009
2017 Zaccone V, Tosoni A, Passaro G, Vallone CV, Impagnatiello M, Li Puma DD, et al., 'Sepsis in Internal Medicine wards: current knowledge, uncertainties and new approaches for management optimization', Annals of Medicine, 49 582-592 (2017)

© 2017 Informa UK Limited, trading as Taylor &amp; Francis Group. Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although... [more]

© 2017 Informa UK Limited, trading as Taylor & Francis Group. Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists¿ increased adherence to guidelines and ¿bundles¿. The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment.Key Messages Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease. At least half of patients affected by sepsis are admitted to Internal Medicine wards. Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization.

DOI 10.1080/07853890.2017.1332776
Citations Scopus - 1
2017 Fonseca C, Brito D, Cernadas R, Ferreira J, Franco F, Rodrigues T, et al., 'For the improvement of Heart Failure treatment in Portugal - Consensus statement', Revista Portuguesa de Cardiologia, 36 1-8 (2017)

© 2016 Sociedade Portuguesa de Cardiologia Heart failure is a syndrome with high prevalence, morbidity and mortality, but awareness of the disease is poor among the general public... [more]

© 2016 Sociedade Portuguesa de Cardiologia Heart failure is a syndrome with high prevalence, morbidity and mortality, but awareness of the disease is poor among the general public and policy makers. This document, which was prepared by a group of experts consisting of cardiologists, internists and general practitioners, aims to set out in detail the problem of heart failure in Portugal at several levels: burden of the disease, diagnosis, treatment and monitoring. To this aim, different aspects of the management of the various stages of the disease are identified and discussed in detail, covering both outpatients and hospitalized patients. In order to optimize the medical care provided to these patients, various short-, medium- and long-term solutions and strategies are put forward that have the potential to improve the integration and use of available resources. The intention is to highlight strategies that are not based on a single model but can be adapted to different regional circumstances, in order to increase awareness and improve management of heart failure in Portugal.

DOI 10.1016/j.repc.2016.10.006
Citations Scopus - 1
2017 Li E, Xu L, Guo W, Chen K, Lyu B, Shen Y, Hu L, 'Understanding the destabilization of a resistive drift mode in EAST core plasmas', Physics of Plasmas, 24 (2017)

© 2017 Author(s). A low-frequency oscillation driven by heavy impurities is frequently observed in the Experimental Advanced Superconducting Tokamak (EAST) H-mode discharges accom... [more]

© 2017 Author(s). A low-frequency oscillation driven by heavy impurities is frequently observed in the Experimental Advanced Superconducting Tokamak (EAST) H-mode discharges accompanied by an Edge Localized Mode-free duration. This instability has been identified as a resistive drift mode according to a two-fluid simulation, showing that the mode stability is determined by the gradient of resistivity profile. Furthermore, the analytic theory also demonstrates that the mode is destabilized by the sharp impurity density gradient agreeing to the observation of intrinsic Mo (Molybdenum) concentration. The destabilization conditions have been derived like LN,z<23LT,z ( LN,z and LT,z are the scale lengths of density and temperature of impurity, respectively). Calculations based on the analytical theory reproduce the characteristic of the mode, which is in agreement with the experimental observations.

DOI 10.1063/1.4976136
Citations Scopus - 1
2017 Laggner FM, Wolfrum E, Cavedon M, Mink F, Bernert M, Dunne MG, et al., 'Pedestal structure and inter-ELM evolution for different main ion species in ASDEX Upgrade', Physics of Plasmas, 24 (2017)

© 2017 EURATOM. In tokamak plasmas with different main ion species, a change in confinement occurs, known as the isotope effect. Experiments comparing hydrogen (H), deuterium (D),... [more]

© 2017 EURATOM. In tokamak plasmas with different main ion species, a change in confinement occurs, known as the isotope effect. Experiments comparing hydrogen (H), deuterium (D), and helium (4He) plasmas have been performed to identify processes that define the pedestal structure and evolution in between the crashes of edge localized modes (ELMs). The pedestal top electron densities and temperatures have been matched to compare the pedestal shape and stability. In the D and H discharges, the pedestal electron temperature profiles do not differ, whereas the density profile in H has shallower gradients. Furthermore, the heat flux across the pedestal in H is roughly a factor of two higher than in D. In4He plasmas at similar stored energy, the pedestal top electron density is roughly a factor of 1.5 larger than in the references owing to the larger effective charge. The peeling-ballooning theory, which is independent of the main ion species mass, can sufficiently describe the pedestal stability in the hydrogenic plasmas. The inter-ELM pedestal evolution has the same sequence of recovery phases for all investigated species, giving evidence that similar mechanisms are acting in the pedestals. This is further supported by a similar evolution of the inter-ELM magnetic signature and the corresponding toroidal structure.

DOI 10.1063/1.4977461
2017 Whittaker R, Economopoulou A, Dias JG, Bancroft E, Ramliden M, Celentano LP, et al., 'Epidemiology of invasive Haemophilus influenzae disease, Europe, 2007¿2014', Emerging Infectious Diseases, 23 396-404 (2017)

© 2017, Centers for Disease Control and Prevention (CDC). All rights reserved. We describe the epidemiology of invasive Haemophilus influenzae disease during 2007-2014 in 12 Europ... [more]

© 2017, Centers for Disease Control and Prevention (CDC). All rights reserved. We describe the epidemiology of invasive Haemophilus influenzae disease during 2007-2014 in 12 European countries and assess overall H. influenzae disease trends by serotype and patient age. Mean annual notification rate was 0.6 cases/100,000 population, with an increasing annual trend of 3.3% (95% CI 2.3% to 4.3%). The notification rate was highest for patients <1 month of age (23.4 cases/100,000 population). Nontypeable H. influenzae (NTHi) caused 78% of all cases and showed increasing trends among persons <1 month and =20 years of age. Serotype f cases showed an increasing trend among persons =60 years of age. Serotype b cases showed decreasing trends among persons 1-5 months, 1-4 years, and =40 years of age. Sustained success of routine H. influenzae serotype b vaccination is evident. Surveillance systems must adopt a broad focus for invasive H. influenzae disease. Increasing reports of NTHi, particularly among neonates, highlight the potential benefit of a vaccine against NTHi.

DOI 10.3201/eid2303.161552
Citations Scopus - 11
2017 Ponti M, Bélanger S, Grimes R, Heard J, Johnson M, Moreau E, et al., 'Screen time and young children: Promoting health and development in a digital world', Paediatrics and Child Health (Canada), 22 461-477 (2017)

© Canadian Paediatric Society 2017. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. The digital landscape is evolving more ... [more]

© Canadian Paediatric Society 2017. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. The digital landscape is evolving more quickly than research on the effects of screen media on the development, learning and family life of young children. This statement examines the potential benefits and risks of screen media in children younger than 5 years, focusing on developmental, psychosocial and physical health. Evidence-based guidance to optimize and support children's early media experiences involves four principles: minimizing, mitigating, mindfully using and modelling healthy use of screens. Knowing how young children learn and develop informs best practice strategies for health care providers.

DOI 10.1093/pch/pxx123
Citations Scopus - 1
2017 Moriyasu F, Furuichi Y, Tanaka A, Takikawa H, Yoshida H, Sakaida I, et al., 'Diagnosis and treatment guidelines for aberrant portal hemodynamics: The Aberrant Portal Hemodynamics Study Group supported by the Ministry of Health, Labor and Welfare of Japan', Hepatology Research, 47 373-386 (2017)

© 2017 The Japan Society of Hepatology Idiopathic portal hypertension (IPH), causing aberrant portal hemodynamics, is a disease with an as yet unidentified cause and no establishe... [more]

© 2017 The Japan Society of Hepatology Idiopathic portal hypertension (IPH), causing aberrant portal hemodynamics, is a disease with an as yet unidentified cause and no established treatment protocol. The Japanese research group on IPH in Japan was set up in 1975 by the Ministry of Health, Labor and Welfare. Extrahepatic portal obstruction and Budd¿Chiari syndrome (BCS) have since been added to the group's research subjects. The aims of the research group are to accurately evaluate the current status of the three diseases in Japan, elucidate their etiology and pathogenesis, and develop new treatments. Due to the long-term efforts of the Japanese research group, aberrant portal hemodynamics has been investigated in a variety of aspects, from epidemiological and pathological studies to molecular biology analyses. As a result, it has been shown that there are abnormal genes in the liver, specific for IPH. In addition, pathological findings of BCS were internationally compared and the difference in findings between Japan and Europe (or North America) has been clarified. Furthermore, it was found that complication rates of hepatocellular carcinoma in BCS were higher in Japan. Based on the research, ¿Diagnosis and treatment of aberrant portal hemodynamics (2001)¿, including diagnostic criteria for aberrant portal hemodynamics, was published in 2001. In 2013, it was revised to ¿Diagnosis and treatment guidelines for aberrant portal hemodynamics (2013)¿ after the incorporation of diagnosis and treatment in accordance with its current status.

DOI 10.1111/hepr.12862
2017 Alberico S, Erenbourg A, Hod M, Yogev Y, Hadar E, Neri F, et al., 'mmediate delivery or expectant management in gestational diabetes at term: the GINEXMAL randomised controlled trial', BJOG: An International Journal of Obstetrics and Gynaecology, 124 669-677 (2017)

© 2016 Royal College of Obstetricians and Gynaecologists Objective: To evaluate maternal and perinatal outcomes after induction of labour versus expectant management in pregnant w... [more]

© 2016 Royal College of Obstetricians and Gynaecologists Objective: To evaluate maternal and perinatal outcomes after induction of labour versus expectant management in pregnant women with gestational diabetes at term. Design: Multicentre open-label randomised controlled trial. Setting: Eight teaching hospitals in Italy, Slovenia, and Israel. Sample: Singleton pregnancy, diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria (IADPSGC), between 38+0and 39+0weeks of gestation, without other maternal or fetal conditions. Methods: Patients were randomly assigned to induction of labour or expectant management and intensive follow-up. Data were analysed by ¿intention to treat¿. Main outcome measures: The primary outcome was incidence of caesarean section. Secondary outcomes were maternal and perinatal mortality and morbidity. Results: A total of 425 women were randomised to the study groups. The incidence of caesarean section was 12.6% in the induction group versus 11.7% in the expectant group. No difference was found between the two groups (relative risk, RR 1.06; 95% confidence interval, 95% CI 0.64¿1.77; P = 0.81). The incidence of non-spontaneous delivery, either by caesarean section or by operative vaginal delivery, was 21.0 and 22.3%, respectively (RR 0.94; 95% CI 0.66¿1.36; P = 0.76). Neither maternal nor fetal deaths occurred. The few cases of shoulder dystocia were solved without any significant birth trauma. Conclusions: In women with gestational diabetes, without other maternal or fetal conditions, no difference was detected in birth outcomes regardless of the approach used (i.e. active versus expectant management). Although the study was underpowered, the magnitude of the between-group difference was very small and without clinical relevance. Tweetable abstract: Immediate delivery or expectant management in gestational diabetes at term?.

DOI 10.1111/1471-0528.14389
Citations Scopus - 7
2017 Bennett M, Castanelli D, Gawthrope I, Hawkins G, Jenkins S, Mitchell S, et al., 'Launch of the ANZCA diploma of advanced diving and hyperbaric medicine', Diving and Hyperbaric Medicine, 47 135 (2017)
2017 Vera-Mendoza I, Domènech E, Taxonera C, Ruiz VV, Marín-Jiménez I, Guardiola J, et al., 'Adalimumab vs azathioprine in the prevention of postoperative Crohn's disease recurrence. A GETECCU randomised trial', Journal of Crohn's and Colitis, 11 1293-1301 (2017)

© 2017 European Crohn¿s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. Background and Aims: Postoperative recurrence of Crohn&apos;s d... [more]

© 2017 European Crohn¿s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. Background and Aims: Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. Methods: We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. Results: We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. Conclusions: ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better.

DOI 10.1093/ecco-jcc/jjx051
Citations Scopus - 4
2017 Parrón I, Planas C, Godoy P, Manzanares-Laya S, Martínez A, Sala MR, et al., 'Effectiveness of hepatitis A vaccination as post-exposure prophylaxis', Human Vaccines and Immunotherapeutics, 13 423-427 (2017)

© 2017 Taylor &amp; Francis. Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadole... [more]

© 2017 Taylor & Francis. Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2¿98.6) for HAV vaccine and 98.3% (95% CI 91.3¿99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.

DOI 10.1080/21645515.2017.1264798
2017 Wyszynski G, Bodek K, Afach S, Bison G, Chowdhuri Z, Daum M, et al., 'Active compensation of magnetic field distortions based on vector spherical harmonics field description', AIP Advances, 7 (2017)

© 2017 Author(s). An analytic solution to the magnetostatic inverse problem in the framework of vector spherical harmonic basis functions is presented. This formalism is used for ... [more]

© 2017 Author(s). An analytic solution to the magnetostatic inverse problem in the framework of vector spherical harmonic basis functions is presented. This formalism is used for the design of a spherical magnetic field compensation system and its performance is compared with an already existing rectangular coil system. The proposed set of spherical coils with 15 degrees of freedom achieves a shielding factor of 1000 or better in a large part of the volume enclosed by the coils for a dipolar type external perturbation.

DOI 10.1063/1.4978394
2017 Kosek MN, Ahmed T, Bhutta Z, Caulfield L, Guerrant R, Houpt E, et al., 'Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study', EBioMedicine, 18 109-117 (2017)

© 2017 The Authors Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune a... [more]

© 2017 The Authors Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N¿=¿22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N¿=¿6363) and plasma alpha-1-acid glycoprotein (AGP) (N¿=¿2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0¿2¿years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Funding Bill & Melinda Gates Foundation.

DOI 10.1016/j.ebiom.2017.02.024
Citations Scopus - 18
2017 Streinu-Cercel A, Streinu-Cercel A, Sandulescu O, Ancu¿a I, Arama V, Arbune M, et al., 'Consensus statement on the management of patients with HCV infection in Romania', GERMS, 7 32-39 (2017)

© GERMS 2017. Background HCV direct-acting antivirals (DAAs) have made treatment easier for both patients and healthcare practitioners, but have also brought new challenges in ter... [more]

© GERMS 2017. Background HCV direct-acting antivirals (DAAs) have made treatment easier for both patients and healthcare practitioners, but have also brought new challenges in terms of patient management and monitoring prior to, during, and after treatment. Methods To sum up and unify the clinical experience of Romanian DAA prescribing physicians, we have organized a Consensus Meeting in November 2016 in Bucharest, Romania. Consensus Statement The Consensus Meeting has provided expert answers to ten significant questions regarding HCV infection, namely: How do we diagnose patients with HCV infection? How do we stage liver disease in patients with HCV infection? How do we monitor patients with HCV infection prior to treatment? Which patients with HCV infection do we treat? When do we start treatment for HCV infection? What regimens do we use for treating HCV infection? How do we monitor patients with HCV infection during treatment? What adverse events should we expect during treatment of HCV infection and how do we prevent/manage them? How do we monitor patients with HCV infection after treatment? How do we expect the landscape of HCV to change in the following years?.

DOI 10.11599/germs.2017.1106
Citations Scopus - 1
2017 Maltby VE, Lea RA, Sanders KA, White N, Benton MC, Scott RJ, Lechner-Scott J, 'Differential methylation at MHC in CD4

© The Author(s). Background: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains unce... [more]

© The Author(s). Background: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4+T cells. This study aimed to confirm this earlier finding in an independent RRMS cohort of treatment-naive female patients. Methods: Total genomic DNA was extracted from CD4+T cells of 28 female RRMS and 22 age-matched healthy controls subjects. DNA was bisulfite-converted and hybridised to Illumina 450K arrays. Beta values for all CpGs were analysed using the DMPFinder function in the MINFI program, and a follow-up prioritisation process was applied to identify the most robust MS-associated DMRs. Results: This study confirmed our previous findings of a hypomethylated DMR at HLA-DRB1 and a hypermethylated DMR at HLA-DRB5 in this RRMS patient cohort. In addition, we identified a large independent DMR at MHC, whereby 11 CpGs in RNF39 were hypermethylated in MS cases compared to controls (max. ¿beta = 0.19, P = 2.1 × 10-4). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. Conclusions: The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.

DOI 10.1186/s13148-017-0371-1
Citations Scopus - 1Web of Science - 1
Co-authors Vicki E Maltby, Jeannette Lechner-Scott
2017 Schmiegel W, Scott RJ, Dooley S, Lewis W, Meldrum CJ, Pockney P, et al., 'Blood-based detection of RAS mutations to guide anti-EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue-based RAS testing', MOLECULAR ONCOLOGY, 11 208-219 (2017) [C1]
DOI 10.1002/1878-0261.12023
Citations Scopus - 13Web of Science - 12
Co-authors Peter Pockney
2017 de Vries PS, Sabater-Lleal M, Chasman DI, Trompet S, Ahluwalia TS, Teumer A, et al., 'Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study', PLOS ONE, 12 (2017) [C1]
DOI 10.1371/journal.pone.0167742
Citations Scopus - 3Web of Science - 2
Co-authors Mark Mcevoy, Christopher Oldmeadow, John Attia, Liz Holliday
2017 Marshall CR, Howrigan DP, Merico D, Thiruvahindrapuram B, Wu W, Greer DS, et al., 'Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects', Nature Genetics, 49 27-35 (2017) [C1]
DOI 10.1038/ng.3725
Citations Scopus - 81Web of Science - 73
Co-authors Brian Kelly, Frans Henskens, Ulrich Schall, Paul Tooney, Carmel Loughland, Pat Michie, Murray Cairns
2017 Naudin C, Smith B, Bond DR, Dun MD, Scott RJ, Ashman LK, et al., 'Characterization of the early molecular changes in the glomeruli of Cd151 -/- mice highlights induction of mindin and MMP-10.', Scientific Reports, 7 15987-15987 (2017) [C1]
DOI 10.1038/s41598-017-15993-3
Co-authors Danielle Bond, Leonie Ashman, Judith Weidenhofer, Matt Dun
2017 Smith-Anttila CJA, Bensing S, Alimohammadi M, Dalin F, Oscarson M, Zhang MD, et al., 'Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1', Autoimmunity, 50 223-231 (2017) [C1]

© 2017 Informa UK Limited, trading as Taylor &amp; Francis Group. Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in ... [more]

© 2017 Informa UK Limited, trading as Taylor & Francis Group. Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.

DOI 10.1080/08916934.2017.1332183
2017 Avery-Kiejda KA, Mathe A, Scott RJ, 'Genome-wide miRNA, gene and methylation analysis of triple negative breast cancer to identify changes associated with lymph node metastases', GENOMICS DATA, 14 1-4 (2017)
DOI 10.1016/j.gdata.2017.07.004
Citations Scopus - 1Web of Science - 1
Co-authors Kelly Kiejda, Andrea Mathe
2017 Biswas M, Dias TH, Daneshi N, Holliday E, Hancock S, Attia J, et al., 'Potential simple and multifactorial drug-gene interactions of tricyclic antidepressantsin older Australians', GSTF Journal of Advances in Medical Research, 2 (2017) [C1]
DOI 10.5176/2345-7201_40
Co-authors John Attia, David Newby, Liz Holliday, Liz Milward, Karen Kerr
2017 Wain LV, Vaez A, Jansen R, Joehanes R, Van Der Most PJ, Erzurumluoglu AM, et al., 'Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney', Hypertension, 70 e4-e19 (2017) [C1]

© 2017 American Heart Association, Inc. Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation inf... [more]

© 2017 American Heart Association, Inc. Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

DOI 10.1161/HYPERTENSIONAHA.117.09438
Citations Scopus - 12Web of Science - 11
Co-authors Christopher Oldmeadow, John Attia, Liz Holliday
2017 Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, et al., 'Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk', Nature Genetics, 49 403-415 (2017) [C1]

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pres... [more]

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

DOI 10.1038/ng.3768
Citations Scopus - 59Web of Science - 57
Co-authors Liz Holliday, John Attia, Christopher Oldmeadow
2017 Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al., 'Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer', Nature Genetics, 49 1767-1778 (2017) [C1]

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We... [more]

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

DOI 10.1038/ng.3785
Citations Scopus - 15Web of Science - 18
2017 Delforce SJ, Lumbers ER, de Meaultsart CC, Wang Y, Proietto A, Otton G, et al., 'Expression of renin-angiotensin system (RAS) components in endometrial cancer', ENDOCRINE CONNECTIONS, 6 9-19 (2017) [C1]
DOI 10.1530/EC-16-0082
Citations Scopus - 2Web of Science - 2
Co-authors E Lumbers, Kirsty Pringle, Nikki Verrills
2017 McLaughlin RL, Schijven D, Van Rheenen W, Van Eijk KR, O'Brien M, Kahn RS, et al., 'Genetic correlation between amyotrophic lateral sclerosis and schizophrenia', Nature Communications, 8 (2017) [C1]
DOI 10.1038/ncomms14774
Citations Scopus - 10
Co-authors Pat Michie, Ulrich Schall, Carmel Loughland, Frans Henskens
2017 Fazekas-Lavu M, Parker A, Spigelman AD, Scott RJ, Epstein RJ, Jensen M, Samaras K, 'Thyroid cancer in a patient with Lynch syndrome - case report and literature review', THERAPEUTICS AND CLINICAL RISK MANAGEMENT, 13 915-918 (2017) [C1]
DOI 10.2147/TCRM.S121812
2017 Dymerska D, Golebiewska K, Kuswik M, Rudnicka H, Scott RJ, Billings R, et al., 'New EPCAM founder deletion in Polish population', Clinical Genetics, 92 649-653 (2017) [C1]
DOI 10.1111/cge.13026
Citations Scopus - 2Web of Science - 2
2017 Abdullah N, Abdul Murad NA, Mohd Haniff EA, Syafruddin SE, Attia J, Oldmeadow C, et al., 'Predicting type 2 diabetes using genetic and environmental risk factors in a multi-ethnic Malaysian cohort', Public Health, 149 31-38 (2017) [C1]

© 2017 The Royal Society for Public Health Objective Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the dis... [more]

© 2017 The Royal Society for Public Health Objective Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene¿environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene¿environment interactions that may explain additional risk variation. Study design This was a case¿control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project. Methods The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R2and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. Results The models including environmental risk factors only had pseudo R2values of 16.5¿28.3% and AUC of 0.75¿0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10-4¿4.83 × 10-12) and increased the pseudo R2by about 1¿2% and AUC by 1¿3%. None of the gene¿environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 < P < 0.05. Conclusion This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene¿environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.

DOI 10.1016/j.puhe.2017.04.003
Co-authors John Attia, Liz Holliday, Christopher Oldmeadow
2017 Michailidou K, Lindström S, Dennis J, Beesley J, Hui S, Kar S, et al., 'Association analysis identifies 65 new breast cancer risk loci', Nature, 551 92-94 (2017) [C1]

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1,... [more]

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

DOI 10.1038/nature24284
Citations Scopus - 33Web of Science - 36
Co-authors John Forbes
2017 Berry NK, Dixon-McIver A, Scott RJ, Rowlings P, Enjeti AK, 'Detection of complex genomic signatures associated with risk in plasma cell disorders.', Cancer genetics, 218-219 1-9 (2017) [C1]
DOI 10.1016/j.cancergen.2017.08.004
Co-authors Anoop Enjeti
2017 Mahurkar S, Moldovan M, Suppiah V, Sorosina M, Clarelli F, Liberatore G, et al., 'Response to interferon-beta treatment in multiple sclerosis patients: A genome-wide association study', Pharmacogenomics Journal, 17 312-318 (2017) [C1]

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-ß) treatmen... [more]

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-ß) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-ß treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-ß-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 106) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10 5) and near ZNF697 (combined P-value 8.15 × 10 5).

DOI 10.1038/tpj.2016.20
Citations Scopus - 4Web of Science - 1
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2016 Kamien B, Dadd T, Buckman M, Ronan A, Dudding T, Meldrum C, et al., 'Somatic-Gonadal Mosaicism Causing Sotos Syndrome', AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 170 3360-3362 (2016)
DOI 10.1002/ajmg.a.37867
Co-authors T Dudding
2016 Chen MM, O'Mara TA, Thompson DJ, Painter JN, Attia J, Black A, et al., 'GWAS meta-analysis of 16 852 women identifies new susceptibility locus for endometrial cancer', HUMAN MOLECULAR GENETICS, 25 2612-2620 (2016) [C1]
DOI 10.1093/hmg/ddw092
Citations Web of Science - 4
Co-authors John Attia, Liz Holliday, Mark Mcevoy
2016 Painter JN, O'Mara TA, Marquart L, Webb PM, Attia J, Medland SE, et al., 'Genetic risk score mendelian randomization shows that obesity measured as body mass index, but not waist:hip ratio, is causal for endometrial cancer', Cancer Epidemiology Biomarkers and Prevention, 25 1503-1510 (2016) [C1]

Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) a... [more]

Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Methods: Logistic regression analysis and fixed effects metaanalysis were used to test for associations between endometrial cancer risk and (i) individual BMI orWHRSNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. Results: The BMIwGRS was significantly associated with endometrial cancer risk (P -= 3.4 × 10-17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR-=1.55; 95% CI, 1.44-1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR -= 1.22; 95% CI, 1.10-1.39; P -= 5.3 × 10-4). There was evidence of directional pleiotropy (P -= 1.5 × 10-4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10-4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. Conclusions: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. Impact: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling.

DOI 10.1158/1055-9965.EPI-16-0147
Citations Scopus - 6Web of Science - 7
Co-authors John Attia, Liz Holliday, Mark Mcevoy
2016 Okbay A, Baselmans BML, De Neve JE, Turley P, Nivard MG, Fontana MA, et al., 'Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses', Nature Genetics, 48 624-633 (2016) [C1]

© 2016 Nature America, Inc. Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subje... [more]

© 2016 Nature America, Inc. Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (P = 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

DOI 10.1038/ng.3552
Citations Scopus - 131Web of Science - 119
Co-authors Christopher Oldmeadow, John Attia, Liz Holliday
2016 Cheng THT, Thompson DJ, O'Mara TA, Painter JN, Glubb DM, Flach S, et al., 'Five endometrial cancer risk loci identified through genome-wide association analysis', Nature Genetics, 48 667-674 (2016) [C1]

© 2016 Nature America, Inc. We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial can... [more]

© 2016 Nature America, Inc. We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r 2 = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.

DOI 10.1038/ng.3562
Citations Scopus - 18Web of Science - 17
Co-authors John Attia, Mark Mcevoy, Liz Holliday
2016 Lener MR, Scott RJ, Kluzniak W, Baszuk P, Cybulski C, Wiechowska-Kozlowska A, et al., 'Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?', International Journal of Cancer, 139 601-606 (2016) [C1]

© 2016 UICC. Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in f... [more]

© 2016 UICC. Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among PaCa patients and assessed their possible association with the risk of disease in Poland. In the study 383 PaCa patients and 4,000 control subjects were genotyped for founder mutations in: BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1 (657del5) and PALB2 (509-510delGA, 172-175delTTGT). A statistically significant association between the 657del5 mutation and an increased risk of pancreatic cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA) was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000 (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509-510delGA and 172-175delTTGT mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8 (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000 (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1 (657del5) was associated with an increased risk of PaCa in heterozygous carriers, indicating that this mutation appears to predispose to cancer of the pancreas. By identifying pancreatic cancer risk groups, founder mutation testing in Poland should be considered for people at risk for PaCa.

DOI 10.1002/ijc.30116
Citations Scopus - 3Web of Science - 2
2016 Purrington KS, Visscher DW, Wang C, Yannoukakos D, Hamann U, Nevanlinna H, et al., 'Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes', Breast Cancer Research and Treatment, 157 117-131 (2016) [C1]

© 2016, Springer Science+Business Media New York. Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is kn... [more]

© 2016, Springer Science+Business Media New York. Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is known about the relationship between histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. The histopathologic features of TN tumors were assessed by central review and 593 TN tumors were subjected to whole genome expression profiling using the Illumina Whole Genome DASL array. TN molecular subtypes were defined based on gene expression data associated with histopathologic features of TN tumors. Gene expression analysis yielded signatures for four TN subtypes (basal-like, androgen receptor positive, immune, and stromal) consistent with previous studies. Expression analysis also identified genes significantly associated with the 12 histological features of TN tumors. Development of signatures using these markers of histopathological features resulted in six distinct TN subtype signatures, including an additional basal-like and stromal signature. The additional basal-like subtype was distinguished by elevated expression of cell motility and glucose metabolism genes and reduced expression of immune signaling genes, whereas the additional stromal subtype was distinguished by elevated expression of immunomodulatory pathway genes. Histopathologic features that reflect heterogeneity in tumor architecture, cell structure, and tumor microenvironment are related to TN subtype. Accounting for histopathologic features in the development of gene expression signatures, six major subtypes of TN breast cancer were identified.

DOI 10.1007/s10549-016-3775-2
Citations Scopus - 6Web of Science - 4
2016 Hungate EA, Vora SR, Gamazon ER, Moriyama T, Best T, Hulur I, et al., 'A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology.', Nature communications, 7 10635 (2016) [C1]
DOI 10.1038/ncomms10635
Citations Scopus - 12Web of Science - 11
2016 Johnson EC, Bjelland DW, Howrigan DP, Abdellaoui A, Breen G, Borglum A, et al., 'No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study', PLOS Genetics, 12 e1006343-e1006343 (2016) [C1]
DOI 10.1371/journal.pgen.1006343
Citations Scopus - 4
Co-authors Frans Henskens, Ulrich Schall, Carmel Loughland, Pat Michie
2016 De Vries PS, Chasman DI, Sabater-Lleal M, Chen MH, Huffman JE, Steri M, et al., 'A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration', Human Molecular Genetics, 25 358-370 (2016) [C1]

© The Author 2015. Published by Oxford University Press. Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentr... [more]

© The Author 2015. Published by Oxford University Press. Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels.We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ~120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

DOI 10.1093/hmg/ddv454
Citations Scopus - 9Web of Science - 10
Co-authors Mark Mcevoy, Christopher Oldmeadow, John Attia, Liz Holliday
2016 McKenzie R, Scott RJ, Otton G, Scurry J, 'Early changes of endometrial neoplasia revealed by loss of mismatch repair gene protein expression in a patient diagnosed with Lynch syndrome', PATHOLOGY, 48 78-80 (2016)
DOI 10.1016/j.pathol.2015.11.003
2016 Thompson ER, Rowley SM, Li N, McInerny S, Devereux L, Wong-Brown MW, et al., 'Panel testing for familial breast cancer: Calibrating the tension between research and clinical care', Journal of Clinical Oncology, 34 1455-1459 (2016) [C1]

© 2016 by American Society of Clinical Oncology. Purpose Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence sup... [more]

© 2016 by American Society of Clinical Oncology. Purpose Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence supporting the role of many of these genes in breast cancer predisposition, results are often reported to families as the definitive explanation for their family history. We assessed the frequency of mutations in 18 genes included in hereditary breast cancer panels among index cases from families with breast cancer and matched population controls. Patients and Methods Cases (n= 2,000) were predominantly breast cancer-affected women referredto specialized Familial Cancer Centers on the basis of a strong family history of breast cancer and BRCA1 and BRCA2 wild type. Controls (n = 1,997) were cancer-free women from the LifePool study. Sequencing data were filtered for known pathogenic or novel loss-of-function mutations. Results Excluding 19 mutations identified in BRCA1 and BRCA2 among the cases and controls, a total of 78 cases (3.9%) and 33 controls (1.6%) were found to carry potentially actionable mutations. A significant excess of mutations was only observed for PALB2 (26 cases, four controls) and TP53 (five cases, zero controls), whereas no mutations were identified in STK11. Among the remaining genes, loss-of function mutations were rare, with similar frequency between cases and controls. Conclusion The frequency ofmutations in most breast cancer panel genes among individuals selected for possible hereditary breast cancer is low and, in many cases, similar or even lower than that observed among cancer-free population controls. Although multigene panels can significantly aid in cancer risk management and expedite clinical translation of new genes, they equally have the potential to provide clinical misinformation and harm at the individual level if the data are not interpreted cautiously.

DOI 10.1200/JCO.2015.63.7454
Citations Scopus - 46Web of Science - 44
Co-authors Michelle Wong-Brown
2016 Binder MD, Fox AD, Merlo D, Johnson LJ, Giuffrida L, Calvert SE, et al., 'Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status', PLoS Genetics, 12 (2016) [C1]

© 2016 Binder et al. Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by gen... [more]

© 2016 Binder et al. Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients.

DOI 10.1371/journal.pgen.1005853
Citations Scopus - 4
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2016 Sanders KA, Benton MC, Lea RA, Maltby VE, Agland S, Griffin N, et al., 'Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+T cells', CLINICAL EPIGENETICS, 8 (2016) [C1]
DOI 10.1186/s13148-016-0253-y
Citations Scopus - 10Web of Science - 9
Co-authors Jeannette Lechner-Scott, Vicki E Maltby
2016 Lener MR, Scott RJ, Wiechowska-Kozlowska A, Serrano-Fernández P, Baszuk P, Jaworska-Bieniek K, et al., 'Serum concentrations of selenium and copper in patients diagnosed with pancreatic cancer', Cancer Research and Treatment, 48 1056-1064 (2016) [C1]

© 2016 by the Korean Cancer Association. Purpose Understanding of the etiology and pathogenesis of pancreatic cancer (PaCa) is still insufficient. This study evaluated the associa... [more]

© 2016 by the Korean Cancer Association. Purpose Understanding of the etiology and pathogenesis of pancreatic cancer (PaCa) is still insufficient. This study evaluated the associations between concentrations of selenium (Se) and copper (Cu) in the serum of PaCa patients. Materials and Methods The study included 100 PaCa patients and 100 control subjects from the same geographical region in Poland. To determine the average concentration of Se, Cu, and ratio Cu:Se in the Polish population, assay for Se and Cu was performed in 480 healthy individuals. Serum levels of Se and Cu were measured using inductively coupled plasma mass spectrometry. Results In the control group, the average Se level was 76 µg/L and Cu 1,098 µg/L. The average Se level among PaCa patients was 60 µg/L and the mean Cu level was 1,432 µg/L. The threshold point at which any decrease in Se concentration was associated with PaCa was 67.45 µg/L. The threshold point of Cu level above which there was an increase in the prevalence of PaCa was 1,214.58 µg/L. In addition, a positive relationship was observed between increasing survival time and Se plasma level. Conclusion This retrospective study suggests that low levels of Se and high levels of Cu might influence development of PaCa and that higher levels of Se are associated with longer survival in patients with PaCa. The results suggest that determining the level of Se and Cu could be incorporated into a risk stratification scheme for the selection and surveillance control examination to complement existing screening and diagnostic procedures.

DOI 10.4143/crt.2015.282
Citations Scopus - 4Web of Science - 3
2016 Painter JN, Kaufmann S, O'Mara TA, Hillman KM, Sivakumaran H, Darabi H, et al., 'A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding', American Journal of Human Genetics, 98 1159-1169 (2016) [C1]

© 2016 American Society of Human Genetics. A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel gen... [more]

© 2016 American Society of Human Genetics. A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer.

DOI 10.1016/j.ajhg.2016.04.012
Citations Scopus - 3Web of Science - 1
2016 Sjursen W, McPhillips M, Scott RJ, Talseth-Palmer BA, 'Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations.', Molecular genetics & genomic medicine, 4 223-231 (2016) [C1]
DOI 10.1002/mgg3.198
Citations Web of Science - 3
Co-authors Bente Talseth-Palmer
2016 Groen K, Maltby VE, Sanders KA, Scott RJ, Tajouri L, Lechner-Scott J, 'Erythrocytes in multiple sclerosis - forgotten contributors to the pathophysiology?', Multiple Sclerosis Journal¿Experimental, Translational and Clinical, 2 2055217316649981-2055217316649981 (2016) [C1]
DOI 10.1177/2055217316649981
Co-authors Jeannette Lechner-Scott, Vicki E Maltby
2016 Wu JQ, Green MJ, Gardiner EJ, Tooney PA, Scott RJ, Carr VJ, Cairns MJ, 'Altered neural signaling and immune pathways in peripheral blood mononuclear cells of schizophrenia patients with cognitive impairment: A transcriptome analysis', Brain, Behavior, and Immunity, 53 194-206 (2016) [C1]

© 2015 Elsevier Inc. Cognitive deficits are a core feature of schizophrenia and contribute significantly to functional disability. We investigated the molecular pathways associate... [more]

© 2015 Elsevier Inc. Cognitive deficits are a core feature of schizophrenia and contribute significantly to functional disability. We investigated the molecular pathways associated with schizophrenia (SZ; n = 47) cases representing both 'cognitive deficit' (CD; n = 22) and 'cognitively spared' (CS; n = 25) subtypes of schizophrenia (based on latent class analysis of 9 cognitive performance indicators), compared with 49 healthy controls displaying 'normal' cognition. This was accomplished using gene-set analysis of transcriptome data derived from peripheral blood mononuclear cells (PBMCs). We detected 27 significantly altered pathways (19 pathways up-regulated and 8 down-regulated) in the combined SZ group and a further 6 pathways up-regulated in the CS group and 5 altered pathways (4 down-regulated and 1 up-regulated) in the CD group. The transcriptome profiling in SZ and cognitive subtypes were characterized by the up-regulated pathways involved in immune dysfunction (e.g., antigen presentation in SZ), energy metabolism (e.g., oxidative phosphorylation), and down-regulation of the pathways involved in neuronal signaling (e.g., WNT in SZ/CD and ERBB in SZ). When we looked for pathways that differentiated the two cognitive subtypes we found that the WNT signaling was significantly down-regulated (FDR < 0.05) in the CD group in accordance with the combined SZ cohort, whereas it was unaffected in the CS group. This suggested suppression of WNT signaling was a defining feature of cognitive decline in schizophrenia. The WNT pathway plays a role in both the development/function of the central nervous system and peripheral tissues, therefore its alteration in PBMCs may be indicative of an important genomic axis relevant to cognition in the neuropathology of schizophrenia.

DOI 10.1016/j.bbi.2015.12.010
Citations Scopus - 9Web of Science - 7
Co-authors Paul Tooney, Murray Cairns
2016 Walker MM, Keely SJ, Scott RJ, Talley NJ, 'Genetics, Mucosal Inflammation and the Environment in Post-Infectious Chronic Gut Syndromes', The American Journal of Gastroenterology Supplements, 3 46-51 (2016) [C1]
DOI 10.1038/ajgsup.2016.14
Co-authors Nicholas Talley, Marjorie Walker, Simon Keely
2016 Hess JL, Tylee DS, Barve R, de Jong S, Ophoff RA, Kumarasinghe N, et al., 'Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia', Schizophrenia Research, 176 114-124 (2016) [C1]

© 2016 The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue functi... [more]

© 2016 The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia.

DOI 10.1016/j.schres.2016.07.006
Citations Scopus - 10Web of Science - 8
Co-authors Murray Cairns, Brian Kelly, Paul Tooney, Ulrich Schall
2016 Chen MM, O'Mara TA, Thompson DJ, Painter JN, Attia J, Black A, et al., 'GWAS meta-analysis of 16 852 women identifies new susceptibility locus for endometrial cancer', Human molecular genetics, 25 2612-2620 (2016)

© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Endometrial cancer is the most common g... [more]

© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Endometrial cancer is the most common gynecological malignancy in the developed world. Although there is evidence of genetic predisposition to the disease, most of the genetic risk remains unexplained. We present the meta-analysis results of four genome-wide association studies (4907 cases and 11 945 controls total) in women of European ancestry. We describe one new locus reaching genome-wide significance (P < 5 × 10 -8) at 6p22.3 (rs1740828; P = 2.29 × 10 -8, OR = 1.20), providing evidence of an additional region of interest for genetic susceptibility to endometrial cancer.

Citations Scopus - 5
Co-authors John Attia, Mark Mcevoy, Liz Holliday
2016 Pelttari LM, Khan S, Vuorela M, Kiiski JI, Vilske S, Nevanlinna V, et al., 'RAD51B in familial breast cancer', PLoS ONE, 11 (2016)

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of m... [more]

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 × 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 × 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

DOI 10.1371/journal.pone.0153788
Citations Scopus - 3
Co-authors T Dudding
2016 Morten BC, Scott RJ, Avery-Kiejda KA, 'Comparison of three different methods for determining cell proliferation in breast cancer cell lines', Journal of Visualized Experiments, 2016 (2016) [C1]

� 2016 Journal of Visualized Experiments. Measuring cell proliferation can be performed by a number of different methods, each with varying levels of sensitivity, reproducibilit... [more]

� 2016 Journal of Visualized Experiments. Measuring cell proliferation can be performed by a number of different methods, each with varying levels of sensitivity, reproducibility and compatibility with high-throughput formatting. This protocol describes the use of three different methods for measuring cell proliferation in vitro including conventional hemocytometer counting chamber, a luminescence-based assay that utilizes the change in the metabolic activity of viable cells as a measure of the relative number of cells, and a multi-mode cell imager that measures cell number using a counting algorithm. Each method presents its own advantages and disadvantages for the measurement of cell proliferation, including time, cost and high-throughput compatibility. This protocol demonstrates that each method could accurately measure cell proliferation over time, and was sensitive to detect growth at differing cellular densities. Additionally, measurement of cell proliferation using a cell imager was able to provide further information such as morphology, confluence and allowed for a continual monitoring of cell proliferation over time. In conclusion, each method is capable of measuring cell proliferation, but the chosen method is user-dependent.

DOI 10.3791/54350
Citations Scopus - 1
Co-authors Kelly Kiejda
2016 Hauberg ME, Roussos P, Grove J, Børglum AD, Mattheisen M, 'Analyzing the Role of MicroRNAs in Schizophrenia in the Context of Common Genetic Risk Variants', JAMA Psychiatry, 73 369-369 (2016) [C1]
DOI 10.1001/jamapsychiatry.2015.3018
Citations Web of Science - 18
Co-authors Frans Henskens, Pat Michie, Ulrich Schall, Brian Kelly, Murray Cairns, Carmel Loughland, Paul Tooney
2016 Morten BC, Scott RJ, Avery-Kiejda KA, 'Comparison of the QuantiGene 2.0 assay and real-time RT-PCR in the detection of p53 isoform mRNA expression in formalin-fixed paraffin-embedded tissues- A preliminary study', PLoS ONE, 11 (2016) [C1]

© 2016 Morten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and repr... [more]

© 2016 Morten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. p53 is expressed as multiple smaller isoforms whose functions in cancer are not well understood. The p53 isoforms demonstrate abnormal expression in different cancers, suggesting they are important in modulating the function of full-length p53 (FLp53). The quantification of relative mRNA expression has routinely been performed using real-time PCR (qPCR). However, there are serious limitations when detecting p53 isoforms using this method, particularly for formalin-fixed paraffin-embedded (FFPE) tissues. The use of FFPE tumours would be advantageous to correlate expression of p53 isoforms with important clinical features of cancer. One alternative method of RNA detection is the hybridization-based QuantiGene 2.0 Assay, which has been shown to be advantageous for the detection of RNA from FFPE tissues. In this pilot study, we compared the QuantiGene 2.0 Assay to qPCR for the detection of FLp53 and its isoform ¿40p53 in matched fresh frozen (FF) and FFPE breast tumours. FLp53 mRNA expression was detected using qPCR in FF and FFPE tissues, but ¿40p53 mRNA was only detectable in FF tissues. Similar results were obtained for the QuantiGene 2.0 Assay. FLp53 relative mRNA expression was shown to be strongly correlated between the two methods (R2= 0.9927, p = 0.0031) in FF tissues, however ¿40p53 was not (R2= 0.4429, p = 0.3345). When comparing the different methods for the detection of FLp53 mRNA from FFPE and FF samples, no correlation (R2= 0.0002, p = 0.9863) was shown using the QuantiGene 2.0 Assay, and in contrast, the level of expression was highly correlated between the two tissues using qPCR (R2= 0.8753, p = 0.0644). These results suggest that both the QuantiGene 2.0 Assay and qPCR methods are inadequate for the quantification of ¿40p53 mRNA in FFPE tissues. Therefore, alternative methods of RNA detection and quantification are required to study the relative expression of ¿40p53 in FFPE samples.

DOI 10.1371/journal.pone.0165930
Co-authors Kelly Kiejda
2016 Johnson NA, Kypri K, Latter J, Attia J, McEvoy M, Dunlop A, Scott R, 'Genetic feedback to reduce alcohol consumption in hospital outpatients with risky drinking: Feasibility and acceptability', Public Health Research and Practice, 26 (2016) [C1]

� 2016 Johnson et al. Objective: There have been no trials in healthcare settings of genetic susceptibility feedback in relation to alcohol consumption. The purpose of this stud... [more]

� 2016 Johnson et al. Objective: There have been no trials in healthcare settings of genetic susceptibility feedback in relation to alcohol consumption. The purpose of this study was to determine the feasibility and acceptability of conducting a full-scale randomised trial estimating the effect of personalised genetic susceptibility feedback on alcohol consumption in hospital outpatients with risky drinking. Methods: Outpatients =18 years of age who reported drinking more than 14 standard drinks in the past week or in a typical week were asked to provide a saliva sample for genetic testing. Genetic susceptibility feedback was posted to participants 6 months after recruitment. The co-primary outcomes were the proportion of participants who (i) provided a saliva sample that could be genotyped, and (ii) spoke with a genetic counsellor. Secondary outcomes included changes in patients' weekly alcohol consumption; scores on scales measuring readiness to change, importance of changing and confidence in ability to change drinking habits; knowledge about which cancers are alcohol-attributable; and acceptability of the saliva collection procedure and the genetic-feedback intervention. McNemar's test and paired t-tests were used to test for differences between baseline and follow-up in proportions and means, respectively. Results: Of 100 participants who provided a saliva sample, 93 had adequate DNA for at least one genotyping assay. Three participants spoke to a genetic counsellor. Patients' readiness to change their drinking, their views on the importance of changing and their stated confidence in their ability to change increased between baseline and follow-up. There was no increase in patients' knowledge about alcohol-attributable cancers nor any reduction in how much alcohol they drank 4 months after receiving the feedback. Most participants (80%) were somewhat comfortable or very comfortable with the process used to collect saliva, 84% understood the genetic feedback, 54% found it useful, 10% had sought support to reduce their drinking after receiving the feedback, and 37% reported that the feedback would affect how much they drink in the future. Conclusion: Results of this study suggest it would be feasible to conduct a methodologically robust trial estimating the effect of genetic susceptibility feedback on alcohol consumption in hospital outpatients with risky drinking.

DOI 10.17061/phrp2641645
Co-authors John Attia, Mark Mcevoy, Kypros Kypri, Natalie Johnson, Joanna Latter, A Dunlop
2016 Wong SQ, Scott R, Fox SB, 'KRAS mutation testing in colorectal cancer: the model for molecular pathology testing in the future', COLORECTAL CANCER, 5 73-80 (2016) [C1]
DOI 10.2217/crc-2015-0009
2016 Southey MC, Goldgar DE, Winqvist R, Pylkäs K, Couch F, Tischkowitz M, et al., 'PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS', Journal of Medical Genetics, 53 800-811 (2016) [C1]

Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence ... [more]

Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T > G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G > A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T > G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95% CI 1.05 to 1.67) (p=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

DOI 10.1136/jmedgenet-2016-103839
Citations Scopus - 29Web of Science - 29
2016 Tan AG, Kifley A, Mitchell P, Rochtchina E, Flood VM, Cumming RG, et al., 'Associations between methylenetetrahydrofolate reductase polymorphisms, serum homocysteine levels, and incident cortical cataract', JAMA Ophthalmology, 134 522-528 (2016) [C1]

Copyright 2016 American Medical Association. All rights reserved. IMPORTANCE Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been shown to influence homocysteine le... [more]

Copyright 2016 American Medical Association. All rights reserved. IMPORTANCE Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been shown to influence homocysteine levels; homocysteine has been implicated as a cataractogenic stressor. OBJECTIVE To investigate the associations of MTHFR polymorphisms and serum homocysteine levels with incident cortical cataract in an older population. DESIGN, SETTING, AND PARTICIPANTS From 1992 to 1994, a population-based cohort study, the Blue Mountains Eye Study, was conducted with 3654 residents (82.4%of eligible participants) of the Blue Mountains region aged 49 years and older. At the second (1997-1999, 5-year follow-up) and third (2002-2004, 10-year follow-up) surveys, 2334 (75.8% of survivors) and 1952 (76.7%of survivors) were examined, respectively. For this report, the second survey serves as baseline when homocysteine levels were assessed, and 5-year incidence of cataract refers to incidence estimated from the second to the third survey. After excluding participants with no follow-up data or DNA or who had previous cortical cataract or cataract surgery, 757 participants were included in gene and environment analyses. This current project on associations with cataract was designed initially March 19, 2013, and completed April 14, 2014. Cataract was assessed using the Wisconsin Cataract Grading system. Two MTHFR polymorphisms, C677T (rs1801133) and A1298C (rs1801131), were included. Serum homocysteine levels were assessed following standard methods. MAIN OUTCOMES AND MEASURES Logistic regression modelswere used to estimate odds ratios (ORs) and 95%confidence intervals for incident cortical cataract, after adjusting for age, sex, smoking status, hypertension, diabetes, education, andmyopia. Path analysis was performed to explore a possible pathway of MTHFR polymorphisms via homocysteine levels to cortical cataract. RESULTS The mean (SD) age of the 1726 participants in the Blue Mountains Eye Study 2 cohort with normal homocysteine levels was 68.3 (8.1) years and 73.2 (8.5) years for those with elevated homocysteine levels. Both the C677T polymorphism (CT/TT vs CC: OR = 1.50; 95%CI = 1.01-2.23) and elevated homocysteine levels (>15 ìmol/L: OR = 2.24; 95% CI = 1.38-3.63) were independently associated with increased risk of cortical cataract. Path analysis showed that the genetic effect on cortical cataract was partially mediated via homocysteine levels. Combined CT/TT genotypes and elevated homocysteine levels were associated with a 3-fold risk of cortical cataract (OR = 3.74; 95%CI = 1.79-7.80). The synergy index of both exposures was 1.34 (95%CI = 0.44-4.01). CONCLUSIONS AND RELEVANCE MTHFR polymorphism and elevated homocysteine levels contributed separately and jointly to increased risk of cortical cataract. If these findings are confirmed, homocysteine levels may be a therapeutic target to reduce risk of cortical cataract in persons carrying genetic risk.

DOI 10.1001/jamaophthalmol.2016.0167
Citations Scopus - 2
Co-authors Liz Holliday
2016 Griffin B, Bushby PA, McCobb E, White SC, Rigdon-Brestle YK, Appel LD, et al., 'The association of shelter veterinarians¿ 2016 veterinary medical care guidelines for spay-neuter programs', Journal of the American Veterinary Medical Association, 249 165-188 (2016)

© 2016, American Veterinary Medical Association. All rights reserved. As community efforts to reduce the overpopulation and euthanasia of unwanted and unowned cats and dogs have i... [more]

© 2016, American Veterinary Medical Association. All rights reserved. As community efforts to reduce the overpopulation and euthanasia of unwanted and unowned cats and dogs have increased, many veterinarians have increasingly focused their clinical efforts on the provision of spay-neuter services. Because of the wide range of geographic and demographic needs, a wide variety of spay-neuter programs have been developed to increase delivery of services to targeted populations of animals, including stationary and mobile clinics, MASH-style operations, shelter services, community cat programs, and services provided through private practitioners. In an effort to promote consistent, high-quality care across the broad range of these programs, the Association of Shelter Veterinarians convened a task force of veterinarians to develop veterinary medical care guidelines for spay-neuter programs. These guidelines consist of recommendations for general patient care and clinical procedures, preoperative care, anesthetic management, surgical procedures, postoperative care, and operations management. They were based on current principles of anesthesiology, critical care medicine, infection control, and surgical practice, as determined from published evidence and expert opinion. They represent acceptable practices that are attainable in spay-neuter programs regardless of location, facility, or type of program. The Association of Shelter Veterinarians envisions that these guidelines will be used by the profession to maintain consistent veterinary medical care in all settings where spay-neuter services are provided and to promote these services as a means of reducing sheltering and euthanasia of cats and dogs.

DOI 10.2460/javma.249.2.165
Citations Scopus - 13
2016 Badawi N, Balde I, Goldsmith S, Karlsson P, McIntyre S, Novak I, et al., 'Australia and the Australian Cerebral Palsy Register for the birth cohort 1993 to 2006', Developmental Medicine and Child Neurology, 58 3-4 (2016)

© 2016 Mac Keith Press. This is a brief background paper for a supplementary issue of Developmental Medicine &amp; Child Neurology by the Australian Cerebral Palsy Register Group.... [more]

© 2016 Mac Keith Press. This is a brief background paper for a supplementary issue of Developmental Medicine & Child Neurology by the Australian Cerebral Palsy Register Group. It provides context for the reader of the supplement including a description of the establishment and development of state and territory cerebral palsy registers in Australia. Developmental Medicine and Child Neurology

DOI 10.1111/dmcn.13002
Citations Scopus - 5
2016 Daar J, Benward J, Collins L, Davis J, Francis L, Gates E, et al., 'Financial ¿risk-sharing¿ or refund programs in assisted reproduction: an Ethics Committee opinion', Fertility and Sterility, 106 e8-e11 (2016)

© 2016 American Society for Reproductive Medicine Financial ¿risk-sharing¿ fee structures in assisted reproduction programs charge patients a higher initial fee but provide reduce... [more]

© 2016 American Society for Reproductive Medicine Financial ¿risk-sharing¿ fee structures in assisted reproduction programs charge patients a higher initial fee but provide reduced fees for subsequent cycles and often a partial or complete refund if treatment fails. This opinion of the ASRM Ethics Committee analyzes the ethical issues raised by these fee structures, including patient selection criteria, conflicts of interest, success rate transparency, and patient¿informed consent. This document replaces the document of the same name, last published in 2013 (Fertil Steril 2013;100:334¿6).

DOI 10.1016/j.fertnstert.2016.07.003
Citations Scopus - 1
2016 Daar J, Benward J, Collins L, Davis J, Francis L, Gates E, et al., 'Oocyte or embryo donation to women of advanced reproductive age: an Ethics Committee opinion', Fertility and Sterility, 106 e3-e7 (2016)

© 2016 American Society for Reproductive Medicine Advanced reproductive age (ARA) is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetr... [more]

© 2016 American Society for Reproductive Medicine Advanced reproductive age (ARA) is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. Oocyte donation reverses the age-related decline in implantation and birth rates of women in their 40s and 50s and restores pregnancy potential beyond menopause. However, obstetrical complications in older patients remain high, particularly related to operative delivery and hypertensive and cardiovascular risks. Physicians should perform a thorough medical evaluation designed to assess the physical fitness of a patient for pregnancy before deciding to attempt transfer of embryos to any woman of advanced reproductive age (>45¿years). Embryo transfer should be strongly discouraged or denied to women of ARA with underlying conditions that increase or exacerbate obstetrical risks. Because of concerns related to the high-risk nature of pregnancy, as well as longevity, treatment of women over the age of 55 should generally be discouraged. This statement replaces the earlier ASRM Ethics Committee document of the same name, last published in 2013 (Fertil Steril 2013;100:337¿40).

DOI 10.1016/j.fertnstert.2016.07.002
Citations Scopus - 8
2016 Céspedes-Garro C, Rodrigues-Soares F, Jiménez-Arce G, Naranjo MEG, Tarazona-Santos E, Fariñas H, et al., 'Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population', Revista de Biologia Tropical, 64 1067-1076 (2016)

© 2016 Universidad de Costa Rica. All Rights Reserved. CYP2C9, CYP2C19 and CYP2D6 metabolize around 40 % of drugs and their genes vary across populations. The Costa Rican populati... [more]

© 2016 Universidad de Costa Rica. All Rights Reserved. CYP2C9, CYP2C19 and CYP2D6 metabolize around 40 % of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro- Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted.

DOI 10.15517/rbt.v64i3.20901
Citations Scopus - 2
2016 García-Cervantes L, Rodríguez-Romo G, Esteban-Cornejo I, Cabanas-Sanchez V, Delgado-Alfonso Á, Castro-Piñero J, et al., 'Perceived environment in relation to objective and self-reported physical activity in Spanish youth. The UP&DOWN study', Journal of Sports Sciences, 34 1423-1429 (2016)

© 2015 Taylor &amp; Francis. The aims of the present study were to assess the association of environmental perception with objective and self-reported physical activity (PA) and... [more]

© 2015 Taylor & Francis. The aims of the present study were to assess the association of environmental perception with objective and self-reported physical activity (PA) and the relation between environmental perception and meeting PA recommendations on children and adolescents. A sample of 1520 youth (770 boys) aged 8-18 years (12.1 ± 2.5 years) from the UP&DOWN study were included in the data analyses. Environmental perception was assessed with the short adapted version of the ALPHA environmental questionnaire. PA was objectively (accelerometers) and self-reported measured (PA Questionnaire for Children, Patient-centered Assessment and Counseling for Exercise Questionnaire and Finnish PA Index). Linear regression models were used to assess the association of environmental perception with PA. Bivariate logistic regression models were used to assess differences between environmental perception and meeting PA recommendations. Environmental perception was positively associated with both objective and self-reported PA. Some differences were found in the association of environmental perception and PA between sex-and age-specific groups. Youth who perceived a more favourable environment were more likely to meet PA recommendations (at least 60 min · day-1of moderate to vigorous PA (MVPA)). Results suggest that environmental perceptions of children and adolescents may play an important role in achieving higher levels of PA.

DOI 10.1080/02640414.2015.1116708
Citations Scopus - 1
2016 Coenraads PJ, 'Opinion of the Scientific Committee on Consumer Safety (SCCS) - Opinion on the fragrance ingredients Tagetes minuta and Tagetes patula extracts and essential oils (phototoxicity only) in cosmetic products', Regulatory Toxicology and Pharmacology, 76 213-214 (2016)

© 2016. Conclusion of the opinion: The SCCS considers a maximum level of 0.01% Tagetes minuta and Tagetes patula extracts and essential oils in leave-on products (except sunscreen... [more]

© 2016. Conclusion of the opinion: The SCCS considers a maximum level of 0.01% Tagetes minuta and Tagetes patula extracts and essential oils in leave-on products (except sunscreen cosmetic products) as safe, provided that the alpha terthienyl (terthiophene) content of the Tagetes extracts and oils does not exceed 0.35%. The Tagetes extracts and oils should not be used as ingredients of sunscreen products.

DOI 10.1016/j.yrtph.2015.11.006
Citations Scopus - 1
2016 Su YY, Huang XS, Pan SY, Peng B, Jiang W, Cao BZ, et al., 'The chinese expert consensus on evaluation of coma after cardiopulmonary resuscitation', Chinese Medical Journal, 129 2123-2127 (2016)
DOI 10.4103/0366-6999.189054
Citations Scopus - 2
2016 López S G, Valdés S G, Roessler B E, Valdivieso D V, 'Declaration of the chilean academy of medicine of law 20.850 ¿on clinical trials of pharmaceutical products and medical devices¿ and of the bylaw that will regulate its application', Revista Chilena de Enfermedades Respiratorias, 32 244-250 (2016)

© 2016, Sociedad Chilena de Enfermedades Respiratorias. All rights reserved. In Chile, high cost treatments required by selected medical conditions are financed by the State, acco... [more]

© 2016, Sociedad Chilena de Enfermedades Respiratorias. All rights reserved. In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1. The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2.The 10 years period during which any adverse event is assumed to have been caused by the medication or device evaluated by the trial, unless the contrary is proven in a judicial process; 3. Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or device is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians¿ interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, or with patients¿ ageing, or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.

2016 Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al., 'Observation of top quark pairs produced in association with a vector boson in pp collisions at root s=8 TeV', JOURNAL OF HIGH ENERGY PHYSICS, (2016)
DOI 10.1007/JHEP01(2016)096
Citations Scopus - 16Web of Science - 8
2016 Scott EM, Halees A, Itan Y, Spencer EG, He Y, Azab MA, et al., 'Characterization of greater middle eastern genetic variation for enhanced disease gene discovery', Nature Genetics, 48 1071-1079 (2016)

© 2016, Nature Publishing Group. All rights reserved. The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguin... [more]

© 2016, Nature Publishing Group. All rights reserved. The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ¿genetic purging¿. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics.

DOI 10.1038/ng.3592
Citations Scopus - 34
2016 Hori M, Ohashi Y, Pan G, Kato M, Kajikawa M, 'Point-of-care device for warfarin monitoring used in the J-ROCKET AF Study', Circulation Journal, 80 1488-1490 (2016)
DOI 10.1253/circj.CJ-16-0287
2016 Braga RD, de Lucena FN, Ribeiro-Rotta RF, Prudente COM, Porto CC, Zanini CRDO, et al., 'A multiprofessional information model for Brazilian primary care: Defining a consensus model towards an interoperable electronic health record', International Journal of Medical Informatics, 90 48-57 (2016)

© 2016 Elsevier Ireland Ltd. Objective: To develop a multiprofessional information model to be used in the decision-making process in primary care in Brazil. Methods: This was an ... [more]

© 2016 Elsevier Ireland Ltd. Objective: To develop a multiprofessional information model to be used in the decision-making process in primary care in Brazil. Methods: This was an observational study with a descriptive and exploratory approach, using action research associated with the Delphi method. A group of 13 health professionals made up a panel of experts that, through individual and group meetings, drew up a preliminary health information records model. The questionnaire used to validate this model included four questions based on a Likert scale. These questions evaluated the completeness and relevance of information on each of the four pillars that composed the model. The changes suggested in each round of evaluation were included when accepted by the majority (= 50%). This process was repeated as many times as necessary to obtain the desirable and recommended consensus level (> 50%), and the final version became the consensus model. Results: Multidisciplinary health training of the panel of experts allowed a consensus model to be obtained based on four categories of health information, called pillars: Data Collection, Diagnosis, Care Plan and Evaluation. Conclusion: The obtained consensus model was considered valid by the experts and can contribute to the collection and recording of multidisciplinary information in primary care, as well as the identification of relevant concepts for defining electronic health records at this level of complexity in health care.

DOI 10.1016/j.ijmedinf.2016.03.004
Citations Scopus - 2
2016 Novotny J, Singh A, Dysoley L, Sovannaroth S, Rekol H, 'Evidence of successful malaria case management policy implementation in Cambodia: results from national ACTwatch outlet surveys', Malaria Journal, 15 (2016)

© 2016 ACTwatch Group et al. Background: For over a decade, Cambodia has implemented a number of policies and innovative strategies to increase access to quality malaria case mana... [more]

© 2016 ACTwatch Group et al. Background: For over a decade, Cambodia has implemented a number of policies and innovative strategies to increase access to quality malaria case management services and address the drivers of multi-drug resistance. This paper utilizes outlet survey trend data collected by the ACTwatch project to demonstrate how changes in Cambodian policy and strategies have led to shifts in anti-malarial markets. Methods: Anti-malarial ACTwatch outlet surveys were conducted in Cambodia in 2009 (June-July), 2011 (June-August) and 2013 (September-October). A census of all outlets with the potential to sell or distribute anti-malarials was conducted within a nationally representative sample of communes. Drug information, sales/distribution in the previous week, and retail price were collected for each anti-malarial in stock. Information on availability of malaria blood testing was also collected. Results: A total of 7833 outlets were enumerated in 2009, 18,584 in 2011, and 16,153 in 2013. The percentage of public health facilities with at least one anti-malarial in stock on the day of the survey increased between 2009 (65.8 %) and 2011 (90.0 %) and remained high in 2013 (82.0 %). Similar trends were found for village malaria workers (VMW). Overall, private sector availability of anti-malarials declined over time and varied by outlet type. By 2013 most anti-malarial stocking public health facilities (81.5 %), VMW (95.4 %), private for-profit health facilities (64.8 %), and pharmacies (71.9 %) had the countries first-line artemisinin-based combination therapy (ACT) treatment in stock. In 2013, 60 % of anti-malarials were delivered through the private sector, 40 % through the public sector, and the most common anti-malarial to be sold or distributed was the first-line ACT, comprising 62.8 % of the national market share. Oral artemisinin monotherapy, which had accounted for 6 % of total anti-malarial market share in 2009, was no longer reportedly sold/distributed in 2013. Malaria blood testing availability remained high over time among public facilities and VMW, with availability over 90 % in 2011 and 2013. Moderate availability was observed in the private sector. Conclusions: Continued implementation of successful public and private sector strategies in support of evolving malaria drug treatment policies will be important to protect the efficacy of anti-malarial medicines and ultimately facilitate malaria elimination in Cambodia by 2025.

DOI 10.1186/s12936-016-1200-2
Citations Scopus - 7
2016 Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, et al., 'No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing', JOURNAL OF MEDICAL GENETICS, 53 298-309 (2016)
DOI 10.1136/jmedgenet-2015-103529
Citations Scopus - 31Web of Science - 27
Co-authors Michelle Wong-Brown
2016 Franke B, Stein JL, Ripke S, Anttila V, Hibar DP, van Hulzen KJE, et al., 'Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept', Nature Neuroscience, 19 420-431 (2016) [C1]
DOI 10.1038/nn.4228
Citations Scopus - 53Web of Science - 55
Co-authors Pat Michie, Ulrich Schall, Carmel Loughland, Murray Cairns, Frans Henskens, Paul Tooney, Brian Kelly
2016 Wong-Brown M, McPhillips M, Gleeson M, Spigelman AD, Meldrum CJ, Dooley S, Scott RJ, 'When is a mutation not a mutation: the case of the c.594-2A\C splice variant in a woman harbouring another BRCA1 mutation in trans.', Hered Cancer Clin Pract, 14 6 (2016) [C1]
DOI 10.1186/s13053-015-0045-y
Co-authors Michelle Wong-Brown
2016 Bolton KA, Avery-Kiejda KA, Holliday EG, Attia J, Bowden NA, Scott RJ, 'A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer', ENDOCRINE CONNECTIONS, 5 115-122 (2016) [C1]
DOI 10.1530/EC-16-0003
Citations Scopus - 1Web of Science - 1
Co-authors John Attia, Kelly Kiejda, Nikola Bowden, Liz Holliday
2016 Li N, Thompson ER, Rowley SM, McInerny S, Devereux L, Goode D, et al., 'Reevaluation of RINT1 as a breast cancer predisposition gene', Breast Cancer Research and Treatment, 159 385-392 (2016) [C1]
DOI 10.1007/s10549-016-3944-3
Citations Scopus - 5Web of Science - 5
Co-authors Michelle Wong-Brown
2016 Thompson DJ, O'Mara TA, Glubb DM, Painter JN, Cheng T, Folkerd E, et al., 'CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer', Endocrine-Related Cancer, 23 77-91 (2016) [C1]

© 2016 The authors. Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancerandwith estradiol (E2) concentrations.We analyzed2937singlenucleo... [more]

© 2016 The authors. Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancerandwith estradiol (E2) concentrations.We analyzed2937singlenucleotidepolymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome widesignificant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10-11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by theobservedeffectonE2concentrations (1.09, CI=1.03-1.21), consistentwith the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associationswith rs727479 were stronger amongwomen with a higher BMI (PinteractionZ0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.

DOI 10.1530/ERC-15-0386
Citations Scopus - 14Web of Science - 14
Co-authors John Attia, Mark Mcevoy, Liz Holliday
2016 Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al., 'Schizophrenia risk from complex variation of complement component 4', Nature, 530 177-183 (2016) [C1]
DOI 10.1038/nature16549
Citations Web of Science - 394
Co-authors Pat Michie, Brian Kelly, Murray Cairns, Paul Tooney, Frans Henskens, Carmel Loughland, Ulrich Schall
2016 Morten BC, Wong-Brown MW, Scott RJ, Avery-Kiejda KA, 'The presence of the intron 3 16 bp duplication polymorphism of p53 (rs17878362) in breast cancer is associated with a low ¿40p53:p53 ratio and better outcome', Carcinogenesis, 37 81-86 (2016) [C1]

© The Author 2015. Published by Oxford University Press. All rights reserved. Breast cancer is the most common female cancer, but it has relatively low rates of p53 mutations, sug... [more]

© The Author 2015. Published by Oxford University Press. All rights reserved. Breast cancer is the most common female cancer, but it has relatively low rates of p53 mutations, suggesting other mechanisms are responsible for p53 inactivation. We have shown that the p53 isoform, ¿40p53, is highly expressed in breast cancer, where it may contribute to p53 inactivation. ¿40p53 can be produced by alternative splicing of p53 in intron 2 and this is regulated by the formation of G-quadruplex structures in p53 intron 3, from which the nucleotides forming these structures overlap with a common polymorphism, rs17878362. rs17878362 alters p53 splicing to decrease fully spliced p53 messenger RNA (mRNA) in vitro following ionizing radiation and this in turn alters ¿40p53:p53. Hence, the presence of rs17878362 may be important in regulating ¿40p53:p53 in breast cancer. This study aimed to determine if rs17878362 was associated with altered ¿40p53 and p53 expression and outcome in breast cancer. We sequenced p53 in breast tumours from 139 patients and compared this with ¿40p53 and p53 mRNA expression. We found that the ratio of ¿40p53:p53 was significantly lower in tumours homozygous for the polymorphic A2 allele compared with those who were wild-type (A1/A1). Furthermore, there was a lower proportion of breast cancers carrying the A2 allele from patients who subsequently developed metastasis compared with those that did not. Finally, we show that patients whose tumours carried the polymorphic A2 allele had significantly better disease-free survival. These results show that rs17878362 is associated with a low ¿40p53:p53 ratio in breast cancer and that this is associated with better outcome.

DOI 10.1093/carcin/bgv164
Citations Scopus - 3Web of Science - 3
Co-authors Kelly Kiejda, Michelle Wong-Brown
2016 Grimson S, Cox AJ, Pringle KG, Burns C, Lumbers ER, Blackwell CC, Scott RJ, 'The prevalence of unique SNPs in the renin-angiotensin system highlights the need for pharmacogenetics in Indigenous Australians', Clinical and Experimental Pharmacology and Physiology, 43 157-160 (2016) [C1]

© 2016 John Wiley &amp; Sons Australia, Ltd. Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compa... [more]

© 2016 John Wiley & Sons Australia, Ltd. Genetic differences between ethnic populations affect susceptibility to disease and efficacy of drugs. This study examined and compared the prevalence of single nucleotide polymorphisms (SNPs) in genes of the renin-angiotensin system (RAS) in a desert community of Indigenous Australians and in non-Indigenous Australians. The polymorphisms were angiotensinogen, AGT G-217A (rs5049); AGT G+174A (rs4762); Angiotensin II type 1 receptor, AGTR1 A+1166C (rs5186); angiotensin converting enzyme, ACE A-240T (rs4291), ACE T-93C (rs4292); renin, REN T+1142C (rs5706). They were measured using allelic discrimination assays. The prevalence of REN T+1142C SNP was similar in the two populations; 99% were homozygous for the T allele. All other SNPs were differently distributed between the two populations (P < 0.0001). In non-Indigenous Australians, the A allele at position 204 of ACE rs4291 was prevalent (61.8%) whereas in the Indigenous Australians the A allele was less prevalent (28%). For rs4292, the C allele had a prevalence of 37.9% in non-Indigenous Australians but in Indigenous Australians the prevalence was only 1%. No Indigenous individuals were homozygous for the C allele of AGTR1 (rs5186). Thus the prevalence of RAS SNPs in this Indigenous Australian desert community was different from non-Indigenous Australians as was the prevalence of cytokine SNPs (as shown in a previous study). These differences may affect susceptibility to chronic renal and cardiovascular disease and may alter the efficacy of drugs used to inhibit the RAS. These studies highlight the need to study the pharmacogenetics of drug absorption, distribution, metabolism and excretion in Indigenous Australians for safe prescribing guidelines.

DOI 10.1111/1440-1681.12525
Co-authors Caroline Blackwell, Kirsty Pringle, E Lumbers
2016 Masson AL, Talseth-Palmer BA, Evans TJ, McElduff P, Spigelman AD, Hannan GN, Scott RJ, 'Copy number variants associated with 18p11.32, DCC and the promoter 1B region of APC in colorectal polyposis patients', Meta Gene, 7 95-104 (2016) [C1]

© 2016 . Familial Adenomatous Polyposis (FAP) is the second most common inherited predisposition to colorectal cancer (CRC) associated with the development of hundreds to thousand... [more]

© 2016 . Familial Adenomatous Polyposis (FAP) is the second most common inherited predisposition to colorectal cancer (CRC) associated with the development of hundreds to thousands of adenomas in the colon and rectum. Mutations in APC are found in ~. 80% polyposis patients with FAP. In the remaining 20% no genetic diagnosis can be provided suggesting other genes or mechanisms that render APC inactive may be responsible. Copy number variants (CNVs) remain to be investigated in FAP and may account for disease in a proportion of polyposis patients. A cohort of 56 polyposis patients and 40 controls were screened for CNVs using the 2.7M microarray (Affymetrix) with data analysed using ChAS (Affymetrix). A total of 142 CNVs were identified unique to the polyposis cohort suggesting their involvement in CRC risk. We specifically identified CNVs in four unrelated polyposis patients among CRC susceptibility genes APC, DCC, MLH1 and CTNNB1 which are likely to have contributed to disease development in these patients. A recurrent deletion was observed at position 18p11.32 in 9% of the patients screened that was of particular interest. Further investigation is necessary to fully understand the role of these variants in CRC risk given the high prevalence among the patients screened.

DOI 10.1016/j.mgene.2015.12.005
Citations Scopus - 3Web of Science - 3
Co-authors Patrick Mcelduff, Bente Talseth-Palmer
2016 Ibrahim-Verbaas CA, Bressler J, Debette S, Schuur M, Smith AV, Bis JC, et al., 'GWAS for executive function and processing speed suggests involvement of the CADM2 gene', Molecular Psychiatry, 21 189-197 (2016) [C1]

© 2016 Macmillan Publishers Limited All rights reserved. To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducte... [more]

© 2016 Macmillan Publishers Limited All rights reserved. To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10 -8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10 -9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10 -4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10 -15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10 -11) and neuron cell-cell adhesion (P-value=1.48 × 10 -13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

DOI 10.1038/mp.2015.37
Citations Scopus - 29Web of Science - 22
Co-authors Liz Holliday, Christopher Oldmeadow, Peter Schofield, John Attia
2016 Talseth-Palmer BA, Bauer DC, Sjursen W, Evans TJ, Mcphillips M, Proietto A, et al., 'Targeted next-generation sequencing of 22 mismatch repair genes identifies Lynch syndrome families', Cancer Medicine, 5 929-941 (2016) [C1]

© 2016 Published by John Wiley &amp; Sons Ltd. Causative germline mutations in mismatch repair (MMR) genes can only be identified in ~50% of families with a clinical diagnosis o... [more]

© 2016 Published by John Wiley & Sons Ltd. Causative germline mutations in mismatch repair (MMR) genes can only be identified in ~50% of families with a clinical diagnosis of the inherited colorectal cancer (CRC) syndrome hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome (LS). Identification of these patients are critical as they are at substantially increased risk of developing multiple primary tumors, mainly colorectal and endometrial cancer (EC), occurring at a young age. This demonstrates the need to develop new and/or more thorough mutation detection approaches. Next-generation sequencing (NGS) was used to screen 22 genes involved in the DNA MMR pathway in constitutional DNA from 14 HNPCC and 12 sporadic EC patients, plus 2 positive controls. Several softwares were used for analysis and functional annotation. We identified 5 exonic indel variants, 42 exonic nonsynonymous single-nucleotide variants (SNVs) and 1 intronic variant of significance. Three of these variants were class 5 (pathogenic) or class 4 (likely pathogenic), 5 were class 3 (uncertain clinical relevance) and 40 were classified as variants of unknown clinical significance. In conclusion, we have identified two LS families from the sporadic EC patients, one without a family history of cancer, supporting the notion for universal MMR screening of EC patients. In addition, we have detected three novel class 3 variants in EC cases. We have, in addition discovered a polygenic interaction which is the most likely cause of cancer development in a HNPCC patient that could explain previous inconsistent results reported on an intronic EXO1 variant.

DOI 10.1002/cam4.628
Citations Scopus - 6Web of Science - 6
Co-authors Bente Talseth-Palmer
2016 Bolton KA, Holliday EG, Attia J, Bowden NA, Avery-Kiejda KA, Scott RJ, 'A novel polymorphic repeat in the upstream regulatory region of the estrogen-induced gene EIG121 is not associated with the risk of developing breast or endometrial cancer', BMC Research Notes, 9 (2016) [C1]

© 2016 The Author(s). Background: The estrogen-induced gene 121 (EIG121) has been associated with breast and endometrial cancers, but its mechanism of action remains unknown. In a... [more]

© 2016 The Author(s). Background: The estrogen-induced gene 121 (EIG121) has been associated with breast and endometrial cancers, but its mechanism of action remains unknown. In a genome-wide search for tandem repeats, we found that EIG121 contains a short tandem repeat (STR) in its upstream regulatory region which has the potential to alter gene expression. The presence of this STR has not previously been analysed in relation to breast or endometrial cancer risk. Results: In this study, the lengths of this STR were determined by PCR, fragment analysis and sequencing using DNA from 223 breast cancer patients, 204 endometrial cancer patients and 220 healthy controls to determine if they were associated with the risk of developing breast or endometrial cancer. We found this repeat to be highly variable with the number of copies of the AG motif ranging from 27 to 72 and having a bimodal distribution. No statistically significant association was identified between the length of this STR and the risk of developing breast or endometrial cancer or age at diagnosis. Conclusions: The STR in the upstream regulatory region of EIG121 is highly polymorphic, but is not associated with the risk of developing breast or endometrial cancer in the cohorts analysed here. While this polymorphic STR in the regulatory region of EIG121 appears to have no impact on the risk of developing breast or endometrial cancer, its association with disease recurrence or overall survival remains to be determined.

DOI 10.1186/s13104-016-2086-3
Citations Scopus - 1
Co-authors Nikola Bowden, Kelly Kiejda, John Attia, Liz Holliday
2016 Bigdeli TB, Ripke S, Bacanu S-A, Lee SH, Wray NR, Gejman PV, et al., 'Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness', American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 171 276-289 (2016) [C1]
DOI 10.1002/ajmg.b.32402
Citations Web of Science - 7
Co-authors Ulrich Schall, Carmel Loughland, Pat Michie, Frans Henskens
2016 Lubinski J, Scott RJ, Sijmons R, Theissen SM, 'Thank you to all our manuscript reviewers in 2015.', Hered Cancer Clin Pract, 14 7 (2016)
DOI 10.1186/s13053-016-0047-4
2016 Pringle KG, Delforce SJ, Wang Y, Ashton KA, Proietto A, Otton G, et al., 'Renin-angiotensin system gene polymorphisms and endometrial cancer', ENDOCRINE CONNECTIONS, 5 128-135 (2016) [C1]
DOI 10.1530/EC-15-0112
Citations Scopus - 3Web of Science - 3
Co-authors Kirsty Pringle, E Lumbers, Caroline Blackwell
2016 Guo ST, Chi MN, Yang RH, Guo XY, Zan LK, Wang CY, et al., 'INPP4B is an oncogenic regulator in human colon cancer', Oncogene, 35 3049-3061 (2016) [C1]

© 2016 Macmillan Publishers Limited. All rights reserved. Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is... [more]

© 2016 Macmillan Publishers Limited. All rights reserved. Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum-and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.

DOI 10.1038/onc.2015.361
Citations Scopus - 14Web of Science - 14
Co-authors Lei Jin, Xu Zhang, Rick Thorne, Stephen Ackland, Chenchen Jiang, Hubert Hondermarck
2016 Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, et al., 'Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function', NATURE COMMUNICATIONS, 7 (2016) [C1]
DOI 10.1038/ncomms10023
Citations Scopus - 89Web of Science - 86
Co-authors Mark Mcevoy, Liz Holliday, John Attia
2016 Couch FJ, Kuchenbaecker KB, Michailidou K, Mendoza-Fandino GA, Nord S, Lilyquist J, et al., 'Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer', NATURE COMMUNICATIONS, 7 (2016) [C1]
DOI 10.1038/ncomms11375
Citations Scopus - 21Web of Science - 23
2016 Minelli C, Dean CH, Hind M, Alves AC, Amaral AFS, Siroux V, et al., 'Association of Forced Vital Capacity with the Developmental Gene NCOR2', PLOS ONE, 11 e0147388-e0147388 (2016) [C1]
DOI 10.1371/journal.pone.0147388
Citations Scopus - 3Web of Science - 3
Co-authors Liz Holliday, John Attia, Christopher Oldmeadow
2016 Srinivasan S, Bettella F, Mattingsdal M, Wang Y, Witoelar A, Schork AJ, et al., 'Genetic Markers of Human Evolution Are Enriched in Schizophrenia', Biological Psychiatry, 80 284-292 (2016) [C1]
DOI 10.1016/j.biopsych.2015.10.009
Citations Web of Science - 16
Co-authors Paul Tooney, Murray Cairns, Ulrich Schall, Pat Michie, Brian Kelly, Carmel Loughland, Frans Henskens
2016 Mehta D, Tropf FC, Gratten J, Bakshi A, Zhu Z, Bacanu S-A, et al., 'Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women.', JAMA psychiatry, 73 497-505 (2016) [C1]
DOI 10.1001/jamapsychiatry.2016.0129
Co-authors Pat Michie, Ulrich Schall, Carmel Loughland, Paul Tooney, Frans Henskens, Murray Cairns
2016 Wang Y, Thompson WK, Schork AJ, Holland D, Chen C-H, Bettella F, et al., 'Leveraging Genomic Annotations and Pleiotropic Enrichment for Improved Replication Rates in Schizophrenia GWAS', PLOS Genetics, 12 e1005803-e1005803 (2016) [C1]
DOI 10.1371/journal.pgen.1005803
Citations Web of Science - 10
Co-authors Ulrich Schall, Carmel Loughland, Frans Henskens, Murray Cairns, Paul Tooney, Brian Kelly, Pat Michie
2016 Mathe A, Wong-Brown M, Locke WJ, Stirzaker C, Braye SG, Forbes JF, et al., 'DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients', SCIENTIFIC REPORTS, 6 (2016) [C1]
DOI 10.1038/srep33435
Citations Scopus - 6Web of Science - 3
Co-authors John Forbes, Andrea Mathe, Michelle Wong-Brown, Kelly Kiejda
2016 Ness AR, Waylen A, Hurley K, Jeffreys M, Penfold C, Pring M, et al., 'Recruitment, response rates and characteristics of 5511 people enrolled in a prospective clinical cohort study: head and neck 5000', Clinical Otolaryngology, 41 804-809 (2016)
DOI 10.1111/coa.12548
Citations Scopus - 3
2016 Mather KA, Thalamuthu A, Oldmeadow C, Song F, Armstrong NJ, Poljak A, et al., 'Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults', Scientific Reports, 6 (2016) [C1]

Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome... [more]

Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest sample to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10-11). The results were replicated in an independent cohort, the Hunter Community Study (p < 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.

DOI 10.1038/srep23675
Citations Scopus - 4Web of Science - 3
Co-authors Christopher Oldmeadow, Mark Mcevoy, Peter Schofield, John Attia, Liz Holliday
2015 Dun MD, Chalkley RJ, Faulkner S, Keene S, Avery-Kiejda KA, Scott RJ, et al., 'Proteotranscriptomic profiling of 231-BR breast cancer cells: Identification of potential biomarkers and therapeutic targets for brain metastasis', Molecular and Cellular Proteomics, 14 2316-2330 (2015) [C1]

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers... [more]

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers or therapeutic targets for risk prediction, diagnosis, and treatment. Here the proteome of the brain metastatic breast cancer cell line 231-BR has been compared with that of the parental cell line MDA-MB-231, which is also metastatic but has no organ selectivity. Using SILAC and nanoLC-MS/MS, 1957 proteins were identified in reciprocal labeling experiments and 1584 were quantified in the two cell lines. A total of 152 proteins were confidently determined to be up- or down-regulated by more than twofold in 231-BR. Of note, 112/152 proteins were decreased as compared with only 40/152 that were increased, suggesting that down-regulation of specific proteins is an important part of the mechanism underlying the ability of breast cancer cells to metastasize to the brain. When matched against transcriptomic data, 43% of individual protein changes were associated with corresponding changes in mRNA, indicating that the transcript level is a limited predictor of protein level. In addition, differential miRNA analyses showed that most miRNA changes in 231-BR were up- (36/45) as compared with down-regulations (9/45). Pathway analysis revealed that proteome changes were mostly related to cell signaling and cell cycle, metabolism and extracellular matrix remodeling. The major protein changes in 231-BR were confirmed by parallel reaction monitoring mass spectrometry and consisted in increases (by more than fivefold) in the matrix metalloproteinase-1, ephrin-B1, stomatin, myc target-1, and decreases (by more than 10-fold) in transglutaminase-2, the S100 calcium-binding protein A4, and L-plastin. The clinicopathological significance of these major proteomic changes to predict the occurrence of brain metastases, and their potential value as therapeutic targets, warrants further investigation.

DOI 10.1074/mcp.M114.046110
Citations Scopus - 19Web of Science - 17
Co-authors Murray Cairns, Matt Dun, Hubert Hondermarck, Kelly Kiejda
2015 Kurlapska A, Serrano-Fernández P, Baszuk P, Gupta S, Starzynska T, Malecka-Panas E, et al., 'Cumulative effects of genetic markers and the detection of advanced colorectal neoplasias by population screening', Clinical Genetics, 88 234-240 (2015) [C1]

© 2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd. Genetic markers associated with colorectal cancer may be used in population screening for the early i... [more]

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Genetic markers associated with colorectal cancer may be used in population screening for the early identification of patients at elevated risk of disease. We genotyped 3059 individuals with no cancer family history for eight markers previously associated with colorectal cancer. After colonoscopy, the genetic profile of cases with advanced colorectal neoplasia (213) was compared with the rest (2846). rs2066847 and rs6983267 were significantly associated with the risk of advanced colorectal neoplasia but with limited effect on their own [odds ratio (OR) 1.59; 95% confidence interval (CI) 1.02-2.41; p=0.033 and OR 1.45; 95% CI 1.02-2.12; p=0.044, respectively]. Cumulative effects, in contrast, were associated with high risk: the combination of rs2066847, rs6983267, rs4779584, rs3802842 and rs4939827 minimized the number of markers considered, while maximizing the relative size of the carrier group and the risk associated to it, for example, for at least two cumulated risk markers, OR is 2.57 (95% CI 1.50-4.71; corrected p-value 0.0079) and for three or more, OR is 3.57 (95% CI 1.91-6.96; corrected p-value 0.00074). The identification of cumulative models of - otherwise - low-risk markers could be valuable in defining risk groups, within an otherwise low-risk population (no cancer family history).

DOI 10.1111/cge.12481
Citations Scopus - 3Web of Science - 3
2015 Stirzaker C, Zotenko E, Song JZ, Qu W, Nair SS, Locke WJ, et al., 'Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value', Nature Communications, 6 1-11 (2015) [C1]
DOI 10.1038/ncomms6899
Citations Scopus - 47Web of Science - 46
Co-authors John Forbes, Kelly Kiejda
2015 Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott RJ, Hall ST, et al., 'Genetic and environmental factors affecting TNF-a responses in relation to sudden infant death syndrome', Frontiers in Immunology, 6 (2015) [C1]

© 2015 Moscovis, Gordon, Al Madani, Gleeson, Scott, Hall, Burns and Blackwell. Dysregulation of the inflammatory responses has been suggested to contribute to the events leading t... [more]

© 2015 Moscovis, Gordon, Al Madani, Gleeson, Scott, Hall, Burns and Blackwell. Dysregulation of the inflammatory responses has been suggested to contribute to the events leading to sudden infant deaths. Our objectives were (1) to analyze a single nucleotide polymorphism (SNP) associated with high levels of tumor necrosis factor-a (TNF-a) responses, TNF G-308A, in sudden infant death syndrome (SIDS) infants, SIDS and control parents, and ethnic groups with different incidences of SIDS; (2) the effects of two risk factors for SIDS, cigarette smoke and virus infection, on TNF-a responses; and (3) to assess effects of genotype, cigarette smoke, and gender on TNF-a responses to bacterial toxins identified in SIDS infants. TNF G-308A genotypes were determined by real-time polymerase chain reaction for SIDS infants from Australia, Germany, and Hungary; parents of SIDS infants and their controls; and populations with high (Aboriginal Australian), medium (Caucasian), and low (Bangladeshi) SIDS incidences. Leukocytes from Caucasian donors were stimulated in vitro with endotoxin or toxic shock syndrome toxin-1 (TSST-1). TNF-a responses were measured by L929 bioassay (IU/ml) and assessed in relation to genotype, smoking status, and gender. There was a significantly higher proportion of the minor allele AA genotype among Australian SIDS infants (6/24, 24%) compared to 3/62 (4.8%) controls (p = 0.03). There were no significant differences in TNF-a responses by TNF G-308A genotypes when assessed in relation to smoking status or gender. Given the rarity of the TNF G-308A A allele in Caucasian populations, the finding that 24% of the Australian SIDS infants tested had this genotype requires further investigation and cautious interpretation. Although non-smokers with the AA genotype had higher TNFa responses to both TSST-1 and endotoxin, there were too few subjects with this rare allele to obtain statistically valid results. No effects of genotype, smoking, or gender were observed for TNF-a responses to these toxins.

DOI 10.3389/fimmu.2015.00374
Citations Scopus - 3Web of Science - 3
Co-authors Maree Gleeson, Caroline Blackwell, Sharron Hall
2015 Carvajal-Carmona LG, O Mara TA, Painter JN, Lose FA, Dennis J, Michailidou K, et al., 'Candidate locus analysis of the TERT¿CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk', Human Genetics, 134 231-245 (2015) [C1]

© 2014, The Author(s). Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT ... [more]

© 2014, The Author(s). Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT¿CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P¿=¿4.9¿×¿10-6to P¿=¿7.7¿×¿10-5). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERTP¿=¿1.5¿×¿10-18, CLPTM1LP¿=¿1.5¿×¿10-19). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.

DOI 10.1007/s00439-014-1515-4
Citations Scopus - 16Web of Science - 16
2015 Moscovis SM, Cox A, Hall ST, Burns CJ, Scott RJ, Blackwell CC, 'Effects of gender, cytokine gene polymorphisms and environmental factors on inflammatory responses', Innate Immunity, 21 523-530 (2015) [C1]

© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. Previous studies have indicated that cytokine gene polymorphisms of Indigenous Australians we... [more]

© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav. Previous studies have indicated that cytokine gene polymorphisms of Indigenous Australians were predominantly associated with strong pro-inflammatory responses. We tested the hypothesis that cells of donors with genetic profiles of inflammatory cytokine single nucleotide polymorphisms (SNPs) similar to Indigenous Australians produce higher pro-inflammatory responses. PBMCs from 14 donors with genetic profiles for a high risk of strong pro-inflammatory responses and 14 with low-risk profiles were stimulated with endotoxin and effects of gender, IFN-¿, cigarette smoke extract (CSE) and testosterone on cytokine responses analysed. Cytokines were calculated from standard curves (Luminex 2.3 software). No significant differences were associated with SNP profile alone. Lower pro-inflammatory responses were observed for cells from males with low- or high-risk profiles. For cells from females with high-risk profiles, anti-inflammatory IL-10 responses were significantly reduced. There was no effect of testosterone levels on responses from males. For females, results from IFN-¿-treated cells showed positive correlations between testosterone levels and IL-1ß responses to endotoxin for both risk groups and TNF-a for the high-risk group. If interactions observed among CSE, IFN-¿, genetic background and testosterone reflect those in vivo, these might contribute to increased incidences of hospitalisations for infectious diseases among Indigenous women.

DOI 10.1177/1753425914553645
Citations Scopus - 6Web of Science - 4
Co-authors Sharron Hall, Caroline Blackwell
2015 Greenop KR, Bailey HD, Miller M, Scott RJ, Attia J, Ashton LJ, et al., 'Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors', Nutrition and Cancer, 67 431-441 (2015) [C1]

© 2015 Taylor &amp; Francis Group, LLC. Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is kno... [more]

© 2015 Taylor & Francis Group, LLC. Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

DOI 10.1080/01635581.2015.998839
Citations Scopus - 8Web of Science - 8
Co-authors John Attia
2015 Wong-Brown MW, Meldrum CJ, Carpenter JE, Clarke CL, Narod SA, Jakubowska A, et al., 'Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer', Breast Cancer Research and Treatment, 150 71-80 (2015) [C1]

© 2015, Springer Science+Business Media New York. Triple-negative breast cancers¿(TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles... [more]

© 2015, Springer Science+Business Media New York. Triple-negative breast cancers¿(TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20¿% of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast c ancer, diagnosed on average at age 58.0¿years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon¿intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6¿%) triple-negative patients. The mutation prevalence was 9.3¿% in Australia and was 9.9¿% in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59¿% of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.

DOI 10.1007/s10549-015-3293-7
Citations Scopus - 31
Co-authors Nikola Bowden, Michelle Wong-Brown, Kelly Kiejda
2015 Thompson ER, Gorringe KL, Rowley SM, Wong-Brown MW, McInerny S, Li N, et al., 'Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls', BREAST CANCER RESEARCH, 17 (2015) [C1]
DOI 10.1186/s13058-015-0627-7
Citations Scopus - 12Web of Science - 11
Co-authors Michelle Wong-Brown
2015 O'Brien AR, Saunders NFW, Guo Y, Buske FA, Scott RJ, Bauer DC, 'VariantSpark: population scale clustering of genotype information.', BMC Genomics, 16 1052 (2015) [C1]
DOI 10.1186/s12864-015-2269-7
Citations Scopus - 9Web of Science - 8
2015 Chan JPL, Thalamuthu A, Oldmeadow C, Armstrong NJ, Holliday EG, McEvoy M, et al., 'Genetics of hand grip strength in mid to late life', Age, 37 1-10 (2015) [C1]

© 2015, American Aging Association. Hand grip strength (GS) is a predictor of mortality in older adults and is moderately to highly heritable, but no genetic variants have been co... [more]

© 2015, American Aging Association. Hand grip strength (GS) is a predictor of mortality in older adults and is moderately to highly heritable, but no genetic variants have been consistently identified. We aimed to identify single nucleotide polymorphisms (SNPs) associated with GS in middle-aged to older adults using a genome-wide association study (GWAS). GS was measured using handheld dynamometry in community-dwelling men and women aged 55¿85 from the Hunter Community Study (HCS, N = 2088) and the Sydney Memory and Ageing Study (Sydney MAS, N = 541). Genotyping was undertaken using Affymetrix microarrays with imputation to HapMap2. Analyses were performed using linear regression. No genome-wide significant results were observed in HCS nor were any of the top signals replicated in Sydney MAS. Gene-based analyses in HCS identified two significant genes (ZNF295, C2CD2), but these results were not replicated in Sydney MAS. One out of eight SNPs previously associated with GS, rs550942, located near the CNTF gene, was significantly associated with GS (p = 0.005) in the HCS cohort only. Study differences may explain the lack of consistent results between the studies, including the smaller sample size of the Sydney MAS cohort. Our modest sample size also had limited power to identify variants of small effect. Our results suggest that similar to various other complex traits, many genetic variants of small effect size may influence GS. Future GWAS using larger samples and consistent measures may prove more fruitful at identifying genetic contributors for GS in middle-aged to older adults.

DOI 10.1007/s11357-015-9745-5
Citations Scopus - 7Web of Science - 7
Co-authors Mark Mcevoy, Liz Holliday, Roseanne Peel, John Attia, Christopher Oldmeadow
2015 Greenop KR, Scott RJ, Attia J, Bower C, de Klerk NH, Norris MD, et al., 'Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case-Control Study', CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 24 931-937 (2015) [C1]
DOI 10.1158/1055-9965.EPI-14-1248
Citations Scopus - 3Web of Science - 2
Co-authors John Attia
2015 Maltby VE, Graves MC, Lea RA, Benton MC, Sanders KA, Tajouri L, et al., 'Genome-wide DNA methylation profiling of CD8+T cells shows a distinct epigenetic signature to CD4+T cells in multiple sclerosis patients', CLINICAL EPIGENETICS, 7 (2015) [C1]
DOI 10.1186/s13148-015-0152-7
Citations Scopus - 24Web of Science - 25
Co-authors Jeannette Lechner-Scott, Vicki E Maltby
2015 Milne E, Greenop KR, Scott RJ, Haber M, Norris MD, Attia J, et al., 'Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia', Cancer Epidemiology Biomarkers and Prevention, 24 48-56 (2015) [C1]

© 2014 American Association for Cancer Research. Background: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood... [more]

© 2014 American Association for Cancer Research. Background: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007). Methods: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed. Results: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation. Conclusions: Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation. Impact: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.

DOI 10.1158/1055-9965.EPI-14-0680
Citations Scopus - 5Web of Science - 3
Co-authors John Attia
2015 Wong-Brown MW, Meldrum CJ, Carpenter JE, Clarke CL, Narod SA, Jakubowska A, et al., 'Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer', Breast Cancer Research and Treatment, 150 71-80 (2015) [C1]

© 2015, Springer Science+Business Media New York. Triple-negative breast cancers¿(TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles... [more]

© 2015, Springer Science+Business Media New York. Triple-negative breast cancers¿(TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20¿% of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0¿years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon¿intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6¿%) triple-negative patients. The mutation prevalence was 9.3¿% in Australia and was 9.9¿% in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59¿% of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.

DOI 10.1007/s10549-015-3293-7
Citations Scopus - 44Web of Science - 40
Co-authors Nikola Bowden, Kelly Kiejda, Michelle Wong-Brown
2015 Davies G, Armstrong N, Bis JC, Bressler J, Chouraki V, Giddaluru S, et al., 'Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)', Molecular Psychiatry, 20 183-192 (2015) [C1]

© 2015 Macmillan Publishers Limited. General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic co... [more]

© 2015 Macmillan Publishers Limited. General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10<sup>-9</sup>, MIR2113; rs17522122, P=2.55 × 10<sup>-8</sup>, AKAP6; rs10119, P=5.67 × 10<sup>-9</sup>, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10<sup>-6</sup>). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10<sup>-17</sup>). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

DOI 10.1038/mp.2014.188
Citations Scopus - 108Web of Science - 100
Co-authors John Attia, Peter Schofield, Christopher Oldmeadow, Liz Holliday
2015 Sapkota Y, Attia J, Gordon SD, Henders AK, Holliday EG, Rahmioglu N, et al., 'Genetic burden associated with varying degrees of disease severity in endometriosis', MOLECULAR HUMAN REPRODUCTION, 21 594-602 (2015) [C1]
DOI 10.1093/molehr/gav021
Citations Scopus - 13Web of Science - 13
Co-authors Mark Mcevoy, Liz Holliday, John Attia
2015 Greenop KR, Hinwood AL, Fritschi L, Scott RJ, Attia J, Ashton LJ, et al., 'Vehicle refuelling, use of domestic wood heaters and the risk of childhood brain tumours: Results from an Australian case-control study', Pediatric Blood and Cancer, 62 229-234 (2015) [C1]

© 2014 Wiley Periodicals, Inc. The aetiology of childhood brain tumours (CBT) is largely unknown. Damage to germ cells after parental exposure to airborne carcinogens, such as vol... [more]

© 2014 Wiley Periodicals, Inc. The aetiology of childhood brain tumours (CBT) is largely unknown. Damage to germ cells after parental exposure to airborne carcinogens, such as volatile organic compounds and polycyclic aromatic hydrocarbons is one plausible pathway. This analysis aimed to investigate whether parental refuelling of vehicles or the use of domestic wood heaters in key time periods relating to the child's birth was associated with an increased risk of CBT. Procedure: Cases <15 years of age were recruited through 10 paediatric oncology centres around Australia; controls were recruited through nationwide random-digit dialling, frequency matched to cases on age, sex and State of residence. Exposure to refuelling and wood heaters was ascertained through questionnaires from both parents. Odds ratios (ORs) and confidence intervals (CIs) were estimated using unconditional logistic regression, adjusting for relevant covariates. Results: Data were available for 306 case and 950 control families. Paternal refuelling =4times/month was associated with an increased risk of CBT (OR 1.59, 95% CI: 1.11, 2.29), and a dose-dependent trend was observed (P=0.004). No association was seen for maternal refuelling. Use of closed, but not open, wood heaters before (OR 1.51, 95% CI: 1.05, 2.15) and after (OR 1.44, 95% CI: 1.03, 2.01) the child's birth was associated with increased risk of CBT, but dose-response relationships were weak or absent. Conclusions: Paternal refuelling of vehicles =4times/month and the use of closed wood heaters before the child's birth may increase the risk of CBT. Replication in larger studies is needed.

DOI 10.1002/pbc.25268
Citations Scopus - 2Web of Science - 2
Co-authors John Attia
2015 Debniak T, Gromowski T, Scott RJ, Gronwald J, Huzarski T, Byrski T, et al., 'Management of ovarian and endometrial cancers in women belonging to HNPCC carrier families: review of the literature and results of cancer risk assessment in Polish HNPCC families', HEREDITARY CANCER IN CLINICAL PRACTICE, 13 (2015) [C1]
DOI 10.1186/s13053-015-0025-2
Citations Scopus - 9Web of Science - 6
2015 Mathe A, Scott RJ, Avery-Kiejda KA, 'MiRNAs and other epigenetic changes as biomarkers in triple negative breast cancer', International Journal of Molecular Sciences, 16 28347-28376 (2015) [C1]

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Triple negative breast cancer (TNBC) is characterised by the lack of receptors for estrogen (ER), progesterone (PR), and ... [more]

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Triple negative breast cancer (TNBC) is characterised by the lack of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Since it cannot be treated by current endocrine therapies which target these receptors and due to its aggressive nature, it has one of the worst prognoses of all breast cancer subtypes. The only treatments remain chemo- and/or radio-therapy and surgery and because of this, novel biomarkers or treatment targets are urgently required to improve disease outcomes. MicroRNAs represent an attractive candidate for targeted therapies against TNBC, due to their natural ability to act as antisense interactors and regulators of entire gene sets involved in malignancy and their superiority over mRNA profiling to accurately classify disease. Here we review the current knowledge regarding miRNAs as biomarkers in TNBC and their potential use as therapeutic targets in this disease. Further, we review other epigenetic changes and interactions of these changes with microRNAs in this breast cancer subtype, which may lead to the discovery of new treatment targets for TNBC.

DOI 10.3390/ijms161226090
Citations Scopus - 20Web of Science - 19
Co-authors Kelly Kiejda, Andrea Mathe
2015 Pan X, Bowman M, Scott RJ, Fitter J, Nicholson RC, Smith R, Zakar T, 'Methylation of the Corticotropin Releasing Hormone Gene Promoter in BeWo Cells: Relationship to Gene Activity', International Journal of Endocrinology, 2015 (2015) [C1]

© 2015 Xin Pan et al. Corticotropin releasing hormone (CRH) production by the human placenta increases exponentially as pregnancy advances, and the rate of increase predicts gesta... [more]

© 2015 Xin Pan et al. Corticotropin releasing hormone (CRH) production by the human placenta increases exponentially as pregnancy advances, and the rate of increase predicts gestational length. CRH gene expression is regulated by cAMP in trophoblasts through a cyclic AMP-response element (CRE), which changes its transcription factor binding properties upon methylation. Here we determined whether methylation of the CRH proximal promoter controls basal and cAMP-stimulated CRH expression in BeWo cells, a well-characterized trophoblastic cell line. We treated the cells with 8-Br-cAMP and the DNA methyltransferase inhibitor 5-aza-2' deoxycytidine (5-AZA-dC) and determined the effects on CRH mRNA level and promoter methylation. Clonal bisulfite sequencing showed partial and allele independent methylation of CpGs in the CRH promoter. CRH mRNA expression and the methylation of a subset of CpGs (including CpG2 in the CRE) increased spontaneously during culture. 8-Br-cAMP stimulated CRH expression without affecting the increase in methylation. 5-AZA-dC decreased methylation and augmented 8-Br-cAMP-stimulated CRH expression, but it blocked the spontaneous increase of CRH mRNA level. We conclude that the CRH promoter is a dynamically and intermediately methylated genomic region in BeWo cells. Promoter methylation did not inhibit CRH gene expression under the conditions employed; rather it determined the contribution of alternative cAMP-independent pathways and cAMP-independent mechanisms to CRH expression control.

DOI 10.1155/2015/861302
Citations Scopus - 5Web of Science - 3
Co-authors Maria Bowman, John Fitter, Roger Smith
2015 Kamien B, Digilio MC, Novelli A, O'Donnell S, Bain N, Meldrum C, et al., 'Narrowing the critical region for overgrowth within 13q14.2-q14.3 microdeletions', European Journal of Medical Genetics, 58 629-633 (2015) [C3]

© 2015 Published by Elsevier Masson SAS. Large chromosomal deletions from 13q13.3 to 13q21.3 have previously been associated with overgrowth. We present two patients with deletion... [more]

© 2015 Published by Elsevier Masson SAS. Large chromosomal deletions from 13q13.3 to 13q21.3 have previously been associated with overgrowth. We present two patients with deletions at 13q14.2q14.3 who have macrocephaly, tall stature relative to their parents, cardiac phenotypes, and intellectual disability. This report narrows the critical region for tall stature, macrocephaly, and possibly cardiac disease. Crown

DOI 10.1016/j.ejmg.2015.10.006
Citations Scopus - 4Web of Science - 3
Co-authors T Dudding
2015 Paszkowska-Szczur K, Scott RJ, Górski B, Cybulski C, Kurzawski G, Dymerska D, et al., 'Polymorphisms in nucleotide excision repair genes and susceptibility to colorectal cancer in the Polish population', Molecular Biology Reports, 42 755-764 (2015) [C1]

© 2014, The Author(s). Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. Genetic polymorp... [more]

© 2014, The Author(s). Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. Genetic polymorphisms in XP genes may be associated with a change in DNA repair capacity, which could be associated with colorectal cancer development. We assessed the association between 94 single nucleotide polymorphisms (SNPs) within seven XP genes (XPA¿XPG) and the colorectal cancer risk in the Polish population. We genotyped 758 unselected patients with colorectal cancer and 1,841 healthy adults. We found that a significantly decreased risk of colorectal cancer was associated with XPC polymorphism rs2228000_CT genotype (OR 0.59; p¿<¿0.0001) and the rs2228000_TT genotype (OR 0.29; p¿<¿0.0001) compared to the reference genotype (CC). And an increased disease risk was associated with the XPD SNP, rs1799793_AG genotype (OR 1.44, p¿=¿0.018) and rs1799793_AA genotype (OR 3.31, p¿<¿0.0001) compared to the reference genotype. Haplotype analysis within XPC, XPD and XPG revealed haplotypes associated with an altered colorectal cancer risk. Stratified analysis by gender showed differences between the association of three SNPs: XPC rs2228000, XPD rs1799793 and XPD rs238406 in females and males. Association analysis between age of disease onset and polymorphisms in XPD (rs1799793) and XPC (rs2228000) revealed differences in the prevalence of these variants in patients under and over 50¿years of age. Our results confirmed that polymorphisms in XPC and XPD may be associated with the risk of colorectal cancer.

DOI 10.1007/s11033-014-3824-z
Citations Scopus - 16Web of Science - 12
2015 Lener M, Muszynska M, Jakubowska A, Jaworska-Bieniek K, Sukiennicki G, Kaczmarek K, et al., 'Selenium as a marker of cancer risk and of selection for control examinations in surveillance', Wspolczesna Onkologia, 1A A60-A61 (2015)

Publication is summarization of existing data being results of literature review and our experience on usefulness of selenium as a diagnostic marker selection for control examinat... [more]

Publication is summarization of existing data being results of literature review and our experience on usefulness of selenium as a diagnostic marker selection for control examinations in surveillance and as a marker of patients with high risk of cancers.

DOI 10.5114/wo.2014.47131
Citations Scopus - 1
2015 Lubinski J, Scott RJ, Sijmons R, Bayliss K, 'Thank you to all our manuscript reviewers in 2014', Hereditary Cancer in Clinical Practice, 1-2 (2015) [O1]

© 2015 Lubinski et al.; licensee BioMed Central. The editors of Hereditary Cancer in Clinical Practice would like to thank all our reviewers who have contributed to the journal in... [more]

© 2015 Lubinski et al.; licensee BioMed Central. The editors of Hereditary Cancer in Clinical Practice would like to thank all our reviewers who have contributed to the journal in 2014. Without the participation of skilful reviewers, no academic journal could succeed, and we are grateful to the committed individuals who have given their time and expertise to the peer review of manuscripts for Hereditary Cancer in Clinical Practice. We look forward to your continued support in 2015.

DOI 10.1186/s13053-015-0029-y
2015 Peyrot WJ, Lee SH, Milaneschi Y, Abdellaoui A, Byrne EM, Esko T, et al., 'The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25 000 subjects', Molecular Psychiatry, 20 735-743 (2015) [C1]

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotro... [more]

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

DOI 10.1038/mp.2015.50
Citations Scopus - 12Web of Science - 11
Co-authors John Attia, Liz Holliday
2015 Nead KT, Sharp SJ, Thompson DJ, Painter JN, Savage DB, Semple RK, et al., 'Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis.', Journal of the National Cancer Institute, 107 (2015) [C1]
DOI 10.1093/jnci/djv178
Citations Scopus - 37Web of Science - 22
Co-authors John Attia, Mark Mcevoy, Liz Holliday
2015 Bulik-Sullivan B, Loh PR, Finucane HK, Ripke S, Yang J, Patterson N, et al., 'LD score regression distinguishes confounding from polygenicity in genome-wide association studies', Nature Genetics, 47 291-295 (2015) [C1]

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statis... [more]

Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.

DOI 10.1038/ng.3211
Citations Scopus - 355Web of Science - 350
Co-authors Ulrich Schall, Frans Henskens, Murray Cairns, Carmel Loughland, Brian Kelly, Pat Michie, Paul Tooney
2015 Sobral-Leite M, Wesseling J, Smit VTHBM, Nevanlinna H, van Miltenburg MH, Sanders J, et al., 'Annexin A1 expression in a pooled breast cancer series: Association with tumor subtypes and prognosis', BMC Medicine, 13 (2015)

© 2015 Sobral-Leite et al. Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known ab... [more]

© 2015 Sobral-Leite et al. Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germline carriership, specific tumor subtypes and survival in breast cancer patients. Methods: Clinical-pathological information and follow-up data were collected from nine breast cancer studies from the Breast Cancer Association Consortium (BCAC) (n = 5,752) and from one study of familial breast cancer patients with BRCA1/2 mutations (n = 107). ANXA1 expression was scored based on the percentage of immunohistochemical staining in tumor cells. Survival analyses were performed using a multivariable Cox model. Results: The frequency of ANXA1 positive tumors was higher in familial breast cancer patients with BRCA1/2 mutations than in BCAC patients, with 48.6% versus 12.4 %, respectively; P <0.0001. ANXA1 was also highly expressed in BCAC tumors that were poorly differentiated, triple negative, EGFR-CK5/6 positive or had developed in patients at a young age. In the first 5 years of follow-up, patients with ANXA1 positive tumors had a worse breast cancer-specific survival (BCSS) than ANXA1 negative (HR<inf>adj</inf> = 1.35; 95 % CI = 1.05-1.73), but the association weakened after 10 years (HR<inf>adj</inf> = 1.13; 95 % CI = 0.91-1.40). ANXA1 was a significant independent predictor of survival in HER2+ patients (10-years BCSS: HR<inf>adj</inf> = 1.70; 95 % CI = 1.17-2.45). Conclusions: ANXA1 is overexpressed in familial breast cancer patients with BRCA1/2 mutations and correlated with poor prognosis features: triple negative and poorly differentiated tumors. ANXA1 might be a biomarker candidate for breast cancer survival prediction in high risk groups such as HER2+ cases.

DOI 10.1186/s12916-015-0392-6
Citations Scopus - 19
2015 Loarer T, Brezinsek S, Philipps V, Romanelli-Gruenhagen S, Alves D, Carvalho I, et al., 'Plasma isotopic change over experiments in JET under Carbon and ITER-Like Wall conditions', Journal of Nuclear Materials, 463 1117-1121 (2015)

© 2014 Elsevier B.V. Abstract Starting with a wall loaded by H2, change over experiments from H2to D2have been carried out in JET-ILW. A series of 13 repetitive pulses (cumulating... [more]

© 2014 Elsevier B.V. Abstract Starting with a wall loaded by H2, change over experiments from H2to D2have been carried out in JET-ILW. A series of 13 repetitive pulses (cumulating 215 s in divertor configuration) have been performed under conditions of: Ip= 2.0 MA, BT= 2.4 T, <ne> = 4.5 × 1019m-3with a constant gas injection of 3.0 × 1021D s-1and 0.5 MW of auxiliary heating by ICRH in L-mode. Gas balance analysis shows that the total amount of H removed from the wall is in the range of 3 × 1022D compared to 2 × 1023D for JET-C. This is consistent with the faster decay of the H plasma concentration and the drop of the retention also by a similar factor when removing all the carbon components. Isotopic plasma wall changeover is also demonstrated to allow for removal of some D/T from the device. However, since plasma change over also contributes to long-term retention by codeposition, in ITER, change over in between each discharge might not be effective to reduce the fuel retention on the long-term.

DOI 10.1016/j.jnucmat.2014.11.012
Citations Scopus - 1
2015 Petersson P, Rubel M, Esser HG, Likonen J, Koivuranta S, Widdowson A, 'Co-deposited layers in the divertor region of JET-ILW', Journal of Nuclear Materials, 463 814-817 (2015)

� 2015 Published by Elsevier B.V. Abstract Tungsten-coated carbon tiles from a poloidal cross-section of the divertor and several types of erosion-deposition probes from the sha... [more]

� 2015 Published by Elsevier B.V. Abstract Tungsten-coated carbon tiles from a poloidal cross-section of the divertor and several types of erosion-deposition probes from the shadowed areas in the divertor were studied using heavy ion elastic recoil detection to obtain quantitative and depth-resolved deposition patterns. Deuterium, beryllium, carbon, nitrogen and oxygen along with tungsten and Inconel components are the main species detected in the studied surface region. The top of Tile 1 in the inner divertor is the main deposition area where the greatest amounts of deposited species are measured. Beryllium and tungsten-containing deposits on the probes (test mirrors and quartz microbalance) indicate that both low-Z and high-Z metals are transported to remote areas. Deposition of nitrogen-15 tracer used for edge cooling only at the end of experimental campaigns in 2012 was also detected giving evidence that nitrogen is effectively retained in wall components.

DOI 10.1016/j.jnucmat.2014.12.077
Citations Scopus - 16
2015 Bergon A, Belzeaux R, Comte M, Pelletier F, Hervé M, Gardiner EJ, et al., 'CX3CR1 is dysregulated in blood and brain from schizophrenia patients', Schizophrenia Research, 168 434-443 (2015) [C1]

© 2015 Elsevier B.V. The molecular mechanisms underlying schizophrenia remain largely unknown. Although schizophrenia is a mental disorder, there is increasing evidence to indicat... [more]

© 2015 Elsevier B.V. The molecular mechanisms underlying schizophrenia remain largely unknown. Although schizophrenia is a mental disorder, there is increasing evidence to indicate that inflammatory processes driven by diverse environmental factors play a significant role in its development. With gene expression studies having been conducted across a variety of sample types, e.g., blood and postmortem brain, it is possible to investigate convergent signatures that may reveal interactions between the immune and nervous systems in schizophrenia pathophysiology. We conducted two meta-analyses of schizophrenia microarray gene expression data (N= 474) and non-psychiatric control (N= 485) data from postmortem brain and blood. Then, we assessed whether significantly dysregulated genes in schizophrenia could be shared between blood and brain. To validate our findings, we selected a top gene candidate and analyzed its expression by RT-qPCR in a cohort of schizophrenia subjects stabilized by atypical antipsychotic monotherapy (N= 29) and matched controls (N= 31). Meta-analyses highlighted inflammation as the major biological process associated with schizophrenia and that the chemokine receptor CX3CR1 was significantly down-regulated in schizophrenia. This differential expression was also confirmed in our validation cohort. Given both the recent data demonstrating selective CX3CR1 expression in subsets of neuroimmune cells, as well as behavioral and neuropathological observations of CX3CR1 deficiency in mouse models, our results of reduced CX3CR1 expression adds further support for a role played by monocyte/microglia in the neurodevelopment of schizophrenia.

DOI 10.1016/j.schres.2015.08.010
Citations Scopus - 10Web of Science - 13
Co-authors Paul Tooney, Ulrich Schall, Brian Kelly, Murray Cairns
2015 Jaervinen AE, Groth M, Airila M, Belo P, Beurskens M, Brezinsek S, et al., 'Interpretation of radiative divertor studies with impurity seeding in type-I ELMy H-mode plasmas in JET-ILW using EDGE2D-EIRENE', Journal of Nuclear Materials, 463 135-142 (2015)

© 2013 EURATOM. Abstract Nitrogen seeded JET-ILW H-mode plasmas have been investigated with EDGE2D-EIRENE. The simulations reproduce the experimentally observed factor of 10 reduc... [more]

© 2013 EURATOM. Abstract Nitrogen seeded JET-ILW H-mode plasmas have been investigated with EDGE2D-EIRENE. The simulations reproduce the experimentally observed factor of 10 reduction in the outer target power deposition when the normalized divertor radiation, Praddiv/PSOL, increases from the unseeded levels of 15% up to the 50% levels required for detachment. At these radiation levels, nitrogen is predicted dominate the total radiation with a contribution of 85%, consistent with previous measurements in JET-C. Due to the low radiative potential of nitrogen at the electron temperatures above 100 eV, more than 80% of the radiation is predicted to occur in the scrape-off layer, making nitrogen a suitable divertor radiator for typical JET divertor conditions with Tearound 30 eV. The simulations reproduce the experimentally observed particle flux reduction at the low-field side target without the need for strong recombination. This is due to strong impurity radiation reducing the power levels entering the deuterium ionization front.

DOI 10.1016/j.jnucmat.2014.10.047
Citations Scopus - 6
2015 Lerche E, Goniche M, Jacquet P, Van Eester D, Bobkov V, Colas L, et al., 'Impact of localized gas injection on ICRF coupling and SOL parameters in JET-ILW H-mode plasmas', Journal of Nuclear Materials, 463 634-639 (2015)

© 2014 Elsevier B.V. Recent JET-ILW [1,2] experiments reiterated the importance of tuning the plasma fuelling in order to optimize ion cyclotron resonance frequency (ICRF) heating... [more]

© 2014 Elsevier B.V. Recent JET-ILW [1,2] experiments reiterated the importance of tuning the plasma fuelling in order to optimize ion cyclotron resonance frequency (ICRF) heating in high power H-mode discharges. By fuelling the plasma from gas injection modules (GIMs) located in the mid-plane and on the top of the machine instead of adopting the more standardly used divertor GIMs, a considerable increase of the ICRF antenna coupling resistances was achieved with moderate gas injection rates (<1.5 × 1022e/s). This effect is explained by an increase of the scrape-off-layer density in front of the antennas when mid-plane and top fuelling is used. By distributing the gas injection to optimize the coupling of all ICRF antenna arrays simultaneously, a substantial increase in the ICRF power capability and reliability was attained. Although similar core/pedestal plasma properties were observed for the different injection cases, the experiments indicate that the RF-induced impurity sources are reduced when switching from divertor to main chamber gas injection.

DOI 10.1016/j.jnucmat.2014.10.074
Citations Scopus - 1
2015 Tamain P, Joffrin E, Bufferand H, Järvinen A, Brezinsek S, Ciraolo G, et al., 'Investigation of the influence of divertor recycling on global plasma confinement in JET ITER-like wall', Journal of Nuclear Materials, 463 450-454 (2015)

© 2014 Elsevier B.V. Abstract The impact of the divertor geometry on global plasma confinement in type I ELMy H-mode has been investigated in the JET tokamak equipped with ITER-Li... [more]

© 2014 Elsevier B.V. Abstract The impact of the divertor geometry on global plasma confinement in type I ELMy H-mode has been investigated in the JET tokamak equipped with ITER-Like Wall. Discharges have been performed in which the position of the strike-points was changed while keeping the bulk plasma equilibrium essentially unchanged. Large variations of the global plasma confinement have been observed, the H98factor changing from typically 0.7 when the outer strike-point is on the vertical or horizontal targets to 0.9 when it is located in the pump duct entrance. Profiles are mainly impacted in the pedestal but core gradient lengths, especially for the density, are also modified. Although substantial differences are observed in the divertor conditions, none seem to correlate directly with the confinement. Modelling with the EDGE2D-EIRENE and SOLEDGE2D-EIRENE transport codes exhibits differences in the energy losses due to neutrals inside the separatrix, but orders of magnitude are too low to explain simply the impact on the confinement.

DOI 10.1016/j.jnucmat.2014.12.021
Citations Scopus - 2
2015 Khalili H, Gong J, Brenner H, Austin TR, Hutter CM, Baba Y, et al., 'Identification of a common variant with potential pleiotropic effect on risk of inflammatory bowel disease and colorectal cancer', Carcinogenesis, 36 999-1007 (2015)

© The Author 2015. Published by Oxford University Press. All rights reserved. Although genome-wide association studies (GWAS) have separately identified many genetic susceptibilit... [more]

© The Author 2015. Published by Oxford University Press. All rights reserved. Although genome-wide association studies (GWAS) have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies. Among 11794 CRC cases and 14190 controls, rs11676348, the susceptibility single nucleotide polymorphism (SNP) for UC, was significantly associated with reduced risk of CRC (P = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (Pheterogeneity= 0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (Pheterogeneity= 0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (Pheterogeneity= 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC.

DOI 10.1093/carcin/bgv086
Citations Scopus - 10
2015 Martius J, Exner M, Piechota H, Simon A, Kraus-Haas M, Triphaus A, 'Prevention and control of catheter-associated urinary tract infections', Hygiene + Medizin, 40 306-314 (2015)
2015 Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Bloma N, Borggrefe M, Camm J, et al., '2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)', European Heart Journal, 36 2793-2867l (2015)
DOI 10.1093/eurheartj/ehv316
Citations Scopus - 678
2015 Barker-Collo S, Bennett DA, Krishnamurthi RV, Parmar P, Feigin VL, Naghavi M, et al., 'Sex differences in stroke incidence, prevalence,mortality and disability-adjusted life years: Results from the global burden of disease study 2013', Neuroepidemiology, 45 203-214 (2015)

© 2015 S. Karger AG, Basel. Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previo... [more]

© 2015 S. Karger AG, Basel. Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Methods: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Findings: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women.

DOI 10.1159/000441103
Citations Scopus - 41
2015 Escarrabill J, Torrente E, Esquinas C, Hernández C, Monsó E, Freixas M, et al., 'Clinical audit of patients hospitalized due to COPD exacerbation. MAG-1 Study', Archivos de Bronconeumologia, 51 483-489 (2015)

© 2014 SEPAR. Hospitalizations for acute exacerbation of COPD (AECOPD) generate high consumption of health resources, frequent readmissions and high mortality. The MAG -1 study ai... [more]

© 2014 SEPAR. Hospitalizations for acute exacerbation of COPD (AECOPD) generate high consumption of health resources, frequent readmissions and high mortality. The MAG -1 study aims to identify critical points to improve the care process of severe AECOPD requiring hospitalization. Methods: Observational study, with review of clinical records of patients admitted to hospitals of the Catalan public network for AECOPD. The centers were classified into 3 groups according to the number of discharges/year. Demographic and descriptive data of the previous year, pharmacological treatment, care during hospitalization and discharge process and follow-up, mortality and readmission at 30 and 90 days were analyzed. Results: A total of 910 patients (83% male) with a mean age of 74.3 (+10.1) years and a response rate of 70% were included. Smoking habit was determined in only 45% of cases, of which 9% were active smokers. In 31% of cases, no previous lung function data were available. Median hospital stay was 7 days (IQR 4-10), increasing according the complexity of the hospital. Mortality from admission to 90 days was 12.4% with a readmission rate of 49%. An inverse relationship between length of hospital stay and readmission within 90 days was observed. Conclusions: In a large number of medical records, smoking habit and lung function tests were not appropriately reported. Average hospital stay increases with the complexity of the hospital, but longer stays appear to be associated with lower mortality at follow-up.

DOI 10.1016/j.arbr.2015.04.008
Citations Scopus - 9
2015 Aaij R, Abellán Beteta C, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, et al., 'Determination of ¿ and -2ß

© 2014 The Authors. Using the latest LHCb measurements of time-dependent CP violation in the Bs0¿K+K- decay, a U-spin relation between the decay amplitudes of Bs0¿K+K- and B0¿p+p-... [more]

© 2014 The Authors. Using the latest LHCb measurements of time-dependent CP violation in the Bs0¿K+K- decay, a U-spin relation between the decay amplitudes of Bs0¿K+K- and B0¿p+p-decay processes allows constraints to be placed on the angle ¿ of the unitarity triangle and on the Bs0 mixing phase -2ßs. Results from an extended approach, which uses additional inputs on B0¿p0p0and B+¿p+p0decays from other experiments and exploits isospin symmetry, are also presented. The dependence of the results on the maximum allowed amount of U-spin breaking is studied. At 68% probability, the value ¿=(63.5-6.7+7.2)° modulo 180° is determined. In an alternative analysis, the value -2ßs=-0.12-0.16+0.14 rad is found. In both measurements, the uncertainties due to U-spin breaking effects up to 50% are included.

DOI 10.1016/j.physletb.2014.12.015
Citations Scopus - 8
2015 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Observation of the B

© 2015 CERN for the benefit of the LHCb Collaboration. Proton-proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of ... [more]

© 2015 CERN for the benefit of the LHCb Collaboration. Proton-proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb-1, are analysed to search for the charmless B0¿¿0¿0decay. More than 600 B0¿(p+p-)(p+p-) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0¿¿0¿0decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0¿¿0¿0decays yielding a longitudinally polarised final state is measured to be fL=0.745-0.058+0.048(stat)±0.034(syst). The B0¿¿0¿0branching fraction, using the B0¿¿K*(892)0decay as reference, is also reported as B(B0¿¿0¿0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10-6.

DOI 10.1016/j.physletb.2015.06.027
Citations Scopus - 11
2015 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Observation of the decay B-

© 2015 CERN for the benefit of the LHCb Collaboration. The decay B-0s¿ ¿(2S)K+p-is observed using a data set corresponding to an integrated luminosity of 3.0fb-1collected by the L... [more]

© 2015 CERN for the benefit of the LHCb Collaboration. The decay B-0s¿ ¿(2S)K+p-is observed using a data set corresponding to an integrated luminosity of 3.0fb-1collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. The branching fraction relative to the B0¿ ¿(2S)K+p-decay mode is measured to be, where fs/fd indicates the uncertainty due to the ratio of probabilities for a b quark to hadronise into a B0sor B0meson. Using an amplitude analysis, the fraction of decays proceeding via an intermediate K*(892)0meson is measured to be 0.645±0.049(stat)±0.049(syst) and its longitudinal polarisation fraction is 0.524±0.056(stat)±0.029(syst). The relative branching fraction for this component is determined to be. In addition, the mass splitting between the B0sand B0mesons is measured as M(B0s)-M(B0)=87.45±0.44(stat)±0.09(syst)MeV/c2.

DOI 10.1016/j.physletb.2015.06.038
Citations Scopus - 1
2015 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Measurement of the CP-violating phase ßin B

© 2015 The Authors. Time-dependent CPviolation is measured in the B0¿J/¿p+p-channel for each p+p-resonant final state using data collected with an integrated luminosity of 3.0fb-1... [more]

© 2015 The Authors. Time-dependent CPviolation is measured in the B0¿J/¿p+p-channel for each p+p-resonant final state using data collected with an integrated luminosity of 3.0fb-1in ppcollisions using the LHCb detector. The final state with the largest rate, J/¿¿0(770), is used to measure the CP-violating angle 2ßeffto be (41.7 ±9.6+2.8-6.3)°. This result can be used to limit the size of penguin amplitude contributions to CPviolation measurements in, for example, B0s¿J/¿¿decays. Assuming approximate SU(3) flavour symmetry and neglecting higher order diagrams, the shift in the CP-violating phase ¿sis limited to be within the interval [-1.05°, +1.18°] at 95% confidence level. Changes to the limit due to SU(3) symmetry breaking effects are also discussed.

DOI 10.1016/j.physletb.2015.01.008
Citations Scopus - 9
2015 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Measurement of the lifetime of the Bc+ meson using the Bc+¿J/¿p+ decay mode', Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics, 742 29-37 (2015)

© 2015 The Authors. The difference in total widths between the Bc+ and B+mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb-1collected by t... [more]

© 2015 The Authors. The difference in total widths between the Bc+ and B+mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb-1collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of Bc+¿J/¿p+ and B+¿J/¿K+decays, the width difference is measured to bedG=GBc+-GB+=4.46±0.14±0.07mm-1c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+meson is used to convert this to a precise measurement of the Bc+ lifetime,tBc+=513.4±11.0±5.7fs, where the first uncertainty is statistical and the second is systematic.

DOI 10.1016/j.physletb.2015.01.010
Citations Scopus - 12
2015 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Study of the rare Bs0 and B0 decays into the p+p-µ+µ- final state', Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics, 743 46-55 (2015)

© 2015 The Authors. A search for the rare decays Bs0¿p+p-µ+µ- and B0¿p+p-µ+µ- is performed in a data set corresponding to an integrated luminosity of 3.0 fb-1 collected by the LHC... [more]

© 2015 The Authors. A search for the rare decays Bs0¿p+p-µ+µ- and B0¿p+p-µ+µ- is performed in a data set corresponding to an integrated luminosity of 3.0 fb-1 collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0¿p+p-µ+µ- and the first evidence of the decay B0¿p+p-µ+µ- are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0¿p+p-µ+µ-)=(8.6±1.5(stat)±0.7(syst)±0.7(norm))×10-8 and B(B0¿p+p-µ+µ-)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))×10-8, where the third uncertainty is due to the branching fraction of the decay B0¿J/¿(¿µ+µ-)K*(892)0(¿K+p-), used as a normalisation.

DOI 10.1016/j.physletb.2015.02.010
2015 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Search for CP violation in D

© 2014 The Authors. A search for time-integrated CP violation in the Cabibbo-suppressed decay D0¿p-p+p0is performed using for the first time an unbinned model-independent techniqu... [more]

© 2014 The Authors. A search for time-integrated CP violation in the Cabibbo-suppressed decay D0¿p-p+p0is performed using for the first time an unbinned model-independent technique known as the energy test. Using proton-proton collision data, corresponding to an integrated luminosity of 2.0fb-1collected by the LHCb detector at a centre-of-mass energy of s=8TeV, the world's best sensitivity to CP violation in this decay is obtained. The data are found to be consistent with the hypothesis of CP symmetry with a p-value of (2.6±0.5)%.

DOI 10.1016/j.physletb.2014.11.043
Citations Scopus - 11
2015 Reis RS, Bernardi JR, Steiner M, Meaney MJ, Levitan RD, Silveira PP, 'Poor infant inhibitory control predicts food fussiness in childhood - A possible protective role of n-3 PUFAs for vulnerable children', Prostaglandins Leukotrienes and Essential Fatty Acids, 97 21-25 (2015)

© 2015 Elsevier Ltd. Intrauterine growth restriction (IUGR) children are more impulsive towards a sweet reward and have altered feeding behavior in adulthood. We hypothesized that... [more]

© 2015 Elsevier Ltd. Intrauterine growth restriction (IUGR) children are more impulsive towards a sweet reward and have altered feeding behavior in adulthood. We hypothesized that early life inhibitory control predicts feeding behaviors later on in childhood, and the consumption of n-3 PUFAs during infancy may protect IUGR children from developing problematic feeding behaviors. 156 children had information on the Early Childhood Behavior Questionnaire (ECBQ) at 18 months, Food Frequency Questionnaire at 48 months and Children's Eating Behavior Questionnaire (CEBQ) at 72 months. There was a significant negative correlation between inhibitory control at 18 months and food fussiness at 72 months. A GLM model predicting food fussiness at 72 months showed significant interaction between n-3 PUFAs, inhibitory control and IUGR, with higher intakes associated with decreased risk for fussiness in IUGR children with poor inhibitory control. Deficits in early inhibitory control predict later food fussiness, and higher intakes of n-3 PUFAs in infancy may protect IUGR children from developing such behavior later.

DOI 10.1016/j.plefa.2015.03.004
Citations Scopus - 2
2015 Neri L, Conway PM, Basilisco G, Altomare DF, Annese V, Badiali D, et al., 'Confirmatory factor analysis of the Patient Assessment of Constipation-Symptoms (PAC-SYM) among patients with chronic constipation', Quality of Life Research, 24 1597-1605 (2015)

© Springer International Publishing Switzerland 2014. Background and aim: PAC-SYM is widely adopted to asses constipation severity. However, it has been validated in a small sampl... [more]

© Springer International Publishing Switzerland 2014. Background and aim: PAC-SYM is widely adopted to asses constipation severity. However, it has been validated in a small sample, few items have been included based on expert opinion and not on empirical grounds, and its factor structure has never been replicated. We aimed at evaluating the psychometric properties of PAC-SYM in patients with chronic constipation. Methods: We enrolled 2,203 outpatients with chronic constipation in two waves. We used wave I sample to test the psychometric properties of the PAC-SYM and wave II sample to cross-validate its factor structure, to assess criterion validity, responsiveness to clinical change, and its minimal clinically important difference. Results: Only a minority of patients reported any rectal tearing (38 %). Deletion of such item leads to a 11-item version (M:PAC-SYM). The remaining items in the rectal domain were moderately correlated with the stool domain. Exploratory factor analysis and confirmatory factor analysis revealed a bifactor structure with two subscales (stool and abdominal symptoms) and a general severity factor. The M:PAC-SYM demonstrated excellent reliability, moderate correlation with SF-12 and treatment satisfaction (r = 0.28-0.45), discrimination across Rome III criteria for functional constipation and abdominal pain, and responsiveness to clinical change (ß = -0.49; ¿2= 0.25). M:PAC-SYM minimal clinically important difference was 0.24. Conclusion: Our analysis shows that the rectal domain may not represent a relevant cluster of symptoms for patients with chronic constipation. We developed a modified version of the PAC-SYM which might better represent symptom severity of most patients seeking care in gastroenterology referral centers.

DOI 10.1007/s11136-014-0886-2
Citations Scopus - 7
2015 Richert K, Emanuel L, Gibson W, Giroux B, Keisler M, Oberg M, et al., 'Comments on NCFS views document: ¿scientific literature in support of forensic science and practice¿', AFTE Journal, 47 109-111 (2015)
2015 Fitzgerald C, Welch S, Taylor S, Harding A, Graudins L, Lawrence D, et al., 'SHPA standards of practice in emergency medicine pharmacy practice: SHPA committee of specialty practice in emergency medicine', Journal of Pharmacy Practice and Research, 45 423-430 (2015)
DOI 10.1002/jppr.1144
Citations Scopus - 4
2015 Andersson L, Archibald AL, Bottema CD, Brauning R, Burgess SC, Burt DW, et al., 'Coordinated international action to accelerate genome-to-phenome with FAANG, the Functional Annotation of Animal Genomes project', Genome Biology, 16 (2015)

© 2015 Andersson et al. We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce compre... [more]

© 2015 Andersson et al. We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species.

DOI 10.1186/s13059-015-0622-4
Citations Scopus - 60
2015 Hackley PC, Warwick PD, Ambrose WA, Cardott BJ, Levine JR, Pashin JC, et al., 'Unconventional energy resources: 2015 review', Natural Resources Research, 24 443-508 (2015)

© 2015 Springer Science+Business Media New York (Outside USA). This paper includes 10 summaries for energy resource commodities including coal and unconventional resources, and an... [more]

© 2015 Springer Science+Business Media New York (Outside USA). This paper includes 10 summaries for energy resource commodities including coal and unconventional resources, and an analysis of energy economics and technology prepared by committees of the Energy Minerals Division of the American Association of Petroleum Geologists. Unconventional energy resources, as used in this report, are those energy resources that do not occur in discrete oil or gas reservoirs held in structural or stratigraphic traps in sedimentary basins. Such resources include coalbed methane, oil shale, U and Th deposits and associated rare earth elements of industrial interest, geothermal, gas shale and liquids, tight gas sands, gas hydrates, and bitumen and heavy oil. Current U.S. and global research and development activities are summarized for each unconventional energy resource commodity in the topical sections of this report, followed by analysis of unconventional energy economics and technology.

DOI 10.1007/s11053-015-9288-6
Citations Scopus - 2
2015 Garvey C, McBride T, Nevin L, Parthasarathy S, Peiperl L, Ross A, et al., 'Progress in Medicine: Experts Take Stock', PLoS Medicine, 12 (2015)
DOI 10.1371/journal.pmed.1001933
Citations Scopus - 1
2015 Moussian B, Letizia A, Martínez-Corrales G, Rotstein B, Casali A, Llimargas M, 'Correction: Deciphering the Genetic Programme Triggering Timely and Spatially-Regulated Chitin Deposition(PLoS Genet, (2015), 11(3))', PLoS Genetics, 11 (2015)
DOI 10.1371/journal.pgen.1005054
2015 Elli L, Maieron R, Martelossi S, Guariso G, Buscarini E, Conte D, et al., 'Transition of gastroenterological patients from paediatric to adult care: A position statement by the Italian Societies of Gastroenterology', Digestive and Liver Disease, 47 734-740 (2015)

© 2015 Editrice Gastroenterologica Italiana S.r.l.. In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutriti... [more]

© 2015 Editrice Gastroenterologica Italiana S.r.l.. In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood.

DOI 10.1016/j.dld.2015.04.002
Citations Scopus - 8
2015 Andersen AB, Thurnham D, Tomkins A, Mussa K, Masilingi C, Fue E, et al., 'Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: A randomised controlled trial', BMC Medicine, 13 (2015)

© 2015 Filteau et al. Background: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that sh... [more]

© 2015 Filteau et al. Background: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. Methods: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5kg/m2who were referred for ART based on CD4 count <350 cells/µL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30g/day (150kcal) from recruitment until 2weeks after starting ART and 250g/day (1,400kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12weeks ART. Results: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12weeks post-ART was 25 cells/µL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). Conclusions: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients.

DOI 10.1186/s12916-014-0253-8
Citations Scopus - 19
2015 Karstoft KI, Galatzer-Levy IR, Statnikov A, Li Z, Shalev AY, Ankri Y, et al., 'Bridging a translational gap: Using machine learning to improve the prediction of PTSD', BMC Psychiatry, 15 (2015)

© 2015 Karstoft et al. Background: Predicting Posttraumatic Stress Disorder (PTSD) is a pre-requisite for targeted prevention. Current research has identified group-level risk-ind... [more]

© 2015 Karstoft et al. Background: Predicting Posttraumatic Stress Disorder (PTSD) is a pre-requisite for targeted prevention. Current research has identified group-level risk-indicators, many of which (e.g., head trauma, receiving opiates) concern but a subset of survivors. Identifying interchangeable sets of risk indicators may increase the efficiency of early risk assessment. The study goal is to use supervised machine learning (ML) to uncover interchangeable, maximally predictive combinations of early risk indicators. Methods: Data variables (features) reflecting event characteristics, emergency department (ED) records and early symptoms were collected in 957 trauma survivors within ten days of ED admission, and used to predict PTSD symptom trajectories during the following fifteen months. A Target Information Equivalence Algorithm (TIE*) identified all minimal sets of features (Markov Boundaries; MBs) that maximized the prediction of a non-remitting PTSD symptom trajectory when integrated in a support vector machine (SVM). The predictive accuracy of each set of predictors was evaluated in a repeated 10-fold cross-validation and expressed as average area under the Receiver Operating Characteristics curve (AUC) for all validation trials. Results: The average number of MBs per cross validation was 800. MBs' mean AUC was 0.75 (95% range: 0.67-0.80). The average number of features per MB was 18 (range: 12-32) with 13 features present in over 75% of the sets. Conclusions: Our findings support the hypothesized existence of multiple and interchangeable sets of risk indicators that equally and exhaustively predict non-remitting PTSD. ML's ability to increase prediction versatility is a promising step towards developing algorithmic, knowledge-based, personalized prediction of post-traumatic psychopathology.

DOI 10.1186/s12888-015-0399-8
Citations Scopus - 23
2015 Agua-Agum J, Ariyarajah A, Aylward B, Blake IM, Brennan R, Cori A, et al., 'West African Ebola epidemic after one year--slowing but not yet under control', The New England journal of medicine, 372 584-587 (2015)
DOI 10.1056/NEJMc1414992
Citations Scopus - 12
2015 Man MS, Rick J, Bower P, Thomas C, Edwards L, Montgomery AA, et al., 'Improving recruitment to a study of telehealth management for long-term conditions in primary care: Two embedded, randomised controlled trials of optimised patient information materials', Trials, 16 (2015)

© 2015 Man et al. Background: Patient understanding of study information is fundamental to gaining informed consent to take part in a randomised controlled trial. In order to meet... [more]

© 2015 Man et al. Background: Patient understanding of study information is fundamental to gaining informed consent to take part in a randomised controlled trial. In order to meet the requirements of research ethics committees, patient information materials can be long and need to communicate complex messages. There is concern that standard approaches to providing patient information may deter potential participants from taking part in trials. The Systematic Techniques for Assisting Recruitment to Trials (MRC-START) research programme aims to test interventions to improve trial recruitment. The aim of this study was to investigate the effect on recruitment of optimised patient information materials (with improved readability and ease of comprehension) compared with standard materials. The study was embedded within two primary care trials involving patients with long-term conditions. Methods: The Healthlines Study involves two linked trials evaluating a telehealth intervention in patients with depression (Healthlines Depression) or raised cardiovascular disease risk (Healthlines CVD). We conducted two trials of a recruitment intervention, embedded within the Healthlines host trials. Patients identified as potentially eligible in each of the Healthlines trials were randomised to receive either the original patient information materials or optimised versions of these materials. Primary outcomes were the proportion of participants randomised (Healthlines Depression) and the proportion expressing interest in taking part (Healthlines CVD). Results: In Healthlines Depression (n = 1364), 6.3 % of patients receiving the optimised patient information materials were randomised into the study compared to 4.0 % in those receiving standard materials (OR = 1.63, 95 % CI = 1.00 to 2.67). In Healthlines CVD (n = 671) 24.0 % of those receiving optimised patient information materials responded positively to the invitation to participate, compared to 21.9 % in those receiving standard materials (OR = 1.12, 95 % CI = 0.78 to 1.61). Conclusions: Evidence from these two embedded trials suggests limited benefits of optimised patient information materials on recruitment rates, which may only be apparent in some patient populations, with no effects on other outcomes. Further embedded trials are needed to provide a more precise estimate of effect, and to explore further how effects vary by trial context, intervention, and patient population.

DOI 10.1186/s13063-015-0820-0
Citations Scopus - 9
2015 Green MJ, Raudino A, Cairns MJ, Wu J, Tooney PA, Scott RJ, Carr VJ, 'Do common genotypes of FK506 binding protein 5 (FKBP5) moderate the effects of childhood maltreatment on cognition in schizophrenia and healthy controls?', Journal of Psychiatric Research, 70 9-17 (2015) [C1]

© 2015. Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in psychotic and other disorders, via their role in regulating glucocorticoid receptor (GR) rece... [more]

© 2015. Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in psychotic and other disorders, via their role in regulating glucocorticoid receptor (GR) receptor sensitivity and effects on the broader function of the HPA system in response to stress. In this study, the effects of four FKBP5 polymorphisms (rs1360780, rs9470080, rs4713902, rs9394309) on IQ and eight other cognitive domains were examined in the context of exposure to childhood maltreatment in 444 cases with schizophrenia and 292 healthy controls (from a total sample of 617 cases and 659 controls obtained from the Australian Schizophrenia Research Bank; ASRB). Participants subjected to any kind of maltreatment (including physical, emotional, or sexual abuse or physical or emotional neglect) in childhood were classified as 'exposed'; cognitive functioning was measured with Repeatable Battery for the Assessment of Neuropsychological Status, the Controlled Oral Word Association Test, and IQ was estimated with the Weschler Test of Adult Reading. Hierarchical regressions were used to test the main effects of genotype and childhood maltreatment, and their additive interactive effects, on cognitive function. For rs1360870, there were significant main effects of genotype and childhood maltreatment, and a significant interaction of genotype with childhood trauma affecting attention in both schizophrenia and healthy participants (C-homozygotes in both groups showed worse attention in the context of maltreatment); in SZ, this SNP also affected global neuropsychological function regardless of exposure to childhood trauma, with T-homozygotes showing worse cognition than other genotypes. The mechanisms of trauma-dependent effects of FKBP5 following early life trauma deserve further exploration in healthy and psychotic samples, in the context of epigenetic effects and perhaps epistasis with other genes. Study of these processes may be particularly informative in subgroups exposed to various other forms of early life adversity (i.e., birth complications, immigration).

DOI 10.1016/j.jpsychires.2015.07.019
Citations Scopus - 6Web of Science - 6
Co-authors Paul Tooney, Murray Cairns
2015 Abdullah N, Abdul Murad NA, Attia J, Oldmeadow C, Mohd Haniff EA, Syafruddin SE, et al., 'Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.', Diabet Med, 32 1377-1384 (2015) [C1]
DOI 10.1111/dme.12735
Citations Scopus - 2Web of Science - 1
Co-authors Liz Holliday, John Attia, Christopher Oldmeadow
2015 Darabi H, McCue K, Beesley J, Michailidou K, Nord S, Kar S, et al., 'Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression', American Journal of Human Genetics, (2015) [C1]

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely ... [more]

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.

DOI 10.1016/j.ajhg.2015.05.002
Citations Scopus - 15Web of Science - 12
2015 Bowden NA, Beveridge NJ, Ashton KA, Baines KJ, Scott RJ, 'Understanding xeroderma pigmentosum complementation groups using gene expression profiling after UV-light exposure', International Journal of Molecular Sciences, 16 15985-15996 (2015) [C1]

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fo... [more]

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Children with the recessive genetic disorder Xeroderma Pigmentosum (XP) have extreme sensitivity to UV-light, a 10,000-fold increase in skin cancers from age 2 and rarely live beyond 30 years. There are seven genetic subgroups of XP, which are all resultant of pathogenic mutations in genes in the nucleotide excision repair (NER) pathway and a XP variant resultant of a mutation in translesion synthesis, POLH. The clinical symptoms and severity of the disease is varied across the subgroups, which does not correlate with the functional position of the affected protein in the NER pathway. The aim of this study was to further understand the biology of XP subgroups, particularly those that manifest with neurological symptoms. Whole genome gene expression profiling of fibroblasts from each XP complementation group was assessed before and after UV-light exposure. The biological pathways with altered gene expression after UV-light exposure were distinct for each subtype and contained oncogenic related functions such as perturbation of cell cycle, apoptosis, proliferation and differentiation. Patients from the subgroups XP-B and XP-F were the only subgroups to have transcripts associated with neuronal activity altered after UV-light exposure. This study will assist in furthering our understanding of the different subtypes of XP which will lead to better diagnosis, treatment and management of the disease.

DOI 10.3390/ijms160715985
Citations Scopus - 7Web of Science - 6
Co-authors Katherine Baines, Nikola Bowden
2015 Serrano-Fernandez P, Dymerska D, Kurzawski G, Derkacz R, Sobieszczanska T, Banaszkiewicz Z, et al., 'Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia', GASTROENTEROLOGY RESEARCH AND PRACTICE, (2015) [C1]
DOI 10.1155/2015/204089
Citations Scopus - 3
2015 Blackwell C, Moscovis S, Hall S, Burns C, Scott RJ, 'Exploring the risk factors for sudden infant deaths and their role in inflammatory responses to infection', Frontiers in Immunology, 6 (2015) [C1]

© 2015 Blackwell, Moscovis, Hall, Burns and Scott. The risk factors for sudden infant death syndrome (SIDS) parallel those associated with susceptibility to or severity of infecti... [more]

© 2015 Blackwell, Moscovis, Hall, Burns and Scott. The risk factors for sudden infant death syndrome (SIDS) parallel those associated with susceptibility to or severity of infectious diseases. There is no evidence that a single infectious agent is associated with SIDS; the common thread appears to be induction of inflammatory responses to infections. In this review, interactions between genetic and environmental risk factors for SIDS are assessed in relation to the hypothesis that many infant deaths result from dysregulation of inflammatory responses to "minor" infections. Risk factors are assessed in relation to three important stages of infection: (1) bacterial colonization (frequency or density); (2) induction of temperature-dependent toxins; (3) induction or control of inflammatory responses. In this article, we review the interactions among risk factors for SIDS for their effects on induction or control of inflammatory responses. The risk factors studied are genetic factors (sex, cytokine gene polymorphisms among ethnic groups at high or low risk of SIDS); developmental stage (changes in cortisol and testosterone levels associated with 2- to 4-month age range); environmental factors (virus infection, exposure to cigarette smoke). These interactions help to explain differences in the incidences of SIDS observed between ethnic groups prior to public health campaigns to reduce these infant deaths.

DOI 10.3389/fimmu.2015.00044
Citations Scopus - 7Web of Science - 7
Co-authors Caroline Blackwell, Sharron Hall
2015 Mavaddat N, Pharoah PDP, Michailidou K, Tyrer J, Brook MN, Bolla MK, et al., 'Prediction of breast cancer risk based on profiling with common genetic variants', Journal of the National Cancer Institute, 107 (2015) [C1]

© 2015 © The Author 2015. Published by Oxford University Press. Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at ... [more]

© 2015 © The Author 2015. Published by Oxford University Press. Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

DOI 10.1093/jnci/djv036
Citations Scopus - 132Web of Science - 120
2015 Movahedi M, Bishop DT, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al., 'Obesity, aspirin, and risk of colorectal cancer in carriers of hereditary colorectal cancer: A prospective investigation in the CAPP2 study', Journal of Clinical Oncology, 33 3591-3597 (2015) [C1]

© 2015 American Society of Clinical Oncology. All rights reserved. Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC)... [more]

© 2015 American Society of Clinical Oncology. All rights reserved. Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). Patients and Methods: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2×2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. Results: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41 X (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). Conclusion: Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

DOI 10.1200/JCO.2014.58.9952
Citations Scopus - 28Web of Science - 22
2015 Debette S, Ibrahim Verbaas CA, Bressler J, Schuur M, Smith A, Bis JC, et al., 'Genome-wide studies of verbal declarative memory in nondemented older people: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium', Biological Psychiatry, 77 749-763 (2015) [C1]

� 2015 Society of Biological Psychiatry. BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed t... [more]

� 2015 Society of Biological Psychiatry. BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. METHODS: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged =45 years. Replication of suggestive associations (p < 5 � 10-6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. RESULTS: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 � 10-10) and replication cohorts (p = 5.65 � 10-8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 � 10-8, and rs6813517 [SPOCK3], p = 2.58 � 10-8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. CONCLUSIONS: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

DOI 10.1016/j.biopsych.2014.08.027
Citations Scopus - 21Web of Science - 21
Co-authors Christopher Oldmeadow, Peter Schofield, John Attia, Liz Holliday, Mark Mcevoy
2015 Greenop KR, Miller M, Bailey HD, Scott RJ, Attia J, Bower C, et al., 'Paternal dietary folate, B6 and B12 intake, and the risk of childhood brain tumors', Nutrition and Cancer, 67 224-230 (2015) [C1]

© 2015, Taylor &amp; Francis Group, LLC. It is biologically plausible that a paternal preconception diet low in nutrients related to DNA integrity could affect sperm DNA and sub... [more]

© 2015, Taylor & Francis Group, LLC. It is biologically plausible that a paternal preconception diet low in nutrients related to DNA integrity could affect sperm DNA and subsequently risk of cancer in the offspring. The aim of this analysis was to investigate whether paternal preconception dietary folate, B6, or B12 intake was associated with the risk of childhood brain tumors (CBT) in an Australian case-control study. Cases <15 years of age were recruited from 10 Australian pediatric oncology centers between 2005 and 2010, and controls from random-digit dialing, frequency-matched to cases on age, sex, and state of residence. Paternal dietary information was obtained by food-frequency questionnaires. Nutrient values were energy adjusted and divided into tertiles for analysis by unconditional logistic regression. In fathers with relevant data (237 cases and 629 controls), no association with dietary folate and B6 and risk of CBT was seen; high B12 intake was associated with an increased risk of CBT (odds ratio highest vs. lowest tertile: 1.74, 95% confidence interval: 1.14, 2.66) without an increasing trend. These results do not support the hypothesis that paternal dietary folate intake influences the risk of CBT. The increased OR observed between dietary B12 intake and risk of CBT is without any certain explanation.

DOI 10.1080/01635581.2015.990571
Citations Scopus - 2Web of Science - 3
Co-authors John Attia
2015 Pundavela J, Roselli S, Faulkner S, Attia J, Scott RJ, Thorne RF, et al., 'Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer', Molecular Oncology, 9 1626-1635 (2015) [C1]
DOI 10.1016/j.molonc.2015.05.001
Citations Scopus - 11Web of Science - 9
Co-authors Marjorie Walker, Phillip Jobling, Rick Thorne, John Forbes, Hubert Hondermarck, John Attia
2015 Garrison JR, Fernyhough C, McCarthy-Jones S, Haggard M, Carr V, Schall U, et al., 'Paracingulate sulcus morphology is associated with hallucinations in the human brain', Nature Communications, 6 (2015) [C1]
DOI 10.1038/ncomms9956
Citations Scopus - 9Web of Science - 7
Co-authors Ulrich Schall, Frans Henskens, Carmel Loughland, Pat Michie
2015 Moir-Meyer GL, Pearson JF, Lose F, The ANECSG, Scott RJ, McEvoy M, et al., 'Rare germline copy number deletions of likely functional importance are implicated in endometrial cancer predisposition', Human Genetics, 134 269-278 (2015) [C1]

© 2014, Springer-Verlag Berlin Heidelberg. Endometrial cancer is the most common invasive gynaecological cancer in women, and relatively little is known about inherited risk facto... [more]

© 2014, Springer-Verlag Berlin Heidelberg. Endometrial cancer is the most common invasive gynaecological cancer in women, and relatively little is known about inherited risk factors for this disease. This is the first genome-wide study to explore the role of common and rare germline copy number variants (CNVs) in predisposition to endometrial cancer. CNVs were called from germline DNA of 1,209 endometrioid endometrial cancer cases and 528 cancer-unaffected female controls. Overall CNV load of deletions or DNA gains did not differ significantly between cases and controls (P¿>¿0.05), but cases presented with an excess of rare germline deletions overlapping likely functional genomic regions including genes (P¿=¿8¿×¿10<sup>-10</sup>), CpG islands (P¿=¿1¿×¿10<sup>-7</sup>) and sno/miRNAs regions (P¿=¿3¿×¿10<sup>-9</sup>). On average, at least one additional gene and two additional CpG islands were disrupted by rare deletions in cases compared to controls. The most pronounced difference was that over 30 sno/miRNAs were disrupted by rare deletions in cases for every single disruption event in controls. A total of 13 DNA repair genes were disrupted by rare deletions in 19/1,209 cases (1.6¿%) compared to one gene in 1/528 controls (0.2¿%; P¿=¿0.007), and this increased DNA repair gene loss in cases persisted after excluding five individuals carrying CNVs disrupting mismatch repair genes MLH1, MSH2 and MSH6 (P¿=¿0.03). There were 34 miRNA regions deleted in at least one case but not in controls, the most frequent of which encompassed hsa-mir-661 and hsa-mir-203. Our study implicates rare germline deletions of functional and regulatory regions as possible mechanisms conferring endometrial cancer risk, and has identified specific regulatory elements as candidates for further investigation.

DOI 10.1007/s00439-014-1507-4
Citations Scopus - 5Web of Science - 4
Co-authors Mark Mcevoy, Liz Holliday, John Attia
2015 Mathe A, Wong-Brown M, Morten B, Forbes JF, Braye SG, Avery-Kiejda KA, Scott RJ, 'Novel genes associated with lymph node metastasis in triple negative breast cancer', Scientific Reports, 5 (2015) [C1]

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop met... [more]

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop metastases and relapse than patients with other breast cancer subtypes. We aimed to identify TNBC-specific genes and genes associated with lymph node metastasis, one of the first signs of metastatic spread. A total of 33 TNBCs were used; 17 of which had matched normal adjacent tissues available, and 15 with matched lymph node metastases. Gene expression microarray analysis was used to reveal genes that were differentially expressed between these groups. We identified and validated 66 genes that are significantly altered when comparing tumours to normal adjacent samples. Further, we identified 83 genes that are associated with lymph node metastasis and correlated these with miRNA-expression. Pathway analysis revealed their involvement in DNA repair, recombination and cell death, chromosomal instability and other known cancer-related pathways. Finally, four genes were identified that were specific for TNBC, of which one was associated with overall survival. This study has identified novel genes involved in LN metastases in TNBC and genes that are TNBC specific that may be used as treatment targets or prognostic indicators in the future.

DOI 10.1038/srep15832
Citations Scopus - 11Web of Science - 10
Co-authors John Forbes, Andrea Mathe, Michelle Wong-Brown, Kelly Kiejda
2015 Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott RJ, Hall ST, et al., 'Virus infections and sudden death in infancy: The role of interferon-¿', Frontiers in Immunology, 6 (2015) [C1]

© 2015 Moscovis, Gordon, Al Madani, Gleeson, Scott, Hall, Burns and Blackwell. Respiratory infections have been implicated in sudden infant death syndrome (SIDS). As interferon-¿ ... [more]

© 2015 Moscovis, Gordon, Al Madani, Gleeson, Scott, Hall, Burns and Blackwell. Respiratory infections have been implicated in sudden infant death syndrome (SIDS). As interferon-¿ (IFN-¿) is a major response to virus infection, we examined (1) the frequency of single nucleotide polymorphism (SNP), IFNG T + 874A, in SIDS infants, their parents, and ethnic groups with different incidences of SIDS; (2) model systems with a monocytic cell line (THP-1) and human peripheral blood monocytes (PBMC) for effects of levels of IFN-¿ on inflammatory responses to bacterial antigens identified in SIDS; (3) interactions between genetic and environmental factors on IFN-¿ responses. IFNG T + 874A genotypes were determined for SIDS infants from three countries; families who had a SIDS death; populations with high (Indigenous Australian), medium (Caucasian), and low (Bangladeshi) SIDS incidences. The effect of IFN-¿ on cytokine responses to endotoxin was examined in model systems with THP-1 cells and human PBMC. The IFN-¿ responses to endotoxin and toxic shock syndrome toxin (TSST-1) were assessed in relation to genotype, gender, and reported smoking. There was a marginal association with IFNG T + 874A genotype and SIDS (p = 0.06). Indigenous Australians had significantly higher proportions of the IFNG T + 874A SNP (TT) associated with high responses of IFN-¿. THP-1 cells showed a dose dependent effect of IFN-¿ on cytokine responses to endotoxin. For PBMC, IFN-¿ enhanced interleukin (IL)-1ß, IL-6, and tumor necrosis factor-a responses but reduced IL-8 and IL-10 responses. Active smoking had a suppressive effect on baseline levels of IFN-¿. There was no effect of gender or genotype on IFN-¿ responses to bacterial antigens tested; however, significant differences were observed between genotypes in relation to smoking. The results indicate virus infections contribute to dysregulation of cytokine responses to bacterial antigens and studies on physiological effects of genetic factors must include controls for recent or concurrent infection and exposure to cigarette smoke.

DOI 10.3389/fimmu.2015.00107
Citations Scopus - 3Web of Science - 3
Co-authors Sharron Hall, Caroline Blackwell, Maree Gleeson
2015 Vilhjálmsson BJ, Yang J, Finucane HK, Gusev A, Lindström S, Ripke S, et al., 'Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores', American Journal of Human Genetics, 97 576-592 (2015) [C1]

© 2015 The American Society of Human Genetics. All rights reserved. Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate... [more]

© 2015 The American Society of Human Genetics. All rights reserved. Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R2increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.

DOI 10.1016/j.ajhg.2015.09.001
Citations Scopus - 88Web of Science - 85
Co-authors Paul Tooney, Pat Michie, Brian Kelly, Ulrich Schall, Frans Henskens, Carmel Loughland
2015 Rush A, Christiansen JH, Farrell JP, Goode SM, Scott RJ, Spring KJ, Byrne JA, 'Biobank classification in an Australian setting', Biopreservation and Biobanking, 13 212-218 (2015) [C1]
DOI 10.1089/bio.2015.0007
Citations Scopus - 5
2015 Painter JN, O'Mara TA, Batra J, Cheng T, Lose FA, Dennis J, et al., 'Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk', HUMAN MOLECULAR GENETICS, 24 1478-1492 (2015) [C1]
DOI 10.1093/hmg/ddu552
Citations Scopus - 25Web of Science - 22
Co-authors Mark Mcevoy, Liz Holliday, John Attia
2015 Gu BJ, Field J, Dutertre S, Ou A, Kilpatrick TJ, Lechner-Scott J, et al., 'A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.', Human molecular genetics, 24 5644-5654 (2015) [C1]
DOI 10.1093/hmg/ddv278
Citations Scopus - 16Web of Science - 16
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2015 Field J, Shahijanian F, Schibeci S, Johnson L, Gresle M, Laverick L, et al., 'The MS risk allele of CD40 is associated with reduced cell-membrane bound expression in antigen presenting cells: Implications for gene function', PLoS ONE, 10 (2015) [C1]

© 2015 Field et al. Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specif... [more]

© 2015 Field et al. Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS.

DOI 10.1371/journal.pone.0127080
Citations Scopus - 11Web of Science - 9
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2015 Hancock DB, Levy JL, Gaddis NC, Glasheen C, Saccone NL, Page GP, et al., 'Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1', Biological Psychiatry, 78 474-484 (2015) [C1]
DOI 10.1016/j.biopsych.2015.01.003
Citations Scopus - 15Web of Science - 18
Co-authors Mark Mcevoy, Liz Holliday, John Attia
2015 Holliday EG, Traylor M, Malik R, Bevan S, Falcone G, Hopewell JC, et al., 'Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke', STROKE, 46 615-+ (2015) [C1]
DOI 10.1161/STROKEAHA.114.007930
Citations Scopus - 18Web of Science - 17
Co-authors Christopher Oldmeadow, Lisa Lincz, Christopher Levi, Liz Holliday, John Attia
2015 Sapkota Y, Low SK, Attia J, Gordon SD, Henders AK, Holliday EG, et al., 'Association between endometriosis and the interleukin 1A (IL1A) locus.', Human Reproduction, 30 239-248 (2015) [C1]
DOI 10.1093/humrep/deu267
Citations Scopus - 30Web of Science - 26
Co-authors John Attia, Mark Mcevoy, Liz Holliday
2015 Finucane HK, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y, Loh P-R, et al., 'Partitioning heritability by functional annotation using genome-wide association summary statistics', Nature Genetics, 47 1228-1235 (2015) [C1]
DOI 10.1038/ng.3404
Co-authors Pat Michie, Ulrich Schall, Frans Henskens, Carmel Loughland, Paul Tooney
2015 Loh P-R, Bhatia G, Gusev A, Finucane HK, Bulik-Sullivan BK, Pollack SJ, et al., 'Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis', Nature Genetics, 47 1385-1392 (2015) [C1]
DOI 10.1038/ng.3431
Co-authors Carmel Loughland, Frans Henskens, Pat Michie, Paul Tooney, Ulrich Schall
2015 O'Mara TA, Glubb DM, Painter JN, Cheng T, Dennis J, Australian National Endometrial Cancer Study Group (ANECS), et al., 'Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.', Endocr Relat Cancer, 22 851-861 (2015) [C1]
DOI 10.1530/ERC-15-0319
Citations Scopus - 6Web of Science - 6
Co-authors John Attia, Liz Holliday, Mark Mcevoy
2015 Ingason A, Giegling I, Hartmann AM, Genius J, Konte B, Friedl M, et al., 'Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case¿control sample of schizophrenia', Translational Psychiatry, 5 e656-e656 (2015) [C1]
DOI 10.1038/tp.2015.151
Co-authors Carmel Loughland, Frans Henskens, Paul Tooney, Ulrich Schall, Brian Kelly, Pat Michie, Murray Cairns
2015 Thompson ER, Gorringe KL, Rowley SM, Li N, McInerny S, Wong-Brown MW, et al., 'Reevaluation of the BRCA2 truncating allele c.9976A \ T (p.Lys3326Ter) in a familial breast cancer context', SCIENTIFIC REPORTS, 5 (2015) [C1]
DOI 10.1038/srep14800
Citations Scopus - 10Web of Science - 9
Co-authors Michelle Wong-Brown
2015 Cropley VL, Scarr E, Fornito A, Klauser P, Bousman CA, Scott R, et al., 'The effect of a muscarinic receptor 1 gene variant on grey matter volume in schizophrenia', Psychiatry Research - Neuroimaging, 234 182-187 (2015) [C1]

© 2015 Elsevier Ireland Ltd. Previous research has demonstrated that individuals with schizophrenia who are homozygous at the c.267C&gt;A single nucleotide polymorphism (rs2067477... [more]

© 2015 Elsevier Ireland Ltd. Previous research has demonstrated that individuals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor (CHRM1) perform less well on the Wisconsin Card Sorting Test (WCST) than those who are heterozygous. This study sought to determine whether variation in the rs2067477 genotype was associated with differential changes in brain structure. Data from 227 patients with established schizophrenia or schizoaffective disorder were obtained from the Australian Schizophrenia Research Bank. Whole-brain voxel-based morphometry was performed to compare regional grey matter volume (GMV) between the 267C/C (N=191) and 267C/A (N=36) groups. Secondary analyses tested for an effect of genotype on cognition (the WCST was not available). Individuals who were homozygous (267C/C) demonstrated significantly reduced GMV in the right precentral gyrus compared to those who were heterozygous (267C/A). These preliminary results suggest that the rs2067477 genotype is associated with brain structure in the right precentral gyrus in individuals with schizophrenia/schizoaffective disorder. Future studies are required to replicate these results and directly link the volumetric reductions with specific cognitive processes.

DOI 10.1016/j.pscychresns.2015.09.004
Citations Scopus - 5Web of Science - 4
Co-authors Paul Tooney, Murray Cairns
2014 Oldmeadow C, Mossman D, Evans T-J, Holliday EG, Tooney PA, Cairns MJ, et al., 'Combined analysis of exon splicing and genome wide polymorphism data predict schizophrenia risk loci.', J Psychiatr Res, 52 44-49 (2014) [C1]
DOI 10.1016/j.jpsychires.2014.01.011
Citations Scopus - 13Web of Science - 11
Co-authors Liz Holliday, Christopher Oldmeadow, John Attia, Murray Cairns, Paul Tooney
2014 Evans T-J, Milne E, Anderson D, de Klerk NH, Jamieson SE, Talseth-Palmer BA, et al., 'Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.', PLoS One, 9 e110255 (2014) [C1]
DOI 10.1371/journal.pone.0110255
Citations Scopus - 7Web of Science - 8
Co-authors Nikola Bowden, John Attia, Bente Talseth-Palmer, Liz Holliday
2014 Avery-Kiejda KA, Braye SG, Forbes JF, Scott RJ, 'The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer', BMC CANCER, 14 (2014) [C1]
DOI 10.1186/1471-2407-14-253
Citations Scopus - 23Web of Science - 21
Co-authors Kelly Kiejda, John Forbes
2014 Gusev A, Lee S, Trynka G, Finucane H, Vilhjálmsson B, Xu H, et al., 'Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases', The American Journal of Human Genetics, 95 535-552 (2014) [C1]
DOI 10.1016/j.ajhg.2014.10.004
Citations Scopus - 185Web of Science - 174
Co-authors Brian Kelly, Paul Tooney, Ulrich Schall, Carmel Loughland, Pat Michie, Frans Henskens
2014 Graves MC, Benton M, Lea RA, Boyle M, Tajouri L, Macartney-Coxson D, et al., 'Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis', Multiple Sclerosis Journal, 20 1033-1041 (2014) [C1]

Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Mod... [more]

Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation arerecognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure andinherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNAmethylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. Afterprioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of amajor effect CpG island in DRB1 in MS cases (pFDR <3 x 10<sup>-3</sup>). In addition, we found 55 non-HLA CpGs that exhibiteddifferential methylation, many of which localise to genes previously linked to MS.Conclusions: Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation toMS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology. © The Author(s) 2013.

DOI 10.1177/1352458513516529
Citations Scopus - 47Web of Science - 36
Co-authors Jeannette Lechner-Scott
2014 Dymerska D, Kurzawski G, Suchy J, Roomere H, Toome K, Metspalu A, et al., 'Lynch syndrome mutations shared by the Baltic States and Poland', Clinical Genetics, 86 190-193 (2014) [C3]
DOI 10.1111/cge.12251
Citations Scopus - 1Web of Science - 2
2014 Holliday EG, Attia J, Hancock S, Koloski N, McEvoy M, Peel R, et al., 'Genome-wide association study identifies two novel genomic regions in irritable bowel syndrome', American Journal of Gastroenterology, 109 770-772 (2014) [C1]
DOI 10.1038/ajg.2014.56
Citations Scopus - 8Web of Science - 9
Co-authors Mark Mcevoy, Liz Holliday, John Attia, Nicholas Talley, Roseanne Peel
2014 Wong-Brown MW, Avery-Kiejda KA, Bowden NA, Scott RJ, 'Low prevalence of germline PALB2 mutations in Australian triple-negative breast cancer', International Journal of Cancer, 134 301-305 (2014) [C1]

Triple-negative breast cancer (TNBC) is a tumour classification that is defined by oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 receptor ... [more]

Triple-negative breast cancer (TNBC) is a tumour classification that is defined by oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 receptor negativity. TNBCs share a similar gene expression profile to BRCA-mutated tumours, have been shown to carry a high proportion of BRCA mutations and have a more adverse prognosis compared to other types of breast tumours. PALB2 has been shown to be a moderate-penetrance breast cancer susceptibility gene and is involved in the same DNA damage repair pathway as BRCA1 and BRCA2; this raises the possibility that germline PALB2 mutations may be involved in the pathogenesis of TNBCs. In our study, we sequenced the coding regions of PALB2 (including intron/exon boundaries) in genomic DNA from 347 patients diagnosed with TNBC to determine the prevalence of deleterious mutations in this population. Two novel truncating mutations (c.758dup and c.2390del) and one previously detected truncating mutation (c.3113+5G>C) were found. In addition, five variants predicted to be protein-affecting were also identified. Our study shows that the prevalence of PALB2 germline mutations in individuals with TNBC is ~1%, similar to the prevalence of PALB2 germline mutation of 1% in familial non-BRCA1/2 breast cancer cohorts. © 2013 UICC.

DOI 10.1002/ijc.28361
Citations Scopus - 8Web of Science - 7
Co-authors Nikola Bowden, Michelle Wong-Brown, Kelly Kiejda
2014 McCarthy-Jones S, Green MJ, Scott RJ, Tooney PA, Cairns MJ, Wu JQ, et al., 'Preliminary evidence of an interaction between the FOXP2 gene and childhood emotional abuse predicting likelihood of auditory verbal hallucinations in schizophrenia', JOURNAL OF PSYCHIATRIC RESEARCH, 50 66-72 (2014) [C1]
DOI 10.1016/j.jpsychires.2013.11.012
Citations Scopus - 11Web of Science - 11
Co-authors Christopher Oldmeadow, Paul Tooney, Murray Cairns
2014 Green MJ, Chia TY, Cairns MJ, Wu J, Tooney PA, Scott RJ, Carr VJ, 'Catechol-O-methyltransferase (COMT) genotype moderates the effects of childhood trauma on cognition and symptoms in schizophrenia', Journal of Psychiatric Research, 49 43-50 (2014) [C1]

The interaction of genetic and environmental factors may affect the course and development of psychotic disorders. We examined whether the effects of childhood trauma on cognition... [more]

The interaction of genetic and environmental factors may affect the course and development of psychotic disorders. We examined whether the effects of childhood trauma on cognition and symptoms in schizophrenia were moderated by the Catechol-O-methyltransferase (COMT) Val158Met polymorphism, a common genetic variant known to affect cognition and prefrontal dopamine levels. Participants were 429 schizophrenia/schizoaffective cases from the Australian Schizophrenia Research Bank (ASRB). Cognitive performance was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Controlled Oral Word Association Test (COWAT), Letter Number Sequencing (LNS) test, and the Wechsler Test of Adult Reading (WTAR). Hierarchical regression was used to test the main effects and additive interaction effects of genotype and childhood trauma in the domains of physical abuse, emotional abuse, and emotional neglect, on cognition and symptom profiles of clinical cases. Consistent with previous findings, COMT Val homozygotes performed worse on cognitive measures in the absence of childhood adversity. In addition, a significant interaction between COMT genotype and physical abuse was associated with better executive function in Val homozygotes, relative to those of the same genotype with no history of abuse. Finally, the severity of positive symptoms was greater in Met carriers who had experienced physical abuse, and the severity of negative symptoms in Met carriers was greater in the presence of emotional neglect. These results suggest that the possible epigenetic modulation of the expression of the COMT Val158Met polymorphism and consequent effects on cognition and symptoms in schizophrenia, with worse outcomes associated with adverse childhood experiences in Met carriers. © 2013 Elsevier Ltd.

DOI 10.1016/j.jpsychires.2013.10.018
Citations Scopus - 31Web of Science - 29
Co-authors Murray Cairns, Paul Tooney
2014 Ripke S, Neale BM, Corvin A, Walters JTR, Farh KH, Holmans PA, et al., 'Biological insights from 108 schizophrenia-associated genetic loci', Nature, 511 421-427 (2014) [C1]

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wid... [more]

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. © 2014 Macmillan Publishers Limited. All rights reserved.

DOI 10.1038/nature13595
Citations Scopus - 2041Web of Science - 2061
Co-authors Carmel Loughland, Ulrich Schall, Frans Henskens, Pat Michie
2014 Pluschke A, Jaaback K, Scott RJ, Lombard J, Yin H, 'Epithelioid trophoblastic tumour simulating a high grade carcinoma', PATHOLOGY, 46 248-250 (2014) [C3]
DOI 10.1097/PAT.0000000000000088
2014 Greenop KR, de Klerk NH, Bower C, Milne E, Miller M, Scott RJ, et al., 'Maternal Dietary Intake of Folate and Vitamins B6 and B12 During Pregnancy and Risk of Childhood Brain Tumors', Nutrition and Cancer, (2014) [C1]

Childhood brain tumors (CBT) are the second most common childhood cancers, yet their etiology is largely unknown. We investigated whether maternal gestational intake of folate and... [more]

Childhood brain tumors (CBT) are the second most common childhood cancers, yet their etiology is largely unknown. We investigated whether maternal gestational intake of folate and vitamins B6 and B12 was associated with CBT risk in a nationwide case-control study conducted 2005-2010. Case children 0-14 years were recruited from all 10 Australian pediatric oncology centers. Control children were recruited by national random digit dialing, frequency matched to cases on age, sex, and state of residence. Dietary intake was ascertained using food frequency questionnaires and adjusted for total energy intake. Data from 293 case and 726 control mothers were analyzed using unconditional logistic regression. The odds ratio (OR) for the highest versus lowest tertile of folate intake was 0.70 [95% confidence interval (CI): 0.48, 1.02]. The ORs appeared lower in mothers who drank alcohol during pregnancy (OR = 0.45, 95% CI: 0.22, 0.93), mothers who took folic acid (OR = 0.67, 95% CI: 0.42, 1.06) or B6/B12 supplements (OR = 0.51, 95% CI: 0.25, 1.06) and in children younger than 5 years (OR = 0.50, 95% CI: 0.27, 0.93). These findings are consistent with folate's crucial role in maintenance of genomic integrity and DNA methylation. Dietary intake of B6 and B12 was not associated with risk of CBT. © 2014 Copyright © Taylor & Francis Group, LLC.

DOI 10.1080/01635581.2014.916326
Citations Scopus - 14Web of Science - 14
Co-authors John Attia
2014 De Vivo I, Prescott J, Setiawan VW, Olson SH, Wentzensen N, Attia J, et al., 'Genome-wide association study of endometrial cancer in E2C2', HUMAN GENETICS, 133 211-224 (2014) [C1]
DOI 10.1007/s00439-013-1369-1
Citations Scopus - 24Web of Science - 23
Co-authors John Attia, Liz Holliday, Mark Mcevoy
2014 Williams FMK, Carter AM, Hysi PG, Surdulescu G, Hodgkiss D, Soranzo N, et al., 'Ischemic stroke is associated with the ABO locus: The EuroCLOT study (vol 73, pg 16, 2013)', ANNALS OF NEUROLOGY, 75 166-167 (2014)
DOI 10.1002/ana.24105
Co-authors John Attia, Christopher Levi, Liz Holliday
2014 Mirecka A, Paszkowska-Szczur K, Scott RJ, Górski B, van de Wetering T, Wokolorczyk D, et al., 'Common variants of xeroderma pigmentosum genes and prostate cancer risk', Gene, 546 156-161 (2014) [C1]

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between severa... [more]

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between several NER gene polymorphisms and PC risk, but most of them evaluated only single SNPs among XP genes and the results remain inconsistent. Out of 94 SNPs located in seven XP genes (XPA-. XPG) a total of 15 SNPs were assayed in 720 unselected patients with PC and compared to 1121 healthy adults. An increased risk of disease was associated with the XPD SNP, rs1799793 (Asp312Asn) AG genotype (OR. = 2.60; p. <. 0.001) and with the AA genotype (OR. = 531; p. <. 0.0001) compared to the control population. Haplotype analysis of XPD revealed one protective haplotype and four associated with an increased disease risk, which showed that the A allele (XPD rs1799793) appeared to drive the main effect on promoting prostate cancer risk. Polymorphism in XPD gene appears to be associated with the risk of prostate cancer. © 2014.

DOI 10.1016/j.gene.2014.06.026
Citations Scopus - 12Web of Science - 12
2014 Liapikou A, Polverino E, Cilloniz C, Peyrani P, Ramirez J, Menendez R, et al., 'A worldwide perspective of nursing home-acquired pneumonia compared with community-acquired pneumonia', Respiratory Care, 59 1078-1085 (2014)

© 2014 by Daedalus Enterprises. BACKGROUND: Nursing home-acquired pneumonia (NHAP) is the leading cause of death among long-term care patients and the second most common cause of ... [more]

© 2014 by Daedalus Enterprises. BACKGROUND: Nursing home-acquired pneumonia (NHAP) is the leading cause of death among long-term care patients and the second most common cause of transfers to acute care facilities. The aim of this study was to characterize the incidence, microbiology, and outcomes for hospitalized patients with community-acquired pneumonia (CAP) and NHAP. METHODS: A secondary analysis of 5,160 patients from the Community-Acquired Pneumonia Organization database was performed. World regions were defined as the United States and Canada (I), Latin America (II), and Europe (III). RESULTS: From a total of 5,160 hospitalized patients with CAP, NHAP was identified in 287 (5.6%) patients. Mean age was 80 y. NHAP distribution by region was 6% in region I, 3% in region II, and 7% in region III. Subjects with NHAP had higher frequencies of neurological disease, diabetes mellitus, congestive heart failure, and renal failure than did subjects with CAP (P < .001). ICU admission was required in 32 (12%) subjects. Etiology was defined in 68 (23%) subjects with NHAP and 1,300 (27%) with CAP. The most common pathogens identified in NHAP included Streptococcus pneumoniae (31%), Staphylococcus species (31%), and Pseudomonas aeruginosa (7%). Presentation of NHAP more frequently included pleural effusions (34% vs 21%, P < .001) and multilobar involvement (31% vs 24%, P < .001). Thirty-day hospital mortality was statistically greater among subjects with NHAP than among those with CAP (42% vs 18%, P < .001). CONCLUSIONS: Worldwide, only a very small proportion of hospitalized patients with CAP present with NHAP; the poor outcomes for these patients may be due primarily to a higher number of comorbidities compared with patients without NHAP.

DOI 10.4187/respcare.02788
Citations Scopus - 23
2014 Piaserico S, Cazzaniga S, Chimenti S, Giannetti A, MacCarone M, Picardo M, et al., 'Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: Results from the Italian Psocare Registry', Journal of the American Academy of Dermatology, 70 257-262 (2014)

Background Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response o... [more]

Background Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. Objective We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. Methods Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. Results In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). Limitations There was a small number of patients with complete follow-up data. Conclusion PASI 75 response in patients who switched from one anti-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first anti-TNF-alfa. © 2013 by the American Academy of Dermatology, Inc.

DOI 10.1016/j.jaad.2013.10.019
Citations Scopus - 26
2014 Borghero G, Pugliatti M, Marrosu F, Marrosu MG, Murru MR, Floris G, et al., 'Genetic architecture of ALS in Sardinia', Neurobiology of Aging, 35 2882.e7-2882.e12 (2014)

© 2014 Elsevier Inc. Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic amyotrophic lateral sclerosis (ALS) provide unique information on... [more]

© 2014 Elsevier Inc. Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic amyotrophic lateral sclerosis (ALS) provide unique information on the genetics of the disease. Our aim was to describe the genetic profile of a consecutive series of ALS patients of Sardinian ancestry. All ALS patients of Sardinian ancestry, identified between 2008 and 2013 through the Italian ALS Genetic Consortium, were eligible to be included in the study. Patients and controls underwent the analysis of TARDBP, C9ORF72, SOD1, and FUS genes. Genetic mutations were identified in 155 out of 375 Sardinian ALS cases (41.3%), more commonly the p.A382T and p.G295S mutations of TARDBP and the GGGGCC hexanucleotide repeat expansion of C9ORF72. One patient had both p.G295S and p.A382T mutations of TARDBP and 8 carried both the heterozygous p.A382T mutation of TARDBP and a repeat expansion of C9ORF72. Patients carrying the p.A382T and the p.G295S mutations of TARDBP and the C9ORF72 repeat expansion shared distinct haplotypes across these loci. Patients with cooccurrence of C9ORF72 and TARDBP p.A382T missense mutation had a significantly lower age at onset and shorter survival. More than 40% of all cases on the island of Sardinia carry a mutation of an ALS-related gene, representing the highest percentage of ALS cases genetically explained outside of Scandinavia. Clinical phenotypes associated with different genetic mutations show some distinctive characteristics, but the heterogeneity between and among families carrying the same mutations implies that ALS manifestation is influenced by other genetic and nongenetic factors.

DOI 10.1016/j.neurobiolaging.2014.07.012
Citations Scopus - 26
2014 Górriz JL, Gutiérrez F, Trullas JC, Arazo P, Arribas JR, Barril G, et al., 'Executive summary of the consensus document on the management of renal disease in HIV-infected patients', Nefrologia, 34 768-788 (2014)

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. Renal function should be monitored in all... [more]

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

DOI 10.3265/Nefrologia.pre2014.Sep.12745
Citations Scopus - 1
2014 Abazov VM, Abbott B, Acharya BS, Adams M, Adams T, Agnew JP, et al., 'Measurement of the differential ¿+2b-jet cross section and the ratio s(¿+2b-jets)/s(¿+b-jet) in pp collisions at vs=1.96TeV', Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics, 737 357-365 (2014)

© 2014. We present the first measurements of the differential cross section ds/dpT¿ for the production of an isolated photon in association with at least two b-quark jets. The mea... [more]

© 2014. We present the first measurements of the differential cross section ds/dpT¿ for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities |y¿|<1.0 and transverse momenta 30<pT¿<200GeV. The b-quark jets are required to have pTjet>15GeV and |yjet|<1.5. The ratio of differential production cross sections for ¿+2 b-jets to ¿+b-jet as a function of pT¿ is also presented. The results are based on the proton-antiproton collision data at s=1.96TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next-to-leading order perturbative QCD calculations as well as predictions based on the kT-factorization approach and those from the sherpa and pythia Monte Carlo event generators.

DOI 10.1016/j.physletb.2014.09.007
Citations Scopus - 3
2014 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Akar S, et al., 'Measurement of the B

© 2014 The Authors. The B0-B0and Bs0Bs0production asymmetries, AP(B0) and AP(Bs0), are measured by means of a time-dependent analysis of B0¿J/¿K*0, B0¿D-p+and Bs0¿Ds-p+ decays, us... [more]

© 2014 The Authors. The B0-B0and Bs0Bs0production asymmetries, AP(B0) and AP(Bs0), are measured by means of a time-dependent analysis of B0¿J/¿K*0, B0¿D-p+and Bs0¿Ds-p+ decays, using a data sample corresponding to an integrated luminosity of 1.0fb-1, collected by LHCb in pp collisions at a centre-of-mass energy of 7TeV. The measurements are performed as a function of transverse momentum and pseudorapidity of the B0and Bs0mesons within the LHCb acceptance. The production asymmetries, integrated over pTand ¿ in the range 4<pT<30GeV/c and 2.5<¿<4.5, are determined to be AP(B0)=(-0.35±0.76±0.28)% and AP(Bs0)=(1.09±2.61±0.66)%, where the first uncertainties are statistical and the second systematic.

DOI 10.1016/j.physletb.2014.10.005
Citations Scopus - 26
2014 Alkhazov G, AlvarezCartelle P, Alves AA, Amato S, Amerio S, Amhis Y, et al., 'A study of CP violation in B± DK± and B± D p ± decays with D K0K± p final states', Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics, 733 36-45 (2014)

© 2014 The Authors. Published by Elsevier B.V. A first study of CP violation in the decay modes B± [KS0Kp±]Dh±and B±[KS0Kp±]Dh±, where h labels a K or p meson and D labels a D0 or... [more]

© 2014 The Authors. Published by Elsevier B.V. A first study of CP violation in the decay modes B± [KS0Kp±]Dh±and B±[KS0Kp±]Dh±, where h labels a K or p meson and D labels a D0 or D0meson, is performed. The analysis uses the LHCb data set collected in pp collisions, corresponding to an integrated luminosity of 3 fb-1. The analysis is sensitive to the CP-violating CKM phase ¿ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of ¿ using other decay modes.

DOI 10.1016/j.physletb.2014.03.051
Citations Scopus - 8
2014 Adare A, Afanasiev S, Aidala C, Ajitanand NN, Akiba Y, Akimoto R, et al., 'PHENIX Collaboration', Nuclear Physics A, 932 627-633 (2014)
DOI 10.1016/S0375-9474(14)00604-6
2014 Aaij R, Adeva B, Adinolfi M, Affolder A, Ajaltouni Z, Albrecht J, et al., 'Evidence for the decay X(3872) ¿ ¿(2S)¿', Nuclear Physics B, 886 665-680 (2014)

© 2014 CERN for the benefit of the LHCb Collaboration. Evidence for the decay mode X(3872) ¿ ¿(2S)¿ in B+¿ X(3872)K+decays is found with a sig-nificance of 4.4 standard deviations... [more]

© 2014 CERN for the benefit of the LHCb Collaboration. Evidence for the decay mode X(3872) ¿ ¿(2S)¿ in B+¿ X(3872)K+decays is found with a sig-nificance of 4.4 standard deviations. The analysis is based on adata sample of proton-proton collisions, corresponding to an integrated luminosity of 3 fbthe X(3872), collected with the LHCb detector, at centre-of-mass energies of 7 and 8 TeV. The ratio of the branching fraction of the X(3872) ¿ ¿(2S)¿ decay to that of the X(3872) ¿ J/¿¿ decay is measured to be B(X(3872) ¿ ¿(2S)¿)/B(X(3872) ¿ J/¿¿) = 2.46 ± 0.64 ± 0.29, where the first uncertainty is statistical and the second is systematic. The measured value does not support a pure DD* molecular interpretation of the X(3872)state.

DOI 10.1016/j.nuclphysb.2014.06.011
Citations Scopus - 38
2014 Abramowicz H, Abt I, Adamczyk L, Adamus M, Aggarwal R, Antonelli S, et al., 'Measurement of beauty and charm production in deep inelastic scattering at HERA and measurement of the beauty-quark mass', Journal of High Energy Physics, 2014 1-56 (2014)

© 2014, The Author(s). Abstract: The production of beauty and charm quarks in ep interactions has been studied with the ZEUS detector at HERA for exchanged four-momentum squared 5... [more]

© 2014, The Author(s). Abstract: The production of beauty and charm quarks in ep interactions has been studied with the ZEUS detector at HERA for exchanged four-momentum squared 5 < Q2< 1000 GeV2using an integrated luminosity of 354 pb-1. The beauty and charm content in events with at least one jet have been extracted using the invariant mass of charged tracks associated with secondary vertices and the decay-length significance of these vertices. Differential cross sections as a function of Q2, Bjorken x, jet trans- verse energy and pseudorapidity were measured and compared with next-to-leading-order QCD calculations. The beauty and charm contributions to the proton structure functions were extracted from the double-differential cross section as a function of x and Q2. The running beauty-quark mass, mbat the scale mb, was determined from a QCD fit at next-to-leading order to HERA data for the first time and found to be mb(mb) = 4.07 ± 0.14 (fit)- 0.07+ 0.01(mod.)- 0.00+ 0.05(param.)- 0.05+ 0.08(theo.) GeV.

DOI 10.1007/JHEP09(2014)127
Citations Scopus - 9
2014 Greenop KR, Peters S, Fritschi L, Glass DC, Ashton LJ, Bailey HD, et al., 'Exposure to household painting and floor treatments, and parental occupational paint exposure and risk of childhood brain tumors: results from an Australian case-control study', CANCER CAUSES & CONTROL, 25 283-291 (2014) [C1]
DOI 10.1007/s10552-013-0330-x
Citations Scopus - 4Web of Science - 4
2014 Greenop KR, Peters S, Bailey HD, Fritschi L, Attia J, Scott RJ, et al., 'Exposure to pesticides and the risk of childhood brain tumors (vol 24, pg 1269, 2013)', CANCER CAUSES & CONTROL, 25 1239-1240 (2014) [O1]
DOI 10.1007/s10552-014-0418-y
Co-authors John Attia
2014 Greenop KR, Peters S, Fritschi L, Glass DC, Ashton LJ, Bailey HD, et al., 'Erratum to: Exposure to household painting and floor treatments, and parental occupational paint exposure and risk of childhood brain tumors: results from an Australian case-control study', Cancer Causes & Control, (2014) [O1]
DOI 10.1007/s10552-014-0419-x
2014 Milne E, Greenop KR, Fritschi L, Attia J, Bailey HD, Scott RJ, et al., 'Childhood and parental diagnostic radiological procedures and risk of childhood brain tumors', Cancer Causes and Control, 25 375-383 (2014) [C1]

Purpose: Childhood brain tumors (CBT) are the second most common type of childhood cancer and the leading cause of childhood cancer mortality. Few causes of CBT are known, but par... [more]

Purpose: Childhood brain tumors (CBT) are the second most common type of childhood cancer and the leading cause of childhood cancer mortality. Few causes of CBT are known, but parental, fetal, and early life exposures are likely to be important given the early age at diagnosis of many cases. We aimed to investigate whether parents' diagnostic radiological procedures before conception, in the mother during pregnancy or the child's procedures were associated with an increased risk of CBT. Methods: This population-based case-control study was conducted between 2005 and 2010. Cases were identified through all ten Australian pediatric oncology centers, and controls via nationwide random-digit dialing; frequency-matched to cases on age, sex and state of residence. Information on radiological exposures in the time periods of interest was obtained for 306 case and 950 control families through mailed questionnaires. Analysis used unconditional logistic regression, adjusting for matching variables and potential confounders. Results: We found no evidence of positive associations between risk of CBT overall and childhood or parental pre-pregnancy radiological procedures. Increased ORs for high-grade gliomas associated with childhood radiological procedures were based on small numbers and may be due to chance. Conclusions: Given the evidence for an increased risk of CBT in cohort studies of computed tomography (CT) in childhood, the lack of such an association in our study may be due to the reduced intensity of CTs after 2001. Future research to investigate the safety of fetal exposure to more intense procedures like CT scans is needed. © 2014 Springer International Publishing Switzerland.

DOI 10.1007/s10552-014-0338-x
Citations Scopus - 1Web of Science - 1
Co-authors John Attia
2014 Moayyeri A, Hsu Y-H, Karasik D, Estrada K, Xiao S-M, Nielson C, et al., 'Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium', HUMAN MOLECULAR GENETICS, 23 3054-3068 (2014) [C1]
DOI 10.1093/hmg/ddt675
Citations Scopus - 48Web of Science - 41
Co-authors Christopher Oldmeadow, Roseanne Peel, Mark Mcevoy, Liz Holliday, John Attia
2014 Purrington KS, Slettedahl S, Bolla MK, Michailidou K, Czene K, Nevanlinna H, et al., 'Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade', HUMAN MOLECULAR GENETICS, 23 6034-6046 (2014) [C1]
DOI 10.1093/hmg/ddu300
Citations Scopus - 8Web of Science - 6
2014 Springelkamp H, Höhn R, Mishra A, Hysi PG, Khor CC, Loomis SJ, et al., 'Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process', Nature Communications, 5 (2014) [C1]

© 2014 Macmillan Publishers Limited. All rights reserved. Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindne... [more]

© 2014 Macmillan Publishers Limited. All rights reserved. Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

DOI 10.1038/ncomms5883
Citations Scopus - 39Web of Science - 40
Co-authors Liz Holliday, John Attia
2014 Wan C, Latter JL, Amirshahi A, Symonds I, Finnie J, Bowden N, et al., 'Progesterone Activates Multiple Innate Immune Pathways in Chlamydia trachomatis-Infected Endocervical Cells', American Journal of Reproductive Immunology, 71 165-177 (2014) [C1]

Problem: Susceptibility to Chlamydia trachomatis infection is increased by oral contraceptives and modulated by sex hormones. We therefore sought to determine the effects of femal... [more]

Problem: Susceptibility to Chlamydia trachomatis infection is increased by oral contraceptives and modulated by sex hormones. We therefore sought to determine the effects of female sex hormones on the innate immune response to C. trachomatis infection. Method of study: ECC-1 endometrial cells, pre-treated with oestradiol or progesterone, were infected with C. trachomatis and the host transcriptome analysed by Illumina Sentrix HumanRef-8 microarray. Primary endocervical epithelial cells, prepared at either the proliferative or secretory phase of the menstrual cycle, were infected with C. trachomatis and cytokine gene expression determined by quantitative RT-PCR analysis. Results: Chlamydia trachomatis yield from progesterone-primed ECC-1 cells was significantly reduced compared with oestradiol-treated cells. Genes upregulated in progesterone-treated and Chlamydia-infected cells only included multiple CC and CXC chemokines, IL-17C, IL-29, IL-32, TNF-a, DEFB4B, LCN2, S100A7-9, ITGAM, NOD2, JAK1, IL-6ST, type I and II interferon receptors, numerous interferon-stimulated genes and STAT6. CXCL10, CXCL11, CX3CL1 and IL-17C, which were also upregulated in infected secretory-stage primary cells, and there was a trend towards higher levels of immune mediators in infected secretory-phase compared with proliferative-phase cells. Conclusion: Progesterone treatment primes multiple innate immune pathways in hormone-responsive epithelial cells that could potentially increase resistance to chlamydial infection. © 2013 John Wiley & Sons Ltd.

DOI 10.1111/aji.12168
Citations Scopus - 9Web of Science - 9
Co-authors Nikola Bowden, Ian Symonds, Joanna Latter
2014 Loth DW, Artigas MS, Gharib SA, Wain LV, Franceschini N, Koch B, et al., 'Genome-wide association analysis identifies six new loci associated with forced vital capacity', NATURE GENETICS, 46 669-677 (2014) [C1]
DOI 10.1038/ng.3011
Citations Scopus - 50Web of Science - 50
Co-authors Christopher Oldmeadow, Liz Holliday, John Attia
2014 Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, et al., 'Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database', Nature Genetics, 46 107-115 (2014) [C1]

The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The Internati... [more]

The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.

DOI 10.1038/ng.2854
Citations Scopus - 183Web of Science - 178
2014 Holliday EG, Traylor M, Malik R, Bevan S, Maguire J, Koblar SA, et al., 'Polygenic Overlap Between Kidney Function and Large Artery Atherosclerotic Stroke', STROKE, 45 3508-+ (2014) [C1]
DOI 10.1161/STROKEAHA.114.006609
Citations Scopus - 4Web of Science - 4
Co-authors Liz Holliday, Mark Mcevoy, Christopher Oldmeadow, John Attia, Christopher Levi
2014 Cox MB, Bowden NA, Scott RJ, Lechner-Scott J, 'Common genetic variants in the plasminogen activation pathway are not associated with multiple sclerosis', Multiple Sclerosis Journal, 20 489-491 (2014) [C1]

Matrix metalloproteinase 9 (MMP9) is involved in multiple sclerosis (MS) aetiology. Previously, we identified differential gene expression of plasminogen activation cascade genes ... [more]

Matrix metalloproteinase 9 (MMP9) is involved in multiple sclerosis (MS) aetiology. Previously, we identified differential gene expression of plasminogen activation cascade genes in MS patients. Based on our gene expression results, we wanted to identify whether polymorphisms in the genes associated with the plasminogen pathway could predict MS risk. We genotyped 1153 trio families, 727 MS cases and 604 healthy controls for 17 polymorphisms in MMP9, plasminogen activator urokinase (PLAU), PLAU receptor (PLAUR) and serpin peptidase inhibitor/clade 2/member B2 (SERPINB2) genes. No associations were found between the 17 polymorphisms and MS. Also, gene expression levels were analysed according to genotype: no associations were observed. In conclusion despite the consistent evidence for the role of MMP9 and the plasminogen activation cascade in MS, we found no associations between genotype nor gene expression. This suggested there are other potentially modifiable factors influencing gene expression in MS. © The Author(s) 2013.

DOI 10.1177/1352458513498127
Citations Scopus - 2Web of Science - 2
Co-authors Jeannette Lechner-Scott, Nikola Bowden
2014 Smith CJA, Bensing S, Maltby VE, Zhang M, Scott RJ, Smith R, et al., 'Intermediate lobe immunoreactivity in a patient with suspected lymphocytic hypophysitis', Pituitary, 17 22-29 (2014) [C1]

Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. Th... [more]

Lymphocytic hypophysitis is an organ-specific autoimmune disease characterised by destruction of pituitary hormone-secreting cells due to attack by self-reactive T lymphocytes. The spectrum of pituitary autoantibodies characterised by indirect immunofluorescence (IF) in these patients has not been substantially defined. The purpose of this study was to determine the spectrum of pituitary autoantibodies in 16 lymphocytic hypophysitis patients. Pituitary sections were prepared from guinea pigs and sera from 16 lymphocytic hypophysitis patients (13 biopsy proven and 3 suspected cases) and 13 healthy controls were evaluated for immunoreactivity to the pituitary tissue by immunofluorescence. A single patient was found to have high titre pituitary autoantibodies against guinea pig pituitary tissue. Immunoreactivity was directed against cells of the intermediate lobe. We present the case report of the patient who is a 24 year old woman that presented with headaches, polyuria and polydipsia. A uniformly enlarged pituitary mass was visible on MRI and a diagnosis of suspected lymphocytic hypophysitis was made. Based on our IF study, we postulate this patient has an autoimmune process directed towards the major cell type in the intermediate lobe, the melanotroph. Pre-adsorption with peptides representing adrenocorticotropic hormone, a-melanocyte stimulating hormone or ß-endorphin did not affect the IF signal suggesting our patient's pituitary autoantibodies may target some other product of Proopiomelanocortin (POMC) processing, such as corticotrophin-like intermediate peptide or ¿-lipoprotein. Alternatively, the autoantibodies may target a peptide completely unrelated to POMC processing. © 2013 Springer Science+Business Media New York.

DOI 10.1007/s11102-013-0461-9
Citations Scopus - 1Web of Science - 1
Co-authors Vicki E Maltby, Roger Smith
2014 Oldmeadow C, Holliday EG, McEvoy M, Scott R, Kwok JBJ, Mather K, et al., 'Concordance between direct and imputed APOE genotypes using 1000 genomes data', Journal of Alzheimer's Disease, 42 391-393 (2014) [C1]

© 2014 - IOS Press and the authors. All rights reserved. There are a growing number of large cohorts of older persons with genome-wide genotyping data available, but APOE is not i... [more]

© 2014 - IOS Press and the authors. All rights reserved. There are a growing number of large cohorts of older persons with genome-wide genotyping data available, but APOE is not included in any of the common microarray platforms. We compared directly measured APOE genotypes with those imputed using microarray data and the '1000 Genomes' dataset in a sample of 320 Caucasians. We find 90% agreement for e2/e3/e4 genotypes and 93% agreement for predicting e4 status, yielding kappa values of 0.81 and 0.84, respectively. More stringent thresholds around allele number estimates can increase this agreement to 90-97% and kappas of 0.90-0.93.

DOI 10.3233/JAD-140846
Citations Scopus - 5Web of Science - 4
Co-authors John Attia, Peter Schofield, Christopher Oldmeadow, Liz Holliday, Mark Mcevoy
2014 Spurdle AB, Couch FJ, Parsons MT, McGuffog L, Barrowdale D, Bolla MK, et al., 'Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia', Breast Cancer Research, 16 3419 (2014) [C1]
DOI 10.1186/s13058-014-0474-y
Citations Scopus - 25Web of Science - 20
Co-authors Mark Parsons
2014 de Zeeuw EL, van Beijsterveldt CEM, Glasner TJ, Bartels M, Ehli EA, Davies GE, et al., 'Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 165 510-520 (2014) [C1]

The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after corr... [more]

The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA meta-analysis of educational attainment in adults were used to calculate polygenic scores in an independent sample of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale. © 2014 Wiley Periodicals, Inc.

DOI 10.1002/ajmg.b.32254
Citations Scopus - 11Web of Science - 11
Co-authors Christopher Oldmeadow, John Attia, Liz Holliday
2014 Greenop KR, Peters S, Bailey HD, Fritschi L, Attia J, Scott RJ, et al., 'Erratum to: Exposure to pesticides and the risk of childhood brain tumors', Cancer Causes and Control, 25 1239-1240 (2014)
DOI 10.1007/s10552-014-0418-y
Co-authors John Attia
2014 Abdullah N, Attia J, Oldmeadow C, Scott RJ, Holliday EG, 'The Architecture of Risk for Type 2 Diabetes: Understanding Asia in the Context of Global Findings', INTERNATIONAL JOURNAL OF ENDOCRINOLOGY, (2014) [C1]
DOI 10.1155/2014/593982
Citations Scopus - 21Web of Science - 6
Co-authors Liz Holliday, John Attia, Christopher Oldmeadow
2014 Zyluk A, Paszkowska-Szczur K, Gupta S, Scott RJ, Lubinski J, Debniak T, 'Dupuytren's disease and the risk of malignant neoplasms', Hereditary Cancer in Clinical Practice, 12 (2014) [C1]

The object of this study was the investigation of the risk of occurrence of malignant neoplasms in 508 patients with Dupuytren&apos;s disease (DD) and in 2157 of their 1st degree ... [more]

The object of this study was the investigation of the risk of occurrence of malignant neoplasms in 508 patients with Dupuytren's disease (DD) and in 2157 of their 1st degree relatives. In the first stage of the study, we evaluated the tumour spectrum as well as the age of the patient at diagnosis of cancers in DD families along with the observed and expected frequencies of malignancies. In the second stage of the study, we examined the distribution of 20 common mutations/polymorphisms in 12 known cancer susceptibility genes among DD patients and 508 matched healthy controls. No such study has been published to date. Results. No significant differences were noted between malignancies diagnosed among members of DD families and the general population. Molecular examination of 20 mutations/polymorphisms in 12 cancer susceptibility genes in Dupuytren's patients and controls showed a statistically significant association of one mutation with Dupuytren disease: D312M in XPD (OR = 1.75, p = 0.004). We observed a tendency toward changed frequencies of occurrence of central nervous system tumors, laryngeal cancer and non-melanoma skin cancers in DD families. The results of our study indicate a lack of a strong association between Dupuytren disease and familial cancer risk. © 2014 Zyluk et al.; licensee BioMed Central Ltd.

DOI 10.1186/1897-4287-12-6
Citations Scopus - 1Web of Science - 1
2014 Masson AL, Talseth-Palmer BA, Evans TJ, Grice DM, Hannan GN, Scott RJ, 'Expanding the genetic basis of copy number variation in familial breast cancer', Hereditary Cancer in Clinical Practice, 12 (2014) [C1]

Introduction: Familial breast cancer (fBC) is generally associated with an early age of diagnosis and a higher frequency of disease among family members. Over the past two decades... [more]

Introduction: Familial breast cancer (fBC) is generally associated with an early age of diagnosis and a higher frequency of disease among family members. Over the past two decades a number of genes have been identified that are unequivocally associated with breast cancer (BC) risk but there remain a significant proportion of families that cannot be accounted for by these genes. Copy number variants (CNVs) are a form of genetic variation yet to be fully explored for their contribution to fBC. CNVs exert their effects by either being associated with whole or partial gene deletions or duplications and by interrupting epigenetic patterning thereby contributing to disease development. CNV analysis can also be used to identify new genes and loci which may be associated with disease risk.Methods: The Affymetrix Cytogenetic Whole Genome 2.7 M (Cyto2.7 M) arrays were used to detect regions of genomic re-arrangement in a cohort of 129 fBC BRCA1/BRCA2 mutation negative patients with a young age of diagnosis (<50 years) compared to 40 unaffected healthy controls (>55 years of age).Results: CNV analysis revealed the presence of 275 unique rearrangements that were not present in the control population suggestive of their involvement in BC risk. Several CNVs were found that have been previously reported as BC susceptibility genes. This included CNVs in RPA3, NBN (NBS1), MRE11A and CYP19A1 in five unrelated fBC patients suggesting that these genes are involved in BC initiation and/or progression. Of special interest was the identification of WWOX and FHIT rearrangements in three unrelated fBC patients.Conclusions: This study has identified a number of CNVs that potentially contribute to BC initiation and/or progression. The identification of CNVs that are associated with known tumour suppressor genes is of special interest that warrants further larger studies to understand their precise role in fBC. © 2014 Masson et al.; licensee BioMed Central Ltd.

DOI 10.1186/1897-4287-12-15
Citations Scopus - 10Web of Science - 9
Co-authors Bente Talseth-Palmer
2014 Scott RJ, Fox SB, Desai J, Grieu F, Amanuel B, Garrett K, et al., 'KRAS mutation testing of metastatic colorectal cancer in Australia: Where are we at?', Asia-Pacific Journal of Clinical Oncology, 10 261-265 (2014) [C1]

Aim: To carry out a nationwide study of KRAS testing in metastatic colorectal cancer as reported by nine major molecular pathology service providers in Australia, including mutati... [more]

Aim: To carry out a nationwide study of KRAS testing in metastatic colorectal cancer as reported by nine major molecular pathology service providers in Australia, including mutation frequencies and turnaround times that might impact on patient care. Methods: Participating laboratories contributed information on KRAS mutation frequencies, including the G13D mutation type, as well as turnaround times for tumor block retrieval and testing. Results: The KRAS mutation frequency observed by nine different test sites for a total of 3688 metastatic colorectal cancers ranged from 34.4% to 40.7%, with an average across all sites of 38.8%. The average frequency of the G13D mutation type among all cases was 8.0%. The median turnaround time was 17 days (range 0-191), with 20% of cases requiring more than 4 weeks for a KRAS test result. The major contributor to long turnaround times was the time taken to retrieve archived blocks of primary tumor, particularly from sources external to the test site. Conclusion: The frequency of KRAS mutations in metastatic colorectal cancer reported by the major Australian test sites is very similar to that reported by other large overseas studies. More widespread introduction of routine testing at the time of initial diagnosis should eliminate the long turnaround times currently being experienced in a significant proportion of cases. Future expansion of testing to include other KRAS and NRAS mutation hotspots may spur the introduction of next-generation sequencing platforms. © 2014 Wiley Publishing Asia Pty Ltd.

DOI 10.1111/ajco.12201
Citations Scopus - 2Web of Science - 2
2014 Moscovis SM, Hall ST, Burns CJ, Scott RJ, Blackwell CC, 'The male excess in sudden infant deaths', INNATE IMMUNITY, 20 24-29 (2014) [C1]
DOI 10.1177/1753425913481071
Citations Scopus - 13Web of Science - 13
Co-authors Sharron Hall, Caroline Blackwell
2014 Baines KJ, Simpson JL, Wood LG, Scott RJ, Fibbens NL, Powell H, et al., 'Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes', Journal of Allergy and Clinical Immunology, 133 997-1007 (2014) [C1]

Background Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. Objective This study aimed to identify and validate a sputu... [more]

Background Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. Objective This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes. Methods An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported. Results From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC); carboxypeptidase A3 (CPA3); deoxyribonuclease I-like 3 (DNASE1L3); IL-1ß (IL1B); alkaline phosphatase, tissue-nonspecific isozyme (ALPL); and chemokine (C-X-C motif) receptor 2 (CXCR2), was reproducible and could significantly (P <.0001) discriminate eosinophilic asthma from other phenotypes, including patients with noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as well as discriminating patients with neutrophilic asthma from those with paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8). The 6-gene signature predicted ICS response (>12% change in FEV1; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. Conclusions A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma. © 2013 American Academy of Allergy, Asthma & Immunology.

DOI 10.1016/j.jaci.2013.12.1091
Citations Scopus - 61Web of Science - 59
Co-authors Jodie Simpson, Peter Gibson, Katherine Baines, Lisa Wood
2014 Gromowski T, Masojc B, Cybulski C, Górski B, Kluzniak W, Paszkowska-Szczur K, et al., 'Prevalence of the E318K and V320I MITF germline mutations in Polish cancer patients and multiorgan cancer risk-a population-based study', Cancer Genetics, (2014) [C1]

The E318K mutation in the MITF gene has been associated with a high risk of melanoma, renal cell carcinoma, and pancreatic cancer; the risk of other cancers has not been evaluated... [more]

The E318K mutation in the MITF gene has been associated with a high risk of melanoma, renal cell carcinoma, and pancreatic cancer; the risk of other cancers has not been evaluated so far. Herein, we examined the possible association of E318K and a novel variant of the MITF gene, V320I, with the risk of cancers of different sites of origin in a Polish population. We assayed for the presence of the E318K and V320I missense mutations in 4,226 patients with one of six various cancers (melanoma or cancer of the kidney, lung, prostate, colon, or breast) and 2,114 controls from Poland. The E318K mutation was detected in 4 of 2,114 participants (0.19%) in the Polish control population, the V320I in 3 of 2,114 participants (0.14%) in the control group. We found no statistically significant differences in the prevalence of the E318K and V320I variants among cases and controls. We found two carriers of the E318K variant among melanoma patients (P = 0.95), one carrier among breast cancer patients (P = 0.77), one carrier among colorectal cancer patients (P = 0.82), and one carrier among kidney cancer patients (P = 0.64). Our study demonstrates a lack of strong association of E318K and V320I with increased risk of melanoma or cancers of the kidney, breast, prostate, lung, or colon. © 2014 Elsevier Inc. All rights reserved.

DOI 10.1016/j.cancergen.2014.03.003
Citations Scopus - 6Web of Science - 6
2014 Shahijanian F, Parnell GP, McKay FC, Gatt PN, Shojoei M, O'Connor KS, et al., 'The CYP27B1 variant associated with an increased risk of autoimmune disease is underexpressed in tolerizing dendritic cells', HUMAN MOLECULAR GENETICS, 23 1425-1434 (2014) [C1]
DOI 10.1093/hmg/ddt529
Citations Scopus - 20Web of Science - 19
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2014 Goris A, van Setten J, Diekstra F, Ripke S, Patsopoulos NA, Sawcer SJ, et al., 'No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis', HUMAN MOLECULAR GENETICS, 23 1916-1922 (2014) [C1]
DOI 10.1093/hmg/ddt574
Citations Web of Science - 8
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2014 Rudnicka H, Masojc B, van de Wetering T, Debniak T, Cybulski C, Gronwald J, et al., 'First recurrent large genomic rearrangement in the BRCA1 gene found in Poland', Cancer Epidemiology, (2014) [C1]

Mutation in the BRCA1 gene increases the risk of the person developing breast and/or ovarian cancer. The prevalence and spectrum of large genomic rearrangements (LGRs) varies cons... [more]

Mutation in the BRCA1 gene increases the risk of the person developing breast and/or ovarian cancer. The prevalence and spectrum of large genomic rearrangements (LGRs) varies considerably among different tested populations. In our previous study we described three LGRs in BRCA1 (exons 13-19, exon 17 and exon 22) in Polish families at high risk of breast and ovarian cancer. In this study we analyzed a group of 550 unselected women with ovarian cancer for the three previously identified LGRs. We used a rapid, single-step and closed-tube method: high-resolution melting analysis (HRMA). In this group of unrelated patients diagnosed with ovarian cancer we found three cases with the same deletions of exon 22. This is the first recurrent large deletion in BRCA1 found in Poland. We conclude that screening for the exon 22 deletion in BRCA1 should be included in the Polish BRCA1 genetic testing panel and possibly extended into other Slavic populations. © 2014 Elsevier Ltd. All rights reserved.

DOI 10.1016/j.canep.2014.05.010
Citations Scopus - 1Web of Science - 1
2014 Avery-Kiejda KA, Braye SG, Mathe A, Forbes JF, Scott RJ, 'Decreased expression of key tumour suppressor microRNAs is associated with lymph node metastases in triple negative breast cancer', BMC Cancer, 14 (2014) [C1]

Background: Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent... [more]

Background: Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent an important subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for molecular biomarkers and treatment targets in breast cancer, but their role in the progression of triple negative breast cancer remains largely unexplored.Methods: This study has investigated miRNA expression profiles in 31 primary triple negative breast cancer cases and in 13 matched lymph node metastases compared with 23 matched normal breast tissues to determine miRNAs associated with the initiation of this disease subtype and those associated with its metastasis.Results: 71 miRNAs were differentially expressed in triple negative breast cancer, the majority of which have previously been associated with breast cancer, including members of the miR-200 family and the miR-17-92 oncogenic cluster, suggesting that the majority of miRNAs involved in the initiation of triple negative breast cancer are not subtype specific. However, the repertoire of miRNAs expressed in lymph node negative and lymph node positive triple negative breast cancers were largely distinct from one another. In particular, miRNA profiles associated with lymph node negative disease tended to be up-regulated, while those associated with lymph node positive disease were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. From this, 27 miRNAs were identified that are associated with metastatic capability in the triple negative breast cancer subtype.Conclusions: These results provide novel insight into the repertoire of miRNAs that contribute to the initiation of and progression to lymph node metastasis in triple negative breast cancer and have important implications for the treatment of this breast cancer subtype. © 2014 Avery-Kiejda et al.; licensee BioMed Central Ltd.

DOI 10.1186/1471-2407-14-51
Citations Scopus - 40Web of Science - 40
Co-authors Kelly Kiejda, Andrea Mathe, John Forbes
2014 Moscovis S, Hall S, Burns C, Scott R, Blackwell C, 'Development of an experimental model for assessing the effects of cigarette smoke and virus infections on inflammatory responses to bacterial antigens', Innate Immunity, 20 647-658 (2014) [C1]

Interactions among major risk factors associated with bacterial infections were assessed in a model system using surrogates for virus infection; IFN-g, and exposure to cigarette s... [more]

Interactions among major risk factors associated with bacterial infections were assessed in a model system using surrogates for virus infection; IFN-g, and exposure to cigarette smoke; cigarette smoke extract (CSE), nicotine and cotinine. Cytokine responses elicited by LPS from THP-1 cells in the presence of these components, or combinations of components, were assessed by multiplex bead assay, i.e. IL-1ß, IL-6, IL-8, IL-10, TNF-a and IFN-¿. IFN-¿-priming significantly increased pro-inflammatory cytokines induced by LPS. CSE suppressed production of pro-inflammatory cytokines IL-1ß, TNF-a and IFN-¿, but enhanced production of IL-8. Nicotine and cotinine suppressed all cytokine responses. In combination, IFN-¿ masked the inhibitory effects of CSE. In relation to the objectives of the study, we concluded that (a) IFN¿ at biologically relevant concentrations significantly enhanced pro-inflammatory responses; (b) CSE, nicotine and cotinine dysregulated the inflammatory response and that the effects of CSE were different from those of the individual components, nicotine and cotinine; (c) when both IFN-¿ and CSE were present, IFN-¿ masked the effect of CSE. There is a need for clinical investigations on the increase in IL-8 responses in relation to exposure to cigarette smoke and increased pro-inflammatory responses in relation to recent viral infection. © 2013 The Author(s).

DOI 10.1177/1753425913503893
Citations Scopus - 6Web of Science - 6
Co-authors Caroline Blackwell, Sharron Hall
2014 Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ, 'The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome.', Carcinogenesis, 35 586-596 (2014) [C1]
DOI 10.1093/carcin/bgt411
Citations Scopus - 28Web of Science - 27
Co-authors Andrea Mathe, Kelly Kiejda, Michelle Wong-Brown
2014 Cox AJ, Moscovis SM, Blackwell CC, Scott RJ, 'Cytokine gene polymorphism among Indigenous Australians.', Innate Immun, 20 431-439 (2014) [C1]
DOI 10.1177/1753425913498911
Citations Scopus - 10Web of Science - 9
Co-authors Caroline Blackwell
2014 Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al., 'Studies of dijet transverse momentum balance and pseudorapidity distributions in pPb collisions at vs

© 2014, CERN for the benefit of the CMS collaboration 2014. Dijet production has been measured in pPb collisions at a nucleon¿nucleon centre-of-mass energy of 5.02 TeV. A data sam... [more]

© 2014, CERN for the benefit of the CMS collaboration 2014. Dijet production has been measured in pPb collisions at a nucleon¿nucleon centre-of-mass energy of 5.02 TeV. A data sample corresponding to an integrated luminosity of 35 nb-1was collected using the Compact Muon Solenoid detector at the Large Hadron Collider. The dijet transverse momentum balance, azimuthal angle correlations, and pseudorapidity distributions are studied as a function of the transverse energy in the forward calorimeters (E4<|¿|<5.2T). For pPb collisions, the dijet transverse momentum ratio and the width of the distribution of dijet azimuthal angle difference are comparable to the same quantities obtained from a simulated pp reference and insensitive to E4<|¿|<5.2T. In contrast, the mean value of the dijet pseudorapidity is found to change monotonically with increasing E4<|¿|<5.2T, indicating a correlation between the energy emitted at large pseudorapidity and the longitudinal motion of the dijet frame. The pseudorapidity distribution of the dijet system in minimum bias pPb collisions is compared with next-to-leading-order perturbative QCD predictions obtained from both nucleon and nuclear parton distribution functions, and the data more closely match the latter.

DOI 10.1140/epjc/s10052-014-2951-y
Citations Scopus - 41
2013 Masson AL, Talseth-Palmer BA, Evans T-J, Grice DM, Duesing K, Hannan GN, Scott RJ, 'Copy number variation in hereditary non-polyposis colorectal cancer', Genes, 4 536-555 (2013) [C1]
DOI 10.3390/genes4040536
Citations Scopus - 4Web of Science - 4
Co-authors Bente Talseth-Palmer
2013 Mechelli R, Umeton R, Policano C, Annibali V, Coarelli G, Ricigliano VAG, et al., 'A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis', PLoS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0063300
Citations Scopus - 19Web of Science - 17
Co-authors Jeannette Lechner-Scott
2013 Köttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, et al., 'Genome-wide association analyses identify 18 new loci associated with serum urate concentrations', Nature Genetics, 45 145-154 (2013)

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Glo... [more]

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. © 2013 Nature America, Inc. All rights reserved.

DOI 10.1038/ng.2500
Co-authors Christopher Oldmeadow, John Attia, Liz Holliday
2013 Terwisscha van Scheltinga AF, Bakker SC, van Haren NEM, Derks EM, Buizer-Voskamp JE, Boos HBM, et al., 'Genetic Schizophrenia Risk Variants Jointly Modulate Total Brain and White Matter Volume', Biological Psychiatry, 73 525-531 (2013) [C1]
DOI 10.1016/j.biopsych.2012.08.017
Citations Scopus - 51Web of Science - 43
Co-authors Pat Michie, Carmel Loughland, Ulrich Schall, Frans Henskens
2013 Wong-Brown MW, McPhillips ML, Hipwell M, Pecenpetelovska G, Dooley S, Meldrum C, Scott RJ, 'cDNA analysis of the BRCA1 unclassified variant c.5194-12G \ A', CLINICAL GENETICS, 84 505-506 (2013) [C3]
DOI 10.1111/cge.12052
Citations Scopus - 1Web of Science - 1
Co-authors Michelle Wong-Brown
2013 Talseth-Palmer BA, Wijnen JT, Barker D, Vasen HFA, Scott RJ, 'Is the reported modifying effect of 8q23.3 and 11q23.1 on colorectal cancer risk for MLH1 mutation carriers valid? Reply', INTERNATIONAL JOURNAL OF CANCER, 133 1764-1764 (2013) [C3]
DOI 10.1002/ijc.28178
Co-authors Bente Talseth-Palmer, Daniel Barker
2013 Talseth-Palmer B, Wijnen JT, Brenne IS, Jagmohan-Changur S, Barker DJ, Ashton KA, et al., 'Combined analysis of three Lynch syndrome cohorts confirms the modifying effects of 8q23.3 and 11q23.1 in MLH1 mutation carriers', International Journal of Cancer, 132 1487-1729 (2013) [C1]
Citations Scopus - 13Web of Science - 13
Co-authors Bente Talseth-Palmer, Daniel Barker
2013 Titmarsh CJ, Moscovis SM, Hall S, Tzanakaki G, Kesanopoulos K, Xirogianni A, et al., 'Comparison of cytokine gene polymorphisms among Greek patients with invasive meningococcal disease or viral meningitis', JOURNAL OF MEDICAL MICROBIOLOGY, 62 694-700 (2013) [C1]
DOI 10.1099/jmm.0.058073-0
Citations Scopus - 8Web of Science - 7
Co-authors Sharron Hall, Caroline Blackwell
2013 Gardiner EJ, Cairns MJ, Liu B, Beveridge NJ, Carr V, Kelly B, et al., 'Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells', JOURNAL OF PSYCHIATRIC RESEARCH, 47 425-437 (2013) [C1]
DOI 10.1016/j.jpsychires.2012.11.007
Citations Scopus - 31Web of Science - 33
Co-authors Brian Kelly, Murray Cairns, Paul Tooney
2013 Van Scheltinga AFT, Bakker SC, Van Haren NEM, Derks EM, Buizer-Voskamp JE, Cahn W, et al., 'Schizophrenia genetic variants are not associated with intelligence', Psychological Medicine, 43 2563-2570 (2013) [C1]

Background Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits... [more]

Background Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. Method IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls. Results Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R2= 0.055, p = 2.1 × 10-7) and with IQ in the entire sample (R2= 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status. Conclusions Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk. © Cambridge University Press 2013.

DOI 10.1017/S0033291713000196
Citations Scopus - 26Web of Science - 21
Co-authors Frans Henskens, Carmel Loughland, Ulrich Schall, Pat Michie
2013 Yadav S, Cotlarciuc I, Munroe PB, Khan MS, Nalls MA, Bevan S, et al., 'Genome-Wide Analysis of Blood Pressure Variability and Ischemic Stroke', Stroke, 44 2703-2709 (2013) [C1]
DOI 10.1161/STROKEAHA.113.002186
Citations Scopus - 11Web of Science - 9
Co-authors John Attia, Liz Holliday, Mark Mcevoy
2013 Köttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, et al., 'Genome-wide association analyses identify 18 new loci associated with serum urate concentrations', Nature Genetics, 45 145-154 (2013) [C1]

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from &gt;140,000 individuals of European ancestry within the ... [more]

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. © 2013 Nature America, Inc. All rights reserved.

DOI 10.1038/ng.2500
Citations Scopus - 256Web of Science - 251
Co-authors Liz Holliday, John Attia, Christopher Oldmeadow
2013 Chen J, Pande M, Huang Y-J, Wei C, Amos CI, Talseth-Palmer BA, et al., 'Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients', CARCINOGENESIS, 34 299-306 (2013) [C1]
DOI 10.1093/carcin/bgs344
Citations Scopus - 7Web of Science - 7
Co-authors Bente Talseth-Palmer
2013 Schache M, Richardson AJ, Mitchell P, Wang JJ, Rochtchina E, Viswanathan AC, et al., 'Genetic association of refractive error and axial length with 15q14 but not 15q25 in the Blue Mountains Eye Study Cohort', Ophthalmology, 120 292-297 (2013) [C1]
Citations Scopus - 15Web of Science - 12
Co-authors John Attia, Liz Holliday
2013 Allemani C, Minicozzi P, Berrino F, Bastiaannet E, Gavin A, Galceran J, et al., 'Predictions of survival up to 10 years after diagnosis for European women with breast cancer in 2000-2002', International Journal of Cancer, 132 2404-2412 (2013)

Few studies have addressed longer-term survival for breast cancer in European women. We have made predictions of 10-year survival for European women diagnosed with breast cancer i... [more]

Few studies have addressed longer-term survival for breast cancer in European women. We have made predictions of 10-year survival for European women diagnosed with breast cancer in 2000-2002. Data for 114,312 adult women (15-99 years) diagnosed with a first primary malignant cancer of the breast during 2000-2002 were collected in the EUROCARE-4 study from 24 population-based cancer registries in 14 European countries. We estimated relative survival at 1, 5, and 10 years after diagnosis for women who were alive at some point during 2000-2002, using the period approach. We also estimated 10-year survival conditional on survival to 1 and 5 years after diagnosis. Ten-year survival exceeded 70% in most regions, but was only 54% in Eastern Europe, with the highest value in Northern Europe (about 75%). Ten-year survival conditional on survival for 1 year was 2-6% higher than 10-year survival in all European regions, and geographic differences were smaller. Ten-year survival for women who survived at least 5 years was 88% overall, with the lowest figure in Eastern Europe (79%) and the highest in the UK (91%). Women aged 50-69 years had higher overall survival than older and younger women (79%). Six cancer registries had adequate information on stage at diagnosis; in these jurisdictions, 10-year survival was 89% for local, 62% for regional and 10% for metastatic disease. Data on stage are not collected routinely or consistently, yet these data are essential for meaningful comparison of population-based survival, which provides vital information for improving breast cancer control. What's new? Policy-makers and health-care planners need accurate data on long-term survival to improve cancer control. This Europe-wide study of 10-year survival identified low survival in Eastern Europe for women with breast cancer in 2000-2002, and wide variation by age at diagnosis. Data on stage at diagnosis are crucial for meaningful comparison of population-based survival, and fundamental for improving breast cancer control, but our analyses confirmed that stage data are not collected routinely or consistently Copyright © 2012 UICC.

DOI 10.1002/ijc.27895
Citations Scopus - 32
2013 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al., 'Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012', Critical Care Medicine, 41 580-637 (2013)

© 2013 by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Objective: To provide an update to the ¿Surviving Sepsis Campaign Guidelines f... [more]

© 2013 by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Objective: To provide an update to the ¿Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,¿ last published in 2008. Design: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of lowquality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Results: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure = 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7¿9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrh...

DOI 10.1097/CCM.0b013e31827e83af
Citations Scopus - 3175
2013 Aristei C, Santucci A, Corvò R, Gardani G, Ricardi U, Scarzello G, et al., 'In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: Results of a multicentre observational study', Bone Marrow Transplantation, 48 908-914 (2013)

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT)... [more]

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates. © 2013 Macmillan Publishers Limited All rights reserved.

DOI 10.1038/bmt.2013.66
Citations Scopus - 6
2013 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al., 'Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012', Intensive Care Medicine, 39 165-228 (2013)

© SCCM and ESICM 2013. Objective: To provide an update to the ¿Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,¿ last published in 2008. Desi... [more]

© SCCM and ESICM 2013. Objective: To provide an update to the ¿Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,¿ last published in 2008. Design: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vicechairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of lowquality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Results: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure = 65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7¿9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress synd...

DOI 10.1007/s00134-012-2769-8
Citations Scopus - 2186
2013 Clarke SM, Li X, Pecl GT, Ward TM, Battaglene S, Frusher S, et al., 'Assessing the risk of climate change to aquaculture: A case study from south-east Australia', Aquaculture Environment Interactions, 3 163-175 (2013)

© Inter-Research 2013. A qualitative screening-level risk assessment was developed to evaluate relative levels of risk from climate change to aquaculture industries. The assessmen... [more]

© Inter-Research 2013. A qualitative screening-level risk assessment was developed to evaluate relative levels of risk from climate change to aquaculture industries. The assessment was applied to 7 major industries in the temperate south-east region of Australia and involved a simple, transparent and repeatable methodology that was appropriate for a range of different aquaculture systems and taxa. Two key stages were involved: the development of comprehensive expertise-based literature reviews or 'species profiles' and a scoring assessment, with the latter providing a defined framework within which industries could be ranked (from high to low risk). In addition to informing the second stage of the risk assessment process, the species' profiles also highlighted important climate change drivers and key information uncertainties and knowledge gaps. There was good resolution among the scoring assessments, with only 2 industries receiving the same risk score. The results indicated that oysters farmed from wild spat (Sydney rock oysters Saccostrea glomerata) were at most risk to climate change, with warm temperate hatchery-based finfish species (yellowtail kingfish Seriola lalandi) being the least at risk. This study provides critical guidance for scientists, resource managers and stakeholders for future research, both in addressing key knowledge gaps and focussing the development of more detailed risk analyses for high risk aquaculture industries in south-east Australia.

DOI 10.3354/aei00058
Citations Scopus - 15
2013 Barzideh J, Scott RJ, Aitken RJ, 'Analysis of the global methylation status of human spermatozoa and its association with the tendency of these cells to enter apoptosis', ANDROLOGIA, 45 424-429 (2013) [C1]
DOI 10.1111/and.12033
Citations Scopus - 14Web of Science - 9
Co-authors John Aitken
2013 Acikyol B, Graham R, Trinder D, House M, Olynyk J, Scott R, et al., 'Brain transcriptome perturbations in the transferrin receptor 2 mutant mouse support the case for brain changes in iron loading disorders, including effects relating to long-term depression and long-term potentiation', Neuroscience, 235 119-128 (2013) [C1]
DOI 10.1016/j.neuroscience.2013.01.014
Citations Scopus - 8Web of Science - 9
Co-authors Liz Milward
2013 Williams FMK, Carter AM, Hysi PG, Surdulescu G, Hodgkiss D, Soranzo N, et al., 'Ischemic stroke is associated with the ABO locus: The EuroCLOT Study', Annals of Neurology, 73 16-31 (2013) [C1]
Citations Scopus - 62Web of Science - 61
Co-authors Liz Holliday, Christopher Levi, John Attia
2013 Greenop KR, Peters S, Bailey HD, Fritschi L, Attia J, Scott RJ, et al., 'Exposure to pesticides and the risk of childhood brain tumors', CANCER CAUSES & CONTROL, 24 1269-1278 (2013) [C1]
DOI 10.1007/s10552-013-0205-1
Citations Scopus - 21Web of Science - 18
Co-authors John Attia
2013 Milne E, Greenop KR, Scott RJ, De Klerk NH, Bower C, Ashton LJ, et al., 'Parental alcohol consumption and risk of childhood acute lymphoblastic leukemia and brain tumors', Cancer Causes and Control, 24 391-402 (2013) [C1]

Purpose: Childhood acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and brain tumors (CBTs) are the leading cause of cancer death in children. In our Aus... [more]

Purpose: Childhood acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and brain tumors (CBTs) are the leading cause of cancer death in children. In our Australian case-control studies of these cancers, we investigated whether parental alcohol consumption before or during pregnancy was associated with risk. Methods: Cases were identified through the ten Australian pediatric oncology centers, and controls were recruited through national random-digit dialling. Detailed information on alcohol consumption, including beverage type, amount, and timing, was collected from 690 case families (388 ALL and 302 CBT) and 1,396 control families. Data were analyzed using unconditional logistic regression. Results: We found no evidence that maternal alcohol use before or during pregnancy was associated with an increased risk of either cancer; rather, there was evidence of inverse associations, particularly with wine. For both cancers, we observed U-shaped associations with paternal alcohol consumption in the year before the pregnancy, possibly driven by reduced risk at moderate levels of beer and wine intake and increased risk associated with high levels of beer intake. Moderate intake of spirits by fathers was associated with an increased risk of CBT but not ALL. These findings would be strengthened by corroboration in other studies. While the inverse associations with wine may be interesting mechanistically, the public health message remains that maternal alcohol use during pregnancy causes serious disorders in the offspring and should be avoided. Conclusions: Our findings suggest that men, as well as women, should limit their alcohol intake when planning a pregnancy. © 2012 Springer Science+Business Media Dordrecht.

DOI 10.1007/s10552-012-0125-5
Citations Scopus - 21Web of Science - 18
2013 Lee SH, Harold D, Nyholt DR, Goddard ME, Zondervan KT, Williams J, et al., 'Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis', HUMAN MOLECULAR GENETICS, 22 832-841 (2013) [C1]
DOI 10.1093/hmg/dds491
Citations Scopus - 91Web of Science - 86
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2013 Cortes A, Field J, Glazov EA, Hadler J, Stankovich J, Brown MA, 'Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes', HUMAN MOLECULAR GENETICS, 22 2283-2292 (2013) [C1]
DOI 10.1093/hmg/ddt062
Citations Scopus - 12Web of Science - 10
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2013 Rietveld CA, Medland SE, Derringer J, Yang J, Esko T, Martin NW, et al., 'GWAS of 126,559 individuals identifies genetic variants associated with educational attainment', Science, 340 1467-1471 (2013) [C1]
Citations Scopus - 289Web of Science - 273
Co-authors John Attia, Liz Holliday, Christopher Oldmeadow
2013 Paszkowska-Szczur K, Scott RJ, Serrano-Fernandez P, Mirecka A, Gapska P, Górski B, et al., 'Xeroderma pigmentosum genes and melanoma risk', International Journal of Cancer, 133 1094-1101 (2013) [C1]
DOI 10.1002/ijc.28123
Citations Scopus - 24Web of Science - 22
2013 Milne E, Greenop KR, Scott RJ, Ashton LJ, Cohn RJ, de Klerk NH, Armstrong BK, 'Parental smoking and risk of childhood brain tumors', International Journal of Cancer, 133 253-259 (2013) [C1]
DOI 10.1002/ijc.28004
Citations Scopus - 16Web of Science - 17
2013 Cox MB, Bowden NA, Scott RJ, Lechner-Scott J, 'Altered expression of the plasminogen activation pathway in peripheral blood mononuclear cells in multiple sclerosis: possible pathomechanism of matrix metalloproteinase activation', Multiple Sclerosis Journal, 19 1268-1274 (2013) [C1]
DOI 10.1177/1352458513475493
Citations Scopus - 3Web of Science - 2
Co-authors Jeannette Lechner-Scott, Nikola Bowden
2013 Green MJ, Cairns MJ, Wu J, Dragovic M, Jablensky A, Tooney PA, et al., 'Genome-wide supported variant MIR137 and severe negative symptoms predict membership of an impaired cognitive subtype of schizophrenia', MOLECULAR PSYCHIATRY, 18 774-780 (2013) [C1]
DOI 10.1038/mp.2012.84
Citations Scopus - 84Web of Science - 76
Co-authors Paul Tooney, Murray Cairns
2013 Green MJ, Cairns MJ, Wu J, Dragovic M, Jablensky A, Tooney PA, et al., 'Genome-wide supported variant MIR137 and severe negative symptoms predict membership of an impaired cognitive subtype of schizophrenia', Molecular Psychiatry, (2013)
DOI 10.1038/mp.2013.48
Citations Scopus - 38
Co-authors Paul Tooney, Murray Cairns
2013 Talseth-Palmer BA, Wijnen JT, Grice DM, Scott RJ, 'Genetic modifiers of cancer risk in Lynch syndrome: a review', FAMILIAL CANCER, 12 207-216 (2013) [C1]
DOI 10.1007/s10689-013-9614-2
Citations Scopus - 9Web of Science - 9
Co-authors Bente Talseth-Palmer
2013 Stambolian D, Wojciechowski R, Oexle K, Pirastu M, Li X, Raffel LJ, et al., 'Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error', Human Molecular Genetics, 22 2754-2764 (2013) [C1]
Citations Scopus - 29Web of Science - 29
Co-authors John Attia, Liz Holliday
2013 Kumarasinghe N, Beveridge NJ, Gardiner E, Scott RJ, Yasawardene S, Perera A, et al., 'Gene expression profiling in treatment-naive schizophrenia patients identifies abnormalities in biological pathways involving AKT1 that are corrected by antipsychotic medication', INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 16 1483-1503 (2013) [C1]
DOI 10.1017/S1461145713000035
Citations Scopus - 26Web of Science - 27
Co-authors Paul Tooney, Ulrich Schall
2013 Bolton KA, Ross JP, Grice DM, Bowden NA, Holliday EG, Avery-Kiejda KA, Scott RJ, 'STaRRRT: a table of short tandem repeats in regulatory regions of the human genome', BMC GENOMICS, 14 (2013) [C1]
DOI 10.1186/1471-2164-14-795
Citations Scopus - 13Web of Science - 12
Co-authors Kelly Kiejda, Nikola Bowden, Liz Holliday
2013 Lener MR, Gupta S, Scott RJ, Tootsi M, Kulp M, Tammesoo M, et al., 'Can selenium levels act as a marker of colorectal cancer risk?', BMC Cancer, 13 xx-xx (2013) [C1]
DOI 10.1186/1471-2407-13-214
Citations Scopus - 13Web of Science - 12
2013 Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, Van Duijn CM, Noble JA, et al., 'Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects', PLOS GENETICS, 9 (2013) [C1]
DOI 10.1371/journal.pgen.1003926
Citations Scopus - 91Web of Science - 78
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2013 Schork AJ, Thompson WK, Pham P, Torkamani A, Roddey JC, Sullivan PF, et al., 'All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs', PLOS GENETICS, 9 (2013) [C1]
DOI 10.1371/journal.pgen.1003449
Citations Scopus - 118Web of Science - 113
Co-authors Ulrich Schall, Carmel Loughland, Frans Henskens, Pat Michie
2013 Talseth-Palmer BA, Wijnen JT, Andreassen EK, Barker D, Jagmohan-Changur S, Tops CM, et al., 'The importance of a large sample cohort for studies on modifier genes influencing disease severity in FAP patients.', Hered Cancer Clin Pract, 11 20 (2013) [C1]
DOI 10.1186/1897-4287-11-20
Citations Scopus - 6Web of Science - 4
Co-authors Daniel Barker, Bente Talseth-Palmer
2013 Talseth-Palmer B, Holliday EG, Evans T-J, McEvoy MA, Attia JR, Grice DM, et al., 'Continuing difficulties in interpreting CNV data: Lessons from a genome-wide CNV association study of Australian HNPCC/lynch syndrome patients', BMC Medical Genomics, 6 1-13 (2013) [C1]
Citations Scopus - 11Web of Science - 10
Co-authors John Attia, Liz Holliday, Bente Talseth-Palmer, Mark Mcevoy
2013 Lin R, Charlesworth J, Stankovich J, Perreau VM, Brown MA, Taylor BV, Moscato P, 'Identity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple Sclerosis', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0056379
Citations Scopus - 11Web of Science - 10
Co-authors Pablo Moscato
2013 Bowden NA, Ashton KA, Vilain RE, Avery-Kiejda KA, Davey RJ, Murray HC, et al., 'Regulators of Global Genome Repair Do Not Respond to DNA Damaging Therapy but Correlate with Survival in Melanoma', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0070424
Citations Scopus - 5Web of Science - 5
Co-authors Nikola Bowden, Xu Zhang, Kelly Kiejda
2013 Picelli S, Lorenzo Bermejo J, Chang-Claude J, Hoffmeister M, Fernandez-Rozadilla C, Carracedo A, et al., 'Meta-Analysis of Mismatch Repair Polymorphisms within the Cogent Consortium for Colorectal Cancer Susceptibility', PLOS ONE, 8 (2013) [C1]
DOI 10.1371/journal.pone.0072091
Citations Scopus - 13Web of Science - 14
Co-authors Bente Talseth-Palmer
2013 Sun C, Young TL, Mackey DA, Van Zuydam NR, Doney ASF, Palmer CNA, et al., 'Genetic loci for retinal arteriolar microcirculation', PLoS One, 8 (2013) [C1]
DOI 10.1371/journal.pone.0065804
Citations Scopus - 7Web of Science - 9
Co-authors Liz Holliday, John Attia
2013 Jensen RA, Sim X, Li X, Cotch MF, Ikram MK, Holliday EG, et al., 'Genome-wide association study of retinopathy in individuals without diabetes', PLoS One, 8 (2013) [C1]
DOI 10.1371/journal.pone.0054232
Citations Scopus - 7Web of Science - 7
Co-authors John Attia, Liz Holliday
2013 Holliday EG, Smith AV, Cornes BK, Buitendijk GHS, Jensen RA, Sim X, et al., 'Insights into the genetic architecture of early stage age-related macular degeneration: A genome-wide association study meta-analysis', PLoS One, 8 (2013) [C1]
DOI 10.1371/journal.pone.0053830
Citations Scopus - 66Web of Science - 61
Co-authors Patrick Mcelduff, Liz Holliday, John Attia
2013 Johnstone DM, Riveros C, Heidari M, Graham RM, Trinder D, Berretta R, et al., 'Evaluation of Different Normalization and Analysis Procedures for Illumina Gene Expression Microarray Data Involving Small Changes', Microarrays, 2 131-152 (2013) [C1]
Co-authors Carlos Riveros, Pablo Moscato, Regina Berretta, Liz Milward
2012 Milne E, Greenop KR, Scott R, Bailey HD, Attia JR, Dalla-Pozza L, et al., 'Parental prenatal smoking and risk of childhood acute lymphoblastic leukemia', American Journal of Epidemiology, 175 43-53 (2012) [C1]
Citations Scopus - 61Web of Science - 56
Co-authors John Attia
2012 Johnstone DM, Graham RM, Trinder D, Delima RD, Riveros RC, Olynyk JK, et al., 'Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading', Brain Research, 1448 144-152 (2012) [C1]
DOI 10.1016/j.brainres.2012.02.006
Citations Scopus - 12Web of Science - 12
Co-authors Pablo Moscato, Liz Milward, Carlos Riveros
2012 Van Der Luijt RB, Devilee P, Easton DF, Peock S, Frost D, Platte R, et al., 'Association of PHB 1630 C \ T and MTHFR 677 C \ T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study', British Journal of Cancer, 106 2016-2024 (2012) [C1]
Citations Scopus - 18Web of Science - 20
2012 Lill CM, Liu T, Schjeide B-MM, Roehr JT, Akkad DA, Damotte V, et al., 'Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects', Journal of Medical Genetics, 49 558-562 (2012) [C1]
Citations Scopus - 18Web of Science - 17
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2012 Ashton KA, Scurry JP, Rutherford J, Otton GR, Scott R, Bowden NA, 'Nodular prurigo of the vulva', Pathology, 44 565-567 (2012) [C3]
Citations Scopus - 4Web of Science - 4
Co-authors Nikola Bowden
2012 Young KMN, Scurry JP, Jaaback KS, Bowden NA, Scott R, 'Bilateral dysgerminoma associated with gonadoblastoma and sex-cord stromal tumour with annular tubules in a 28-year-old fertile woman with normal karyotype', Pathology, 44 257-260 (2012) [C3]
Citations Scopus - 4Web of Science - 3
Co-authors Nikola Bowden
2012 Cheng YC, Anderson CD, Bione S, Keene K, Maguire JM, Nalls M, et al., 'Are myocardial infarction-associated single-nucleotide polymorphisms associated with ischemic stroke?', Stroke, 43 980-U143 (2012) [C1]
Citations Scopus - 17Web of Science - 18
Co-authors Lisa Lincz, Pablo Moscato, John Attia, Liz Holliday, Christopher Levi
2012 Bailey HD, Miller M, Langridge A, De Klerk NH, Van Bockxmeer FM, Attia JR, et al., 'Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and the risk of childhood acute lymphoblastic leukemia', Nutrition and Cancer, 64 1122-1130 (2012) [C1]
DOI 10.1080/01635581.2012.707278
Citations Scopus - 24Web of Science - 21
Co-authors John Attia
2012 Leu C, De Kovel CGF, Zara F, Striano P, Pezzella M, Robbiano A, et al., 'Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies', Epilepsia, 53 308-318 (2012)

© 2011 International League Against Epilepsy. Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable ... [more]

© 2011 International League Against Epilepsy. Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Methods: Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. Key Findings: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Significance: Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype- genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes.

DOI 10.1111/j.1528-1167.2011.03379.x
Citations Scopus - 21
2012 Sant M, Minicozzi P, Lagorio S, Børge Johannesen T, Marcos-Gragera R, Francisci S, et al., 'Survival of European patients with central nervous system tumors', International Journal of Cancer, 131 173-185 (2012)

We present estimates of population-based 5-year relative survival for adult Europeans diagnosed with central nervous system tumors, by morphology (14 categories based on cell line... [more]

We present estimates of population-based 5-year relative survival for adult Europeans diagnosed with central nervous system tumors, by morphology (14 categories based on cell lineage and malignancy grade), sex, age at diagnosis and region (UK and Ireland, Northern, Central, Eastern and Southern Europe) for the most recent period with available data (2000-2002). Sources were 39 EUROCARE cancer registries with continuous data from 1996 to 2002. Survival time trends (1988 to 2002) were estimated from 24 cancer registries with continuous data from 1988. Overall 5-year relative survival was 85.0% for benign, 19.9% for malignant tumors. Benign tumor survival ranged from 90.6% (Northern Europe) to 77.4% (UK and Ireland); for malignant tumors the range was 25.1% (Northern Europe) to 15.6% (UK and Ireland). Survival decreased with age at diagnosis and was slightly better for women (malignant tumors only). For glial tumors, survival varied from 83.5% (ependymoma and choroid plexus) to 2.7% (glioblastoma); and for non-glioma tumors from 96.5% (neurinoma) to 44.9% (primitive neuroectoderm tumor/medulloblastoma). Survival differences between regions narrowed after adjustment for morphology and age, and were mainly attributable to differences in morphology mix; however UK and Ireland and Eastern Europe patients still had 40% and 30% higher excess risk of death, respectively, than Northern Europe patients (reference). Survival for benign tumors increased from 69.3% (1988-1990) to 77.1% (2000-2002); but survival for malignant tumors did not improve indicating no useful advances in treatment over the 14-year study period, notwithstanding major improvement in the diagnosis and treatment of other solid cancers. Copyright © 2011 UICC.

DOI 10.1002/ijc.26335
Citations Scopus - 29
2012 Dasmahapatra KK, Walters JR, Briscoe AD, Davey JW, Whibley A, Nadeau NJ, et al., 'Butterfly genome reveals promiscuous exchange of mimicry adaptations among species', Nature, 487 94-98 (2012)

The evolutionary importance of hybridization and introgression has long been debated. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by t... [more]

The evolutionary importance of hybridization and introgression has long been debated. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation. We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12, 669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation. © 2012 Macmillan Publishers Limited.

DOI 10.1038/nature11041
Citations Scopus - 475
2012 Oberaigner W, Minicozzi P, Bielska-Lasota M, Allemani C, De Angelis R, Mangone L, et al., 'Survival for Ovarian Cancer in Europe: The across-country variation did not shrink in the past decade', Acta Oncologica, 51 441-453 (2012)

Background. Survival for ovarian cancer is the poorest of all gynaecological cancer sites. Our aim was to present the most up-to-date survival estimate for ovarian cancer by age a... [more]

Background. Survival for ovarian cancer is the poorest of all gynaecological cancer sites. Our aim was to present the most up-to-date survival estimate for ovarian cancer by age and morphology and to answer the question whether survival for ovarian cancer improved in Europe during the 1990s. Material and methods. This analysis was performed with data from the EUROCARE database. We considered all adult women diagnosed with ovarian cancer between 1995 and 2002 and life status followed up until the end of 2003. A total of 97 691 cases were contributed by 72 European cancer registries in 24 countries. We estimated the most up-to-date relative survival for a mean of 23 661 patients followed up in 20002003 using the period hybrid approach and described the relative survival trends from the beginning of 1990s. Results and conclusion. Overall, the European age-standardised one-year, five-year and five-year conditional on surviving one-year relative survival were 67.2% (95% CI 66.667.8), 36.1% (95% CI 35.436.8) and 53.7% (95% CI 52.854.7), respectively. Five-year relative survival was 58.6% (95% CI 57.459.8), 37.1% (95% CI 36.138.1) and 20.5% (95% CI 19.121.9) in women aged 1554, 5574 and 7599 years, respectively. The age-standardised five-year relative survival was 38.1% (95% CI 36.939.3) for serous tumours and 51.9% (95% CI 49.054.9) for mucinous cancers and the crude five-year relative survival was 85.6% (95% CI 81.290.0) for germ cell cancers. Overall, the age-standardised five-year relative survival increased from 32.4% (95% CI 31.733.2) in 19911993 to 36.3% (95% CI 35.537.0) in 20002003. There is a need to better understand the reasons for the wide variation in survival of ovarian cancer in Europe. Actions aiming to harmonise the protocols for therapy should contribute to narrowing the wide gap in survival and research on screening and early detection of ovarian cancer should be enforced. © 2012 Informa Healthcare.

DOI 10.3109/0284186X.2011.653437
Citations Scopus - 42
2012 Aaij R, Abellan Beteta C, Adeva B, Adinolfi M, Adrover C, Affolder A, et al., 'Measurement of the CP-violating phase F

© 2012 Elsevier B.V. Measurement of the mixing-induced CP-violating phase Fsin B0sdecays is of prime importance in probing new physics. Here 7421 ± 105 signal events from the domi... [more]

© 2012 Elsevier B.V. Measurement of the mixing-induced CP-violating phase Fsin B0sdecays is of prime importance in probing new physics. Here 7421 ± 105 signal events from the dominantly CP-odd final state J/¿p+p-are selected in 1 fb-1of pp collision data collected at v s = 7 TeV with the LHCb detector. A timedependent fit to the data yields a value of Fs= -0.019+0.173+0.004-0.174-0.003rad, consistent with the Standard Model expectation. No evidence of direct CP violation is found.

DOI 10.1016/j.physletb.2012.06.032
Citations Scopus - 17
2012 Alexander A, Barnett-Cowan M, Bartmess E, Bosco FA, Brandt M, Carp J, et al., 'An open, large-scale, collaborative effort to estimate the reproducibility of psychological science', Perspectives on Psychological Science, 7 657-660 (2012)

© The Author(s) 2012. Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replicati... [more]

© The Author(s) 2012. Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings.

DOI 10.1177/1745691612462588
Citations Scopus - 187
2012 Smith CJ, Bensing S, Burns C, Robinson PJ, Kasperlik-Zaluska AA, Scott R, et al., 'Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis; immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays', European Journal of Endocrinology, 166 391-398 (2012) [C1]
Citations Scopus - 30Web of Science - 28
2012 Orsi L, Rudant J, Bonaventure A, Goujon-Bellec S, Corda E, Evans T-J, et al., 'Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE)', Leukemia, 26 2561-2564 (2012) [C1]
Citations Scopus - 45Web of Science - 41
2012 Talseth-Palmer B, Scott R, Vasen HFA, Wijnen JT, '8q23.3 and 11q23.1 as modifying loci influencing the risk for CRC in Lynch syndrome', European Journal of Human Genetics, 20 487-488 (2012) [C3]
Citations Scopus - 3Web of Science - 3
Co-authors Bente Talseth-Palmer
2012 Milne E, Greenop KR, Bower C, Miller M, Van Bockxmeer FM, Scott R, et al., 'Maternal use of folic acid and other supplements and risk of childhood brain tumors', Cancer Epidemiology Biomarkers and Prevention, 21 1933-1941 (2012) [C1]
Citations Scopus - 35Web of Science - 34
2012 Long J, Zheng W, Xiang Y-B, Lose F, Thompson D, Tomlinson I, et al., 'Genome-wide association study identifies a possible susceptibility locus for endometrial cancer', Cancer Epidemiology, Biomarkers & Prevention, 21 980-987 (2012) [C1]
Citations Scopus - 24Web of Science - 23
2012 Nyholt DR, Low S-K, Anderson CA, Painter JN, Uno S, Morris AP, et al., 'Genome-wide association meta-analysis identifies new endometriosis risk loci', Nature Genetics, 44 1355-1359 (2012) [C1]
Citations Scopus - 148Web of Science - 128
Co-authors Liz Holliday, John Attia, Mark Mcevoy
2012 Holliday EG, Maguire JM, Evans T-J, Koblar SA, Jannes J, Sturm J, et al., 'Common variants at 6p21.1 are associated with large artery atherosclerotic stroke', Nature Genetics, 44 1147-1153 (2012) [C1]
Citations Scopus - 99Web of Science - 90
Co-authors Roseanne Peel, Lisa Lincz, Wayne Smith, Pablo Moscato, John Attia, Mark Parsons, Christopher Oldmeadow, Christopher Levi, Liz Holliday, Mark Mcevoy
2012 Okada Y, Sim X, Go MJ, Wu J-Y, Gu D, Takeuchi F, et al., 'Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations', Nature Genetics, 44 904-909 (2012) [C1]
Citations Scopus - 121Web of Science - 121
Co-authors John Attia, Christopher Oldmeadow, Liz Holliday
2012 Gardiner EJ, Beveridge NJ, Wu JQ, Carr VJ, Scott R, Tooney PA, Cairns MJ, 'Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells', Molecular Psychiatry, 17 827-840 (2012) [C1]
Citations Scopus - 117Web of Science - 107
Co-authors Murray Cairns, Paul Tooney
2012 Johnstone DM, Graham RM, Trinder D, Riveros RC, Olynyk JK, Scott R, et al., 'Changes in brain transcripts related to Alzheimer's disease in a model of HFE hemochromatosis are not consistent with increased Alzheimer's disease risk', Journal of Alzheimers Disease, 30 791-803 (2012) [C1]
Citations Scopus - 6Web of Science - 6
Co-authors Liz Milward, Carlos Riveros, Pablo Moscato
2012 Yan J, Liu J, Lin CY, Scott R, Lechner-Scott J, Brown MA, et al., 'Interleukin-6 gene promoter-572 C allele may play a role in rate of disease progression in multiple sclerosis', International Journal of Molecular Sciences, 13 13667-13679 (2012) [C1]
DOI 10.3390/ijms131013667
Citations Scopus - 11Web of Science - 10
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2012 Mathers JC, Movahedi M, Macrae F, Mecklin J-P, Moeslein G, Olschwang S, et al., 'Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial', LANCET ONCOLOGY, 13 1242-1249 (2012) [C1]
DOI 10.1016/S1470-2045(12)70475-8
Citations Scopus - 48Web of Science - 42
2012 Cox MB, Ban M, Bowden NA, Baker A, Scott R, Lechner-Scott J, 'Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis', Multiple Sclerosis Journal, 18 16-22 (2012) [C1]
DOI 10.1177/1352458511415562
Citations Scopus - 31Web of Science - 30
Co-authors Jeannette Lechner-Scott, Nikola Bowden
2012 Reeves SG, Meldrum C, Groombridge C, Spigelman A, Suchy J, Kurzawski G, et al., 'DNA repair gene polymorphisms and risk of early onset colorectal cancer in Lynch syndrome', Cancer Epidemiology, 36 183-189 (2012) [C1]
Citations Scopus - 14Web of Science - 12
2012 Kurzawski G, Dymerska D, Serrano-Fernandez P, Trubicka J, Masojc BO, Jakubowska A, Scott R, 'DNA and RNA analyses in detection of genetic predisposition to cancer', Hereditary Cancer in Clinical Practice, 10 17 (2012) [C1]
Citations Scopus - 1Web of Science - 1
2012 Kim K-T, Carroll AP, Mashkani B, Cairns MJ, Small D, Scott R, 'MicroRNA-16 Is down-regulated in mutated FLT3 expressing murine myeloid FDC-P1 cells and interacts with Pim-1', PLOS One, 7 (2012) [C1]
DOI 10.1371/journal.pone.0044546
Citations Scopus - 11Web of Science - 3
Co-authors Murray Cairns
2012 Wu JQ, Wang X, Beveridge NJ, Tooney PA, Scott R, Carr VJ, Cairns MJ, 'Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia', PLoS One, 7 (2012) [C1]
DOI 10.1371/journal.pone.0036351
Citations Scopus - 40Web of Science - 40
Co-authors Murray Cairns, Paul Tooney
2012 Kim K-T, Mossman D, Small D, Scott R, 'Gene expression profiling of human myeloid leukemic MV4-11 cells treated with 5-Aza-2-deoxycytidine', Journal of Cancer Therapy, 3 177-182 (2012) [C1]
2011 Ritchie ME, Ruijie L, Carvalho BS, Irizarry RA, Bahlo M, Booth DR, et al., 'Comparing genotyping algorithms for Illumina's Infinium whole-genome SNP BeadChips', BMC Bioinformatics, 12 68-79 (2011) [C1]
DOI 10.1186/1471-2105-12-68
Citations Scopus - 24Web of Science - 23
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2011 Kiejda KA, Bowden NA, Croft AJ, Scurr LL, Kairupan CF, Ashton KA, et al., 'P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation', BMC Cancer, 11 203-219 (2011) [C1]
DOI 10.1186/1471-2407-11-203
Citations Scopus - 53Web of Science - 45
Co-authors Kelly Kiejda, Xu Zhang, Nikola Bowden, Bente Talseth-Palmer
2011 Hondow HL, Fox SB, Mitchell G, Scott R, Beshay V, Wong SQ, et al., 'A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes', BMC Cancer, 11 265 (2011) [C1]
DOI 10.1186/1471-2407-11-265
Citations Scopus - 23Web of Science - 16
2011 Patsopoulos NA, De Bakker PIW, Esposito F, Reischl J, Lehr S, Bauer D, et al., 'Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci', Annals of Neurology, 70 897-912 (2011) [C1]
DOI 10.1002/ana.22609
Citations Scopus - 199Web of Science - 188
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2011 Talseth-Palmer B, Scott R, 'Genetic variation and its role in malignancy', International Journal of Biomedical Science, 7 158-171 (2011) [C1]
Citations Scopus - 2
Co-authors Bente Talseth-Palmer
2011 De Bakker PIW, Kappos L, Polman CH, Chibnik LB, Hafler DA, Matthews PM, et al., 'Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data', Genome Medicine, 3 1-11 (2011) [C1]
DOI 10.1186/gm217
Citations Scopus - 44Web of Science - 41
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2011 Mossman D, Scott R, 'Long term transcriptional reactivation of epigenetically silenced genes in colorectal cancer cells requires DNA hypomethylation and histone acetylation', PLoS ONE, 6 (2011) [C1]
DOI 10.1371/journal.pone.0023127
Citations Scopus - 31Web of Science - 22
2011 Jaworowska E, Trubicka J, Lener MR, Masojc B, Zlowocka-Perlowska E, McKay JD, et al., 'Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population', PLoS ONE, 6 (2011) [C1]
DOI 10.1371/journal.pone.0025057
Citations Scopus - 27Web of Science - 23
2011 Ma GZM, Stankovich J, Kilpatrick TJ, Binder MD, Field J, Bahlo M, et al., 'Polymorphisms in the receptor tyrosine kinase MERTK gene are associated with multiple sclerosis susceptibility', PLoS ONE, 6 1-6 (2011) [C1]
DOI 10.1371/journal.pone.0016964
Citations Scopus - 21Web of Science - 16
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2011 Reid A, Glass DC, Bailey HD, Milne E, De Klerk NH, Downie P, et al., 'Risk of childhood acute lymphoblastic leukaemia following parental occupational exposure to extremely low frequency electromagnetic fields', British Journal of Cancer, 105 1409-1413 (2011) [C1]
DOI 10.1038/bjc.2011.365
Citations Scopus - 10Web of Science - 6
Co-authors John Attia
2011 Matthews D, 'Case: Cerebral Aneurysm Ruptured During Surgery:Mr Kt (By His Mother And Litigation Friend Mrs Ft) V Southampton University Hospitals Nhs Trust', Clinical Risk, 17 237-238 (2011)
DOI 10.1258/cr.2011.011002
Citations Scopus - 1
2011 Vilain RE, Dudding TE, Braye SG, Groombridge C, Meldrum C, Spigelman AD, et al., 'Can a familial gastrointestinal tumour syndrome be allelic with Waardenburg syndrome?', Clinical Genetics, 79 554-560 (2011) [C3]
DOI 10.1111/j.1399-0004.2010.01489.x
Citations Scopus - 9Web of Science - 8
Co-authors T Dudding, Stephen Ackland, Leonie Ashman
2011 Talseth-Palmer B, Brenne IS, Ashton KA, Evans T-J, McPhillips M, Groombridge C, et al., 'Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in lynch syndrome', Journal of Medical Genetics, 48 279-284 (2011) [C1]
DOI 10.1136/jmg.2010.079962
Citations Scopus - 35Web of Science - 29
Co-authors Bente Talseth-Palmer
2011 Zacharin M, Bajpai A, Chow CW, Catto-Smith A, Stratakis C, Wong-Brown M, Scott R, 'Gastrointestinal polyps in McCune Albright syndrome', Journal of Medical Genetics, 48 458-461 (2011) [C1]
DOI 10.1136/jmg.2010.086330
Citations Scopus - 14Web of Science - 13
Co-authors Michelle Wong-Brown
2011 O'Gorman C, Freeman S, Taylor BV, Butzkueven H, Broadley SA, Bahlo M, et al., 'Familial recurrence risks for multiple sclerosis in Australia', Journal of Neurology, Neurosurgery and Psychiatry, 82 1351-1354 (2011) [C1]
DOI 10.1136/jnnp.2010.233064
Citations Scopus - 12Web of Science - 12
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2011 Bailey HD, Armstrong BK, De Klerk NH, Fritschi L, Attia JR, Scott R, et al., 'Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia', International Journal of Cancer, 129 1678-1688 (2011) [C1]
Citations Scopus - 18Web of Science - 18
Co-authors John Attia
2011 The International Multiple Sclerosis Consortium, Control TWTC, Cox MB, Lechner-Scott J, Scott R, 'Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis', Nature, 476 214-219 (2011) [C1]
Citations Scopus - 1390Web of Science - 1287
Co-authors Jeannette Lechner-Scott
2011 Baines KJ, Simpson JL, Wood LG, Scott R, Gibson PG, 'Systemic upregulation of neutrophil a-defensins and serine proteases in neutrophilic asthma', Thorax, 66 942-947 (2011) [C1]
Citations Scopus - 39Web of Science - 35
Co-authors Lisa Wood, Katherine Baines, Peter Gibson, Jodie Simpson
2011 Baines KJ, Simpson JL, Wood LG, Scott R, Gibson PG, 'Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples', Journal of Allergy and Clinical Immunology, 127 153.e9-160.e9 (2011) [C1]
DOI 10.1016/j.jaci.2010.10.024
Citations Scopus - 124Web of Science - 110
Co-authors Jodie Simpson, Peter Gibson, Katherine Baines, Lisa Wood
2011 Kiejda KA, Wong-Brown M, Scott R, 'Genetic markers in breast cancer - How far have we come from BRCA1?', Asia-Pacific Journal of Molecular Medicine, 1 1-15 (2011) [C1]
Co-authors Michelle Wong-Brown, Kelly Kiejda
2011 Burn J, Gerdes A-M, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al., 'Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: An analysis from the CAPP2 randomised controlled trial', Lancet, 378 2081-2087 (2011) [C1]
DOI 10.1016/S0140-6736(11)61049-0
Citations Scopus - 463Web of Science - 396
2011 Wong-Brown M, Nordfors C, Mossman D, Pecenpetelovska G, Kiejda KA, Talseth-Palmer B, et al., 'BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer', Breast Cancer Research and Treatment, 127 853-859 (2011) [C1]
DOI 10.1007/s10549-011-1443-0
Citations Scopus - 67Web of Science - 60
Co-authors Nikola Bowden, Kelly Kiejda, Michelle Wong-Brown, Bente Talseth-Palmer
2011 Yotova V, Lefebvre J-F, Moreau C, Gbeha E, Hovhannesyan K, Bourgeois S, et al., 'An X-linked haplotype of Neandertal origin is present among all non-African populations', Molecular Biology and Evolution, 28 1957-1962 (2011) [C1]
DOI 10.1093/molbev/msr024
Citations Scopus - 31Web of Science - 30
2011 Oldmeadow CJ, Riveros RC, Holliday EG, Scott R, Moscato PA, Wang JJ, et al., 'Sifting the wheat from the chaff: Prioritizing GWAS results by identifying consistency across analytical methods', Genetic Epidemiology, 35 745-754 (2011) [C1]
DOI 10.1002/gepi.20622
Citations Scopus - 8Web of Science - 7
Co-authors Carlos Riveros, Liz Holliday, Christopher Oldmeadow, Pablo Moscato, John Attia
2011 Avery-Kiejda KA, Wong MW, Scott RJ, 'Genetic Markers in Breast Cancer- How Far Have We Come from BRCA1?', MEDICINE AND HEALTH-KUALA LUMPUR, 6 1-24 (2011)
Co-authors Kelly Kiejda
2011 Milne E, Royle JA, Bennett LC, De Klerk NH, Bailey HD, Bower C, et al., 'Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: Results from an Australian case-control study', Cancer Causes & Control, 22 207-218 (2011) [C1]
DOI 10.1007/s10552-010-9688-1
Citations Scopus - 15Web of Science - 13
Co-authors John Attia
2011 Maguire JM, Thakkinstian A, Levi CR, Lincz L, Bisset L, Sturm J, et al., 'Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 polymorphisms on 90-day ischemic stroke functional outcome: A novel finding', Journal of Stroke and Cerebrovascular Diseases, 20 134-144 (2011) [C1]
DOI 10.1016/j.jstrokecerebrovasdis.2009.10.011
Citations Scopus - 36Web of Science - 33
Co-authors Lisa Lincz, John Attia, Christopher Levi
2011 Gwas Consortium, Henskens FA, Loughland CM, Michie PT, Schall UA, Scott R, 'Genome-wide association study identifies five new schizophrenia loci', Nature Genetics, 43 969-U77 (2011) [C1]
Citations Scopus - 1084Web of Science - 1061
Co-authors Ulrich Schall, Pat Michie, Frans Henskens, Carmel Loughland
2011 Australian Ntl Endometrial Cancer Study Group, Scott R, Ashton KA, Proietto AM, Otton GR, Ntl Study Of Endometrical Cancer Genetics Group, 'Genome-wide association study identifies a common variant associated with risk of endometrial cancer', Nature Genetics, 43 451-455 (2011) [C1]
DOI 10.1038/ng.812
Citations Scopus - 91Web of Science - 86
2011 Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ, et al., 'Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease', Nature Genetics, 43 1241-1248 (2011) [C1]
Citations Scopus - 150Web of Science - 137
Co-authors John Attia, Liz Holliday
2010 Dymerska D, Serrano-Fernandez P, Suchy J, Plawski A, Slomski R, Kaklewski K, et al., 'Combined iPLEX and TaqMan assays to screen for 45 common mutations in Lynch Syndrome and FAP patients', Journal of Molecular Diagnostics, 12 82-90 (2010) [C1]
DOI 10.2353/jmoldx.2010.090063
Citations Scopus - 4Web of Science - 4
2010 Attia JR, Thakkinstian A, McElduff P, Milne E, Dawson S, Scott R, et al., 'Detecting genotyping error using measures of degree of Hardy-Weinberg disequilibrium', Statistical Applications in Genetics and Molecular Biology, 9 17 (2010) [C1]
DOI 10.2202/1544-6115.1463
Citations Scopus - 14Web of Science - 11
Co-authors John Attia, Patrick Mcelduff
2010 Ikram MK, Xueling S, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, et al., 'Four Novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation In Vivo', Plos Genetics, 6 1-12 (2010) [C1]
DOI 10.1371/journal.pgen.1001184
Citations Scopus - 78Web of Science - 73
Co-authors Liz Holliday, John Attia
2010 Talseth-Palmer B, McPhillips M, Groombridge C, Spigelman A, Scott R, 'MSH6 and PMS2 mutation positive Australian Lynch syndrome families: Novel mutations, cancer risk and age of diagnosis of colorectal cancer', Hereditary Cancer in Clinical Practice, 8 1-10 (2010) [C1]
DOI 10.1186/1897-4287-8-5
Citations Scopus - 17Web of Science - 16
Co-authors Bente Talseth-Palmer
2010 Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, Gilbert M, et al., 'Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk', Cancer Epidemiology, 34 328-337 (2010) [C1]
DOI 10.1016/j.canep.2010.03.005
Citations Scopus - 39Web of Science - 40
Co-authors Mark Mcevoy, Ian Symonds, John Attia
2010 Jensen CJ, Stankovich J, Van der Walt A, Bahlo M, Taylor BV, van der Mei IAF, et al., 'Multiple Sclerosis Susceptibility-Associated SNPs Do Not Influence Disease Severity Measures in a Cohort of Australian MS Patients', PLOS ONE, 5 (2010) [C1]
DOI 10.1371/journal.pone.0010003
Citations Scopus - 31Web of Science - 28
Co-authors Pablo Moscato, Jeannette Lechner-Scott
2010 Cox MB, Cairns MJ, Gandhi KS, Carroll AP, Moscovis CC, Stewart GJ, et al., 'MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood', Plos One, 5 e12132 (2010) [C1]
DOI 10.1371/journal.pone.0012132
Citations Scopus - 150Web of Science - 130
Co-authors Murray Cairns, Pablo Moscato, Jeannette Lechner-Scott
2010 Riveros RC, Mellor D, Gandhi KS, McKay FC, Cox MB, Berretta RE, et al., 'A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis', Plos One, 5 1-28 (2010) [C1]
DOI 10.1371/journal.pone.0014176
Citations Scopus - 30Web of Science - 28
Co-authors Pablo Moscato, Regina Berretta, Jeannette Lechner-Scott, Carlos Riveros
2010 Tomlinson IPM, Dunlop M, Campbell H, Zanke B, Gallinger S, Hudson T, et al., 'Erratum: COGENT (COlorectal cancer GENeTics): An international consortium to study the role of polymorphic variation on the risk of colorectal cancer (British Journal of Cancer 102 (447-454) DOI: 10.1038/sj.bjc.6605338))', British Journal of Cancer, 102 455 (2010)
DOI 10.1038/sj.bjc.6605518
2010 Mattace-Raso FUS, Hofman A, Verwoert GC, Wittemana JCM, Wilkinson I, Cockcroft J, et al., 'Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ¿Establishing normal and reference values¿', European Heart Journal, 31 2338-2350 (2010)

© The Author 2010. Aims Carotid¿femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estim... [more]

© The Author 2010. Aims Carotid¿femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

DOI 10.1093/eurheartj/ehq165
Citations Scopus - 706
2010 Mari A, Nofrate V, Skyler JS, Ferrannini E, 'Progression of beta cell dysfunction in subjects at risk for type 1 diabetes', Journal of the American College of Nutrition, 29 435-436 (2010)
DOI 10.1080/07315724.2010.10719873
Citations Scopus - 1
2010 Notare MSMA, 'I2TS 2009 and LatinCom 2009', IEEE Latin America Transactions, 8 319-322 (2010)

This special number of the IEEE Latin America Transactions includes a selection of the best papers presented at the three events I2TS 2009 and LatinCom 2009. © 2010, The Institute... [more]

This special number of the IEEE Latin America Transactions includes a selection of the best papers presented at the three events I2TS 2009 and LatinCom 2009. © 2010, The Institute of Electrical and Electronics Engineers, Inc.

DOI 10.1109/TLA.2010.5595120
2010 Loughland CM, Draganic D, McCabe KL, Richards JM, Nasir MA, Allen J, et al., 'Australian Schizophrenia Research Bank: A database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia', Australian and New Zealand Journal of Psychiatry, 44 1029-1035 (2010) [C1]
DOI 10.3109/00048674.2010.501758
Citations Web of Science - 51
Co-authors Pat Michie, Ulrich Schall, Paul Tooney, Carmel Loughland, Frans Henskens
2010 Field J, Browning SR, Johnson LJ, Danoy P, Varney MD, Tait BD, et al., 'A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis', PLoS ONE, 5 (2010) [C1]

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases a... [more]

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each P=4×10-6). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (P=0:001) and were highly significant in the combined dataset (P=6 × 10-8). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set P = 9 × 10-9, replication set P = 7 × 10-4, combined P=2 × 10-10). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association. © 2010 Field et al.

DOI 10.1371/journal.pone.0013454
Citations Scopus - 33Web of Science - 25
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2010 Bowden NA, Ashton KA, Kiejda KA, Zhang XD, Hersey P, Scott R, 'Nucleotide excision repair gene expression after cisplatin treatment in melanoma', Cancer Research, 70 7918-7926 (2010) [C1]
Citations Scopus - 17Web of Science - 13
Co-authors Kelly Kiejda, Nikola Bowden, Xu Zhang
2010 Holliday EG, Scott R, Attia JR, 'Evidence-based medicine in the era of biomarkers: Teaching a new dog old tricks?', Clinical Pharmacology and Therapeutics, 88 740-742 (2010) [C2]
DOI 10.1038/clpt.2010.214
Citations Scopus - 5Web of Science - 3
Co-authors Liz Holliday, John Attia
2010 Milne E, Royle JA, Miller M, Bower C, De Klerk NH, Bailey HD, et al., 'Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring', International Journal of Cancer, 126 2690-2699 (2010) [C1]
DOI 10.1002/ijc.24969
Citations Scopus - 45Web of Science - 37
Co-authors John Attia
2010 Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, et al., 'BRCA1-associated breast and ovarian cancer risks in Poland: No association with commonly studied polymorphisms', Breast Cancer Research and Treatment, 119 201-211 (2010) [C1]
DOI 10.1007/s10549-009-0390-5
Citations Scopus - 59Web of Science - 55
2010 Dudding TE, Lawrence O, Winship I, Froyen G, Vandewalle J, Scott R, Shelling AN, 'Array comparative genomic hybridization for the detection of submicroscopic copy number variations of the X chromosome in women with premature ovarian failure', Human Reproduction, 25 3159-3160 (2010) [C3]
Citations Scopus - 15Web of Science - 10
Co-authors T Dudding
2010 McEvoy MA, Smith WT, D'Este CA, Duke JM, Peel R, Schofield PW, et al., 'Cohort Profile: The Hunter Community Study', International Journal of Epidemiology, 39 1452-1463 (2010) [C1]
DOI 10.1093/ije/dyp343
Citations Scopus - 78Web of Science - 75
Co-authors Roseanne Peel, Ben Ewald, Julie Byles, Wayne Smith, Peter Schofield, Mark Mcevoy, John Attia, Mddah01, Catherine Deste
2010 Baines KJ, Simpson JL, Bowden NA, Scott R, Gibson PG, 'Differential gene expression and cytokine production from neutrophils in asthma phenotypes', European Respiratory Journal, 35 522-531 (2010) [C1]
DOI 10.1183/09031936.00027409
Citations Scopus - 52Web of Science - 47
Co-authors Katherine Baines, Nikola Bowden, Jodie Simpson, Peter Gibson
2010 Scott R, 'Genetics of colorectal cancers', VIRCHOWS ARCHIV, 457 101-102 (2010) [C1]
2010 Gandhi KS, McKay FC, Cox MB, Riveros RC, Armstrong N, Heard RN, et al., 'The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis', Human Molecular Genetics, 19 2134-2143 (2010) [C1]
DOI 10.1093/hmg/ddq090
Citations Scopus - 68Web of Science - 61
Co-authors Jeannette Lechner-Scott, Pablo Moscato, Carlos Riveros
2010 Out AA, Tops CMJ, Nielsen M, Weiss MM, Van Minderhout IJHM, Fokkema IFAC, et al., 'Leiden Open Variation Database of the MUTYH Gene', Human Mutation, 31 1205-1215 (2010) [C1]
DOI 10.1002/humu.21343
Citations Scopus - 43Web of Science - 40
2010 Booth DR, Heard RN, Stewart GJ, Cox M, Scott R, Lechner-Scott J, et al., 'Lack of support for association between the KIF1B rs10492972[C] variant and multiple sclerosis', Nature Genetics, 42 469-470 (2010) [C3]
Citations Scopus - 21Web of Science - 17
Co-authors Jeannette Lechner-Scott
2010 Cox AJ, Gleeson M, Pyne DB, Callister R, Fricker PA, Scott R, 'Cytokine gene polymorphisms and risk for Upper Respiratory Symptoms in highly-trained athletes', Exercise Immunology Review, 16 8-21 (2010) [C1]
Citations Scopus - 19Web of Science - 16
Co-authors Robin Callister, Maree Gleeson
2010 Scott R, 'Have the roles of two functional polymorphisms in breast cancer, R72P in P53 and MDM2-309 in MDM2, become clearer?', Breast Cancer Research, 12 1-3 (2010) [C3]
DOI 10.1186/bcr2474
Citations Scopus - 1Web of Science - 1
2010 Esposito F, Patsopoulos NA, Cepok S, Kockum I, Leppa V, Booth DR, et al., 'IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci', Genes and Immunity, 11 397-405 (2010) [C1]
DOI 10.1038/gene.2010.28
Citations Scopus - 43Web of Science - 35
Co-authors Jeannette Lechner-Scott
2010 Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, Scott R, 'Toll-Like Receptor (TLR) and Nucleosome-binding Oligomerization Domain (NOD) gene polymorphisms and endometrial cancer risk', BMC Cancer, 10 1-7 (2010) [C1]
DOI 10.1186/1471-2407-10-382
Citations Scopus - 32Web of Science - 29
Co-authors Ian Symonds, Mark Mcevoy, John Attia
2010 Mossman D, Kim K-T, Scott R, 'Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists', BMC Cancer, 10 1-10 (2010) [C1]
DOI 10.1186/1471-2407-10-366
Citations Scopus - 62Web of Science - 54
2010 Trubicka J, Grabowska-Klujszo E, Suchy J, Masojc B, Serrano-Fernandez P, Kurzawski G, et al., 'Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility', BMC Cancer, 10 1-6 (2010) [C1]
DOI 10.1186/1471-2407-10-420
Citations Scopus - 18Web of Science - 16
2009 Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, et al., 'Estrogen receptor polymorphisms and the risk of endometrial cancer', BJOG: An International Journal of Obstetrics and Gynaecology, 116 1053-1061 (2009) [C1]
DOI 10.1111/j.1471-0528.2009.02185.x
Citations Scopus - 38Web of Science - 36
Co-authors John Attia, Ian Symonds, Mark Mcevoy
2009 Whitehall V, Tran K, Umapathy A, Grieu F, Hewitt C, Evans T-J, et al., 'A Multicenter Blinded Study to Evaluate KRAS Mutation Testing Methodologies in the Clinical Setting', JOURNAL OF MOLECULAR DIAGNOSTICS, 11 543-552 (2009) [C1]
DOI 10.2353/jmoldx.2009.090057
Citations Scopus - 104Web of Science - 96
2009 Gapska P, Scott R, Serrano-Fernandez P, Huzarski T, Byrski T, Kladny J, et al., 'Vitamin D receptor variants and breast cancer risk in the Polish population', Breast Cancer Research and Treatment, 115 629-633 (2009) [C1]
DOI 10.1007/s10549-008-0107-1
Citations Scopus - 19Web of Science - 15
2009 Ashton KA, Proietto AM, Otton GR, Symonds IM, Scott R, 'Genetic variants in MUTYH are not associated with endometrial cancer risk', Hereditary Cancer in Clinical Practice, 7 1-5 (2009) [C1]
DOI 10.1186/1897-4287-7-3
Citations Scopus - 10Web of Science - 8
Co-authors Ian Symonds
2009 Lubinski J, Sijmons RH, Scott R, 'Hereditary cancer in clinical practice transfers to BioMed Central', Hereditary Cancer in Clinical Practice, 7 Article 1 (2009) [C3]
DOI 10.1186/1897-4287-7-1
2009 Gapska P, Scott R, Serrano-Fernandez P, Mirecka A, Rassoud I, Gorski B, et al., 'Vitamin D receptor variants and the malignant melanoma risk: A population-based study', Cancer Epidemiology, 33 103-107 (2009) [C1]
DOI 10.1016/j.canep.2009.06.006
Citations Scopus - 26Web of Science - 25
2009 Milne E, Royle JA, De Klerk NH, Blair E, Bailey H, Cole C, et al., 'Fetal growth and risk of childhood acute lymphoblastic leukemia: Results from an Australian case-control study', American Journal of Epidemiology, 170 221-228 (2009) [C1]
DOI 10.1093/aje/kwp117
Citations Scopus - 33Web of Science - 29
Co-authors John Attia
2009 Stankovich J, Butzkueven H, Marriott M, Chapman C, Tubridy N, Tait BD, et al., 'HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis', Tissue Antigens, 74 17-21 (2009)

Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence susceptibility to multiple sclerosis (MS), but their contribution if any to the clinical course of MS ... [more]

Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence susceptibility to multiple sclerosis (MS), but their contribution if any to the clinical course of MS remains uncertain. Here, we have investigated DRB1 alleles in a large sample of 1230 Australian MS cases, with some enrichment for subjects with primary progressive (PPMS) disease (n = 246) and 1210 healthy controls. Using logistic regression, we found that DRB1*1501 was strongly associated with risk (P = 7 × 10-45), as expected, and after adjusting for DRB1*1501, a predisposing effect was also observed for DRB1*03 (P = 5 × 10-7). Individuals homozygous for either DRB1*15 or DRB1*03 were considerably more at risk of MS than heterozygotes and non-carriers. Both the DRB1*04 and the DRB1*01/DRB1*15 genotype combination, respectively, protected against PPMS in comparison to subjects with relapsing disease. Together, these data provide further evidence of heterogeneity at the DRB1 locus and confirm the importance of HLA variants in the phenotypic expression of MS. © 2009 John Wiley & Sons A/S.

DOI 10.1111/j.1399-0039.2009.01262.x
Citations Scopus - 34
Co-authors Jeannette Lechner-Scott
2009 Shi Z, Johnstone DM, Talseth-Palmer B, Evans T-J, Spigelman AD, Groombridge C, et al., 'Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age', International Journal of Cancer, 125 78-83 (2009) [C1]
DOI 10.1002/ijc.24304
Co-authors Liz Milward, Bente Talseth-Palmer
2009 Weidenhofer JC, Scott R, Tooney PA, 'Investigation of the expression of genes affecting cytomatrix active zone function in the amygdala in schizophrenia: Effects of antipsychotic drugs', Journal of Psychiatric Research, 43 282-290 (2009) [C1]
DOI 10.1016/j.jpsychires.2008.04.001
Citations Scopus - 10Web of Science - 11
Co-authors Judith Weidenhofer, Paul Tooney
2009 Tomlinson IPM, Dunlop M, Campbell H, Zanke B, Gallinger S, Hudson T, et al., 'COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer', British Journal of Cancer, 102 447-454 (2009) [C1]
DOI 10.1038/sj.bjc.6605338
Citations Scopus - 37Web of Science - 32
2009 Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, et al., 'Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer', Gynecologic Oncology, 113 109-114 (2009) [C1]
DOI 10.1016/j.ygyno.2008.12.036
Citations Scopus - 34Web of Science - 34
Co-authors John Attia, Mark Mcevoy, Ian Symonds
2009 Attia JR, Ioannidis JPA, Thakkinstian A, McEvoy MA, Scott R, Minelli C, et al., 'How to use an article about genetic association A: Background concepts', JAMA: Journal of the American Medical Association, 301 74-81 (2009) [C1]
DOI 10.1001/jama.2008.901
Citations Scopus - 75Web of Science - 76
Co-authors John Attia, Mark Mcevoy
2009 Attia JR, Ioannidis JPA, Thakkinstian A, McEvoy MA, Scott R, Minelli C, et al., 'How to use an article about genetic association B: Are the results of the study valid?', JAMA: Journal of the American Medical Association, 301 191-197 (2009) [C1]
DOI 10.1001/jama.2008.946
Citations Scopus - 106Web of Science - 108
Co-authors Mark Mcevoy, John Attia
2009 Attia JR, Ioannidis JPA, Thakkinstian A, McEvoy MA, Scott R, Minelli C, et al., 'How to use an article about genetic association C: What are the results and will they help me in caring for my patients?', JAMA: Journal of the American Medical Association, 301 304-308 (2009) [C1]
DOI 10.1001/jama.2008.993
Citations Scopus - 51Web of Science - 49
Co-authors Mark Mcevoy, John Attia
2009 Lubinski J, Korzen M, Gorski B, Cybulski C, Debniak T, Jakubowska A, et al., 'Genetic contribution to all cancers: The first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology', Breast Cancer Research and Treatment, 114 121-126 (2009) [C1]
DOI 10.1007/s10549-008-9974-8
Citations Scopus - 8Web of Science - 8
2009 Baines KJ, Simpson JL, Scott R, Gibson PG, 'Immune responses of airway neutrophils are impaired in asthma', Experimental Lung Research, 35 554-569 (2009) [C1]
DOI 10.1080/01902140902777490
Citations Scopus - 25Web of Science - 23
Co-authors Jodie Simpson, Katherine Baines, Peter Gibson
2009 Simpson JL, Baines KJ, Boyle MJ, Scott R, Gibson PG, 'Oncostatin M (OSM) is increased in asthma with incompletely reversible airflow obstruction', Experimental Lung Research, 35 781-794 (2009) [C1]
DOI 10.3109/01902140902906412
Citations Scopus - 23Web of Science - 24
Co-authors Peter Gibson, Katherine Baines, Jodie Simpson
2009 Umapathy A, Whitehall V, Tran K, Grieu F, Hewitt C, Evans TJ, et al., 'A multicentre study to evaluate k-ras mutation testing methodologies in the clinical setting', JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 24 A240-A240 (2009) [E3]
2009 Reeves SG, Meldrum C, Groombridge C, Spigelman AD, Suchy J, Kurzawski G, et al., 'MTHFR 677 C\T and 1298 A\C polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer', European Journal of Human Genetics, 17 629-635 (2009) [C1]
DOI 10.1038/ejhg.2008.239
Co-authors Patrick Mcelduff
2009 Kaput J, Cotton RGH, Hardman L, Watson M, Aqeel AIA, Al-Aama JY, et al., 'Planning the Human Variome Project: The Spain report', Human Mutation, 30 496-510 (2009) [C1]
DOI 10.1002/humu.20972
Citations Scopus - 37Web of Science - 34
2009 Bahlo M, Booth DR, Broadley SA, Brown MA, Foote SJ, Griffiths LR, et al., 'Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20', Nature Genetics, 41 824-828 (2009) [C1]
DOI 10.1038/ng.396
Citations Scopus - 377Web of Science - 313
Co-authors Jeannette Lechner-Scott, Pablo Moscato
2009 Kladny J, Suchy J, Klujszo-Grabowska E, Kacperski T, Scott R, Kurzawski G, Lubinski J, 'Clinical characteristics of tumors derived from colorectal cancer patients who harbor the Tumor Necrosis Factor beta-1031T/T and NOD2 3020insC polymorphism', Cancer Epidemiology, 33 161-163 (2009) [C1]
DOI 10.1016/j.canep.2009.06.004
Citations Scopus - 2Web of Science - 1
2009 Cotton RGH, Al Aqeel AI, Al-Mulla F, Carrera P, Claustres M, Ekong R, et al., 'Capturing all disease-causing mutations for clinical and research use: Toward an effortless system for the Human Variome Project', Genetics in Medicine, 11 843-849 (2009) [C1]
DOI 10.1097/gim.0b013e3181c371c5
Citations Scopus - 33Web of Science - 28
2009 Talseth-Palmer B, Bowden NA, Meldrum C, Nicholl J, Thompson E, Friend K, et al., 'A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology', Cytogenetic and Genome Research, 124 94-101 (2009) [C1]
DOI 10.1159/000200093
Citations Scopus - 5Web of Science - 5
Co-authors Nikola Bowden, Bente Talseth-Palmer
2008 Simpson JL, Powell H, Boyle MJ, Scott R, Gibson PG, 'Clarithromycin targets neutrophilic airway inflammation in refractory asthma', American Journal of Respiratory and Critical Care Medicine, 177 148-155 (2008) [C1]
DOI 10.1164/rccm.200707-1134oc
Citations Scopus - 314Web of Science - 279
Co-authors Jodie Simpson, Peter Gibson
2008 Kiejda KA, Zhang XD, Adams LJ, Scott R, Vojtesek B, Lane DP, Hersey P, 'Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin', Clinical Cancer Research, 14 1659-1668 (2008) [C1]
DOI 10.1158/1078-0432.ccr-07-1422
Citations Scopus - 73Web of Science - 67
Co-authors Kelly Kiejda, Xu Zhang
2008 Bowden NA, Scott R, Tooney PA, 'Altered gene expression in the superior temporal gyrus in schizophrenia', BMC Genomics, 9 1-12 (2008) [C1]
DOI 10.1186/1471-2164-9-199
Citations Scopus - 39Web of Science - 40
Co-authors Nikola Bowden, Paul Tooney
2008 Jakubowska A, Menkiszak J, Gorski B, Huzarski T, Byrski T, Benner A, et al., 'Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism', BMC Cancer, 8 1-5 (2008) [C1]
DOI 10.1186/1471-2407-8-90
Citations Scopus - 5Web of Science - 6
2008 Suchy J, Klujszo-Grabowska E, Kladny J, Cybulski C, Wokolorczyk D, Szymanska-Pasternak J, et al., 'Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk', BMC Cancer, 8 1-7 (2008) [C1]
DOI 10.1186/1471-2407-8-112
Citations Scopus - 32Web of Science - 25
2008 Ashton KA, Proietto AM, Otton GR, Symonds IM, McEvoy MA, Attia JR, et al., 'The influence of the Cyclin D1 870 G\A polymorphism as an endometrial cancer risk factor', BMC Cancer, 8 1-6 (2008) [C1]
DOI 10.1186/1471-2407-8-272
Citations Scopus - 9Web of Science - 7
Co-authors Mark Mcevoy, Ian Symonds, John Attia
2008 Dudding TE, Heron J, Thakkinstian A, Nurk E, Golding J, Pembrey M, et al., 'Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: A genetic association study and meta-analysis', Journal of Thrombosis and Haemostasis, 6 1868-1875 (2008) [C1]
DOI 10.111/j.1538-7836.2008.03134.x
Citations Scopus - 40Web of Science - 34
Co-authors John Attia, T Dudding
2008 Talseth-Palmer B, Bowden NA, Hill A, Meldrum C, Scott R, 'Whole genome amplification and its impact on CGH array profiles', BMC Research Notes, 1 108 (2008) [C1]
DOI 10.1186/1756-0500-1-56
Citations Scopus - 18
Co-authors Nikola Bowden, Bente Talseth-Palmer
2008 Scott R, Crooks R, Meldrum C, 'Gene symbol: STK11. Disease: Peutz-Jeghers Syndrome.', Human genetics, 124 300 (2008) [C3]
Citations Scopus - 3
2008 Debniak T, Van De Wetering T, Scott R, Nagay L, Cybulski C, Gorski B, et al., 'Low prevalence of CDKN2A/ARF mutations among early-onset cancers of breast, pancreas and malignant melanoma in Poland', European Journal of Cancer Prevention, 17 389-391 (2008) [C1]
DOI 10.1097/cej.0b013e3282f75eb1
Citations Scopus - 12Web of Science - 9
2008 Lewicke A, Sazonov E, Corwin MJ, Neuman M, Schuckers S, 'Sleep Versus Wake Classification From Heart Rate Variability Using Computational Intelligence: Consideration of Rejection in Classification Models', IEEE Transactions on Biomedical Engineering, 55 108-118 (2008)

Reliability of classification performance is important for many biomedical applications. A classification model which considers reliability in the development of the model such th... [more]

Reliability of classification performance is important for many biomedical applications. A classification model which considers reliability in the development of the model such that unreliable segments are rejected would be useful, particularly, in large biomedical data sets. This approach is demonstrated in the development of a technique to reliably determine sleep and wake using only the electrocardiogram (ECG) of infants. Typically, sleep state scoring is a time consuming task in which sleep states are manually derived from many physiological signals. The method was tested with simultaneous 8-h ECG and polysomnogram (PSG) determined sleep scores from 190 infants enrolled in the collaborative home infant monitoring evaluation (CHIME) study. Learning vector quantization (LVQ) neural network, multilayer perceptron (MLP) neural network, and support vector machines (SVMs) are tested as the classifiers. After systematic rejection of difficult to classify segments, the models can achieve 85%¿87% correct classification while rejecting only 30% of the data. This corresponds to a Kappa statistic of 0.65¿0.68. With rejection, accuracy improves by about 8% over a model without rejection. Additionally, the impact of the PSG scored indeterminate state epochs is analyzed. The advantages of a reliable sleep/wake classifier based only on ECG include high accuracy, simplicity of use, and low intrusiveness. Reliability of the classification can be built directly in the model, such that unreliable segments are rejected. © 2008, IEEE. All rights reserved.

DOI 10.1109/TBME.2007.900558
Citations Scopus - 42
2008 Zoboli A, Boscardin M, Bosisio L, Betta GFD, Piemonte C, Ronchin S, Zorzi N, 'Double-Sided, Double-Type-Column 3-D Detectors: Design, Fabrication, and Technology Evaluation', IEEE Transactions on Nuclear Science, 55 2775-2784 (2008)

We report on the latest results from the development of 3-D silicon radiation detectors at Fondazione Bruno Kessler of Trento (FBK), Italy (formerly ITC-IRST). Building on the res... [more]

We report on the latest results from the development of 3-D silicon radiation detectors at Fondazione Bruno Kessler of Trento (FBK), Italy (formerly ITC-IRST). Building on the results obtained from previous devices (3-D Single-Type-Column), a new detector concept has been defined, namely 3-D-DDTC (Double-sided Double-Type Column), which involves columnar electrodes of both doping types, etched from alternate wafer sides, stopping a short distance (d) from the opposite surface. Simulations prove that, if d is kept small with respect to the wafer thickness, this approach can yield charge collection properties comparable to those of standard 3-D detectors, with the advantage of a simpler fabrication process. Two wafer layouts have been designed with reference to this technology, and two fabrication runs have been performed. Technological and design aspects are reported in this paper, along with simulation results and initial results from the characterization of detectors and test structures belonging to the first 3-D-DDTC batch. © 2008, IEEE. All rights reserved.

DOI 10.1109/TNS.2008.2002885
Citations Scopus - 53
2008 Bolotnikov AE, Abdul-Jabbar NM, Babalola OS, Camarda GS, Cui Y, Hossain AM, et al., 'Effects of Te Inclusions on the Performance of CdZnTe Radiation Detectors', IEEE Transactions on Nuclear Science, 55 2757-2764 (2008)

Te inclusions existing at high concentrations in CdZnTe (CZT) material can degrade the performance of CZT detectors. These microscopic defects trap the free electrons generated by... [more]

Te inclusions existing at high concentrations in CdZnTe (CZT) material can degrade the performance of CZT detectors. These microscopic defects trap the free electrons generated by incident radiation, so entailing significant fluctuations in the total collected charge and thereby strongly affecting the energy resolution of thick (long-drift) detectors. Such effects were demonstrated in thin planar detectors, and, in many cases, they proved to be the dominant cause of the low performance of thick detectors, wherein the fluctuations in the charge losses accumulate along the charge¿s drift path. We continued studying this effect using different tools and techniques. We employed a dedicated beam-line recently established at BNL¿s National Synchrotron Light Source for characterizing semiconductor radiation detectors, along with an IR transmission microscope system, the combination of which allowed us to correlate the concentration of defects with the devices¿ performances. We present here our new results from testing over 50 CZT samples grown by different techniques. Our goals are to establish tolerable limits on the size and concentrations of these detrimental Te inclusions in CZT material, and to provide feedback to crystal growers to reduce their numbers in the material. © 2008, IEEE. All rights reserved.

DOI 10.1109/TNS.2008.2003355
Citations Scopus - 53
2008 Bott SC, Haas DM, Eshaq Y, Ueda U, Lebedev SV, Chittenden JP, et al., 'Quantitative Measurements of Wire Ablation in Tungsten X-pinches at 80 kA', IEEE Transactions on Plasma Science, 36 2759-2764 (2008)

This paper investigates the ablation of wires in two-wire tungsten X-pinches driven by an 80-kA current over 50 ns. High-resolution imaging using a Nomarski interferometer allows ... [more]

This paper investigates the ablation of wires in two-wire tungsten X-pinches driven by an 80-kA current over 50 ns. High-resolution imaging using a Nomarski interferometer allows measurements close to the X-pinch cross point, where the ablation ¿flare¿ structure is observed to clearly develop during the drive-current rise time. Electron density profiles are recovered as a function of both distance normal to the wire and of time. Results compare favorably to the rocket model of wire ablation. In addition, the density contrast over the ablation ¿stream¿ and ¿gap¿ structure is measured and compared to similar measurements made using quantitative radiography on the 1-MA 250-ns MAGPIE generator at Imperial College London, London, U.K. © 2008, IEEE. All rights reserved.

DOI 10.1109/TPS.2008.2003964
Citations Scopus - 10
2008 Borio D, Camoriano L, Presti LL, 'Two-Pole and Multi- ole Notch Filters: A Computationally Effective Solution for GNSS Interference Detection and Mitigation', IEEE Systems Journal, 2 38-47 (2008)

In a global navigation satellite system (GNSS) receiver, the presence of detection and mitigation units, capable of reducing the impact of disturbing signals, can extremely enhanc... [more]

In a global navigation satellite system (GNSS) receiver, the presence of detection and mitigation units, capable of reducing the impact of disturbing signals, can extremely enhance the position accuracy. However, the presence of such units is usually limited to professional receivers that dispose of additional computational power that can be used for interference detection and mitigation. In this paper, the two-pole notch filter, that is the natural extension of the one-pole notch filter, is proposed as computationally effective solution for interference detection and mitigation. The notch filter structure and the adaptive algorithm employed for tracking the disturbing signal are analyzed, and an interference detection unit, based on the adaptive algorithm convergence, is proposed. The two-pole notch filter coupled with the detection unit is used as elementary block for the design of a multi-pole notch filter that can efficiently mitigate more than one CW interference. Theoretical and simulative analyses show the feasibility and the good performance of the proposed method. © 2008, IEEE. All rights reserved.

DOI 10.1109/JSYST.2007.914780
Citations Scopus - 41
2008 Froyen G, Corbett M, Vandewalle J, Jarvela I, Lawrence O, Meldrum C, et al., 'Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation', American Journal of Human Genetics, 82 432-443 (2008) [C1]
DOI 10.1016/j.ajhg.2007.11.002
Citations Scopus - 121Web of Science - 117
Co-authors A Hackett
2008 Foster RC, Byrnes EM, Meldrum C, Griffith R, Ross G, Upjohn E, et al., 'Association of paediatric mastocytosis with a polymorphism resulting in an amino acid substitution (M541L) in the transmembrane domain of c-KIT', British Journal of Dermatology, 159 1160-1169 (2008) [C1]
DOI 10.1111/j.1365-2133.2008.08827.x
Citations Scopus - 38Web of Science - 34
Co-authors Leonie Ashman
2008 Zlowocka E, Cybulski C, Gorski B, Debniak T, Slojewski M, Wokolorczyk D, et al., 'Germline mutations in the CHEK2 kinase gene are associated with an increased risk of bladder cancer', International Journal of Cancer, 122 583-586 (2008) [C1]
DOI 10.1002/ijc.23099
Citations Scopus - 16Web of Science - 15
2008 Talseth-Palmer B, Ashton KA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott R, 'Aurora-A and Cyclin D1 polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer', International Journal of Cancer, 122 1273-1277 (2008) [C1]
DOI 10.1002/ijc.23177
Citations Scopus - 25Web of Science - 21
Co-authors Bente Talseth-Palmer
2008 Reeves SG, Rich D, Meldrum CJ, Colyvas KJ, Kurzawski G, Suchy J, et al., 'IGF1 is a modifier of disease risk in hereditary non-polyposis colorectal cancer', International Journal of Cancer, 123 1339-1343 (2008) [C1]
DOI 10.1002/ijc.23668
Citations Scopus - 22Web of Science - 20
Co-authors Kim Colyvas
2008 Burn J, Bishop T, Mecklin J-P, Macrae F, Moslein G, Olschwang S, et al., 'Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome', New England Journal of Medicine, 359 2567-2578 (2008) [C1]
DOI 10.1056/NEJMoa0801297
Citations Scopus - 159Web of Science - 143
2008 Jaworowska E, Serrano-Fernandez P, Tarnowska C, Lubinski J, Brzosko M, Flicinski J, et al., 'Familial association of laryngeal, lung, stomach and early-onset breast cancer', Breast Cancer Research and Treatment, 112 359-361 (2008) [C1]
DOI 10.1007/s10549-007-9869-0
Citations Scopus - 1Web of Science - 1
2008 Reeves SG, Mossman D, Meldrum CJ, Kurzawski G, Suchy J, Lubinski J, Scott R, 'The-149C \ T SNP within the Delta DNMT3B gene, is not associated with early disease onset in hereditary non-polyposis colorectal cancer', Cancer Letters, 265 39-44 (2008) [C1]
DOI 10.1016/j.canlet.2008.02.005
Citations Scopus - 12Web of Science - 11
2008 Jakubowska A, Gronwald J, Menklszak J, Gorski B, Huzarski T, Byrski T, et al., 'The VEGF_936_C \ T 3 ' UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women', Cancer Letters, 262 71-76 (2008) [C1]
DOI 10.1016/j.canlet.2007.11.029
Citations Scopus - 40Web of Science - 36
2008 Debniak B, Kowalska E, Jakubowska A, Gronwald J, Wokolorczyk D, Maleszka R, et al., 'Common variants of DNA repair genes and malignant melanoma', European Journal of Cancer, 44 110-114 (2008) [C1]
DOI 10.1016/j.ejca.2007.10.006
Citations Scopus - 25Web of Science - 25
2008 Beveridge NJ, Tooney PA, Carroll AP, Gardiner EJ, Bowden NA, Scott R, et al., 'Dysregulation of miRNA 181b in the temporal cortex in schizophrenia', Human Molecular Genetics, 17 1156-1168 (2008) [C1]
DOI 10.1093/hmg/ddn005
Citations Scopus - 224Web of Science - 213
Co-authors Paul Tooney, Nikola Bowden, Murray Cairns
2008 Scott R, 'Variable phenotypic expression in HNPCC and the search for modifier genes', European Journal of Human Genetics, 16 531-532 (2008) [C2]
DOI 10.1038/ejhg.2008.46
Citations Scopus - 6Web of Science - 4
2007 Jaworowska E, Serrano-Fernandez P, Tarnowska C, Lubinski J, Kram A, Masojc B, et al., 'Clinical and epidemiological features of familial laryngeal cancer in Poland', Cancer Detection and Prevention, 31 270-275 (2007) [C1]
DOI 10.1016/j.cdp.2006.06.007
Citations Scopus - 4Web of Science - 1
2007 Bowden NA, Scott R, Tooney PA, 'Altered expression of regulator of G-protein signalling 4 (RGS4) mRNA in the superior temporal gyrus in schizophrenia', Schizophrenia Research, 89 165-168 (2007) [C1]
DOI 10.1016/j.schres.2006.09.003
Citations Scopus - 37Web of Science - 39
Co-authors Nikola Bowden, Paul Tooney
2007 The International Breast Cancer Study Group, Forbes JF, 'Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: Results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93', Annals of Oncology, 18 1177-1184 (2007) [C1]
DOI 10.1093/annonc/mdm091
Citations Scopus - 9
Co-authors Stephen Ackland, John Forbes
2007 Attia JR, Thakkinstian A, Wang Y, Lincz L, Parsons MW, Sturm J, et al., 'The PAI-1 4G/5G gene polymorphism and ischemic stroke: An association study and meta-analysis', Journal of Stroke and Cerebrovascular Diseases, 16 173-179 (2007) [C1]
DOI 10.1016/j.jstrokecerebrovasdis.2007.03.002
Citations Scopus - 33
Co-authors John Attia, Mark Parsons, Christopher Levi, Lisa Lincz
2007 Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, et al., 'The RAD51 135 G \ C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers', Cancer Epidemiology Biomarkers & Prevention, 16 270-275 (2007) [C1]
DOI 10.1158/1055-9965.epi-06-0562
Citations Scopus - 56Web of Science - 56
2007 Lubinski J, Korzen M, Gorski B, Cybulski C, Debniak T, Jakubowska A, et al., 'Breast cancer susceptibility genes', Journal of the Balkan Union of Oncology, 12 S23-S29 (2007) [C1]
Citations Scopus - 7Web of Science - 8
2007 Scott R, 'Dear Readers', Hereditary Cancer in Clinical Practice, 5 1 (2007)
2007 Scott RJ, 'Dear readers', Hereditary Cancer in Clinical Practice, 5 181 (2007)
2007 Mhaidat NM, Zhang XD, Allen J, Kiejda KA, Scott R, Hersey P, 'Temozolomide induces senescence but not apoptosis in human melanoma cells', British Journal of Cancer, 97 1225-1233 (2007) [C1]
DOI 10.1038/sj.bjc.6604017
Citations Scopus - 46Web of Science - 44
Co-authors Kelly Kiejda, Xu Zhang
2007 Bowden NA, Croft A, Scott R, 'Gene expression profiling in familial adenomatous polyposis adenomas and desmoid disease', Hereditary Cancer in Clinical Practice, 5 79-96 (2007) [C1]
DOI 10.1186/1897-4287-5-2-79
Citations Scopus - 7Web of Science - 5
Co-authors Nikola Bowden
2007 Kairupan C, Scott R, 'Base excision repair and the role of MUTYH', Hereditary Cancer in Clinical Practice, 5 199-209 (2007) [C1]
DOI 10.1186/1897-4287-5-4-199
Citations Scopus - 7Web of Science - 7
2007 Scott R, 'Response to 'Variability in the clinical phenotype among families with HNPCC': The potential importance of the location of the mutation in the gene by Dr. Prathap Bandipalliant', International Journal of Cancer, 120 2278 (2007) [C3]
DOI 10.1002/ijc.22347
2007 Talseth-Palmer B, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott R, 'MDM2 SNP309 T \ G alone or in combination with the TP53 R72P polymorphism does not appear to influence disease expression and age of diagnosis of colorectal cancer in HNPCC patients', International Journal of Cancer, 120 563-565 (2007) [C1]
DOI 10.1002/ijc.22339
Citations Scopus - 33Web of Science - 32
Co-authors Bente Talseth-Palmer
2007 Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, et al., 'Integrin 3 Leu33Pro polymorphism increases BRCA1-associated ovarian cancer risk', Journal of Medical Genetics, 44 408-411 (2007) [C1]
DOI 10.1136/jmg.2006.047498
Citations Scopus - 12
2007 Easton DF, Search Collaborators Including, Forbes JF, 'Genome-wide association study identifies novel breast cancer susceptibility loci', Nature, 447 1087-1093 (2007) [C1]
DOI 10.1038/nature05887
Citations Scopus - 1640
Co-authors T Dudding, John Forbes
2007 Talseth-Palmer B, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott R, 'Lack of association between genetic polymorphisms in cytokine genes and disease expression in patients with hereditary non-polyposis colorectal cancer', Scandinavian Journal of Gastroenterology, 42 628-632 (2007) [C1]
DOI 10.1080/00365520601106699
Citations Scopus - 12Web of Science - 11
Co-authors Bente Talseth-Palmer
2007 Simpson JL, Grissell TV, Douwes J, Scott R, Boyle MJ, Gibson PG, 'Innate immune activation in neutrophilic asthma and bronchiectasis', Thorax, 62 211-218 (2007) [C1]
DOI 10.1136/thx.2006.061358
Citations Scopus - 195Web of Science - 186
Co-authors Jodie Simpson, Peter Gibson
2007 Jakubowska A, Gronwald J, Menkiszak J, Go B, Huzarski T, Byrski T, et al., 'Methylenetetrahydrofolate reductase polymorphisms modify BRCA1-associated breast and ovarian cancer risks', Breast Cancer Research and Treatment, 104 299-308 (2007) [C1]
DOI 10.1007/s10549-006-9417-3
Citations Scopus - 35Web of Science - 35
2007 Jakubowska A, Gronwald J, Gorski B, Huzarski T, Byrski T, Benner A, et al., 'The 3 ' untranslated region C \ T polymorphism of prohibitin is a breast cancer risk modifier in Polish women carrying a BRCA1 mutation', Breast Cancer Research and Treatment, 104 67-74 (2007) [C1]
DOI 10.1007/s10549-006-9389-3
Citations Scopus - 11Web of Science - 13
2007 Matyjasik J, Cybulski C, Masojc B, Jakubowska A, Serrano-Fernandez P, Gorski B, et al., 'CYP1B1 and predisposition to breast cancer in Poland', Breast Cancer Research and Treatment, 106 383-388 (2007) [C1]
DOI 10.1007/s10549-007-9500-4
Citations Scopus - 16Web of Science - 11
2006 Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJP, et al., 'STKII status and intussusception risk in Peutz-Jeghers syndrome', Journal of Medical Genetics, 43 41-43 (2006) [C1]
DOI 10.1136/jmg.2005.040535
Citations Scopus - 28Web of Science - 24
2006 Reeves SG, Meldrum C, Scott R, 'Re: IGF-1 gene polymorphism and risk for hereditary nonpolyposis colorectal cancer (Letter)', Journal of the National Cancer Institute, 98 1664-1665 (2006) [C3]
DOI 10.1093/jnci/djj452
Citations Scopus - 6Web of Science - 5
2006 Weidenhofer JC, Bowden NA, Scott R, Tooney PA, 'Altered gene expression in the amygdala in schizophrenia: Up-regulation of genes located in the cytomatrix active zone', Molecular and Cellular Neuroscience, 31 243-250 (2006) [C1]
DOI 10.1016/j.mcn.2005.09.013
Citations Scopus - 39Web of Science - 41
Co-authors Paul Tooney, Nikola Bowden, Judith Weidenhofer
2006 Talseth-Palmer B, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott R, 'Age of diagnosis of colorectal cancer in HNPCC patients is more complex than that predicted by R72P polymorphism in TP53', International Journal of Cancer, 118 2479-2484 (2006) [C1]
DOI 10.1002/ijc.21661
Citations Scopus - 28Web of Science - 26
Co-authors Bente Talseth-Palmer
2006 Lener MR, Oszutowska D, Castaneda J, Kurzawski G, Suchy J, Nej-Wolosiak K, et al., 'Prevalence of the NOD32 3020insC mutation in aggregations of breast and lung cancer', Breast Cancer Research and Treatment, 95 141-145 (2006) [C1]
DOI 10.1007/s10549-005-9057-z
Citations Scopus - 17Web of Science - 19
2006 Jaworowska E, Masojc B, Tarnowska C, Brzosko M, Flicinski J, Serrano-Fernandez P, et al., 'Association between early-onset breast and laryngeal cancers', Breast Cancer Research and Treatment, 97 215-219 (2006) [C1]
DOI 10.1007/s10549-005-9116-5
Citations Scopus - 11Web of Science - 10
2006 Debniak T, Scott R, Huzarski T, Byrski T, Masojc B, Van De Wetering T, et al., 'XPD common variants and their association with melanoma and breast cancer risk', Breast Cancer Research and Treatment, 98 209-215 (2006) [C1]
DOI 10.1007/s10549-005-9151-2
Citations Scopus - 40Web of Science - 38
2006 Masojc B, Mierzejewski M, Cybulski C, Van De Wetering T, Debniak T, Gorski B, et al., 'Cancer familial aggregation (CFA) and G446A polymorphism in ARLTS1 gene', Breast Cancer Research and Treatment, 99 59-62 (2006) [C1]
DOI 10.1007/s10549-006-9180-5
Citations Scopus - 14Web of Science - 13
2006 Dedniak T, Scott R, Huzarski T, Byrski T, Rozmiarek A, Debniak B, et al., 'CDKN2A common variant and multi-organ cancer risk - a population-based study (Short report)', International Journal of Cancer, 118 3180-3182 (2006) [C1]
DOI 10.1002/ijc.21760
Citations Scopus - 16Web of Science - 14
2006 Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott R, Roberts-Thomson JM, et al., 'IL6 G-174C Associated With Sudden Infant Death Syndrome in a Caucasian Australian Cohort', Human Immunology, 67 819-825 (2006) [C1]
DOI 10.1016/j.humimm.2006.07.010
Citations Scopus - 35Web of Science - 35
Co-authors Caroline Blackwell, Sharron Hall, Maree Gleeson
2006 Chow E, Meldrum CJ, Crooks R, Macrae FA, Spigelman AD, Scott RJ, 'An updated mutation spectrum in an Australian series of Peutz-Jeghers Syndrome patients provides further evidence for only one gene locus', JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 21 A262-A262 (2006)
2006 Bowden NA, Weidenhofer JC, Scott R, Schall U, Todd J, Michie PT, Tooney PA, 'Preliminary investigation of gene expression profiles in peripheral blood lymphocytes in schizophrenia', Schizophrenia Research, 82 175-183 (2006) [C1]
DOI 10.1016/j.schres.2005.11.012
Citations Scopus - 84Web of Science - 77
Co-authors Judith Weidenhofer, Paul Tooney, Nikola Bowden, Ulrich Schall, Pat Michie, Juanita Todd
2006 Hitchins M, Suter C, Wong J, Cheong K, Hawkins N, Leggett B, et al., 'Germline epimutations of APC are not associated with inherited colorectal polyposis (Letter)', Gut, 55 586-587 (2006) [C3]
Citations Scopus - 11Web of Science - 11
2006 Debniak T, Scott R, Masojc B, Serrano-Fernandez P, Huzarski T, Byrski T, et al., 'MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk', International Journal of Cancer, 119 2597-2602 (2006) [C1]
DOI 10.1002/ijc.22210
Citations Scopus - 30Web of Science - 27
2006 Simpson JL, Scott R, Boyle MJ, Gibson PG, 'Inflammatory subtypes in asthma: Assessment and identification using induced sputum', Respirology, 11 54-61 (2006) [C1]
DOI 10.1111/j.1440-1843.2006.00784.x
Citations Scopus - 426Web of Science - 399
Co-authors Jodie Simpson, Peter Gibson
2006 Milne E, Van Bockxmeer FM, Robertson L, Brisbane JM, Ashton LJ, Scott R, Armstrong BK, 'Buccal DNA collection: Comparison of buccal swabs with FTA cards (short communication)', Cancer Epidemiology Biomarkers & Prevention, 15 816-819 (2006) [C1]
DOI 10.1158/1055-9965.EPI-05-0753
Citations Scopus - 42Web of Science - 41
2006 Ashton KA, Meldrum CJ, McPhillips ML, Suchy J, Kurzawski G, Lubinski J, Scott R, 'The association of the COMT V158M polymorphism with endometrial/ovarian cancer in HNPCC families adhering to the Amsterdam criteria', Hereditary Cancer in Clinical Practice, 4 94-102 (2006) [C1]
DOI 10.1186/1897-4287-4-2-94
Citations Scopus - 3
2006 Mossman D, Scott R, 'Epimutations, inheritance and causes of aberrant DNA methylation in cancer', Hereditary Cancer in Clinical Practice, 4 75-80 (2006) [C1]
DOI 10.1186/1897-4287-4-2-75
Citations Scopus - 1
2006 Bowden NA, Tooney PA, Scott R, 'Gene expression profiling of xeroderma pigmentosum', Hereditary Cancer in Clinical Practice, 4 103-110 (2006) [C1]
DOI 10.1186/1897-4287-4-2-103
Citations Scopus - 2
Co-authors Paul Tooney, Nikola Bowden
2006 Scott RJ, Moscovis SM, Hall ST, Gleeson M, Roberts-Thompson J, Blackwell CC, 'The influence of infection on cytokine gene polymorphisms in evolution', Before Farming, (2006) [C2]
Co-authors Maree Gleeson
2006 D¿bniak T, Scott RJ, Huzarski T, Byrski T, Rozmiarek A, D¿bniak B, et al., 'Erratum: CDKN2A common variant and multi-organ cancer risk - A population-based study (International Journal of Cancer (2006) 118 (3180-3182))', International Journal of Cancer, 119 2502 (2006)
DOI 10.1002/ijc.22188
2006 Milne E, Van Bockxmeer FM, Robertson L, Brisbane JM, Ashton LJ, Scott RJ, et al., 'Erratum: Buccal DNA collection: Comparison of buccal swabs with FTA cards (Cancer Epidemiology Biomarkers and Prevention (April 2006) 15 (816-819))', Cancer Epidemiology Biomarkers and Prevention, 15 1056 (2006)
DOI 10.1158/1055-9965.EPI-15-5-COR
2006 D¿bniak T, Cybulski C, Kurzawski G, Górski B, Huzarski T, Byrski T, et al., 'Low-risk genes and multi-organ cancer risk in the Polish population', Hereditary Cancer in Clinical Practice, 4 52-55 (2006)
Citations Scopus - 3
2006 Scott RJ, 'Hereditary Cancer in Clinical Practice: Editorial', Hereditary Cancer in Clinical Practice, 4 73 (2006)
2006 Talseth-Palmer B, Meldrum C, Suchy J, Kurzawski G, Lubinski J, Scott R, 'Genetic polymorphisms in xenobiotic clearance genes and their influence on disease expression in hereditary nonpolyposis colorectal cancer patients', Cancer Epidemiology Biomarkers & Prevention, 15 2307-2310 (2006) [C1]
DOI 10.1158/1055-9965.EPI-06-0040
Citations Scopus - 20Web of Science - 17
Co-authors Bente Talseth-Palmer
2006 Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJP, et al., 'Frequency and spectrum of cancers in the Peutz-Jeghers syndrome', Clinical Cancer Research, 12 3209-3215 (2006) [C1]
DOI 10.1158/1078-0432.CCR-06-0083
Citations Scopus - 408Web of Science - 343
2006 Weidenhofer J, Bowden NA, Scott RJ, Tooney PA, 'Dysfunction of genes regulating membrane exocytosis in schizophrenia', AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY, 40 A129-A129 (2006)
Co-authors Nikola Bowden, Judith Weidenhofer, Paul Tooney
2006 Kurzawski G, Suchy J, Lener M, Klujszo-Grabowska E, Kladny J, Safranow K, et al., 'Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study)', Clinical Genetics, 69 40-47 (2006) [C1]
DOI 10.1111/j.1399-0004.2006.00550.x
Citations Scopus - 19Web of Science - 23
2006 Chow E, Meldrum CJ, Crooks R, Macrae F, Spigelman AD, Scott R, 'An updated mutation spectrum in an Australian series of PJS patients provides further evidence for only one gene locus', Clinical Genetics, 70 409-414 (2006) [C1]
DOI 10.1111/j.1399-0004.2006.00704.x
Citations Scopus - 19Web of Science - 17
2006 Suchy J, Kurzawski G, Jakubowska K, Rac ME, Safranow K, Kladny J, et al., 'Frequency and nature of hMSH6 germline mutations in Polish patients with colorectal, endometrial and ovarian cancers (letter)', Clinical Genetics, 70 68-70 (2006) [C3]
Citations Scopus - 5Web of Science - 5
2005 Debniak T, Scott R, Huzarski T, Byrski T, Rozmiarek A, Debniak B, et al., 'CDKN2A common variants and their association with melanoma risk: A population-based study', Cancer Research, 65 835-839 (2005) [C1]
Citations Scopus - 53Web of Science - 51
2005 Hitchins M, Williams R, Cheong K, Halani N, Lin VAP, Packham D, et al., 'MLH1 Germline Epimutations as a Factor in Hereditary Nonpolyposis Colorectal Cancer', Gastroenterology, 129 1392-1399 (2005) [C1]
DOI 10.1053/j.gastro.2005.09.003
Citations Scopus - 131Web of Science - 123
2005 Weir L, Spigelman AD, Scott R, Kirk J, Zeckendorf S, Sitas F, 'The NSW & ACT Hereditary Cancer Registers', Australian Family Physician, 34 53-57 (2005) [C3]
Citations Scopus - 1
2005 Blackwell CC, Moscovis SM, Gordon AE, Al Madani OM, Hall S, Gleeson M, et al., 'Cytokine responses and sudden infant death: genetic, developmental, and environmental risk factors', Journal of Leukocyte Biology, 78 1242-1254 (2005) [C1]
DOI 10.1189/jlb.0505253
Citations Scopus - 63Web of Science - 62
Co-authors Caroline Blackwell, Sharron Hall, Maree Gleeson
2005 Kairupan CF, Meldrum CJ, Crooks R, Milward EA, Spigelman AD, Burgess B, et al., 'Mutation analysis of the MYH gene in an Australian series of colorectal polyposis patients with or without germline APC mutations', International Journal of Cancer, 116 73-77 (2005) [C1]
DOI 10.1002/ijc.20983
Citations Scopus - 30Web of Science - 25
Co-authors Liz Milward
2005 Gronwald J, Jauch A, Cybulski C, Schoell B, Bohm-Steuer B, Lener M, et al., 'Comparison of genomic abnormalities between BRCAX and sporadic breast cancers studied by comparative genomic hybridization', International Journal of Cancer, 114 230-236 (2005) [C1]
DOI 10.1002/ijc.20723
Citations Scopus - 28Web of Science - 23
2005 Scott RJ, 'Hereditary Cancer in Clinical Practice: Editorial', Hereditary Cancer in Clinical Practice, 3 85 (2005)
2005 Greenhalgh RM, Brown LC, Epstein D, Kwong GPS, Powell JT, Sculpher MJ, et al., 'Endovascular aneurysm repair versus open repair in patients with abdominal aortic aneurysm (EVAR trial 1): Randomized controlled trial', The Lancet, 365 2179-2186 (2005)

© 2005, Lancet Publishing Group. All rights reserved. Background Although endovascular aneurysm repair (EVAR) has a lower 30-day operative mortality than open repair, the long-ter... [more]

© 2005, Lancet Publishing Group. All rights reserved. Background Although endovascular aneurysm repair (EVAR) has a lower 30-day operative mortality than open repair, the long-term results of EVAR are uncertain. We instigated EVAR trial 1 to compare these two treatments in terms of mortality, durability, health-related quality of life (HRQL), and costs for patients with large abdominal aortic aneurysm (AAA). Methods We did a randomised controlled trial of 1082 patients aged 60 years or older who had aneurysms of at least 5·5 cm in diameter and who had been referred to one of 34 hospitals proficient in the EVAR technique. We assigned patients who were anatomically suitable for EVAR and fit for an open repair to EVAR (n=543) or open repair (n=539). Our primary endpoint was all-cause mortality, with secondary endpoints of aneurysm-related mortality, HRQL, postoperative complications, and hospital costs. Analyses were by intention to treat. Findings 94% (1017 of 1082) of patients complied with their allocated treatment and 209 died by the end of follow-up on Dec 31, 2004 (53 of aneurysm-related causes). 4 years after randomisation, all-cause mortality was similar in the two groups (about 28%; hazard ratio 0·90, 95% CI 0·69-1·18, p=0·46), although there was a persistent reduction in aneurysm-related deaths in the EVAR group (4% vs 7%; 0·55, 0·31-0·96, p=0·04). The proportion of patients with postoperative complications within 4 years of randomisation was 41% in the EVAR group and 9% in the open repair group (4·9, 3·5-6·8, p<0·0001). After 12 months there was negligible difference in HRQL between the two groups. The mean hospital costs per patient up to 4 years were UK£13 257 for the EVAR group versus £9946 for the open repair group (mean difference £3311, SE 690). Interpretation Compared with open repair, EVAR offers no advantage with respect to all-cause mortality and HRQL, is more expensive, and leads to a greater number of complications and reinterventions. However, it does result in a 3% better aneurysm-related survival. The continuing need for interventions mandates ongoing surveillance and longer follow-up of EVAR for detailed cost-effectiveness assessment.

DOI 10.1016/S0140-6736(05)66627-5
Citations Scopus - 1044
2005 Chekanov S, Derrick M, Magill S, Miglioranzi S, Musgrave B, Repond J, et al., 'Measurement of charm fragmentation ratios and fractions in photoproduction at HERA', European Physical Journal C, 44 351-366 (2005)

© 2005, Springer New York LLC. All rights reserved. The production of D*+, D0, D+, D+sand ¿+ccharm hadrons and their antiparticles in ep scattering at HERA was measured with the Z... [more]

© 2005, Springer New York LLC. All rights reserved. The production of D*+, D0, D+, D+sand ¿+ccharm hadrons and their antiparticles in ep scattering at HERA was measured with the ZEUS detector using an integrated luminosity of 79 pb-1. The measurement has been performed in the photoproduction regime with the exchanged-photon virtuality Q2< 1GeV2and for photon-proton centre-of-mass energies in the range 130<W < 300 GeV. The charm hadrons were reconstructed in the range of transverse momentumpT(D,¿c) > 3.8GeV and pseudorapidity |¿(D,¿c)| < 1.6. The production cross sections were used to determine the ratio of neutral and charged D-meson production rates, Ru/d, the strangeness-suppression factor, ¿s, and the fraction of charged D mesons produced in a vector state, Pdv. The measured Ru/dand ¿svalues agree with those obtained in deep inelastic scattering and in e+e-annihilations. The measured Pdvvalue is smaller than, but consistent with, the previous measurements. The fractions of c quarks hadronising as a particular charm hadron, f(c ¿ D, ¿c), were derived in the given kinematic range. The measured open-charm fragmentation fractions are consistent with previous results, although the measured f(c ¿ D*+) is smaller and f(c ¿ ¿+c) is larger than those obtained in e+e-annihilations. These results generally support the hypothesis that fragmentation proceeds independently of the hard sub-process.

DOI 10.1140/epjc/s2005-02397-3
Citations Scopus - 13
2005 Davis B, Filax G, Sumara D, Walsh S, 'Performing an archive of feeling: Experiences of normalizing structures in teaching and teacher education', Journal of Curriculum and Pedagogy, 2 173-214 (2005)

The reader¿s theatre text that follows is a written text documenting and representing as public culture experiences of ¿insidious trauma¿ that most often languish in private lives... [more]

The reader¿s theatre text that follows is a written text documenting and representing as public culture experiences of ¿insidious trauma¿ that most often languish in private lives and emotions. We are indebted to the work of Cvetkovich (2003) on ¿insidious trauma¿ and Boler (1999) on the presence/absence of emotion in producing our public ¿archive.¿ Our text is deliberately polyvocal and fragmented to draw attention to and mirror the way in which insidious trauma pulses in education. We write as a collective to produce this counter-normative text as a deliberative part of our strategy to resist the normative practices of academe and elsewhere that continuously produce and reproduce social inequities. © 2005 Taylor and Francis Group, LLC.

DOI 10.1080/15505170.2005.10411565
Citations Scopus - 6
2005 Simpson JL, Scott R, Boyle MJ, Gibson PG, 'Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma', American Journal of Respiratory and Critical Care Medicine, 172 559-565 (2005) [C1]
DOI 10.1164/rccm.200503-369OC
Citations Scopus - 117Web of Science - 106
Co-authors Peter Gibson, Jodie Simpson
2005 Weber W, Scott R, 'Case report: Familial gastric cancer and chordoma in the same family', Hereditary Cancer in Clinical Practice, 3 81-84 (2005) [C2]
Citations Scopus - 1Web of Science - 2
2005 McPhillips M, Meldrum CJ, Scott R, Creegan R, Edkins E, 'Deletion mutations in an Australian series of HNPCC patients', Hereditary Cancer in Clinical Practice, 3 43-47 (2005) [C2]
Citations Scopus - 1Web of Science - 1
2005 Ashton KA, Meldrum CJ, McPhillips ML, Kairupan CF, Scott R, 'Frequency of the common MYH mutations (G382D and Y165C) in MMR mutation positive and negative HNPCC patients', Hereditary Cancer in Clinical Practice, 3 65-70 (2005) [C1]
DOI 10.1186/1897-4287-3-2-65
Citations Scopus - 11Web of Science - 10
2005 Scott R, Meldrum C, 'Missense mutations in cancer predisposing genes: can we make sense of them?', Hereditary Cancer in Clinical Practice, 3 123-127 (2005) [C1]
DOI 10.1186/1897-4287-3-3-123
2004 Marazita ML, Murray JC, Lidral AC, Arcos-Burgos M, Cooper ME, Goldstein T, et al., 'Meta-analysis of 13 genome scans reveals multiple cleft lip/palate genes with novel loci on 9q21 and 2q32-35', American Journal of Human Genetics, 75 161-173 (2004) [C1]
DOI 10.1086/422475
Citations Scopus - 145Web of Science - 138
2004 Kurzawski G, Suchy J, Lubinski J, Scott RJ, 'NOD2 and colorectal cancer: Guilt by non-association - Response', CANCER RESEARCH, 64 5525-5526 (2004)
2004 Kurzawski G, Suchy J, Kladny J, Grabowska E, Mierzejewski M, Jakubowska A, et al., 'The NOD2 3020insC Mutation and the Risk of Colorectal Cancer', Cancer Research, 64 1604-1606 (2004) [C1]
DOI 10.1158/0008-5472.CAN-03-3791
Citations Scopus - 79Web of Science - 74
2004 Kurzawski G, Suchy J, Lubinski J, Scott R, 'NOD2 and colorectal cancer: guilt by non-association', Cancer Research, 64 5525-5526 (2004) [C1]
2004 Scott R, Meldrum CJ, 'Response to De Vos et al', Clinical Genetics, 66 568 (2004) [C3]
2004 Thompson E, Meldrum CJ, Crooks R, McPhillips M, Thomas LS, Spigelman AD, Scott R, 'Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations', Clinical Genetics, 65 215-225 (2004) [C1]
DOI 10.1111/j.1399-0004.2004.00214.x
Citations Scopus - 39Web of Science - 35
2004 Lim W, Olschwang S, Keller J, Westerman A, Menko F, Boardman L, et al., 'Relative frequency and morphology of cancers in STK11 mutation carriers', Gastroenterology, 126 1788-1794 (2004) [C1]
DOI 10.1053/j.gastro.2004.03.014
Citations Scopus - 155Web of Science - 126
2004 Debniak T, Gorski B, Scott R, Cybulski C, Medrek K, Zlowocka E, et al., 'Germline Mutation and Large Deletion Analysis of the CDKN2A and ARF Genes in Families with Multiple Melanoma or an Aggregation of Maligant Melanoma and Breast Cancer', International Journal of Cancer, 110 558-562 (2004) [C1]
DOI 10.1002/ijc.20163
Citations Scopus - 24Web of Science - 21
2004 Smith CJ, Crock PA, King BR, Meldrum CJ, Scott R, 'Phenotype-Genotype Correlations in a Series of Wolfram Syndrome Families', Diabetes Care, 27 2003-2009 (2004) [C1]
DOI 10.2337/diacare.27.8.2003
Citations Scopus - 52Web of Science - 47
Co-authors Bruce King
2004 Rodgers A, Ezzati M, Vander Hoorn S, Lopez AD, Lin RB, Murray CJL, et al., 'Distribution of major health risks: Findings from the global burden of disease study', PLoS Medicine, 1 044-055 (2004)

Background: Most analyses of risks to health focus on the total burden of their aggregate effects. The distribution of risk-factor-attributable disease burden, for example by age ... [more]

Background: Most analyses of risks to health focus on the total burden of their aggregate effects. The distribution of risk-factor-attributable disease burden, for example by age or exposure level, can inform the selection and targeting of specific interventions and programs, and increase cost-effectiveness. Methods and Findings: For 26 selected risk factors, expert working groups conducted comprehensive reviews of data on risk-factor exposure and hazard for 14 epidemiological subregions of the world, by age and sex. Age-sex-subregion-population attributable fractions were estimated and applied to the mortality and burden of disease estimates from the World Health Organization Global Burden of Disease database. Where possible, exposure levels were assessed as continuous measures, or as multiple categories. The proportion of risk-factor-attributable burden in different population subgroups, defined by age, sex, and exposure level, was estimated. For major cardiovascular risk factors (blood pressure, cholesterol, tobacco use, fruit and vegetable intake, body mass index, and physical inactivity) 43%-61% of attributable disease burden occurred between the ages of 15 and 59 y, and 87% of alcohol-attributable burden occurred in this age group. Most of the disease burden for continuous risks occurred in those with only moderately raised levels, not among those with levels above commonly used cut-points, such as those with hypertension or obesity. Of all disease burden attributable to being underweight during childhood, 55% occurred among children 1-3 standard deviations below the reference population median, and the remainder occurred among severely malnourished children, who were three or more standard deviations below median. Conclusions: Many major global risks are widely spread in a population, rather than restricted to a minority. Population-based strategies that seek to shift the whole distribution of risk factors often have the potential to produce substantial reductions in disease burden. © 2004 Rodgers et al.

DOI 10.1371/journal.pmed.0010027
Citations Scopus - 152
2004 Scott R, 'DNA mismatch repair genes and hereditary non-polyposis colorectal cancer', J Gastro Hepatol, 19 465-466 (2004) [C1]
DOI 10.1111/j.1440-1746.2004.03425.x
2004 Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott R, Roberts-Thomson JM, et al., 'Interleukin-10 and sudden infant death syndrome', FEMS Immunology and Medical Microbiology, 42 130-138 (2004) [C1]
DOI 10.1016/j.femsim.2004.06.020
Citations Scopus - 38Web of Science - 36
Co-authors Sharron Hall, Caroline Blackwell, Maree Gleeson
2004 Moscovis SM, Gordon AE, Hall ST, Gleeson M, Scott R, Roberts-Thomson JM, et al., 'Interleukin 1-b responses to bacterial toxins and sudden infant death syndrome', FEMS Immunology and Medical Microbiology, 42 139-145 (2004) [C1]
DOI 10.1016/j.femsim.2004.06.005
Citations Scopus - 29Web of Science - 29
Co-authors Caroline Blackwell, Sharron Hall, Maree Gleeson
2004 Blackwell CC, Moscovis SM, Gordon AE, Al Madani OM, Hall ST, Gleeson M, et al., 'Ethnicity, infection and sudden infant death syndrome', FEMS Immunology and Medical Microbiology, 42 53-65 (2004) [C1]
DOI 10.1016/j.femsim.2004.06.007
Citations Scopus - 34Web of Science - 27
Co-authors Maree Gleeson, Caroline Blackwell, Sharron Hall
2004 Spigelman AD, Burgess BT, Groombridge C, Scott R, 'Genetic testing: a round table conversation', Internal Medicine Journal, 34 587-588 (2004) [C1]
DOI 10.1111/j.1445-5994.2004.00679.x
2004 Scott R, Ashton KA, 'Familial breast and bowel cancer: Does it exist?', Hereditary Cancer in Clinical Practice, 2 25-59 (2004) [C1]
DOI 10.1186/1897-4287-2-1-25
2004 Scott R, 'DNA Double Strand Break Repair and its Association with Inherited Predispositions to Breast Cancer', Hereditary Cancer in Clinical Practice, 2 37-43 (2004) [C1]
DOI 10.1186/1897-4287-2-1-37
2004 Gawdis-Wojnarska B, Brzoska M, Flicinski J, Marlicz K, Starzynska T, Scott R, Lubinski J, 'Nuclear Pedigree Criteria for the Identification of Individuals Suspected to be at Risk of an Inherited Predisposition to Gastric Cancer', Hereditary Cancer in Clinical Practice, 2 65-68 (2004) [C1]
DOI 10.1186/1897-4287-2-2-65
2004 Scott R, Crooks R, Rose L, Attia JR, Thakkinstian A, Thomas L, et al., 'Germline Missense Changes in the APC Gene and Their Relationship to Disease', Hereditary Cancer in Clinical Practice, 2 81-91 (2004) [C1]
DOI 10.1186/1897-4287-2-2-81
Co-authors John Attia
2004 Liu X, Sinn H-P, Ulmer HU, Scott R, Hamann U, 'Intronic TP53 Germline Sequence Variants Modify the Risk in German Breast/Ovarian Cancer Families', Hereditary Cancer in Clinical Practice, 2 139-145 (2004) [C1]
DOI 10.1186/1897-4287-2-3-139
2003 Meldrum CJ, McPhillips M, Crooks R, Thomas L, Edkins T, Creegan R, et al., 'A comparison between denaturing gradient gel electrophoresis and denaturing high performance liquid chromatography in detecting mutations in genes associated with hereditary non-polyposis colorectal cancer (HNPCC) and the identification of 9 new mutations previously unidentified by DGGE', Hereditary Cancer in Clinical Practice, 1 39-48 (2003) [C1]
DOI 10.1186/1897-4287-1-1-39
2003 Scott RJ, Vajdic CM, Armstrong BK, Ainsworth CJ, Meldrum CJ, Aitken JF, Kricker A, 'Erratum: BRCA2 mutations in a population-based series of patients with ocular melanoma (International Journal of Cancer (2003) 102 (188-191))', International Journal of Cancer, 105 882 (2003)
2003 Górski B, D¿bniak T, Masojc B, Mierzejewski M, M¿drek K, Cybulski C, et al., 'Erratum: Germline 657del5 mutation in the NBSI gene in breast cancer patients (International Journal Cancer (2003) 106 (379-381))', International Journal of Cancer, 106 984 (2003)
2003 Gorski B, Debniak T, Mosojc B, Mierzejewski M, Medrek K, Cybulski C, et al., 'Germline 657del5 mutation in the NBS1 gene in breast cancer patients', International Journal of Cancer, 106 379-381 (2003) [C1]
DOI 10.1002/ijc.11231
Citations Scopus - 67Web of Science - 67
2003 Lubinski W, Kurzawski G, Suchy J, Szych Z, Penkala K, Palacz O, et al., 'Electro-Oculographic and Electroretinographic Studies in HNPCC Gene Mutation Carriers', Ophthalmic Research, 35 281-294 (2003) [C1]
DOI 10.1159/000072149
Citations Scopus - 1
2003 Jakubowska A, Scott R, Menkiszak J, Gronwald J, Byrski T, Huzarski T, et al., 'A high frequency of BRCA2 gene mutations in Polish families with ovarian and stomach cancer', European Journal of Human Genetics, 11 955-958 (2003) [C1]
DOI 10.1038/sj.ejhg.5201064
Citations Scopus - 28Web of Science - 20
2003 Heister JA, Schael S, Barate R, Brunelière R, De Bonis I, Decamp D, et al., 'Search for the standard model higgs boson at LEP', Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics, 565 61-75 (2003)

© 2016, Elsevier. All rights reserved. The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have collected a total of 2461 pb-1of e+e-collision data at centre-of-mass energies... [more]

© 2016, Elsevier. All rights reserved. The four LEP collaborations, ALEPH, DELPHI, L3 and OPAL, have collected a total of 2461 pb-1of e+e-collision data at centre-of-mass energies between189 and 209 GeV. The data are used to search for the Standard Model Higgs boson. The search results of the four collaborations are combined and examined in a likelihood test for their consistency with two hypotheses: the background hypothesis and the signal plus background hypothesis. The corresponding confidences have been computed as functions of the hypothetical Higgs boson mass. A lower bound of114.4 GeV/c2is established, at the 95% confidence level, on the mass of the Standard Model Higgs boson. The LEP data are also used to set upper bounds on the HZZ coupling for various assumptions concerning the decay of the Higgs boson.

DOI 10.1016/S0370-2693(03)00614-2
Citations Scopus - 1206
2002 Scott R, Crooks R, Meldrum C, Thomas L, Smith C, Mowat D, et al., 'Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients', Clinical Genetics, 62 282-287 (2002) [C1]
Citations Scopus - 42Web of Science - 37
2002 Scott R, Vajdic C, Armstrong B, Ainsworth C, Meldrum C, Aitken J, Kricker A, 'BRCA2 Mutations in a Population-Based Series of Patients with Ocular Melanoma', International Journal of Cancer, 102 188-191 (2002) [C1]
Citations Scopus - 30
2002 Niu J, Dorahy DJ, Gu X, Scott R, Draganic B, Ahmed N, Agrez MV, 'Integrin expression in colon cancer cells is regulated by the cytoplasmic domain of the 6 integrin subunit', International Journal of Cancer, 99(4) 529-537 (2002) [C1]
Citations Scopus - 33Web of Science - 30
2002 Hamann U, Liu X, Lange S, Ulmer H, Benner A, Scott R, 'Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany', Journal of Medical Genetics, 39:e12 1 of 6 (2002) [C1]
Citations Scopus - 8
2002 Kurzawski G, Safranow K, Suchy J, Chlubek D, Scott R, Lubinski J, 'Mutation analysis of MLH1 and MSH2 genes performed by denaturing high-performance liquid chromatography', Journal of Biochemical and Biophysical Methods, 51 89-100 (2002) [C1]
Citations Scopus - 42Web of Science - 42
2002 Ward R, Meldrum C, Williams R, Mokany E, Scott R, Turner J, et al., 'Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer', Journal of Cancer Research and Clinical Oncology, 128(8) 403-411 (2002) [C1]
DOI 10.1007/s00432-002-0361-2
Citations Scopus - 27Web of Science - 21
2002 Ahmed N, Niu J, Dorahy DJ, Gu X, Andrews S, Meldrum C, et al., 'Direct integrin v 6-ERK binding: implications for tumour growth', Oncogene, 21 1370-1380 (2002) [C1]
DOI 10.1038/sj.onc.1205286
Citations Scopus - 73Web of Science - 71
2002 Mural RJ, Adams MD, Myers EW, Smith HO, Gabor Miklos GL, Wides R, et al., 'A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome', Science, 296 1661-1671 (2002)

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a... [more]

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human