Browsing by Author "McGill University"
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Publication Metadata only The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis(2020-01-01) Chen He; Brooke Levis; Kira E. Riehm; Nazanin Saadat; Alexander W. Levis; Marleine Azar; Danielle B. Rice; Ankur Krishnan; Yin Wu; Ying Sun; Mahrukh Imran; Jill Boruff; Pim Cuijpers; Simon Gilbody; John P.A. Ioannidis; Lorie A. Kloda; Dean McMillan; Scott B. Patten; Ian Shrier; Roy C. Ziegelstein; Dickens H. Akena; Bruce Arroll; Liat Ayalon; Hamid R. Baradaran; Murray Baron; Anna Beraldi; Charles H. Bombardier; Peter Butterworth; Gregory Carter; Marcos Hortes Nisihara Chagas; Juliana C.N. Chan; Rushina Cholera; Kerrie Clover; Yeates Conwell; Janneke M. De Man-Van Ginkel; Jesse R. Fann; Felix H. Fischer; Daniel Fung; Bizu Gelaye; Felicity Goodyear-Smith; Catherine G. Greeno; Brian J. Hall; Patricia A. Harrison; Martin Härter; Ulrich Hegerl; Leanne Hides; Stevan E. Hobfoll; Marie Hudson; Thomas N. Hyphantis; Masatoshi Inagaki; Khalida Ismail; Nathalie Jetté; Mohammad E. Khamseh; Kim M. Kiely; Yunxin Kwan; Femke Lamers; Shen Ing Liu; Manote Lotrakul; Sonia R. Loureiro; Bernd Löwe; Laura Marsh; Anthony McGuire; Sherina Mohd-Sidik; Tiago N. Munhoz; Kumiko Muramatsu; Flávia L. Osório; Vikram Patel; Brian W. Pence; Philippe Persoons; Angelo Picardi; Katrin Reuter; Alasdair G. Rooney; Iná S. Da Silva Dos Santos; Juwita Shaaban; Abbey Sidebottom; Adam Simning; Lesley Stafford; Sharon Sung; Pei Lin Lynnette Tan; Alyna Turner; Henk C.P.M. Van Weert; Jennifer White; Mary A. Whooley; Kirsty Winkley; Mitsuhiko Yamada; Brett D. Thombs; Andrea Benedetti; Melbourne Institute; Melbourne School of Psychological Sciences; San Francisco VA Health Care System; Mackay Medical College; Calvary Mater Newcastle; Duke-NUS Medical School Singapore; City of Minneapolis; Hunter Medical Research Institute, Australia; Niigata Seiryo University; Bar-Ilan University School of Social Work; Makerere University; Concordia University; University Medical Center Utrecht; Royal Women's Hospital, Carlton; Harvard T.H. Chan School of Public Health; KU Leuven– University Hospital Leuven; University of Queensland; Mackay Memorial Hospital Taiwan; University of New South Wales (UNSW) Australia; University of Edinburgh; Yong Loo Lin School of Medicine; Shimane University; Charité – Universitätsmedizin Berlin; Universiti Putra Malaysia; The University of North Carolina at Chapel Hill; KU Leuven; Iran University of Medical Sciences; Prince of Wales Hospital Hong Kong; University of Rochester Medical Center; University of California, San Francisco; Neuroscience Research Australia; Universidade de Macau; Lady Davis Institute for Medical Research; UNC School of Medicine; Technical University of Munich; Monash University; Deakin University; National Center of Neurology and Psychiatry Kodaira; University of Newcastle, Faculty of Health and Medicine; University of York; Saint Joseph's College of Maine; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; University of Aberdeen; University of Pittsburgh; University of Washington, Seattle; Universidade Federal de Pelotas; Icahn School of Medicine at Mount Sinai; Stanford University; King's College London; Istituto Superiore Di Sanita; Singapore Institute of Mental Health; Australian National University; Vrije Universiteit Amsterdam; Goethe-Universität Frankfurt am Main; Centre universitaire de santé McGill; Johns Hopkins Bloomberg School of Public Health; University of Auckland; Nanyang Technological University; Universitätsklinikum Hamburg-Eppendorf und Medizinische Fakultät; Panepistimion Ioanninon; Chinese University of Hong Kong; Harvard Medical School; School of Medical Sciences - Universiti Sains Malaysia; McGill University; Tan Tock Seng Hospital; Baylor College of Medicine; University of Calgary; Amsterdam UMC - University of Amsterdam; Johns Hopkins School of Medicine; Private Practice for Psychotherapy and Psycho-oncology; STAR-Stress; National Institute of Science and Technology; Allina Health© 2019 S. Karger AG, Basel. All rights reserved. Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.Publication Metadata only Acquisition of arylsulfatase A onto the mouse sperm surface during epididymal transit(2003-10-01) Wattana Weerachatyanukul; Hongbin Xu; Araya Anupriwan; Euridice Carmona; Michael Wade; Louis Hermo; Solange Maria Da Silva; Peter Rippstein; Prasert Sobhon; Prapee Sretarugsa; Nongnuj Tanphaichitr; Ottawa Hospital Research Institute; University of Ottawa, Canada; Health Canada; McGill University; Mahidol University; The Ottawa HospitalArylsulfatase A (AS-A) is localized to the sperm surface and participates in sperm-zona pellucida binding. We investigated how AS-A, usually known as an acrosomal enzyme, trafficked to the sperm surface. Immunocytochemistry of the mouse testis confirmed the existence of AS-A in the acrosomal region of round and elongating spermatids. However, immunofluorescence and flow cytometry indicated the absence of AS-A on the surface of live testicular sperm. In contrast, positive AS-A staining was observed in the heads of live caudal epididymal and vas deferens sperm. The results suggested that acquisition of AS-A on the sperm surface occurred during epididymal transit. Immunocytochemistry of the epididymis revealed AS-A in narrow and apical cells in the initial segment and in clear cells in all epididymal regions. However, these epithelial cells are in the minority and are not involved in secretory activity. In the caudal epididymis and vas deferens, AS-A was also localized to principal cells, the major epithelial cells. Because principal cells have secretory activity, they may secrete AS-A into the epididymal fluid. This hypothesis was supported by our results revealing the presence of AS-A in the epididymal and vas deferens fluid (determined by immunoblotting and ELISA) and an AS-A transcript in the epididymis (by reverse transcription polymerase chain reaction). Alexa-430 AS-A bound to epididymal sperm with high affinity (K d = 46 nM). This binding was inhibited by treatment of sperm with an antibody against sperm surface sulfogalactosylglycerolipid. This finding suggests that AS-A in the epididymal fluid may deposit onto sperm via its affinity to sulfogalactosylglycerolipid.Publication Metadata only Antimicrobial host defence peptide, LL-37, as a potential vaginal contraceptive(2014-01-01) Nopparat Srakaew; Charlene D. Young; Arpornrad Sae-Wu; Hongbin Xu; Krista L. Quesnel; Riccardo Di Brisco; Kessiri Kongmanas; Duriya Fongmoon; Greanggrai Hommalai; Wattana Weerachatyanukul; Susan H. Hall; Yong Lian Zhang; Luigi Panza; Laura Franchini; Federica Compostella; Terry W. Pearson; Robert E. Hancock; Richard J. Oko; Louis S. Hermo; Nongnuj Tanphaichitr; Ottawa Hospital Research Institute; University of Ottawa, Canada; Mahidol University; The University of North Carolina at Chapel Hill; Chinese Academy of Sciences; Universita degli Studi del Piemonte Orientale Amedeo Avogadro, Novara; Universita degli Studi di Milano; University of Victoria; The University of British Columbia; Queen's University, Kingston; McGill UniversitySTUDY QUESTIONDoes antimicrobial peptide, LL-37, inhibit sperm fertilizing ability?SUMMARY ANSWEROur results indicate that LL-37 inhibits mouse and human sperm fertilizing ability.WHAT IS KNOWN ALREADYLL-37, a cationic antimicrobial peptide, exerts its microbicidal effects through the disruption of microbial cytoplasmic membranes following its interaction with microbial surface anionic phospholipids. ALL-38 (an LL-37 close analogue: LL-37 + Ala at the N-terminus) is produced in the vagina 2-6 h post-intercourse from its precursor hCAP-18, a seminal plasma component. At this time, motile sperm have already swum into the uterine cavity, thus unexposed to ALL-38. Since sperm contain a substantial amount of acidic sulfogalactosylglycerolipid (SGG) on their surface, treatment of sperm with LL-37 may cause their membrane disruption in an analogous manner to that occurring on microbial membranes.STUDY DESIGN, SIZE AND DURATIONMouse/human sperm treated (2-30 min) with LL-37 in a physiological concentration range (up to 10.8 μM) were assessed for SGG-dependent LL-37 binding, and parameters relevant to fertilizing ability, namely motility and intactness of the sperm acrosome and plasma membrane. Ability of mouse sperm to fertilize eggs in vitro was also evaluated. Each study was performed with greater than or equal to three different sperm samples. The efficacy of LL-37 to inhibit sperm fertilizing ability in vivo was determined in female mice (n = 26 each for LL-37 treatment and no treatment), using sperm retrieved from 26 males.PARTICIPANTS/MATERIALS, SETTING, METHODSHuman sperm samples were donated by fertile men. LL-37 was chemically synthesized and was biotinylated for sperm binding studies. Sperm motility was assessed by videomicroscopy and the acrosomal status by Coomassie blue staining of acrosome-intact mouse sperm or the exposure of CD46, an inner acrosomal membrane protein, of acrosome reacted human sperm. Sperm membrane permeabilization/disruption was assessed by the loss of hypo-osmotic swelling response, an incorporation of Sytox Green (a membrane impermeable fluorescent DNA dye), and electron microscopy. Mouse IVF was scored by the presence of two pronuclei in eggs 6 h post-insemination. Ability of mouse sperm to fertilize eggs in vivo was determined by the pregnancy outcome of female mice injected transcervically with sperm with or without LL-37.MAIN RESULTS AND THE ROLE OF CHANCEBiotinylated LL-37 bound to both mouse and human sperm and the binding was partially dependent on sperm surface SGG. Mouse and human sperm became immotile and underwent a premature acrosome reaction upon treatment with LL-37 at 3.6 and 10.8 μM, respectively. The initial action of LL-37 on both mouse and human sperm appeared to be through permeabilization/ disruption of sperm surface membranes evidenced by the loss of hypo-osmotic swelling response, Sytox Green staining and electron microscopy revealing ultrastructural damage. Mouse sperm treated with 3.6 μM LL-37 lost the ability to fertilize eggs both in vitro and in vivo. All 26 female mice inseminated with sperm and LL-37 did not become pregnant. No apparent damage to the reproductive tract was observed as revealed by histological characterization in LL-37-inseminated mice and these females resumed fecundity following mating with fertile males.LIMITATIONS, REASONS FOR CAUTIONDirect demonstration that LL-37 treated human sperm fail to fertilize eggs was limited by legal restrictions on obtaining human eggs for such use.WIDER IMPLICATIONS OF THE FINDINGSOur results reveal selective inhibitory effects of LL-37 on sperm fertilizing ability in mice without apparent impairment to the female reproductive tract. LL-37 is therefore a promising candidate to be developed into a vaginal contraceptive with microbicidal activity.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation (OPP1024509), Canadian Institutes of Health Research (MOP119438 & CCI82413) and International Collaboration and Exchanges NSFC of China (No.30611120525). There are no competing interests to declare. © The Author 2014.Publication Metadata only Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead(2015-06-01) William H. Goodson; Leroy Lowe; David O. Carpenter; Michael Gilbertson; Abdul Manaf Ali; Adela Lopez de Cerain Salsamendi; Ahmed Lasfar; Amancio Carnero; Amaya Azqueta; Amedeo Amedei; Amelia K. Charles; Andrew R. Collins; Andrew Ward; Anna C. Salzberg; Annamaria Colacci; Ann Karin Olsen; Arthur Berg; Barry J. Barclay; Binhua P. Zhou; Carmen Blanco-Aparicio; Carolyn J. Baglole; Chenfang Dong; Chiara Mondello; Chia Wen Hsu; Christian C. Naus; Clement Yedjou; Colleen S. Curran; Dale W. Laird; Daniel C. Koch; Danielle J. Carlin; Dean W. Felsher; Debasish Roy; Dustin G. Brown; Edward Ratovitski; Elizabeth P. Ryan; Emanuela Corsini; Emilio Rojas; Eun Yi Moon; Ezio Laconi; Fabio Marongiu; Fahd Al-Mulla; Ferdinando Chiaradonna; Firouz Darroudi; Francis L. Martin; Frederik J. Van Schooten; Gary S. Goldberg; Gerard Wagemaker; Gladys Nangami; Gloria M. Calaf; Graeme Williams; Gregory T. Wolf; Gudrun Koppen; Gunnar Brunborg; H. Kim Lyerly; Harini Krishnan; Hasiah Ab Hamid; Hemad Yasaei; Hideko Sone; Hiroshi Kondoh; Hosni K. Salem; Hsue Yin Hsu; Hyun Ho Park; Igor Koturbash; Isabelle R. Miousse; A. Ivana Scovassi; James E. Klaunig; Jan Vondráček; Jayadev Raju; Jesse Roman; John Pierce Wise; Jonathan R. Whitfield; Jordan Woodrick; Joseph A. Christopher; Josiah Ochieng; Juan Fernando Martinez-Leal; Judith Weisz; Julia Kravchenko; Jun Sun; Kalan R. Prudhomme; Kannan Badri Narayanan; Karine A. Cohen-Solal; Kim Moorwood; Laetitia Gonzalez; Laura Soucek; Le Jian; Leandro S. D'Abronzo; Liang Tzung Lin; Lin Li; Linda Gulliver; Lisa J. McCawley; Lorenzo Memeo; Louis Vermeulen; Luc Leyns; Luoping Zhang; Getting to Know Cancer; Lancaster University; University at Albany State University of New York; Getting to Know Cancer; Universiti Sultan Zainal Abidin; Universidad de Navarra; Rutgers Biomedical and Health Sciences; Hospital Universitario Virgen del Rocio; Universita degli Studi di Firenze; University of Reading; Universitetet i Oslo; University of Bath; Penn State College of Medicine; Environmental Protection and Health Prevention Agency; Norwegian Institute of Public Health; National Research Council Canada; University of Kentucky; Centro Nacional de Investigaciones Oncologicas; McGill University; Consiglio Nazionale delle Ricerche; National Center for Advancing Translational Sciences; The University of British Columbia; Jackson State University; University of Wisconsin Madison; Western University; Stanford University School of Medicine; National Institute of Environmental Health Sciences; City University of New York; Colorado State University; The Johns Hopkins School of Medicine; Universita degli Studi di Milano; Universidad Nacional Autonoma de Mexico; Sejong University; Universita degli Studi di Cagliari; University of Kuwait; University of Milano - Bicocca; College of North Atlantic; Maastricht University; Rowan University; Hacettepe Universitesi; Meharry Medical College; Columbia University Medical Center; Universidad de Tarapaca de Arica; University of Michigan Medical School; Flemish Institute for Technological Research; Duke University Medical Center; Universiti Putra Malaysia; Brunel University London; National Institute for Environmental Studies of Japan; Kyoto University Hospital; Cairo University; Tzu Chi University; Yeungnam University; University of Arkansas for Medical Sciences; Indiana University; Academy of Sciences of the Czech Republic; Toxicology Research Division; University of Louisville; Louisville Veterans Administration Medical Center; University of Southern Maine; Vall d`Hebron Institut de Oncologia; Lombardi Comprehensive Cancer Center; University of Cambridge; Department of Cell Biology; Rush University; Oregon State University; The Cancer Institute of New Jersey; Vrije Universiteit Brussel; Institucio Catalana de Recerca I Estudis Avancats; Curtin University; Department of Health Western Australia; University of California, Davis; Taipei Medical University; Chinese University of Hong Kong; University of Otago; Vanderbilt University; Mediterranean Institute of Oncology; Academic Medical Centre, University of Amsterdam; University of California, Berkeley; National Cancer Institute; Universita degli Studi di Napoli Federico II; Centre de recherche en cancérologie de Lyon; United States Army; Istituto Italiano di Tecnologia; California Pacific Medical Center© The Author 2015. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.Publication Metadata only Averting biodiversity collapse in tropical forest protected areas(2012-09-13) William F. Laurance; D. Carolina Useche; Julio Rendeiro; Margareta Kalka; Corey J.A. Bradshaw; Sean P. Sloan; Susan G. Laurance; Mason Campbell; Kate Abernethy; Patricia Alvarez; Victor Arroyo-Rodriguez; Peter Ashton; Julieta Benítez-Malvido; Allard Blom; Kadiri S. Bobo; Charles H. Cannon; Min Cao; Richard Carroll; Colin Chapman; Rosamond Coates; Marina Cords; Finn Danielsen; Bart De Dijn; Eric Dinerstein; Maureen A. Donnelly; David Edwards; Felicity Edwards; Nina Farwig; Peter Fashing; Pierre Michel Forget; Mercedes Foster; George Gale; David Harris; Rhett Harrison; John Hart; Sarah Karpanty; W. John Kress; Jagdish Krishnaswamy; Willis Logsdon; Jon Lovett; William Magnusson; Fiona Maisels; Andrew R. Marshall; Deedra McClearn; Divya Mudappa; Martin R. Nielsen; Richard Pearson; Nigel Pitman; Jan Van Der Ploeg; Andrew Plumptre; John Poulsen; Mauricio Quesada; Hugo Rainey; Douglas Robinson; Christiane Roetgers; Francesco Rovero; Frederick Scatena; Christian Schulze; Douglas Sheil; Thomas Struhsaker; John Terborgh; Duncan Thomas; Robert Timm; J. Nicolas Urbina-Cardona; Karthikeyan Vasudevan; S. Joseph Wright; Juan Carlos Arias-G.; Luzmila Arroyo; Mark Ashton; Philippe Auzel; Dennis Babaasa; Fred Babweteera; Patrick Baker; Olaf Banki; Margot Bass; Inogwabini Bila-Isia; Stephen Blake; Warren Brockelman; Nicholas Brokaw; Carsten A. Brühl; Sarayudh Bunyavejchewin; Jung Tai Chao; Jerome Chave; Ravi Chellam; Connie J. Clark; José Clavijo; Robert Congdon; Richard Corlett; H. S. Dattaraja; Chittaranjan Dave; Glyn Davies; Beatriz De Mello Beisiegel; Rosa De Nazaré Paes Da Silva; Anthony Di Fiore; Arvin Diesmos; Rodolfo Dirzo; Diane Doran-Sheehy; Mitchell Eaton; James Cook University, Australia; Smithsonian Tropical Research Institute; University of Adelaide; University of Stirling; Duke University; Universidad Nacional Autonoma de Mexico; Royal Botanic Gardens, Kew; World Wildlife Fund; University of Dschang; Xishuangbanna Tropical Botanical Garden Chinese Academy of Sciences; McGill University; Columbia University in the City of New York; Nordic Foundation for Development and Ecology; Bart de Dijn Environmental Consultancy; Florida International University; Universitat Marburg; California State University Fullerton; Muséum national d’histoire naturelle (MNHN); United States Geological Survey; King Mongkuts University of Technology Thonburi; Royal Botanic Garden Edinburgh; Tshuapa-Lomami-Lualaba Project; Virginia Polytechnic Institute and State University; Smithsonian National Museum of Natural History; Ashoka Trust for Research in EcologyandtheEnvironment (ATREE); University of Twente; Instituto Nacional de Pesquisas Da Amazonia; Wildlife Conservation Society; University of York; La Selva Biological Station; Nature Conservation Foundation; Kobenhavns Universitet; Leiden University; Wildlife Conservation Society Uganda; Woods Hole Oceanographic Institution; Oregon State University; Museo delle Scienze; University of Pennsylvania; Universitat Wien; Bwindi Impenetrable National Park; University of Kansas Lawrence; Pontificia Universidad Javeriana; Wildlife Institute of India; Unidad de Parques Nacionales Naturales de Colombia; Museo Historia Nat. Noel Kempff M.; Yale University; Institute of Tropical Forest Conservation; Budongo Conservation Field Station; Monash University; Utrecht University; Finding Species; University of Kent; Mahidol University; University of Puerto Rico; Universitat Koblenz-Landau; National Park, Wildlife and Plant Conservation Department, Thailand; Taiwan Forestry Research Institute; Universite Paul Sabatier Toulouse III; Wildlife Conservation Society; Universidad Central de Venezuela; National University of Singapore; Indian Institute of Science, Bangalore; World Wide Fund for Nature (WWF); World Wide Fund for Nature (WWF); Instituto Chico Mendes de Conservação de Biodiversidade; O Conselho Regional de Engenhara; University of Texas at Austin; National Museum of the Philippines; Stanford University; Stony Brook University; University of Colorado at Boulder; Wildlife Conservation Society; University of Calgary; Max Planck Institute for Evolutionary Anthropology; Montclair State University; University of California, San Diego; Field Museum of Natural History; Universitat de Barcelona; Kenya Institute for Public Policy Research and Analysis; Missouri Botanical Garden; University of Leeds; Wild Chimpanzee Foundation; Dinghushan Biosphere Reserve; Tunghai University; Clemson University; Osaka City University; Instituto Florestal; Botanical Research Institute of Texas; South China Botanical Garden; Anglia Ruskin University; Fundación para la Conservación del Bosque Chiquitano; Universitat Ulm; Mbarara University of Science and Technology; Conservation International; Society of Subtropical Ecology; Royal HaskoningDHV; Boston University; Centre Suisse de Recherches Scientifiques Abidjan; Universidade Estadual de Londrina; University of Alabama; Parque Estadual Horto Florestal; Royal Society for the Protection of Birds; National Taiwan University; Julius-Maximilians-Universitat Wurzburg; Organization for Tropical Studies; USDA International Institute of Tropical Forestry; Makerere University; Green Capacity, Inc.; Museu Paraense Emilio Goeldi; Ohio State University; Wildlife Conservation Society; Universidade Federal do Para; Lukuru Wildlife Research Foundation; Aarhus Universitet; Nagoya University; University of Waterloo; Kent State University; Institute of Entomology, Biology Centre of the Academy of Sciences of the Czech Republic; University of Washington, Seattle; PNG Institute of Biological Research; Anton de Kom Universiteit van Suriname; Pondicherry University; Fundação Florestal; Research Centre for Biology; The University of Georgia; Strix Wildlife Consultancy; Southern Illinois University at Carbondale; Zoological Society of Milwaukee; Danum Valley Field Centre; University of Oxford; San Diego State University; Museum fur Naturkunde; City University of New York; National Institutes for the Humanities, Research Institute for Humanity and Nature; Hochschule Karlsruhe - Technik und Wirtschaft; National Zoological Park; Gola Forest Programme; Wake Forest University; University of California, Los Angeles; University of Southern California; Institute of Applied Ethnobotany; Texas A and M University; Universitat Gottingen; Wildlife Conservation Society; Centre for Cellular and Molecular Biology india; Paluma Environmental Education Centre; Empresa Brasileira de Pesquisa Agropecuaria - Embrapa; Treasure Valley Math and Science Center; Rice University; Resources Himalaya Foundation; Gunung Palung National ParkThe rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the worlds major tropical regions. Our analysis reveals great variation in reserve health: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines. © 2012 Macmillan Publishers Limited. All rights reserved.Publication Metadata only Communication strategies in tissue culture and seed research in Thailand(1993-09-01) Y. Yuthavong; K. Phornsadja; A. Chungcharoen; T. O. Eisemon; C. H. Davis; Thailand National Science and Technology Development Agency; Mahidol University; Kasetsart University; McGill University; Centre de Recherches Pour Le Developpement InternationalThailand has a growing demand for improved science-based technologies in the agricultural sector. Traditionally strong in agricultural research, Thailand is encouraging agricultural applications of biotechnology through focused research funding. This article provides a brief account of the status of scientific research in the Thai orchid and seed industries, and examines communication behavior of researchers and innovators in Thai universities, research institutions and firms. Researchers produce relatively few written communications in tissue culture and seed technologies, and technology diffusion relies mainly on personal interactions between the researchers, intermediaries, and users of innovations. © 1993 Akadémiai Kiadó.Publication Metadata only A comparison of bivariate, multivariate random-effects, and Poisson correlated gamma-frailty models to meta-analyze individual patient data of ordinal scale diagnostic tests(2017-11-01) Gabrielle Simoneau; Brooke Levis; Pim Cuijpers; John P.A. Ioannidis; Scott B. Patten; Ian Shrier; Charles H. Bombardier; Flavia de Lima Osório; Jesse R. Fann; Dwenda Gjerdingen; Femke Lamers; Manote Lotrakul; Bernd Löwe; Juwita Shaaban; Lesley Stafford; Henk C.P.M. van Weert; Mary A. Whooley; Karin A. Wittkampf; Albert S. Yeung; Brett D. Thombs; Andrea Benedetti; McGill University; Lady Davis Institute for Medical Research; Vrije Universiteit Amsterdam; Stanford University; University of Calgary; University of Washington, Seattle; Universidade de Sao Paulo - USP; University of Minnesota Twin Cities; VU University Medical Center; Mahidol University; Universitätsklinikum Hamburg-Eppendorf und Medizinische Fakultät; School of Medical Sciences - Universiti Sains Malaysia; Royal Women's Hospital, Carlton; Academic Medical Centre, University of Amsterdam; VA Medical Center; Massachusetts General Hospital; Centre universitaire de santé McGill© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Individual patient data (IPD) meta-analyses are increasingly common in the literature. In the context of estimating the diagnostic accuracy of ordinal or semi-continuous scale tests, sensitivity and specificity are often reported for a given threshold or a small set of thresholds, and a meta-analysis is conducted via a bivariate approach to account for their correlation. When IPD are available, sensitivity and specificity can be pooled for every possible threshold. Our objective was to compare the bivariate approach, which can be applied separately at every threshold, to two multivariate methods: the ordinal multivariate random-effects model and the Poisson correlated gamma-frailty model. Our comparison was empirical, using IPD from 13 studies that evaluated the diagnostic accuracy of the 9-item Patient Health Questionnaire depression screening tool, and included simulations. The empirical comparison showed that the implementation of the two multivariate methods is more laborious in terms of computational time and sensitivity to user-supplied values compared to the bivariate approach. Simulations showed that ignoring the within-study correlation of sensitivity and specificity across thresholds did not worsen inferences with the bivariate approach compared to the Poisson model. The ordinal approach was not suitable for simulations because the model was highly sensitive to user-supplied starting values. We tentatively recommend the bivariate approach rather than more complex multivariate methods for IPD diagnostic accuracy meta-analyses of ordinal scale tests, although the limited type of diagnostic data considered in the simulation study restricts the generalization of our findings.Publication Metadata only Components of the COPD assessment test (CAT) associated with a diagnosis of COPD in a random population sample(2012-04-01) Natya Raghavan; Yuk Miu Lam; Katherine A. Webb; Jordan A. Guenette; Naparat Amornputtisathaporn; Ramya Raghavan; Wan C. Tan; Jean Bourbeau; Denis E. O'Donnell; Queen's University, Kingston; Mahidol University; Oakridges Heart Clinic; The University of British Columbia; McGill UniversityThe aim of this study was to determine if components of the COPD Assessment Test (CAT), a validated health status impairment instrument, had additional utility in identifying patients at risk for COPD in whom spirometry testing is appropriate. This study was part of the Canadian Obstructive Lung Disease prevalence study. Consenting participants ≥ 40 years of age were identified by random digit dialing. Smoking history, 8-item CAT scores, and post-bronchodilator spirometry were recorded for each. Stepwise logistic regression analysis was used to identify variables related to the presence of airway obstruction and a final logistic model was developed which best predicted COPD in this sample. Of the 801 individuals approached, 532 were included: 51 (9.6%) had COPD, the majority (92%) of whom fit GOLD I or II severity criteria. Items that correlated significantly with a COPD diagnosis included the CAT total score (p = 0.01) and its breathlessness (p < 0.0001) and phlegm (p = 0.001) components. The final logistic model included: age ( < 55 or ≥55 years), smoking status (current, former, never) and the CAT breathlessness score (ordinal scale 05). The area under the receiver-operating characteristic curve for this model was 0.77, sensitivity was 77.6%, specificity was 64.9% and the positive likelihood ratio was 2.21. In summary, the triad of smoking history, age at least 55 years and the presence of exertional breathlessness were key elements of a simple model which had reliable measurement properties when tested in a random population. This may help identify patients at risk for COPD for whom spirometry testing is recommended. © 2012 Informa Healthcare USA, Inc.Publication Metadata only Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial(2016-09-01) Gustavo Saposnik; Leonardo G. Cohen; Muhammad Mamdani; Sepideth Pooyania; Michelle Ploughman; Donna Cheung; Jennifer Shaw; Judith Hall; Peter Nord; Sean Dukelow; Yongchai Nilanont; Felipe De los Rios; Lisandro Olmos; Mindy Levin; Robert Teasell; Ashley Cohen; Kevin Thorpe; Andreas Laupacis; Mark Bayley; Saint Michael's Hospital University of Toronto; National Institutes of Health, Bethesda; Li Ka Shing Knowledge Institute; Riverview Health Centre; Memorial University of Newfoundland; University of Toronto; Providence Healthcare; Foothills Medical Centre; Mahidol University; Hospital Nacional Cayetano Heredia; Fundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia; McGill University; Western University© 2016 Elsevier Ltd Background Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. Methods In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18–85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. Findings The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43·7 s [IQR 26·1–68·0] to 29·7 s [21·4–45·2], 32·0% reduction for VRWii vs 38·0 s [IQR 28·0–64·1] to 27·1 s [21·2–45·5], 28·7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345]; p=0·70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0·60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4·1 s, 95% CI −14·4 to 22·6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups. Interpretation In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. Simple, low-cost, and widely available recreational activities might be as effective as innovative non-immersive virtual reality technologies. Funding Heart and Stroke Foundation of Canada and Ontario Ministry of Health.Publication Metadata only Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: A systematic review and individual participant data meta-analysis(2020-06-01) Yin Wu; Yin Wu; Yin Wu; Brooke Levis; Kira E. Riehm; Nazanin Saadat; Alexander W. Levis; Marleine Azar; Danielle B. Rice; Danielle B. Rice; Jill Boruff; Pim Cuijpers; Simon Gilbody; John P.A. Ioannidis; Lorie A. Kloda; Dean McMillan; Scott B. Patten; Scott B. Patten; Ian Shrier; Ian Shrier; Roy C. Ziegelstein; Dickens H. Akena; Bruce Arroll; Liat Ayalon; Hamid R. Baradaran; Hamid R. Baradaran; Murray Baron; Murray Baron; Charles H. Bombardier; Peter Butterworth; Peter Butterworth; Gregory Carter; Marcos H. Chagas; Juliana C.N. Chan; Juliana C.N. Chan; Juliana C.N. Chan; Rushina Cholera; Yeates Conwell; Janneke M. De Man-Van Ginkel; Jesse R. Fann; Felix H. Fischer; Daniel Fung; Daniel Fung; Daniel Fung; Daniel Fung; Bizu Gelaye; Felicity Goodyear-Smith; Catherine G. Greeno; Brian J. Hall; Brian J. Hall; Patricia A. Harrison; Martin Härter; Ulrich Hegerl; Leanne Hides; Stevan E. Hobfoll; Marie Hudson; Marie Hudson; Thomas Hyphantis; Masatoshi Inagaki; Nathalie Jetté; Nathalie Jetté; Nathalie Jetté; Mohammad E. Khamseh; Kim M. Kiely; Kim M. Kiely; Yunxin Kwan; Femke Lamers; Shen Ing Liu; Shen Ing Liu; Shen Ing Liu; Shen Ing Liu; Manote Lotrakul; Sonia R. Loureiro; Bernd Löwe; Anthony McGuire; Sherina Mohd-Sidik; Tiago N. Munhoz; Kumiko Muramatsu; Flávia L. Osório; Flávia L. Osório; Vikram Patel; Vikram Patel; Brian W. Pence; Philippe Persoons; Philippe Persoons; Angelo Picardi; Katrin Reuter; Alasdair G. Rooney; Iná S. Santos; Juwita Shaaban; Abbey Sidebottom; Adam Simning; Lesley Stafford; Lesley Stafford; Sharon Sung; Sharon Sung; Pei Lin Lynnette Tan; Alyna Turner; Alyna Turner; Melbourne Institute; Melbourne School of Psychological Sciences; Mackay Medical College; Duke-NUS Medical School Singapore; City of Minneapolis; Hunter Medical Research Institute, Australia; Niigata Seiryo University; Makerere University; Concordia University; University Medical Center Utrecht; Royal Women's Hospital, Carlton; Harvard T.H. Chan School of Public Health; KU Leuven– University Hospital Leuven; The University of Queensland; Mackay Memorial Hospital Taiwan; University of New South Wales (UNSW) Australia; The University of Edinburgh; Yong Loo Lin School of Medicine; Shimane University; Charité – Universitätsmedizin Berlin; Universiti Putra Malaysia; The University of North Carolina at Chapel Hill; KU Leuven; Iran University of Medical Sciences; Universitäts Klinikum Freiburg und Medizinische Fakultät; Prince of Wales Hospital Hong Kong; University of Rochester Medical Center; Neuroscience Research Australia; Universidade de Macau; Lady Davis Institute for Medical Research; UNC School of Medicine; Deakin University; University of Newcastle, Faculty of Health and Medicine; University of York; Saint Joseph's College of Maine; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; University of Pittsburgh; University of Washington, Seattle; Universidade Federal de Pelotas; Icahn School of Medicine at Mount Sinai; Stanford University; University of Aberdeen School of Medicine, Medical Sciences and Nutrition; Istituto Superiore Di Sanita; Singapore Institute of Mental Health; The Australian National University; Vrije Universiteit Amsterdam; Universidade de Sao Paulo - USP; Goethe-Universität Frankfurt am Main; University of Auckland; Nanyang Technological University; Johns Hopkins University; Universitätsklinikum Hamburg-Eppendorf und Medizinische Fakultät; Panepistimion Ioanninon; Chinese University of Hong Kong; Bar-Ilan University; Harvard Medical School; School of Medical Sciences - Universiti Sains Malaysia; McGill University; Tan Tock Seng Hospital; University of Calgary; STAR-Stress; National Institute of Science and Technology; Allina HealthCopyright © Cambridge University Press 2019. Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.Methods We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.Results 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).Conclusions PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.Publication Metadata only Ethanol production from selected lignocellulosic hydrolysates by genome shuffled strains of Scheffersomyces stipitis(2011-11-01) Paramjit K. Bajwa; Chetsada Phaenark; Nicola Grant; Xiao Zhang; Michael Paice; Vincent J.J. Martin; Jack T. Trevors; Hung Lee; University of Guelph; Universite Concordia; FPInnovations - Pulp and Paper Division; Mahidol University; McGill University; Washington State University Tri-CitiesTwo genome-shuffled Scheffersomyces stipitis strains, GS301 and GS302, exhibiting improved tolerance to hardwood spent sulphite liquor, were tested for growth and fermentation performance on three wood hydrolysates: (a) steam-pretreated enzymatically hydrolyzed poplar hydrolysate from Mascoma Canada, (b) steam pretreated poplar hydrolysate from University of British Columbia Forest Products Biotechnology Laboratory, and (c) mixed hardwoods pre-hydrolysate from FPInnovations (FPI). In the FPI hydrolysate, the wild type (WT) died off within 25. h, while GS301 and GS302 survived beyond 100. h. In fermentation tests, GS301 and GS302 completely utilized glucose and xylose in each hydrolysate and produced 0.39-1.4% (w/v) ethanol. In contrast, the WT did not utilize or poorly utilized glucose and xylose and produced non-detectable to trace amounts of ethanol. The results demonstrated cross tolerance of the mutants to inhibitors in three different wood hydrolysates and reinforced the utility of mating-based genome shuffling approach in industrial yeast strain improvement. © 2011 Elsevier Ltd.Publication Metadata only Ethical issues in haemophilia(2006-07-01) Donna DiMichele; A. Chuansumrit; A. J. London; A. R. Thompson; C. G. Cooper; R. M. Killian; L. F. Ross; D. Lillicrap; J. Kimmelman; Weill Cornell Medical College; Mahidol University; Carnegie Mellon University; Puget Sound Blood Center; University of Chicago; Queen's University, Kingston; McGill University; New York-Presbyterian/Weill CornellEthical issues surrounding both the lack of global access to care as well as the implementation of advancing technologies, continue to challenge the international haemophilia community. Haemophilia is not given the priority it deserves in most developing countries. Given the heavy burdens of sickness and disease and severe resource constraints, it may not be possible to provide effective treatment to all who suffer from the various 'orphan' diseases. Nevertheless, through joint efforts, some package of effective interventions can be deployed for a significant number of those who are afflicted with 'orphan' diseases. With cost-effective utilization of limited resources, a national standard of care is possible and affordable. Gene-based diagnosis carries attendant ethical concerns whether for clinical testing or for research purposes, even as the list of its potential benefits to the haemophilia community grows rapidly. As large-scale genetic sequencing becomes quicker and cheaper, moving from the research to the clinic, we will face decisions about the implementation of prenatal, neonatal and other screening programs. Such debates will require input from not just the health care professionals but from all stakeholders in the haemophilia community. Finally, long-term therapeutic success gene transfer in small and large animal models raises the question of when and in which patient population the novel therapeutic approach should first be studied in humans with haemophilia. Although gene therapy represents a worthy goal, the central question for the haemophilia community should be whether it wishes to volunteer itself as a model for a much broader set of innovations. © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Ltd.Publication Metadata only The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort(2013-11-01) J. Lee; C. A. Peschken; C. Muangchan; E. Silverman; C. Pineau; C. D. Smith; H. Arbillaga; M. Zummer; A. Clarke; S. Bernatsky; M. Hudson; C. Hitchon; P. R. Fortin; J. E. Pope; Western University; University of Manitoba; St. Joseph's Health Care London; Mahidol University; Hospital for Sick Children University of Toronto; McGill University; The Ottawa Hospital; University of Calgary; Cent. Rech. Maisonneuve-Rosemont; University of Montreal; University of TorontoObjectives: Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Methods: Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. Results: Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p0.05): juvenileonset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate 25 mm/hr (1.9 [1.1-3.4]), proteinuria 0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. Conclusions: The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.Publication Metadata only Genetic diversity in human erythrocyte pyruvate kinase(2012-01-01) J. Berghout; S. Higgins; C. Loucoubar; A. Sakuntabhai; K. C. Kain; P. Gros; McGill University; University of Toronto; Institut Pasteur, Paris; Mahidol UniversityPreviously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium falciparum replication ex vivo. Here, we have sequenced the human PKLR gene in 387 individuals from malaria-endemic and other regions in order to assess genetic variability in different geographical regions and ethnic groups. Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%). Haplotype distribution and allele frequency varied considerably with geography. Neutrality testing suggested positive selection of the genein the sub-Saharan African and Pakistan populations. It is possible that such positive selection involves the malarial parasite. © 2012 Macmillan Publishers Limited All rights reserved.Publication Metadata only Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium(2019-12-01) Oliver A. Cornely; Ana Alastruey-Izquierdo; Dorothee Arenz; Sharon C.A. Chen; Eric Dannaoui; Bruno Hochhegger; Martin Hoenigl; Henrik E. Jensen; Katrien Lagrou; Russell E. Lewis; Sibylle C. Mellinghoff; Mervyn Mer; Zoi D. Pana; Danila Seidel; Donald C. Sheppard; Roger Wahba; Murat Akova; Alexandre Alanio; Abdullah M.S. Al-Hatmi; Sevtap Arikan-Akdagli; Hamid Badali; Ronen Ben-Ami; Alexandro Bonifaz; Stéphane Bretagne; Elio Castagnola; Methee Chayakulkeeree; Arnaldo L. Colombo; Dora E. Corzo-León; Lubos Drgona; Andreas H. Groll; Jesus Guinea; Claus Peter Heussel; Ashraf S. Ibrahim; Souha S. Kanj; Nikolay Klimko; Michaela Lackner; Frederic Lamoth; Fanny Lanternier; Cornelia Lass-Floerl; Dong Gun Lee; Thomas Lehrnbecher; Badre E. Lmimouni; Mihai Mares; Georg Maschmeyer; Jacques F. Meis; Joseph Meletiadis; C. Orla Morrissey; Marcio Nucci; Rita Oladele; Livio Pagano; Alessandro Pasqualotto; Atul Patel; Zdenek Racil; Malcolm Richardson; Emmanuel Roilides; Markus Ruhnke; Seyedmojtaba Seyedmousavi; Neeraj Sidharthan; Nina Singh; János Sinko; Anna Skiada; Monica Slavin; Rajeev Soman; Brad Spellberg; William Steinbach; Ban Hock Tan; Andrew J. Ullmann; Jörg J. Vehreschild; Maria J.G.T. Vehreschild; Thomas J. Walsh; P. Lewis White; Nathan P. Wiederhold; Theoklis Zaoutis; Arunaloke Chakrabarti; Manchester University NHS Foundation Trust; Duke University Medical Center; Public Health Wales; Universidade Federal de Ciencias da Saúde de Porto Alegre; Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore; Ministry of Health Oman; American University of Beirut Medical Center; Szent Laszlo Hospital; Hospital General Universitario Gregorio Marañon; Cancer Research Institute of Slovak Academy of Sciences; Peter Maccallum Cancer Centre; Universitätsklinikum Würzburg; Erasmus MC; KU Leuven– University Hospital Leuven; Hopital Europeen Georges-Pompidou; Københavns Universitet; University of California, San Diego; The Children's Hospital of Philadelphia; University of Southern California; Universite Paris Descartes; National and Kapodistrian University of Athens; Nijmegen Interdenominational Hospital Canisius-Wilhelmina; Alma Mater Studiorum Università di Bologna; Universidad Complutense de Madrid; University of Melbourne; Centro Nacional de Microbiologia; The University of Sydney; Université Paris-Sud; University of Cologne; University of Lagos College of Medicine; Lukas-Krankenhaus; Centre Hospitalier Universitaire Vaudois; P.D. Hinduja National Hospital and Medical Research Centre; Monash University; Mohammed V University in Rabat; University of Texas Health Science Center at San Antonio; New York Presbyterian Hospital; Singapore General Hospital; North-Western State Medical University named after I.I. Mechnikov; Mazandaran University of Medical Sciences; Klinikum Ernst von Bergmann; National Institute of Allergy and Infectious Diseases; University of Witwatersrand; Harbor-UCLA Medical Center; IRCCS Istituto Giannina Gaslini - Ospedale Pediatrico; University of Aberdeen; Pontificia Universidade Catolica do Rio Grande do Sul; Hospital General de Mexico; Aristotle University of Thessaloniki; Universidade Federal de Sao Paulo; University of Pittsburgh Medical Center; Hacettepe University, Faculty of Medicine; Faculty of Medicine, Siriraj Hospital, Mahidol University; Tel Aviv Sourasky Medical Center; Uniklinik Köln; Medizinische Universitat Innsbruck; Amrita Institute of Medical Sciences India; Goethe-Universität Frankfurt am Main; Universitätsklinikum Münster; Medizinische Universität Graz; Tel Aviv University, Sackler Faculty of Medicine; University of Manchester; Hippokration General Hospital; Hospital General "Dr. Manuel Gea González"; Universitätsklinikum Heidelberg; The Catholic University of Korea; McGill University; Institute of Hematology and Blood Transfusion; Postgraduate Institute of Medical Education & Research, Chandigarh; Universidade Federal do Rio de Janeiro; Center of Expertise in Microbiology; Westerdijk Fungal Biodiversity Institute; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne; Ion Ionescu de la Brad University; Vedanta Institute of Medical Sciences© 2019 Elsevier Ltd Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the “One World One Guideline” initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.Publication Metadata only Global implementation of genomic medicine: We are not alone(2015-06-03) Teri A. Manolio; Marc Abramowicz; Fahd Al-Mulla; Warwick Anderson; Rudi Balling; Adam C. Berger; Steven Bleyl; Aravinda Chakravarti; Wasun Chantratita; Rex L. Chisholm; Vajira H.W. Dissanayake; Michael Dunn; Victor J. Dzau; Bok Ghee Han; Tim Hubbard; Anne Kolbe; Bruce Korf; Michiaki Kubo; Paul Lasko; Erkki Leego; Surakameth Mahasirimongkol; Partha P. Majumdar; Gert Matthijs; Howard L. McLeod; Andres Metspalu; Pierre Meulien; Satoru Miyano; Yaakov Naparstek; P. Pearl O'Rourke; George P. Patrinos; Heidi L. Rehm; Mary V. Relling; Gad Rennert; Laura Lyman Rodriguez; Dan M. Roden; Alan R. Shuldiner; Sukdeb Sinha; Patrick Tan; Mats Ulfendahl; Robyn Ward; Marc S. Williams; John E.L. Wong; Eric D. Green; Geofrey S. Ginsburg; National Human Genome Research Institute; Université libre de Bruxelles (ULB); University of Kuwait; Australian Government; University of Luxembourg; Institute of Medicine - Washington; Intermountain Healthcare; The Johns Hopkins School of Medicine; Mahidol University; Northwestern University Feinberg School of Medicine; University of Colombo Faculty of Medicine; Wellcome Trust; National Academy of Medicine; Korea National Institute of Health; King's College London; National Health Committee; University of Alabama at Birmingham; Riken; McGill University; University of Tartu; Thailand Ministry of Public Health; Indian Statistical Institute, Kolkata; KU Leuven; Moffitt Cancer Center; Genome Canada; Institute of Medical Science The University of Tokyo; Hadassah University Medical Centre; Partners HealthCare; Panepistimion Patron; St. Jude Children's Research Hospital; Carmel Medical Center; Vanderbilt University School of Medicine; University of Maryland School of Medicine; Ministry of Science And Technology, India; Duke-NUS Medical School Singapore; Swedish Research Council; University of Queensland; Geisinger Health System; National University of Singapore; Duke University; Genomics England© 2015, American Association for the Advancement of Science. All rights reserved. Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual eforts might beneft from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Eforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in eforts to improve clinical care worldwide.Publication Metadata only Guidelines for the use and interpretation of assays for monitoring autophagy(2012-04-01) Daniel J. Klionsky; Fabio C. Abdalla; Hagai Abeliovich; Robert T. Abraham; Abraham Acevedo-Arozena; Khosrow Adeli; Lotta Agholme; Maria Agnello; Patrizia Agostinis; Julio A. Aguirre-Ghiso; Hyung Jun Ahn; Ouardia Ait-Mohamed; Slimane Ait-Si-Ali; Takahiko Akematsu; Shizuo Akira; Hesham M. Al-Younes; Munir A. Al-Zeer; Matthew L. Albert; Roger L. Albin; Javier Alegre-Abarrategui; Maria Francesca Aleo; Mehrdad Alirezaei; Alexandru Almasan; Maylin Almonte-Becerril; Atsuo Amano; Ravi Amaravadi; Shoba Amarnath; Amal O. Amer; Nathalie Andrieu-Abadie; Vellareddy Anantharam; David K. Ann; Shailendra Anoopkumar-Dukie; Hiroshi Aoki; Nadezda Apostolova; Giuseppe Arancia; John P. Aris; Katsuhiko Asanuma; Nana Y.O. Asare; Hisashi Ashida; Valerie Askanas; David S. Askew; Patrick Auberger; Misuzu Baba; Steven K. Backues; Eric H. Baehrecke; Ben A. Bahr; Xue Yuan Bai; Yannick Bailly; Robert Baiocchi; Giulia Baldini; Walter Balduini; Andrea Ballabio; Bruce A. Bamber; Edward T.W. Bampton; Gábor Bánhegyi; Clinton R. Bartholomew; Diane C. Bassham; Robert C. Bast; Henri Batoko; Boon Huat Bay; Isabelle Beau; Daniel M. Béchet; Thomas J. Begley; Christian Behl; Christian Behrends; Soumeya Bekri; Bryan Bellaire; Linda J. Bendall; Luca Benetti; Laura Berliocchi; Henri Bernardi; Francesca Bernassola; Sébastien Besteiro; Ingrid Bhatia-Kissova; Xiaoning Bi; Martine Biard-Piechaczyk; Janice S. Blum; Lawrence H. Boise; Paolo Bonaldo; David L. Boone; Beat C. Bornhauser; Karina R. Bortoluci; Ioannis Bossis; Frédéric Bost; Jean Pierre Bourquin; Patricia Boya; Michaël Boyer-Guittaut; Peter V. Bozhkov; Nathan R. Brady; Claudio Brancolini; Andreas Brech; Jay E. Brenman; University of Michigan, Ann Arbor; Universidade Federal de Sao Carlos; Hebrew University of Jerusalem; Pfizer Inc.; MRC Mammalian Genetics Unit; Hospital for Sick Children University of Toronto; Linkopings universitet; Universita degli Studi di Palermo; KU Leuven; New York University; Korea Institute of Science and Technology; Universite Paris 7- Denis Diderot; York University; Osaka University; The University of Jordan; Max Planck Institute for Infection Biology; Institut Pasteur, Paris; VAAAHS; University of Oxford; Universita degli Studi di Brescia, Facolta di Medicina e Chirurgia; Scripps Research Institute; Cleveland Clinic Foundation; Centro de Investigacion y de Estudios Avanzados; University of Pennsylvania; National Cancer Institute; Ohio State University; Universite Paul Sabatier Toulouse III; Iowa State University; City of Hope National Med Center; Griffith University; Niigata University; Universitat de Valencia, Facultad de Medicina y Odontologia; Istituto Superiore Di Sanita, Rome; University of Florida College of Medicine; Juntendo University; Norwegian Institute of Public Health; Kyoto University; Keck School of Medicine of USC; University of Cincinnati College of Medicine; Centre Mediterraneen de Medecine Moleculaire; Universite Nice Sophia Antipolis; Kogakuin University of Technology and Engineering; University of Massachusetts Medical School; University of North Carolina-Pembroke; General Hospital of People's Liberation Army; Universite de Strasbourg; University of Arkansas for Medical Sciences; Universita degli Studi di Urbino Carlo Bo; TIGEM Telethon Institute of Genetics and Medicine; Baylor College of Medicine; University of Toledo; University of Leicester; Semmelweis Egyetem; University of Texas MD Anderson Cancer Center; Universite Catholique de Louvain; Yong Loo Lin School of Medicine; Universite Paris-Sud XI; Universite d' Auvergne Clermont-FD 1; University at Albany State University of New York; Klinikum der Johannes-Gutenberg-Universitat und Fachbereich Medizin; Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universitat Frankfurt am Main; CHU Hopitaux de Rouen; The University of Sydney; Merck & Co., Inc.; Universita degli studi Magna Graecia di Catanzaro; INRA Montpellier; Universita degli Studi di Roma Tor Vergata; CNRS Centre National de la Recherche Scientifique; Comenius University; Western University of Health Sciences; CNRS UM1; Indiana University School of Medicine Indianapolis; Emory University School of Medicine; Universita degli Studi di Padova; University of Chicago; Kinderspital Zurich; Universidade Federal de Sao Paulo; University of Maryland; CSIC - Centro de Investigaciones Biologicas (CIB); Universite de Franche-Comte; Sveriges lantbruksuniversitet; Universitat Heidelberg; Universita degli Studi di Udine; Universitetet i Oslo; University of North Carolina School of Medicine; de Duve Institute; University of Wisconsin School of Medicine and Public Health; Virginia Commonwealth University; University of Rochester Medical Center; 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Royal North Shore Hospital; Weatherall Institute of Molecular Medicine; Nuffield Department of Clinical Medicine; Universitat Bern; Consorzio Mario Negri Sud; The Johns Hopkins School of Medicine; Hong Kong Polytechnic University; University of Chemistry and Technology, Prague; Lomonosov Moscow State University; Mahidol University; Centro Nacional de Investigaciones Oncologicas; Hebei Medical University; Charité – Universitätsmedizin Berlin; Mayo Clinic in Jacksonville, Florida; Indian Institute of Science Education and Research Thiruvananthapuram; Academy of Athens; UCL; SAIC-Frederick; Instituto Nacional de Cancer; Heinrich Heine Universitat; CASE School of Medicine; Wuhan University; University of the Ryukyus; University of York; University of Texas Medical School at Houston; Yokohama City University School of Medicine; University of Exeter; Chinese Academy of Sciences; Institute of Genetics and Developmental Biology Chinese Academy of Sciences; University of Birmingham; Universita degli Studi dell'Insubria; Okayama University Medical School; University of Cambridge; University of Manchester; University of Southern California; University of Belgrade; UniversitatsSpital Bern; University of Pittsburgh Medical Center; Jozef Stefan Institute; Francis Marion University; OHSU School of Medicine; IRCCS Casa Sollievo della Sofferenza; Vrije Universiteit Brussel; Universiteit Gent; KU Leuven– University Hospital Leuven; Hospital Clinic Barcelona; Universidad Complutense de Madrid; Universitat Autònoma de Barcelona; Komarov Botanical Institute, Russian Academy of Sciences; Cardiff University; Texas A and M Institute for Biosciences and Technology; North Shore University Hospital; National Tsing Hua University; Chinese Academy of Medical Sciences; Changzheng Hospital; Nijmegen Centre for Molecular Life Sciences - NCMLS; University of Utah, School of Medicine; House Research Institute; University of Science and Technology of China; University of Sheffield; University Health Network University of Toronto; Fujian University of Traditional Chinese Medicine; Xi'an Jiaotong University; University of Southampton; Wuhan Institute of Virology Chinese Academy of Sciences; University of Oklahoma Health Sciences Center; Henan University of Technology; University of Kansas Lawrence; Mayo Clinic; Nagahama Institute of Bio-Science and Technology; National Research Institute of Fisheries Science, FRA; Okinawa Institute of Science and Technology Graduate University; OIST Graduate University; Vanderbilt Ingram Cancer Center; Weis Center for Research; University of Shizuoka; INRA Centre de Recherche de Versailles-Grignon; Chosun University; Icahn School of Medicine at Mount Sinai; Keio University School of Medicine; Toronto General Research Institute University of Toronto; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; University of Virginia; National Institute of Biological Sciences, Beijing; Leiden University Medical Center - LUMC; University of Newcastle Faculty of Medicine and Health Sciences; Peking University Health Science Center; University of California, Berkeley; Goteborgs Universitet; Max Planck Institut fur Psychiatrie; Centre Hospitalier Universitaire de Nice; Istituto Neurologico Mediterraneo Neuromed, Pozzilli; The Cancer Institute of New Jersey; Universite de Lyon; Panepistimio Kritis; Santo Tomas University; Johannes Gutenberg Universitat Mainz; University of RzeszowIn 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.Publication Metadata only How to use an article about genetic association - C: What are the results and will they help me in caring for my patients?(2009-01-21) John Attia; John P.A. Ioannidis; Ammarin Thakkinstian; Mark McEvoy; Rodney J. Scott; Cosetta Minelli; John Thompson; Claire Infante-Rivard; Gordon Guyatt; Royal Newcastle Hospital; Hunter Medical Research Institute, Australia; John Hunter Hospital; University of Ioannina, School of Medicine; Tufts University School of Medicine; Mahidol University; University of Newcastle, Australia; Hunter Area Pathology Service; University of Newcastle Faculty of Medicine and Health Sciences; National Heart and Lung Institute; University of Leicester; McGill University; McMaster University, Faculty of Health SciencesIn the first 2 articles of this series, we reviewed the basic genetics concepts necessary to understand genetic association studies, and we enumerated the major issues in judging the validity of these studies. In this third article, we review the issues relating to the applicability of the results in the clinical situation. How large and precise are the associations? Many genetic effects are expected to be smaller in magnitude than traditional risk factors. Does the genetic association improve predictive power beyond easily measured clinical variables? In some cases, the additional genetic information adds only a small increment in the predictive ability of a diagnostic or prognostic test. What are the absolute vs relative effects? Even if the genetic risk is high in relative terms, the baseline risk may be very low in absolute terms. Is the risk-associated allele likely to be present in my patient? A risk allele may have a strong effect but be rare in a particular ethnic group. Is the patient likely better off knowing the genetic information? Given that genes cannot be modified, one must weigh whether the genetic information is likely to be helpful in planning other health interventions or initiating behavior change. ©2009 American Medical Association. All rights reserved.Publication Metadata only How to use an article about genetic association A: Background concepts(2009-01-07) John Attia; John P.A. Ioannidis; Ammarin Thakkinstian; Mark McEvoy; Rodney J. Scott; Cosetta Minelli; John Thompson; Claire Infante-Rivard; Gordon Guyatt; Hunter Medical Research Institute, Australia; John Hunter Hospital; University of Ioannina, School of Medicine; Tufts University School of Medicine; Mahidol University; Hunter Area Pathology Service; National Heart and Lung Institute; University of Leicester; McGill University; McMaster University, Faculty of Health Sciences; University of Newcastle, AustraliaThis is the first in a series of 3 articles serving as an introduction to clinicians wishing to read and critically appraise genetic association studies. We summarize the key concepts in genetics that clinicians must understand to review these studies, including the structure of DNA, transcription and translation, patterns of inheritance, Hardy-Weinberg equilibrium, and linkage disequilibrium. We review the types of DNA variation, including single-nucleotide polymorphisms (SNPs), insertions, and deletions, and how these can affect protein function. We introduce the idea of genetic association for both single-candidate gene and genome-wide association studies, in which thousands of genetic variants are tested for association with disease. We use the APOE polymorphism and its association with dementia as a case study to demonstrate the concepts and introduce the terminology used in this field. The second and third articles will focus on issues of validity and applicability. ©2009 American Medical Association. All rights reserved.Publication Metadata only How to use an article about genetic association B: Are the results of the study valid?(2009-01-14) John Attia; John P.A. Ioannidis; Ammarin Thakkinstian; Mark McEvoy; Rodney J. Scott; Cosetta Minelli; John Thompson; Claire Infante-Rivard; Gordon Guyatt; University of Newcastle, Australia; University of Ioannina, School of Medicine; Tufts University School of Medicine; Mahidol University; Hunter Area Pathology Service; University of Newcastle Faculty of Medicine and Health Sciences; National Heart and Lung Institute; University of Leicester; McGill University; McMaster University, Faculty of Health Sciences; Royal Newcastle HospitalIn the first article of this series, we reviewed the basic genetics concepts necessary to understand genetic association studies. In this second article, we enumerate the major issues in judging the validity of these studies, framed as critical appraisal questions. Was the disease phenotype properly defined and accurately recorded by someone blind to the genetic information? Have any potential differences between disease and nondisease groups, particularly ethnicity, been properly addressed? In genetic studies, one potential cause of spurious associations is differences between cases and controls in ethnicity, a situation termed population stratification. Was measurement of the genetic variants unbiased and accurate? Methods for determining DNA sequence variation are not perfect and may have some measurement error. Do the genotype proportions observe Hardy-Weinberg equilibrium? This simple mathematic rule about the distribution of genetic groups may be one way to check for errors in reading DNA information. Have the investigators adjusted their inferences for multiple comparisons? Given the thousands of genetic markers tested in genome-wide association studies, the potential for false-positive and false-negative results is much higher than in traditional medical studies, and it is particularly important to look for replication of results. ©2009 American Medical Association. All rights reserved.
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