The ISF takes its direction from a Council chaired by Dr Mervyn Singer. This prestigious group of international experts in sepsis meet regularly to identify educational needs and develop synergistic programs and activities.
Dr. Mervyn Singer – ISF Chair
Mervyn Singer is Professor of Intensive Care Medicine at University College London, UK. He was appointed a UK NIHR (National Institute of Health Research) Senior Investigator in 2009 and has been Editor-in-Chief of Intensive Care Medicine Experimental since 2012. He co-chaired the International Consensus Task Force that developed the new ‘Sepsis-3’ international definitions of sepsis (Singer et al, JAMA 2016) and sat on the recent Surviving Sepsis Campaign Committee. He advises the UK Department of Health and NHS England on sepsis and antimicrobial resistance. He has co-written/co-edited several textbooks including the ‘Oxford Textbook of Critical Care’ (OUP), the ‘Oxford Handbook of Critical Care’ (OUP), ‘Inflammation: From molecular and cellular mechanisms to the clinic’ (Wiley) and Critical Care Clinics – Sepsis (Elsevier). He was awarded Honorary Membership of the European Society of Intensive Care Medicine in 2017.
His areas of research interest in sepsis is on (i) mechanisms of multi-organ failure, especially the roles of mitochondrial dysfunction and myocardial depression; (ii) mechanisms and management of septic shock; (iii) management of infection and infection control and (iv) monitoring of organ perfusion and perfusion adequacy. There is a strong translational emphasis to his studies, with development and trialling of novel therapeutics, diagnostics and monitors. Research funding comes from the UK Medical Research Council, the Wellcome Trust, NIHR, Innovate UK, and the European Commission, and from strong industry links. He has also been Principal Investigator or Co-Investigator for numerous academic and industry-led multi-centre trials in sepsis.
Dr. Thierry Calandra – ISF Chair Elect and Treasurer
Thierry Calandra is Professor of medicine and Head of the Infectious Diseases Service at the University Hospital in Lausanne, Switzerland. He received his MD degree from the University of Lausanne, Switzerland and his PhD degree from the University of Utrecht, The Netherlands. He is board certified in infectious diseases and internal medicine.
Thierry is a member of Swiss Academy of Medical Sciences and an honorary life member of the Australasian Society for infectious Diseases. He is serving or has served on the Research Council of the Swiss National Science Foundation, on Program Committees for annual meeting of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) of the American Society for Microbiology. He is a Past-president or a Past-chair of the Swiss Society for Infectious Diseases, the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and the Fungal Infection Network of Switzerland. He also is a former member of the Steering Committee of the Mycoses Study Group (MSG) and a member of the Council of the International Sepsis Forum since 1999.
In 2017, Thierry received the prestigious Award for Excellence in Clinical Microbiology and Infectious Diseases of the European Society of Microbiology and Infectious Diseases (ESCMID), an award that recognizes and rewards an outstanding lifetime contribution in the areas of science, education or professional affairs in clinical microbiology and/or infectious diseases. He also is recipient of the Cloëtta Prize awarded by the Max Cloëtta Foundation for distinguished achievements in medical research. Other honors and awards include research awards from the Swiss National Science Foundation, the Leenaards Foundation, the Swiss Society of Infectious Diseases and the Jürg Tschopp Prize for Life Sciences of the University of Lausanne.
Thierry’s research interests focuses on innate immunity, sepsis, bacterial and fungal infections in critically ill patients and in immunocompromised hosts. Thierry has published close to 300 monographs, book chapters and peer-reviewed articles, which appeared in prestigious biomedical journals such as Nature, Nature Medicine, Nature Reviews Immunology, The New England Journal of Medicine, The Lancet, The Proceedings of the National Academy of Sciences, The Journal of the American Medical Association, The Journal of Experimental Medicine and Clinical Infectious Diseases.
Thierry is a member of many national and international societies, including the Swiss Society for Infectious Diseases, the European Society of Clinical Microbiology and Infectious Diseases, the European Society of Intensive Care Medicine, the European Organization for Research and Treatment of Cancer, the Infectious Diseases Society of America, the American Society for Microbiology, the International Endotoxin and Innate Immunity Society, the International Immunocompromised Host and the Mycoses Study Group Education and Research Consortium.
Dr. Simon Finfer – ISF Immediate Past Chair and Secretary
MBBS FRCP FRCA FCICM FAHMS MD
Simon Finfer is a Professorial Fellow in the Critical Care and Trauma Division at The George Institute for Global Health. He is a practicing critical care physician with an appointment as a Senior Staff Specialist at Royal North Shore Hospital and Director of Intensive Care at the Sydney Adventist Hospital, the largest not-for-profit hospital in New South Wales.
Simon is an Adjunct Professor at the University of New South Wales, and a Clinical Professor at the University of Sydney. He is a past-Chair of the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. He chairs the Council of the International Sepsis Forum, and is a member of the Global Sepsis Alliance Executive Board. Simon is a member of the World Sepsis Day Steering Committee and co-chaired the 1st World Sepsis Congress, a two-day free online congress that attracted 14,000 registrants with podcast downloads exceeding 65,000.
His postgraduate qualifications include Fellowships of the Royal Colleges of Physicians, the Royal College of Anaesthetists and the College of Intensive Care Medicine. He was elected to the ANZICS Honour Roll in 2011 and in 2012 he was awarded an honorary doctorate (Doctor of Medicine) by The Friedrich-Schiller University in Germany, an honour awarded once every 10 years. He is a Fellow of the Australian Academy of Health and Medical Sciences.
Simon’s major research interest is the design and conduct of large scale randomised controlled trials in critical care. Simon is active in forging major international research collaborations that have conducted large scale clinical trials and epidemiological research to improve the treatment of critically ill and injured patients. Many such trials have been conducted with industry partners and Simon has served on the steering committees of both investigator initiated and industry sponsored trials. He has published over 150 peer reviewed papers, many in the most prestigious journal in the world. He is frequently invited to lecture at major international conferences.
Simon is an Editor of The Oxford Textbook of Critical Care (2nd Ed.), the Critical Care Section Editor for The Oxford Textbook of Medicine (6th Ed.), and was a guest editor for The New England Journal of Medicine from 2012 – 2014.
Dr Derek Angus – ISF Past Chair
Professor and Vice Chair of Research in the Department of Critical Care Medicine with secondary appointments in Medicine and Health Policy and Management, and Director of the CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Laboratory at the University of Pittsburgh in Pittsburgh, Pennsylvania. He earned his medical degree and completed his residency training in Internal Medicine at the University of Glasgow in Glasgow, United Kingdom. Subsequently, he completed his Fellowship in Critical Care Medicine, combined with a Masters in Public Health degree at the University of Pittsburgh.
Dr Angus is a Fellow of the Royal College of Physicians and is a Fellow of the American College of Chest Physicians and the American College of Critical Care Medicine. He specializes in the epidemiologic, economic and health services research aspects of critical illness and ICU organization and delivery. He has studied the development and application of cost-effectiveness analysis in critical care, the capability and impact of alternative ICU organizational models, traditional and novel ICU risk prediction tools, and the incidence, cost and short- and long-term outcomes of critical illnesses such as sepsis and respiratory failure.
Dr Angus has attracted considerable research funding for these studies, authored or co-authored more than 350 publications, including more than 90 peer-reviewed articles, and lectured at scientific congresses nationally and internationally. Dr. Angus is currently leading three large NIH multicenter studies in the critically ill-GenIMS (Genetic and Inflammatory Markers of Sepsis), EA-PAC (Economic Analysis of the Pulmonary Artery Catheter), and ProNOx (Prolonged Outcomes in Neonatal Respiratory Failure after Nitric Oxide)
Dr. Kenneth Baillie – ISF Fellow
Wellcome-Beit Intermediate Clinical Fellow, Group Leader at the Roslin Institute, University of Edinburgh, and honorary consultant in critical care medicine at the Royal Infirmary, Edinburgh. Dr Baillie graduated from the University of Edinburgh with a BSc(Hons) in Physiology in 1999 and MBChB in 2002. After basic training in internal medicine and anesthesia, he was appointed as a clinical lecturer on the ECAT (Edinburgh Clinical Academic Track) at the University of Edinburgh in 2008, and completed a PhD in statistical genetics in 2012.
He is a Fellow of the Royal College of Anaesthetists, the Faculty of Intensive Care Medicine, and the Royal College of Physicians of Edinburgh and is a Deputy Director of Research for the Intensive Care Society. He has published work in Nature, Science and Cell.
The core focus of his laboratory is translational genomics: making use of genome-scale data from technologies such as whole-genome sequencing, CAGE and high-throughput genome editing to better understand and treat critical illness. Dr Baillie led two genetic studies (GenISIS and MOSAIC-WP7) which discovered the first human gene associated with susceptibility to life-threatening influenza. Working with the FANTOM5 consortium, he showed that a simple machine-learning approach to a transcriptomic expression atlas produces tractable new insights into the function of poorly-understood parts of the genome. He developed the network density analysis approach to draw direct inferences about disease from GWAS data, including therapeutic targets, mechanisms of pathogenesis, and discovery of disease endotypes.
Dr. Flavia Machado
Flavia Machado is professor of Intensive Care at the Federal University of São Paulo in São Paulo, Brazil. She is head of the Intensive Care Session of Anesthesiology, Pain and Intensive Care Department in this institution. Machado is board certified in internal medicine, infectious diseases and critical care.
She received her MD from the Federal University of Minas Gerais (UFMG) and her residence training in internal medicine at the Medical Sciences University in Belo Horizonte, and also a Masters in Infectious Diseases. Subsequently, she completed her fellowship in Infectious Diseases as well as Critical Care training and a PHD degree at the University of São Paulo.
Dr. Machado is one of the founders of the Latin America Sepsis Institute – LASI. She has the president between 2008-2011 and vice president between 2012-2015. She is currently its CEO. LASI is devoted to quality improvement process in Brazilian hospitals as well as to coordinate multicenter studies in sepsis field.
She is part of the executive board of the Global Sepsis Alliance as well as the executive committee for the World Sepsis Day. She serves on the 2012 and 2016 of the Surviving Sepsis Campaign International Guidelines. She is also member of the Executive Committee and the Scientific Committee of the Brazilian Research in Intensive Care Network – BRICNET. She is also a member (founder) of the Latin America Intensive Care Network (LIVEN). She is the scientific director for the Associação de Medicina Intensiva Brasileira – AMIB (2018-2019).
Flavia is well published in the fields of sepsis and hemodynamics. Her research focuses primarily on improving the care and outcomes of critically ill patients with sepsis as well as on quality improvement process. She lectured at scientific congresses nationally and internationally and is also an author or co-author of numerous invited book chapters as well as editor of critical care books. She has received multiple grants from the Sao Paulo State Research Foundation. Dr Machado is a member of many medical societies, including the Brazilian Critical Care Society, the Society of Critical Care Medicine and the European Society of Critical Care Medicine. Dr. Machado is the former editor-in-chief of “Revista Brasileira de Terapia Intensiva”, the official journal of the Brazilian Critical Care Association and the Portuguese Critical Care Association (2010 to 2015).
She integrates the International Sepsis Forum (ISF) council since 2014.
Dr. John Marshall – Past ISF Chair
Professor of surgery at the University of Toronto and attending surgeon at the Toronto General Hospital, University Health Network. He is also a practicing intensivist who serves as Director of Research Inter-departmental Division of Critical Care Medicine, University of Toronto. He received his MD from the University of Toronto and his fellowship in general surgery at Dalhousie University. Subsequent to this, he pursued a fellowship in critical care and surgical immunobiology at McGill University.
He has authored more than 150 peer-reviewed papers and textbook chapters. He is formerly editor in chief of the journal Sepsis and serves on the editorial boards of Critical Care, Current Opinion in Critical Care, and Shock. He is a member of a number of professional societies in surgery, critical care medicine, and the basic science of inflammation. He is councilor of the Shock Society, and a member of the executive board of the Canadian Critical Care Trials Group.
Dr Marshall’s research interests include the basic and clinical biology of inflammation and the mechanisms of its resolution through programmed cell death, as well as the epidemiology and natural history of sepsis and the multiple organ dysfunction syndrome. He has been an active basic and clinical investigator in these areas and has lectured widely on inflammation and its role in the pathogenesis of the morbidity of critical illness.
Dr. Jean-Paul Mira
Received his medical degree from Reims Medical School in 1990 and since then has developed his career in medicine and research both in France and in the USA where he spent 3 years at the Scripps Research Institute in California.
His research interests are genetic predisposition to sepsis, cellular responses to micro-organisms, membrane dynamics, Toll-like Receptor signaling, functional genomics and sepsis-induced immune-suppression. Jean-Paul is well published in the fields of immunology and critical care.
Dr. Tom van der Poll – Past ISF Chair
Professor of Medicine and Chair of the Department of Medicine in the Academic Medical Center, University of Amsterdam, the Netherlands. Van der Poll is board certified in Internal Medicine and Infectious Diseases. His training included a postdoctoral research fellowship in Cornell University Medical College in New York (1993-1995). Van der Poll is a former Fellow of the Royal Dutch Academy of Arts and Sciences (1995-2000). Van der Poll’s research focuses on pneumonia and sepsis, particularly on pathogenesis, the host response and biomarkers. He published > 800 articles on this topic. Van der Poll has served as a member of Data Safety and Clinical Monitoring Boards of several pivotal phase III sepsis and pneumonia trials evaluating immunomodulatory agents.
Dr. Hallie Prescott
Dr. Hallie Prescott is an Assistant Professor at the University of Michigan and a Core Investigator at the VA Center for Clinical Management Research. She is board-certified in internal medicine, critical care medicine, and pulmonary medicine, and practices clinically at the University of Michigan Health System and the Ann Arbor Veterans Affairs Hospital.
Hallie’s research program focuses on long-term outcomes and recovery after sepsis, with a focus on subsequent healthcare utilization and hospital readmission among sepsis survivors. Her research is funded by US National Institutes of Health and Department of Veterans Affairs. She has broad experience with quantitative methods and advanced statistical modeling, including health services research, clinical epidemiology, and “Big Data” analytic methods.
Hallie has a strong track record of peer reviewed publications in high-impact journals and recognition within the critical care research community. She co-chaired the 2018 ISF Colloquium “Understanding and Enhancing Sepsis Survivorship”, and is a co-Vice Chair of the 2020 Surviving Sepsis Campaign Guidelines. She was awarded the 2017 Joe Rae Wright Award for outstanding science from American Thoracic Society (given to a single junior physician-scientist across pulmonary, critical care, and sleep medicine each year).
Dr. Adrienne G. Randolph
Dr. Randolph is Professor of Anaesthesia and Pediatrics at Harvard Medical School and a Senior Associate in Critical Care Medicine at Boston Children’s Hospital in Massachusetts, USA . She has been an attending physician in the Medical-Surgical pediatric ICU there for over 20 years. Dr. Randolph is the founder and first Chair of the Pediatric Acute Lung Injury and Sepsis Investigator’s (PALISI) Network, a clinical research consortium of over 80 pediatric ICUs in the U.S. and Canada. Dr. Randolph has been a Council member of the International Sepsis Forum since 2011. She is also active in many other professional societies including the Society for Critical Care Medicine, the Society for Pediatric Research and the American Thoracic Society. She is a Fellow of the American Academy of Pediatrics and the American College of Critical Care Medicine and member of the American Pediatric Society. She helped lead the consensus meeting where the 2005 definition of sepsis in infants and children was developed and has coauthored multiple national guidelines on best sepsis diagnosis and management practices for adults and children. She has published numerous multicenter trials and cohort studies in the area of sepsis, acute lung injury and severe pneumonia in children. She has received grants from the National Institutes of Health and the Centers for Disease Control and Prevention to study life-threatening and fatal influenza infection and leads a 40 center Pediatric Critical Care Influenza (PICFLU) Study Group. Her current research is focused on genetic susceptibility and immune response to severe infections and their sequelae in infants, children and adolescents. She also performs clinical-translational research on innate immune suppression and mechanisms underlying viral-bacterial coinfection in severe sepsis with a focus on Staphylococcus aureus toxins.
Dr. Kathryn (Kathy) Rowan
Dr Rowan is Director of Scientific & Strategic Development and Clinical Trials Unit Director at the Intensive Care National Audit & Research Centre (ICNARC). Kathy is an honorary Professor at the London School of Hygiene & Tropical Medicine, University of London. Following her PhD from the University of Oxford, in 1994, Kathy founded ICNARC, a not-for-profit organisation in the UK, to facilitate improvements in critical care – for patients and for those who care for them. ICNARC manages a broad programme of clinical audit and clinical/health services research, nationally and internationally. The ICNARC database of almost two million critical care admissions serves as a resource for studies on the epidemiology of critical illness and as a platform for randomised clinical trials – with the aim to inform practice and policy in critical care within the NHS. In 2004, Kathy was awarded the Humphry Davy Medal by the UK Royal College of Anaesthetists as a mark of distinction for her significant contribution to critical care. Kathy has co-authored 200+ peer-reviewed papers and won over £20m in research grants (£9m as Chief Investigator). Kathy is a member of the Council of the International Sepsis Forum.
Dr. Christopher Seymour
Dr. Seymour is Associate Professor of Critical Care and Emergency Medicine at the University of Pittsburgh School of Medicine. He is core faculty member in the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center in the Department of Critical Care. Dr. Seymour received his medical degree from the University of Pennsylvania before completing his internship and residency in Internal Medicine at the Hospital of the University of Pennsylvania. He then completed a fellowship in Pulmonary and Critical Care Medicine at the University of Washington, where he obtained master’s degree in clinical epidemiology at the University of Washington, School of Public Health. Dr. Seymour’s research program focuses on the development of early diagnostic and prognostic models to facilitate treatments for those with acute illness, particularly during prehospital and emergency care. His current NIH/NIGMS funded research (K23, R35), seeks to identify sepsis endotypes to target treatment in the emergency department. He spends his clinical time attending the Medical Intensive Care Unit at UPMC-Mercy Hospital.
Dr. Manu Shankar-Hari – ISF Fellow
Clinician-scientist in Intensive Care Medicine, and group lead for a translational research group at King’s College London.
Dr Shankar-Hari offers broad translational research skills, with clinical expertise allied to formal research training in basic science (Immunology PhD), and in epidemiology/ health services research (MSc). Currently funded by a prestigious UK NIHR Clinician Scientist Award to undertake a multi-centre randomised clinical trial of vaccinating sepsis survivors seeking to reduce reinfection risk and a large cohort study to explore longer-term outcomes following sepsis in the UK context using national databases.
Dr Shankar-Hari’s translational research is deeply influenced by CA Janeway’s work on lymphocyte receptor diversity, and G Rose’s conceptual arguments entitled ‘Sick individuals and sick populations’, which is reflected in the research programme he leads on
Immunobiology Lymphocyte abnormalities during in sepsis and in sepsis survivors
Translational epidemiology Methods to enrich sepsis and ARDS populations for immune therapy
Proximate (biological) determinants of critical illness and outcomes
Dr. Charles Sprung
Director Emeritus of the General Intensive Care Unit in the Department of Anesthesiology and Critical Care Medicine at Hadassah Hebrew University Medical Center where he has worked for the last 30 years. He was trained at the State University of New York- Downstate Medical Center in Internal Medicine and Critical Care Medicine. He was the Director of the Section of Critical Care Medicine in the Department of Medicine at the VA Medical Center and the University of Miami for 13 years. He graduated the University of Miami School of Law in 1988.
Professor Sprung was a council member of the Society of Critical Care Medicine (SCCM) from 1987 – 1994 and a council member of the European Society of Intensive Care Medicine (ESICM) from 1996-2010 and the Executive Committee from 2000-2010. He was the ESICM Treasurer from 2007-2010. He was the Chairman of the Committee on Ethics Section of the SCCM from 1987 to 1994 (and since that time has remained a member) and Chairman of the ESICM from 1996 to 2001 and again from 2004-2007 (he has remained a member of the Section for all these years).
Professor Sprung has been active in research particularly studying sepsis, septic shock and ethical issues for 35 years. He was a member of the ACCP/SCCM consensus conference on definitions of sepsis in 1991 and again in 2002. He has participated in many sepsis studies as an investigator, coordinator, clinical evaluation committee member or Safety and Efficacy Monitoring Committee member or chairman including those of encephalopathy and treatments with corticosteroids, monoclonal antibodies to endotoxin and tumor necrosis factor, interleukin-1 receptor antagonist, antithrombin III, tissue factor pathway inhibitor, human activated protein C and recombinant platelet-activating factor. His latest multicenter sepsis study “Corticosteroid therapy of septic shock- Corticus” was published in The New England Journal of Medicine. He has been the Coordinator of several multi-center studies in ethics including End of Life Decision Making and Procedures in European Intensive Care Units – ETHICUS, Systematic Study of General Ethical Principles Involved in End of Life Decisions for Patients in European Intensive Care Units – ETHICATT and Triage Decision Making for the Elderly in European Intensive Care units – ELDICUS. He has published extensively in all of these areas and has more than 300 original articles and 50 books or book chapters.
Dr. Jean-Louis Vincent- Past ISF Chair
Professor Vincent is Professor of intensive care medicine at the University of Brussels (Université Libre de Bruxelles) and intensivist in the Department of Intensive Care at Erasme University Hospital in Brussels. He obtained his PhD degree at the University of Brussels in 1982.
He is a Past-President of the World Federation of Societies of Intensive and Critical Care Medicine (WFSICCM), the European Society of Intensive Care Medicine (ESICM), the European Shock Society (ESS), the Belgian Society of Intensive Care Medicine (SIZ), and the International Sepsis Forum (ISF). He was a Council member of the Society of Critical Care Medicine (SCCM) from 2011-2013. He is member of the Belgian Royal Academy of Medicine.
Dr. Vincent has signed more than 900 original articles, some 400 book chapters and review articles, 1000 original abstracts, and has edited 102 books. He is co-editor of the “Textbook of Critical Care” (Elsevier Saunders) and the “Encyclopedia of Intensive Care Medicine” (Springer).
He is the editor-in-chief of Critical Care, Current Opinion in Critical Care, and ICU Management & Practice and member of the editorial boards of about 30 other journals, including Critical Care Medicine (senior editor), the American Journal of Respiratory and Critical Care Medicine (AJRCCM), PLoS Medicine, Lancet Infectious Diseases, Intensive Care Medicine, Shock, Journal of Critical Care and Annals of Intensive Care.
Dr Vincent has received several awards including including the College Medalist Award of the American College of Chest Physicians, the Society Medal (lifetime award) of the European Society of Intensive Care Medicine, the Distinguished Investigator Award, the Lifetime Achievement Award of the Society of Critical Care Medicine, and the prestigious Belgian scientific award of the FRS-FNRS (Prix Scientifique Joseph Maisin-Sciences biomédicales cliniques), he was awarded the title of Baron by King Albert II of Belgium.
His name appears more than 1000 times in Pubmed, and his work has been cited more than 150,000 times; his H-index is 159.
Professor W. Joost Wiersinga, MD, PhD, MBA
Professor of Medicine, Head, Division of Infectious Diseases, Department of Medicine, Academic Medical Center, University of Amsterdam, the Netherlands. He received his medical training at the University of Amsterdam with additional courses at the Mayo Clinic (Rochester, Minnesota) and the National Institutes of Health (NIH, Bethesda, MD). He serves on the executive committee of the ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS) and currently chairs the European Sepsis Academy.
Dr. Wiersinga received his PhD thesis entitled “On Toll-like receptors and the innate immune response in melioidosis”, cum laude, from the University of Amsterdam. During this period he worked in Bangkok at the Wellcome Trust Overseas Programme (supervisor professor Sharon Peacock). Previous awards included the O’Callaghan PhD award, the Andreas Bonn medallion, the GSK ICAAC award, the ESCMID Young Investigator Award and the ANZICS Global Rising Star Award 2015.
Dr. Wiersinga divides his time between patient care, teaching and research in the Center for Experimental Molecular Medicine (CEMM) all at the Academic Medical Center, Amsterdam. The focus of his Translational infectious diseases research group is on host-pathogen interactions and innate immune responses in sepsis with a special interest in pneumonia, cellulitis and melioidosis as well as optimization of antibiotic therapy. Recent interests include the role of the gut microbiota during sepsis. His work has been published in among others Nat Rev Microbiol, Gut, JAMA Internal Medicine, PLoS Medicine and N Engl J Med.