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International audience ; Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions.Methods and analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

International audience ; Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions.Methods and analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

International audience ; Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions.Methods and analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

Introduction Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. Methods and analysis This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. ; This work is supported by the European Union's Horizon 2020 research and innovation programme (grant n ̊ 848158). ; Peer reviewed

Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards the shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. Methods and analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shapes an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life-course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.

Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards shared risk of these diseases and the development of coordinated preventive and therapeutic interventions. Methods and analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union's Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shape an individual's physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk. Ethics and dissemination: The study has been approved by the Ethics Board of the European Commission. The results ...

Researchers increasingly use meta-analysis to synthesize the results of several studies in order to estimate a common effect. When the outcome variable is continuous, standard meta-analytic approaches assume that the primary studies report the sample mean and standard deviation of the outcome. However, when the outcome is skewed, authors sometimes summarize the data by reporting the sample median and one or both of (i) the minimum and maximum values and (ii) the first and third quartiles, but do not report the mean or standard deviation. To include these studies in meta-analysis, several methods have been developed to estimate the sample mean and standard deviation from the reported summary data. A major limitation of these widely used methods is that they assume that the outcome distribution is normal, which is unlikely to be tenable for studies reporting medians. We propose two novel approaches to estimate the sample mean and standard deviation when data are suspected to be non-normal. Our simulation results and empirical assessments show that the proposed methods often perform better than the existing methods when applied to non-normal data. ; anadian Institutes of Health Research (CIHR) KRS-134297 Fonds de recherche du Quebec -Sante (FRQS) Canadian Institutes of Health Research (CIHR) Canadian Institutes of Health Research (CIHR) FRQS Masters Training Awards Vanier Canada Graduate Scholarship FRQS Postdoctoral Training Fellowship Research Institute of the McGill University Health Centre G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University Cumming School of Medicine, University of Calgary Alberta Health Services through the Calgary Health Trust Hotchkiss Brain Institute Senior Health Scholar award from Alberta Innovates Health Solutions Health Research Council of New Zealand Lundbeck International Tehran University of Medical Sciences M-288 Department of Education, National Institute on Disability and Rehabilitation Research, Spinal Cord Injury Model Systems: University of Washington H133N060033 Baylor College of Medicine H133N060003 University of Michigan System H133N060032 National Health and Medical Research Council of Australia 1002160 Safe Work Australia Australian Research Council FT130101444 European Foundation for Study of Diabetes Chinese Diabetes Society Lilly Foundation Asia Diabetes Foundation Liao Wun Yuk Diabetes Memorial Fund United States National Institute of Mental Health (NIMH) grant 5F30MH096664 United States Department of Health & Human Services National Institutes of Health (NIH) - USA United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Fogarty International Center (FIC) United States Department of Health & Human Services National Institutes of Health (NIH) - USA National Cancer Center United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) NIH Office of Research for Women's Health through the Fogarty Global Health Fellows Program Consortium 1R25TW00934001 American Recovery and Reinvestment Act United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) R24MH071604 / R34 MH072925/ K02 MH65919 / P30 DK50456 / R24 MH56858 / RO1 MH073687 /RO1-MH069666 / R34MH084673 /R24 MH071604 United States Department of Health & Human Services Centers for Disease Control & Prevention - USA R49 CE002093 St Anne's Community Services, Leeds, UK US National Center for Medical Rehabilitation Research RO1 HD39415 Federal Ministry of Education & Research (BMBF) 01GY1150 United States Department of Health & Human Services National Institutes of Health (NIH) - USA T37 MD001449 / T32 GM07356 Ohio Board of Regents Research and Development Administration Office, University of Macau MYRG2015-00109-FSS Federal Ministry of Education & Research (BMBF) 01 GD 9802/4 ; 01 GD 0101 Federation of German Pension Insurance Institute Federal Ministry of Education & Research (BMBF) Perpetual Trustees Flora and Frank Leith Charitable Trust Jack Brockhoff Foundation Grosvenor Settlement Sunshine Foundation Danks Trust Canadian Institutes of Health Research (CIHR) FRN 83518 Scleroderma Society of Canada Scleroderma Society of Ontario Scleroderma Society of Saskatchewan Sclerodermie Quebec Cure Scleroderma Foundation Inova Diagnostics Inc Euroimmun FRQS Canadian Arthritis Network Lady Davis Institute of Medical Research of the Jewish General Hospital, Montreal, QC FRQS Senior Investigator Award National Strategic Reference Framework European Union (EU) Greek Ministry of Education, Lifelong Learning and Religious Affairs (ARISTEIA-ABREVIATE) 1259 Ministry of Health, Labour and Welfare, Japan UK National Institute for Health Research under its Programme Grants for Applied Research Programme RP-PG-0606-1142 Canada Research Chair in Neurological Health Services Research AIHS Population Health Investigator Award National Health and Medical Research Council of Australia 1088313 Netherlands Organization for Health Research and Development 945-03-047 National Health Research Institutes - Taiwan NHRI-EX97-9706PI Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 49086 Reitoria de Pesquisa da Universidade de Sao Paulo 09.1.01689.17.7 Banco Santander 10.1.01232.17.9 Pfizer medical faculty of the University of Heidelberg, Germany 121/2000 Research University Grant Scheme from Universiti Putra Malaysia, Malaysia Postgraduate Research Student Support Accounts of the University of Auckland, New Zealand National Program for Centers of Excellence (PRONEX/FAPERGS/CNPq, Brazil) Pfizer US Pharmaceutical Inc. PQ-CNPq-2 301321/2016-7 Belgian Ministry of Public Health and Social Affairs Pfizer Ministry of Health, Italy UK National Health Service Lothian Neuro-Oncology Endowment Fund Universiti Sains Malaysia United States Department of Health & Human Services United States Health Resources & Service Administration (HRSA) R40MC07840 United States Department of Health & Human Services Agency for Healthcare Research & Quality R36 HS018246 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Research Resources (NCRR) TL1 RR024135 University of Melbourne Hunter Medical Research Institute Innovatiefonds Zorgverzekeraars Netherlands Organization for Health Research and Development (ZonMw) Mental Health Program 100.003.005 100.002.021 Academic Medical Center/University of Amsterdam Fund for Innovation and Competitiveness of the Chilean Ministry of Economy, Development and Tourism, through the Millennium Scientific Initiative IS130005 US Department of Veteran Affairs US Department of Veteran Affairs United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) R01 HL079235 American Federation for Ageing Research Robert Wood Johnson Foundation (RWJF) Ischemia Research and Education Foundation