Suchergebnisse

Funding Information: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) Reference 104036/Z/14/Z). CG is supported by The Medical Research Council and The University of Edinburgh through the Precision Medicine Doctoral Training program. SRC is supported by the UK Medical Research Council [MR/R024065/1] and a National Institutes of Health (NIH) research grant R01AG054628. Acknowledgements The authors thank all of the STRADL and Generation Scotland participants for their time and effort taking part in this study. We would also like to thank all of the research assistants, clinicians and technicians for their help in the collecting this data. ; Peer reviewed ; Publisher PDF

Funding: JW and NARG thank the Wellcome Trust (080088, 086827, 075470), The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) for funding. MGN was supported by a Vici grant of the Netherlands Organisation for Scientific Research. AJPB and DMM were funded by STRIFE, ERC-2009-AdG-249793 and AJPB additionally by FINSysB, PITN-GA-2008-214004 and the BBSRC [BB/F00513X/1]. MDL was supported by the MRC (MR/J008230/1). GDB and SV were funded by the Wellcome Trust (086558) and TB and MK were funded by the Deutsche Forschungsgemeinschaft (Bi 696/3-1; Bi 696/5-2; Bi 696/10-1). MS was supported by the Deutsche Forschungsgemeinschaft (Sch 897/1-3) and the National Institute of Dental and Craniofacial Research (R01 DE017514-01). TDK and RKSM were funded by the National Institute of Health (AR056296, AI101935) and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Peer reviewed ; Publisher PDF

As breast-milk substitutes became increasingly sophisticated and heavily marketed in the mid-twentieth century, bottle-feeding became regarded worldwide as safe, convenient, normal and even preferable to breastfeeding. From 1975, research conducted in the developing world, particularly Gambia, began to converge with work on immunology and child psychology to reassert the value of mothers' own milk. At the same time, growing understanding of physiology, reproductive and developmental biology shifted interest from the composition of infant formulae to the biology of infant feeding. Insights from comparative zoology, dairy science and animal husbandry, shared with research in human lactation and 'naturalization' of childbirth all helped to de-medicalize infant feeding. Chaired by Professor Lawrence Weaver, this Witness Seminar was attended by representatives from women's groups, pressure groups and international organizations, including Baby Milk Action, IBFAN, La Leche League, the National Childbirth Trust, WHO and UNICEF, as well as paediatricians, obstetricians, physiologists, nutritional scientists, zoologists, psychologists and members of industry. The discussion addressed the critical events, scientific advances, and social and political steps that drove the resurgence of breastfeeding, focusing not only on the nutritional science but also on the social context in which the changes took place. Participants included: Mr James Akre, Professor Elizabeth Alder, Mrs Phyll Buchanan, Professor Forrester Cockburn, Ms Rosie Dodds, Mrs Jill Dye, Professor Fiona Dykes, Ms Hilary English, Miss Chloe Fisher, Professor Anna Glasier, Professor Lars Hanson, Dr Elisabet Helsing, Dr Edmund Hey, Professor Peter Howie, Professor Alan McNeilly, Professor Kim Michaelsen, Mrs Rachel O'Leary, Ms Gabrielle Palmer, Professor Malcolm Peaker, Dr Ann Prentice,Professor Mary Renfrew, Mrs Patti Rundall, Ms Ellena Salariya, Dr Felicity Savage, Professor Roger Short, Dr Mary Smale, Dr Alison Spiro, Dr Penny Stanway, Dr Tilli Tansey, Mrs Jenny Warren, Mr John Wells, Professor Brian Wharton, Professor Roger Whitehead, Dr Anthony Williams, Miss Carol Williams and Dr Michael Woolridge.

Genome-wide association studies have been tremendously successful in identifying genetic variants associated with complex diseases. The majority of association signals are intergenic and evidence is accumulating that a high proportion of signals lie in enhancer regions. We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. Here we report numerous looping interactions and provide evidence that only a minority of interactions are common to both B- and T-cell lines, suggesting interactions may be highly cell-type specific; some disease-associated SNPs do not interact with the nearest gene but with more compelling candidate genes (for example, FOXO1, AZI2) often situated several megabases away; and finally, regions associated with different autoimmune diseases interact with each other and the same promoter suggesting common autoimmune gene targets (for example, PTPRC, DEXI and ZFP36L1). ; We thank Frank Dudbridge for providing the R scripts to analyse the interaction data. We would like to acknowledge the Faculty of Life Sciences Genomics Facility, the assistance given by IT Services and the use of the Computational Shared Facility at The University of Manchester. This work was funded by Arthritis Research UK (grant numbers 20385, 20571 (K.D.)); Wellcome Trust Research Career Development Fellowship (G.O., AM 095684); Wellcome Trust (097820/Z/11/B); S.E. is supported through the European Union's FP7 Health Programme, under the grant agreement FP7-HEALTH-F2-2012-305549 (Euro-TEAM). A.Y. is supported by the Innovative Medicines Initiative (BeTheCure project 115142); C.W. by the Wellcome Trust (089989); C.W. and N.C. by the Wellcome Trust (091157), JDRF (9-2011-253) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). The research leading to ...

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8) ; Peer reviewed ; Publisher PDF

The 1974 reorganization of the National Health Service was largely seen as a disaster for the public health profession. The post of Medical Officer of Health, with its links to local government, was replaced by the community physician, located within health services. The technician-manager rather than the activist role predominated: community medicine doctors carried little weight by comparison with their clinical colleagues. Chaired by Professor Virginia Berridge this Witness Seminar examined the decline and rise of 'public health' both nationally and internationally in the 1980s and 1990s: the impact of the 1988 Acheson Report on public health medicine on a demoralized profession; the role of new ideas about health promotion imported from the international scene; the rise of evidence-based medicine and health services research, and their impact on public health; and the movement for multidisciplinary public health (MDPH) as a new avenue for public health from the 1990s. Participants included Professor Sir Donald Acheson, Professor John Ashton, Professor Nick Black, Professor David Blane, Dr Tim Carter, Sir Iain Chalmers, Dr Aileen Clarke, Dr June Crown, Dr Jeff French, Professor Alan Glynn, Ms Shirley Goodwin, Professor Rod Griffiths, Professor Walter Holland, Professor Klim McPherson, Dr Ornella Moscucci, Dr Geoffrey Rivett, Professor Alwyn Smith and Professor Ann Taket.

Unrelieved pain caused by cancer is experienced by more than 5 million people worldwide, and over the past 50 years has been accepted as unnecessary by both clinicians and politicians. Major innovations in the understanding of pain and our ability to treat it have been made. This Witness Seminar, chaired by Professor David Clark, describes the development of clinics, the introduction of the hospice in Britain, and global implementation of innovative technologies for cancer pain relief and advances in research during the latter part of the twentieth century, including the '3-step pain ladder' to pain relief. International health planners argue that the outstanding challenge is to put this knowledge into practice in healthcare settings around the world, often where resources are limited. An extract from an annotated Physiological Society interview with Patrick Wall in 1999 plus a note on the optimal potential for benefit of morphine by Professor Jan Stjernswärd appear as appendices. Participants include Professor Sir Michael Bond, Dr Suresh Kumar, Dr Colin, Murray Parkes, Dame Cicely Saunders, Professor Jan Stjernswärd, the late Dr Mark Swerdlow, Dr Robert Twycross and Professor Duncan Vere.

This transcript considers the origins and impact of the MRC Applied Psychology Unit's work from 1944 to 1998. Psychologists, clinicians, and industrial, ergonomic and occupational psychologists discuss the evolution of work from quite narrow postwar industrial and military concerns to more recent applications in, for example, ageing, dyslexia, depression, form design, information and semantics. Those who contributed included Professor Alan Baddeley, Dr Philip Barnard, Dr Ivan Brown, Professor Sergio Della Sala, Mr David C Duncan, Professor Richard Gregory (Chair), Professor John Groeger, Professor Graham Hitch, Professor Robert Logie, Dr Brandon Lush, Professor William Marslen-Wilson, Professor Peter McLeod, Professor Pat Rabbitt, Professor Graham Richards, Dr David Tyrrell, Professor John West. Introduction by Geoff Bunn and Lois Reynolds, 19 illus, biographical notes, subject and name index, 111pp.

Acknowledgments The authors thank the Wellcome Trust Sanger Institute's core sequencing teams for generating sequence data. Funding This study was funded by the Biotechnology and Biological Sciences Research Council, BBSRC Institute Strategic Programme for Gut Health and Food Safety, grant BB/J004529/1; 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051) (to P.S., J.P., A.W.W.); core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (to A.W.W. and the Rowett Institute of Nutrition and Health, University of Aberdeen); the Association for International Cancer Research (AICR), Scotland, grant number 120234 (to H.O.A.); and the Junta de Castilla y León, Spain (SAN196/VA16/07 and SAN196/VA17/07). ; Peer reviewed ; Publisher PDF

Acknowledgements This research has been conducted using the UK Biobank Resource: application number 4844. We are grateful to the families who took part in GS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team that includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award 'STratifying Resilience and Depression Longitudinally' (STRADL) Reference 104036/Z/14/Z). We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. DJP, IJD and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged ; Peer reviewed ; Publisher PDF

AstraZeneca ; European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.) ; Wellcome Trust (102696 and 206194)

This project was funded by DPUK through MRC (grant no. MR/L023784/2) and the UK Medical Research Council Award to the University of Oxford (grant no. MC_PC_17215). L.S is funded by the Virtual Brain Cloud from European comission (grant no. H2020-SC1-DTH-2018-1). C.R.B is funded by National Institutes of Health (NIH) research grant R01AG054628. S.R.C is funded by National Institutes of Health (NIH) research grant (R01AG054628), Medical Research Council (MR/R024065/1), Age UK and Economic and Social Research Council. R.E.M. was supported by Alzheimer's Research UK major project grant ARUKPG2017B-10. C.H was supported by an MRC Human Genetics Unit programme grant "Quantitative traits in health and disease" (U.MC_UU_00007/10). H.C.W received funding from Wellcome Trust. J.W is funded by TauRx pharmaceuticals Ltd and received Educational grant from Biogen paid to Alzheimer Scotland/Brain Health Scotland. G.W received GRAMPIAN UNIVERSITY HOSPITALS NHS TRUST, Scottish Government—Chief Scientist Office, ROLAND SUTTON ACADEMIC TRUST, Medical Research Scotland, Sutton Academic Trust and ROLAND SUTTON ACADEMIC TRUST. J.M.W received Wellcome Trust Strategic Award, MRC UK Dementia Research Institute and MRC project grants, Fondation Leducq, Stroke Association, British Heart Foundation, Alzheimer Society, and the European Union H2020 PHC-03-15 SVDs@Target grant (666881). D.S received MRC (MR/S010351/1), MRC (MR/W002388/1) and MRC (MR/W002566/1). A.M is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 847776. In addition, A.M has received grant support from The Sackler Trust, outside of the work presented. N.B received grant to institution from GSK as part of GSK/Oxford FxG initiative. A.N.H received John Black Charitable Fund-Rosetrees, H2020 funding from European Comission-Project Virtual Brain Cloud, AI for the Discovery of new therapies in Parkinson's (A2926), Rising Start Initiative—stage 2, Brain-Gut Microbiome (Call: PAR-18-296; Award ID: 1U19AG063744-01), Gut-liver-brain biochemical axis in Alzheimer's disease (5RF1AG057452-01), Virtual Brain Cloud (Call: H2020-SC1-DTH- 2018-1; Grant agreement ID: 826421). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006) and is currently supported by the Wellcome Trust (216767/Z/19/Z). Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" [STRADL] Reference 104036/Z/14/Z). We are grateful to all the families who took part; the general practitioners and the Scottish School of Primary Care for their help in recruiting them; and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants, and nurses. ; Peer reviewed ; Publisher PDF

The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation. ; This work was supported by funds from the Wellcome Trust WT090323MA and MRC G1000236. MR/L018373/1. This work was also supported by a Wellcome Trust Principal Research Fellowship (WT101835) to PJL and a Wellcome Trust Senior Fellowship (108070/Z/15/Z) to MPW and a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140). JAP was supported by NIH/NIDDK grant K01 DK098285. BV was supported by projects MEYS – NPS I – LO1413 and Czech Science Foundation P206/12/G151. ER was supported by MH CZ-DRO (MMCI, 00209805). CC and JT were supported by grant G0901682 from the MRC and funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 695551), with partial funding from the National Institute of Health Cambridge Biomedical Research Centre.

Supported by Wellcome Trust project grant 088208 to A.L.D., J.M.W., D.M.P., I.C.Z., and J.F.M. Wellbeing of Women research training fellowship 318 to D.J.C., Scottish Government work package 4.2 to J.M.W., J.S.M., and R.P.A., as well as funding from the National Institute for Health Research University College London Hospitals Biomedical Research Centre A.L.D. and D.M.P., the British Heart Foundation to I.C.Z., and Ark Therapeutics Oy, Kuopio, Finland, which supplied adenovirus vectors free of charge. ; Peer reviewed ; Publisher PDF