Institution
John Radcliffe Hospital
Healthcare•Oxford, Oxfordshire, United Kingdom•
About: John Radcliffe Hospital is a healthcare organization based out in Oxford, Oxfordshire, United Kingdom. It is known for research contribution in the topics: Population & Antigen. The organization has 14491 authors who have published 23670 publications receiving 1459015 citations.
Topics: Population, Antigen, Transplantation, Cytotoxic T cell, Immune system
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John Radcliffe Hospital1, Warner Chilcott2, University of Miami3, University of Oxford4, Lille University of Science and Technology5, University of Western Ontario6, University of Chicago7, University of Paris8, University of Pennsylvania9, Medical University of Vienna10, Icahn School of Medicine at Mount Sinai11, University of Cincinnati12, French Institute of Health and Medical Research13, University of California, San Diego14
TL;DR: The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC and needs further testing before it can be applied as an outcome measure in clinical trials or clinical practice.
Abstract: Background Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC) Objective To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated Design A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0–11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0–100 visual analogue scale κ Statistics tested inter- and intraobserver variability for each descriptor A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors Results There was 76% agreement for ‘severe’, but 27% agreement for ‘normal’ appearances between phase I investigators and the central reader In phase 2, weighted κ values ranged from 034 to 065 and 030 to 045 within and between observers for the 10 descriptors The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR 2 , Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity) Conclusion The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice
448 citations
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TL;DR: In the first study of the prognosis of ≥50% asymptomatic carotid stenosis to be initiated in the last 10 years, the risk of stroke on intensive contemporary medical treatment was low.
Abstract: Background and Purpose— The annual risk of ischemic stroke distal to ≥50% asymptomatic carotid stenoses was ≈2% to 3% in early cohort studies and subsequent randomized trials of endarterectomy. This risk might have fallen in recent years owing to improvements in medical treatment, but there are no published prognostic data from studies initiated within the last 10 years. Methods— In a population-based study of all patients with transient ischemic attack (TIA) or stroke in the Oxford Vascular Study, we studied the risk of TIA and stroke in patients with ≥50% contralateral asymptomatic carotid stenoses recruited consecutively from 2002 to 2009 and given intensive contemporary medical treatment. Results— Of 1153 consecutively imaged patients presenting with stroke or TIA, 101 (8.8%) had ≥50% asymptomatic carotid stenoses (mean age, 75 years; 39% women; 40% age ≥80 years). During 301 patient-years of follow-up (mean, 3 years), there were 6 ischemic events in the territory of an asymptomatic stenosis, 1 minor ...
448 citations
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TL;DR: It is shown that the activation level and the differentiation state of T-cells are closely related and may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system.
Abstract: Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis However, the basis of this association remains unclear Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naive CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells HIV disease progression correlates with increased proportions of highly differentiated CD8(+) T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process It can be driven by excessive levels of immune stimulation This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system
448 citations
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Broad Institute1, Harvard University2, University of Liège3, University of Oxford4, Wellcome Trust Sanger Institute5, Montreal Heart Institute6, University of Southern Denmark7, Katholieke Universiteit Leuven8, John Radcliffe Hospital9, Wellcome Trust Centre for Human Genetics10, Karolinska Institutet11, Ikerbasque12, Illumina13, University of Kiel14, Örebro University15, Cedars-Sinai Medical Center16, Lancaster University17, University of Western Australia18, Western General Hospital19, Norwegian University of Life Sciences20, Wellcome Trust21, University of Groningen22, University Medical Center Groningen23, University of Pittsburgh24, King's College London25, University of the Witwatersrand26, Université de Montréal27, Yale University28
TL;DR: The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.
Abstract: Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.
447 citations
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TL;DR: Assessment of the epidemiological characteristics of malaria in Kilifi, Kenya during a period of decreasing transmission intensity finds sustained reduction in exposure to infection leads to changes in mean age and presentation of disease similar to those described in multisite studies.
447 citations
Authors
Showing all 14542 results
Name | H-index | Papers | Citations |
---|---|---|---|
Douglas G. Altman | 253 | 1001 | 680344 |
Salim Yusuf | 231 | 1439 | 252912 |
David J. Hunter | 213 | 1836 | 207050 |
Mark I. McCarthy | 200 | 1028 | 187898 |
Stuart H. Orkin | 186 | 715 | 112182 |
Richard Peto | 183 | 683 | 231434 |
Ralph M. Steinman | 171 | 453 | 121518 |
Adrian L. Harris | 170 | 1084 | 120365 |
Rory Collins | 162 | 489 | 193407 |
Nicholas J. White | 161 | 1352 | 104539 |
David W. Johnson | 160 | 2714 | 140778 |
David Cella | 156 | 1258 | 106402 |
Edmund T. Rolls | 153 | 612 | 77928 |
Martin A. Nowak | 148 | 591 | 94394 |
Kypros H. Nicolaides | 147 | 1302 | 87091 |