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Stephen J Chapman

Bio: Stephen J Chapman is an academic researcher from University of Oxford. The author has contributed to research in topics: Dislocation & Nonlinear system. The author has an hindex of 37, co-authored 160 publications receiving 5715 citations. Previous affiliations of Stephen J Chapman include Wellcome Trust Centre for Human Genetics & Veterans Health Administration.


Papers
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Journal ArticleDOI
TL;DR: In this paper, a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis was conducted.
Abstract: Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.

457 citations

Journal ArticleDOI
TL;DR: Insight is provided into the genetic architecture of infectious disease susceptibility and immune molecules and pathways that are directly relevant to the human host defence are identified.
Abstract: Recent genome-wide studies have reported novel associations between common polymorphisms and susceptibility to many major infectious diseases in humans In parallel, an increasing number of rare mutations underlying susceptibility to specific phenotypes of infectious disease have been described Together, these developments have highlighted a key role for host genetic variation in determining the susceptibility to infectious disease They have also provided insights into the genetic architecture of infectious disease susceptibility and identified immune molecules and pathways that are directly relevant to the human host defence

429 citations

Journal ArticleDOI
Josephine M. Bryant1, Josephine M. Bryant2, Dorothy M Grogono3, Dorothy M Grogono2, Daniela Rodriguez-Rincon2, Isobel Everall1, Karen Brown2, Karen Brown3, Pablo Moreno4, Deepshikha Verma5, Emily Hill5, Judith Drijkoningen2, Peter H. Gilligan6, Charles R. Esther6, Peadar G. Noone6, Olivia Giddings6, Scott C. Bell7, Scott C. Bell8, Rachel Thomson8, Claire E. Wainwright9, Claire E. Wainwright8, Chris Coulter, Sushil Pandey, Michelle Wood7, Michelle Wood8, Rebecca E Stockwell7, Rebecca E Stockwell8, Kay A. Ramsay7, Kay A. Ramsay8, Laura J. Sherrard7, Timothy J. Kidd10, Timothy J. Kidd8, Nassib Jabbour11, Graham R. Johnson11, Luke D. Knibbs8, Lidia Morawska11, Peter D. Sly8, Andrew Jones12, Diana Bilton12, Ian F. Laurenson, Michael Ruddy13, Stephen Bourke14, Ian C. J. W. Bowler15, Stephen J Chapman15, Andrew Clayton16, Mairi Cullen17, Owen J. Dempsey18, Miles Denton19, M. Desai9, Richard J Drew, Frank Edenborough, Jason T. Evans13, Jonathan Folb20, Thomas Daniels21, Helen Humphrey21, Barbara Isalska17, Søren Jensen-Fangel22, Bodil Jönsson23, Andrew M Jones17, Terese L. Katzenstein24, Troels Lillebaek25, Gordon MacGregor26, Sarah Mayell, Michael Millar27, Deborah E. Modha28, Edward F. Nash29, C. O'Brien14, Deirdre O'Brien, Chandra Ohri28, Caroline S. Pao27, Daniel Peckham19, Felicity Perrin30, Audrey Perry14, Tania Pressler24, Laura Prtak, Tavs Qvist24, Ali Robb14, Helen Rodgers31, Kirsten Schaffer, Nadia Shafi3, Jakko van Ingen32, Martin Walshaw, Danie Watson27, Noreen West12, Joanna L. Whitehouse29, Charles S. Haworth3, Simon R. Harris1, Diane J. Ordway5, Julian Parkhill1, R. Andres Floto2, R. Andres Floto3 
11 Nov 2016-Science
TL;DR: Using whole-genome analysis of a global collection of clinical isolates, it is shown that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally.
Abstract: Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

396 citations

11 Nov 2016
TL;DR: In this paper, the authors used whole-genome analysis of a global collection of clinical isolates to show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones.
Abstract: Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

344 citations

Journal ArticleDOI
01 Aug 2010-Thorax
TL;DR: This document, which will use the term ‘local anaesthetic thoracoscopy’, aims to consider the following issues and to make appropriate recommendations on the basis of evidence where available.
Abstract: Thoracoscopy under local anaesthetic and intravenous sedation, also known as local anaesthetic thoracoscopy, medical thoracoscopy or pleuroscopy, is increasingly being performed by chest physicians in the UK. In 1999, 11 centres across the UK offered a local anaesthetic thoracoscopy service, increasing to 17 centres in May 20041 and 37 centres in 2009 (Dr N Downer, personal communication). This document, which will use the term ‘local anaesthetic thoracoscopy’, aims to consider the following issues and to make appropriate recommendations on the basis of evidence where available: Creation of this guideline followed the Appraisal of Guidelines Research and Evaluation/Scottish Intercollegiate Guidelines Network (AGREE/SIGN) methodology of evidence assessment and integration (see introduction to pleural disease guidelines). Is there a need for a physician-based local anaesthetic thoracoscopy service in the UK? The majority of local anaesthetic thoracoscopy is carried out in the context of an undiagnosed exudative pleural effusion, the commonest cause of which is malignancy.2 This section of the document will therefore focus mainly on local anaesthetic thoracoscopy in the context of malignant disease. ### The increasing burden of pleural disease Malignant pleural effusion is a common clinical problem. Although the incidence of lung cancer in the UK is falling, the incidence of other cancers is rising. With increasing life expectancy in an ageing population and at current cancer incidence rates, an additional 100 000 cases of cancer per year are expected by 2025.3 Up to 15% of patients who die with malignancy have a pleural effusion at autopsy.4 Studies suggest that exudative effusions are caused by malignancy …

297 citations


Cited by
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Journal ArticleDOI
TL;DR: To the best of our knowledge, there is only one application of mathematical modelling to face recognition as mentioned in this paper, and it is a face recognition problem that scarcely clamoured for attention before the computer age but, having surfaced, has attracted the attention of some fine minds.
Abstract: to be done in this area. Face recognition is a problem that scarcely clamoured for attention before the computer age but, having surfaced, has involved a wide range of techniques and has attracted the attention of some fine minds (David Mumford was a Fields Medallist in 1974). This singular application of mathematical modelling to a messy applied problem of obvious utility and importance but with no unique solution is a pretty one to share with students: perhaps, returning to the source of our opening quotation, we may invert Duncan's earlier observation, 'There is an art to find the mind's construction in the face!'.

3,015 citations

Journal ArticleDOI
TL;DR: This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response and medical implications are discussed.
Abstract: Summary: The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.

2,565 citations

Journal ArticleDOI
TL;DR: The function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF, and it is shown that it acts as a bridging adaptor in the initiation of TLR signalling.
Abstract: Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM. Recent insights have revealed additional functions for MyD88 apart from NF-kappaB activation, including activation of the transcription factors IRF1, IRF5 and IRF7, and also a role outside the TLRs in interferon-gamma signalling. Biochemical information on MAL and TRAM has shown that both act as bridging adaptors, with MAL recruiting MyD88 to TLR2 and TLR4, and TRAM recruiting TRIF to TLR4 to allow for IRF3 activation. Finally, the function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF. These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling.

2,474 citations

01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

2,187 citations

Dissertation
01 Oct 1948
TL;DR: In this article, it was shown that a metal should be superconductive if a set of corners of a Brillouin zone is lying very near the Fermi surface, considered as a sphere, which limits the region in the momentum space completely filled with electrons.
Abstract: IN two previous notes1, Prof. Max Born and I have shown that one can obtain a theory of superconductivity by taking account of the fact that the interaction of the electrons with the ionic lattice is appreciable only near the boundaries of Brillouin zones, and particularly strong near the corners of these. This leads to the criterion that the metal should be superconductive if a set of corners of a Brillouin zone is lying very near the Fermi surface, considered as a sphere, which limits the region in the momentum space completely filled with electrons.

2,042 citations