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Plymouth, United Kingdom

Smith A.J.,University of Bristol | Dieppe P.,Universities of Plymouth and Exeter | Howard P.W.,Royal Derby Hospital | Blom A.W.,University of Bristol
The Lancet | Year: 2012

Background Implant survival after conventional total hip replacement (THR) is often poor in younger patients, so alternatives such as hip resurfacing, with various sizes to fit over the femoral head, have been explored. We assessed the survival of different sizes of metal-on-metal resurfacing in men and women, and compared this survival with those for conventional stemmed THRs. Methods We analysed the National Joint Registry for England and Wales (NJR) for primary THRs undertaken between 2003 and 2011. Our analysis involved multivariable flexible parametric survival models to estimate the covariateadjusted cumulative incidence of revision adjusting for the competing risk of death. Findings The registry included 434 560 primary THRs, of which 31 932 were resurfacings. In women, resurfacing resulted in worse implant survival than did conventional THR irrespective of head size. Predicted 5-year revision rates in 55-year-old women were 8·3% (95% CI 7·2-9·7) with a 42 mm resurfacing head, 6·1% (5·3-7·0) with a 46 mm resurfacing head, and 1·5% (0·8-2·6) with a 28 mm cemented metal-on-polyethylene stemmed THR. In men with smaller femoral heads, resurfacing resulted in poor implant survival. Predicted 5-year revision rates in 55-year-old men were 4·1% (3·3-4·9) with a 46 mm resurfacing head, 2·6% (2·2-3·1) with a 54 mm resurfacing head, and 1·9% (1·5-2·4) with a 28 mm cemented metal-on-polyethylene stemmed THR. Of male resurfacing patients, only 23% (5085 of 22076) had head sizes of 54 mm or above. Interpretation Hip resurfacing only resulted in similar implant survivorship to other surgical options in men with large femoral heads, and inferior implant survivorship in other patients, particularly women. We recommend that resurfacing is not undertaken in women and that preoperative measurement is used to assess suitability in men. Before further new implant technology is introduced we need to learn the lessons from resurfacing and metal-onmetal bearings.

Warshow U.M.,Universities of Plymouth and Exeter | Warshow U.M.,South West Liver Unit | Riva A.,Institute of Hepatology | Hegazy D.,Universities of Plymouth and Exeter | And 6 more authors.
Journal of Viral Hepatitis | Year: 2012

A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment-naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV-Ab+ and HCV-RNA)) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL-6 (on average more than 100-fold, P = 0.001) and IL-8 (on average more than 10-fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor-alpha (TNF-α; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon-alpha (IFN-α) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro-inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin-6 and interleukin-8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort. © 2012 Blackwell Publishing Ltd.

Sparrow D.B.,Victor Chang Cardiac Research Institute | Sparrow D.B.,University of New South Wales | Sillence D.,University of Sydney | Wouters M.A.,Victor Chang Cardiac Research Institute | And 4 more authors.
European Journal of Human Genetics | Year: 2010

Spondylocostal dysostosis (SCD) is an inherited disorder with abnormal vertebral segmentation that results in extensive hemivertebrae, truncal shortening and abnormally aligned ribs. It arises during embryonic development by a disruption of formation of somites (the precursor tissue of the vertebrae, ribs and associated tendons and muscles). Four genes causing a subset of autosomal recessive forms of this disease have been identified: DLL3 (SCDO1: MIM 277300), MESP2 (SCDO2: MIM 608681), LFNG (SCDO3: MIM609813) and HES7 (SCDO4). These genes are all essential components of the Notch signalling pathway, which has multiple roles in development and disease. Previously, only a single SCD-causative missense mutation was described in HES7. In this study, we have identified two new missense mutations in the HES7 gene in a single family, with only individuals carrying both mutant alleles being affected by SCD. In vitro functional analysis revealed that one of the mutant HES7 proteins was unable to repress gene expression by DNA binding or protein heterodimerization. © 2010 Macmillan Publishers Limited All rights reserved.

Lambe P.,Universities of Plymouth and Exeter | Waters C.,Universities of Plymouth and Exeter | Bristow D.,Universities of Plymouth and Exeter
Medical Teacher | Year: 2012

Background: The United Kingdom Clinical Aptitude Test (UKCAT) is designed to increase diversity and fairness in selection to study medicine. Aim: The aim of this study is to determine if differences in: access to support and advice, in modes of preparation, type of school/college attended, level of achievement in mathematics, gender and age influence candidate performance in the UKCAT and thereby unfairly advantage some candidates over others. Methods: Confidential, self-completed, on-line questionnaire of applicants to study on an undergraduate medical degree course who had taken the UKCAT in 2010. Results: Differentials in access to support and advice, in modes of preparation, type of school/college attended, in level of achievement in mathematics, gender and age were found to be associated with candidate performance in the UKCAT. Conclusion: The findings imply that the UKCAT may disadvantage some candidate groups. This inequity would likely be improved if tutors and career advisors in schools and colleges were more informed about the UKCAT and able to offer appropriate advice on preparation for the test. © 2012 Informa UK Ltd All rights reserved.

Thurairajah P.H.,Universities of Plymouth and Exeter | Hegazy D.,Universities of Plymouth and Exeter | Demaine A.,Universities of Plymouth and Exeter | Kaminski E.R.,Universities of Plymouth and Exeter | And 2 more authors.
Journal of Infectious Diseases | Year: 2011

Introduction. Hepatitis C virus (HCV)-specific T lymphocyte responses have been demonstrated in peripheral blood from injection drug users (IDUs) persistently HCV antibody and RNA negative despite high-risk behavior. We have termed these apparently HCV resistant cases "Exposed Uninfecteds" (EUs), and have studied the evolution of T-cell responses to determine if they are protective in nature. Methods. Twenty-one EU cases were studied using a questionnaire to ascertain injecting behavior details. Peripheral blood mononuclear cells were isolated from whole blood and an interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay used to detect T-cell responses to a panel of HCV proteins. EU cases were subdivided by injecting drug patterns into (1) cases in rehabilitation who stopped injecting, (2) prisoners (infrequent/noninjectors), and (3) cases who continued to inject. Results. EUs continuing to inject had significantly stronger (P < .01) and more frequent (P < .05) HCV-specific IFN-γ ELISPOT responses than controls or noninjecting EUs. EUs in rehabilitation lost their T-cell responses during follow-up, while those continuing to inject maintained them. Conclusions. HCV-specific T-cell responses in EU cases wane within months of cessation of injection drug use. Maintenance of these T-cell responses appears to be dependent on continuing HCV exposure through injection drug use. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

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