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Simon Whyte

Manuela Wiessner, Andreas Roos, Christopher J Munn, Ranjith Viswanathan, Tamieka Whyte, Dan Cox, Benedikt Schoser, Caroline Sewry, Helen Roper, Rahul Phadke, Chiara Marini Bettolo, Rita Barresi, Richard Charlton, Carsten G Bönnemann, Osório Abath Neto, Umbertina C Reed, Edmar Zanoteli, Cristiane Araújo Martins Moreno, Birgit Ertl-Wagner, Rolf Stucka, Christian De Goede, Tamiris Borges da Silva, Denisa Hathazi, Margherita Dell'Aica, René P Zahedi, Simone Thiele, Juliane Müller, Helen Kingston, Susanna Müller, Elizabeth Curtis, Maggie C Walter, Tim M Strom, Volker Straub, Kate Bushby, Francesco Muntoni, Laura E Swan, Hanns Lochmüller, Jan Senderek
Phosphoinositides are small phospholipids that control diverse cellular downstream signaling events. Their spatial and temporal availability is tightly regulated by a set of specific lipid kinases and phosphatases. Congenital muscular dystrophies are hereditary disorders characterized by hypotonia and weakness from birth with variable eye and central nervous system involvement. In individuals exhibiting congenital muscular dystrophy, early-onset cataracts, and mild intellectual disability but normal cranial magnetic resonance imaging, we identified bi-allelic mutations in INPP5K, encoding inositol polyphosphate-5-phosphatase K...
March 2, 2017: American Journal of Human Genetics
Andrew McGovern, William Hinton, Ana Correa, Neil Munro, Martin Whyte, Simon de Lusignan
PURPOSE: The University of Surrey-Lilly Real World Evidence (RWE) diabetes cohort has been established to provide insights into the management of type 2 diabetes mellitus (T2DM). There are 3 areas of study due to be conducted to provide insights into T2DM management: exploration of medication adherence, thresholds for changing diabetes therapies, and ethnicity-related or socioeconomic-related disparities in management. This paper describes the identification of a cohort of people with T2DM which will be used for these analyses, through a case finding algorithm, and describes the characteristics of the identified cohort...
November 24, 2016: BMJ Open
Matthias Görges, Nicholas C West, Simon D Whyte
BACKGROUND: Feedback of performance data can improve professional practice and outcomes. Vital signs are not routinely used for quality improvement because of their limited access. Intraoperative hypothermia has been associated with deleterious effects, including surgical site infections and bleeding. We speculated that providing feedback could help keep temperature monitoring and management a priority in the anesthesiologist's mind, thereby improving perioperative temperature management...
March 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Barbara C Baehr, Robert Whyte
Six new species of the peacock spider genus Maratus Karsch, 1878 are described from Australia: M. eliasi sp. nov., M. julianneae sp. nov., M. licunxini sp. nov., M. michaelorum sp. nov. and M. ottoi sp. nov. from Queensland, and M. kiwirrkurra sp. nov. from Western  Australia. Five species groups are further documented within the genus and new records, detailed SEM and automontage images are provided for six previously described species: M. anomalus Karsch, 1878, M. chrysomelas (Simon, 1909), M. digitatus Otto & Hill, 2012, M...
August 24, 2016: Zootaxa
Claire S Whyte, Irina N Chernysh, Marco M Domingues, Simon Connell, John W Weisel, Robert A S Ariens, Nicola J Mutch
Polyphosphate (polyP) binds to fibrin(ogen) and alters fibrin structure, generating a heterogeneous network composed of 'knots' interspersed by large pores. Here we show platelet-derived polyP elicits similar structural changes in fibrin and examine the mechanism by which polyP alters fibrin structure. Polymerisation of fibrinogen with thrombin and CaCl2 was studied using spinning disk confocal (SDC) microscopy. PolyP delayed fibrin polymerisation generating shorter protofibrils emanating from a nucleus-type structure...
October 28, 2016: Thrombosis and Haemostasis
Eric Edison, Martin Whyte, Jeremy van Vlymen, Simon Jones, Piers Gatenby, Simon de Lusignan, Jill Shawe
BACKGROUND: The aims of this study are the following: to describe the female population of reproductive age having bariatric surgery in the UK, to assess the age and ethnicity of women accessing surgery, and to assess the effect of bariatric surgery on factors that underlie fertility and pregnancy outcomes. METHODS: Demographic details, comorbidities, and operative type of women aged 18-45 years were extracted from the National Bariatric Surgery Registry (NBSR)...
December 2016: Obesity Surgery
Matthias Görges, Nicholas C West, Wesley Cheung, Guohai Zhou, Firoz Miyanji, Simon D Whyte
BACKGROUND: Underbody forced air warming is a method commonly used for intraoperative temperature maintenance in children. We previously reported that preoperative forced air warming of children undergoing spinal surgery substantially reduces the incidence and duration of intraoperative hypothermia (<36°C). OBJECTIVE: The aim of this study was to evaluate the effects of preoperative warming before spinal deformity surgery on surgical site infection rate, length of hospitalization, and bleeding (estimated blood loss and incidence of cell salvaged and/or allogeneic packed red blood cell transfusions)...
September 2016: Paediatric Anaesthesia
Conor G McAloon, Michael L Doherty, Paul Whyte, Luke O'Grady, Simon J More, Locksley L McV Messam, Margaret Good, Peter Mullowney, Sam Strain, Martin J Green
Bovine paratuberculosis is a disease characterised by chronic granulomatous enteritis which manifests clinically as a protein-losing enteropathy causing diarrhoea, hypoproteinaemia, emaciation and, eventually death. Some evidence exists to suggest a possible zoonotic link and a national voluntary Johne's Disease Control Programme was initiated by Animal Health Ireland in 2013. The objective of this study was to estimate herd-level true prevalence (HTP) and animal-level true prevalence (ATP) of paratuberculosis in Irish herds enrolled in the national voluntary JD control programme during 2013-14...
June 1, 2016: Preventive Veterinary Medicine
Rita Faria, Simon Walker, Sophie Whyte, Simon Dixon, Stephen Palmer, Mark Sculpher
Cost-effective interventions are often implemented slowly and suboptimally in clinical practice. In such situations, a range of implementation activities may be considered to increase uptake. A framework is proposed to use cost-effectiveness analysis to inform decisions on how best to invest in implementation activities. This framework addresses 2 key issues: 1) how to account for changes in utilization in the future in the absence of implementation activities; and 2) how to prioritize implementation efforts between subgroups...
February 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
Anne L Robertson, Nikolay V Ogryzko, Katherine M Henry, Catherine A Loynes, Matthew J Foulkes, Marco M Meloni, Xingang Wang, Christopher Ford, Malcolm Jackson, Philip W Ingham, Heather L Wilson, Stuart N Farrow, Roberto Solari, Roderick J Flower, Simon Jones, Moira K B Whyte, Stephen A Renshaw
Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments. It is therefore important to develop drug discovery strategies that can identify new therapeutics specifically targeting neutrophils, either by promoting their clearance or by preventing their recruitment...
June 1, 2016: Disease Models & Mechanisms
Simon J C Davies, Benoit H Mulsant, Alastair J Flint, Barnett S Meyers, Anthony J Rothschild, Ellen M Whyte, Margaret M Kirshner, Denise Sorisio, Bruce G Pollock, Robert R Bies
OBJECTIVE: We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction. METHODS: We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression...
May 2016: Human Psychopharmacology
Sophie Whyte, Simon Dixon, Rita Faria, Simon Walker, Stephen Palmer, Mark Sculpher, Stefanie Radford
BACKGROUND: Timely implementation of recommended interventions can provide health benefits to patients and cost savings to the health service provider. Effective approaches to increase the implementation of guidance are needed. Since investment in activities that improve implementation competes for funding against other health generating interventions, it should be assessed in term of its costs and benefits. OBJECTIVE: In 2010, the National Institute for Health and Care Excellence released a clinical guideline recommending natriuretic peptide (NP) testing in patients with suspected heart failure...
March 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Thomas Whyte, Tom Gibson, David Eager, Bruce Milthorpe
OBJECTIVE: Facial impacts are both common and injurious for helmeted motorcyclists who crash; however, there is no facial impact requirement in major motorcycle helmet standards. This study examined the effect of full-face motorcycle helmet protection on brain injury risk in facial impacts using a test device with biofidelic head and neck motion. A preliminary investigation of energy absorbing foam in the helmet chin bar was carried out. METHOD: Flat-faced rigid pendulum impacts were performed on a THOR dummy in an unprotected (no helmet) and protected mode (two full-face helmet conditions)...
March 3, 2016: Injury Prevention: Journal of the International Society for Child and Adolescent Injury Prevention
Andrew McGovern, Zayd Tippu, William Hinton, Neil Munro, Martin Whyte, Simon de Lusignan
INTRODUCTION: Treatment options for type 2 diabetes are becoming increasingly complex with people often prescribed multiple medications, and may include both oral and injectable therapies. There is ongoing debate about which drug classes provide the optimum second-line and third-line treatment options. In the real world, patient adherence and persistence determines medication effectiveness. A better understanding of adherence may help inform the choice of second-line and third-line drug classes...
February 29, 2016: BMJ Open
Conor G McAloon, Paul Whyte, Simon J More, Martin J Green, Luke O'Grady, AnaBelen Garcia, Michael L Doherty
Bovine paratuberculosis is a disease characterized by chronic granulomatous enteritis causing protein-losing enteropathy. Adverse effects on animal productivity are key drivers in the attempt to control paratuberculosis at the farm level. Economic models require an accurate estimation of the production effects associated with paratuberculosis. The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of paratuberculosis on milk production. A total of 20 effect estimates from 15 studies were included in the final meta-analysis...
February 2016: Journal of Dairy Science
Matthias Görges, Simon D Whyte, Shubhayan Sanatani, Joy Dawes, Carolyne J Montgomery, J Mark Ansermino
BACKGROUND: Clinical indications for the perioperative use of dexmedetomidine in pediatric anesthesia are accumulating. However, in 2013, dexmedetomidine was added to the list of medications with possible risk of prolonging the QT interval and/or inducing Torsades de Pointes. Unfortunately, current evidence for dexmedetomidine-induced QT prolongation is sparse and somewhat contradictory. OBJECTIVE: The purpose of this study was to evaluate temporal changes in corrected QT interval (QTc) after a rapid bolus administration of dexmedetomidine under total intravenous anesthesia (TIVA) with a standardized propofol and remifentanil administration...
December 2015: Paediatric Anaesthesia
Fadil M Hannan, Sarah A Howles, Angela Rogers, Treena Cranston, Caroline M Gorvin, Valerie N Babinsky, Anita A Reed, Clare E Thakker, Detlef Bockenhauer, Rosalind S Brown, John M Connell, Jacqueline Cook, Ken Darzy, Sarah Ehtisham, Una Graham, Tony Hulse, Steven J Hunter, Louise Izatt, Dhavendra Kumar, Malachi J McKenna, John A McKnight, Patrick J Morrison, M Zulf Mughal, Domhnall O'Halloran, Simon H Pearce, Mary E Porteous, Mushtaqur Rahman, Tristan Richardson, Robert Robinson, Isabelle Scheers, Haroon Siddique, William G Van't Hoff, Timothy Wang, Michael P Whyte, M Andrew Nesbit, Rajesh V Thakker
The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeostasis. To elucidate the role of AP2σ2 in Ca(2+) o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3...
September 15, 2015: Human Molecular Genetics
Jenny C Taylor, Hilary C Martin, Stefano Lise, John Broxholme, Jean-Baptiste Cazier, Andy Rimmer, Alexander Kanapin, Gerton Lunter, Simon Fiddy, Chris Allan, A Radu Aricescu, Moustafa Attar, Christian Babbs, Jennifer Becq, David Beeson, Celeste Bento, Patricia Bignell, Edward Blair, Veronica J Buckle, Katherine Bull, Ondrej Cais, Holger Cario, Helen Chapel, Richard R Copley, Richard Cornall, Jude Craft, Karin Dahan, Emma E Davenport, Calliope Dendrou, Olivier Devuyst, Aimée L Fenwick, Jonathan Flint, Lars Fugger, Rodney D Gilbert, Anne Goriely, Angie Green, Ingo H Greger, Russell Grocock, Anja V Gruszczyk, Robert Hastings, Edouard Hatton, Doug Higgs, Adrian Hill, Chris Holmes, Malcolm Howard, Linda Hughes, Peter Humburg, David Johnson, Fredrik Karpe, Zoya Kingsbury, Usha Kini, Julian C Knight, Jonathan Krohn, Sarah Lamble, Craig Langman, Lorne Lonie, Joshua Luck, Davis McCarthy, Simon J McGowan, Mary Frances McMullin, Kerry A Miller, Lisa Murray, Andrea H Németh, M Andrew Nesbit, David Nutt, Elizabeth Ormondroyd, Annette Bang Oturai, Alistair Pagnamenta, Smita Y Patel, Melanie Percy, Nayia Petousi, Paolo Piazza, Sian E Piret, Guadalupe Polanco-Echeverry, Niko Popitsch, Fiona Powrie, Chris Pugh, Lynn Quek, Peter A Robbins, Kathryn Robson, Alexandra Russo, Natasha Sahgal, Pauline A van Schouwenburg, Anna Schuh, Earl Silverman, Alison Simmons, Per Soelberg Sørensen, Elizabeth Sweeney, John Taylor, Rajesh V Thakker, Ian Tomlinson, Amy Trebes, Stephen R F Twigg, Holm H Uhlig, Paresh Vyas, Tim Vyse, Steven A Wall, Hugh Watkins, Michael P Whyte, Lorna Witty, Ben Wright, Chris Yau, David Buck, Sean Humphray, Peter J Ratcliffe, John I Bell, Andrew O M Wilkie, David Bentley, Peter Donnelly, Gilean McVean
To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy...
July 2015: Nature Genetics
Simon J C Davies, Benoit H Mulsant, Alastair J Flint, Barnett S Meyers, Anthony J Rothschild, Ellen M Whyte, Margaret M Kirshner, Denise Sorisio, Bruce G Pollock, Robert R Bies
BACKGROUND AND OBJECTIVE: Clinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods. METHODS: The Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline...
November 2015: Clinical Pharmacokinetics
Conor G McAloon, Paul Whyte, Simon J More, Luke O'Grady, Michael L Doherty
Paratuberculosis is a challenging disease to control at farm level, in part due to the poor sensitivity of diagnostic tests and a prolonged incubation period. Simulation studies have highlighted on-farm management to be the most important factor in preventing on-farm spread. A risk assessment (RA) and management plan (MP) approach (collectively, RAMP) has been adopted around the world as the most appropriate method of controlling disease in infected farms. However, there are problems with RAMP that remain to be resolved...
June 15, 2015: Preventive Veterinary Medicine
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