Showing papers by "University of Birmingham published in 2011"
TL;DR: How to interpret funnel plot asymmetry, recommends appropriate tests, and explains the implications for choice of meta-analysis model are described.
Abstract: Funnel plots, and tests for funnel plot asymmetry, have been widely used to examine bias in the results of meta-analyses. Funnel plot asymmetry should not be equated with publication bias, because it has a number of other possible causes. This article describes how to interpret funnel plot asymmetry, recommends appropriate tests, and explains the implications for choice of meta-analysis model
4,518 citations
TL;DR: Summary estimates of treatment effect from random effects meta-analysis give only the average effect across all studies, but inclusion of prediction intervals, which estimate the likely effect in an individual setting, could make it easier to apply the results to clinical practice.
Abstract: Summary estimates of treatment effect from random effects meta-analysis give only the average effect across all studies. Inclusion of prediction intervals, which estimate the likely effect in an individual setting, could make it easier to apply the results to clinical practice
1,855 citations
TL;DR: A mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands is revealed, accounting for many of the known features of the CD28–CTLA- 4 system.
Abstract: Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.
1,414 citations
TL;DR: An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4, and a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals was identified.
Abstract: We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10−7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
1,312 citations
TL;DR: This review summarises current knowledge about production volumes, physico-chemical properties, analysis, environmental occurrence, fate and behaviour and human exposure to the "novel" brominated flame retardants (NBFRs).
1,186 citations
TL;DR: The ecotoxicological literature shows that concentrations of Ag NPs below the current and future PECs, as low as just a few ng L(-1), can affect prokaryotes, invertebrates and fish indicating a significant potential, though poorly characterised, risk to the environment.
1,115 citations
TL;DR: Advances in nanotechnology and polymer science, and the development of novel surface designs 'bioinspired' by nature, are expected to have a significant impact on theDevelopment of a new generation of environmentally friendly marine coatings.
Abstract: 'Marine biofouling', the undesired growth of marine organisms such as microorganisms, barnacles and seaweeds on submerged surfaces, is a global problem for maritime industries, with both economic and environmental penalties. The primary strategy for combating marine fouling is to use biocide-containing paints, but environmental concerns and legislation are driving science and technology towards non-biocidal solutions based solely on physico-chemical and materials properties of coatings. Advances in nanotechnology and polymer science, and the development of novel surface designs 'bioinspired' by nature, are expected to have a significant impact on the development of a new generation of environmentally friendly marine coatings.
994 citations
TL;DR: Of the contemporary bleeding risk stratification schemas, the new HAS-BLED scheme offers useful predictive capacity for bleeding over previously published schemas and may be simpler to apply.
940 citations
Indiana University1, Pasteur Institute2, Washington University in St. Louis3, University of British Columbia4, Cubist Pharmaceuticals5, University of Turku6, Lahey Hospital & Medical Center7, Harvard University8, University of Medicine and Dentistry of New Jersey9, The Evergreen State College10, Wayne State University11, Tufts University12, Northeastern University13, University of California, Los Angeles14, University of Notre Dame15, University of Birmingham16, MedImmune17, Rockefeller University18, Université catholique de Louvain19, Cardiff University20, Cold Spring Harbor Laboratory21, Robert Koch Institute22, McMaster University23, University of Oklahoma24
TL;DR: To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011.
Abstract: The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis.
929 citations
Newcastle University1, Royal Melbourne Hospital2, University of Eastern Finland3, Princess Anne Hospital4, St Mary's Hospital5, University of Birmingham6, University of Copenhagen7, Western General Hospital8, Queen Mary University of London9, St George's Hospital10, Karolinska Institutet11, Queen's University Belfast12, University of Cape Town13, Churchill Hospital14, John Hunter Hospital15, Imperial College London16, Leiden University17, University of Leeds18, Leiden University Medical Center19, Erasmus University Rotterdam20, Creighton University Medical Center21
TL;DR: The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer, and long-term follow-up of participants randomly assigned to aspirin or placebo is reported.
828 citations
TL;DR: In this paper, the authors demonstrate the squeezed-light enhancement of GEO600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3-4 years.
Abstract: Around the globe several observatories are seeking the first direct detection of gravitational waves (GWs). These waves are predicted by Einstein’s general theory of relativity1 and are generated, for example, by black-hole binary systems2. Present GW detectors are Michelson-type kilometre-scale laser interferometers measuring the distance changes between mirrors suspended in vacuum. The sensitivity of these detectors at frequencies above several hundred hertz is limited by the vacuum (zero-point) fluctuations of the electromagnetic field. A quantum technology—the injection of squeezed light3—offers a solution to this problem. Here we demonstrate the squeezed-light enhancement of GEO 600, which will be the GW observatory operated by the LIGO Scientific Collaboration in its search for GWs for the next 3–4 years. GEO 600 now operates with its best ever sensitivity, which proves the usefulness of quantum entanglement and the qualification of squeezed light as a key technology for future GW astronomy4.
TL;DR: A three-year study by the CIRP's Collaborative Working Group on Surface Integrity and Functional Performance of Components as discussed by the authors reported recent progress in experimental and theoretical investigations on surface integrity in material removal processes.
TL;DR: Doing quantitative research in education with SPSS, 2nd edition, by Daniel Muijs, London, Sage, 2011, 347 pp., £44.95 (paperback), ISBN: 978-1-84920-324-1 This is a nice book to introduce students...
Abstract: Doing quantitative research in education with SPSS, 2nd edition, by Daniel Muijs, London, Sage, 2011, 347 pp., £44.95 (paperback), ISBN: 978-1-84920-324-1 This is a nice book to introduce students ...
TL;DR: In this article, the authors focus on B2B SMEs and their social networking practices, particularly, usage, perceived barriers, and the measurement of effectiveness of SNS as a marketing tool.
TL;DR: In this article, the authors present the results of a pilot study, which deployed a qualitative GIS technique to analyse the effectiveness of walked interviews in capturing data relating to people's understanding of place, concluding that the data generated through walking interviews are profoundly informed by the landscapes in which they take place, emphasising the importance of environmental features in shaping discussions.
TL;DR: Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
Abstract: Background Wegener9s granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. Objective To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease. Methods Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models. Results The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate Conclusion Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
TL;DR: Whether implementing additional “train-low” strategies to increase the training adaptation leads to enhanced performance in well-trained individuals is unclear.
Abstract: An athlete’s carbohydrate intake can be judged by whether total daily intake and the timing of consumption in relation to exercise maintain adequate carbohydrate substrate for the muscle and central nervous system (‘‘high carbohydrate availability’’) or whether carbohydrate fuel sources are limiting for the daily exercise programme (‘‘low carbohydrate availability’’). Carbohydrate availability is increased by consuming carbohydrate in the hours or days prior to the session, intake during exercise, and refuelling during recovery between sessions. This is important for the competition setting or for high-intensity training where optimal performance is desired. Carbohydrate intake during exercise should be scaled according to the characteristics of the event. During sustained high-intensity sports lasting *1 h, small amounts of carbohydrate, including even mouth-rinsing, enhance performance via central nervous system effects. While 30–60 g h 71 is an appropriate target for sports of longer duration, events42.5 h may benefit from higher intakes of up to 90 g h 71 . Products containing special blends of different carbohydrates may maximize absorption of carbohydrate at such high rates. In real life, athletes undertake training sessions with varying carbohydrate availability. Whether implementing additional ‘‘train-low’’ strategies to increase the training adaptation leads to enhanced performance in well-trained individuals is unclear.
TL;DR: It is shown that the aryl hydrocarbon receptor (AhR) is a crucial regulator in maintaining IEL numbers in both the skin and the intestine, and that AhR deficiency or the lack of AhR ligands compromises the maintenance of IELs and the control of the microbial load and composition.
University of Glasgow1, University of Salerno2, Max Planck Society3, University of Southampton4, University of Paris-Sud5, University of Nice Sophia Antipolis6, Washington State University7, Istituto Nazionale di Fisica Nucleare8, University of Warsaw9, University of Naples Federico II10, University of Birmingham11, Cardiff University12, University of Rome Tor Vergata13, Moscow State University14, California Institute of Technology15, VU University Amsterdam16, fondazione bruno kessler17, Leibniz University of Hanover18, University of Cambridge19, University of Tübingen20, University of Urbino21, University of Jena22, University of the Balearic Islands23, Northwestern University24, University of Minnesota25, University of Savoy26, Pennsylvania State University27, University of Pisa28, Roma Tre University29, Sapienza University of Rome30, University of Mississippi31
TL;DR: In this article, a special focus is set on evaluating the frequency band below 10 Hz where a complex mixture of seismic, gravity gradient, suspension thermal and radiation pressure noise dominates, including the most relevant fundamental noise contributions.
Abstract: Advanced gravitational wave detectors, currently under construction, are expected to directly observe gravitational wave signals of astrophysical origin. The Einstein Telescope (ET), a third-generation gravitational wave detector, has been proposed in order to fully open up the emerging field of gravitational wave astronomy. In this paper we describe sensitivity models for ET and investigate potential limits imposed by fundamental noise sources. A special focus is set on evaluating the frequency band below 10 Hz where a complex mixture of seismic, gravity gradient, suspension thermal and radiation pressure noise dominates. We develop the most accurate sensitivity model, referred to as ET-D, for a third-generation detector so far, including the most relevant fundamental noise contributions.
TL;DR: The relationship between the number of eggs and live birth, across all female age groups, suggests that the numberof eggs in IVF is a robust surrogate outcome for clinical success.
Abstract: methods:Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female. results:The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6‐13]. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to!15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006‐2007, the predicted LBR for women with 15 eggs retrieved in age groups 18‐34, 35‐37, 38‐39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991. conclusion:The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is!15.
TL;DR: Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection and show that tyrosine kinase inhibitors have substantial antiviral activity.
Abstract: Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection.
TL;DR: The Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of the Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management.
Abstract: The Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of the Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidaemia, obesity, and glycaemic control in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: (1) one abnormal cardiovagal test result identifies possible or early CAN; (2) at least two abnormal cardiovagal test results are required for definite or confirmed CAN; and (3) the presence of orthostatic hypotension in addition to abnormal heart rate test results identifies severe or advanced CAN. Progressive stages of CAN are associated with increasingly worse prognosis. CAN assessment is relevant in clinical practice for (1) diagnosis of CAN clinical forms, (2) detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, orthostatic hypotension, non-dipping, QT interval prolongation), (3) risk stratification for diabetic complications and cardiovascular morbidity and mortality, and (4) modulation of targets of diabetes therapy. Evidence on the cost-effectiveness of CAN testing is lacking. Apart from the preventive role of intensive glycaemic control in type 1 diabetes, recommendations cannot be made for most therapeutic approaches to CAN.
National Institutes of Natural Sciences, Japan1, National Institute of Information and Communications Technology2, Raman Research Institute3, Waseda University4, Osaka Institute of Technology5, Kyoto University6, Osaka City University7, Japan Aerospace Exploration Agency8, University of Electro-Communications9, Kindai University10, National Institute of Advanced Industrial Science and Technology11, Tokyo Institute of Technology12, Goddard Space Flight Center13, University of Tokyo14, Hiroshima University15, Ochanomizu University16, Liverpool John Moores University17, Nagoya University18, Nihon University19, Rikkyo University20, Tokyo Keizai University21, Yamanashi Eiwa College22, Rochester Institute of Technology23, Stanford University24, California Institute of Technology25, Hirosaki University26, Niigata University27, Tokai University28, Tohoku University29, Osaka University30, National Defense Academy of Japan31, University of Tübingen32, Hosei University33, University of Wisconsin–Milwaukee34, Tokyo University of Science35, University of Birmingham36
TL;DR: The initial development of a multidimensional measure designed to assess psychological need thwarting, an under-studied area of conceptual and practical importance is outlined, and suggestions are made regarding the use of the PNTS in research pertaining to the darker side of sport participation.
Abstract: Research in self-determination theory (Ryan & Deci, 2002) has shown that satisfaction of autonomy, competence, and relatedness needs in sport contexts is associated with enhanced engagement, performance, and well-being This article outlines the initial development of a multidimensional measure designed to assess psychological need thwarting, an under-studied area of conceptual and practical importance Study 1 generated a pool of items designed to tap the negative experiential state that occurs when athletes perceive their needs for autonomy, competence, and relatedness to be actively undermined Study 2 tested the factorial structure of the questionnaire using confirmatory factor analysis The supported model comprised 3 factors, which represented the hypothesized interrelated dimensions of need thwarting The model was refined and cross-validated using an independent sample in Study 3 Overall, the psychological need thwarting scale (PNTS) demonstrated good content, factorial, and predictive validity, as well as internal consistency and invariance across gender, sport type, competitive level, and competitive experience The conceptualization of psychological need thwarting is discussed, and suggestions are made regarding the use of the PNTS in research pertaining to the darker side of sport participation
TL;DR: The T cell protein cytotoxic T lymphocyte antigen 4 (CTLA4) was identified as a crucial negative regulator of the immune system over 15 years ago, but its mechanisms of action are still under debate.
Abstract: The T cell protein cytotoxic T lymphocyte antigen 4 (CTLA4) was identified as a crucial negative regulator of the immune system over 15 years ago, but its mechanisms of action are still under debate. It has long been suggested that CTLA4 transmits an inhibitory signal to the cells that express it. However, not all the available data fit with a cell-intrinsic function for CTLA4, and other studies have suggested that CTLA4 functions in a T cell-extrinsic manner. Here, we discuss the data for and against the T cell-intrinsic and -extrinsic functions of CTLA4.
TL;DR: It is shown that a simple deterministically constructed cycle reservoir is comparable to the standard echo state network methodology and the (short-term) of linear cyclic reservoirs can be made arbitrarily close to the proved optimal value.
Abstract: Reservoir computing (RC) refers to a new class of state-space models with a fixed state transition structure (the reservoir) and an adaptable readout form the state space. The reservoir is supposed to be sufficiently complex so as to capture a large number of features of the input stream that can be exploited by the reservoir-to-output readout mapping. The field of RC has been growing rapidly with many successful applications. However, RC has been criticized for not being principled enough. Reservoir construction is largely driven by a series of randomized model-building stages, with both researchers and practitioners having to rely on a series of trials and errors. To initialize a systematic study of the field, we concentrate on one of the most popular classes of RC methods, namely echo state network, and ask: What is the minimal complexity of reservoir construction for obtaining competitive models and what is the memory capacity (MC) of such simplified reservoirs? On a number of widely used time series benchmarks of different origin and characteristics, as well as by conducting a theoretical analysis we show that a simple deterministically constructed cycle reservoir is comparable to the standard echo state network methodology. The (short-term) of linear cyclic reservoirs can be made arbitrarily close to the proved optimal value.
K. Aamodt1, A. Abrahantes Quintana, Dagmar Adamová2, Andrew Marshall Adare3 +938 more•Institutions (80)
TL;DR: In this paper, the centrality dependence of the chargedparticle multiplicity density at midrapidity in Pb-Pb collisions at root s(NN) = 2: 76 TeV is presented.
Abstract: The centrality dependence of the charged-particle multiplicity density at midrapidity in Pb-Pb collisions at root s(NN) = 2: 76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor of 2 from peripheral (70%-80%) to central (0%-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions.
TL;DR: The clinical and genetic features of VHL disease are reviewed, the molecular pathogenesis is reviewed and clinical management and tumour surveillance strategies are outlined.
Abstract: The autosomal dominantly inherited disorder von Hippel–Lindau disease (VHL) is caused by germline mutations in the VHL tumour suppressor gene (TSG). VHL mutations predispose to the development of a variety of tumours (most commonly retinal and central nervous system haemangioblastomas, clear cell renal carcinoma and phaeochromocytomas). Here, we review the clinical and genetic features of VHL disease, briefly review the molecular pathogenesis and outline clinical management and tumour surveillance strategies.
K. Aamodt1, A. Abrahantes Quintana, Dagmar Adamová2, Andrew Marshall Adare3 +909 more•Institutions (76)
TL;DR: In this article, the authors measured the transverse momentum spectra of primary charged particles in Pb-Pb collisions at root s(NN) = 2.76 TeV at the ALICE Collaboration at the LHC.