Showing papers by "University of Warwick published in 2010"

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Inverse problems: A Bayesian perspective

Abstract: The subject of inverse problems in differential equations is of enormous practical importance, and has also generated substantial mathematical and computational innovation. Typically some form of regularization is required to ameliorate ill-posed behaviour. In this article we review the Bayesian approach to regularization, developing a function space viewpoint on the subject. This approach allows for a full characterization of all possible solutions, and their relative probabilities, whilst simultaneously forcing significant modelling issues to be addressed in a clear and precise fashion. Although expensive to implement, this approach is starting to lie within the range of the available computational resources in many application areas. It also allows for the quantification of uncertainty and risk, something which is increasingly demanded by these applications. Furthermore, the approach is conceptually important for the understanding of simpler, computationally expedient approaches to inverse problems.

Sleep Duration and All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies

Abstract: Background: Increasing evidence suggests an association between both short and long duration of habitual sleep with adverse health outcomes. Objectives: To assess whether the population longitudinal evidence supports the presence of a relationship between duration of sleep and all-cause mortality, to investigate both short and long sleep duration and to obtain an estimate of the risk. Methods: We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. We included studies if they were prospective, had follow-up >3 years, had duration of sleep at baseline, and all-cause mortality prospectively. We extracted relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model. We carried out sensitivity analyses and assessed heterogeneity and publication bias. Results: Overall, the 16 studies analyzed provided 27 independent cohort samples. They included 1,382,999 male and female participants (follow-up range 4 to 25 years), and 112,566 deaths. Sleep duration was assessed by questionnaire and outcome through death certification. In the pooled analysis, short duration of sleep was associated with a greater risk of death (RR: 1.12; 95% CI 1.06 to 1.18; P <0.01) with no evidence of publication bias (P = 0.74) but heterogeneity between studies (P = 0.02). Long duration of sleep was also associated with a greater risk of death (1.30; [1.22 to 1.38]; P < 0.0001) with no evidence of publication bias (P = 0.18) but significant heterogeneity between studies (P < 0.0001). Conclusion: Both short and long duration of sleep are significant predictors of death in prospective population studies.

Quantity and Quality of Sleep and Incidence of Type 2 Diabetes A systematic review and meta-analysis

Abstract: OBJECTIVE - To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes and to obtain an estimate of the risk. RESEARCH DESIGN AND METHODS - We conducted a systematic search of publications using MEDLINE (1955-April 2009), EMBASE, and the Cochrane Library and manual searches Without language restrictions. We included studies if they were prospective with follow-up >3 years and had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RRs) and 95% Cl and pooled them using random-effects models. We performed sensitivity analysis and assessed heterogeneity and publication bias. RESULTS - we included 10 Studies (13 independent cohort Samples; 107,756 male and female participants, follow-up range 4.2-32 years, and 3,586 incident cases Of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of development Of type 2 diabetes. For short duration of sleep (: 8-9 h/night), the RR was 1.48 (1.13-1.96, P = 0.005); for difficulty in initiating sleep, the RR was 1.57 (1.25-1.97, P < 0.0001); and for difficulty in maintaining sleep, the RR was 1.84 (1.39-2.43, P < 0.0001). CONCLUSIONS - Quantity and quality of sleep consistently and significantly predict the risk Of the development Of type 2 diabetes. The mechanisms Underlying this relation may differ between short and long sleepers.

Innovation in Governance and Public Services: Past and Present

Abstract: Three approaches to innovation in the public sector in the post war period are identified and analysed for their implications for policy-makers, managers and citizens. Various relationships are identified between innovation and improvement in public services. The traditional bias of the literature that innovation is necessarily functional is undermined. Important lessons for policy, practice and research include the need to develop an understanding of innovation which is not over-reliant on the private sector manufacturing literature but reflects the distinctive contexts and purposes of the public sector.

Condition Monitoring for Device Reliability in Power Electronic Converters: A Review

Abstract: Condition monitoring (CM) has already been proven to be a cost effective means of enhancing reliability and improving customer service in power equipment, such as transformers and rotating electrical machinery. CM for power semiconductor devices in power electronic converters is at a more embryonic stage; however, as progress is made in understanding semiconductor device failure modes, appropriate sensor technologies, and signal processing techniques, this situation will rapidly improve. This technical review is carried out with the aim of describing the current state of the art in CM research for power electronics. Reliability models for power electronics, including dominant failure mechanisms of devices are described first. This is followed by a description of recently proposed CM techniques. The benefits and limitations of these techniques are then discussed. It is intended that this review will provide the basis for future developments in power electronics CM.

Fresh fruit and vegetables as vehicles for the transmission of human pathogens

Abstract: Much research into food-borne human pathogens has focused on transmission from foods of animal origin. However, recent investigations have identified fruits and vegetables are the source of many disease outbreaks. Now believed to be a much larger contributor to produce-associated outbreaks than previously reported, norovirus outbreaks are commonly caused by contamination of foods from hands of infected workers. Although infections with Shiga toxin-producing E. coli O157 have been linked to beef more often than to any other food product, severe outbreaks have been traced to consumption of contaminated radish sprouts and pre-packaged spinach. Similarly, while infections with Salmonella have mainly been linked to consumption of foods of animal origin, many outbreaks have been traced to contaminated fresh produce. E. coli O157 binds to lettuce leaves by alternative mechanisms involving the filamentous type III secretions system, flagella and the pilus curli. Association of Salmonella with fresh produce appears to be serovar-specific involving flagella, curli, cellulose, and O antigen capsule. A better understanding of plant, microbiological, environmental, processing and food handling factors that facilitate contamination will allow development of evidence-based policies, procedures and technologies aimed at reducing the risk of contamination of fresh produce.

The anatomy of anatomy: A review for its modernization

Abstract: Anatomy has historically been a cornerstone in medical education regardless of nation or specialty. Until recently, dissection and didactic lectures were its sole pedagogy. Teaching methodology has been revolutionized with more reliance on models, imaging, simulation, and the Internet to further consolidate and enhance the learning experience. Moreover, modern medical curricula are giving less importance to anatomy education and to the acknowledged value of dissection. Universities have even abandoned dissection completely in favor of user-friendly multimedia, alternative teaching approaches, and newly defined priorities in clinical practice. Anatomy curriculum is undergoing international reformation but the current framework lacks uniformity among institutions. Optimal learning content can be categorized into the following modalities: (1) dissection/prosection, (2) interactive multimedia, (3) procedural anatomy, (4) surface and clinical anatomy, and (5) imaging. The importance of multimodal teaching, with examples suggested in this article, has been widely recognized and assessed. Nevertheless, there are still ongoing limitations in anatomy teaching. Substantial problems consist of diminished allotted dissection time and the number of qualified anatomy instructors, which will eventually deteriorate the quality of education. Alternative resources and strategies are discussed in an attempt to tackle these genuine concerns. The challenges are to reinstate more effective teaching and learning tools while maintaining the beneficial values of orthodox dissection. The UK has a reputable medical education but its quality could be improved by observing international frameworks. The heavy penalty of not concentrating on sufficient anatomy education will inevitably lead to incompetent anatomists and healthcare professionals, leaving patients to face dire repercussions. Anat Sci Educ 3: 83–93, 2010. © 2010 American Association of Anatomists.

Stereocontrolled ring-opening polymerisation of lactide

Abstract: The important advances and current trends in the stereocontrolled ring-opening polymerisation of lactide are discussed in this tutorial review. Microstructures, structural characterisation methods and the properties of stereoregular poly(lactide)s are examined. The application of metal-based catalysts dominates this area although simple anionic polymerisation and organocatalytic routes that demonstrate control of the polymer tacticity are discussed.

Objective confirmation of subjective measures of human well-being: evidence from the U.S.A.

Abstract: A huge research literature, across the behavioral and social sciences, uses information on individuals' subjective well-being. These are responses to questions--asked by survey interviewers or medical personnel--such as, "How happy do you feel on a scale from 1 to 4?" Yet there is little scientific evidence that such data are meaningful. This study examines a 2005-2008 Behavioral Risk Factor Surveillance System random sample of 1.3 million U.S. citizens. Life satisfaction in each U.S. state is measured. Across America, people's answers trace out the same pattern of quality of life as previously estimated, from solely nonsubjective data, in one branch of economics (so-called "compensating differentials" neoclassical theory, originally from Adam Smith). There is a state-by-state match (r = 0.6, P < 0.001) between subjective and objective well-being. This result has some potential to help to unify disciplines.

Hydrogen generation from formic acid and alcohols using homogeneous catalysts

Abstract: This tutorial review describes recent progress in the development of homogeneous catalytic methodology for the direct generation of hydrogen gas from formic acid and alcohols.

Handling of the generation of primary events in Gauss, the LHCb simulation framework

Abstract: The LHCb simulation application. Gauss, consists or two independent phases, the generation of the primary event and the tracking of particles produced in the experimental setup. For the LHCh experimental program it is particularly important to model IS meson decays: the KvtGcn code developed in CLEO and BaBah has been chosen and customized for non-coherent B production as necuring in pp collisions at the LHC, The initial proton-proto n collision is provided by a different generator engine, currently PYTHIA 6 for massive prwluclion of signal and generic pp collisions events. Beam gas events, background events originating from proton halo, cosmics and calibration events for different detectors can be generated in addition to pp collisions. Different generator packages as available in the physics community or specifically developed in LHCb are used for the different purposes. Running conditions affecting the events generated such as the size of the luminous region, the number of collisions occuring in a bunch crossing and the number of spill-over events from neighbouring bunches are modeled via dedicated algorithms appropriately configured. The design of the generator phase of Gauss will be described: a modular structure with well defined interfaces specific to the various tasks, e.g. pp collisions, particles' decays, selections, etc. has been chosen. Different implementations are available for the various tasks allowing selecting and combining them as most appropriate at run time as in the case of Pythia 6 im pp collisions or HIJING for beam gas. The advantages of such structure, allowing for example to adopt transparently new generators packages will be discussed.

Prosocial Spending and Well-Being: Cross-Cultural Evidence for a Psychological Universal

Abstract: This research provides the first support for a possible psychological universal: human beings around the world derive emotional benefits from using their financial resources to help others (prosocial spending). Analyzing survey data from 136 countries, we show that prosocial spending is consistently associated with greater happiness. To test for causality, we conduct experiments within two very different countries (Canada and Uganda) and show that spending money on others has a consistent, causal impact on happiness. In contrast to traditional economic thought--which places self-interest as the guiding principle of human motivation--our findings suggest that the reward experienced from helping others may be deeply ingrained in human nature, emerging in diverse cultural and economic contexts.

Money and Happiness Rank of Income, Not Income, Affects Life Satisfaction

Abstract: Does money buy happiness, or does happiness come indirectly from the higher rank in society that money brings? We tested a rank-income hypothesis, according to which people gain utility from the ranked position of their income within a comparison group. The rank hypothesis contrasts with traditional reference-income hypotheses, which suggest that utility from income depends on comparison to a social reference-group norm. We found that the ranked position of an individual’s income predicts general life satisfaction, whereas absolute income and reference income have no effect. Furthermore, individuals weight upward comparisons more heavily than downward comparisons. According to the rank hypothesis, income and utility are not directly linked: Increasing an individual’s income will increase his or her utility only if ranked position also increases and will necessarily reduce the utility of others who will lose rank.

Spin-orbit angle measurements for six southern transiting planets New insights into the dynamical origins of hot Jupiters

Abstract: Context. Several competing scenarios for planetary-system formation and evolution seek to explain how hot Jupiters came to be so close to their parent stars. Most planetary parameters evolve with time, making it hard to distinguish between models. The obliquity of an orbit with respect to the stellar rotation axis is thought to be more stable than other parameters such as eccentricity. Most planets, to date, appear aligned with the stellar rotation axis; the few misaligned planets so far detected are massive (\textgreater2 M-J). Aims. Our goal is to measure the degree of alignment between planetary orbits and stellar spin axes, to search for potential correlations with eccentricity or other planetary parameters and to measure long term radial velocity variability indicating the presence of other bodies in the system. Methods. For transiting planets, the Rossiter-McLaughlin effect allows the measurement of the sky-projected angle beta between the stellar rotation axis and a planet's orbital axis. Using the HARPS spectrograph, we observed the Rossiter-McLaughlin effect for six transiting hot Jupiters found by the WASP consortium. We combine these with long term radial velocity measurements obtained with CORALIE. We used a combined analysis of photometry and radial velocities, fitting model parameters with the Markov Chain Monte Carlo method. After obtaining beta we attempt to statistically determine the stribution of the real spin-orbit angle psi. Results. We found that three of our targets have beta above 90 degrees: WASP-2b: beta = 153 degrees(+11)(-15), WASP-15b: beta = 139.6 degrees(+5.2)(-4.3) and WASP-17b: beta = 148.5 degrees(+5.1)(-4.2); the other three (WASP-4b, WASP-5b and WASP-18b) have angles compatible with 0 degrees. We find no dependence between the misaligned angle and planet mass nor with any other planetary parameter. All six orbits are close to circular, with only one firm detection of eccentricity e = 0.00848(-0.00095)(+0.00085) in WASP-18b. No long-term radial acceleration was detected for any of the targets. Combining all previous 20 measurements of beta and our six and transforming them into a distribution of psi we find that between about 45 and 85% of hot Jupiters have psi \textgreater 30 degrees. Conclusions. Most hot Jupiters are misaligned, with a large variety of spin-orbit angles. We find observations and predictions using the Kozai mechanism match well. If these observational facts are confirmed in the future, we may then conclude that most hot Jupiters are formed from a dynamical and tidal origin without the necessity to use type I or II migration. At present, standard disc migration cannot explain the observations without invoking at least another additional process.

Searches for Lepton Flavor Violation in the Decays tau(+/-) -> e(+/-)gamma and tau(+/-) -> mu(+/-)gamma

Abstract: Searches for lepton-flavor-violating decays of a tau lepton to a lighter mass lepton and a photon have been performed with the entire data set of (963 +/- 7) x 10(6) tau decays collected by the BABAR detector near the Y(4S), Y(3S) and Y(2S) resonances. The searches yield no evidence of signals and we set upper limits on the branching fractions of B(tau(+/-) -> e(+/-)gamma) mu(+/-)gamma) < 4.4 X 10(-8) at 90% confidence level.

Early intervention in psychosis.

Abstract: Early intervention in psychosis services produce better clinical outcomes than generic teams and are also cost-effective. Clinical gains made within such services are robust as long as the interventions are actively provided. Longer-term data show that some of these gains are lost when care is transferred back to generic teams. This paper argues that sustaining these early gains requires both a reappraisal of generic services and an understanding of the active ingredients of early intervention, which can be tailored for longer input in cases with poorer outcome trajectories.

Signatures of adaptation to obligate biotrophy in the Hyaloperonospora arabidopsidis genome

Abstract: Many oomycete and fungal plant pathogens are obligate biotrophs, which extract nutrients only from living plant tissue and cannot grow apart from their hosts. Although these pathogens cause substantial crop losses, little is known about the molecular basis or evolution of obligate biotrophy. Here, we report the genome sequence of the oomycete Hyaloperonospora arabidopsidis (Hpa), an obligate biotroph and natural pathogen of Arabidopsis thaliana. In comparison with genomes of related, hemibiotrophic Phytophthora species, the Hpa genome exhibits dramatic reductions in genes encoding (i) RXLR effectors and other secreted pathogenicity proteins, (ii) enzymes for assimilation of inorganic nitrogen and sulfur, and (iii) proteins associated with zoospore formation and motility. These attributes comprise a genomic signature of evolution toward obligate biotrophy.

Measurement of single-cell dynamics.

Abstract: Populations of cells are almost always heterogeneous in function and fate. To understand the plasticity of cells, it is vital to measure quantitatively and dynamically the molecular processes that underlie cell-fate decisions in single cells. Early events in cell signalling often occur within seconds of the stimulus, whereas intracellular signalling processes and transcriptional changes can take minutes or hours. By contrast, cell-fate decisions, such as whether a cell divides, differentiates or dies, can take many hours or days. Multiparameter experimental and computational methods that integrate quantitative measurement and mathematical simulation of these noisy and complex processes are required to understand the highly dynamic mechanisms that control cell plasticity and fate.