1,010 research outputs found

    Unified Analysis of Switched-Capacitor Resonant Converters

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    The QCD transition temperature: results with physical masses in the continuum limit

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    The transition temperature (TcT_c) of QCD is determined by Symanzik improved gauge and stout-link improved staggered fermionic lattice simulations. We use physical masses both for the light quarks (mudm_{ud}) and for the strange quark (msm_s). Four sets of lattice spacings (NtN_t=4,6,8 and 10) were used to carry out a continuum extrapolation. It turned out that only NtN_t=6,8 and 10 can be used for a controlled extrapolation, NtN_t=4 is out of the scaling region. Since the QCD transition is a non-singular cross-over there is no unique TcT_c. Thus, different observables lead to different numerical TcT_c values even in the continuum and thermodynamic limit. The peak of the renormalized chiral susceptibility predicts TcT_c=151(3)(3) MeV, wheres TcT_c-s based on the strange quark number susceptibility and Polyakov loops result in 24(4) MeV and 25(4) MeV larger values, respectively. Another consequence of the cross-over is the non-vanishing width of the peaks even in the thermodynamic limit, which we also determine. These numbers are attempted to be the full result for the TT≠\neq0 transition, though other lattice fermion formulations (e.g. Wilson) are needed to cross-check them.Comment: 13 pages 5 figures. Final version, published in Phys.Lett.

    Design and analysis of switched-capacitor-based step-up resonant converters

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    Development of a childhood obesity prevention programme with a focus on UK South Asian communities

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    OBJECTIVE: We report the development of a childhood obesity prevention intervention for UK South Asian primary school-aged children, guided by the UK Medical Research Council (MRC) framework for complex intervention development and evaluation. METHODS: We combined information gained from a literature review, stakeholder focus groups, an expert group, review of local resources and mapping to the Analysis Grid for Environments Linked to Obesity (ANGELO framework) in an intervention development process. The study took place in 2007 in Birmingham, UK. RESULTS: Contextual information from the stakeholder focus groups was essential for informing intervention development. The expert group defined guiding principles for the intervention. Informing intervention design by assessing existing local resources addressed intervention sustainability. The use of the ANGELO framework ensured a comprehensive environmental approach to intervention development. The intervention consisted of two broad processes; increasing children's physical activity levels through school, and increasing skills of families through activity-based learning. The developed intervention is being evaluated in a major study. CONCLUSIONS: The intervention development process has resulted in a tailored intervention programme to prevent childhood obesity in UK South Asian communities, but also intervention processes that could be applied to other communities and tailored to local context

    HumanMethylation450K array–identified biomarkers predict tumour recurrence/progression at initial diagnosis of high-risk non-muscle Invasive bladder cancer

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    Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/ or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HRNMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable diseas

    A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors

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    SummaryAim: Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels. Methods: This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis. Results: At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels. Conclusion: The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease. © 2010 Blackwell Publishing Ltd

    Dynamics of liquid He-4 in confined geometries from Time-Dependent Density Functional calculations

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    We present numerical results obtained from Time-Dependent Density Functional calculations of the dynamics of liquid He-4 in different environments characterized by geometrical confinement. The time-dependent density profile and velocity field of He-4 are obtained by means of direct numerical integration of the non-linear Schrodinger equation associated with a phenomenological energy functional which describes accurately both the static and dynamic properties of bulk liquid He-4. Our implementation allows for a general solution in 3-D (i.e. no symmetries are assumed in order to simplify the calculations). We apply our method to study the real-time dynamics of pure and alkali-doped clusters, of a monolayer film on a weakly attractive surface and a nano-droplet spreading on a solid surface.Comment: q 1 tex file + 9 Ps figure

    Genome-wide meta-analysis identifies novel genes associated with recurrence and progression in non–muscle-invasive bladder cancer

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    Background Non–muscle-invasive bladder cancer (NMIBC) is characterized by frequent recurrences and a risk of progression in stage and grade. Increased knowledge of underlying biological mechanisms is needed. Objective To identify single nucleotide polymorphisms (SNPs) associated with recurrence-free (RFS) and progression-free (PFS) survival in NMIBC. Design, setting, and participants We analyzed outcome data from 3400 newly diagnosed NMIBC patients from the Netherlands, the UK, Canada, and Spain. We generated genome-wide germline SNP data using Illumina OmniExpress and Infinium Global Screening Array in combination with genotype imputation. Outcome measurements and statistical analysis Cohort-specific genome-wide association studies (GWASs) for RFS and PFS were performed using a Cox proportional hazard model. Results were combined in a fixed-effect inverse-variance weighted meta-analysis. Candidate genes for the identified SNP associations were prioritized using functional annotation, gene-based analysis, expression quantitative trait locus analysis, and transcription factor binding site databases. Tumor expression levels of prioritized genes were tested for association with RFS and PFS in an independent NMIBC cohort. Results and limitations This meta-analysis revealed a genome-wide significant locus for RFS on chromosome 14 (lead SNP rs12885353, hazard ratio [HR] C vs T allele 1.55, 95% confidence interval [CI] 1.33–1.82, p = 4.0 × 10–8), containing genes G2E3 and SCFD1. Higher expression of SCFD1 was associated with increased RFS (HR 0.70, 95% CI 0.59–0.84, pFDR = 0.003). Twelve other loci were suggestively associated with RFS (p < 10–5), pointing toward 18 additional candidate genes. For PFS, ten loci showed suggestive evidence of association, indicating 36 candidate genes. Expression levels of ten of these genes were statistically significantly associated with PFS, of which four (IFT140, UBE2I, FAHD1, and NME3) showed directional consistency with our meta-analysis results and published literature. Conclusions In this first prognostic GWAS in NMIBC, we identified several novel candidate loci and five genes that showed convincing associations with recurrence or progression. Patient summary In this study, we searched for inherited DNA changes that affect the outcome of non–muscle-invasive bladder cancer (NMIBC). We identified several genes that are associated with disease recurrence and progression. The roles and mechanisms of these genes in NMIBC prognosis should be investigated in future studies
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