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Introduction: The VisiTag module (CARTO3) provides an objective assessment of radiofrequency (RF) ablation parameters. This study aimed to determine the predictive value and optimal VisiTag threshold settings for prediction of gaps in mature atrial scar, as assessed non‐invasively using cardiac magnetic resonance (CMR) imaging. Methods: Twenty‐four subjects (11 paroxysmal atrial fibrillation) underwent first‐time RF ablation with operators blinded to VisiTag data. Three‐dimensional late gadolinium enhancement (LGE) CMR scans were performed at 3 months (1.3 × 1.3 × 4 mm3). A survey of UK operators defined the standard VisiTag settings ("Force," 8 g; "Time," 10 seconds; "Percentage Time," 50%; "Range," 3 mm; "Impedance" and "Temperature" "off"). Each ablation procedure was exported 27 times, varying single VisiTag parameters from default values. The presence of gaps in VisiTag markers (18 sectors) was assessed for each export and compared with gaps in CMR enhancement. Results: At default settings, VisiTag gaps were specific (97.5%) but less sensitive (50.4%) for CMR gaps. Sensitivity improved at higher thresholds (89.2% at 20 g, 85.6% at 30 seconds, 88.5% impedance 10 Ω, 92.8% temperature 42°C), but with a lower positive predictive value (PPV) (42.3%, 42.7%, 41.1%, and 37.7%, respectively, vs 90.9% at baseline). "Force" thresholds demonstrated stable PPV from 2 to 8 g (P = 0.24), but a rapid fall at forces more than 10 g. The binomial logistic regression model explained 41.7% of gaps; χ2(4), 148; P < 0.0001, correctly classifying 82% of cases (specificity 94.9%, sensitivity 56.8%). Conclusion: Gaps in VisiTags predict gaps in CMR LGE enhancement with high specificity at default settings. Sensitivity may be improved using more stringent thresholds but at the potential cost of unnecessary ablation, particularly when a force more than 10 g is stipulated. [ABSTRACT FROM AUTHOR]

Background: Priority setting, identification of unmet and changing healthcare needs, service and policy planning, and the capacity to evaluate the impact of health interventions requires valid and reliable methods for quantifying disease and injury burden. The methodology developed for the Global Burden of Disease (GBD) studies has been adopted to estimate the burden of disease in national, regional and global projects. However, there has been little validation of the methods for estimating injury burden using empirical data. Objective: To provide valid estimates of the burden of non-fatal injury using empirical data. Setting: Data from prospective cohort studies of injury outcomes undertaken in the UK, USA, Australia, New Zealand and The Netherlands. Design and participants: Meta-analysis of deidentified, patient-level data from over 40 000 injured participants in six prospective cohort studies: Victorian State Trauma Registry, Victorian Orthopaedic Trauma Outcomes Registry, UK Burden of Injury study, Prospective Outcomes of Injury study, National Study on Costs and Outcomes of Trauma and the Dutch Injury Patient Survey. Analysis: Data will be systematically analysed to evaluate and refine injury classification, development of disability weights, establishing the duration of disability and handling of cases with more than one injury in burden estimates. Developed methods will be applied to incidence data to compare and contrast various methods for estimating non-fatal injury burden. Contribution to the field: The findings of this international collaboration have the capacity to drive how injury burden is measured for future GBD estimates and for individual country or region-specific studies. [ABSTRACT FROM AUTHOR]

This article examines a report on the likely impact of the spending cuts on women. The report, Unravelling Equality: A Human Rights and Equality Impact Assessment of the Spending Cuts on Women in Coventry, concludes that the public spending cuts will increase inequality between women and men. For some women the cuts may have serious negative effects on their human rights. The article argues that this report provides a blueprint for the kind of analysis which should be carried out all over the country to ensure that the impact of spending cuts on women is better understood and acted upon. [ABSTRACT FROM AUTHOR]

Describes the MILTON model of health care policy and management in Great Britain. Issues on health care policy and management; Factors influencing the development of health policy; Health care aspect of World Bank's economic agenda.

Corporate governance was once something akin to a minority, even elite, interest and unlikely to ever become a feature of popular (and especially public sector) management culture. This is no longer true. This article draws upon a post reform assessment of boardroom practice in English District Health Authorities as a means of reflecting upon matters of governance and to illuminate the case for both policy and practice change. Whilst the data derive from Health Authorities, the findings have significance for the boards of other NHS bodies and a relevance to other parts of the public and not-for-profit sector(s) experiencing or contemplating similar changes. [ABSTRACT FROM AUTHOR]

We assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases and 25 quantitative traits that has been made available on the individuals in UKB, using a unified pipeline for PRS evaluation. We also release a benchmarking software tool to enable like-for-like performance evaluation for different PRSs for the same disease or trait. Extensive benchmarking shows the PRSs in the UKB Release to outperform a broad set of 76 published PRSs. For many of the diseases and traits we also validate the PRS algorithms in a separate cohort (100,000 Genomes Project). The availability of PRSs for 53 traits on the same set of individuals also allows a systematic assessment of their properties, and the increased power of these PRSs increases the evidence for their potential clinical benefit., Competing Interests: Peter Donnelly and Gil McVean are partners in Peptide Groove LLP. Deborah Thompson, Daniel Wells, Saskia Selzam, Iliana Peneva, Rachel Moore, Kevin Sharp, William Tarran, Edward Beard,Fernando Riveros-Mckay, Carla Giner-Delgado, Duncan Palmer, Priyanka Seth, James Harrison, Gil McVean, Vincent Plagnol, Peter Donnelly and Michael Weale are current or former employees of Genomics plc, and are or have been in possession of stock or stock options for Genomics plc. Peter Donnelly and Gil McVean are Founders and Directors of Genomics plc, and Peter Donnelly is the CEO of Genomics plc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Thompson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease., Design: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry., Results: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10 -10 and 0.002 (OR allelic =1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33)., Conclusion: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: . Diarrhea is a well-established problem in travellers, with military personnel at especially high risk. This study aimed to characterise the spectrum of pathogens causing diarrhea in UK military personnel in South Sudan, and assess the utility of culture-independent testing for etiology and antimicrobial resistance in a logistically challenging and austere environment., Methods: . All military personnel presenting with diarrhea were admitted to the UK Level 2 Medical Treatment Facility in Bentiu, South Sudan. Samples were tested for etiology utilising multiplex PCR-based diagnostics (BioFire FilmArray). In addition, the presence of carbapenemase resistance genes was determined using the geneXpert Carba-R platform., Results: . Over 5 months, 127 samples were tested. The vast majority of pathogens detected were diarrheagenic Escherichia coli. The presence of either enterotoxigenic (ETEC) or enteropathogenic (EPEC) E. coli was a significant predictor of the other being present. In this study patients presenting with vomiting were 32 times more likely to have norovirus than not (p < 0.001). No carbapenem resistance was detected., Conclusions: . Diarrhea in UK military personnel in South Sudan was determined to be predominantly bacterial, with norovirus presenting a distinct clinical and epidemiological pattern. Multiplex PCR and molecular resistance point of care testing were robust and effective in this environment., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Objective: Previously generated genetic risk scores (GRSs) for type 1 diabetes (T1D) have not captured all known information at non-HLA loci or, particularly, at HLA risk loci. We aimed to more completely incorporate HLA alleles, their interactions, and recently discovered non-HLA loci into an improved T1D GRS (termed the "T1D GRS2") to better discriminate diabetes subtypes and to predict T1D in newborn screening studies., Research Design and Methods: In 6,481 case and 9,247 control subjects from the Type 1 Diabetes Genetics Consortium, we analyzed variants associated with T1D both in the HLA region and across the genome. We modeled interactions between variants marking strongly associated HLA haplotypes and generated odds ratios to create the improved GRS, the T1D GRS2. We validated our findings in UK Biobank. We assessed the impact of the T1D GRS2 in newborn screening and diabetes classification and sought to provide a framework for comparison with previous scores., Results: The T1D GRS2 used 67 single nucleotide polymorphisms (SNPs) and accounted for interactions between 18 HLA DR-DQ haplotype combinations. The T1D GRS2 was highly discriminative for all T1D (area under the curve [AUC] 0.92; P < 0.0001 vs. older scores) and even more discriminative for early-onset T1D (AUC 0.96). In simulated newborn screening, the T1D GRS2 was nearly twice as efficient as HLA genotyping alone and 50% better than current genetic scores in general population T1D prediction., Conclusions: An improved T1D GRS, the T1D GRS2, is highly useful for classifying adult incident diabetes type and improving newborn screening. Given the cost-effectiveness of SNP genotyping, this approach has great clinical and research potential in T1D., (© 2019 by the American Diabetes Association.)

Introduction: Traumatic injury is a leading contributor to the global disease burden in children and adolescents, but methods used to estimate burden do not account for differences in patterns of injury and recovery between children and adults. A lack of empirical data on postinjury disability in children has limited capacity to derive valid disability weights and describe the long-term individual and societal impacts of injury in the early part of life. The aim of this study is to establish valid estimates of the burden of non-fatal injury in children and adolescents., Methods and Analysis: Five longitudinal studies of paediatric injury survivors <18 years at the time of injury (Australia, Canada, UK and USA) and two whole-of-population linked administrative data paediatric studies (Australia and Wales) will be analysed over a 3-year period commencing 2018. Meta-analysis of deidentified patient-level data (n≈2,600) from five injury-specific longitudinal studies (Victorian State Trauma Registry; Victorian Orthopaedic Trauma Outcomes Registry; UK Burden of Injury; British Columbia Children's Hospital Longitudinal Injury Outcomes; Children's Health After Injury) and >1 million children from two whole-of-population cohorts (South Australian Early Childhood Data Project and Wales Electronic Cohort for Children). Systematic analysis of pooled injury-specific cohort data using a variety of statistical techniques, and parallel analysis of whole-of-population cohorts, will be used to develop estimated disability weights for years lost due to disability, establish appropriate injury classifications and explore factors influencing recovery., Ethics and Dissemination: The project was approved by the Monash University Human Research Ethics Committee project number 12 311. Results of this study will be submitted for publication in internationally peer-reviewed journals. The findings from this project have the capacity to improve the validity of paediatric injury burden measurements in future local and global burden of disease studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Priority setting, identification of unmet and changing healthcare needs, service and policy planning, and the capacity to evaluate the impact of health interventions requires valid and reliable methods for quantifying disease and injury burden. The methodology developed for the Global Burden of Disease (GBD) studies has been adopted to estimate the burden of disease in national, regional and global projects. However, there has been little validation of the methods for estimating injury burden using empirical data., Objective: To provide valid estimates of the burden of non-fatal injury using empirical data., Setting: Data from prospective cohort studies of injury outcomes undertaken in the UK, USA, Australia, New Zealand and The Netherlands., Design and Participants: Meta-analysis of deidentified, patient-level data from over 40 000 injured participants in six prospective cohort studies: Victorian State Trauma Registry, Victorian Orthopaedic Trauma Outcomes Registry, UK Burden of Injury study, Prospective Outcomes of Injury study, National Study on Costs and Outcomes of Trauma and the Dutch Injury Patient Survey., Analysis: Data will be systematically analysed to evaluate and refine injury classification, development of disability weights, establishing the duration of disability and handling of cases with more than one injury in burden estimates. Developed methods will be applied to incidence data to compare and contrast various methods for estimating non-fatal injury burden., Contribution to the Field: The findings of this international collaboration have the capacity to drive how injury burden is measured for future GBD estimates and for individual country or region-specific studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.