Interhospital variation in the RATPAC trial (Randomised Assessment of Treatment using Panel Assay of Cardiac markers)

Background: The RATPAC trial showed that using a point-of-care panel of CK-MB(mass), myoglobin and troponin at baseline and 90 min increased the proportion of patients successfully discharged home, leading to reduced median length of initial hospital stay. However, it did not change mean hospital stay and may have increased mean costs per patient. The aim of this study was to explore variation in outcome and costs between participating hospitals. Methods: RATPAC was a pragmatic multicentre randomised controlled trial (N=2243) and economic analysis comparing diagnostic assessment using the panel to standard care for patients with acute chest pain due to suspected myocardial infarction at six hospitals. The difference in the proportion of patients successfully discharged (primary outcome) and mean costs per patient between the participating hospitals was compared. Results: Point-of-care assessment led to a higher proportion of successful discharges in four hospitals, a lower proportion in one and was equivocal in another. The OR (95% CI) for the primary outcome varied from 0.12 (0.01 to 1.03) to 11.07 (6.23 to 19.66) with significant heterogeneity between the centres (

The West Midland Space Sector Strengths, Underpinning Assets, and Market

This report outlines the key findings from the West Midlands Space Cluster project. The project has:• mapped regional space activities in industry, academia and beyond • developed a vision for how the region could become a major player in space industry – identified the regional specialisms and networking opportunities• assessed the opportunities for the regional supply chain to join these developments and hence the realise growth potential for the regionThere have been four key stages of research, these are:• Phase 1 – Secondary Data Analysis of Space Sector Firms in the Region • Phase 2 – Secondary Data Analysis of Underlying Assets in the Region • Phase 3: Interviews with Key Stakeholders • Phase 4: Local Space Leadership GroupThe project was led by WMREDI/City-REDI and supported by Professor Kai Bongs (Director of Innovation – College for Engineering and Physical Sciences) and Tariq Ali (Deputy Pro-Vice Chancellor for Strategic Partnerships, University of Birmingham, and Vice-Provost for Research & Innovation).This report developed in partnership with the West Midlands Combined Authority, Greater Birmingham and Solihull Local Enterprise Partnership (GBSLEP), the Black Country LEP and Coventry and Warwickshire LEP, under the UKSA Local Space Sector Cluster and Supply Chain Development Funding Call

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy : Insights From Wave Intensity Analysis and Magnetic Resonance

Background: Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives: Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods: Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results: Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions: Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment

Enter Mercury, Sleeping: Delivering Prayers on the Early Modern Stage

This is the author accepted manuscript. The final version is available from CUP via the DOI in this recor

When will we learn? Improving lessons learned practice in construction

This article was accepted for publication in the International Journal of Project Management [© Elsevier]. The definitive version will be available at: http://dx.doi.org/10.1016/j.ijproman.2012.10.005Purpose: The aim of the research is to improve lessons learned practices within construction contractor organisations. This will result in contractors' project teams having access to the most relevant lessons at the most appropriate time, in the most appropriate format. Scope: The research was based on the responses of 41 large UK contractor organisations to a questionnaire survey, detailed interviews with nine companies and three focus groups. The respondents were senior and middle managers variously involved in business improvement, knowledge management, and technical services. Results: The questionnaire survey identified methods, tools and processes used to collect lessons learned. The interviews and the focus groups uncovered the diverging requirements of corporate vs. site-based staff. The data contributed to the development of a project learning model and a conceptual model from which a Project Learning Roadmap was derived to support business leaders to improve their project lessons learned processes. This will enable organisations to develop individual solutions tailored to stakeholders' needs

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio