Are routinely collected NHS administrative records suitable for endpoint identification in clinical trials? Evidence from the West of Scotland coronary prevention study

Background: Routinely collected electronic patient records are already widely used in epidemiological research. In this work we investigated the potential for using them to identify endpoints in clinical trials.<p></p> Methods: The events recorded in the West of Scotland Coronary Prevention Study (WOSCOPS), a large clinical trial of pravastatin in middle-aged hypercholesterolaemic men in the 1990s, were compared with those in the record-linked deaths and hospitalisations records routinely collected in Scotland.<p></p> Results: We matched 99% of fatal study events by date. We showed excellent matching (97%) of the causes of fatal endpoint events and good matching (.80% for first events) of the causes of nonfatal endpoint events with a slightly lower rate of mismatching of record linkage than study events (19% of first study myocardial infarctions (MI) and 4% of first record linkage MIs not matched as MI). We also investigated the matching of non-endpoint events and showed a good level of matching, with .78% of first stroke/TIA events being matched as stroke/TIA. The primary reasons for mismatches were record linkage data recording readmissions for procedures or previous events, differences between the diagnoses in the routinely collected data and the conclusions of the clinical trial expert adjudication committee, events occurring outside Scotland and therefore being missed by record linkage data, miscoding of cardiac events in hospitalisations data as ‘unspecified chest pain’, some general miscoding in the record linkage data and some record linkage errors.<p></p> Conclusions: We conclude that routinely collected data could be used for recording cardiovascular endpoints in clinical trials and would give very similar results to rigorously collected clinical trial data, in countries with unified health systems such as Scotland. The endpoint types would need to be carefully thought through and an expert endpoint adjudication committee should be involved.<p></p&gt

A measurement technique to determine the calibration accuracy of an electromagnetic tracking system to radiation isocenter

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135100/1/mp3910.pd

Factors Affecting Trypanosome Maturation in Tsetse Flies

Trypanosoma brucei brucei infections which establish successfully in the tsetse fly midgut may subsequently mature into mammalian infective trypanosomes in the salivary glands. This maturation is not automatic and the control of these events is complex. Utilising direct in vivo feeding experiments, we report maturation of T. b. brucei infections in tsetse is regulated by antioxidants as well as environmental stimuli. Dissection of the maturation process provides opportunities to develop transmission blocking vaccines for trypanosomiasis. The present work suggests L-cysteine and/or nitric oxide are necessary for the differentiation of trypanosome midgut infections in tsetse

Electrical, morphological and structural properties of RF magnetron sputtered Mo thin films for application in thin film photovoltaic solar cells

Molybdenum (Mo) thin films were deposited using radio frequency magnetron sputtering, for application as a metal back contact material in ‘‘substrate configuration’’ thin film solar cells. The variations of the electrical, morphological, and structural properties of the deposited films with sputtering pressure, sputtering power and post-deposition annealing were determined. The electrical conductivity of the Mo films was found to increase with decreasing sputtering pressure and increasing sputtering power. X-ray diffraction data showed that all the films had a (110) preferred orientation that became less pronounced at higher sputtering power while being relatively insensitive to process pressure. The lattice stress within the films changed from tensile to compressive with increasing sputtering power and the tensile stress increased with increasing sputtering pressure. The surface morphology of the films changed from pyramids to cigar-shaped grains for a sputtering power between 100 and 200 W, remaining largely unchanged at higher power. These grains were also observed to decrease in size with increasing sputtering pressure. Annealing the films was found to affect the resistivity and stress of the films. The resistivity increased due to the presence of residual oxygen and the stress changed from tensile to compressive. The annealing step was not found to affect the crystallisation and grain growth of the Mo films

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

The Panchromatic Afterglow of GW170817: The full uniform dataset, modeling, comparison with previous results and implications

We present the full panchromatic afterglow light curve data of GW170817, including new radio data as well as archival optical and X-ray data, between 0.5 and 940 days post-merger. By compiling all archival data, and reprocessing a subset of it, we have ensured that the panchromatic dataset is uniform and therefore immune to the differences in data processing or flux determination methods used by different groups. Simple power-law fits to the uniform afterglow light curve indicate a t^(0.86±0.04) rise, a t^(−1.90±0.12) decline, and a peak occurring at 155±4 days. The afterglow is optically thin throughout its evolution, consistent with a single spectral index (−0.569±0.002) across all epochs. This gives a precise and updated estimate of the electron power-law index, p=2.138±0.004. By studying the diffuse X-ray emission from the host galaxy, we place a conservative upper limit on the hot ionized ISM density, <0.01 cm⁻³, consistent with previous afterglow studies. Using the late-time afterglow data we rule out any long-lived neutron star remnant having magnetic field strength between 10^(10.4) G and 10¹⁶ G. Our fits to the afterglow data using an analytical model that includes VLBI proper motion from Mooley et al (2018), and a structured jet model that ignores the proper motion, indicates that the proper motion measurement needs to be considered while seeking an accurate estimate of the viewing angle

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes