Early coronary angiography and survival after out-of-hospital cardiac arrest: a systematic review and meta-analysis

Background: Although acute myocardial infarction is a common cause of out-of-hospital cardiac arrest (OHCA), the role of early coronary angiography in OHCA remains uncertain. We conducted a meta-analysis of observational studies to determine the association of early coronary angiography with survival in OHCA. Methods: We searched multiple electronic databases for published studies on early coronary angiography in OHCA between 1 January 1990 and 18 January 2017. Studies were included if (1) restricted to only OHCA, (2) included an exposure group that underwent early coronary angiography within 1  day of arrest onset and a concurrent control group that did not undergo early coronary angiography, and (3) reported survival outcomes. We used a random-effects model to obtain pooled OR. I2 statistics and Cochran's Q test were used to determine between-study heterogeneity. Results: A total of 17 studies with 14 972 patients were included, of whom 6424 (44%) received early coronary angiography. Early coronary angiography was associated with higher odds of survival (pooled OR 2.54 (95% CI 1.94 to 3.33)) and survival with favourable neurological outcome (pooled OR 2.37 (95%  CI 1.71 to 3.28)). However, there was substantial heterogeneity in our pooled estimate (I2=88%  and p value for Cochran's test <0.0001 for both outcomes). The large heterogeneity in pooled estimates was reduced after including adjusted estimates when available, and was explained by differences in methodological rigour and characteristics of included studies. Conclusion: Among patients resuscitated from OHCA, early coronary angiography is associated with increased survival to discharge and favourable neurological outcome

Clinical Fellowships in Surgical Training: Analysis of a National Pan-specialty Workforce Survey

BACKGROUND: Fellowship posts are increasingly common and offer targeted opportunities for training and personal development. Despite international demand, there is little objective information quantifying this effect or the motivations behind undertaking such a post. The present study investigated surgical trainees’ fellowship aims and intentions. METHODS: An electronic, 38-item, self-administered questionnaire survey was distributed in the United Kingdom via national and regional surgical mailing lists and websites via the Association of Surgeons in Training, Royal Surgical Colleges, and Specialty Associations. RESULTS: In all, 1,581 fully completed surveys were received, and 1,365 were included in the analysis. These represented trainees in core or higher training programs or research from all specialties and training regions: 66 % were male; the mean age was 32 years; 77.6 % intended to or had already completed a fellowship. Plastic surgery (95.2 %) and cardiothoracic (88.6 %) trainees were most likely to undertake a fellowship, with pediatrics (51.2 %), and urology (54.3 %) the least likely. Fellowship uptake increased with seniority (p < 0.01) and was positively correlated (p = 0.016, r = 0.767) with increasing belief that fellowships are necessary to the attainment of clinical competence, agreed by 73.1 %. Fellowship aims were ranked in descending order of importance as attaining competence, increasing confidence, and attaining subspecialist skills. CONCLUSIONS: Over three-quarters of trainees have or will undertake a clinical fellowship, varying with gender, specialty, and seniority. Competence, confidence, and subspecialty skills development are the main aims. The findings will influence workforce planning, and perceptions that current training does not deliver sufficient levels of competence and confidence merit further investigation

Long-range potential fluctuations and 1/f noise in hydrogenated amorphous silicon

We present a microscopic theory of the low-frequency voltage noise (known as "1/f" noise) in micrometer-thick films of hydrogenated amorphous silicon. This theory traces the noise back to the long-range fluctuations of the Coulomb potential produced by deep defects, thereby predicting the absolute noise intensity as a function of the distribution of defect activation energies. The predictions of this theory are in very good agreement with our own experiments in terms of both the absolute intensity and the temperature dependence of the noise spectra.Comment: 8 pages, 3 figures, several new parts and one new figure are added, but no conceptual revision

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth \u3e29X and analyze genotypes with four quantitative traits—plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

Lifetime Risks for Cardiovascular Disease Mortality by Cardiorespiratory Fitness Levels Measured at Ages 45, 55, and 65 Years in Men The Cooper Center Longitudinal Study

ObjectivesThe purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).BackgroundHigher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.MethodsWe followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event.ResultsDifferences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors.ConclusionsA single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors

Measuring the impact of ambulatory red blood cell transfusion on home functional status: study protocol for a pilot randomized controlled trial

SPIRIT 2013: SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Checklist for clinical trial protocols. (DOCX 65 kb

Three-Dimensional Printed Hydroxyapatite Bone Substitutes Designed by a Novel Periodic Minimal Surface Algorithm Are Highly Osteoconductive

Autologous bone remains the gold standard bone substitute in clinical practice. Therefore, the microarchitecture of newly developed synthetic bone substitutes, which reflects the spatial distribution of materials in the scaffold, aims to recapitulate the natural bone microarchitecture. However, the natural bone microarchitecture is optimized to obtain a mechanically stable, lightweight structure adapted to the biomechanical loading situation. In the context of synthetic bone substitutes, the application of a Triply Periodic Minimum Surface (TPMS) algorithm can yield stable lightweight microarchitectures that, despite their demanding architectural complexity, can be produced by additive manufacturing. In this study, we applied the TPMS derivative Adaptive Density Minimal Surfaces (ADMS) algorithm to produce scaffolds from hydroxyapatite (HA) using a lithography-based layer-by-layer methodology and compared them with an established highly osteoconductive lattice microarchitecture. We characterized them for compression strength, osteoconductivity, and bone regeneration. The in vivo results, based on a rabbit calvaria defect model, showed that bony ingrowth into ADMS constructs as a measure of osteoconduction depended on minimal constriction as it limited the maximum apparent pore diameter in these scaffolds to 1.53 mm. Osteoconduction decreased significantly at a diameter of 1.76 mm. The most suitable ADMS microarchitecture was as osteoconductive as a highly osteoconductive orthogonal lattice microarchitecture in noncritical- and critical-size calvarial defects. However, the compression strength and microarchitectural integrity in vivo were significantly higher for scaffolds with their microarchitecture based on the ADMS algorithm when compared with high-connectivity lattice microarchitectures. Therefore, bone substitutes with high osteoconductivity can be designed with the advantages of the ADMS-based microarchitectures. As TPMS and ADMS microarchitectures are true lightweight structures optimized for high mechanical stability with a minimal amount of material, such microarchitectures appear most suitable for bone substitutes used in clinical settings to treat bone defects in weight-bearing and non-weight-bearing sites

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth &gt;29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia