COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases.

Epidemiological studies suggest that individuals with comorbid conditions including diabetes, chronic lung, inflammatory and vascular disease, are at higher risk of adverse COVID-19 outcomes. Genome-wide association studies have identified several loci associated with increased susceptibility and severity for COVID-19. However, it is not clear whether these associations are genetically determined or not. We used a Phenome-Wide Association (PheWAS) approach to investigate the role of genetically determined COVID-19 susceptibility on disease related outcomes. PheWAS analyses were performed in order to identify traits and diseases related to COVID-19 susceptibility and severity, evaluated through a predictive COVID-19 risk score. We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10). Our study identifies significant association of genetically determined COVID-19 with increased blood clot events in leg and lungs. The reported associations between both COVID-19 susceptibility and severity and other diseases adds to the identification and stratification of individuals at increased risk, adverse outcomes and long-term effects

Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/thy.2020.0393

Measurement of absolute γ-ray emission probabilities in the decay of 227Ac in equilibrium with its progeny

Abstract The emission probabilities of γ rays produced in the 227Ac decay series were determined by high-resolution γ-ray spectrometry of sources with standardised activity. The sources were prepared quantitatively on glass discs by drop deposition of a solution with 227Ac in radioactive equilibrium with its daughter nuclides. Their activity was measured by a primary standardisation technique based on alpha-particle counting at a defined low solid angle. Four laboratories performed γ-ray spectrometry and derived absolute γ-ray intensities. Mean values were calculated and compared with literature data and the currently recommended evaluated data. New values on certain γ-ray emission probabilities are proposed

measurement of absolute γ ray emission probabilities in the decay of 235u

Abstract Accurate measurements were performed of the photon emission probabilities following the α decay of 235U to 231Th. Sources of highly enriched 235U were characterised in terms of isotopic composition by mass spectrometry and their activities were standardised by means of alpha-particle counting at a low defined solid angle. The standardised sources were subsequently measured by high-resolution γ-ray spectrometry with calibrated high-purity germanium detectors to determine the photon emission probabilities. Four laboratories participated in this work and reported emission probabilities for 33 γ-ray lines. Most of them agree with previously published evaluated data. In addition, new values are proposed for γ-lines which have been measured only once in the past

Preparation and certification of 243Am spike reference material: IRMM-0243 : Certified reference material for the amount content of 243Am and n(241Am)7n(243Am) isotope amount ratio

This report describes the preparation and certification of IRMM-0243, a 243Am spike reference material. It is certified for the amount content of 243Am and the isotope amount ratios of n(241Am)/n(243Am) and n(242mAm)/n(243Am). Furthermore, the material is certified for the amount contents of 241Am and total Am, the mass fractions of 243Am, 241Am and total Am, the isotope amount and mass fractions (e.g. isotopic composition) and the molar mass of Am. The material was produced in compliance with ISO/IEC 17034:2016 and certified in accordance with ISO Guide 35:2006. The material was prepared by dilution of an americium starting solution in nitric acid and dispensing of the solution into glass ampoules. In total 587 units were produced. Between-unit homogeneity was quantified and stability during dispatch and storage were assessed in accordance with ISO Guide 35:2006. The characterisation of the amount content of 243Am was performed by Isotope Dilution Mass Spectrometry (IDMS) using a 241Am spike, produced from highly enriched 241Pu material. The isotope amount ratios of n(241Am)/n(243Am) and n(242mAm)/n(243Am) were measured by Thermal Ionisation Mass Spectrometry (TIMS). The certified values were verified by alpha particle spectrometry, alpha particle counting at a defined solid angle (DSA) and high-resolution gamma-ray spectrometry as independent verification methods. The uncertainties of the certified values were estimated in compliance with the Guide to the Expression of Uncertainty in Measurement (GUM) [ ] and include uncertainties related to possible inhomogeneity, instability and characterisation. The main purpose of this material is for use as a spike isotopic reference material for the quantification of americium by IDMS in unknown samples. A unit of IRMM-0243 consists of a glass ampoule with a screw cap containing about 3.5 mL nitric acid solution (c = 1 mol/L) with an americium mass fraction of about 1.5 μg/g solution. The material is a true solution; therefore there is no recommended minimum sample intake to be taken into account.JRC.G.2-Standards for Nuclear Safety, Security and Safeguard

Understanding Resource Consumption in the Home, Community and Society through Behaviour and Social Practice Theories

The practices and behaviours of individuals influences resource consumption at many scales and are shaped by a multitude of psychological, social, and technical factors. This conceptual paper examines the differences between socio-psychological and social practice theories, building on the Chalk and Cheese debate in the literature. Insight is provided into their potential value in understanding resource consumption studies at different scales: the individual, the home, community, and societal. Each theory has its own qualitative and quantitative methods which allude to different conclusions and recommendations for resource consumption initiatives. We review the debate surrounding the application of both theories, adding our voice to the potential for both theories to be used at different scales and for different time periods, along with comments on the interlocking nature of practices. Design and technology changes can lead to quicker changes in behaviour and practices, whereby socio-psychological theories offer insights into changes in mind frame, values, and social norms

No Clinically Relevant Effect of Heart Rate Increase and Heart Rate Recovery During Exercise on Cardiovascular Disease: A Mendelian Randomization Analysis

Background: Reduced heart rate (HR) increase (HRI), recovery (HRR), and higher resting HR are associated with cardiovascular (CV) disease, but causal inferences have not been deduced. We investigated causal effects of HRI, HRR, and resting HR on CV risk, all-cause mortality (ACM), atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke (IS) using Mendelian Randomization. Methods: 11 variants for HRI, 11 for HRR, and two sets of 46 and 414 variants for resting HR were obtained from four genome-wide association studies (GWASs) on UK Biobank. We performed a lookup on GWASs for CV risk and ACM in UK Biobank (N = 375,367, 5.4% cases and N = 393,165, 4.4% cases, respectively). For CAD, AF, and IS, we used publicly available summary statistics. We used a random-effects inverse-variance weighted (IVW) method and sensitivity analyses to estimate causality. Results: IVW showed a nominally significant effect of HRI on CV events (odds ratio [OR] = 1.0012, P = 4.11 × 10–2) and on CAD and AF. Regarding HRR, IVW was not significant for any outcome. The IVW method indicated statistically significant associations of resting HR with AF (OR = 0.9825, P = 9.8 × 10–6), supported by all sensitivity analyses, and a nominally significant association with IS (OR = 0.9926, P = 9.82 × 10–3). Conclusion: Our findings suggest no strong evidence of an association between HRI and HRR and any outcome and confirm prior work reporting a highly significant effect of resting HR on AF. Future research is required to explore HRI and HRR associations further using more powerful predictors, when available

The role of thyroid function in borderline personality disorder and schizophrenia: a Mendelian Randomisation study.

BACKGROUND: Genome-wide association studies have reported a genetic overlap between borderline personality disorder (BPD) and schizophrenia (SCZ). Epidemiologically, the direction and causality of the association between thyroid function and risk of BPD and SCZ are unclear. We aim to test whether genetically predicted variations in TSH and FT4 levels or hypothyroidism are associated with the risk of BPD and SCZ. METHODS: We employed Mendelian Randomisation (MR) analyses using genetic instruments associated with TSH and FT4 levels as well as hypothyroidism to examine the effects of genetically predicted thyroid function on BPD and SCZ risk. Bidirectional MR analyses were employed to investigate a potential reverse causal association. RESULTS: Genetically predicted higher FT4 was not associated with the risk of BPD (OR: 1.18; P = 0.60, IVW) or the risk of SCZ (OR: 0.93; P = 0.19, IVW). Genetically predicted higher TSH was not associated with the risk of BPD (OR: 1.11; P = 0.51, IVW) or SCZ (OR: 0.98, P = 0.55, IVW). Genetically predicted hypothyroidism was not associated with BPD or SCZ. We found no evidence for a reverse causal effect between BPD or SCZ on thyroid function. CONCLUSIONS: We report evidence for a null association between genetically predicted FT4, TSH or hypothyroidism with BPD or SCZ risk. There was no evidence for reverse causality

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants