Effect of multiple forging and annealing on microstructure and mechanical properties of a high-manganese steel

The effect of multiple forging and annealing on the microstructure and mechanical properties of a high-manganese steel is considered. An austenitic high-manganese steel, Fe-0.03C-28Mn-1.5Al (all in wt.%), with an average grain size of about 37 qm was used as th initial material in this study. Multiple forging at room temperature was carried out up to a total true strain of 2. Multiple forging was accompanied by deformation twinning and resulted in significant strengthening. The steel samples subjected to multiple forging demonstrate an increase in the strength properties with an increase in the total strain, while elongation decrease

The Microstructure and Strength of UFG 6060 alloy after superplastic deformation at a lower homologous temperature

The paper reports on the features of low-temperature superplasticity of the heat-treatable aluminum Al-Mg-Si alloy in the ultrafine-grained state at temperatures below 0.5 times the melting point as well as on its post-deformation microstructure and tensile strengt

Paragraph: A graph-based structural variant genotyper for short-read sequence data

Accurate detection and genotyping of structural variations (SVs) from short-read data is a long-standing area of development in genomics research and clinical sequencing pipelines. We introduce Paragraph, an accurate genotyper that models SVs using sequence graphs and SV annotations. We demonstrate the accuracy of Paragraph on whole-genome sequence data from three samples using long-read SV calls as the truth set, and then apply Paragraph at scale to a cohort of 100 short-read sequenced samples of diverse ancestry. Our analysis shows that Paragraph has better accuracy than other existing genotypers and can be applied to population-scale studies. © 2019 The Author(s)

Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology

Background: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines. Methods: A total of 6187 patients (18–80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012–2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. Results: A total of 2846 (46%) patients had no diabetes, 1158 (19%) newly diagnosed diabetes and 2183 (35 %) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60%, respectively. A blood pressure target of 9.0% (>75 mmol/mol). Of the patients with diabetes 69% reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (≈40%) and only 27% of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets. Conclusions: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease

Detection of long repeat expansions from PCR-free whole-genome sequence data

Identifying large expansions of short tandem repeats (STRs) such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step towards integrating WGS into precision medicine. We have developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3,001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2,786/2,789, 95% CI [0.997, 1.00]) of the wild type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples where every sample had one of eight different pathogenic repeat expansions including those associated with fragile X syndrome, Friedreich's ataxia and Huntington's disease and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions. The software is licensed under GPL v3.0 and the source code is freely available on GitHub

Проблема отказов от иммунодиагностики туберкулеза: результаты многоцентрового социологического исследования

The objective: to study the reasons for the refusal of legally authorized representatives of children to conduct mass immunodiagnosis of tuberculosis using a representative sample of population and to outline possible ways to change this negative situation.Subjects and methods: A cross-sectional multi-center study was conducted. In 8 regions of the Russian Federation, the survey was conducted in 1,059 legally authorized representatives of children refusing to undergo mass immunodiagnostics of tuberculosis. The following main reasons for refusal were found out: fear of side effects and complications (32.6%), distrust in the quality of the test (29.7%), lack of understanding of the need to examine a child for tuberculosis. 72.2% of respondents demonstrated poor awareness of the problem of tuberculosis – they denied this problem or associated it with a different social environment, which was fertile ground for negative information received through various channels. To solve this problem, it is necessary to intensify health education in various groups of the population, including work with religious communities. Additional resources can be used such as targeted social advertisements, which will allow covering with health education propaganda of 33.1% of people who do not want to receive information about tuberculosis, expanding the regulation for the use of alternative methods of screening for tuberculosis.The authors state that they have no conflict of interests.Цель исследования: на репрезентативной выборке изучить причины отказа законных представителей детей от проведения мероприятий по массовой иммунодиагностике туберкулеза и наметить возможные пути корректировки данного негативного явления.Материалы и методы: одномоментное многоцентровое исследование. В 8 субъектах Российской Федерации проведено анкетирование 1 059 законных представителей детей, отказывающихся от мероприятий по массовой иммунодиагностике туберкулеза. Установлено, что основными причинами их отказа явились: страх побочных реакций и осложнений (32,6%), недоверие качеству теста (29,7%), отсутствие смыслового мотива обследования ребенка на туберкулез. У 72,2% респондентов установлена недостаточная информированность о проблеме туберкулеза ‒ ее отрицание или смещение в иную социальную среду, что явилось благодатной почвой для негативной информации, получаемой по различным каналам. Для решения данной проблемы необходимо активизировать санитарно-просветительскую работу с различными группами населения, в том числе работу с религиозными общинами. Дополнительными ресурсами могут быть: использование тематической целевой социальной рекламы, которая позволит вести санитарную пропаганду среди 33,1% лиц, не желающих получать информацию о туберкулезе, расширение нормативной базы для применения альтернативных методов обследования на туберкулез.Авторы заявляют об отсутствии у них конфликта интересов

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons