Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

The ABC130 barrel module prototyping programme for the ATLAS strip tracker

For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Fear of failure among young elite athletes

Fear of failure has negative psychological and physiological effects on children in achievement settings. Perceiving the consequences of failure to be aversive provides the basis for fear of failure, and the anticipation of threatening outcome ehcits fear. This thesis focuses on investigating fear of failure in the sport domain, specifically among young elite athletes.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The developmental origins of fear of failure in adolescent athletes: Examining parental practices

Objectives: We investigated the developmental origins of fear of failure (FF) in adolescent athletes by examining how parental sport socialization practices in daily parent-child interaction contribute to the development of FF in the child-athlete. Method: Three intact families of adolescent athletes (ages 13-14 years) participated in the study; three athletes and six parents. Each mother, father and athlete was interviewed separately three times over a 3-4 week period. Interviews with parents ranged between 90 and 200 min and with the athletes between 60 and 106 min. Social constructionist epistemology underpinned the study. Results: Data analyses revealed three categories of parental sport socialization practices that can contribute to young athletes' FF: punitive behavior, controlling behavior, and high expectations for achievement. These practices appear to be grounded in the parents' belief that losing competitions will lead to aversive consequences for their child's sporting progression and career. Therefore, they employed these practices in an attempt to ensure their child's success in competitions. Conclusions: Such parental socialization practices and negative responses to their child's failure can contribute to the child's FF development; as the child appraises these practices and responses to be aversive consequences of failure and, subsequently, fears failure. The present study represents the first endeavor to examine the developmental origins of FF in young athletes and its findings enhance conceptual understanding of FF in the youth sport context, contributing to theory and practice

Why young elite athletes fear failure: Consequences of failure

Fear of failure can have negative effects on children in achievement settings, affecting many aspects of their lives. Perceiving the consequences of failure to be aversive provides the basis for fear of failure, and the anticipation of a threatening outcome elicits fear. Problems attributed to fear of failure in achievement settings are prevalent. Sport is a popular and significant achievement domain for children and adolescents and there is a lack of research on fear of failure in sport among this age group. Therefore, the aim of the present study was to investigate fear of failure in the sport domain among young elite athletes, and to explore their perceptions of the consequences of failure. Interviews were conducted individually with nine athletes aged 14 - 17 years (5 males, 4 females). Analysis identified and organized perceived consequences of failure into themes and categories. Results revealed that the most commonly perceived aversive consequences of failure were diminished perception of self, no sense of achievement, and the emotional cost of failure. These findings are consistent with those reported in adult population, suggesting the potential for generalizing existing results to young elite athletes

Players' perception of coaches' contribution to their mental toughness

This study examined elite rugby players' perceptions of the mechanisms by which their coaches contribute to the development and maintenance of their mental toughness. Seventeen elite rugby players (Mage = 28.6 years; SD = 6.1 years) from the Swiss National Rugby Team were interviewed individually. Qualitative data analysis based on personal construct psychology (Kelly, 1955/1991) revealed three dimensions of the coaches' role: (1) expertise, (2) instruction, and (3) development. The findings show that the nature of the coach-athlete relationship and interactions can help to develop and maintain mental toughness. Moreover, coaches have a particularly strong influence during the development stage, when athletes express great interest in their coaches' behaviour as a model for improving their own mental toughness. The findings have both practical and theoretical implications and are valuable for coaches, athletes, sport practitioners and scholars, informing their understanding of athletes' mental toughness and the coach-athlete working relationship. Further, they inform coaching scientists and practitioners in their endeavours to design educational programmes for coaches

From teacher to friend: the evolving nature of the coach-athlete relationship

OBJECTIVES: The aim of the present study was to explore the nature and development of the coach-athlete relationship from the perspective of both an athlete and a coach. METHOD: Two coaches (1 female and 1 male; aged 42 and 48, respectively) and eight elite level swimmers (competing at international level; 4 females and 4 males; Mage18.6 years, SD = 3.1 years) from the Swiss National Swimming team were interviewed individually. Interviews ranged between 60 and 90 minutes and were audio-recorded. The athletes and their respective coaches had been working together for an average of 3.5 years. RESULTS: Data analysis revealed that the coach-athlete relationship gradually evolved over time, and that three specific dimensions operated in the development of this relationship: (1) developing bonds; (2) developing co-operation; and, (3)power relation. CONCLUSIONS: The coach-athlete relationship occurs naturally and evolves over time. This evolution in the relationship is beneficial to the athlete’s personal growth, mental strength, and athletic development. The study enhances knowledge and has theoretical and practical implications for the coach-athlete dyad