Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Will women interact with technology to increase physical activity?

Background: Cardiovascular disease continues to be one of the leading causes of death for women. New approaches need to be identified that will enable women to recognize modifiable risk factors (i.e., smoking, diabetes, physical inactivity, high blood pressure, high blood cholesterol and obesity) and target their efforts towards prevention. Technology is increasingly being accessed by individuals to understand components of their health. A sensor-based activity monitor, with the novel web-based platform VivametricaTM and a small amount of personal health information, can provide a personalized cardiovascular health risk score. Objectives: The objectives of this study were to examine: 1) if women would wear a Garmin Vivosmart® HR Wrist Tracker (GVWT) and access VivametricaTM to assess information about their cardiovascular health risk; 2) whether using the VivametricaTM tools would lead women to increase their physical activity, as measured by their daily step counts; and 3) women’s opinions about using VivametricaTM. This study was undertaken in two phases using quantitative then qualitative methods. The first phase addressed objectives #1 and #2. The second phase addressed objective #3. Methods: Phase one was a prospective observational study involving thirty-six English speaking women aged 45-64 years old, without physical disabilities. Participants wore a GVWT for 12 weeks and were instructed in how to access the VivametricaTM platform. The number of times participants accessed VivametricaTM and participants’ physical activity (step count) were streamed via the GVWT to VivametricaTM. The number of steps data were analyzed from those participants who accessed VivametricaTM (during the 12 week period) using Wilcoxon signed rank test to compare the median number of steps walked during the participants’ first 14 days (T1) with median number of steps walked during the last 14 days (T2). Phase two was a qualitative descriptive study whereby all participants in phase one engaged in semi-structured audio-recorded interviews. Qualitative content analysis, using the technology assessment model, was used to analyze the text data. Results: Twenty-six (72%) participants accessed VivametricaTM over the course of the study. The median number of steps at baseline and at 12 weeks were 9329 steps (range 5406-18228 steps) and 10181 steps (range 5398-21401 steps) respectively. There was no significant change in number of steps taken by the participants over the 12 week period (Z = -1.143, p =.253). Although the change in steps was not statistically significant, it represents an average increase in daily steps of 9%, which is clinically important. Four themes were identified from the qualitative interviews. They were: confusion, convenience, measurement, and sleep. Confusion resulted for some participants when two forms of technology were introduced at the same time. The participants expected using the technology to be convenient and effortless. Yet, having to sign onto a computer to see their health scores was frustrating for many women. The GVWT was effortless when in the mode of collecting steps. However, if a participant wanted to capture other activity, such as cycling, they needed to change the mode. The women did not like having to adjust any settings on the GVWT. The value of measurement meant different things to different women. Knowing their health scores and activity awareness were valued by the participants. However, some participants found having missed data (e.g., in the case of forgetting to wear the GVWT not appropriately changing the mode on the GVWT) frustrating and discouraging. Finally, participants sought out other information when using the technology and this was focused on their sleep patterns. Some participants changed their behavior to achieve better sleep. Discussion: VivametricaTM provides more than activity data, thereby allowing a unique option for individuals to access personal health risk information. This innovative technology has great potential for supporting women to understand their personal CVD risk. However, people who use this technology need to be trained and supported with resources to enable them to use this technology to its capacity

Higher, Faster, Stronger, Drunker?

In light of the increasing number of girls participating in sports, the pressures associated with big time sports, and interest in preventing alcohol-related problems in female athletes, the purpose of this viewpoint is to examine the prevalence of alcohol abuse in female athletes and to provide coaches and teachers with suggestions for education and prevention. Some of these include a continual increase in the competition, negotiating relationships with teammates and coaches, performance anxiety or fear of failure, decreased social interaction due to competition, time management issues, burnout, and coping with injuries (Storch, Storch, Killiany, & Roberti, 2005)

Can Physical Activity Interventions Change Perceived Exercise Benefits and Barriers?

This study examined changes in physical activity and perceived exercise benefits, barriers, and benefit-to-barrier differences in mothers and daughters who participated in 12-week home-based (HB) and university-based (UB) physical activity interventions. Two (group) by two (time) repeated measures ANOVAs and effect sizes showed an increase in physical activity in both groups. Mothers in both groups reported a significant decrease in exercise barriers (p = .01, ES = .41). Exercise benefits and barriers did not change for daughters, nor did exercise benefits change for mothers. These two interventions were successful at increasing physical activity, but changes in EBBS scales differed by age and point in time measures were taken. This information can be used to plan better interventions for girls and women

Connect To Care (C2C): protocol for two-site randomized controlled pilot trial to improve outcomes for patients with hazardous drinking and PTSD and/or depression symptoms

Abstract Background In studies of the general population and of military veterans, many primary care patients with hazardous drinking and PTSD and/or depression (abbreviated here as HD +) do not initiate or engage with alcohol-related care. To address this gap in care, we identified and will pilot test a promising evidence-based intervention, Connect To Care (C2C). C2C is a strengths-based approach, delivered by a Care Coach by telephone and/or video, with four components: (1) identifying and leveraging patient strengths to facilitate care initiation, (2) collaborative decision-making around a menu of care options, (3) identifying and resolving barriers to care, and (4) monitoring and facilitating progress toward care initiation by, for example, checking on barriers, identifying solutions, and revisiting care options. Methods/Design Aim 1 will involve adapting C2C for use in Veterans Affairs’ (VA) primary care. We will use an iterative process that includes focus groups and semi-structured interviews with key stakeholders (patients, primary care providers, and VA national policy leaders). In Aim 2, we will conduct a two-site, pilot randomized controlled trial to determine the feasibility of conducting a larger scale trial to test C2C’s effectiveness, ascertain the acceptability of C2C among primary care patients with HD + , and explore the efficacy of C2C to improve veteran patients’ initiation of and engagement in alcohol care, and their alcohol and mental health (PTSD, depression) outcomes, at 3-month follow-up. We will explore explanatory mechanisms by which C2C is effective. Discussion Study findings are likely to have implications for clinical practice to enhance current approaches to linking patients with HD + to alcohol care by applying a practical intervention such as C2C. The results may improve treatment outcomes for people with HD + by drawing on patients’ strengths to problem-solve barriers to care following a process of shared decision-making with a coach. In addition to possibly accelerating the translation of C2C into practice, study findings will also support additional research in terms of a planned effectiveness-implementation hybrid trial, adding to this study’s potential for high impact. Trial registration: ClinicalTrials.gov Identifier: NCT05023317

A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development

International audienceGenetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5. In other probands, we identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to neurodevelopment. Several of the new candidates interact with each other or with known speech-related genes. Moreover, they show significant clustering within a single co-expression module of genes highly expressed during early human brain development. This study highlights gene regulatory pathways in the developing brain that may contribute to acquisition of proficient speech

Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A02: a Paradigm for Virus Evolution and Persistence?

It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag 71-79 GY9), and one from the Nef protein (Nef 159-167 YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef 159-167 YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag 71-79 GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat 28-35 SL8, which reproducibly selects for escape variants during acute infection, and Gag 181-189 CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection

Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?

It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag(71-79) GY9), and one from the Nef protein (Nef(159-167) YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef(159-167) YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag(71-79) GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat(28-35) SL8, which reproducibly selects for escape variants during acute infection, and Gag(181-189) CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection