Musculoskeletal Injuries and Outcomes Pre- and Post- Emergency Medicine Training Program

Introduction: Musculoskeletal injuries (MSI) comprise a large portion of the trauma burden in low- and middle-income countries (LMIC). Rwanda recently launched its first emergency medicine training program (EMTP) at the University Teaching Hospital-Kigali (UTH-K), which may help to treat such injuries; yet no current epidemiological data is available on MSI in Rwanda.Methods: We conducted this pre-post study during two data collection periods at the UTH-K from November 2012 to July 2016. Data collection for MSI is limited and thus is specific to fractures. We included all patients with open, closed, or mixed fractures, hereafter referred to as MSI. Gathered information included demographics and outcomes including death, traumatic complications, and length of hospital stay, before and after the implementation of the EMTP.Results: We collected data from 3609 patients. Of those records, 691 patients were treated for fractures, and 674 of them had sufficient EMTP data measured for inclusion in the analysis of results (279 from pre-EMTP and 375 from post-EMTP). Patient demographics demonstrate that a majority of MSI cases are male (71.6% male vs 28.4% female) and young (64.3% below 35 years of age). Among mechanisms of injury, major causes included road traffic accidents (48.1%), falls (34.2%), and assault (6.0%). There was also an observed association between EMTP and trends of the three primary outcomes: a reduction of death in the emergency department (ED) from those with MSI by 89.9%, from 2.51% to 0.25% (p = 0.0077); a reduction in traumatic complications for MSI patients by 71.7%, from 3.58% to 1.01% (p = 0.0211); and a reduction in duration of stay in the ED among those with MSI by 52.7% or 2.81 days on average, from 5.33 to 2.52 days (p = 0.0437).Conclusion: This study reveals the current epidemiology of MSI morbidity and mortality for a major Rwandan teaching hospital and the potential impacts of EM training implementation among those with MSI. Residency training programs such as EMTP appear capable of reducing mortality, complications, and ED length of stay among those with MSI caused by fractures. Such findings underscore the efficacy and importance of investments in educating the next generation of health professionals to combat prevalent MSI within their communities

Closing gaps to our origins : EUVO: the ultraviolet-visible window into the Universe

This article reproduces the contents of the White Paper entitled by the same name submitted to the call issued by the European Space Agency soliciting ideas from the scientific community for the science themes that should be covered during the Voyage 2050 planning cycle. This contribution focus in the investigation of the emergence of life and the role that astronomy has to play in it. Three fundamental areas of activity are identified: [1] measuring the chemical enrichment of the Universe, [2] investigating planet formation and searching for exoplanets with signatures of life and, [3] determining the abundance of amino acids and the chemical routes to amino acid and protein growth in astronomical bodies. This proposal deals with the first two. The building blocks of life in the Universe began as primordial gas processed in stars and mixed at galactic scales. The mechanisms responsible for this development are not well-understood and have changed over the intervening 13 billion years. To follow the evolution of matter over cosmic time, it is necessary to study the strongest (resonance) transitions of the most abundant species in the Universe. Most of them are in the ultraviolet (UV; 950 Å - 3000 Å ) spectral range that is unobservable from the ground; the “missing” metals problem cannot be addressed without this access. Habitable planets grow in protostellar discs under ultraviolet irradiation, a by-product of the accretion process that drives the physical and chemical evolution of discs and young planetary systems. The electronic transitions of the most abundant molecules are pumped by this UV field that is the main oxidizing agent in the disc chemistry and provides unique diagnostics of the planet-forming environment that cannot be accessed from the ground. Knowledge of the variability of the UV radiation field is required for the astrochemical modelling of protoplanetary discs, to understand the formation of planetary atmospheres and the photochemistry of the precursors of life. Earth’s atmosphere is in constant interaction with the interplanetary medium and the solar UV radiation field. The exosphere of the Earth extends up to 35 planetary radii providing an amazing wealth of information on our planet’s winds and the atmospheric compounds. To access to it in other planetary systems, observation of the UV resonance transitions is required. The investigation for the emergence of life calls for the development of large astronomical facilities, including instrumentation in optical and UV wavelengths. In this contribution, the need to develop a large observatory in the optical and in the UV is revealed, in order to complete the scientific goals to investigate the origin of life, inaccessible through other frequencies in the electromagnetic spectrum

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe