Impact of Trauma System Structure on Injury Outcomes : A Systematic Review and Meta-Analysis

The effectiveness of trauma systems in decreasing injury mortality and morbidity has been well demonstrated. However, little is known about which components contribute to their effectiveness. We aimed to systematically review the evidence of the impact of trauma system components on clinically important injury outcomes. We searched MEDLINE, EMBASE, Cochrane CENTRAL, and BIOSIS/Web of Knowledge, gray literature and trauma association Web sites to identify studies evaluating the association between at least one trauma system component and injury outcome. We calculated pooled effect estimates using inverse-variance random-effects models. We evaluated quality of evidence using GRADE criteria. We screened 15,974 records, retaining 41 studies for qualitative synthesis and 19 for meta-analysis. Two recommended trauma system components were associated with reduced odds of mortality: inclusive design (odds ratio [OR] = 0.72 [0.65-0.80]) and helicopter transport (OR = 0.70 [0.55-0.88]). Pre-Hospital Advanced Trauma Life Support was associated with a significant reduction in hospital days (mean difference [MD] = 5.7 [4.4-7.0]) but a nonsignificant reduction in mortality (OR = 0.78 [0.44-1.39]). Population density of surgeons was associated with a nonsignificant decrease in mortality (MD = 0.58 [-0.22 to 1.39]). Trauma system maturity was associated with a significant reduction in mortality (OR = 0.76 [0.68-0.85]). Quality of evidence was low or very low for mortality and healthcare utilization. This review offers low-quality evidence for the effectiveness of an inclusive design and trauma system maturity and very-low-quality evidence for helicopter transport in reducing injury mortality. Further research should evaluate other recommended components of trauma systems and non-fatal outcomes and explore the impact of system component interactions.Peer reviewe

Impact of Trauma System Structure on Injury Outcomes : A Systematic Review and Meta-Analysis

The effectiveness of trauma systems in decreasing injury mortality and morbidity has been well demonstrated. However, little is known about which components contribute to their effectiveness. We aimed to systematically review the evidence of the impact of trauma system components on clinically important injury outcomes. We searched MEDLINE, EMBASE, Cochrane CENTRAL, and BIOSIS/Web of Knowledge, gray literature and trauma association Web sites to identify studies evaluating the association between at least one trauma system component and injury outcome. We calculated pooled effect estimates using inverse-variance random-effects models. We evaluated quality of evidence using GRADE criteria. We screened 15,974 records, retaining 41 studies for qualitative synthesis and 19 for meta-analysis. Two recommended trauma system components were associated with reduced odds of mortality: inclusive design (odds ratio [OR] = 0.72 [0.65-0.80]) and helicopter transport (OR = 0.70 [0.55-0.88]). Pre-Hospital Advanced Trauma Life Support was associated with a significant reduction in hospital days (mean difference [MD] = 5.7 [4.4-7.0]) but a nonsignificant reduction in mortality (OR = 0.78 [0.44-1.39]). Population density of surgeons was associated with a nonsignificant decrease in mortality (MD = 0.58 [-0.22 to 1.39]). Trauma system maturity was associated with a significant reduction in mortality (OR = 0.76 [0.68-0.85]). Quality of evidence was low or very low for mortality and healthcare utilization. This review offers low-quality evidence for the effectiveness of an inclusive design and trauma system maturity and very-low-quality evidence for helicopter transport in reducing injury mortality. Further research should evaluate other recommended components of trauma systems and non-fatal outcomes and explore the impact of system component interactions.Peer reviewe

Clinical, environmental, and genetic risk factors for substance use disorders : characterizing combined effects across multiple cohorts

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (N-EUR = 12,659) and African (N-AFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.Peer reviewe

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Measurement of quark- and gluon-like jet fractions using jet charge in PbPb and pp collisions at 5.02 TeV

The momentum-weighted sum of the electric charges of particles inside a jet, known as jet charge, is sensitive to the electric charge of the particle initiating the parton shower. This paper presents jet charge distributions in root sNN = 5.02 TeV lead-lead (PbPb) and proton-proton (pp) collisions recorded with the CMS detector at the LHC. These data correspond to integrated luminosities of 404 mu b(-1)and 27.4 pb(-1)for PbPb and pp collisions, respectively. Leveraging the sensitivity of the jet charge to fundamental differences in the electric charges of quarks and gluons, the jet charge distributions from simulated events are used as templates to extract the quark- and gluon-like jet fractions from data. The modification of these jet fractions is examined by comparing pp and PbPb data as a function of the overlap of the colliding Pb nuclei (centrality). This measurement tests the color charge dependence of jet energy loss due to interactions with the quark-gluon plasma. No significant modification between different centrality classes and with respect to pp results is observed in the extracted quark- and gluon-like jet fractions.Peer reviewe

Study of Z boson production in pPb collisions at √sNN=5.02 TeV

The production of Z bosons in pPb collisions at root S-NN = 5.02 TeV is studied by the CMS experiment via the electron and muon decay channels. The inclusive cross section is compared to pp collision predictions, and found to scale with the number of elementary nucleon-nucleon collisions. The differential cross sections as a function of the Z boson rapidity and transverse momentum are measured. Though they are found to be consistent within uncertainty with theoretical predictions both with and without nuclear effects, the forward-backward asymmetry suggests the presence of nuclear effects at large rapidities. These results provide new data for constraining nuclear parton distribution functions

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity