Strain-level fitness in the gut microbiome is an emergent property of glycans and a single metabolite.

The human gut microbiota resides within a diverse chemical environment challenging our ability to understand the forces shaping this ecosystem. Here, we reveal that fitness of the Bacteroidales, the dominant order of bacteria in the human gut, is an emergent property of glycans and one specific metabolite, butyrate. Distinct sugars serve as strain-variable fitness switches activating context-dependent inhibitory functions of butyrate. Differential fitness effects of butyrate within the Bacteroides are mediated by species-level variation in Acyl-CoA thioesterase activity and nucleotide polymorphisms regulating an Acyl-CoA transferase. Using in vivo multi-omic profiles, we demonstrate Bacteroides fitness in the human gut is associated together, but not independently, with Acyl-CoA transferase expression and butyrate. Our data reveal that each strain of the Bacteroides exists within a unique fitness landscape based on the interaction of chemical components unpredictable by the effect of each part alone mediated by flexibility in the core genome.

C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation.

Clostridioides difficile infection (CDI) is a major cause of healthcare-associated gastrointestinal infections1,2. The exaggerated colonic inflammation caused by C. difficile toxins such as toxin B (TcdB) damages tissues and promotes C. difficile colonization3-6, but how TcdB causes inflammation is unclear. Here we report that TcdB induces neurogenic inflammation by targeting gut-innervating afferent neurons and pericytes through receptors, including the Frizzled receptors (FZD1, FZD2 and FZD7) in neurons and chondroitin sulfate proteoglycan 4 (CSPG4) in pericytes. TcdB stimulates the secretion of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from neurons and pro-inflammatory cytokines from pericytes. Targeted delivery of the TcdB enzymatic domain, through fusion with a detoxified diphtheria toxin, into peptidergic sensory neurons that express exogeneous diphtheria toxin receptor (an approach we term toxogenetics) is sufficient to induce neurogenic inflammation and recapitulates major colonic histopathology associated with CDI. Conversely, mice lacking SP, CGRP or the SP receptor (neurokinin 1 receptor) show reduced pathology in both models of caecal TcdB injection and CDI. Blocking SP or CGRP signalling reduces tissue damage and C. difficile burden in mice infected with a standard C. difficile strain or with hypervirulent strains expressing the TcdB2 variant. Thus, targeting neurogenic inflammation provides a host-oriented therapeutic approach for treating CDI.

Functional genomic screens with death rate analyses reveal mechanisms of drug action.

A common approach for understanding how drugs induce their therapeutic effects is to identify the genetic determinants of drug sensitivity. Because 'chemo-genetic profiles' are performed in a pooled format, inference of gene function is subject to several confounding influences related to variation in growth rates between clones. In this study, we developed Method for Evaluating Death Using a Simulation-assisted Approach (MEDUSA), which uses time-resolved measurements, along with model-driven constraints, to reveal the combination of growth and death rates that generated the observed drug response. MEDUSA is uniquely effective at identifying death regulatory genes. We apply MEDUSA to characterize DNA damage-induced lethality in the presence and absence of p53. Loss of p53 switches the mechanism of DNA damage-induced death from apoptosis to a non-apoptotic death that requires high respiration. These findings demonstrate the utility of MEDUSA both for determining the genetic dependencies of lethality and for revealing opportunities to potentiate chemo-efficacy in a cancer-specific manner.

Ecological Changes Exacerbating the Spread of Invasive Ticks has Driven the Dispersal of Severe Fever with Thrombocytopenia Syndrome Virus Throughout Southeast Asia.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus recognized by the World Health Organization as an emerging infectious disease of growing concern. Utilizing phylodynamic and phylogeographic methods, we have reconstructed the origin and transmission patterns of SFTSV lineages and the roles demographic, ecological, and climatic factors have played in shaping its emergence and spread throughout Asia. Environmental changes and fluctuations in tick populations, exacerbated by the widespread use of pesticides, have contributed significantly to its geographic expansion. The increased adaptability of Lineage L2 strains to the Haemaphysalis longicornis vector has facilitated the dispersal of SFTSV through Southeast Asia. Increased surveillance and proactive measures are needed to prevent further spread to Australia, Indonesia, and North America.

Dengue Virus Serotype 3 Origins and Genetic Dynamics, Jamaica.

We identified 3 clades of dengue virus serotype 3 belonging to genotype III isolated during 2019-2020 in Jamaica by using whole-genome sequencing and phylogenomic and phylogeographic analyses. The viruses likely originated from Asia in 2014. Newly expanded molecular surveillance efforts in Jamaica will guide appropriate public health responses.

Physiological and transcriptomic response to methyl-coenzyme M reductase limitation in Methanosarcina acetivorans.

Methyl-coenzyme M reductase (MCR) catalyzes the final step of methanogenesis, the microbial metabolism responsible for nearly all biological methane emissions to the atmosphere. Decades of biochemical and structural research studies have generated detailed insights into MCR function in vitro, yet very little is known about the interplay between MCR and methanogen physiology. For instance, while it is routinely stated that MCR catalyzes the rate-limiting step of methanogenesis, this has not been categorically tested. In this study, to gain a more direct understanding of MCR's control on the growth of Methanosarcina acetivorans, we generate a strain with an inducible mcr operon on the chromosome, allowing for careful control of MCR expression. We show that MCR is not growth rate-limiting in substrate-replete batch cultures. However, through careful titration of MCR expression, growth-limiting state(s) can be obtained. Transcriptomic analysis of M. acetivorans experiencing MCR limitation reveals a global response with hundreds of differentially expressed genes across diverse functional categories. Notably, MCR limitation leads to strong induction of methylsulfide methyltransferases, likely due to insufficient recycling of metabolic intermediates. In addition, the mcr operon is not transcriptionally regulated, i.e., it is constitutively expressed, suggesting that the overabundance of MCR might be beneficial when cells experience nutrient limitation or stressful conditions. Altogether, we show that there is a wide range of cellular MCR concentrations that can sustain optimal growth, suggesting that other factors such as anabolic reactions might be rate-limiting for methanogenic growth. IMPORTANCE: Methane is a potent greenhouse gas that has contributed to ca. 25% of global warming in the post-industrial era. Atmospheric methane is primarily of biogenic origin, mostly produced by microorganisms called methanogens. Methyl-coenzyme M reductase (MCR) catalyzes methane formatio in methanogens. Even though MCR comprises ca. 10% of the cellular proteome, it is hypothesized to be growth-limiting during methanogenesis. In this study, we show that Methanosarcina acetivorans cells grown in substrate-replicate batch cultures produce more MCR than its cellular demand for optimal growth. The tools outlined in this study can be used to refine metabolic models of methanogenesis and assay lesions in MCR in a higher-throughput manner than isolation and biochemical characterization of pure protein.

Performance of HCV core antigen and PCR testing in a predominantly genotype 3 population.

Hepatitis C core antigen (HCVcAg) is becoming increasingly recognized as an alternative to molecular testing for the confirmation of chronic hepatitis C. However, there are limited data on the performance of this assay in a genotype 3 (GT3) predominant country like Pakistan. We conducted a study to evaluate the diagnostic performance of HCVcAg against the HCV polymerase chain reaction (PCR) molecular test. HCV antibody-positive patients requiring confirmatory testing were recruited from August to October 2018 at the Pakistan Kidney and Liver Institute and Research Center (PKLI&RC), Lahore, Pakistan. Patients with previously known diagnoses or treatment histories were excluded. The Abbott HCV Ag assay was used for HCVcAg testing. Results ≥3.00 fmol/L were considered positive for HCVcAg. The Abbott RealTime HCV assay was used for PCR testing with a lower detection limit of ≥12 IU/mL. We computed the sensitivity, specificity and correlation of HCVcAg against HCV PCR. A total of 394 patients were recruited. The median age of the patients was 42 years. Most participants were females (51.5%, n = 203), 30.7% (n = 121) had HTN, 10.4% DM (n = 41) and 5% had APRI ≥2. The overall sensitivity was 98.0% and the specificity was 98.6%. The lowest detection limit of cAg was an HCV RNA value of 4657 IU/mL. The levels of cAg were highly correlated with those of HCV RNA by Spearman's rank correlation test (r = 0.935, p < .001). HCVcAg represents a suitable alternative with high sensitivity and specificity compared with HCV PCR in the GT3-predominant population and can be incorporated into algorithms to improve linkage to care.

High prevalence of hepatitis B virus among MSM living with HIV in India.

People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5%-19%). Being between the ages of 25-34, and 35-44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviours such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programmes to increase early screening, vaccinations and HBV literacy are urgently needed. Integrating HBV and HIV programmes for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections.

Use of HBV RNA and to predict change in serological status and disease activity in CHB.

BACKGROUND AND AIMS: Predicting changes in disease activity and serological endpoints is necessary for the management of patients with chronic hepatitis B (CHB). We examined whether HBV RNA and hepatitis B core-related antigen (HBcrAg), two specialized virological markers proposed to reflect the activity of covalently closed circular DNA, may improve the ability to predict not sustained inactive carrier phase, spontaneous alanine aminotransferase (ALT) flare, HBeAg loss, and HBsAg loss. APPROACH AND RESULTS: Among eligible participants enrolled in the North American Hepatitis B Research Network Adult Cohort Study, we evaluated demographic, clinical, and virologic characteristics, including HBV RNA and HBcrAg, to predict not sustained inactive carrier phase, ALT flare, HBeAg loss, and HBsAg loss through a series of Cox proportional hazard or logistic regression models, controlling for antiviral therapy use. Among the study population, 54/103 participants experienced not sustained inactive carrier phase, 41/1006 had a spontaneous ALT flare, 83/250 lost HBeAg, and 54/1127 lost HBsAg. HBV RNA or HBcrAg were predictive of all 4 events. However, their addition to models of the readily available host (age, sex, race/ethnicity), clinical (ALT, use of antiviral therapy), and viral factors (HBV DNA), which had acceptable-excellent accuracy (e.g., AUC = 0.72 for ALT flare, 0.92 for HBeAg loss, and 0.91 for HBsAg loss), provided only small improvements in predictive ability. CONCLUSION: Given the high predictive ability of readily available markers, HBcrAg and HBV RNA have a limited role in improving the prediction of key serologic and clinical events in patients with CHB.

Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Modeling photo-generated charge extraction in bulk heterojunction nanoparticles.

We present a drift-diffusion model for predicting currents generated through the absorption of solar energy inside bulk heterojunction organic nanoparticles, which are, for example, promising nanomaterials for photo-catalytic water splitting. By coupling a model of the internal microstructure of the nanoparticle with the electronic properties, we show how different characteristics of the microstructure influence the efficiency of the conversion of solar energy into electrical energy. Our model provides a foundation for using computational modeling to optimize the design of photocatalytic nanoparticles.

Remote myocardial fibrosis predicts adverse outcome in patients with myocardial infarction on clinical cardiovascular magnetic resonance imaging.

BACKGROUND: Heart failure (HF) most commonly occurs in patients who have had a myocardial infarction (MI), but factors other than MI size may be deterministic. Fibrosis of myocardium remote from the MI is associated with adverse remodeling. We aimed to 1) investigate the association between remote myocardial fibrosis, measured using cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV), and HF and death following MI, 2) identify predictors of remote myocardial fibrosis in patients with evidence of MI and determine the relationship with infarct size. METHODS: Multicenter prospective cohort study of 1199 consecutive patients undergoing CMR with evidence of MI on late gadolinium enhancement. Median follow-up was 1133 (895-1442) days. Cox proportional hazards modeling was used to identify factors predictive of the primary outcome, a composite of first hospitalization for HF (HHF) or all-cause mortality, post-CMR. Linear regression modeling was used to identify determinants of remote ECV. RESULTS: Remote myocardial fibrosis was a strong predictor of primary outcome (χ2: 15.6, hazard ratio [HR]: 1.07 per 1% increase in ECV, 95% confidence interval [CI]: 1.04-1.11, p < 0.001) and was separately predictive of both HHF and death. The strongest predictors of remote ECV were diabetes, sex, natriuretic peptides, and body mass index, but, despite extensive phenotyping, the adjusted model R2 was only 0.283. The relationship between infarct size and remote fibrosis was very weak. CONCLUSION: Myocardial fibrosis, measured using CMR ECV, is a strong predictor of HHF and death in patients with evidence of MI. The mechanisms underlying remote myocardial fibrosis formation post-MI remain poorly understood, but factors other than infarct size appear to be important.

Statistical Distribution of Binary Ligands within Rhodium-Organic Octahedra Tunes Microporosity in Their Assemblies.

Structure-porosity relationships for metal-organic polyhedra (MOPs) are hardly investigated because they tend to be amorphized after activation, which inhibits crystallographic characterization. Here, we show a mixed-ligand strategy to statistically distribute two distinct carbazole-type ligands within rhodium-based octahedral MOPs, leading to systematic tuning of the microporosity in the resulting amorphous solids.

Hetero-bimetallic paddlewheel complexes for enhanced CO2 reduction selectivity in MOFs: a first principles study.

The reduction of carbon dioxide (CO2) into value-added feedstock materials, fine chemicals, and fuels represents a crucial approach for meeting contemporary chemical demands while reducing dependence on petrochemical sources. Optimizing catalysts for the CO2 reduction reaction (CO2RR) can entail employing first principles methodology to identify catalysts possessing desirable attributes, including the ability to form diverse products or selectively produce a limited set of products, or exhibit favorable reaction kinetics. In this study, we investigate CO2RR on bimetallic Cu-based paddlewheel complexes, aiming to understand the impact metal substitution with Mn(II), Co(II), or Ni(II) has on bimetallic paddlewheel metal-organic frameworks. Substituting one of the Cu sites of the paddlewheel complex with Mn results in a more catalytically active Cu center, poised to produce substantial quantities of formic acid (HCOOH) and smaller quantities of methane (CH4) with a suppressed production of C2 products such as ethanol (CH3CH2OH) or ethylene (C2H4). Moreover, the presence of Mn significantly reduces the limiting potential for CO2 reduction from 2.22 eV on the homo-bimetallic Cu paddlewheel complex to 1.19 eV, thereby necessitating a smaller applied potential. Conversely, within the Co-substituted paddlewheel complex, the Co site emerges as the primary catalytic center, selectively yielding CH4 as the sole reduced CO2 product, with a limiting potential of 1.22 eV. Notably, the Co site faces significant competition from H2 production due to a lower limiting potential of 0.81 eV for hydrogen reduction. Our examination of the Cu-Ni paddlewheel complex, featuring a Ni substituent site, reveals two catalytically active centers, each promoting distinct reductive processes. Both the Ni and Cu sites exhibit a propensity for HCOOH formation, with the Ni site favoring further reduction to CH4, whereas the Cu site directs the reaction towards methanol (CH3OH) production. This study holds significance in informing and streamlining future experimental efforts for synthesizing and evaluating novel catalysts with superior capabilities for CO2 reduction.

High Accuracy Ab Initio Potential Energy Curves and Dipole Moment Functions for the X1Σ+ and a3Π Spin States of the CF+ Diatomic Molecule.

Potential energy curves and dipole moment functions constructed using high-accuracy ab initio methods allow for an in-depth examination of the electronic structure of diatomic molecules. Ab initio computations serve as a valuable complement to experimental data, offering insights into the nature of short-lived molecules such as those encountered within the interstellar medium (ISM). While laboratory experiments provide critical groundwork, the ISM's conditions often permit longer lifetimes for lower stability molecules, enabling unique observations. The CF+ diatomic molecule is one such molecule that has been observed spectroscopically in the ISM. Previous experimental and theoretical work have examined different spectroscopic aspects of the CF+ molecule, but the development of newer, more complete potential energy curves and dipole moment functions allows for even greater insight. We constructed both potential energy curves and dipole moment functions for the ground X1Σ+ and first excited a3Π states of CF+ for both the 12C and 13C isotopologues. The potential energy curves were constructed using coupled cluster with single, double, and perturbative triple excitations (CCSD(T)) at the complete basis set limit with corrections from full triple, quadruple, quintuple, and hextuple excitations within a finite-basis coupled cluster wave function as well as corrections from full configuration interaction and relativistic effects. Rovibrational wave functions were calculated using a vibrational Hamiltonian matrix, which moves beyond the harmonic oscillator approximation. The equilibrium bond length, vibrational constant, and rotational constant were reproduced to within 0.00013 Å, 0.28 cm-1, and 0.00045 cm-1, respectively, of experimental values. Experimental transition energies from rovibrational spectra were reproduced with an error of no larger than 0.63 cm-1. The triplet excited state (a3Π) was found to have a longer equilibrium bond length at 1.21069 Å, a vibrational constant of 1611.29 cm-1, and a rotational constant of 1.56376 cm-1. Rovibrational line lists for the 12C and 13C isotopologues for both the X1Σ+ and the excited a3Π states were generated.

Mild Traumatic Brain Injury Characteristics and Symptoms in Preschool Children: How Do They Differ to School Age Children? A Multicenter Prospective Observational Study.

OBJECTIVE: To investigate if preschool children differ to school age children with mild traumatic brain injury (TBI) with respect to injury causes, clinical presentation, and medical management. DESIGN: A secondary analysis of a dataset from a large, prospective and multisite cohort study on TBI in children aged 0-18 years, the Australian Paediatric Head Injury Rules Study. SETTING: Nine pediatric emergency departments (ED) and 1 combined adult and pediatric ED located across Australia and New Zealand. PARTICIPANTS: 7080 preschool aged children (2-5 years) were compared with 5251 school-age children (6-12 years) with mild TBI (N= (N=12,331) MAIN OUTCOME MEASURES: Clinical report form on medical symptoms, injury causes, and management. RESULTS: Preschool children were less likely to be injured with a projectile than school age children (P<.001). Preschool children presented with less: loss of consciousness (P<.001), vomiting (P<.001), drowsiness (P=.002), and headache (P<.001), and more irritability and agitation (P=.003), than school-age children in the acute period after mild TBI. Preschool children were less likely to have neuroimaging of any kind (P<.001) or to be admitted for observation than school age children (P<.001). CONCLUSIONS: Our large prospective study has demonstrated that preschool children with mild TBI experience a different acute symptom profile to older children. There are significant clinical implications with symptoms post-TBI used in medical management to aid decisions on neuroimaging and post-acute intervention.

Using a Mock Circulatory Loop as a Regulatory Science Tool to Simulate Different Heart Failure Conditions.

Mechanical circulatory support (MCS) device therapy is one of the primary treatment options for end-stage heart failure (HF), whereby a mechanical pump is integrated with the failing heart to maintain adequate tissue perfusion. The ISO 14708-5:2020 standard prescribes generic guidelines for nonclinical device evaluation and system performance testing of MCS devices using a mock circulatory loop (MCL). However, the utility of MCLs in premarket regulatory submissions of MCS devices is ambiguous, and the specific disease states that the device is intended to treat are not usually simulated. Hence, we aim to outline the potential of MCLs as a valuable regulatory science tool for characterizing MCS device systems by adequately representing target clinical-use HF conditions on the bench. Target pathophysiologic hemodynamics of HF conditions (i.e., cardiogenic shock (CS), left ventricular (LV) hypertrophy secondary to hypertension, and coronary artery disease), along with a healthy adult at rest and a healthy adult during exercise are provided as recommended test conditions. The conditions are characterized based on LV, aorta, and left atrium pressures using recommended cardiac hemodynamic indices such as systolic, diastolic, and mean arterial pressure, mean cardiac output (CO), cardiac cycle time, and systemic vascular resistance. This study is a first step toward standardizing MCLs to generate well-defined target HF conditions used to evaluate MCS devices.

Palmar Fibromatosis, Updated Review With Relationship to the A1 Pulley, Trigger Finger, and Presence of the Sonographic Comb Sign.

OBJECTIVES: Updated retrospective review of the sonographic appearance of palmar fibromatosis (PF) with evaluation of the utility of the Comb Sign previously described in plantar fibromas. Additional evaluation was conducted on the location relative to the flexor tendon, anatomic proximity of palmar fibromas to the A1 pulley and evaluate any potential association with trigger finger. METHODS: Medical record and imaging review was performed from 2017 to 2023, for patients with a new onset ultrasound or clinical diagnosis of PF. Clinical associations and imaging morphology were reviewed including presence of the Comb Sign, fibroma association with the A1 pulley, and fibroma association with trigger finger. RESULTS: Exactly 87 total fibromas in 53 patients were evaluated. The Comb Sign was present in 39% of fibromas, usually seen in transverse plane, more prevalent in multifocal disease and larger fibromas. Most (72%) palmar fibromas were within 1 cm of, contacted, or covered the A1 pulley (P < .001). Lateral extension beyond the flexor tendon axis can be seen (44%). Trigger finger and tenosynovitis were rare. However, volume and SI dimension of fibromas were associated with tenosynovitis (P < .0001) and all nine patients with concomitant trigger finger had fibromas within 1 cm from the A1 pulley. CONCLUSIONS: The Comb Sign can aid in sonographic diagnosis of PF. Lateral extension of fibromas can occur. Most palmar fibromas have a significant intimate association with the A1 pulley, and presence of trigger finger with adjacent palmar fibroma can exist and is important for hand surgeons to know preoperatively.

Temporal and spatial distribution of health, labor, and crop benefits of climate change mitigation in the United States.

Societal benefits from climate change mitigation accrue via multiple pathways. We examine the US impacts of emission changes on several factors that are affected by both climate and air quality responses. Nationwide benefits through midcentury stem primarily from air quality improvements, which are realized rapidly, and include human health, labor productivity, and crop yield benefits. Benefits from reduced heat exposure become large around 2060, thereafter often dominating over those from improved air quality. Monetized benefits are in the tens of trillions of dollars for avoided deaths and tens of billions for labor productivity and crop yield increases and reduced hospital expenditures. Total monetized benefits this century are dominated by health and are much larger than in previous analyses due to improved understanding of the human health impacts of exposure to both heat and air pollution. Benefit-cost ratios are therefore much larger than in prior studies, especially those that neglected clean air benefits. Specifically, benefits from clean air exceed costs in the first decade, whereas benefits from climate alone exceed costs in the latter half of the century. Furthermore, monetized US benefits largely stem from US emissions reductions. Increased emphasis on the localized, near-term air quality-related impacts would better align policies with societal benefits and, by reducing the mismatch between perception of climate as a risk distant in space and time and the need for rapid action to mitigate long-term climate change, might help increase acceptance of mitigation policies.

Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.