Evaluating the Sensitivity of HeatWave Definitions among North Carolina Physiographic Regions

Exposure to extreme heat is a known risk factor that is associated with increased heat-related illness (HRI) outcomes. The relevance of heat wave definitions (HWDs) could change across health conditions and geographies due to the heterogenous climate profile. This study compared the sensitivity of 28 HWDs associated with HRI emergency department visits over five summer seasons (2011–2016), stratified by two physiographic regions (Coastal and Piedmont) in North Carolina. The HRI rate ratios associated with heat waves were estimated using the generalized linear regression framework assuming a negative binomial distribution. We compared the Akaike Information Criterion (AIC) values across the HWDs to identify an optimal HWD. In the Coastal region, HWDs based on daily maximum temperature with a threshold \u3e 90th percentile for two or more consecutive days had the optimal model fit. In the Piedmont region, HWD based on the daily minimum temperature with a threshold value \u3e 90th percentile for two or more consecutive days was optimal. The HWDs with optimal model performance included in this study captured moderate and frequent heat episodes compared to the National Weather Service (NWS) heat products. This study compared the HRI morbidity risk associated with epidemiologic-based HWDs and with NWS heat products. Our findings could be used for public health education and suggest recalibrating NWS heat products

Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria mitochondrial disorder: case report and literature review

Background: Leigh syndrome is a rare, genetic, and severe mitochondrial disorder characterized by neuromuscular issues (ataxia, seizure, hypotonia, developmental delay, dystonia) and ocular abnormalities (nystagmus, atrophy, strabismus, ptosis). It is caused by pathogenic variants in either mitochondrial or nuclear DNA genes, with an estimated incidence rate of 1 per 40,000 live births.Case presentation: Herein, we present an infant male with nystagmus, hypotonia, and developmental delay who carried a clinical diagnosis of Leigh-like syndrome. Cerebral magnetic resonance imaging changes further supported the clinical evidence of an underlying mitochondrial disorder, but extensive diagnostic testing was negative. Trio exome sequencing under a research protocol uncovered compound-heterozygous missense variants in the HTRA2 gene (MIM: #606441): NM_013247.5:c.1037A>T:(p.Glu346Val) (maternal) and NM_013247.5:c.1172T>A:(p.Val391Glu) (paternal). Both variants are absent from public databases, making them extremely rare in the population. The maternal variant is adjacent to an exon-intron boundary and predicted to disrupt splicing, while the paternal variant alters a highly conserved amino acid and is predicted to be damaging by nearly all in silico tools. Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria, type VIII (MGCA8), an extremely rare autosomal recessive disorder with fewer than ten families reported to date. Variant interpretation is challenging given the paucity of known disease-causing variants, and indeed we assess both paternal and maternal variants as Variants of Uncertain Significance under current American College of Medical Genetics guidelines. However, based on the inheritance pattern, suggestive evidence of pathogenicity, and significant clinical correlation with other reported MGCA8 patients, the clinical care team considers this a diagnostic result.Conclusion: Our findings ended the diagnostic odyssey for this family and provide further insights into the genetic and clinical spectrum of this critically under-studied disorder

Effect of oxidant concentration, exposure time, and seed particles on secondary organic aerosol chemical composition and yield

We performed a systematic intercomparison study of the chemistry and yields of secondary organic aerosol (SOA) generated from OH oxidation of a common set of gas-phase precursors in a Potential Aerosol Mass (PAM) continuous flow reactor and several environmental chambers. In the flow reactor, SOA precursors were oxidized using OH concentrations ranging from 2.0 × 10[superscript 8] to 2.2 × 10[superscript 10] molec cm[superscript −3] over exposure times of 100 s. In the environmental chambers, precursors were oxidized using OH concentrations ranging from 2 × 10[superscript 6] to 2 × 10[superscript 7] molec cm[superscript −3] over exposure times of several hours. The OH concentration in the chamber experiments is close to that found in the atmosphere, but the integrated OH exposure in the flow reactor can simulate atmospheric exposure times of multiple days compared to chamber exposure times of only a day or so. In most cases, for a specific SOA type the most-oxidized chamber SOA and the least-oxidized flow reactor SOA have similar mass spectra, oxygen-to-carbon and hydrogen-to-carbon ratios, and carbon oxidation states at integrated OH exposures between approximately 1 × 10[superscript 11] and 2 × 10[superscript 11] molec cm[superscript −3] s, or about 1–2 days of equivalent atmospheric oxidation. This observation suggests that in the range of available OH exposure overlap for the flow reactor and chambers, SOA elemental composition as measured by an aerosol mass spectrometer is similar whether the precursor is exposed to low OH concentrations over long exposure times or high OH concentrations over short exposure times. This similarity in turn suggests that both in the flow reactor and in chambers, SOA chemical composition at low OH exposure is governed primarily by gas-phase OH oxidation of the precursors rather than heterogeneous oxidation of the condensed particles. In general, SOA yields measured in the flow reactor are lower than measured in chambers for the range of equivalent OH exposures that can be measured in both the flow reactor and chambers. The influence of sulfate seed particles on isoprene SOA yield measurements was examined in the flow reactor. The studies show that seed particles increase the yield of SOA produced in flow reactors by a factor of 3 to 5 and may also account in part for higher SOA yields obtained in the chambers, where seed particles are routinely used.National Science Foundation (U.S.). Atmospheric Chemistry Program (Grant AGS-1056225)National Science Foundation (U.S.). Atmospheric Chemistry Program (Grant AGS-1245011

Marsbee - Swarm of Flapping Wing Flyers for Enhanced Mars Exploration

Mars exploration has received significant interest from academia, industry, government, and the general public. Despite continued interest, flying on Mars remains challenging, mainly due to the ultra-thin Martian atmospheric density. Although the gravitational acceleration on Mars is 38 percent of Earth's 9.8 meters per second squared, the Martian atmospheric density is only 1.3 percent of the air density on Earth. The aerodynamic forces are proportional to the ambient fluid density. Therefore, flying near the surface of Mars has been considered nearly impossible. The proposed mission architecture (Fig. 1) consists of a Mars rover (already existing) that serves as a mobile base for Marsbees - a deployable swarm of small bio-inspired flapping wing vehicles. In one ConOps scenario, each Marsbee would carry an integrated stereographic video camera and the swarm could construct a 3D topographic map of the local surface for rover path planning. These flying scouts would provide a "third-dimension" to the rover capabilities. In other scenarios, each part of the swarm of Marsbees could carry pressure and temperature sensors for atmospheric sampling, or small spectral analyzers for identification of mineral outcroppings. In each scenario, the rover acts as a recharging and deployment/return station and data and communication hub. Human exploration of Mars is one of the major objectives of NASA and commercial entities such as SpaceX and Boeing. The identified innovations unique to the bio-inspired flapping Marsbee provide viable multi-mode flying mobility for Martian atmospheric and terrain exploration. A swarm of Marsbees provides an enhanced reconfigurable Mars exploration system that is resilient to individual component failures. These Marsbees can carry sensors and wireless communication devices in combination with a Mars rover and helicopters. These enhanced sensing and information gathering abilities can contribute to the following NASA Mars mission objectives: i) "Determine the habitability of an environment", ii) "Obtain surface weather measurements to validate global atmospheric models", and iii) "Prepare for human exploration on Mars." Various commercial entities, e.g. SpaceX and Boeing, are investing in technologies to transport humans to Mars

Cysteine Redox Potential Determines Pro-Inflammatory IL-1β Levels

Cysteine (Cys) and its disulfide, cystine (CySS) represent the major extracellular thiol/disulfide redox control system. The redox potential (E(h)) of Cys/CySS is centered at approximately -80 mV in the plasma of healthy adults, and oxidation of E(h) Cys/CySS is implicated in inflammation associated with various diseases.The purpose of the present study was to determine whether oxidized E(h) Cys/CySS is a determinant of interleukin (IL)-1beta levels. Results showed a 1.7-fold increase in secreted pro-IL-1beta levels in U937 monocytes exposed to oxidized E(h) Cys/CySS (-46 mV), compared to controls exposed to a physiological E(h) of -80 mV (P<0.01). In LPS-challenged mice, preservation of plasma E(h) Cys/CySS from oxidation by dietary sulfur amino acid (SAA) supplementation, was associated with a 1.6-fold decrease in plasma IL-1beta compared to control mice fed an isonitrogenous SAA-adequate diet (P<0.01). Analysis of E(h) Cys/CySS and IL-1beta in human plasma revealed a significant positive association between oxidized E(h) Cys/CySS and IL-1beta after controlling for age, gender, and BMI (P<0.001).These data show that oxidized extracellular E(h) Cys/CySS is a determinant of IL-1beta levels, and suggest that strategies to preserve E(h) Cys/CySS may represent a means to control IL-1beta in inflammatory disease states

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

SLC35A2â CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

Pathogenic de novo variants in the Xâ linked gene SLC35A2 encoding the major Golgiâ localized UDPâ galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2â congenital disorders of glycosylation (CDG; formerly CDGâ IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin Nâ glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2â CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2â dependent UDPâ galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wildâ type to mutant alleles in fibroblasts from affected individuals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/1/humu23731_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/2/humu23731-sup-0001-Supp_Mat__2019.2.10_.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/3/humu23731.pd

Systematic Conservation Planning in the Face of Climate Change: Bet-Hedging on the Columbia Plateau

Systematic conservation planning efforts typically focus on protecting current patterns of biodiversity. Climate change is poised to shift species distributions, reshuffle communities, and alter ecosystem functioning. In such a dynamic environment, lands selected to protect today's biodiversity may fail to do so in the future. One proposed approach to designing reserve networks that are robust to climate change involves protecting the diversity of abiotic conditions that in part determine species distributions and ecological processes. A set of abiotically diverse areas will likely support a diversity of ecological systems both today and into the future, although those two sets of systems might be dramatically different. Here, we demonstrate a conservation planning approach based on representing unique combinations of abiotic factors. We prioritize sites that represent the diversity of soils, topographies, and current climates of the Columbia Plateau. We then compare these sites to sites prioritized to protect current biodiversity. This comparison highlights places that are important for protecting both today's biodiversity and the diversity of abiotic factors that will likely determine biodiversity patterns in the future. It also highlights places where a reserve network designed solely to protect today's biodiversity would fail to capture the diversity of abiotic conditions and where such a network could be augmented to be more robust to climate-change impacts