While fetal growth is a tightly regulated process, it is sensitive to environmental exposures that occur during pregnancy. Many commonly used consumer products contain chemicals that can disturb ...processes underlying fetal growth. However, mixtures of these chemicals have been minimally examined. We investigated associations between prenatal exposure to 33 consumer product chemicals (nine organophosphate ester flame retardant OPE metabolites, 12 phthalate metabolites, and 12 phenols) and the odds of small- or large-for-gestational age (SGA and LGA) births.
This case-control study was comprised of SGA (N = 31), LGA (N = 28), and appropriate for gestational age control (N = 31) births selected from the larger LIFECODES cohort. Biomarkers of exposure to consumer product chemicals were quantified in maternal urine collected from up to three study visits during pregnancy. In a single-pollutant approach, odds ratios (OR) and 95% confidence intervals (CI) of SGA and LGA associated with an interquartile range (IQR)-increase in exposure biomarkers were estimated using multinomial logistic regression. In a multi-pollutant approach, quantile g-computation was used to jointly estimate the OR (95% CI) of SGA and LGA per simultaneous one quartile-change in all biomarkers belonging to each chemical class.
Among the 33 biomarkers analyzed, 20 were detected in at least 50% of the participants. After adjusting for potential confounders, we observed reduced odds of LGA in association with higher urinary concentrations of several exposure biomarkers. For example, an IQR-increase in the OPE metabolite, diphenyl phosphate, was associated with lower odds of LGA (OR: 0.40 95% CI: 0.18, 0.87). Using quantile g-computation, we estimated lower odds of an LGA birth for higher OPE metabolite concentrations (OR: 0.49 95% CI: 0.27, 0.89) and phthalate metabolite concentrations (OR: 0.23 95% CI: 0.07, 0.73). Associations between consumer product chemicals and SGA were largely null.
Joint exposure to OPEs and phthalates was associated with lower odds of delivering LGA. Associations with LGA could indicate a specific impact of these exposures on the high end of the birth weight spectrum. Future work to understand this nuance in the associations between consumer product chemical mixtures and fetal growth is warranted.
Summary
Healthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We ...conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID‐19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self‐reporting. The primary endpoint was the incidence of laboratory‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure‐related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR range) follow‐up of 32 (18–48 0–116) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID‐19 subsequently reported a COVID‐19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID‐19 transmission.
We search for an isotropic stochastic gravitational-wave background (GWB) in the newly released 11 year data set from the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). ...While we find no evidence for a GWB, we place constraints on a population of inspiraling supermassive black hole (SMBH) binaries, a network of decaying cosmic strings, and a primordial GWB. For the first time, we find that the GWB constraints are sensitive to the solar system ephemeris (SSE) model used and that SSE errors can mimic a GWB signal. We developed an approach that bridges systematic SSE differences, producing the first pulsar-timing array (PTA) constraints that are robust against SSE errors. We thus place a 95% upper limit on the GW-strain amplitude of AGWB < 1.45 × 10−15 at a frequency of f = 1 yr−1 for a fiducial f−2/3 power-law spectrum and with interpulsar correlations modeled. This is a factor of ∼2 improvement over the NANOGrav nine-year limit calculated using the same procedure. Previous PTA upper limits on the GWB (as well as their astrophysical and cosmological interpretations) will need revision in light of SSE systematic errors. We use our constraints to characterize the combined influence on the GWB of the stellar mass density in galactic cores, the eccentricity of SMBH binaries, and SMBH-galactic-bulge scaling relationships. We constrain the cosmic-string tension using recent simulations, yielding an SSE-marginalized 95% upper limit of G < 5.3 × 10−11-a factor of ∼2 better than the published NANOGrav nine-year constraints. Our SSE-marginalized 95% upper limit on the energy density of a primordial GWB (for a radiation-dominated post-inflation universe) is GWB(f) h2 < 3.4 × 10−10.
Developing expertise in flexible bronchoscopy is limited by inadequate opportunities to train on difficult airways. The new ORSIM bronchoscopy simulator aims to address this by creating virtual ...patients with difficult airways. This study aims to provide evidence on the validity and reliability of the ORSIM for assessment of subjects on both normal and abnormal airway simulations.
Novice, trainee, and expert subjects performed seven simulations of varying difficulty and scored the perceived difficulty for each. Time to completion was measured. Three blinded raters independently scored videos of each subject's performance. We measured inter-rater agreement and the difference in raters’ scores between subject groups.
We recruited 28 study subjects, generating 196 videos for analysis. Expert subjects consistently completed the scenarios faster than novices. Overall performance scores showed significant differences between subject groups (P<0.0001). Inter-rater reliability of scores was >0.8.
Our results provide initial evidence on the validity and reliability of the ORSIM bronchoscopy simulator, supporting its potential value in training and assessment.
Throughout the last decade, great advances have been made in our understanding of how DNA-templated cellular processes occur in the native chromatin environment. Proteins that regulate transcription, ...replication, DNA repair, mitosis and other processes must be targeted to specific regions of the genome and granted access to DNA, which is normally tightly packaged in the higher-order chromatin structure of eukaryotic nuclei. Massive multiprotein complexes have been discovered, which facilitate access to DNA and recruitment of downstream effectors through three distinct mechanisms: chemical modification of histone amino-acid residues, ATP-dependent chromatin remodeling and histone exchange. The yeast Spt-Ada-Gcn5-Acetyl transferase (SAGA) transcriptional co-activator complex regulates numerous cellular processes through coordination of multiple histone post-translational modifications. SAGA is known to generate and interact with a number of histone modifications, including acetylation, methylation, ubiquitylation and phosphorylation. Although best characterized for its role in regulating transcriptional activation, SAGA is also required for optimal transcription elongation, mRNA export and perhaps nucleotide excision repair. Here, we discuss findings from recent years that have elucidated the function of this 1.8-MDa complex in multiple cellular processes, and how misregulation of the homologous complexes in humans may ultimately play a role in development of disease.
Magnetic reconnection is a fundamental physical process in plasmas whereby stored magnetic energy is converted into heat and kinetic energy of charged particles. Reconnection occurs in many ...astrophysical plasma environments and in laboratory plasmas. Using measurements with very high time resolution, NASA's Magnetospheric Multiscale (MMS) mission has found direct evidence for electron demagnetization and acceleration at sites along the sunward boundary of Earth's magnetosphere where the interplanetary magnetic field reconnects with the terrestrial magnetic field. We have (i) observed the conversion of magnetic energy to particle energy; (ii) measured the electric field and current, which together cause the dissipation of magnetic energy; and (iii) identified the electron population that carries the current as a result of demagnetization and acceleration within the reconnection diffusion/dissipation region.
Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by ...antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.
We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I
statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.
We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.
Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.
PROSPERO CRD42018029432.
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