In asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. ...This review covers recent developments in our understanding of this interaction: the "microbial hypothesis" and the "farm effect"; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures. We propose a unified framework for understanding how all these phenomena interact to drive asthma pathogenesis. Finally, we point out some future challenges for continued research in this field, in particular the need for multiomic integration, as well as the potential utility of asthma endotyping.
ObjectivePublic attitudes about drug addiction and mental illness were compared.MethodsA Web-based national survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment ...effectiveness, and policy support in regard to drug addiction and mental illness.ResultsRespondents held significantly more negative views toward persons with drug addiction. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them. Respondents were more willing to accept discriminatory practices against persons with drug addiction, more skeptical about the effectiveness of treatments, and more likely to oppose policies aimed at helping them.ConclusionsDrug addiction is often treated as a subcategory of mental illness, and insurance plans group them together under the rubric of “behavioral health.” Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches to reducing stigma and advancing public policy.
The novel human coronavirus disease 2019 (COVID-19) pandemic has claimed more than 600,000 lives worldwide, causing tremendous public health, social, and economic damages. Although the risk factors ...of COVID-19 are still under investigation, environmental factors, such as urban air pollution, may play an important role in increasing population susceptibility to COVID-19 pathogenesis.
We conducted a cross-sectional nationwide study using zero-inflated negative binomial models to estimate the association between long-term (2010–2016) county-level exposures to NO2, PM2.5, and O3 and county-level COVID-19 case-fatality and mortality rates in the United States. We used both single- and multi-pollutant models and controlled for spatial trends and a comprehensive set of potential confounders, including state-level test positive rate, county-level health care capacity, phase of epidemic, population mobility, population density, sociodemographics, socioeconomic status, race and ethnicity, behavioral risk factors, and meteorology.
From January 22, 2020, to July 17, 2020, 3,659,828 COVID-19 cases and 138,552 deaths were reported in 3,076 US counties, with an overall observed case-fatality rate of 3.8%. County-level average NO2 concentrations were positively associated with both COVID-19 case-fatality rate and mortality rate in single-, bi-, and tri-pollutant models. When adjusted for co-pollutants, per interquartile-range (IQR) increase in NO2 (4.6 ppb), COVID-19 case-fatality rate and mortality rate were associated with an increase of 11.3% (95% CI 4.9%–18.2%) and 16.2% (95% CI 8.7%–24.0%), respectively. We did not observe significant associations between COVID-19 case-fatality rate and long-term exposure to PM2.5 or O3, although per IQR increase in PM2.5 (2.6 μg/m3) was marginally associated, with a 14.9% (95% CI 0.0%–31.9%) increase in COVID-19 mortality rate when adjusted for co-pollutants.
Long-term exposure to NO2, which largely arises from urban combustion sources such as traffic, may enhance susceptibility to severe COVID-19 outcomes, independent of long-term PM2.5 and O3 exposure. The results support targeted public health actions to protect residents from COVID-19 in heavily polluted regions with historically high NO2 levels. Continuation of current efforts to lower traffic emissions and ambient air pollution may be an important component of reducing population-level risk of COVID-19 case fatality and mortality.
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•One of the first US studies on air pollution exposures and COVID-19 death outcomes•Urban air pollutants, especially NO2, may enhance population susceptibility to death fromCOVID-19•Reduction in air pollution would have avoided over 14,000 COVID-19 deaths in the US as of July 17, 2020•Public health actions needed to protect populations from COVID-19 in areas with historically high NO2 exposure•Expansion of efforts to lower air pollution may reduce population-level risk of COVID-19
Physician‐scientists comprise a unique and valuable part of the biomedical workforce, but for decades there has been concern about the number of physicians actively engaged in research. Reports have ...outlined the challenges facing physician‐scientists, and programs have been initiated to encourage and facilitate research careers for medically trained scientists. Many of these initiatives have demonstrated successful outcomes, but there has not been a recent summary of the impact of the past decade of effort. This report compiles available data from surveys of medical education and physician research participation to assess changes in the physician‐scientist workforce from 2011–2020. Several trends are positive: rising enrollments in MD‐PhD programs, greater levels of interest in research careers among matriculating medical students, more research experience during medical school and rising numbers of physicians in academic medicine, and an increase in first R01 grants to physician‐scientists. However, there are now decreased levels of interest in research careers among graduating medical students, a steady decline in MDs applying for NIH loan repayment program support, an increased age at first R01 grant success for physicians, and fewer physicians reporting research as their primary work activity: all of these indicators create concern for the stability of the career path. Despite a recommendation by the Physician‐Scientist Workforce in 2014 to create “real‐time” reporting on NIH grants and grantees to help the public assess trends, this initiative has not been completed. Better information is still needed to fully understand the status of the physician‐scientist workforce, and to assess efforts to stabilize this vulnerable career path.
Exposure to atmospheric fine particulate matter (PM2.5) is associated with cardiorespiratory morbidity and mortality, but the mechanisms are not well understood. We assess the hypothesis that PM2.5 ...induces oxidative stress in the body via catalytic generation of reactive oxygen species (ROS). A dithiothreitol (DTT) assay was used to measure the ROS-generation potential of water-soluble PM2.5. Source apportionment on ambient (Atlanta, GA) PM2.5 was performed using the chemical mass balance method with ensemble-averaged source impact profiles. Linear regression analysis was used to relate PM2.5 emission sources to ROS-generation potential and to estimate historical levels of DTT activity for use in an epidemiologic analysis for the period of 1998–2009. Light-duty gasoline vehicles (LDGV) exhibited the highest intrinsic DTT activity, followed by biomass burning (BURN) and heavy-duty diesel vehicles (HDDV) (0.11 ± 0.02, 0.069 ± 0.02, and 0.052 ± 0.01 nmol min–1 μg–1 source, respectively). BURN contributed the largest fraction to total DTT activity over the study period, followed by LDGV and HDDV (45, 20, and 14%, respectively). DTT activity was more strongly associated with emergency department visits for asthma/wheezing and congestive heart failure than PM2.5. This work provides further epidemiologic evidence of a biologically plausible mechanism, that of oxidative stress, for associations of adverse health outcomes with PM2.5 mass and supports continued assessment of the utility of the DTT activity assay as a measure of ROS-generating potential of particles.
Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma.
In this study, we tested whether developmental trajectories of the ...nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma.
Children participating in the Childhood Origins of Asthma study (N = 285) provided nasopharyngeal mucus samples in the first 2 years of life, during routine healthy study visits (at 2, 4, 6, 9, 12, 18, and 24 months of age), and during episodes of respiratory illnesses, all of which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and we correlated these with presence of asthma at 6, 8, 11, 13, and 18 years of age.
Of the 4 microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood.
In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma.
The development and understanding of the mechanical properties of neutron-irradiated FeCrAl alloys is increasingly a critical need as these alloys continue to become more mature for nuclear reactor ...applications. This study focuses on the mechanical properties of model FeCrAl alloys and of a commercial FeCrAl alloy neutron-irradiated to up to 13.8 displacements per atom (dpa) at irradiation temperatures between 320 and 382 °C. Tensile tests were completed at room temperature and at 320 °C, and a subset of fractured tensile specimens was examined by scanning electron microscopy. Results showed typical radiation hardening and embrittlement indicative of high chromium ferritic alloys with strong chromium composition dependencies at lower doses. At and above 7.0 dpa, the mechanical properties saturated for both the commercial and model FeCrAl alloys, although brittle cleavage fracture was observed at the highest dose in the model FeCrAl alloy with the highest chromium content (18 wt %). The results suggest the composition and microstructure of FeCrAl alloys plays a critical role in the mechanical response of FeCrAl alloys irradiated near temperatures relevant to light water reactors.
Whereas associations between air pollution and respiratory morbidity for adults 65 years and older are well documented in the United States, the evidence for people under 65 is less extensive. To ...address this gap, the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program collected respiratory emergency department (ED) data from 17 states.
To estimate age-specific acute effects of ozone and fine particulate matter (particulate matter ≤2.5 mm in aerodynamic diameter PM
) on respiratory ED visits.
We conducted time-series analyses in 894 counties by linking daily respiratory ED visits with estimated ozone and PM
concentrations during the week before the date of the visit. Overall effect estimates were obtained with a Bayesian hierarchical model to combine county estimates for each pollutant by age group (children, 0-18; adults, 19-64; adults ≥ 65, and all ages) and by outcome group (acute respiratory infection, asthma, chronic obstructive pulmonary disease, pneumonia, and all respiratory ED visits).
Rate ratios (95% credible interval) per 10-μg/m
increase in PM
and all respiratory ED visits were 1.024 (1.018-1.029) among children, 1.008 (1.004-1.012) among adults younger than 65 years, and 1.002 (0.996-1.007) among adults 65 and older. Per 20-ppb increase in ozone, rate ratios were 1.017 (1.011-1.023) among children, 1.051 (1.046-1.056) among adults younger than 65, and 1.033 (1.026-1.040) among adults 65 and older. Associations varied in magnitude by age group for each outcome group.
These results address a gap in the evidence used to ensure adequate public health protection under national air pollution policies.
Background
Diarrhoea is a major cause of death and disease, especially among young children in low‐income countries. In these settings, many infectious agents associated with diarrhoea are spread ...through water contaminated with faeces.
In remote and low‐income settings, source‐based water quality improvement includes providing protected groundwater (springs, wells, and bore holes), or harvested rainwater as an alternative to surface sources (rivers and lakes). Point‐of‐use water quality improvement interventions include boiling, chlorination, flocculation, filtration, or solar disinfection, mainly conducted at home.
Objectives
To assess the effectiveness of interventions to improve water quality for preventing diarrhoea.
Search methods
We searched the Cochrane Infectious Diseases Group Specialized Register (11 November 2014), CENTRAL (the Cochrane Library, 7 November 2014), MEDLINE (1966 to 10 November 2014), EMBASE (1974 to 10 November 2014), and LILACS (1982 to 7 November 2014). We also handsearched relevant conference proceedings, contacted researchers and organizations working in the field, and checked references from identified studies through 11 November 2014.
Selection criteria
Randomized controlled trials (RCTs), quasi‐RCTs, and controlled before‐and‐after studies (CBA) comparing interventions aimed at improving the microbiological quality of drinking water with no intervention in children and adults.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data. We used meta‐analyses to estimate pooled measures of effect, where appropriate, and investigated potential sources of heterogeneity using subgroup analyses. We assessed the quality of evidence using the GRADE approach.
Main results
Forty‐five cluster‐RCTs, two quasi‐RCTs, and eight CBA studies, including over 84,000 participants, met the inclusion criteria. Most included studies were conducted in low‐ or middle‐income countries (LMICs) (50 studies) with unimproved water sources (30 studies) and unimproved or unclear sanitation (34 studies). The primary outcome in most studies was self‐reported diarrhoea, which is at high risk of bias due to the lack of blinding in over 80% of the included studies.
Source‐based water quality improvements
There is currently insufficient evidence to know if source‐based improvements such as protected wells, communal tap stands, or chlorination/filtration of community sources consistently reduce diarrhoea (one cluster‐RCT, five CBA studies, very low quality evidence). We found no studies evaluating reliable piped‐in water supplies delivered to households.
Point‐of‐use water quality interventions
On average, distributing water disinfection products for use at the household level may reduce diarrhoea by around one quarter (Home chlorination products: RR 0.77, 95% CI 0.65 to 0.91; 14 trials, 30,746 participants, low quality evidence; flocculation and disinfection sachets: RR 0.69, 95% CI 0.58 to 0.82, four trials, 11,788 participants, moderate quality evidence). However, there was substantial heterogeneity in the size of the effect estimates between individual studies.
Point‐of‐use filtration systems probably reduce diarrhoea by around a half (RR 0.48, 95% CI 0.38 to 0.59, 18 trials, 15,582 participants, moderate quality evidence). Important reductions in diarrhoea episodes were shown with ceramic filters, biosand systems and LifeStraw® filters; (Ceramic: RR 0.39, 95% CI 0.28 to 0.53; eight trials, 5763 participants, moderate quality evidence; Biosand: RR 0.47, 95% CI 0.39 to 0.57; four trials, 5504 participants, moderate quality evidence; LifeStraw®: RR 0.69, 95% CI 0.51 to 0.93; three trials, 3259 participants, low quality evidence). Plumbed in filters have only been evaluated in high‐income settings (RR 0.81, 95% CI 0.71 to 0.94, three trials, 1056 participants, fixed effects model).
In low‐income settings, solar water disinfection (SODIS) by distribution of plastic bottles with instructions to leave filled bottles in direct sunlight for at least six hours before drinking probably reduces diarrhoea by around a third (RR 0.62, 95% CI 0.42 to 0.94; four trials, 3460 participants, moderate quality evidence).
In subgroup analyses, larger effects were seen in trials with higher adherence, and trials that provided a safe storage container. In most cases, the reduction in diarrhoea shown in the studies was evident in settings with improved and unimproved water sources and sanitation.
Authors' conclusions
Interventions that address the microbial contamination of water at the point‐of‐use may be important interim measures to improve drinking water quality until homes can be reached with safe, reliable, piped‐in water connections. The average estimates of effect for each individual point‐of‐use intervention generally show important effects. Comparisons between these estimates do not provide evidence of superiority of one intervention over another, as such comparisons are confounded by the study setting, design, and population.
Further studies assessing the effects of household connections and chlorination at the point of delivery will help improve our knowledge base. As evidence suggests effectiveness improves with adherence, studies assessing programmatic approaches to optimising coverage and long‐term utilization of these interventions among vulnerable populations could also help strategies to improve health outcomes.
16 April 2019
Update pending
Studies awaiting assessment
The CIDG is currently examining a new search conducted in April 2019 for potentially relevant studies. These studies have not yet been incorporated into this Cochrane Review.
Physician scientists (researchers with either M.D. or M.D.‐Ph.D. degrees) have the unique potential to combine clinical perspectives with scientific insight, and their participation in biomedical ...research has long been an important topic for policymakers and educators. Given the recent changes in the research environment, an update and extension of earlier studies of this population was needed. Our findings show that physician scientists are less likely to take a major role in biomedical research than they were in the past. The number of physician scientists receiving postdoctoral research training and career development awards is at an all‐time low. Physician scientists today, on average, receive their first major research award (R01 equivalent) at a later age than in the 1980s. The number of first‐time R01‐equivalent awards to physicians is at the same level as it was 30 yr ago, but physicians now represent a smaller percentage of the grant recipients. The long‐term decline in the number of physicians entering research careers was temporarily halted during the period of substantial U.S. National Institutes of Health (NIH) budget growth (1998–2003). These gains are lost, however, in the subsequent years when NIH budgets failed to keep pace with rising costs.—Garrison, H. H., Deschamps, A. M. NIH research funding and early career physician scientists: continuing challenges in the 21st century. FASEB J. 28, 1049–1058 (2014). www.fasebj.org
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