Updated global estimates of respiratory mortality in adults ≥ 30 years of age attributable to long-term ozone exposure

BACKGROUND: Relative risk estimates for long-term ozone (O3) exposure and respiratory mortality from the American Cancer Society Cancer Prevention Study II (ACS CPS-II) cohort have been used to estimate global O3-attributable mortality in adults. Updated relative risk estimates are now available for the same cohort based on an expanded study population with longer follow-up. OBJECTIVES: We estimated the global burden and spatial distribution of respiratory mortality attributable to long-term O3 exposure in adults ≥30 y of age using updated effect estimates from the ACS CPS-II cohort. METHODS: We used GEOS-Chem simulations (2×2.5º grid resolution) to estimate annual O3 exposures, and estimated total respiratory deaths in 2010 that were attributable to long-term annual O3 exposure based on the updated relative risk estimates and minimum risk thresholds set at the minimum or fifth percentile of O3 exposure in the most recent CPS-II analysis. These estimates were compared with attributable mortality based on the earlier CPS-II analysis, using 6-mo average exposures and risk thresholds corresponding to the minimum or fifth percentile of O3 exposure in the earlier study population. RESULTS: We estimated 1.04–1.23 million respiratory deaths in adults attributable to O3 exposures using the updated relative risk estimate and exposure parameters, compared with 0.40–0.55 million respiratory deaths attributable to O3 exposures based on the earlier CPS-II risk estimate and parameters. Increases in estimated attributable mortality were larger in northern India, southeast China, and Pakistan than in Europe, eastern United States, and northeast China. CONCLUSIONS: These findings suggest that the potential magnitude of health benefits of air quality policies targeting O3, health co-benefits of climate mitigation policies, and health implications of climate change-driven changes in O3 concentrations, are larger than previously thought

Increased Expression of Interleukin-6 Family Members and Receptors in Urinary Bladder with Cyclophosphamide-Induced Bladder Inflammation in Female Rats

Recent studies suggest that janus-activated kinases–signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, members of the interleukin (IL)-6 family of cytokines including, leukemia inhibitory factor (LIF), IL-6, and ciliary neurotrophic factor (CNTF) and associated receptors, IL-6 receptor (R) α, LIFR, and gp130 were examined in the urinary bladder in control and CYP-treated rats. Cytokine and receptor transcript and protein expression and distribution were determined in urinary bladder after CYP-induced cystitis using quantitative, real-time polymerase chain reaction (Q-PCR), western blotting, and immunohistochemistry. Acute (4 h; 150 mg/kg; i.p.), intermediate (48 h; 150 mg/kg; i.p.), or chronic (75 mg/kg; i.p., once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Q-PCR analyses revealed significant (p ≤ 0.01) CYP duration- and tissue- (e.g., urothelium, detrusor) dependent increases in LIF, IL-6, IL-6Rα, LIFR, and gp130 mRNA expression. Western blotting demonstrated significant (p ≤ 0.01) increases in IL-6, LIF, and gp130 protein expression in whole urinary bladder with CYP treatment. CYP-induced cystitis significantly (p ≤ 0.01) increased LIF-immunoreactivity (IR) in urothelium, detrusor, and suburothelial plexus whereas increased gp130-IR was only observed in urothelium and detrusor. These studies suggest that IL-6 and LIF may be potential upstream chemical mediators that activate JAK/STAT signaling in urinary bladder pathways

Development of the Low Emissions Analysis Platform – Integrated Benefits Calculator (LEAP-IBC) tool to assess air quality and climate co-benefits : Application for Bangladesh

Low- and middle-income countries have the largest health burdens associated with air pollution exposure, and are particularly vulnerable to climate change impacts. Substantial opportunities have been identified to simultaneously improve air quality and mitigate climate change due to overlapping sources of greenhouse gas and air pollutant emissions and because a subset of pollutants, short-lived climate pollutants (SLCPs), directly contribute to both impacts. However, planners in low- and middle-income countries often lack practical tools to quantify the air pollution and climate change impacts of different policies and measures. This paper presents a modelling framework implemented in the Low Emissions Analysis Platform – Integrated Benefits Calculator (LEAP-IBC) tool to develop integrated strategies to improve air quality, human health and mitigate climate change. The framework estimates emissions of greenhouse gases, SLCPs and air pollutants for historical years, and future projections for baseline and mitigation scenarios. These emissions are then used to quantify i) population-weighted annual average ambient PM2.5 concentrations across the target country, ii) household PM2.5 exposure of different population groups living in households cooking using different fuels/technologies and iii) radiative forcing from all emissions. Health impacts (premature mortality) attributable to ambient and household PM2.5 exposure and changes in global average temperature change are then estimated. This framework is applied in Bangladesh to evaluate the air quality and climate change benefits from implementation of Bangladesh's Nationally Determined Contribution (NDC) and National Action Plan to reduce SLCPs. Results show that the measures included to reduce GHGs in Bangladesh's NDC also have substantial benefits for air quality and human health. Full implementation of Bangladesh's NDC, and National SLCP Plan would reduce carbon dioxide, methane, black carbon and primary PM2.5 emissions by 25%, 34%, 46% and 45%, respectively in 2030 compared to a baseline scenario. These emission reductions could reduce population-weighted ambient PM2.5 concentrations in Bangladesh by 18% in 2030, and avoid approximately 12,000 and 100,000 premature deaths attributable to ambient and household PM2.5 exposures, respectively, in 2030. As countries are simultaneously planning to achieve the climate goals in the Paris Agreement, improve air quality to reduce health impacts and achieve the Sustainable Development Goals, the LEAP-IBC tool provides a practical framework by which planners can develop integrated strategies, achieving multiple air quality and climate benefits

Integrated assessment of global climate, air pollution, and dietary, malnutrition and obesity health impacts of food production and consumption between 2014 and 2018

Agriculture accounts for approximately 10% of global greenhouse gas emissions and is simultaneously associated with impacts on human health through food consumption, and agricultural air pollutant emissions. These impacts are often quantified separately, and there is a lack of modelling tools to facilitate integrated assessments. This work presents a new model that integrates assessment of agricultural systems on (i) human health indirectly through dietary, obesity and malnutrition health risks from food consumption, (ii) human health directly through exposure to air pollutants from agricultural emissions, and (iii) greenhouse gas emissions. In the model, national food demand is the starting point from which the livestock and crop production systems that meet this are represented. The model is applied for 2014–2018 to assess the robustness of the GHG emissions and health burden results that this integrated modelling framework produces compared to previous studies that have quantified these variables independently. Methane and nitrous oxide emissions globally in 2018 were estimated to be 129 and 4.4 million tonnes, respectively, consistent with previous estimates. Agricultural systems were also estimated to emit 44 million tonnes of ammonia. An estimated 4.1 million deaths were associated with dietary health risks, 6.0 million with overweight/obesity, and 730 thousand infant deaths from malnutrition, consistent with previous studies. Agricultural air pollutant emissions were estimated to be associated with 537 thousand premature deaths attributable to fine particulate matter (PM2.5) exposure, and 184 thousand premature deaths from methane-induced ground-level ozone. These health impacts provide substantial opportunities to design integrated strategies that mitigate climate change, and improve human health, and also highlight possible trade-offs that the expansion of agricultural production could have due to increased emissions. The model presented here provides for the consistent evaluation of the implications of different agricultural strategies to meet food demand while minimising human health and climate change impacts

Estimates of the global burden of ambient PM2.5, ozone, and NO2 on asthma incidence and emergency room visits

Abstract Background: Asthma is the most prevalent chronic respiratory disease worldwide, affecting 358 million people in 2015. Ambient air pollution exacerbates asthma among populations around the world and may also contribute to new-onset asthma. Objectives: We aimed to estimate the number of asthma emergency room visits and new onset asthma cases globally attributable to fine particulate matter (PM2.5), ozone, and nitrogen dioxide (NO2) concentrations. Methods: We used epidemiological health impact functions combined with data describing population, baseline asthma incidence and prevalence, and pollutant concentrations. We constructed a new dataset of national and regional emergency room visit rates among people with asthma using published survey data. Results: We estimated that 9–23 million and 5–10 million annual asthma emergency room visits globally in 2015 could be attributable to ozone and PM2.5, respectively, representing 8–20% and 4–9% of the annual number of global visits, respectively. The range reflects the application of central risk estimates from different epidemiological meta-analyses. Anthropogenic emissions were responsible for ∼37% and 73% of ozone and PM2.5 impacts, respectively. Remaining impacts were attributable to naturally occurring ozone precursor emissions (e.g., from vegetation, lightning) and PM2.5 (e.g., dust, sea salt), though several of these sources are also influenced by humans. The largest impacts were estimated in China and India. Conclusions: These findings estimate the magnitude of the global asthma burden that could be avoided by reducing ambient air pollution. We also identified key uncertainties and data limitations to be addressed to enable refined estimation. https://doi.org/10.1289/EHP376

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10−9) and 10p11.21 (P = 3.6 × 10−8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10−3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10−3) and increased seizure-like events (P = 6.8 × 10−7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10−3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease

Suicide and Suicide Risk in Lesbian, Gay, Bisexual, and Transgender Populations: Review and Recommendations

Despite strong indications of elevated risk of suicidal behavior in lesbian, gay, bisexual, and transgender people, limited attention has been given to research, interventions or suicide prevention programs targeting these populations. This article is a culmination of a three-year effort by an expert panel to address the need for better understanding of suicidal behavior and suicide risk in sexual minority populations, and stimulate the development of needed prevention strategies, interventions and policy changes. This article summarizes existing research findings, and makes recommendations for addressing knowledge gaps and applying current knowledge to relevant areas of suicide prevention practice

Estimating the New Keynesian Phillips Curve for Italian Manufacturing Sectors

The purpose of this paper is to test the general validity of the NKPC previsions for the Italian manufacturing industries. In particular we are interested in estimating the extent to which the degree of nominal inertia and the fraction of backward-looking price-setters differ from industry to industry. We attempt to address this issue by testing three different model specifications: a pure forward-looking model versus a hybrid model where an income labour share marginal cost measure is considered, and a modified hybrid model specification where marginal costs are corrected to include intermediate inputs. Our results show that the backward-looking component is statistically significant and quantitatively large for all industries. Moreover, this estimate does not depend on the models specification. Conversely, the parameter measuring the extent of price rigidity is sensitive to the definition of firms cost. Interpreting the overall results, we conclude that price-setting behaviour is not totally homogeneous among Italian firms

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570