Evaluating the sensitivity of mortality attributable to pollution to modeling Choices: A case study for Colorado.

We evaluated the sensitivity of estimated PM2.5 and NO2 health impacts to varying key input parameters and assumptions including: 1) the spatial scale at which impacts are estimated, 2) using either a single concentration-response function (CRF) or using racial/ethnic group specific CRFs from the same epidemiologic study, 3) assigning exposure to residents based on home, instead of home and work locations for the state of Colorado. We found that the spatial scale of the analysis influences the magnitude of NO2, but not PM2.5, attributable deaths. Using county-level predictions instead of 1 km2 predictions of NO2 resulted in a lower estimate of mortality attributable to NO2 by âˆ¼ 50 % for all of Colorado for each year between 2000 and 2020. Using an all-population CRF instead of racial/ethnic group specific CRFs results in a 130 % higher estimate of annual mortality attributable for the white population and a 40 % and 80 % lower estimate of mortality attributable to PM2.5 for Black and Hispanic residents, respectively. Using racial/ethnic group specific CRFs did not result in a different estimation of NO2 attributable mortality for white residents, but led to âˆ¼ 50 % lower estimates of mortality for Black residents, and 290 % lower estimate for Hispanic residents. Using NO2 based on home instead of home and workplace locations results in a smaller estimate of annual mortality attributable to NO2 for all of Colorado by 2 % each year and 0.3 % for PM2.5. Our results should be interpreted as an exercise to make methodological recommendations for future health impact assessments of pollution.

The Social Cost of Ozone-Related Mortality Impacts From Methane Emissions.

Atmospheric methane directly affects surface temperatures and indirectly affects ozone, impacting human welfare, the economy, and environment. The social cost of methane (SC-CH4) metric estimates the costs associated with an additional marginal metric ton of emissions. Current SC-CH4 estimates do not consider the indirect impacts associated with ozone production from changes in methane. We use global model simulations and a new BenMAP webtool to estimate respiratory-related deaths associated with increases in ozone from a pulse of methane emissions in 2020. By using an approach consistent with the current SC-CH4 framework, we monetize and discount annual damages back to present day values. We estimate that the methane-ozone mechanism is attributable to 760 (95% CI: 330-1200) respiratory-related deaths per million metric tons of methane globally, for a global net present damage of $1800/mT (95% CI: $760-$2800/Mt CH4; 2% Ramsey discount rate); this would double the current SC-CH4 if included. These physical impacts are consistent with recent studies, but comparing direct costs is challenging. Economic damages are sensitive to uncertainties in the exposure and health risks associated with tropospheric ozone, assumptions about future projections of NOx emissions, socioeconomic conditions, and mortality rates, monetization parameters, and other factors. Our estimates are highly sensitive to uncertainties in ozone health risks. We also develop a reduced form model to test sensitivities to other parameters. The reduced form tool runs with a user-supplied emissions pulse, as well as socioeconomic and precursor projections, enabling future integration of the methane-ozone mechanism into the SC-CH4 modeling framework.

Estimates of Quality-Adjusted Life-Year Loss for Injuries in the United States.

PURPOSE: The goal of this study is to develop an approach for estimating nationally representative quality-adjusted life-year (QALY) loss from injury and poisoning conditions using data collected in the Medical Expenditure Panel Survey (MEPS) and the National Health Interview Survey (NHIS). METHODS: This study uses data from the 2002-2015 NHIS and MEPS surveys. Injuries were identified in the MEPS medical events file and through self-reporting of medical conditions. We restricted our model to 163,731 adults, for which we predict a total of 294,977 EQ-5D scores using responses to the self-administered questionnaire. EQ-5D scores were modeled using age, sex, comorbidities, and binary indicators of the presence and duration of injury at the time of the health status questionnaire. These models consider nonlinearity over time during the first 3 y following the injury event. RESULTS: Injuries are identified in MEPS using medical events that provide a reasonable proxy for the date of injury occurrence. Health-related quality of life (HRQL) decrements can be estimated using binary indicators of injury during different time periods. When grouped into 29 injury categories, most categories were statistically significant predictors of HRQL scores in the first year after injury. For these groups of injuries, mean first-year QALY loss estimates range from 0.005 (sprains and strains of joints and adjacent muscles, n = 7067) to 0.109 (injury to nerves and spinal cord, n = 71). Fewer estimates are significant in the second and third years after injury, which may reflect a return to baseline HRQL. CONCLUSION: This research presents both a framework for estimating QALY loss for short-lived medical conditions and nationally representative, community-based HRQL scores associated with a wide variety of injury and poisoning conditions. HIGHLIGHTS: This research provides a catalog of nationally representative, preference-based EQ-5D score decrements associated with surviving a large set of injuries, based on patient-reported health status.Mean first-year QALY loss estimates range from 0.005 (sprains and strains of joints and adjacent muscles, n = 7067) to 0.109 (injury to nerves and spinal cord, n = 71).This article presents a novel methodology for assessing quality-of-life impacts for acute conditions by calculating the time elapsed between injury and health status elicitation. Researchers may explore adapting these methods to study other short-lived conditions and health states, such as COVID-19 or chemotherapy.

Estimates of the Global Burden of Ambient [Formula: see text], Ozone, and [Formula: see text] on Asthma Incidence and Emergency Room Visits.

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 ([Formula: see text]), ozone, and nitrogen dioxide ([Formula: see text]) 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 9­23 million and 5­10 million annual asthma emergency room visits globally in 2015 could be attributable to ozone and [Formula: see text], respectively, representing 8­20% and 4­9% 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 [Formula: see text] and 73% of ozone and [Formula: see text] impacts, respectively. Remaining impacts were attributable to naturally occurring ozone precursor emissions (e.g., from vegetation, lightning) and [Formula: see text] (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/EHP3766.

Heat-Related Health Impacts under Scenarios of Climate and Population Change.

Recent assessments have found that a warming climate, with associated increases in extreme heat events, could profoundly affect human health. This paper describes a new modeling and analysis framework, built around the Benefits Mapping and Analysis Program-Community Edition (BenMAP), for estimating heat-related mortality as a function of changes in key factors that determine the health impacts of extreme heat. This new framework has the flexibility to integrate these factors within health risk assessments, and to sample across the uncertainties in them, to provide a more comprehensive picture of total health risk from climate-driven increases in extreme heat. We illustrate the framework's potential with an updated set of projected heat-related mortality estimates for the United States. These projections combine downscaled Coupled Modeling Intercomparison Project 5 (CMIP5) climate model simulations for Representative Concentration Pathway (RCP)4.5 and RCP8.5, using the new Locating and Selecting Scenarios Online (LASSO) tool to select the most relevant downscaled climate realizations for the study, with new population projections from EPA's Integrated Climate and Land Use Scenarios (ICLUS) project. Results suggest that future changes in climate could cause approximately from 3000 to more than 16,000 heat-related deaths nationally on an annual basis. This work demonstrates that uncertainties associated with both future population and future climate strongly influence projected heat-related mortality. This framework can be used to systematically evaluate the sensitivity of projected future heat-related mortality to the key driving factors and major sources of methodological uncertainty inherent in such calculations, improving the scientific foundations of risk-based assessments of climate change and human health.

Zygotic loss of ZEN-4/MKLP1 results in disruption of epidermal morphogenesis in the C. elegans embryo.

ZEN-4/MKLP1 is required maternally for cytokinesis in Caenorhabditis elegans, but was originally identified in a screen for zygotic lethal, enclosure abnormal (Zen) mutants. We report that zen-4(w35) homozygotes exhibit stochastic failures in cytokinesis in multiple lineages. Remarkably, multinucleate epidermal cells show directional migration, even when there are as few as half the normal number of cells. Temperature shift experiments and analysis of zen-4::gfp expression confirm that the epidermal requirement for zen-4 function precedes morphogenesis. Driving expression of wild-type zen-4 by means of an epithelial-specific transgene can rescue many epidermal morphogenetic defects in zen-4 mutants. Early expression of unc-119 in epidermal precursors made this promoter unsuitable as a neuronal-specific driver in this context. Our results indicate that zygotic zen-4 function is required for correct division of epidermal precursors and, hence, indirectly for normal morphogenesis and that the epidermal morphogenetic program is surprisingly robust even in the absence of zen-4 function.

Characterization of Caenorhabditis elegans homologs of the Down syndrome candidate gene DYRK1A.

The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.