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2.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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3.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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4.
  • Armstrong, Ben, et al. (författare)
  • The Role of Humidity in Associations of High Temperature with Mortality : A Multicountry, Multicity Study
  • 2019
  • Ingår i: Journal of Environmental Health Perspectives. - : The National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 127:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature.Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset.Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques.Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1–3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly.Discussion:The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify.
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5.
  • Chen, Kai, et al. (författare)
  • Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities
  • 2021
  • Ingår i: The Lancet Planetary Health. - 2542-5196. ; 5:4, s. e191-e199
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods: We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings: Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation: This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants. Funding: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council.
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6.
  • Gasparrini, Antonio, et al. (författare)
  • Mortality risk attributable to high and low ambient temperature : a multicountry observational study
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:9991, s. 369-375
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although studies have provided estimates of premature deaths attributable to either heat or cold in selected countries, none has so far offered a systematic assessment across the whole temperature range in populations exposed to different climates. We aimed to quantify the total mortality burden attributable to non-optimum ambient temperature, and the relative contributions from heat and cold and from moderate and extreme temperatures.METHODS: We collected data for 384 locations in Australia, Brazil, Canada, China, Italy, Japan, South Korea, Spain, Sweden, Taiwan, Thailand, UK, and USA. We fitted a standard time-series Poisson model for each location, controlling for trends and day of the week. We estimated temperature-mortality associations with a distributed lag non-linear model with 21 days of lag, and then pooled them in a multivariate metaregression that included country indicators and temperature average and range. We calculated attributable deaths for heat and cold, defined as temperatures above and below the optimum temperature, which corresponded to the point of minimum mortality, and for moderate and extreme temperatures, defined using cutoffs at the 2·5th and 97·5th temperature percentiles.FINDINGS: We analysed 74 225 200 deaths in various periods between 1985 and 2012. In total, 7·71% (95% empirical CI 7·43-7·91) of mortality was attributable to non-optimum temperature in the selected countries within the study period, with substantial differences between countries, ranging from 3·37% (3·06 to 3·63) in Thailand to 11·00% (9·29 to 12·47) in China. The temperature percentile of minimum mortality varied from roughly the 60th percentile in tropical areas to about the 80-90th percentile in temperate regions. More temperature-attributable deaths were caused by cold (7·29%, 7·02-7·49) than by heat (0·42%, 0·39-0·44). Extreme cold and hot temperatures were responsible for 0·86% (0·84-0·87) of total mortality.INTERPRETATION: Most of the temperature-related mortality burden was attributable to the contribution of cold. The effect of days of extreme temperature was substantially less than that attributable to milder but non-optimum weather. This evidence has important implications for the planning of public-health interventions to minimise the health consequences of adverse temperatures, and for predictions of future effect in climate-change scenarios.FUNDING: UK Medical Research Council.
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7.
  • Lee, Jae Young, et al. (författare)
  • Predicted temperature-increase-induced global health burden and its regional variability
  • 2019
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 131
  • Tidskriftsartikel (refereegranskat)abstract
    • An increase in the global health burden of temperature was projected for 459 locations in 28 countries worldwide under four representative concentration pathway scenarios until 2099. We determined that the amount of temperature increase for each 100 ppm increase in global CO2 concentrations is nearly constant, regardless of climate scenarios. The overall average temperature increase during 2010-2099 is largest in Canada (1.16 °C/100 ppm) and Finland (1.14 °C/100 ppm), while it is smallest in Ireland (0.62 °C/100 ppm) and Argentina (0.63 °C/100 ppm). In addition, for each 1 °C temperature increase, the amount of excess mortality is increased largely in tropical countries such as Vietnam (10.34%p/°C) and the Philippines (8.18%p/°C), while it is decreased in Ireland (-0.92%p/°C) and Australia (-0.32%p/°C). To understand the regional variability in temperature increase and mortality, we performed a regression-based modeling. We observed that the projected temperature increase is highly correlated with daily temperature range at the location and vulnerability to temperature increase is affected by health expenditure, and proportions of obese and elderly population.
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8.
  • Lee, Whanhee, et al. (författare)
  • Mortality burden of diurnal temperature range and its temporal changes : a multi-country study
  • 2018
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 110, s. 123-130
  • Tidskriftsartikel (refereegranskat)abstract
    • Although diurnal temperature range (DTR) is a key index of climate change, few studies have reported the health burden of DTR and its temporal changes at a multi-country scale. Therefore, we assessed the attributable risk fraction of DTR on mortality and its temporal variations in a multi-country data set. We collected time-series data covering mortality and weather variables from 308 cities in 10 countries from 1972 to 2013. The temporal change in DTR-related mortality was estimated for each city with a time-varying distributed lag model. Estimates for each city were pooled using a multivariate meta-analysis. The results showed that the attributable fraction of total mortality to DTR was 2.5% (95% eCI: 2.3-2.7%) over the entire study period. In all countries, the attributable fraction increased from 2.4% (2.1-2.7%) to 2.7% (2.4-2.9%) between the first and last study years. This study found that DTR has significantly contributed to mortality in all the countries studied, and this attributable fraction has significantly increased over time in the USA, the UK, Spain, and South Korea. Therefore, because the health burden of DTR is not likely to reduce in the near future, countermeasures are needed to alleviate its impact on human health.
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9.
  • Liu, Cong, et al. (författare)
  • Coarse particulate air pollution and daily mortality : a global study in 205 cities
  • 2022
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 206:8, s. 999-1007
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE: The associations between ambient coarse particulate matter (PM2.5-10) and daily mortality is not fully understood at a global scale.OBJECTIVES: To evaluate the short-term associations between PM2.5-10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide.METHODS: We collected daily mortality (total, cardiovascular, respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5-10 were computed as the difference between inhalable and fine particulate matter. A two-stage time-series analytic approach was applied, with over-dispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5-10 from co-pollutants (fine particulate matter, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure-response relationship curves were pooled and regional analyses were conducted.MEASUREMENTS AND MAIN RESULTS: A 10 μg/m3 increase in PM2.5-10 concentration on lag 0-1 day was associated with increments of 0.51% (95% confidence interval [CI]: 0.18%, 0.84%), 0.43% (95%CI: 0.15%, 0.71%) and 0.41% (95%CI: 0.06%, 0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all co-pollutants in two-pollutant models, especially for PM2.5. The exposure-response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds.CONCLUSIONS: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5-10 and total, cardiovascular and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5-10.
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10.
  • Masselot, Pierre, et al. (författare)
  • Differential mortality risks associated with PM2.5 components : a multi-country, multi-city study
  • 2022
  • Ingår i: Epidemiology. - : Wolters Kluwer. - 1044-3983 .- 1531-5487. ; 33:2, s. 167-175
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality.METHODS: We applied a two-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators.RESULTS: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95%CI: 1.0030-1.0097) to 1.0102 (95%CI:1.0070-1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95%CI: 1.0067-1.0133) to 1.0037 (95%CI: 0.9998- 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk.CONCLUSIONS: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.
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11.
  • Meng, Xia, et al. (författare)
  • Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality : multilocation analysis in 398 cities.
  • 2021
  • Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 372
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol.DESIGN: Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis.SETTING: 398 cities in 22 low to high income countries/regions.MAIN OUTCOME MEASURES: Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018.RESULTS: On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities.CONCLUSIONS: This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2.
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12.
  • Rai, Masna, et al. (författare)
  • Heat-related cardiorespiratory mortality : effect modification by air pollution across 482 cities from 24 countries
  • 2023
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 174
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. Objectives: We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries.Methods: Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model.Results: Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6–7.7), 11.3% (95%CI 11.2–11.3), and 14.3% (95% CI 14.1–14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5–1.6), 5.1 (95%CI 5.1–5.2), and 8.7 (95%CI 8.7–8.8) at low, medium, and high levels of O3, respectively.Discussion: We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development.
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13.
  • Tobías, Aurelio, et al. (författare)
  • Geographical Variations of the Minimum Mortality Temperature at a Global Scale : A Multicountry Study
  • 2021
  • Ingår i: Environmental epidemiology. - : Wolters Kluwer. - 2474-7882. ; 5:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Minimum mortality temperature (MMT) is an important indicator to assess the temperature-mortality association, indicating long-term adaptation to local climate. Limited evidence about the geographical variability of the MMT is available at a global scale.Methods: We collected data from 658 communities in 43 countries under different climates. We estimated temperature-mortality associations to derive the MMT for each community using Poisson regression with distributed lag nonlinear models. We investigated the variation in MMT by climatic zone using a mixed-effects meta-analysis and explored the association with climatic and socioeconomic indicators.Results: The geographical distribution of MMTs varied considerably by country between 14.2 and 31.1 °C decreasing by latitude. For climatic zones, the MMTs increased from alpine (13.0 °C) to continental (19.3 °C), temperate (21.7 °C), arid (24.5 °C), and tropical (26.5 °C). The MMT percentiles (MMTPs) corresponding to the MMTs decreased from temperate (79.5th) to continental (75.4th), arid (68.0th), tropical (58.5th), and alpine (41.4th). The MMTs indreased by 0.8 °C for a 1 °C rise in a community's annual mean temperature, and by 1 °C for a 1 °C rise in its SD. While the MMTP decreased by 0.3 centile points for a 1 °C rise in a community's annual mean temperature and by 1.3 for a 1 °C rise in its SD.Conclusions: The geographical distribution of the MMTs and MMTPs is driven mainly by the mean annual temperature, which seems to be a valuable indicator of overall adaptation across populations. Our results suggest that populations have adapted to the average temperature, although there is still more room for adaptation.
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14.
  • Vicedo-Cabrera, Ana M, et al. (författare)
  • Short term association between ozone and mortality : global two stage time series study in 406 locations in 20 countries
  • 2020
  • Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 368
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide.DESIGN: Two stage time series analysis.SETTING: 406 cities in 20 countries, with overlapping periods between 1985 and 2015, collected from the database of Multi-City Multi-Country Collaborative Research Network.POPULATION: Deaths for all causes or for external causes only registered in each city within the study period.MAIN OUTCOME MEASURES: Daily total mortality (all or non-external causes only).RESULTS: A total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 µg/m3 increase in ozone during the current and previous day was associated with an overall relative risk of mortality of 1.0018 (95% confidence interval 1.0012 to 1.0024). Some heterogeneity was found across countries, with estimates ranging from greater than 1.0020 in the United Kingdom, South Africa, Estonia, and Canada to less than 1.0008 in Mexico and Spain. Short term excess mortality in association with exposure to ozone higher than maximum background levels (70 µg/m3) was 0.26% (95% confidence interval 0.24% to 0.28%), corresponding to 8203 annual excess deaths (95% confidence interval 3525 to 12 840) across the 406 cities studied. The excess remained at 0.20% (0.18% to 0.22%) when restricting to days above the WHO guideline (100 µg/m3), corresponding to 6262 annual excess deaths (1413 to 11 065). Above more lenient thresholds for air quality standards in Europe, America, and China, excess mortality was 0.14%, 0.09%, and 0.05%, respectively.CONCLUSIONS: Results suggest that ozone related mortality could be potentially reduced under stricter air quality standards. These findings have relevance for the implementation of efficient clean air interventions and mitigation strategies designed within national and international climate policies.
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