The Experts below are selected from a list of 427935 Experts worldwide ranked by ideXlab platform
Joel Schwartz - One of the best experts on this subject based on the ideXlab platform.
-
the Concentration Response between long term pm2 5 exposure and mortality a meta regression approach
Environmental Research, 2018Co-Authors: Alina Vodonos, Yara Abu Awad, Joel SchwartzAbstract:Abstract Background Long-term exposure to ambient fine particulate matter (≤ 2.5 μg/m3 in aerodynamic diameter; PM2.5) is significantly associated with increased risk of premature mortality. Our goal was to provide an updated meta-analysis of all-cause and cause-specific mortality associated with exposure to PM2.5 and to better estimate the risk of death as a function of air pollution levels. Methods We systematically searched all published cohort studies examining the association between long term exposure to PM2.5 and mortality. We applied multivariate linear random effects meta-analysis with random effects for cohort, and study within cohort. Meta-regression techniques were used to test whether study population or analytic characteristics modify the PM2.5 -mortality association and to estimate the shape of the Concentration-Response curve. Results A total of 53 studies that provided 135 estimates of the quantitative association between the risk of mortality and exposure to PM2.5 were included in the meta-analysis. There were 39 studies from North America, 8 from Europe, and 6 from Asia. Since 2015, 17 studies of long-term air pollution exposure have been published, covering, wider geographic areas with a wider range of mean exposures (e.g. 20 μg/m3). A penalized spline showed the slope decreased at higher Concentrations but appeared to level off. We found that the inverse transform of average PM2.5 well approximated that spline and provided a parametric estimate that fit better than a linear or logarithmic term for average PM2.5. In addition, we found that studies using space time exposure models or fixed monitors at Zip-code scale (as compared to land use regression method), or additionally controlling for area level socio-economic status, or with mean exposure less than 10 μg/m3 were associated with higher mortality effect estimates. Conclusions This meta-analysis provides strong evidence for the adverse effect of PM2.5 on mortality, that studies with poorer exposure have lower effect size estimates, that more control for SES increases effect size estimates, and that significant effects are seen below 10 µg/m3. The Concentration -Response function produced here can be further applied in the global health risk assessment of air particulate matter.
-
empirical bayes and adjusted estimates approach to estimating the relation of mortality to exposure of pm10
Risk Analysis, 2005Co-Authors: Alain Le Tertre, Joel Schwartz, Giota TouloumiAbstract:In the framework of the APHEIS program (Air Pollution and Health: A European Information System), a health impact assessment of air pollution in 26 European cities was performed for particles of an aerodynamic diameter less than or equal to 10 µm (PM10). For shortterm effects, it was based on overall estimates from the APHEA-2 project (Air Pollution and Health: A European Approach). These city-specific risk assessments require city-specific Concentration-Response functions, raising the question of which Concentration-Response is most appropriate. Estimates from city-specific models are more specific, but have greater uncertainty than those provided from multicity analyses. We compared several estimates derived from the city-specific analyses in cities that were part of the APHEA-2 project, as well as in a city that was not included in APHEA-2 but was part of the APHEIS project. These estimates were: the estimates from a local regression model, the adjusted estimates based on two significant effect modifiers identified through meta-regression models, and the city-specific empirical Bayes (shrunken) estimates and their underlying distribution. The shrunken and adjusted estimates were used to improve the estimation of city-specific Concentration-Response function. From these different estimates, attributable numbers of deaths per year were calculated. The advantages and limits of the different approaches are discussed through real data and in a simulation study.
-
the Concentration Response relation between pm 2 5 and daily deaths
Environmental Health Perspectives, 2002Co-Authors: Joel Schwartz, Francine Laden, Antonella ZanobettiAbstract:Particulate air pollution at commonly occurring Concentrations is associated with daily deaths. Recent attention has focused on the shape of the Concentration-Response curve, particularly at low doses. Several recent articles have reported that particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) was associated with daily deaths with no evidence of a threshold. These reports have used smoothing or spline methods in individual cities and pooled the results across multiple cities to obtain estimates that are more robust. To date, fine particulate matter (aerodynamic diameter Less than or equal to 2.5 microm; PM(2.5)), a component of PM(10), has not been examined in this regard. We examined this association in a hierarchical model in six U.S. cities. In the first stage, we fit log-linear models including smooth functions of PM(2.5) in each city, controlling for season, weather, and day of the week. These smooth functions allowed for nonlinearities in the city-specific associations. We combined the estimated curves across cities using a hierarchical model that allows for heterogeneity. We found an essentially linear relationship down to 2 microg/m(3). The same approach was applied to examine the Concentration Response to traffic particles, controlling for particles from other sources. Once again, the association showed no sign of a threshold. The magnitude of the association suggests that controlling fine particle pollution would result in thousands of fewer early deaths per year.
-
the Concentration Response relation between air pollution and daily deaths
Environmental Health Perspectives, 2001Co-Authors: Joel Schwartz, Ferran Ballester, Marc Saez, S Perezhoyos, Juan Bellido, Koldo Cambra, Federico Arribas, Alvaro Canada, Maria Jose Perezboillos, Jordi SunyerAbstract:Studies on three continents have reported associations between various measures of airborne particles and daily deaths. Sulfur dioxide has also been associated with daily deaths, particularly in Europe. Questions remain about the shape of those associations, particularly whether there are thresholds at low levels. We examined the association of daily Concentrations of black smoke and SO(2) with daily deaths in eight Spanish cities (Barcelona, Bilbao, Castellon, Gijon, Oviedo, Valencia, Vitoria, and Zaragoza) with different climates and different environmental and social characteristics. We used nonparametric smoothing to estimate the shape of the Concentration-Response curve in each city and combined those results using a metasmoothing technique developed by Schwartz and Zanobetti. We extended their method to incorporate random variance components. Black smoke had a nearly linear association with daily deaths, with no evidence of a threshold. A 10 microg/m(3) increase in black smoke was associated with a 0.88% increase in daily deaths (95% confidence interval, 0.56%-1.20%). SO(2) had a less plausible association: Daily deaths increased at very low Concentrations, but leveled off and then decreased at higher Concentrations. These findings held in both one- and two-pollutant models and held whether we optimized our weather and seasonal model in each city or used the same smoothing parameters in each city. We conclude that the association with particle levels is more convincing than for SO(2), and without a threshold. Linear models provide an adequate estimation of the effect of particulate air pollution on mortality at low to moderate Concentrations.
Molly S Shoichet - One of the best experts on this subject based on the ideXlab platform.
-
colloidal drug formulations can explain bell shaped Concentration Response curves
ACS Chemical Biology, 2014Co-Authors: Shawn C Owen, Allison K Doak, Ahil N Ganesh, Lyudmila Nedyalkova, Christopher K Mclaughlin, Brian K Shoichet, Molly S ShoichetAbstract:Drug efficacy does not always increase sigmoidally with Concentration, which has puzzled the community for decades. Unlike standard sigmoidal curves, bell-shaped Concentration–Response curves suggest more complex biological effects, such as multiple-binding sites or multiple targets. Here, we investigate a physical property-based mechanism for bell-shaped curves. Beginning with the observation that some drugs form colloidal aggregates at relevant Concentrations, we determined Concentration–Response curves for three aggregating anticancer drugs, formulated both as colloids and as free monomer. Colloidal formulations exhibited bell-shaped curves, losing activity at higher Concentrations, while monomeric formulations gave typical sigmoidal curves, sustaining a plateau of maximum activity. Inverting the question, we next asked if molecules with bell-shaped curves, reported in the literature, form colloidal aggregates at relevant Concentrations. We selected 12 molecules reported to have bell-shaped concentrati...
Jordi Sunyer - One of the best experts on this subject based on the ideXlab platform.
-
the Concentration Response relation between air pollution and daily deaths
Environmental Health Perspectives, 2001Co-Authors: Joel Schwartz, Ferran Ballester, Marc Saez, S Perezhoyos, Juan Bellido, Koldo Cambra, Federico Arribas, Alvaro Canada, Maria Jose Perezboillos, Jordi SunyerAbstract:Studies on three continents have reported associations between various measures of airborne particles and daily deaths. Sulfur dioxide has also been associated with daily deaths, particularly in Europe. Questions remain about the shape of those associations, particularly whether there are thresholds at low levels. We examined the association of daily Concentrations of black smoke and SO(2) with daily deaths in eight Spanish cities (Barcelona, Bilbao, Castellon, Gijon, Oviedo, Valencia, Vitoria, and Zaragoza) with different climates and different environmental and social characteristics. We used nonparametric smoothing to estimate the shape of the Concentration-Response curve in each city and combined those results using a metasmoothing technique developed by Schwartz and Zanobetti. We extended their method to incorporate random variance components. Black smoke had a nearly linear association with daily deaths, with no evidence of a threshold. A 10 microg/m(3) increase in black smoke was associated with a 0.88% increase in daily deaths (95% confidence interval, 0.56%-1.20%). SO(2) had a less plausible association: Daily deaths increased at very low Concentrations, but leveled off and then decreased at higher Concentrations. These findings held in both one- and two-pollutant models and held whether we optimized our weather and seasonal model in each city or used the same smoothing parameters in each city. We conclude that the association with particle levels is more convincing than for SO(2), and without a threshold. Linear models provide an adequate estimation of the effect of particulate air pollution on mortality at low to moderate Concentrations.
Gerald F Smith - One of the best experts on this subject based on the ideXlab platform.
-
the minimum significant ratio a statistical parameter to characterize the reproducibility of potency estimates from Concentration Response assays and estimation by replicate experiment studies
Journal of Biomolecular Screening, 2006Co-Authors: Brian J Eastwood, Mark W Farmen, Philip W Iversen, Trelia J Craft, Jeffrey K Smallwood, Kim E Garbison, Neil W Delapp, Gerald F SmithAbstract:The authors show by illustration that procedures used to validate the reliability of single-Concentration high-throughput screens such as the signal window and Z' factor do not ensure sufficient reliability in potency estimates from Concentration Response assays. They develop the minimum significant ratio as a statistical parameter to characterize the fold change between 2 compounds run in the same experiment that can be considered a real difference and use this parameter to characterize the reliability of the assay. They adapt methods described by Bland and Altman to develop a simple set of 2 experiments to estimate the minimum significant ratio and show that this protocol can identify assays that lack reproducibility. The methods are then extended to validate the equivalency of the same assay run by multiple laboratories.
Antonella Zanobetti - One of the best experts on this subject based on the ideXlab platform.
-
the Concentration Response relation between pm 2 5 and daily deaths
Environmental Health Perspectives, 2002Co-Authors: Joel Schwartz, Francine Laden, Antonella ZanobettiAbstract:Particulate air pollution at commonly occurring Concentrations is associated with daily deaths. Recent attention has focused on the shape of the Concentration-Response curve, particularly at low doses. Several recent articles have reported that particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) was associated with daily deaths with no evidence of a threshold. These reports have used smoothing or spline methods in individual cities and pooled the results across multiple cities to obtain estimates that are more robust. To date, fine particulate matter (aerodynamic diameter Less than or equal to 2.5 microm; PM(2.5)), a component of PM(10), has not been examined in this regard. We examined this association in a hierarchical model in six U.S. cities. In the first stage, we fit log-linear models including smooth functions of PM(2.5) in each city, controlling for season, weather, and day of the week. These smooth functions allowed for nonlinearities in the city-specific associations. We combined the estimated curves across cities using a hierarchical model that allows for heterogeneity. We found an essentially linear relationship down to 2 microg/m(3). The same approach was applied to examine the Concentration Response to traffic particles, controlling for particles from other sources. Once again, the association showed no sign of a threshold. The magnitude of the association suggests that controlling fine particle pollution would result in thousands of fewer early deaths per year.