Exposures to Mixtures of Air Pollutants: Analysis of Biological, Personal and Area Monitoring.

The objective of this dissertation is to understand the nature and significance of exposures to volatile organic compounds (VOCs) by characterizing exposure distributions, trends, mixtures, and determinants. VOC data were drawn from two datasets: the Relationship between Indoor, Outdoor and Personal Air study (RIOPA), the National Health and Nutrition Examination Survey (NHANES). The RIOPA study collected outdoor, indoor and personal VOCs twice in three U.S. cities. NHANES, nationally representative samples, collected both blood and personal VOCs. To estimate extreme exposures, generalized extreme value (GEV) distributions were fitted to the top 5 and 10% of VOCs. Simulated extreme value datasets were compared to observations. VOC trends in 1988 - 2004 were evaluated using linear quantile regression models at three quantiles. VOC mixtures were identified using positive matrix factorization (PMF) and by toxicological mode of action. Dependency structures of mixture components were examined using copulas. Results from copulas and multivariate lognormal models were compared to observations. Exposure determinants were identified using linear mixed-effect models. Extreme value exposures fitted the GEV distributions. Lognormal distributions significantly underestimated the likelihood of extrema. In NHANES, most VOCs showed decreasing trends at all quantiles. Trends varied by VOC and quantile, and were grouped into three patterns: similar decreases at all quantiles, most rapid decreases at upper quantiles, and fastest declines at central quantiles. Four VOC mixtures were identified by PMF (gasoline vapor, vehicle exhaust, chlorinated solvents and disinfection by-products, and cleaning products and odorants). Three mixtures were identified by toxicological mode of action (hematopoietic, liver and renal tumors). The dependency structures of the VOC mixtures fitted Gumbel and t copulas. The copulas accurately reproduced risk predictions, and performed better than multivariate lognormal distributions. The analysis of VOC determinants showed that exposures were affected by indoor concentrations, city, and some personal activities, household characteristics and meteorological factors. Exposure data feature extreme values, temporal changes, dependency structures, and other complex characteristics. Advanced statistical methods can improve estimates exposures and risks, and are needed to develop control and management guidelines and policies. These results extend our understanding of and ability to model VOC exposures.PhDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97924/1/joefcsu_1.pd

Novel Nanohybrids of Silver Particles on Clay Platelets for Inhibiting Silver-Resistant Bacteria

We develop a novel nanohybrid showing a strong antibacterial activity on all of the tested pathogens, including methicillin-resistant Staphylococcus auerus and silver-resistant E. coli. The nanohybrid consists of silver nanoparticles (AgNPs) supported on 1 nm-thick silicate platelets (NSPs). The AgNP/NSP nanohybrid enables to encapsulate bacteria and triggers death signals from the cell membrane. The geographic shape of the NSPs concentrates AgNPs but impedes their penetration into attached cells, mitigating the detrimental effect of silver ion deposition in applied tissues. Moreover, the tightly tethered AgNPs on NSP surface achieve a stronger biocidal effect than silver nitrate, but bypassing Ag+ mechanism, on silver-resistant bacteria. This nanohybrid presents an effective and safe antimicrobial agent in a new perspective

A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome

The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We searched literature on CAG between 1995 and 2010 and performed a meta-analysis to determine its overall efficacy using a random-effects or fixed-effects model. Thirty five trials with a total of 1029 AML (n = 814) and MDS (n = 215) patients were included for analysis. The CR rate of AML (57.9%) was significantly higher than that of MDS (45.7%) (p < 0.01). No difference in CR was noted between the new (56.7%) and relapsed/refractory AML (60.1%) (p > 0.05). The CR rate was also significantly higher in patients with favorable (64.5%) and intermediate (69.6%) karyotypes than those with unfavorable one (29.5%) (p < 0.05). Remarkably, the CR rate of CAG was significantly higher than those of non-CAG regimens (odds ratio 2.43). CAG regimen was well tolerated, with cardiotoxicity in 2.3% and early death in 5.2% of the cases. In conclusion, CAG regimen was an effective and safe regimen for the treatment of AML, and may be more effective than non-CAG regimens. Randomized controlled trials are strongly recommended to evaluate its efficacy and safety in comparison with the current standard treatment

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

[[alternative]]出生前後二手菸暴露與嬰兒健康

[[abstract]]環境菸煙(Environmental tobacco smoke, ETS)是種常見的室內空氣污染，且嬰幼童是暴露於ETS的高危險群。故本研究目的在評估出生前後暴露於ETS，對出生結果，含早產、低出生體重、與small for gestational age(SGA)，及兒童健康，含急診與住院的影響。方法：我們是「台灣出生世代研究(Taiwan Birth Cohort Study)」的前導研究，在母親產後6個月，以自答式問卷訪談了2,048位研究對象，最後共有1,725份含母親及其活產胎兒的完整資料。研究中利用regression models分析出生前後暴露於ETS對出生結果與兒童健康的不良影響，並以test for trend探討暴露於ETS的頻率與兩者間的關係。結果：研究發現母親在懷孕期間暴露到ETS的頻率，會與嬰兒的早產、SGA、急診和住院有顯著相關。再者，懷孕期間或生產後為主動吸菸的母親，會與嬰兒的低出生體重、SGA、急診和住院相關，但該相關除SGA外，其他則在校正後消失。此外，若父親在母親懷孕期間或生產後為主動吸菸者，嬰兒會呈現較高的住院風險，並與父親的抽菸量成正比。最後，研究發現在懷孕期間暴露到ETS的母親，比沒有暴露到的母親其嬰兒之出生體重較少222.3克。結論：在台灣，雖然母親的抽菸率非常低，但研究中仍發現，出生前後所暴露到的ETS會對兒童造成影響。為此，出生前後的ETS暴露在公共衛生上所造成地潛在不良效應，應該更被重視。[[abstract]]Environmental tobacco smoke (ETS) is a common indoor pollutant. Fetuses, neonates, and young children are most at risk from ETS exposure. In this study, we evaluated the relationship of exposure to prenatal and postnatal ETS to birth outcomes (including preterm delivery [PTD], low birth weight [LBW], and small for gestational age [SGA]) and child health outcomes (including emergency visits and hospitalizations). Methods: In this pilot project of the Taiwan Birth Cohort Study, we used a self-reported questionnaire. We interviewed 2,048 mothers 6 months after their deliveries and recruited 1,725 mother-newborn pairs. We analyzed the association of adverse birth outcome and child health with exposure to prenatal and postnatal ETS using regression models, and analyzed relationships between birth outcome and child health and frequency of exposure to prenatal and postnatal ETS using the test for trend. Results: We found a significant association between exposure to ETS during pregnancy and PTD, SGA, emergency visits, and hospitalizations of infants. In addition, infant exposure to ETS via maternal smoking during or after pregnancy contributed to significant crude relationships between LBW, SGA, emergency visits, and hospitalizations, but these relationships were completely explained by the effects of covariates other than SGA. We also observed that paternal smoking during or after pregnancy dose-dependently increased hospitalization risks of infants. Moreover, the mean adjusted BW decrement was 222.3 g in newborns exposed to ETS from maternal smokers. Conclusions: Although maternal smoking risks are very low in Taiwan, prenatal or postnatal ETS exposure still impacts children. Our findings highlight the emerging challenge of prenatal and postnatal ETS exposure to the public health

Volatile Organic Compounds (VOCs) in Conventional and High Performance School Buildings in the U.S.

Exposure to volatile organic compounds (VOCs) has been an indoor environmental quality (IEQ) concern in schools and other buildings for many years. Newer designs, construction practices and building materials for “green” buildings and the use of “environmentally friendly” products have the promise of lowering chemical exposure. This study examines VOCs and IEQ parameters in 144 classrooms in 37 conventional and high performance elementary schools in the U.S. with the objectives of providing a comprehensive analysis and updating the literature. Tested schools were built or renovated in the past 15 years, and included comparable numbers of conventional, Energy Star, and Leadership in Energy and Environmental Design (LEED)-certified buildings. Indoor and outdoor VOC samples were collected and analyzed by thermal desorption, gas chromatography and mass spectroscopy for 94 compounds. Aromatics, alkanes and terpenes were the major compound groups detected. Most VOCs had mean concentrations below 5 µg/m3, and most indoor/outdoor concentration ratios ranged from one to 10. For 16 VOCs, the within-school variance of concentrations exceeded that between schools and, overall, no major differences in VOC concentrations were found between conventional and high performance buildings. While VOC concentrations have declined from levels measured in earlier decades, opportunities remain to improve indoor air quality (IAQ) by limiting emissions from building-related sources and by increasing ventilation rates

Extreme value analyses of VOC exposures and risks: A comparison of RIOPA and NHANES datasets

Extreme value theory, which characterizes the behavior of tails of distributions, is potentially well-suited to model exposures and risks of pollutants. In this application, it emphasizes the highest exposures, particularly those that may be high enough to present acute or chronic health risks. The present study examines extreme value distributions of exposures and risks to volatile organic compounds (VOCs).Exposures of 15 different VOCs were measured in the Relationship between Indoor, Outdoor and Personal Air (RIOPA) study, and ten of the same VOCs were measured in the nationally representative National Health and Nutrition Examination Survey (NHANES). Both studies used similar sampling methods and study periods. Using the highest 5 and 10% of measurements, generalized extreme value (GEV), Gumbel and lognormal distributions were fit to each VOC in these two large studies. Health risks were estimated for individual VOCs and three VOC mixtures. Simulated data that matched the three types of distributions were generated and compared to observations to evaluate goodness-of-fit. The tail behavior of exposures, which clearly neither fit normal nor lognormal distributions for most VOCs in RIOPA, was usually best fit by the 3-parameter GEV distribution, and often by the 2-parameter Gumbel distribution. In contrast, lognormal distributions significantly underestimated both the level and likelihood of extrema. Among the RIOPA VOCs, 1,4-dichlorobenzene (1,4-DCB) caused the greatest risks, e.g., for the top 10% extrema, all individuals had risk levels above 10 -4, and 13% of them exceeded 10 -2. NHANES had considerably higher concentrations of all VOCs with two exceptions, methyl tertiary-butyl ether and 1,4-DCB. Differences between these studies can be explained by sampling design, staging, sample demographics, smoking and occupation.This analysis shows that extreme value distributions can represent peak exposures of VOCs, which clearly are neither normally nor lognormally distributed. These exposures have the greatest health significance, and require accurate modeling. © 2012 Elsevier Ltd

Modeling exposures to air pollutant mixtures: Application of copula methods to the RIOPA data

Distributions of personal exposures to volatile organic compound (VOC) mixtures are modeled using multivariate methods including copulas. The data used are the personal VOC exposures collected for 306 participants in the RIOPA study. Factor analyses identified five groups of compounds: gasoline-related compounds (Mix 1); terpenes (Mix 2); chlorinated cleaning solvents (Mix 3); chlorine disinfection by-products (Mix 4); and foam emissions (Mix 5). Multivariate distributions of each group were fitted to four candidate copulas (Gaussian, Gumbel, Clayton, Frank). Gaussian copulas best fit Mixes 1, 3 and 4, and Clayton copulas best fit Mixes 2 and 5. Binary mixtures mostly followed Clayton copulas. This work indicates that co-exposures to extreme concentrations may be overestimated using standard multinormal distributions. More generally, copulas can model dependency structures with great flexibility given the many families of copulas available, and they allow any forms of marginal distributions, which is advantageous over conventional multinormal distributions