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1.  Association between length of gestation and cervical DNA methylation of PTGER2 and LINE 1-HS 
Epigenetics  2014;9(8):1083-1091.
Worldwide, more than 1 in 10 infants is born prior to 37 weeks gestation. Preterm birth can lead to increased mortality risk and poor life-long health and neurodevelopmental outcomes. Whether environmental risk factors affect preterm birth through epigenetic phenomena is largely unstudied. We sought to determine whether preterm risk factors, such as smoke exposure and education, were associated with cervical DNA methylation in the prostaglandin E receptor 2 gene (PTGER2) and a repetitive element, long interspersed nuclear element-1 Homo sapiens-specific (LINE 1-HS). Second, we aimed to determine whether mid-pregnancy DNA methylation of these regions in cervical samples could predict the length of gestation. We obtained a cervical swab between 16–19 weeks gestation from 80 women participating in a Mexico City birth cohort, used pyrosequencing to analyze DNA methylation of PTGER2 and LINE 1-HS, and examined associations with maternal covariates. We used accelerated failure time models to analyze associations of DNA methylation with the length of gestation. DNA methylation of both sequences was associated with Pap smear inflammation. LINE 1-HS methylation was associated with smoke exposure, BMI and parity. In adjusted models, gestations were 3.3 days longer (95%CI 0.6, 6.0) for each interquartile range of PTGER2 DNA methylation. Higher LINE 1-HS methylation was associated with shorter gestations (-3.3 days, 95%CI -6.5, -0.2). In conclusion, cervical DNA methylation was associated with risk factors for preterm birth and the length of gestation.
doi:10.4161/epi.29170
PMCID: PMC4164493  PMID: 24827772
Cervix; DNA methylation; epigenetics; LINE 1; Preterm birth; PTGER2
2.  The effect of oxidative stress polymorphisms on the association between long-term black carbon exposure and lung function among elderly men 
Thorax  2014;70(2):133-137.
Background
Black carbon (BC) is a pro-oxidant, traffic-related pollutant linked with lung function decline. We evaluated the influence of genetic variation in the oxidative stress pathway on the association between long-term BC exposure and lung function decline.
Methods
Lung function parameters (FVC and FEV1) were measured during one or more study visits between 1995 and 2011 (n=651 participants) among an elderly cohort: the Normative Aging Study. Residential BC exposure levels were estimated using a spatiotemporal land use regression model. We evaluated whether oxidative stress variants, combined into a genetic score, modify the association between 1-year and 5-year moving averages of BC exposure and lung function levels and rates of decline, using linear mixed models.
Results
We report stronger associations between long-term BC exposure and increased rate of lung function decline, but not baseline lung function level, among participants with higher oxidative stress allelic risk profiles compared with participants with lower risk profiles. Associations were strongest when evaluating 5-year moving averages of BC exposure. A 0.5 μg/m3 increase in 5-year BC exposure was associated with a 0.1% yearly increase in FVC (95% CI −0.5 to 0.7) among participants with low genetic risk scores and a 1.3% yearly decrease (95% CI −1.8 to −0.8) among those with high scores (p-interaction=0.0003).
Discussion
Our results suggest that elderly men with high oxidative stress genetic scores may be more susceptible to the effects of BC on lung function decline. The results, if confirmed, should inform air-quality recommendations in light of a potentially susceptible subgroup.
doi:10.1136/thoraxjnl-2014-206179
PMCID: PMC4509588  PMID: 25414198
3.  Impacts of elevated atmospheric CO2 on nutrient content of important food crops 
Scientific Data  2015;2:150036.
One of the many ways that climate change may affect human health is by altering the nutrient content of food crops. However, previous attempts to study the effects of increased atmospheric CO2 on crop nutrition have been limited by small sample sizes and/or artificial growing conditions. Here we present data from a meta-analysis of the nutritional contents of the edible portions of 41 cultivars of six major crop species grown using free-air CO2 enrichment (FACE) technology to expose crops to ambient and elevated CO2 concentrations in otherwise normal field cultivation conditions. This data, collected across three continents, represents over ten times more data on the nutrient content of crops grown in FACE experiments than was previously available. We expect it to be deeply useful to future studies, such as efforts to understand the impacts of elevated atmospheric CO2 on crop macro- and micronutrient concentrations, or attempts to alleviate harmful effects of these changes for the billions of people who depend on these crops for essential nutrients.
doi:10.1038/sdata.2015.36
PMCID: PMC4508823  PMID: 26217490
4.  What weather variables are important in predicting heat-related mortality? A new application of statistical learning methods 
Environmental research  2014;132:350-359.
Hot weather increases risk of mortality. Previous studies used different sets of weather variables to characterize heat stress, resulting in variation in heat-mortality- associations depending on the metric used. We employed a statistical learning method – random forests – to examine which of various weather variables had the greatest impact on heat-related mortality. We compiled a summertime daily weather and mortality counts dataset from four U.S. cities (Chicago, IL; Detroit, MI; Philadelphia, PA; and Phoenix, AZ) from 1998 to 2006. A variety of weather variables were ranked in predicting deviation from typical daily all-cause and cause-specific death counts. Ranks of weather variables varied with city and health outcome. Apparent temperature appeared to be the most important predictor of heat-related mortality for all-cause mortality. Absolute humidity was, on average, most frequently selected one of the top variables for all-cause mortality and seven cause-specific mortality categories. Our analysis affirms that apparent temperature is a reasonable variable for activating heat alerts and warnings, which are commonly based on predictions of total mortality in next few days. Additionally, absolute humidity should be included in future heat-health studies. Finally, random forests can be used to guide choice of weather variables in heat epidemiology studies.
doi:10.1016/j.envres.2014.04.004
PMCID: PMC4091921  PMID: 24834832
Absolute humidity; Climate; Heat; Mortality; Random forests; Temperature; Weather
5.  Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults 
Objectives
Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects.
Methods
25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM2.5) and sulphate (SO42−) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status.
Results
A 5.8 mg/l elevation in CRP was associated with decreases of between −8% and −33% for time and frequency domain HRV outcomes. A 5.1 μg/m3 increase in SO42− on the day before the health assessment was associated with a decrease of −6.7% in the SD of normal RR intervals (SDNN) (95% CI −11.8% to −1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM2.5.
Conclusions
Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation.
doi:10.1136/oem.2009.050625
PMCID: PMC4472481  PMID: 20519749
6.  Relation of Long-term Exposure to Air Pollution to Brachial Artery Flow-Mediated Dilation and Reactive Hyperemia 
The American journal of cardiology  2014;113(12):2057-2063.
Long-term exposure to ambient air pollution has been associated with cardiovascular morbidity and mortality. Impaired vascular responses may in part explain these findings, but the association of such long-term exposure with measures of both conduit artery and microvascular function have not been widely reported. We evaluated the association between residential proximity to a major roadway (primary or secondary highway) and spatially resolved average fine particulate matter (PM2.5) and baseline brachial artery diameter and mean flow velocity, flow mediated dilation % and hyperemic flow velocity, in the Framingham Offspring and Third Generation Cohorts. We examined 5,112 participants (2,731 (53%) women, mean age 49±14 years). Spatially resolved average PM2.5 was associated with lower flow mediated dilation% and hyperemic flow velocity. An interquartile range difference in PM2.5 (1.99 μg/m3) was associated with −0.16% (95%CI: −0.27%, −0.05%) lower FMD% and −0.72 (95%CI: −1.38, −0.06) cm/s lower hyperemic flow velocity %. Residential proximity to a major roadway was negatively associated with flow mediated dilation %. Compared to living ≥400 m away, living <50 m from a major roadway was associated with 0.32% lower flow mediated dilation (95% confidence interval (CI): −0.58%, −0.06%), but results for hyperemic flow velocity had wide confidence intervals −0.68 cm/s (95%CI: −2.29, 0.93). In conclusion, residential proximity to a major roadway and higher levels of spatially resolved estimates of PM2.5 at participant residences are associated with impaired conduit artery and microvascular function in this large community-based cohort of middle-aged and elderly adults.
doi:10.1016/j.amjcard.2014.03.048
PMCID: PMC4066389  PMID: 24793676
Air Pollution; Brachial Artery; Microvessels; Endothelium; Vascular
7.  Relationship between Outdoor Temperature and Blood Pressure 
Objectives
Cardiovascular mortality has been linked to changes in outdoor temperature. However, the mechanisms behind these effects are not well established. We aimed to study the effect of outdoor temperature on blood pressure (BP), as increased BP is a risk factor of cardiovascular deaths.
Methods
The study population consisted of men aged 53–100 years living in the Boston area. We used a mixed effects model to estimate the effect of three temperature variables: ambient, apparent, and dew point temperature (DPT), on repeated measures (every 3–5 years) of diastolic and systolic blood pressure. Random intercepts for subjects and several possible confounders were used in the models, including black carbon (BC) and barometric pressure.
Results
We found modest associations between diastolic BP and ambient temperature, and apparent temperature. In the basic models, increases in diastolic BP in association with a 5°C decrease in 7-day moving averages of temperatures were 1.01% (95% CI: −0.06 – 2.09), and 1.55% (95%, CI: 0.61 – 2.49) for ambient and apparent temperature, respectively. Excluding extreme temperatures made these associations stronger (2.13%, 95% CI: 0.66 – 3.63, and 1.65%, 95% CI: 0.41 – 2.90, for ambient and apparent temperature, respectively). Effect estimates for dew point temperature were close to null. The effect of apparent temperature on systolic BP was similar (1.30% increase (95% CI: 0.32 – 2.29) for a 5°C decrease in 7-day moving average).
Conclusions
Cumulative exposure to decreasing ambient and apparent temperature may increase BP. These findings suggest that increase in BP could be a mechanism behind cold-, but not heat-related cardiovascular mortality.
doi:10.1136/oem.2010.056507
PMCID: PMC4437584  PMID: 20864465
Cardiovascular; Blood pressure; Climate; Epidemiology; Temperature
8.  Outdoor temperature is associated with serum HDL and LDL 
Environmental research  2010;111(2):281-287.
Background
While exposures to high and low air temperatures are associated with cardiovascular mortality, the underlying mechanisms are poorly understood. The risk factors for cardiovascular disease include high levels of total cholesterol and low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL). We investigated whether temperature was associated with changes in circulating lipid levels, and whether this might explain part of the association with increased cardiovascular events.
Methods
The study cohort consisted of 478 men in the greater Boston area with a mean age of 74.2 years. They visited the clinic every 3–5 years between 1995–2008 for physical examination and to complete questionnaires. We excluded from analyses all men taking statin medication and all days with missing data, resulting in a total of 862 visits. Associations between three temperature variables (ambient, apparent, and dew point temperature) and serum lipid levels (total cholesterol, HDL, LDL, and triglycerides) were studied with linear mixed models that included possible confounders such as air pollution and a random intercept for each subject.
Results
We found that HDL decreased −1.76% (95% CI: −3.17 – −0.32, lag 2 days), and −5.58% (95% CI: −8.87 – −2.16, moving average of 4 weeks) for each 5°C increase in mean ambient temperature. For the same increase in mean ambient temperature, LDL increased by 1.74% (95% CI: 0.07 – 3.44, lag 1 day) and 1.87% (95% CI: 0.14 – 3.63, lag 2 days). These results were also similar for apparent and dew point temperatures. No changes were found in total cholesterol or triglycerides in relation to temperature increase.
Conclusions
Changes in HDL and LDL levels associated with an increase in ambient temperature may be among the underlying mechanisms of temperature-related cardiovascular mortality.
doi:10.1016/j.envres.2010.12.001
PMCID: PMC4437587  PMID: 21172696
cardiovascular; cholesterol; cohort; high-density lipoprotein; low-density lipoprotein; temperature
9.  Effects of Short-term Exposure to Inhalable Particulate Matter on DNA Methylation of Tandem Repeats 
There is compelling evidence that particulate matter (PM) increases lung cancer risk by triggering systemic inflammation, and leukocyte DNA hypomethylation. However, previous investigations focused on repeated element sequences from LINE-1 and Alu families. Tandem repeats, which display a greater propensity to mutate, and are often hypomethylated in cancer patients, have never been investigated in individuals exposed to PM. We measured methylation of three tandem repeats (SATα, NBL2, D4Z4) by polymerase chain reaction–pyrosequencing on blood samples from truck drivers and office workers (60 per group) in Beijing, China. We used lightweight monitors to measure personal PM2.5 (PM with aerodynamic diameter ≤2.5 µm) and elemental carbon (EC, a tracer of PM from vehicular traffic). Ambient PM10 data were obtained from air quality measuring stations. Overall, an interquartile increase in personal PM2.5 and ambient PM10 levels was associated with a significant covariate-adjusted decrease in SATα methylation (−1.35% 5-methyl cytosine [5mC], P = 0.01; and −1.33%5mC; P = 0.01, respectively). Effects from personal PM2.5 and ambient PM10 on SATα methylation were stronger in truck drivers (−2.34%5mC, P = 0.02; −1.44%5mC, P = 0.06) than office workers (−0.95%5mC, P = 0.26; −1.25%5mC, P = 0.12, respectively). Ambient PM10 was negatively correlated with NBL2 methylation in truck drivers (−1.38%5mC, P = 0.03) but not in office workers (1.04%5mC, P = 0.13). Our result suggests that PM exposure is associated with hypomethylation of selected tandem repeats. Measuring tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify individuals with biological effects and potential cancer risk from PM exposure.
doi:10.1002/em.21838
PMCID: PMC4426495  PMID: 24436168
Air pollution; epigenetics; epidemiology
10.  Effects of airborne fine particles (PM2.5) on Deep Vein Thrombosis Admissions in North Eastern United States 
Background
Literature relating air pollution exposure to DVT and pulmonary embolism (PE), in spite of biological plausibility, is sparse. No comprehensive study examining associations between both short and long term exposure to Particulate matter (PM)2.5 and DVT or PE has been published to date. Using a novel PM2.5 prediction model we study whether long and short term PM2.5 exposure is associated with DVT and PE admissions among elderly across the northeastern USA.
Methods
We estimated daily exposure of PM2.5 in each zipcode. We investigated long and short-term effects of PM2.5 on DVT and PE hospital admissions. There were 453,413 DVT and 151,829 PE admissions in the study. For short term exposure, we performed a case crossover analysis matching on month and year and defined the hazard period as lag 01 (exposure of day of admission and previous day). For the long term association, we used a Poisson regression.
Results
A 10-µg/m3 increase in short term exposure was associated with a 0.63 % increase in DVT admissions (95% CI = 0.03 to 1.25) and a 6.98 % (95% CI = 5.65 to 8.33) increase in long term exposure admissions. For PE, the associated risks were 0.38 (95% CI = −0.68 to 1.25) and 2.67 % (95% CI = 5.65 to 8.33). These results persisted when analyses were restricted to location-periods meeting the current EPA annual standard of 12-µg/m3.
Conclusions
Our findings showed that PM2.5 exposure was associated with DVT and PE hospital admissions, and that current standards are not protective of this result.
doi:10.1111/jth.12873
PMCID: PMC4424156  PMID: 25678264
Air Pollution; Public health; Epidemiology; Environment; Venous Thrombosis; Deep-Venous Thrombosis
11.  Health effects of multi-pollutant profiles 
Environment international  2014;71:13-19.
Background
The association between exposure to particle mass and mortality is well established; however, there are still uncertainties as to whether certain chemical components are more harmful than others. Moreover, understanding the health effects associated with exposure to pollutants mixtures may lead to new regulatory strategies.
Objectives
Recently we have introduced a new approach that uses cluster analysis to identify distinct air pollutant mixtures by classifying days into groups based on their pollutant concentration profiles. In Boston during the years 1999–2009, we examined whether the effect of PM2.5 on total mortality differed by distinct pollution mixtures.
Methods
We applied a time series analysis to examine the association of PM2.5 with daily deaths. Subsequently, we included an interaction term between PM2.5 and the pollution mixture clusters.
Results
We found a 1.1 % increase (95% CI: 0.0, 2.2) and 2.3% increase (95% CI: 0.9–3.7) in total mortality for a 10 µg/m3 increase in the same day and the two-day average of PM2.5 respectively. The association is larger in a cluster characterized by high concentrations of the elements related to primary traffic pollution and oil combustion emissions with a 3.7% increase (95% CI: 0.4, 7.1) in total mortality, per 10 µg/m3 increase in the same day average of PM2.5.
Conclusions
Our study shows a higher association of PM2.5 on total mortality during days with a strong contribution of traffic emissions, and fuel oil combustion. Our proposed method to create multi-pollutant profiles is robust, and provides a promising tool to identify multi-pollutant mixtures which can be linked to the health effects.
doi:10.1016/j.envint.2014.05.023
PMCID: PMC4383187  PMID: 24950160
Total mortality; fine particulate air pollution; pollutant mixtures
12.  In Vivo Kinematics of the Thumb Carpometacarpal Joint During Three Isometric Functional Tasks 
Background
The thumb carpometacarpal (CMC) joint is often affected by osteoarthritis—a mechanically mediated disease. Pathomechanics of the CMC joint, however, are not thoroughly understood due to a paucity of in vivo data.
Questions/purposes
We documented normal, in vivo CMC joint kinematics during isometric functional tasks. We hypothesized there would be motion of the CMC joint during these tasks and that this motion would differ with sex and age group. We also sought to determine whether the rotations at the CMC joint were coupled and whether the trapezium moved with respect to the third metacarpal.
Methods
Forty-six asymptomatic subjects were CT-scanned in a neutral position and during three functional tasks (key pinch, jar grasp, jar twist), in an unloaded and a loaded position. Kinematics of the first metacarpal, third metacarpal, and the trapezium were then computed.
Results
Significant motion was identified in the CMC joint during all tasks. Sex did not have an effect on CMC joint kinematics. Motion patterns differed with age group, but these differences were not systematic across the tasks. Rotation at the CMC joint was generally coupled and posture of the trapezium relative to the third metacarpal changed significantly with thumb position.
Conclusions
The healthy CMC joint is relatively stable during key pinch, jar grasp, and jar twist tasks, despite sex and age group.
Clinical Relevance
Our findings indicate that directionally coupled motion patterns in the CMC joint, which lead to a specific loading profile, are similar in men and women. These patterns, in addition to other, nonkinematic influences, especially in the female population, may contribute to the pathomechanics of the osteoarthritic joint.
doi:10.1007/s11999-013-3063-y
PMCID: PMC3940759  PMID: 23681597
13.  Occupational Determinants of Cumulative Lead Exposure: Analysis of Bone Lead Among Men in the VA Normative Aging Study 
Objectives
To examine the relation between occupation and cumulative lead exposure—assessed by measuring bone lead—in a community-dwelling population
Method
We measured bone lead concentration with K-shell X-Ray Fluorescence in 1,320 men in the Normative Aging Study. We categorized job titles into 14 broad US Census Bureau categories. We used ordinary least squares regression to estimate bone lead by job categories adjusted for other predictors.
Results
Service Workers, Construction and Extractive Craft Workers, and Installation, Maintenance and Repair Craft Workers had the highest bone lead concentrations. Including occupations significantly improved the overall model (p<0.001) and reduced by −15% to −81% the association between bone lead and education categories.
Conclusion
Occupation significantly predicts cumulative lead exposure in a community-dwelling population, and accounts for a large proportion of the association between education and bone lead.
doi:10.1097/JOM.0000000000000127
PMCID: PMC3982188  PMID: 24709766
biomarker; bone lead; job exposure matrix; job title; occupation
15.  Pessimistic orientation in relation to telomere length in older men: the VA Normative Aging Study 
Psychoneuroendocrinology  2014;42:68-76.
Background
Recent research suggests pessimistic orientation is associated with shorter leukocyte telomere length (LTL). However, this is the first study to look not only at effects of pessimistic orientation on average LTL at multiple time points, but also at effects on the rate of change in LTL over time.
Methods
Participants were older men from the VA Normative Aging Study (n=490). The Life Orientation Test (LOT) was used to measure optimistic and pessimistic orientations at study baseline, and relative LTL by telomere to single copy gene ratio (T:S ratio) was obtained repeatedly over the course of the study (1999-2008). A total of 1,010 observations were included in the analysis. Linear mixed effect models with a random subject intercept were used to estimate associations.
Results
Higher pessimistic orientation scores were associated with shorter average LTL (percent difference by 1-SD increase in pessimistic orientation (95% CI): -3.08 (-5.62, -0.46)), and the finding was maintained after adjusting for the higher likelihood that healthier individuals return for follow-up visits (-3.44 (-5.95,-0.86)). However, pessimistic orientation scores were not associated with rate of change in LTL over time. No associations were found between overall optimism and optimistic orientation subscale scores and LTL.
Conclusion
Higher pessimistic orientation scores were associated with shorter LTL in older men. While there was no evidence that pessimistic orientation was associated with rate of change in LTL over time, higher levels of pessimistic orientation were associated with shorter LTL at baseline and this association persisted over time.
doi:10.1016/j.psyneuen.2014.01.001
PMCID: PMC4070424  PMID: 24636503
Optimism; Pessimism; Telomere length
16.  Prenatal Air Pollution Exposure and Newborn Blood Pressure 
Environmental Health Perspectives  2015;123(4):353-359.
Background
Air pollution exposure has been associated with increased blood pressure in adults.
Objective:
We examined associations of antenatal exposure to ambient air pollution with newborn systolic blood pressure (SBP).
Methods:
We studied 1,131 mother–infant pairs in a Boston, Massachusetts, area pre-birth cohort. We calculated average exposures by trimester and during the 2 to 90 days before birth for temporally resolved fine particulate matter (≤ 2.5 μm; PM2.5), black carbon (BC), nitrogen oxides, nitrogen dioxide, ozone (O3), and carbon monoxide measured at stationary monitoring sites, and for spatiotemporally resolved estimates of PM2.5 and BC at the residence level. We measured SBP at a mean age of 30 ± 18 hr with an automated device. We used mixed-effects models to examine associations between air pollutant exposures and SBP, taking into account measurement circumstances; child’s birth weight; mother’s age, race/ethnicity, socioeconomic position, and third-trimester BP; and time trend. Estimates represent differences in SBP associated with an interquartile range (IQR) increase in each pollutant.
Results:
Higher mean PM2.5 and BC exposures during the third trimester were associated with higher SBP (e.g., 1.0 mmHg; 95% CI: 0.1, 1.8 for a 0.32-μg/m3 increase in mean 90-day residential BC). In contrast, O3 was negatively associated with SBP (e.g., –2.3 mmHg; 95% CI: –4.4, –0.2 for a 13.5-ppb increase during the 90 days before birth).
Conclusions:
Exposures to PM2.5 and BC in late pregnancy were positively associated with newborn SBP, whereas O3 was negatively associated with SBP. Longitudinal follow-up will enable us to assess the implications of these findings for health during later childhood and adulthood.
Citation:
van Rossem L, Rifas-Shiman SL, Melly SJ, Kloog I, Luttmann-Gibson H, Zanobetti A, Coull BA, Schwartz JD, Mittleman MA, Oken E, Gillman MW, Koutrakis P, Gold DR. 2015. Prenatal air pollution exposure and newborn blood pressure. Environ Health Perspect 123:353–359; http://dx.doi.org/10.1289/ehp.1307419
doi:10.1289/ehp.1307419
PMCID: PMC4384198  PMID: 25625652
17.  Long- and Short-Term Exposure to PM2.5 and Mortality 
Epidemiology (Cambridge, Mass.)  2013;24(4):555-561.
Background
Many studies have reported associations between ambient particulate matter (PM) and adverse health effects, focused on either short-term (acute) or long-term (chronic) PM exposures. For chronic effects, the studied cohorts have rarely been representative of the population. We present a novel exposure model combining satellite aerosol optical depth and land-use data to investigate both the long- and short-term effects of PM2.5 exposures on population mortality in Massachusetts, United States, for the years 2000–2008.
Methods
All deaths were geocoded. We performed two separate analyses: a time-series analysis (for short-term exposure) where counts in each geographic grid cell were regressed against cell-specific short-term PM2.5 exposure, temperature, socioeconomic data, lung cancer rates (as a surrogate for smoking), and a spline of time (to control for season and trends). In addition, for long-term exposure, we performed a relative incidence analysis using two long-term exposure metrics: regional 10 × 10 km PM2.5 predictions and local deviations from the cell average based on land use within 50 m of the residence. We tested whether these predicted the proportion of deaths from PM-related causes (cardiovascular and respiratory diseases).
Results
For short-term exposure, we found that for every 10-μg/m3 increase in PM2.5 exposure there was a 2.8% increase in PM-related mortality (95% confidence interval [CI] = 2.0–3.5). For the long-term exposure at the grid cell level, we found an odds ratio (OR) for every 10-μg/m3 increase in long-term PM2.5 exposure of 1.6 (CI = 1.5–1.8) for particle-related diseases. Local PM2.5 had an OR of 1.4 (CI = 1.3– 1.5), which was independent of and additive to the grid cell effect.
Conclusions
We have developed a novel PM2.5 exposure model based on remote sensing data to assess both short- and long-term human exposures. Our approach allows us to gain spatial resolution in acute effects and an assessment of long-term effects in the entire population rather than a selective sample from urban locations.
doi:10.1097/EDE.0b013e318294beaa
PMCID: PMC4372644  PMID: 23676266
18.  Temporal and spatial assessments of minimum air temperature using satellite surface temperature measurements in Massachusetts, USA 
Although meteorological stations provide accurate air temperature observations, their spatial coverage is limited and thus often insufficient for epidemiological studies. Satellite data expand spatial coverage, enhancing our ability to estimate near surface air temperature (Ta). However, the derivation of Ta from surface temperature (Ts) measured by satellites is far from being straightforward. In this study, we present a novel approach that incorporates land use regression, meteorological variables and spatial smoothing to first calibrate between Ts and Ta on a daily basis and then predict Ta for days when satellite Ts data were not available. We applied mixed regression models with daily random slopes to calibrate Moderate Resolution Imaging Spectroradiometer (MODIS) Ts data with monitored Ta measurements for 2003. Then, we used a generalized additive mixed model with spatial smoothing to estimate Ta in days with missing Ts. Out-of-sample tenfold cross-validation was used to quantify the accuracy of our predictions. Our model performance was excellent for both days with available Ts and days without Ts observations (mean out-of-sample R2=0.946 and R2=0.941 respectively). Furthermore, based on the high quality predictions we investigated the spatial patterns of Ta within the study domain as they relate to urban vs. non-urban land uses.
doi:10.1016/j.scitotenv.2012.05.095
PMCID: PMC4372645  PMID: 22721687
Air temperature; Surface temperature; MODIS; Epidemiology; Exposure error
19.  Associations between arrhythmia episodes and temporally and spatially resolved black carbon and particulate matter in elderly patients 
Objectives
Ambient air pollution has been associated with sudden deaths, some of which are likely due to ventricular arrhythmias. Defibrillator discharge studies have examined the association of air pollution with arrhythmias in sensitive populations. No studies have assessed this association using residence-specific estimates of air pollution exposure.
Methods
In the Normative Aging Study, we investigated the association between temporally-and spatially-resolved black carbon (BC) and PM2.5 and arrhythmia episodes (bigeminy, trigeminy or couplets episodes) measured as ventricular ectopy (VE) by 4-min electrocardiogram (ECG) monitoring in repeated measures of 701 subjects, during the years 2000 to 2010.
We used a binomial distribution (having or not a VE episode) in a mixed effect model with a random intercept for subject, controlling for seasonality, temperature, day of the week, medication use, smoking, having diabetes, BMI and age. We also examined whether these associations were modified by genotype or phenotype.
Results
We found significant increases in VE with both pollutants and lags; for the estimated concentration averaged over the three days prior to the health assessment we found increases in the odds of having VE with an OR of 1.52 (95% CI: 1.19–1.94) for an IQR (0.30 μg/m3) increase in BC and an OR of 1.39 (95% CI: 1.12–1.71) for an IQR (5.63 μg/m3) increase in PM2.5. We also found higher effects in subjects with the GSTT1 and GSTM1 variants and in obese (P-values<0.05).
Conclusion
Increased levels of short-term traffic related pollutants may increase the risk of ventricular arrhythmia in elderly subjects.
doi:10.1136/oemed-2013-101526
PMCID: PMC4371778  PMID: 24142987
arrhythmia episodes; spatially-resolved black carbon and particulate matter; traffic pollution; elderly
20.  Effects of prenatal community violence and ambient air pollution on childhood wheeze in an urban population 
Background:
Prenatal exposures to stress and physical toxins influence children’s respiratory health, albeit few studies consider these factors together.
Objectives:
To concurrently examine effects of prenatal community-level psychosocial (exposure to community violence, ECV) and physical (air pollution) stressors on repeated wheeze in 708 urban children followed to age 2 years.
Methods:
Multi-item ECV reported by mothers in pregnancy was summarized into a continuous score using Rasch modeling. Prenatal black carbon (BC) exposure was estimated using land-use regression (LUR) modeling; particulate matter (PM2.5) was estimated using LUR incorporating satellite data. Mothers reported child’s wheeze every 3 months. Effects of ECV and air pollutants on repeated wheeze (≥2 episodes) were examined using logistic regression. Interactions between ECV and pollutants were examined.
Results:
Mothers were primarily Black (29%) and Hispanic (55%) with lower education (62% with ≤12 years); 87 children (12%) wheezed repeatedly. In models examining concurrent exposures, ECV [OR=1.95 (95% CI: 1.13-3.36), highest vs. lowest tertile] and BC [OR=1.84 (95% CI: 1.08-3.12), ≥median vs.
Conclusions:
These findings suggest that both prenatal community violence and air pollution may contribute to respiratory health in these urban children. Moreover, place-based psychosocial stressors may impact host resistance such that physical pollutants may have adverse effects, even at relatively lower levels.
doi:10.1016/j.jaci.2013.09.023
PMCID: PMC3943665  PMID: 24200349
community violence; prenatal stress; traffic air pollution; particulate matter; repeated wheeze; prenatal exposure
Epigenetics  2014;9(3):448-458.
The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-γ), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999–2009). We repeatedly measured methylation at multiple CpG sites within each gene’s promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN-γ and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICAM-1 protein through a decrease in ICAM-1 methylation.
doi:10.4161/epi.27584
PMCID: PMC4053463  PMID: 24385016
air pollution; traffic; gene-specific DNA methylation; effect modification; mediation analysis; elderly
Genome Biology  2015;16(1):25.
Background
DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age.
Results
Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43.
Conclusions
DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0584-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s13059-015-0584-6
PMCID: PMC4350614  PMID: 25633388
Environmental Health  2015;14:10.
Background
There is mixed evidence suggesting that air pollution may be associated with increased risk of developing psychiatric disorders. We aimed to investigate the association between air pollution and non-specific perceived stress, often a precursor to development of affective psychiatric disorders.
Methods
This longitudinal analysis consisted of 987 older men participating in at least one visit for the Veterans Administration Normative Aging Study between 1995 and 2007 (n = 2,244 visits). At each visit, participants were administered the 14-item Perceived Stress Scale (PSS), which quantifies stress experienced in the previous week. Scores ranged from 0–56 with higher scores indicating increased stress. Differences in PSS score per interquartile range increase in moving average (1, 2, and 4-weeks) of air pollution exposures were estimated using linear mixed-effects regression after adjustment for age, race, education, physical activity, anti-depressant medication use, seasonality, meteorology, and day of week. We also evaluated effect modification by season (April-September and March-October for warm and cold season, respectively).
Results
Fine particles (PM2.5), black carbon (BC), nitrogen dioxide, and particle number counts (PNC) at moving averages of 1, 2, and 4-weeks were associated with higher perceived stress ratings. The strongest associations were observed for PNC; for example, a 15,997 counts/cm3 interquartile range increase in 1-week average PNC was associated with a 3.2 point (95%CI: 2.1-4.3) increase in PSS score. Season modified the associations for specific pollutants; higher PSS scores in association with PM2.5, BC, and sulfate were observed mainly in colder months.
Conclusions
Air pollution was associated with higher levels of perceived stress in this sample of older men, particularly in colder months for specific pollutants.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-14-10) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-14-10
PMCID: PMC4417295  PMID: 25627872
Aged; Air pollution; Male; Particulate matter; Prospective studies; Stress; Psychological
Epidemiology (Cambridge, Mass.)  2013;24(6):809-819.
Background
Extremes of temperature have been associated with short-term increases in daily mortality. We identified subpopulations with increased susceptibility to dying during temperature extremes, based on personal demographics, small-area characteristics and preexisting medical conditions.
Methods
We examined Medicare participants in 135 U.S. cities and identified preexisting conditions based on hospitalization records prior to their deaths, from 1985–2006. Personal characteristics were obtained from the Medicare records, and area characteristics were assigned based on zip-code of residence. We conducted a case-only analysis of over 11 million deaths, and evaluated modification of the risk of dying associated with extremely hot days and extremely cold days, continuous temperatures, and water-vapor pressure. Modifiers included preexisting conditions, personal characteristics, zip-code-level population characteristics, and land-cover characteristics. For each effect modifier, a city-specific logistic regression model was fitted and then an overall national estimate was calculated using meta-analysis.
Results
People with certain preexisting conditions were more susceptible to extreme heat, with an additional 6% (95% confidence interval= 4% – 8%) increase in the risk of dying on an extremely hot day in subjects with previous admission for atrial fibrillation, an additional 8% (4%–12%) in subjects with Alzheimer disease, and an additional 6% (3%–9%) in subjects with dementia. Zip-code level and personal characteristics were also associated with increased susceptibility to temperature.
Conclusions
We identified several subgroups of the population who are particularly susceptible to temperature extremes, including persons with atrial fibrillation.
doi:10.1097/01.ede.0000434432.06765.91
PMCID: PMC4304207  PMID: 24045717
American Journal of Epidemiology  2013;179(2):192-199.
We investigated associations between short-term exposure to air pollution and central augmentation index and augmentation pressure, correlates of arterial stiffness, in a cohort of elderly men in the Boston, Massachusetts, metropolitan area. This longitudinal analysis included 370 participants from the Veterans Affairs Normative Aging Study with up to 2 visits between 2007 and 2011 (n = 445). Augmentation index (as %) and augmentation pressure (in mmHg) were measured at each visit by using radial artery applanation tonometry for pulse wave analysis and modeled in a mixed effects regression model as continuous functions of moving averages of air pollution exposures (over 4 hours and 1, 3, 7, and 14 days). The results suggest that short-term changes in air pollution were associated with augmentation index and augmentation pressure at several moving averages. Interquartile range (IQR) increases in 3-day average exposure to particles with aerodynamic diameter less than 2.5 μm (3.6-μg/m3 IQR increase) and sulfate (1.4-μg/m3 IQR increase) and 1-day average exposure to particle number counts (8,741-counts/cm3 IQR increase) were associated with augmentation index values that were 0.8% (95% confidence interval (CI): 0.2, 1.4), 0.6% (95% CI: 0.1, 1.2), and 1.7% (95% CI: 0.4, 2.9) higher, respectively. Overall, the findings were similar for augmentation pressure. The findings support the hypothesis that exposure to air pollution may affect vascular function.
doi:10.1093/aje/kwt271
PMCID: PMC3873113  PMID: 24227017
air pollution; particulate matter; pulse wave analysis

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