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1.  Butyrylcholinesterase genotype and enzyme activity in relation to Gulf War illness: preliminary evidence of gene-exposure interaction from a case–control study of 1991 Gulf War veterans 
Environmental Health  2015;14:4.
Background
Epidemiologic studies have implicated wartime exposures to acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War illness (GWI), the multisymptom condition linked to military service in the 1991 Gulf War. It is unclear, however, why some veterans developed GWI while others with similar exposures did not. Genetic variants of the enzyme butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE-inhibiting chemicals, and may confer differences in biological responses to these compounds. The current study assessed BChE enzyme activity and BChE genotype in 1991 Gulf War veterans to evaluate possible association of this enzyme with GWI.
Methods
This case–control study evaluated a population-based sample of 304 Gulf War veterans (144 GWI cases, meeting Kansas GWI criteria, and 160 controls). BChE enzyme activity levels and genotype were compared, overall, in GWI cases and controls. Potential differences in risk associated with cholinergic-related exposures in theater were explored using stratified analyses to compare associations between GWI and exposures in BChE genetic and enzyme activity subgroups.
Results
Overall, GWI cases and controls did not differ by mean BChE enzyme activity level or by BChE genotype. However, for the subgroup of Gulf War veterans with less common, generally less active, BChE genotypes (K/K, U/AK, U/A, A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with GWI (OR = 40.00, p = 0.0005) was significantly greater than for veterans with the more common U/U and U/K genotypes (OR = 2.68, p = 0.0001).
Conclusions
Study results provide preliminary evidence that military personnel with certain BChE genotypes who used PB during the 1991 Gulf War may have been at particularly high risk for developing GWI. Genetic differences in response to wartime exposures are potentially important factors in GWI etiology and should be further evaluated in conjunction with exposure effects.
doi:10.1186/1476-069X-14-4
PMCID: PMC4305390  PMID: 25575675
Butyrylcholinesterase; Gulf War illness; Gulf War veterans; Pyridostigmine bromide; Gene-environment interaction
2.  Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5–9 years – a prospective study 
Environmental Health  2015;14:2.
Background
In animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5–9 years of age.
Methods
Maternal sera from the INUENDO cohort (2002–2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010–2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses.
Results
In the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (β (95% CI) =1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (β (95% CI) = 0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties.
Conclusions
Prenatal exposure to PFOS and PFOA may have a small to moderate effect on children’s neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-14-2) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-14-2
PMCID: PMC4298045  PMID: 25567242
Behaviour; Child; Child development; Cohort study; Motor development; Perfluorooctanoate (PFOA); Perfluorooctane sulfonate (PFOS); Prenatal exposure, Delayed effects
3.  A path forward in the debate over health impacts of endocrine disrupting chemicals 
Environmental Health  2014;13(1):118.
Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate.
doi:10.1186/1476-069X-13-118
PMCID: PMC4298083  PMID: 25533907
Endocrine disruptor; UNEP; WHO; State of the science
4.  Hematological and hepatic alterations in nonsmoking residents exposed to benzene following a flaring incident at the British petroleum plant in Texas City 
Environmental Health  2014;13(1):115.
Objective
Human exposure to benzene is associated with multiple adverse health effects with an increased risk of developing carcinogenesis. Benzene exposure is known to affect many critical organs including the hematological, hepatic, renal, lung, and cardiac functions. The purpose of this study is to examine the health effects of benzene exposure among nonsmoking subjects from a prolonged flaring incident that occurred at the British petroleum (BP) refinery in the Texas City, Texas.
Methods
The study included nonsmoking subjects who had been exposed and unexposed to benzene. Using medical charts, clinical data including white blood cell (WBC) counts, platelet counts, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) in nonsmoking subjects exposed to benzene were reviewed and analyzed and compared with unexposed adults.
Results
A total of 1422 nonsmoking subjects (benzene exposed, n = 1093 and unexposed, n = 329) were included. Benzene exposed subjects had significantly higher levels of WBC (× 103 per μL) counts (7.7 ± 2.2 versus 6.8 ± 1.7, P = 0.001) and platelet (× 103 per μL) counts (288.8 ± 59.0 versus 245.3 ± 54.4, P = 0.001) compared with the unexposed subjects. The mean serum creatinine (mg/dL) levels were also significantly increased in the benzene exposed group compared with the unexposed group (1.1 ± 0.4 versus 0.8 ± 0.2, P = 0.001). Serum levels of ALP (IU/L) was significantly elevated in the benzene exposed subjects compared with the unexposed subjects (87.3 ± 22.6 versus 69.6 ± 16.5, P = 0.001). Similarly, benzene exposed subjects had significantly higher levels of AST and ALT compared with those unexposed subjects.
Conclusion
Benzene exposure from the prolonged BP flaring incident caused significant alterations in hematological and liver markers indicating that these nonsmoking residents exposed to refinery chemicals may be at a higher risk of developing hepatic or blood related disorders.
doi:10.1186/1476-069X-13-115
PMCID: PMC4298119  PMID: 25526767
Benzene poisoning; Blood disorders; Chemical exposure; Health impact; Hematological toxicity; Hepatotoxicity; Nonsmoking; Petroleum refinery
5.  Accidental exposure to gas emissions from transit goods treated for pest control 
Environmental Health  2014;13:110.
Background
International phytosanitary standards ISPM 15 require (since 2007) fumigation or heat treatment for shipping and storage. Those dealing with fumigated freight might be accidentally exposed. In this paper we report a series of three accidents of six storage room workers in a medium sized company regularly importing electronic production parts from abroad.
Methods
Patients (n = 6, aged from 32–54 yrs.) and control group (n = 30, mean 40 yrs.) donated blood and urine samples. The fumigants: ethylene oxide, methyl bromide, chloropicrin, ethylene dichloride, other halo-alkanes and solvents were analyzed by headspace gas chromatography/mass spectrometry (GCMS). For the quantitation of long term exposure/s, macromolecular reaction products (hemoglobin adducts) were used (with GCMS) as molecular dosimeter; additionally 8-OHdG and circulating mtDNA (cmtDNA) were analyzed as nonspecific biological effect markers.
Results
The hemoglobin adducts N-methyl valine (MEV) and N-(2-hydroxy ethyl) valine (HEV) were elevated after exposure to the alkylating chemicals methyl bromide and ethylene oxide. Under the consideration of known elimination kinetics and the individual smoking status (biomonitored with nicotine metabolite cotinine and tobacco specific hemoglobin adduct: N-(2 cyan ethyl) valines, CEV), the data allow theoretical extrapolation to the initial protein adduct concentrations at the time of the accident (the MEV/CEV levels were from 1,616 pmol/g globin to 1,880 pmol/g globin and HEV/CEV levels from 1,407 pmol/g globin to 5,049 pmol/g globin, and correlated with inhaled 0.4-1.5 ppm ethylene oxide. These integrated, extrapolated internal doses, calculated on the basis of biological exposure equivalents, confirmed the clinical diagnosis for three patients, showing severe intoxication symptoms. Both, cmtDNA and 8-OHdG, as non-specific biomarkers of toxic effects, were elevated in four patients.
Conclusion
The cases reported here, stress the importance of a suitable risk assessment and control measures. We put emphasis on the necessity of human biomonitoring guidelines and the urgency for the relevant limit values.
doi:10.1186/1476-069X-13-110
PMCID: PMC4320564  PMID: 25495528
Fumigants; Methyl bromide; Ethylene oxide; Hemoglobin adducts; Past exposure; Transit goods and production parts; Off gassing; Human biomonitoring
6.  A conceptual approach to a citizens’ observatory – supporting community-based environmental governance 
Environmental Health  2014;13:107.
In recent years there has been a trend to view the Citizens’ Observatory as an increasingly essential tool that provides an approach for better observing, understanding, protecting and enhancing our environment. However, there is no consensus on how to develop such a system, nor is there any agreement on what a Citizens’ Observatory is and what results it could produce. The increase in the prevalence of Citizens’ Observatories globally has been mirrored by an increase in the number of variables that are monitored, the number of monitoring locations and the types of participating citizens. This calls for a more integrated approach to handle the emerging complexities involved in this field, but before this can be achieved, it is essential to establish a common foundation for Citizens’ Observatories and their usage. There are many aspects to a Citizens’ Observatory. One view is that its essence is a process that involves environmental monitoring, information gathering, data management and analysis, assessment and reporting systems. Hence, it requires the development of novel monitoring technologies and of advanced data management strategies to capture, analyse and survey the data, thus facilitating their exploitation for policy and society. Practically, there are many challenges in implementing the Citizens’ Observatory approach, such as ensuring effective citizens’ participation, dealing with data privacy, accounting for ethical and security requirements, and taking into account data standards, quality and reliability. These concerns all need to be addressed in a concerted way to provide a stable, reliable and scalable Citizens’ Observatory programme. On the other hand, the Citizens’ Observatory approach carries the promise of increasing the public’s awareness to risks in their environment, which has a corollary economic value, and enhancing data acquisition at low or no cost. In this paper, we first propose a conceptual framework for a Citizens’ Observatory programme as a system that supports and promotes community-based environmental governance. Next, we discuss some of the challenges involved in developing this approach. This work seeks to initiate a debate and help defining what is the Citizens’ Observatory, its potential role in environmental governance, and its validity as a tool for environmental research.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-107) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-107
PMCID: PMC4320485  PMID: 25495204
Citizens’ Observatory; Citizen science; Environmental governance; Environmental monitoring; Top-down and bottom-up approach; Public participation
7.  Indoor air pollution exposure from use of indoor stoves and fireplaces in association with breast cancer: a case-control study 
Environmental Health  2014;13:108.
Background
Previous studies suggest that polycyclic aromatic hydrocarbons (PAHs) may adversely affect breast cancer risk. Indoor air pollution from use of indoor stoves and/or fireplaces is an important source of ambient PAH exposure. However, the association between indoor stove/fireplace use and breast cancer risk is unknown. We hypothesized that indoor stove/fireplace use in a Long Island, New York study population would be positively associated with breast cancer and differ by material burned, and the duration and timing of exposure. We also hypothesized that the association would vary by breast cancer subtype defined by p53 mutation status, and interact with glutathione S-transferases GSTM1, T1, A1 and P1 polymorphisms.
Methods
Population-based, case-control resources (1,508 cases/1,556 controls) were used to conduct unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
Results
Breast cancer risk was increased among women reporting ever burning synthetic logs (which may also contain wood) in their homes (OR = 1.42, 95% CI 1.11, 1.84), but not for ever burning wood alone (OR = 0.93, 95% CI 0.77, 1.12). For synthetic log use, longer duration >7 years, older age at exposure (>20 years; OR = 1.65, 95% CI 1.02, 2.67) and 2 or more variants in GSTM1, T1, A1 or P1 (OR = 1.71, 95% CI 1.09, 2.69) were associated with increased risk.
Conclusions
Burning wood or synthetic logs are both indoor PAH exposure sources; however, positive associations were only observed for burning synthetic logs, which was stronger for longer exposures, adult exposures, and those with multiple GST variant genotypes. Therefore, our results should be interpreted with care and require replication.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-108) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-108
PMCID: PMC4320487  PMID: 25495350
Polycyclic aromatic hydrocarbons; GST; p53; Cancer; Breast
8.  Air pollution events from forest fires and emergency department attendances in Sydney, Australia 1996–2007: a case-crossover analysis 
Environmental Health  2014;13(1):105.
Background
Severe air pollution generated by forest fires is becoming an increasingly frequent public health management problem. We measured the association between forest fire smoke events and hospital emergency department (ED) attendances in Sydney from 1996–2007.
Methods
A smoke event occurred when forest fires caused the daily citywide average concentration of particulate matter (PM10 or PM2.5) to exceed the 99th percentile of the entire study period. We used a time-stratified case-crossover design and conditional logistic regression models adjusted for meteorology, influenza epidemics, and holidays to estimate odds ratios (OR) and 95% confidence intervals (CI) for ED attendances on event days compared with non-event days for all non-trauma ED attendances and selected cardiorespiratory conditions.
Results
The 46 validated fire smoke event days during the study period were associated with same day increases in ED attendances for all non-trauma conditions (1.03, 95% CI 1.02, 1.04), respiratory conditions (OR 1.07, 95% CI 1.04, 1.10), asthma (OR 1.23, 95% CI 1.15, 1.30), and chronic obstructive pulmonary disease (OR 1.12, 95% CI 1.02, 1.24). Positive associations persisted for one to three days after the event. Ischaemic heart disease ED attendances were increased at a lag of two days (OR 1.07, 95% CI 1.01, 1.15) while arrhythmias had an inverse association at a lag of two days (OR 0.91, 95% CI 0.83, 0.99). In age-specific analyses, no associations present in children less than 15 years of age for any outcome, although a non-significant trend towards a positive association was seen with childhood asthma. A further association between smoke event and heart failure attendances was present for the 15–65 year age group, but not older adults at a lag of two days (OR 1.37 95% CI 1.05, 1.78).
Conclusion
Smoke events were associated with an immediate increase in presentations for respiratory conditions and a lagged increase in attendances for ischaemic heart disease and heart failure. Respiratory impacts were either absent or considerably attenuated in those <15 years. Similar to previous studies we found inconsistent associations between fire smoke and cardiovascular diseases. Better characterisation of the spectrum of population health risks is needed to guide public heath responses to severe smoke events as this exposure becomes increasingly common with global climate change
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-105) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-105
PMCID: PMC4271508  PMID: 25491235
Forest fires; Air pollution; Emergency departments attendances; Case crossover; Respiratory; Cardiovascular
9.  Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh 
Environmental Health  2014;13(1):101.
Background
Early life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine.
Methods
Between March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation.
Results
Arsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 μg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 μg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant’s urine increased non-significantly by 0.13 μg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant’s urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine.
Conclusions
We observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization’s maximum permissible limit (WHO Permissible Limit 15 μg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.
doi:10.1186/1476-069X-13-101
PMCID: PMC4265415  PMID: 25471535
Arsenic; Human milk; Bangladesh
10.  PM2.5 in Beijing – temporal pattern and its association with influenza 
Environmental Health  2014;13(1):102.
Background
Air pollution in Beijing, especially PM2.5, has received increasing attention in the past years. Despite Beijing being one of the most polluted cities in the world, there has still been a lack of quantitative research regarding the health impact of PM2.5 on the impact of diseases in Beijing. In this study, we aimed to characterize temporal pattern of PM2.5 and its potential association with human influenza in Beijing.
Methods
Based on the data collected on hourly ambient PM2.5 from year 2008 to 2013 and on monthly human influenza cases from 2008 and 2011, we investigated temporal patterns of PM2.5 over the five-year period and utilized the wavelet approach to exploring the potential association between PM2.5 and influenza.
Results
Our results found that ambient PM2.5 pollution was severe in Beijing with PM2.5 concentrations being significantly higher than the standards of the World Health Organization, the US EPA, and the Chinese EPA in the majority of days during the study period. Furthermore, PM2.5 concentrations in the winter heating seasons were higher than those in non-heating seasons despite high variations. We also found significant association between ambient PM2.5 peak and human influenza case increase with a delayed effect (e.g. delayed effect of PM2.5 on influenza).
Conclusions
Ambient PM2.5 concentrations were significantly associated with human influenza cases in Beijing, which have important implications for public health and environmental actions.
doi:10.1186/1476-069X-13-102
PMCID: PMC4271358  PMID: 25471661
Air pollution; PM2.5; Temporal pattern; Association; Influenza; Beijing
11.  Chemicals having estrogenic activity can be released from some bisphenol a-free, hard and clear, thermoplastic resins 
Environmental Health  2014;13(1):103.
Background
Chemicals that have estrogenic activity (EA) can potentially cause adverse health effects in mammals including humans, sometimes at low doses in fetal through juvenile stages with effects detected in adults. Polycarbonate (PC) thermoplastic resins made from bisphenol A (BPA), a chemical that has EA, are now often avoided in products used by babies. Other BPA-free thermoplastic resins, some hypothesized or advertised to be EA-free, are replacing PC resins used to make reusable hard and clear thermoplastic products such as baby bottles.
Methods
We used two very sensitive and accurate in vitro assays (MCF-7 and BG1Luc human cell lines) to quantify the EA of chemicals leached into ethanol or water/saline extracts of fourteen unstressed or stressed (autoclaving, microwaving, UV radiation) thermoplastic resins. Estrogen receptor (ER)-dependent agonist responses were confirmed by their inhibition with the ER antagonist ICI 182,780.
Results
Our data showed that some (4/14) unstressed and stressed BPA-free thermoplastic resins leached chemicals having significant levels of EA, including one polystyrene (PS), and three Tritan™ resins, the latter reportedly EA-free. Exposure to UV radiation in natural sunlight resulted in an increased release of EA from Tritan™ resins. Triphenyl-phosphate (TPP), an additive used to manufacture some thermoplastic resins such as Tritan™, exhibited EA in both MCF-7 and BG1Luc assays. Ten unstressed or stressed glycol-modified polyethylene terephthalate (PETG), cyclic olefin polymer (COP) or copolymer (COC) thermoplastic resins did not release chemicals with detectable EA under any test condition.
Conclusions
This hazard survey study assessed the release of chemicals exhibiting EA as detected by two sensitive, widely used and accepted, human cell line in vitro assays. Four PC replacement resins (Tritan™ and PS) released chemicals having EA. However, ten other PC-replacement resins did not leach chemicals having EA (EA-free-resins). These results indicate that PC-replacement plastic products could be made from EA-free resins (if appropriate EA-free additives are chosen) that maintain advantages of re-usable plastic items (price, weight, shatter resistance) without releasing chemicals having EA that potentially produce adverse health effects on current or future generations.
doi:10.1186/1476-069X-13-103
PMCID: PMC4298073  PMID: 25477047
BG1Luc; Bisphenol A; Tritan; Estrogenic activity; MCF-7; Thermoplastic resins
12.  Effect of ambient temperature on emergency department visits in Shanghai, China: a time series study 
Environmental Health  2014;13(1):100.
Background
Many studies have examined the association between ambient temperature and mortality. However, less evidence is available on the temperature effects on gender- and age-specific emergency department visits, especially in developing countries. In this study, we examined the short-term effects of daily ambient temperature on emergency department visits (ED visits) in Shanghai.
Methods
Daily ED visits and daily ambient temperatures between January 2006 and December 2011 were analyzed. After controlling for secular and seasonal trends, weather, air pollution and other confounding factors, a Poisson generalized additive model (GAM) was used to examine the associations between ambient temperature and gender- and age-specific ED visits. A moving average lag model was used to evaluate the lag effects of temperature on ED visits.
Results
Low temperature was associated with an overall 2.76% (95% confidence interval (CI): 1.73 to 3.80) increase in ED visits per 1°C decrease in temperature at Lag1 day, 2.03% (95% CI: 1.04 to 3.03) and 2.45% (95% CI: 1.40 to 3.52) for males and females. High temperature resulted in an overall 1.78% (95% CI: 1.05 to 2.51) increase in ED visits per 1°C increase in temperature on the same day, 1.81% (95% CI: 1.08 to 2.54) among males and 1.75% (95% CI: 1.03 to 2.49) among females. The cold effect appeared to be more acute among younger people aged <45 years, whereas the effects were consistent on individuals aged ≥65 years. In contrast, the effects of high temperature were relatively consistent over all age groups.
Conclusions
These findings suggest a significant association between ambient temperature and ED visits in Shanghai. Both cold and hot temperatures increased the relative risk of ED visits. This knowledge has the potential to advance prevention efforts targeting weather-sensitive conditions.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-100) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-100
PMCID: PMC4258028  PMID: 25424196
Ambient temperature; Emergency department visits; Generalized additive model
13.  Evaluation of contaminated drinking water and preterm birth, small for gestational age, and birth weight at Marine Corps Base Camp Lejeune, North Carolina: a cross-sectional study 
Environmental Health  2014;13(1):99.
Background
Births during 1968-1985 at Camp Lejeune were exposed to drinking water contaminated with trichloroethylene (TCE), tetrachloroethylene (PCE), and benzene.
Methods
We conducted a cross-sectional study to evaluate associations between residential prenatal exposure to contaminated drinking water at Camp Lejeune during 1968–1985 and preterm birth, small for gestational age (SGA), term low birth weight (TLBW), and mean birth weight (MBW) deficit. Birth certificates identified mothers residing at Camp Lejeune at delivery. We analyzed exposure data for the entire pregnancy and individual trimesters. For each period examined, births were categorized as unexposed if mothers did not reside at Camp Lejeune or if their residence on base received uncontaminated drinking water. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels at residences. For PCE and TCE, the exposed group was divided into four levels: < median value, ≥ median value, ≥75th percentile, and ≥90th percentile. For benzene, the exposed group was categorized as <1 part per billion (ppb) versus ≥1 ppb because of sparse data. Magnitude of effect estimates and exposure response relationships were used to assess associations. Confidence intervals (CIs) indicated precision of estimates.
Results
For the highest TCE exposure category during the entire pregnancy, odds ratios (ORs) were 1.5 (95% CI: 1.2, 1.9) and 1.3 (95% CI: 0.8, 2.2) for SGA and TLBW, respectively, and reduced MBW β = −78.3 g (95% CI: −115.0, −41.7). The OR =1.3 (95% CI: 1.0, 1.6) for preterm birth and the highest PCE exposure category during the entire pregnancy. Monotonic exposure-response relationships were observed for benzene exposure during the entire pregnancy and TLBW (highest category OR =1.5, 85% CI: 0.9, 2.3). Although a monotonic association between benzene and adjusted MBW difference was also observed (highest category β = −36.2 g, 95% CI: −72.3, −0.1), the association disappeared when TCE was also added to the model. We found no evidence suggesting any other associations between outcomes and exposures.
Conclusion
Findings suggested associations between in utero exposures to TCE and SGA, TLBW and reduced MBW; benzene and TLBW; and PCE and preterm birth.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-99) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-99
PMCID: PMC4247681  PMID: 25413571
Low birth weight; Preterm birth; Small for gestational age; Volatile organic compounds; Solvents; Military exposures
14.  Pesticide use, erythrocyte acetylcholinesterase level and self-reported acute intoxication symptoms among vegetable farmers in Nepal: a cross-sectional study 
Environmental Health  2014;13(1):98.
Background
As pesticide use is increasing and proper handling training is lacking, exposure to pesticides and intoxications are an important public health problems among farmers in developing countries. This study describes pesticide use among farmers and compares symptoms of possible acute intoxication and Erythrocyte Acetylcholinesterase(AChE) levels among vegetable farmers with a control group of blood donors in Nepal.
Methods
A cross-sectional study was carried out among 90 pesticide-exposed farmers and a control group of 90 blood donors. Participants were randomly selected and data were gathered through questionnaires, observation and blood test. Chi-square test, logistic regression and Student’s t-test were used for data analysis to describe pesticide use and compare symptoms and AChE levels between the two groups. This study was approved by Nepal Health Research Council.
Results
The majority of pesticides used were WHO class II, classified as moderately hazardous. The mean numbers of personal protective equipment used by farmers were 2.22 (95% CI: 1.89; 2.54). Out of five hygienic practices asked, farmers followed 3.63 (95% CI: 3.40; 3.86) hygienic practices on the average. Farmers reported more symptoms of possible pesticide intoxication in the past month than did controls, mean 5.47 (95% CI: 4.70; 6.25) versus 2.02 (95% CI: 1.63; 2.40) (p < 0.05). The mean haemoglobin-adjusted AChE(Q) was significantly lower among farmers compared to controls, 28.92 (95% CI: 28.28; 29.56) U/g versus 30.05 (95% CI: 29.51; 30.60) U/g, (p = 0.01). The risk of a farmer having lower Q level was about 3 times (OR = 2.95; 95% CI: 1.16; 7.51) greater than controls.
Conclusion
Nepalese farmers exposed to pesticides have significantly more symptoms of possible pesticide intoxication than a control group of healthy individuals. A lower mean haemoglobin- adjusted AChE level was seen among farmers compared to the controls. The use of highly toxic pesticides, inadequate use of personal protective equipment and poor hygienic practices might explain the reason for symptoms of pesticide intoxication and a lower AChE level among farmers. Education and information of farmers should be undertaken to remediate these problems.
doi:10.1186/1476-069X-13-98
PMCID: PMC4277821  PMID: 25409889
Farmers; Carbamates; Erythrocyte acetylcholinesterase; Haemoglobin; Organophosphates; Pesticides; Nepal
15.  Maternal residential proximity to chlorinated solvent emissions and birth defects in offspring: a case–control study 
Environmental Health  2014;13(1):96.
Background
Some studies have noted an association between maternal occupational exposures to chlorinated solvents and birth defects in offspring, but data are lacking on the potential impact of industrial air emissions of these solvents on birth defects.
Methods
With data from the Texas Birth Defects Registry for births occurring in 1996–2008, we examined the relation between maternal residential proximity to industrial air releases of chlorinated solvents and birth defects in offspring of 60,613 case-mothers and 244,927 control-mothers. Maternal residential exposures to solvent emissions were estimated with metrics that took into account residential distances to industrial sources and annual amounts of chemicals released. Logistic regression was used to generate odds ratios and 95% confidence intervals for the associations between residential proximity to emissions of 14 chlorinated solvents and selected birth defects, including neural tube, oral cleft, limb deficiency, and congenital heart defects. All risk estimates were adjusted for year of delivery and maternal age, education, race/ethnicity, and public health region of residence.
Results
Relative to exposure risk values of 0, neural tube defects were associated with maternal residential exposures (exposure risk values >0) to several types of chlorinated solvents, most notably carbon tetrachloride (adjusted odds ratio [aOR] 1.42, 95% confidence interval [CI] 1.09, 1.86); chloroform (aOR 1.40, 95% CI 1.04, 1.87); ethyl chloride (aOR 1.39, 95% CI 1.08, 1.79); 1,1,2-trichloroethane (aOR 1.56, 95% CI 1.11, 2.18); and 1,2,3-trichloropropane (aOR 1.49, 95% CI 1.08, 2.06). Significant associations were also noted between a few chlorinated solvents and oral cleft, limb deficiency, and congenital heart defects. We observed stronger associations between some emissions and neural tube, oral cleft, and heart defects in offspring of mothers 35 years or older, such as spina bifida with carbon tetrachloride (aOR 2.49, 95% CI 1.09, 5.72), cleft palate with 1,2-dichloroethane (aOR 1.93, 95% 1.05, 3.54), cleft lip with or without cleft palate with ethyl chloride (aOR 1.81, 95% CI 1.06, 3.07), and obstructive heart defects with trichloroethylene (aOR 1.43, 95% CI 1.08, 1.88).
Conclusions
These findings suggest that maternal residential proximity to industrial emissions of chlorinated solvents might be associated with selected birth defects in offspring, especially among older mothers.
doi:10.1186/1476-069X-13-96
PMCID: PMC4247650  PMID: 25406847
Air pollution; Chlorinated solvents; Congenital heart defects; Limb deficiency defects; Neural tube defects; Oral cleft defects
16.  Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico 
Environmental Health  2014;13(1):97.
Background
There are potential adverse health risks to the mother and fetus from exposure to pesticides. Thus, studies of exposure to pesticides among pregnant women are of interest as they will assist with understanding the potential burden of exposure globally, identifying sources of exposure, and designing epidemiology studies.
Methods
We measured urinary concentrations of the insect repellent N-N-diethyl-meta-toluamide (DEET) and two of its metabolites [3-diethyl-carbamoyl benzoic acid (DCBA) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB)], four pyrethroid insecticide metabolites [4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA); 3-phenoxybenzoic acid (3-PBA); trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA); and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA)], and two chlorophenoxy herbicides [2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)] in 54 pregnant women from Puerto Rico at three separate time points (20 ± 2 weeks, 24 ± 2 weeks, and 28 ± 2 weeks of gestation). We calculated the distributions of the biomarker concentrations and compared them to those of women of reproductive age from the general U.S. population where available, and estimated the within-subject temporal variability of these repeated measurements. We also collected questionnaire data on demographics, consumption of select fruits, vegetables, and legumes in the past 48-hr, and pest-related issues, and associations between these variables and biomarker concentrations were examined.
Results
We found that 95th percentile urinary concentrations of DEET, 3-PBA, trans-DCCA, and 2,4-D were lower than women of reproductive age on the U.S. mainland, whereas 95th percentile urinary concentrations of 4-F-3-PBA, cis-DBCA, and 2,4,5-T were similar. DCBA, the only urinary biomarker detected in >50% of the samples, showed fair to good reproducibility across pregnancy (intraclass correlation coefficient: 0.60). Women were more likely (p <0.05) to have greater urinary concentrations of pesticide biomarkers if they were less educated (DCBA and trans-DCCA), unemployed (DHMB), or married (2,4-D), had consumed collards or spinach in past 48-hr (2,4-D) or had been using insect repellent since becoming pregnant (DCBA), or were involved with residential applications of pesticides (trans-DCCA).
Conclusions
We identified concentrations and predictors of several pesticides among pregnant women in Puerto Rico. Further research is needed to understand what aspects of the predictors identified lead to greater exposure, and whether exposure during pregnancy is associated with adverse health.
doi:10.1186/1476-069X-13-97
PMCID: PMC4258050  PMID: 25409771
Biomarker; Pesticides; Pregnancy; Urine; Women
17.  Longitudinal analysis of the association between removal of dental amalgam, urine mercury and 14 self-reported health symptoms 
Environmental Health  2014;13(1):95.
Background
Mercury vapor poses a known health risk with no clearly established safe level of exposure. Consequently there is debate over whether the level of prolonged exposure to mercury vapor from dental amalgam fillings, combining approximately 50% mercury with other metals, is sufficiently high to represent a risk to health. The objective of our study is to determine if mercury exposure from amalgam fillings is associated with risk of adverse health effects.
Methods
In a large longitudinal non-blind sample of participants from a preventative health program in Calgary, Canada we compared number of amalgam fillings, urine mercury measures and changes in 14 self-reported health symptoms, proposed to be mercury dependent sub-clinical measures of mental and physical health. The likelihood of change over one year in a sample of persons who had their fillings removed was compared to a sample of persons who had not had their fillings removed. We use non-parametric statistical tests to determine if differences in urine mercury were statistically significant between sample groups. Logistic regression models were used to estimate the likelihood of observing symptom improvement or worsening in the sample groups.
Results
At baseline, individuals with dental amalgam fillings have double the measured urine mercury compared to a control group of persons who have never had amalgam fillings. Removal of amalgam fillings decreases measured urine mercury to levels in persons without amalgam fillings. Although urine mercury levels in our sample are considered by Health Canada to be too low to pose health risks, removal of amalgam fillings reduced the likelihood of self-reported symptom deterioration and increased the likelihood of symptom improvement in comparison to people who retained their amalgam fillings.
Conclusions
Our findings suggest that mercury exposure from amalgam fillings adversely impact health and therefore are a health risk. The use of safer alternative materials for dental fillings should be encouraged to avoid the increased risk of health deterioration associated with unnecessary exposure to mercury.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-95) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-95
PMCID: PMC4273453  PMID: 25404430
18.  Short-term airborne particulate matter exposure alters the epigenetic landscape of human genes associated with the mitogen-activated protein kinase network: a cross-sectional study 
Environmental Health  2014;13(1):94.
Background
Exposure to air particulate matter is known to elevate blood biomarkers of inflammation and to increase cardiopulmonary morbidity and mortality. Major components of airborne particulate matter typically include black carbon from traffic and sulfates from coal-burning power plants. DNA methylation is thought to be sensitive to these environmental toxins and possibly mediate environmental effects on clinical outcomes via regulation of gene networks. The underlying mechanisms may include epigenetic modulation of major inflammatory pathways, yet the details remain unclear.
Methods
We sought to elucidate how short-term exposure to air pollution components, singly and/or in combination, alter blood DNA methylation in certain inflammation-associated gene networks, MAPK and NF-κB, which may transmit the environmental signal(s) and influence the inflammatory pathway in vivo. To this end, we utilized a custom-integrated workflow—molecular processing, pollution surveillance, biostatical analysis, and bioinformatic visualization—to map novel human (epi)gene pathway-environment interactions.
Results
Specifically, out of 84 MAPK pathway genes considered, we identified 11 whose DNA methylation status was highly associated with black carbon exposure, after adjusting for potential confounders—age, sulfate exposure, smoking, blood cell composition, and blood pressure. Moreover, after adjusting for these confounders, multi-pollutant analysis of synergistic DNA methylations significantly associated with sulfate and BC exposures yielded 14 MAPK genes. No associations were found with the NF-κB pathway.
Conclusion
Exposure to short-term air pollution components thus resulted in quantifiable epigenetic changes in the promoter areas of MAPK pathway genes. Bioinformatic mapping of single- vs. multi-exposure-associated epigenetic changes suggests that these alterations might affect biological pathways in nuanced ways that are not simply additive or fully predictable via individual-level exposure assessments.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-94) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-94
PMCID: PMC4273424  PMID: 25395096
19.  Primary prevention of lead poisoning in children: a cross-sectional study to evaluate state specific lead-based paint risk reduction laws in preventing lead poisoning in children 
Environmental Health  2014;13(1):93.
Background
Children younger than 72 months are most at risk of environmental exposure to lead from ingestion through normal mouthing behavior. Young children are more vulnerable to lead poisoning than adults because lead is absorbed more readily in a child’s gastrointestinal tract. Our focus in this study was to determine the extent to which state mandated lead laws have helped decrease the number of new cases of elevated blood-lead levels (EBLL) in homes where an index case had been identified.
Methods
A cross-sectional study was conducted to compare 682 residential addresses, identified between 2000 and 2009, in two states with and one state without laws to prevent childhood lead poisoning among children younger than 72 months, to determine whether the laws were effective in preventing subsequent cases of lead poisoning detected in residential addresses after the identification of an index case. In this study, childhood lead poisoning was defined as the blood lead level (BLL) that would have triggered an environmental investigation in the residence. The two states with lead laws, Massachusetts (MA) and Ohio (OH), had trigger levels of ≥25 μg/dL and ≥15 μg/dL respectively. In Mississippi (MS), the state without legislation, the trigger level was ≥15 μg/dL.
Results
The two states with lead laws, MA and OH, were 79% less likely than the one without legislation, MS, to have residential addresses with subsequent lead poisoning cases among children younger than 72 months, adjusted OR = 0.21, 95% CI (0.08-0.54).
Conclusions
For the three states studied, the evidence suggests that lead laws such as those studied herein effectively reduced primary exposure to lead among young children living in residential addresses that may have had lead contaminants.
doi:10.1186/1476-069X-13-93
PMCID: PMC4240897  PMID: 25380793
Children; Prevention; Law; Lead Poisoning
20.  The effect of exposure to biomass smoke on respiratory symptoms in adult rural and urban Nepalese populations 
Environmental Health  2014;13(1):92.
Background
Half of the world’s population is exposed to household air pollution from biomass burning. This study aimed to assess the relationship between respiratory symptoms and biomass smoke exposure in rural and urban Nepal.
Methods
A cross-sectional study of adults (16+ years) in a rural population (n = 846) exposed to biomass smoke and a non-exposed urban population (n = 802) in Nepal. A validated questionnaire was used along with measures of indoor air quality (PM2.5 and CO) and outdoor PM2.5.
Results
Both men and women exposed to biomass smoke reported more respiratory symptoms compared to those exposed to clean fuel. Women exposed to biomass were more likely to complain of ever wheeze (32.0 % vs. 23.5%; p = 0.004) and breathlessness (17.8% vs. 12.0%, p = 0.017) compared to males with tobacco smoking being a major risk factor. Chronic cough was similar in both the biomass and non-biomass smoke exposed groups whereas chronic phlegm was reported less frequently by participants exposed to biomass smoke. Higher PM2.5 levels (≥2 SDs of the 24-hour mean) were associated with breathlessness (OR = 2.10, 95% CI 1.47, 2.99) and wheeze (1.76, 1.37, 2.26).
Conclusions
The study suggests that while those exposed to biomass smoke had higher prevalence of respiratory symptoms, urban dwellers (who were exposed to higher ambient air pollution) were more at risk of having productive cough.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-92) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-92
PMCID: PMC4232609  PMID: 25374400
Respiratory symptoms; Breathlessness; Phlegm; Solid fuel; Household air pollution
21.  Social stressors and air pollution across New York City communities: a spatial approach for assessing correlations among multiple exposures 
Environmental Health  2014;13(1):91.
Background
Recent toxicological and epidemiological evidence suggests that chronic psychosocial stress may modify pollution effects on health. Thus, there is increasing interest in refined methods for assessing and incorporating non-chemical exposures, including social stressors, into environmental health research, towards identifying whether and how psychosocial stress interacts with chemical exposures to influence health and health disparities. We present a flexible, GIS-based approach for examining spatial patterns within and among a range of social stressors, and their spatial relationships with air pollution, across New York City, towards understanding their combined effects on health.
Methods
We identified a wide suite of administrative indicators of community-level social stressors (2008–2010), and applied simultaneous autoregressive models and factor analysis to characterize spatial correlations among social stressors, and between social stressors and air pollutants, using New York City Community Air Survey (NYCCAS) data (2008-2009). Finally, we provide an exploratory ecologic analysis evaluating possible modification of the relationship between nitrogen dioxide (NO2) and childhood asthma Emergency Department (ED) visit rates by social stressors, to demonstrate how the methods used to assess stressor exposure (and/or consequent psychosocial stress) may alter model results.
Results
Administrative indicators of a range of social stressors (e.g., high crime rate, residential crowding rate) were not consistently correlated (rho = - 0.44 to 0.89), nor were they consistently correlated with indicators of socioeconomic position (rho = - 0.54 to 0.89). Factor analysis using 26 stressor indicators suggested geographically distinct patterns of social stressors, characterized by three factors: violent crime and physical disorder, crowding and poor access to resources, and noise disruption and property crimes. In an exploratory ecologic analysis, these factors were differentially associated with area-average NO2 and childhood asthma ED visits. For example, only the ‘violent crime and disorder’ factor was significantly associated with asthma ED visits, and only the ‘crowding and resource access’ factor modified the association between area-level NO2 and asthma ED visits.
Conclusions
This spatial approach enabled quantification of complex spatial patterning and confounding between chemical and non-chemical exposures, and can inform study design for epidemiological studies of separate and combined effects of multiple urban exposures.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-91) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-91
PMCID: PMC4240877  PMID: 25374310
Air pollution; GIS; Social stressors; Spatial confounding; Susceptibility
22.  Distribution of metals exposure and associations with cardiometabolic risk factors in the “Modeling the Epidemiologic Transition Study” 
Environmental Health  2014;13(1):90.
Background
Metals are known endocrine disruptors and have been linked to cardiometabolic diseases via multiple potential mechanisms, yet few human studies have both the exposure variability and biologically-relevant phenotype data available. We sought to examine the distribution of metals exposure and potential associations with cardiometabolic risk factors in the “Modeling the Epidemiologic Transition Study” (METS), a prospective cohort study designed to assess energy balance and change in body weight, diabetes and cardiovascular disease risk in five countries at different stages of social and economic development.
Methods
Young adults (25–45 years) of African descent were enrolled (N = 500 from each site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly selected 150 blood samples (N = 30 from each site) to determine concentrations of selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at baseline and to examine associations with cardiometabolic risk factors.
Results
Median (interquartile range) metal concentrations (μg/L) were: arsenic 8.5 (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were significant differences in metals concentrations by: site location, paid employment status, education, marital status, smoking, alcohol use, and fish intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1, 95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values were significantly associated with elevated fasting glucose. These associations increased when models were further adjusted for percent body fat: arsenic (OR 5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and mercury were also related with increased odds of elevated fasting glucose, but the associations were not statistically significant. Arsenic was significantly associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I. 1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body fat.
Conclusions
While not consistent for all cardiometabolic disease markers, these results are suggestive of potentially important associations between metals exposure and cardiometabolic risk. Future studies will examine these associations in the larger cohort over time.
doi:10.1186/1476-069X-13-90
PMCID: PMC4240881  PMID: 25374160
Arsenic; Cadmium; Cardiometabolic; Diabetes; Endocrine disruption; Lead; Mercury; Metals exposure; Obesity; Risk factor
23.  Air concentrations of volatile compounds near oil and gas production: a community-based exploratory study 
Environmental Health  2014;13(1):82.
Background
Horizontal drilling, hydraulic fracturing, and other drilling and well stimulation technologies are now used widely in the United States and increasingly in other countries. They enable increases in oil and gas production, but there has been inadequate attention to human health impacts. Air quality near oil and gas operations is an underexplored human health concern for five reasons: (1) prior focus on threats to water quality; (2) an evolving understanding of contributions of certain oil and gas production processes to air quality; (3) limited state air quality monitoring networks; (4) significant variability in air emissions and concentrations; and (5) air quality research that misses impacts important to residents. Preliminary research suggests that volatile compounds, including hazardous air pollutants, are of potential concern. This study differs from prior research in its use of a community-based process to identify sampling locations. Through this approach, we determine concentrations of volatile compounds in air near operations that reflect community concerns and point to the need for more fine-grained and frequent monitoring at points along the production life cycle.
Methods
Grab and passive air samples were collected by trained volunteers at locations identified through systematic observation of industrial operations and air impacts over the course of resident daily routines. A total of 75 volatile organics were measured using EPA Method TO-15 or TO-3 by gas chromatography/mass spectrometry. Formaldehyde levels were determined using UMEx 100 Passive Samplers.
Results
Levels of eight volatile chemicals exceeded federal guidelines under several operational circumstances. Benzene, formaldehyde, and hydrogen sulfide were the most common compounds to exceed acute and other health-based risk levels.
Conclusions
Air concentrations of potentially dangerous compounds and chemical mixtures are frequently present near oil and gas production sites. Community-based research can provide an important supplement to state air quality monitoring programs.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-82) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-82
PMCID: PMC4216869  PMID: 25355625
Benzene; Community monitoring; Formaldehyde; Grab and passive samples; Hydraulic fracturing; Hydrogen sulfide; Oil and gas
24.  Acclimatization across space and time in the effects of temperature on mortality: a time-series analysis 
Environmental Health  2014;13(1):89.
Background
Climate change has increased the days of unseasonal temperature. Although many studies have examined the association between temperature and mortality, few have examined the timing of exposure where whether this association varies depending on the exposure month even at the same temperature. Therefore, we investigated monthly differences in the effects of temperature on mortality in a study comprising a wide range of weather and years, and we also investigated heterogeneity among regions.
Methods
We analyzed 38,005,616 deaths from 148 cities in the U.S. from 1973 through 2006. We fit city specific Poisson regressions to examine the effect of temperature on mortality separately for each month of the year, using penalized splines. We used cluster analysis to group cities with similar weather patterns, and combined results across cities within clusters using meta-smoothing.
Results
There was substantial variation in the effects of the same temperature by month. Heat effects were larger in the spring and early summer and cold effects were larger in late fall. In addition, heat effects were larger in clusters where high temperatures were less common, and vice versa for cold effects.
Conclusions
The effects of a given temperature on mortality vary spatially and temporally based on how unusual it is for that time and location. This suggests changes in variability of temperature may be more important for health as climate changes than changes of mean temperature. More emphasis should be placed on warnings targeted to early heat/cold temperature for the season or month rather than focusing only on the extremes.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-89) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-89
PMCID: PMC4271464  PMID: 25352015
Temperature and mortality; Acclimation; Acclimatization; Climate change; Global warming
25.  Longitudinal analysis of health outcomes after exposure to toxics, Willits California, 1991–2012: application of the cohort-period (cross-sequential) design 
Environmental Health  2014;13(1):88.
Background
About 1963, a factory in Willits, Mendocino County (County), California added chrome plating to the manufacture of steel products. After years of residents reporting high illness rates, the State undertook a series of investigations. They found exposures had been high and warranted further research into possible health effects. Applying the seldom-used cross-sequential design, we tested if Willits had an excess rate of adverse health conditions, compared to people of the same sex and cohort living in the rest of county (ROC). This is the first report on long-term health outcomes for Willits.
Methods
Hospital discharge data for 1991–2012 were searched to find admissions for people born between 1940 and 1989 who ever gave the County as their residence. Diagnoses and procedures were classified to Level 1 (body systems) of the Multi-level Clinical Classification Software (CCS). We analyzed 796,917 diagnoses and 289,980 procedures found on 117,799 admissions of 43,234 patients who lived in the County at some time between 1991 and 2012. Of these, 7,564 lived in Willits. We summarized data to the person-level then the group level over cohort-period (cross-sequential) to control the age by time relationship, then calculated incidence rates, relative risk, and excess case statistics, each with confidence limits. A secondary analysis focused on whether Willits differed markedly from the rest of County (ROC). Specifically, other than the presence of the Plant, did Willits differ so much that those differences could plausibly explain outcome differences?
Results
Illness was excessive in the exposed group (Willits) compared to the unexposed (ROC). Overall number of excess cases attributable to living in Willits was estimated: Men, 301 (95% confidence limit (CL) 200–398), women: 696 (CL 569–820).
Conclusions
This study demonstrates the strength of the cross-sequential design. Willits and ROC had comparable disadvantages relative to the State. Yet, when stratified by cohort, Willits had more illness per population. Little is known about the health effect of chemicals used at Willits on a non-occupationally exposed population. We recommend a follow-up study to evaluate the long-term health of people who lived in Willits during childhood and the reproductive age.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-069X-13-88) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-069X-13-88
PMCID: PMC4223849  PMID: 25342458
Cross-sequential; Cohort-by-period; Longitudinal; Population health; Data linkage; Non-occupational exposure; Hexavalent chromium (Cr6)

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