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At least 1,675 records · Page 93
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Clinically applicable 53-Gene prognostic assay predicts chemotherapy benefit in gastric cancer: A multicenter study

BACKGROUND:We previously established a 53-gene prognostic signature for overall survival (OS) of gastric cancer patients. This retrospective multi-center study aimed to develop a clinically applicable gene expression detection assay and to investigate the prognostic value of this signature. METHODS:A TCGA gastric adenocarcinoma cohort (TCGA-STAD) was used for comparing 53-gene signature with other gene signatures. A high-throughput mRNA hybridization gene expression assay was developed to quantify the expression of 53-genes in formalin-fixed paraffin-embedded tissues of 540 patients enrolled from three hospitals. 180 patents were randomly selected from two hospitals to build a prognostic prediction model based on the 53-gene signature using leave-p-out (one-third out) cross-validation method together with Cox regression and Kaplan-Meier analysis, and the model was assessed on three validation cohorts. FINDINGS:In the evaluation phase, studies based on TCGA-STAD showed that the 53-gene signature was significantly superior to other three prognostic signatures and was independent of TCGA molecular subtypes and clinical factors. For clinical validation and utility, the prognostic scores were generated using the newly developed assay, which was reliable and sensitive, in 100 sampling training sets and were significantly associated with OS in 100 sampling validation sets. The scores were significantly associated with OS in three independent and combined validation cohorts, and in patients with stages II and III/IV. The multivariate Cox regression demonstrated that the prognostic power of the score was independent of clinical factors, consistent with those findings in the TCGA dataset. Finally, patients with good prognostic scores exhibited significantly a better 5-year OS rate from adjuvant FOLFOX chemotherapy after surgery than from other chemotherapies. INTERPRETATION:The 53-gene prognostic score system is clinically applicable for predicting the OS of patients independent of clinical factors in gastric cancers, which could also be a promising predictive biomarker for FOLFOX regimen. FUNDING:Chinese National Science and Technology, National Natural Science Foundation and Natural Science Foundation of Jiangsu Province.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

On the variable effects of climate change on Pacific salmon

Pacific salmon are sensitive to changes in water temperature and streamflow. Climate change and water management may alter the streamflow and temperature regimes to which local species have adapted, hence affecting the survival and growth of juvenile salmon. This study estimates the changes in smolt survival rates of Chinook (Oncorhynchus tshawytscha) and Steelhead (Oncorhynchus mykiss) in Columbia River Basin (CRB) due to climatic changes and water management practices (reservoir regulation and water extraction). A multivariate nonlinear regression model is developed between juvenile survival rate and streamflow as well as stream temperature, and incorporates the inherent nonlinearity between survival rate and stream temperature. Using streamflow and stream temperature simulations from a state-of-the-art integrated earth system model, results indicate that climatic changes may reduce basin average juvenile Steelhead survival rates and smolt Chinook survival in Snake River by the 2080s. Water management, on the other hand, can alleviate the reduction in Chinook and Steelhead survival rates induced by climate change through mitigation of stream temperature warming. Integration of the nonlinear response of survival rate to stream temperature in addition to considering water management impacts on streamflow and temperature reduces the overestimate of the negative impacts from climate change. Furthermore, stream warming likely benefits juvenile survival in areas where the current stream temperature is lower than the optimal temperature zone. Our findings add new insights on climate and human impacts on juvenile salmon survival in CRB that are useful for conservation planning.

Zhang, Xiao↗
DOE OSTI2020

An open source fast fluid dynamics model for data center thermal management

Although computational fluid dynamics (CFD) has been widely adopted to improve data center thermal management, the high computational demand limits its applications, such as multivariate optimal design and operation. Fast fluid dynamics (FFD), which has been applied for fast airflow simulation, shows great potential. However, few research applied FFD for optimal design and operation of data center thermal management. This research improves the FFD model for data centers and conducts a comprehensive evaluation and demonstration. First, the FFD model is improved by solving the advection and diffusion equations together using an upwind scheme instead of a semi-Lagrangian advection solver in the conventional FFD model. Second, new features for data centers are added, such as a pressure correction method to simulate plenum airflow and dynamic boundary conditions for IT racks. The new FFD model is first validated with two indoor environment cases and the results show that the new FFD model has slightly better overall prediction accuracy and faster speed compared to the conventional FFD model. It is also observed that both FFD models achieve acceptable accuracy, except for a few localized disparities with experimental data, which might be due to simplified handling of turbulence viscosity near the boundaries. Furthermore, validation with a real data center shows that the FFD model achieves a similar level of accuracy as CFD when compared to the experimental measurements with some level of uncertainties. It is then demonstrated for data center optimal design and operation, which saves 53.4–58.8% of annual energy while still meeting the thermal requirements. In conclusion, with a much faster speed and comparable accuracy compared to CFD, the FFD model parallelized on a graphics processing unit is promising for practical model-based data center early design and operation.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2014

Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women

Objective: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. Methods: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. Results: The geometric means of TSH, TT3, FT4 and mercury were 1.1 μU/L, 2.4 nmol/L, 10.5 pmol/L and 7.7 μg/L, respectively. Mercury levels were marginally significantly associated with TT3 (β: −0.05; 95%CI: −0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (−0.08; 95%CI: −0.15, −0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant. Conclusion: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed. - Highlights: • We studied the relationship between mercury and thyroid hormones among pregnant. • Mercury was marginally significantly associated with TT3, but not with TSH or FT4. • This association was stronger among the iodine supplement. • These results could be of public health concern, but further research is needed.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: The HOME Study

Bisphenol A (BPA), an endocrine disruptor used in consumer products, may perturb thyroid function. Prenatal BPA exposure may have sex-specific effects on thyroid hormones (THs). Our objectives were to investigate whether maternal urinary BPA concentrations during pregnancy were associated with THs in maternal or cord serum, and whether these associations differed by newborn sex or maternal iodine status. We measured urinary BPA concentrations at 16 and 26 weeks gestation among pregnant women in the HOME Study (2003–2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine (T{sub 4}) and triiodothyronine (T{sub 3}) were measured in maternal serum at 16 weeks (n=181) and cord serum at delivery (n=249). Associations between BPA concentrations and maternal or cord serum TH levels were estimated by multivariable linear regression. Mean maternal urinary BPA was not associated with cord THs in all newborns, but a 10-fold increase in mean BPA was associated with lower cord TSH in girls (percent change=−36.0%; 95% confidence interval (CI): −58.4, −1.7%), but not boys (7.8%; 95% CI: −28.5, 62.7%; p-for-effect modification=0.09). We observed no significant associations between 16-week BPA and THs in maternal or cord serum, but 26-week maternal BPA was inversely associated with TSH in girls (−42.9%; 95% CI: −59.9, −18.5%), but not boys (7.6%; 95% CI: −17.3, 40.2%; p-for-effect modification=0.005) at birth. The inverse BPA–TSH relation among girls was stronger, but less precise, among iodine deficient versus sufficient mothers. Prenatal BPA exposure may reduce TSH among newborn girls, particularly when exposure occurs later in gestation. - Highlights: • Examined associations of BPA with thyroid hormones in pregnant women and newborns. • Assessed effect modification of BPA–thyroid hormone associations by newborn sex. • Greater BPA related to decreased thyroid stimulating hormone in girls' cord serum. • Results may suggest window of susceptibility to BPA in later gestation. • BPA potentially has greatest adverse effect on girls with iodine deficient mothers.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water was assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m{sup 2}, corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young children in rural Bangladesh. Better selenium status appears to be protective. However, it is important to follow up these children to assess potential long-term consequences of these findings. - Highlights: • Bangladesh has high levels of arsenic and cadmium in drinking water and food • We assessed toxic exposure, kidney and cardiovascular function in Bangladeshi children • Cadmium appeared to decrease estimated glomerular filtration rate in girls • These effects were somewhat alleviated by selenium.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

The effects of heavy metals and their interactions with polycyclic aromatic hydrocarbons on the oxidative stress among coke-oven workers

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic constituents of particulate air pollution that may be related to the increased risk of cardiopulmonary events. We aim to investigate the effects of the toxic heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb), and their interactions with PAHs on oxidative stress among coke-oven workers. A total of 1333 male workers were recruited in this study. We determined their urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Multivariate linear regression models were used to analyze the effects of these metals and their interactions with PAHs on 8-OHdG and 8-iso-PGF2α levels. It was found that only urinary As and Ni showed marginal or significant positive linear dose-dependent effects on 8-OHdG in this study population, especially among smokers (β=0.103, P=0.073 and β=0.110, P=0.002, respectively). After stratifying all participants by the quartiles of ΣOH-PAH, all five metals showed linear association with 8-OHdG in the highest quartile subgroup (Q4) of ΣOH-PAHs. However, these five urinary metals showed significantly consistent linear associations with 8-iso-PGF2α in all subjects and each stratum. Urinary ΣOH-PAHs can significant modify the effects of heavy metals on oxidative stress, while co-exposure to both high levels of ΣOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso-PGF2α (all P{sub interaction}≤0.005). This study showed evidence on the interaction effects of heavy metals and PAHs on increasing the oxidative stress, and these results warrant further investigation in more longitudinal studies. - Highlights: • Heavy metals and PAHs are predominate toxic constituents of particulate matters. • Urinary As and Ni showed linear dose-dependent effects on 8-OHdG and 8-iso-PGF2α. • PAHs significant interact with toxic metal in increasing 8-OHdG and 8-iso-PGF2α. • Co-exposure to high PAHs and toxic metals contribute to highest oxidative stress.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: The MIREC study

Background: Lead, mercury, cadmium and arsenic are some of the most common toxic metals to which Canadians are exposed. The effect of exposure to current low levels of toxic metals on fetal growth restriction is unknown. Objective: The aim of this study was to examine relationships between exposure to lead, mercury, cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA) birth. Methods: Lead, mercury, cadmium and arsenic levels were measured in blood samples from the first and third trimesters in 1835 pregnant women from across Canada. Arsenic species in first trimester urine were also assessed. Relative risks and 95% confidence intervals were estimated using log binomial multivariate regression. Important covariates including maternal age, parity, pre-pregnancy BMI, and smoking, were considered in the analysis. An exploratory analysis was performed to examine potential effect modification of these relationships by single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes. Results: No association was found between blood lead, cadmium or arsenic and risk for SGA. We observed an increased risk for SGA for the highest compared to the lowest tertile of exposure for mercury (>1.6 µg/L, RR=1.56.; 95% CI=1.04–2.58) and arsenobetaine (>2.25 µg/L, RR=1.65; 95% CI=1.10–2.47) after adjustment for the effects of parity and smoking. A statistically significant interaction was observed in the relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA between strata of GSTO1 A104A (p for interaction=0.02). A marginally significant interaction was observed in the relationship between blood lead and SGA between strata of GSTP1 A114V (p for interaction=0.06). Conclusions: These results suggest a small increase in risk for SGA in infants born to women exposed to mercury and arsenic. Given the conflicting evidence in the literature this warrants further investigation in other pregnant populations. - Highlights: • Metals measured in blood or urine of pregnant women. • No association between blood lead, cadmium or arsenic and SGA. • Small increased risk for highest tertile of blood mercury. • Small increased risk for highest tertile of urinary arsenobetaine. • Further research needed to confirm observed associations.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Self-reported sunscreen use and urinary benzophenone-3 concentrations in the United States: NHANES 2003–2006 and 2009–2012

Background: Sunscreens protect against skin cancer and other harmful effects of solar ultraviolet radiation (UVR). Epidemiologic and public health surveys often rely on self-reported sunscreen use to estimate sun exposure and avoidance, but questions remain about the validity of self-reports. Benzophenone-3 (BP-3), a common sunscreen ingredient, can be detected in the urine. Prior studies suggest that BP-3 concentrations increase after application of sunscreen. Objectives: The goal of this study was to assess the validity of self-reported frequency of sunscreen use in relation to urinary BP-3 concentrations in a representative sample of the general US population, including in sub-groups defined by age, sex and race/ethnicity. Methods: To assess the relationship between categorical self-reported sunscreen use and creatinine-corrected urinary BP-3 concentrations, we conducted a linear regression adjusted for age, sex, race/ethnicity, six-month time period, body mass index, education, and sun avoidance behaviors. We tested for effect modification by age, sex, ethnicity and time period of measurement using multiplicative interaction terms and a F test. Results: BP-3 was positively associated with self-reported frequency of sunscreen use across all ages, sexes, race/ethnicities, and time periods. Crude and multivariate adjusted models were all statistically significant. R-square was relatively low for all models, ranging from 0.15 to 0.43. Conclusions: Urinary BP-3 is positively associated with self-reported frequency of sunscreen use in the general US population, even in groups with overall low sunscreen use. These results suggest that self-report is a valid, although weak, way of assessing relative frequencies of sunscreen usage in a population-based study. - Highlights: • Urinary benzophenone-3 (BP-3) is a metabolite of a common sunscreen ingredient. • We modeled urinary BP-3 against self-reported sunscreen usage. • We observed a positive association between sunscreen use and urinary BP-3. • R{sup 2} was low, suggesting self-report is a valid but weak way to assess sunscreen use.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Prenatal exposure to polycyclic aromatic hydrocarbons/aromatics, BDNF and child development

Objectives: Within a New York City (NYC) birth cohort, we assessed the associations between polycyclic aromatic hydrocarbon (PAH) and other aromatic DNA adducts and brain derived neurotrophic factor (BDNF) concentrations in umbilical cord blood, and neurodevelopment at age 2 years and whether BDNF is a mediator of the associations between PAH/aromatic-DNA adducts and neurodevelopment. Methods: PAH/aromatic-DNA adduct concentrations in cord blood were measured in 505 children born to nonsmoking African-American and Dominican women residing in NYC, and a subset was assessed for neurodevelopment at 2 years using the Bayley Scales of Infant Development Mental Development Index (MDI). A spectrum of PAH/aromatic-DNA adducts was measured using the {sup 32}P-postlabeling assay; DNA adducts formed by benzo[a]pyrene (B[a]P), a representative PAH, were measured by High Performance Liquid Chromatography (HPLC)/fluorescence. BDNF mature protein in cord blood plasma was quantified by an ELISA. Multivariate regression analysis, adjusting for potential confounders, was conducted. Results: PAH/aromatic-DNA adduct concentration measured by postlabeling was inversely associated with BDNF concentration (p=0.02) and with MDI scores at 2 years (p=0.04). BDNF level was positively associated with MDI scores (p=0.003). Restricting to subjects having all three measures (PAH/aromatic-DNA adducts by postlabeling, MDI, and BDNF), results were similar but attenuated (p=0.13, p=0.05, p=0.01, respectively). Associations between B[a]P-DNA adducts and BDNF and B[a]P-DNA adducts and MDI at age 2 years were not significant. At age 3 years, the positive association of BDNF with MDI was not observed. Conclusions: The results at age 2 suggest that prenatal exposure to a spectrum of PAH/aromatic pollutants may adversely affect early neurodevelopment, in part by reducing BDNF levels during the fetal period. However, the same relationship was not seen at age 3. - Highlights: • Cord blood Polycyclic Aromatic Hydrocarbon (PAH)/aromatic-DNA adducts were assayed. • Brain Derived Neurotrophic Factor (BDNF) concentration was measured concurrently. • Associations between biomarkers and neurodevelopment at age 2 years were assessed. • Adduct level was inversely associated with BDNF concentration and neurodevelopment. • BDNF level was positively associated with neurodevelopment scores at age 2 years.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Incidence of nephrolithiasis in relation to environmental exposure to lead and cadmium in a population study

Whether environmental exposure to nephrotoxic agents that potentially interfere with calcium homeostasis, such as lead and cadmium, contribute to the incidence of nephrolithiasis needs further clarification. We investigated the relation between nephrolithiasis incidence and environmental lead and cadmium exposure in a general population. In 1302 participants randomly recruited from a Flemish population (50.9% women; mean age, 47.9 years), we obtained baseline measurements (1985–2005) of blood lead (BPb), blood cadmium (BCd), 24-h urinary cadmium (UCd) and covariables. We monitored the incidence of kidney stones until October 6, 2014. We used Cox regression to calculate multivariable-adjusted hazard ratios for nephrolithiasis. At baseline, geometric mean BPb, BCd and UCd was 0.29 µmol/L, 9.0 nmol/L, and 8.5 nmol per 24 h, respectively. Over 11.5 years (median), nephrolithiasis occurred in 40 people. Contrasting the low and top tertiles of the distributions, the sex- and age-standardized rates of nephrolithiasis expressed as events per 1000 person-years were 0.68 vs. 3.36 (p=0.0016) for BPb, 1.80 vs. 3.28 (p=0.11) for BCd, and 1.65 vs. 2.95 (p=0.28) for UCd. In continuous analysis, with adjustments applied for sex, age, serum magnesium, and 24-h urinary volume and calcium, the hazard ratios expressing the risk associated with a doubling of the exposure biomarkers were 1.35 (p=0.015) for BPb, 1.13 (p=0.22) for BCd, and 1.23 (p=0.070) for UCd. In conclusion, our results suggest that environmental lead exposure is a risk factor for nephrolithiasis in the general population. - Highlights: • Prevalence and incidence rates of nephrolithiasis are increasing worldwide. • Lead and cadmium interfere with calcium homeostasis and might cause nephrolithiasis. • Environmental exposure to lead, not cadmium, predicts nephrolithiasis in the population. • Safety standards for environmental lead exposure need to account for nephrolithiasis. • Reducing environmental exposure to lead remains a priority.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Maternal body burden of cadmium and offspring size at birth

Increasing evidence suggests an inverse association between cadmium (Cd) and size at birth, potentially greatest among female neonates. We evaluated whether greater maternal body burden of Cd is associated with reduced neonatal anthropometry (birthweight, birth length, head circumference, and ponderal index) and assessed whether these associations differ by infant sex. The analytic sample for the present study (n=396) was derived from a subcohort of 750 women randomly drawn from among all participants (N=4344) in the Omega Study, a prospective pregnancy cohort. Creatinine-corrected Cd in maternal clean-catch spot urine samples (U-Cd) was quantified by inductively coupled plasma mass spectrometry. Continuous log{sub 2}-transformed Cd (log{sub 2}-Cd) and U-Cd tertiles (low<0.29 μg/g creatinine, middle 0.29–0.42 μg/g creatinine, high≥0.43 μg/g creatinine) were used in multivariable linear regression models. Females had reduced birth length with greater U-Cd tertile, whereas males birth length marginally increased [β(95% CI) females: low=reference, middle=−0.59 cm (−1.37, 0.19), high=−0.83 cm (−1.69, 0.02), p-trend=0.08; males: low=reference, middle=0.18 cm (−0.59, 0.95), high=0.78 cm (–0.04, 1.60), p-trend=0.07; p for interaction=0.03]. The log{sub 2}-Cd by infant sex interaction was statistically significant for ponderal index [p=0.003; β(95% CI): female=0.25 kg/m{sup 3} (−0.20, 0.70); male=−0.63 kg/m{sup 3} (−1.01, −0.24)] and birth length [p<0.001; β(95% CI): female=−0.47 cm (−0.74, −0.20), male=0.32 cm (0.00, 0.65)]. Our findings suggest potential sex-specific reversal of Cd’s associations on birth length and contribute to the evidence suggesting Cd impairs fetal growth. - Highlights: • Cadmium levels in the general population potentially adversely affect size at birth. • Maternal urinary cadmium was inversely related to birth length among female infants. • For male infants, maternal cadmium was positively associated with birth length. • Maternal cadmium was also inversely related to ponderal index among male infants.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort

Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148 Bq/m{sup 3}) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74 Bq/m{sup 3}) radon levels (HR=1.63, 95% CI:1.23–2.18), and there was evidence of a dose-response relationship (HR{sub continuous}=1.38, 95% CI:1.15–1.65 per 100 Bq/m{sup 3}; p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. - Highlights: • This is the first prospective, general population study of residential radon and risk of hematologic cancer. • Findings from this study suggest that residential radon exposure may be a risk factor for lymphoid malignancies. • The biologic mechanism for the association between radon exposure and lymphoma risk may be different than for lung cancer. • Confirmation of this association would warrant strengthened public health efforts to mitigate residential radon risks.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Placental biomarkers of PAH exposure and glutathione-S-transferase biotransformation enzymes in an obstetric population from Tijuana, Baja California, Mexico

Environmental exposures along the US-Mexico border have the potential to adversely affect the maternal-fetal environment. The purpose of this study was to assess placental biomarkers of environmental exposures in an obstetric population at the California-Baja California border in relation to detoxifying enzymes in the placenta and nutritional status. This study was conducted on consenting, full-term, obstetric patients (n=54), delivering in a hospital in Tijuana, Baja California (BC), Mexico. Placental polyaromatic hydrocarbon (PAH)-DNA adducts were measured in addition to placental glutathione-S-transferase (GST) activity and genotype, maternal serum folate, and maternal and umbilical cord blood lead and cadmium levels. A questionnaire was administered to the mothers to determine maternal occupation in a maquiladora, other exposures, and obstetric indicators. In univariate analysis, maternal serum folate levels were inversely correlated with total PAH-DNA adducts (rho=−0.375, p=0.007); adduct #1 (rho=−0.388, p=0.005); and adduct #3 (rho =−0.430, p=0.002). Maternal lead levels were significantly positively correlated with cord blood lead levels (rho=0.512, p<0.001). Cadmium levels were generally very low but significantly higher in mothers exposed to environmental tobacco smoke (ETS) (either at work or at home, n=10). In multivariate analysis, only maternal serum folate levels remained as a significant negative predictor of total DNA-PAH adducts levels in placenta. These findings affirm that placental tissue is a valuable and readily available source of human tissue for biomonitoring; and indicate that further study of the role of nutrition in detoxification and mitigation of environmental exposures in pregnant women is warranted. - Highlights: • Maternal-fetal environment susceptible to toxic exposures at US-Mexico border. • Lower serum folate was correlated with higher PAH-DNA adduct levels at birth. • Placental DNA adducts in GST mu (-) cord blood were higher than GST(+) genotype. • Blood lead levels in Mexican women were higher than reported to NHANES. • Cadmium levels in mothers exposed to ETS correlated with total PAH-DNA adducts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater arsenic polluted areas in Asia. • Urinary cadmium was negatively associated with salivary telomere length. • Urinary arsenic was not significantly associated with salivary telomere length.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Iodine nutritional status and thyroid effects of exposure to ethylenebisdithiocarbamates

Introduction: Italy is still characterized by a mild iodine deficiency and is among the most intensive users of chemical products for agriculture in Europe. The aim of this study was i) to evaluate thyroid effects of exposure to mancozeb, a fungicide widely used in agriculture, in a sample of Italian grapevine workers, and ii) to verify whether the iodine intake may modulate the risk of thyroid disruption due to the mancozeb metabolite ethylenthiourea (ETU). Methods: One hundred seventy-seven occupationally exposed male workers (29 from Chianti, a mild iodine deficient area, and 148 from Bolzano an iodine sufficient province) and 74 non-occupationally exposed male controls (34 from Chianti and 40 from Bolzano) were enrolled in the study. Serum biomarkers of thyroid function, as well as urinary iodine and ETU concentrations were assessed. Moreover all the recruited subjects underwent clinical examination and thyroid ultrasound. Results: Multivariate comparisons showed lower mean serum levels of FT4 in Chianti-workers as compared to Bolzano-workers. Moreover, an increased urinary iodine excretion (>250 µg/L) was more frequently found among more exposed workers (ETU>20 µg/L) than among less exposed ones and this effect was more pronounced in Chianti- than in Bolzano-workers. Chianti-workers also showed a significantly higher frequency of very low thyroid volume (≤6.0 ml) as compared to controls. Conclusions: These findings showed a mild thyroid disrupting effect due to occupational exposure to mancozeb, more pronounced in workers residing in an area characterized by a mild to moderate iodine deficiency as compared to workers residing in an area covered by a long-lasting iodine prophylaxis program. - Highlights: • Thyroid is vulnerable to endocrine disrupting effects due to environmental exposures. • Mancozeb is a fungicide widely used in agriculture worldwide. • Mancozeb is broken down into ethylenthiourea (ETU) which has anti-thyroid activity. • Iodine intake may modulate thyroid disruption due to occupational exposure to ETU.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation

High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timiá¹£ County, Romania. Women (n=94) with planned pregnancies of 5–20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1 µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study. - Highlights: • We assessed low level drinking water arsenic as a predictor of fecundability. • Arsenic did not affect time to pregnancy among women conceiving quickly. • Arsenic increased time to pregnancy among women taking longer to conceive. • Low level drinking water arsenic may adversely impact women with lower fecundity.

54 ENVIRONMENTAL SCIENCES↗