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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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DOE OSTI2016

Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis

GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was previously characterized as a tumor suppressor that regulates and requires merlin to suppress cell proliferation. However, the role of GTPBP4 in the metastasis of colorectal carcinoma (CRC) remains unelucidated. Here, we observed that GTPBP4 was detected at higher levels in CRC metastatic tissues than that in the primary tumor tissues. Notably, up-regulation of GTPBP4 was closely correlated with tumor metastasis in CRCs. Kaplan-Meier and multivariate Cox regression analysis indicated GTPBP4 as an independent prognostic factor for CRC patients (hazard ratio = 2.693, 95% confident interval: 1.193–6.083, p = 0.017). Functional studies established that knockdown of GTPBP4 impeded, whereas ectopic expression of GTPBP4 enhanced cell motility and tumor metastasis in CRC cells. Interestingly, mechanistic investigations suggested that GTPBP4 may disorganize actin cytoskeleton through repressing RhoA signaling. Taken together, our research uncovered that GTPBP4 promotes CRC metastasis by disrupting actin cytoskeleton, which is mediated by the reduced RhoA activity. Strategies targeting GTPBP4 will be promising for CRC patients with metastases. - Highlights: • Up-regulation of GTPBP4 is detected in CRC metastatic tissues and closely correlated with tumor metastasis. • Increase of GTPBP4 is closely associated with poor prognosis. • GTPBP4 promotes cell motility and tumor metastasis in CRC cells. • GTPBP4 induces filamentous actin rearrangement specifically by repressing the activity of RhoA. • GTPBP4 may be a novel therapeutic target for CRC patients with metastasis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

High expression of CREPT promotes tumor growth and is correlated with poor prognosis in colorectal cancer

CREPT (cell cycle-related and expression elevated protein in tumor) is highly expressed in many kinds of cancer, and has been shown to be prognostic in certain cancers. However, the clinical significance of CREPT in colorectal cancer (CRC) has not been sufficiently investigated. In this study, we examined the CREPT expression in 225 clinical CRC tissues and paired adjacent normal tissues, and analyzed the correlation between CREPT expression and other clinicopathological features. We also evaluated the biological function of CREPT both in vitro and in vivo using knockdown or overexpressing CRC cells. Our results showed that CREPT expressed in 175 of 225 (77.8%) CRC patients and the CREPT expression was significantly associated with tumor differentiation (P = 0.000), Dukes' stages (P = 0.013) and metastasis (P = 0.038). Patients with high CREPT expression tended to have shorter survival time. Multivariate analysis showed that positive CREPT expression can be used as an independent predictor for CRC prognosis. CREPT knockdown cells showed inhibited cell proliferation and arrested cell cycle, while CREPT overexpressing cells showed increased proliferation and promoted cell cycle. In addition, CREPT overexpression significantly promoted tumor growth in vivo. Mechanism study showed that CREPT may regulate cell proliferation and cell cycle through the regulation on cyclin D3, CDK4 and CDK6. - Highlights: • CREPT expression was associated with decreased overall survival in CRC. • CREPT expression is correlated with tumor progression in CRC. • Overexpression of CREPT promoted tumor growth both in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer

Tenascin-C (TNC), as a member of the extracellular matrix (ECM), plays an important role in cancer cell proliferation and migration and tumor invasion in various types of cancer. Here, we attempted to investigate the role of TNC as a prognostic factor in prostate cancer. We studied TNC expression via immunohistochemistry in 145 prostate cancer tissue samples. The clinicopathological relevance of TNC expression was examined, as well as other cancer-associated fibroblasts (CAFs)-related factors. Our results showed that the high levels of TNC expression in prostate cancer stroma was significantly associated with lymph node metastasis (P = 0.024) and clinical stage (P = 0.032). Furthermore, TNC was positively correlated with increased micro-vessel density (MVD) (P = 0.017) and tumor associated macrophage (TAM) population (P = 0.025). In both univariate and multivariate Cox regression analyses, TNC (P < 0.001) was an independent poor prognostic factor for overall survival in prostate cancer patients. Moreover, over-expression of TNC (P < 0.001), SMA (P = 0.042) and vimentin (P = 0.010) were significantly correlated with the lower overall survival. In addition, TNC expression in prostate cancer stroma was significantly associated with FSP1 (P = 0.011), SMA (P = 0.021), and vimentin (P = 0.002). In conclusion, our study revealed that high level of TNC as a potential biomarker of CAFs was significantly correlated with the poor prognosis for prostate cancer patients. - Highlights: • The cancer stroma carries a significant prognostic information. • TNC and CAFs are important in promoting tumor growth and metastasis. • CAFs could affect the invasive potential of cancer cells by producing TNC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Expression and prognostic role of orphan receptor GPR110 in glioma

Glioma is the most common type of malignancy in the central nervous system, which has a poor prognosis due to its rapid progression and diffuse invasion. Identification of novel biomarkers for glioma would be invaluable for studying disease mechanism and improving prognosis. Orphan G protein-coupled receptor 110 (GPR110) belongs to the subfamily VI of adhesion GPCR. The knowledge of the ligand, signaling pathway or physiology function of GPR110 is poorly elucidated. The potential role of GPR110 as an oncogene in mouse has been recently reported by mutagenesis screen. However, its expression and role in human glioma hasn't been identified. Here in the current study, we initially explored the RNA and protein expression of GPR110 in patients with glioma. Statistical analysis proved that GPR110 was highly expressed in some patients, which was correlated with advanced disease stages. Furthermore, univariate and multivariate analyses revealed its role as an independent prognostic biomarker for the overall survival of glioma patients. Interestingly, cellular studies showed that overexpression or knockdown of GPR110 in U87 cells didn't affect cell proliferation and migration. However, the invasion of U87 cells was significantly enhanced by GPR110-overepxression, while inhibited by GPR110-knockdown. The detailed mechanisms remain further investigation although our results suggested the possible participation of STAT3 instead of ERK in the GPR110 signaling pathways. - Highlights: • GPR110 was highly expressed in glioma than normal brain tissues. • High GPR110 indicates poor overall survival of glioma patients. • GPR110 enhance cell invasion without affecting cell proliferation and migration. • GPR110 inhibit the activation of STAT3, but not ERK protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in Southern China and Southeast Asia compared with Western countries. The standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to satisfactory treatment, it can cause local recurrence and distant metastases in some patients after treatment by radiation. We retrospectively reviewed 108 NPC patients (7th AJCC Ⅲ-Ⅳa) who have received intensity modulated radiation therapy (IMRT) between August 2008 and January 2012 at Xiangya Hospital of Central South University. Ninety-eight patients with >60% reduction of tumor size after radiation treatment were regarded as radiation sensitive, Ten patients with <40% reduction of tumor size after radiation treatment were regarded as radiation resistant. Using immunohistochemistry, we found that the high expression rate of Ki-67 in radiation resistant and radiation sensitive patients was 80.0% and 42.6%, respectively, and the difference was statistically significant (p = 0.025). The 5-year progress free survival rates in patients with low and high expression of Ki-67 was 70.7% and 48.0%, respectively, and the difference was statistically significant (p = 0.0008). Multivariate Cox regression analysis identified that high expression of Ki-67 was an independent negative prognostic factor in nasopharyngeal carcinoma patients [Hazard ratio (95% CI), 2.098(1.101, 3.996); p = 0.024]. These results demonstrate that high expression of Ki-67 contributes to radiation resistance and acts a poor prognosis indicator in patients with locally advanced nasopharyngeal carcinoma. - Highlights: • Radiation resistance remains a serious obstacle in some locally advanced nasopharyngeal carcinoma patients after treatment by radiation. • The proportion of Ki67 + cells after radiotherapy provided an independent variable of responsiveness to radiotherapy in squamous cell carcinoma of the head and neck. • The expression of Ki67 association with radiation resistance in locally advanced nasopharyngeal carcinoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Prognostic significance of high YY1AP1 and PCNA expression in colon adenocarcinoma

Highlights: • YY1AP1 expression might play an important role in the tumorgenesis of colon adenocarcinoma. • YY1AP1 expression is related with colon adenocarcinoma patient M-class/distant metastasis. • High YY1AP1 indicates poor overall survival of colon adenocarcinoma patients. • Cox proportional-hazards model analysis indicated YY1AP1 as an independent predictor for overall survival. To investigate the relationship between YY1AP1 and various clinicopathological features of colon adenocarcinoma (COAD), we conducted immunohistochemical (IHC) analyses of human tissue microarrays. We found that YY1AP1 protein expression was significantly higher in tumor tissue of the colon and liver, and was significantly lower in tumor tissue of the kidney. An analysis that employed the SurvExpress database indicated that increased expression of YY1AP1 mRNA was significantly associated with the overall survival of COAD patients. To clarify the validity of YY1AP1 or PCNA as determined by the IHC analysis was performed on 59 paired samples from COAD and adjacent normal tissue. Statistically significant differences of immunoreactivity for YY1AP1 or PCNA protein expression was observed between COAD tissue and adjacent normal tissue. High protein expression levels of YY1AP1 and PCNA were also found to be significantly correlated with M-class and distant metastasis. We also determined that YY1AP1 was correlated with PCNA expression in COAD samples, and Kaplan-Meier survival curves indicated that YY1AP1 protein expression was significantly associated with poor survival. Finally, a univariate analysis demonstrated that YY1AP1 protein expression was related to YY1AP1 score, and multivariate analysis revealed that the YY1AP1 protein expression level was an independent risk factor of overall COAD survival. Taken together, our findings indicate that YY1AP1 expression plays an important role in the tumorigenesis and progression of COAD and could serve as a clinical prognostic indicator for COAD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Downregulated miR-1247-5p associates with poor prognosis and facilitates tumor cell growth via DVL1/Wnt/β-catenin signaling in breast cancer

The abnormal expression of microRNAs is a key hallmark of breast cancer. Nevertheless, the biological roles of miR-1247-5p in breast cancer remain unknown. In this study, we revealed that miR-1247-5p expression was markedly decreased in breast cancer. It was a valuable diagnostic biomarker for breast cancer with the area under the curve of more than 0.80. Reduced miR-1247-5p expression was significantly correlated with patient age, tumor size, and poor prognosis in The Cancer Genome Atlas cohort including 839 breast cancer patients. Multivariate Cox regression analysis demonstrated that miR-1247-5p was an independent prognostic indicator for overall survival (hazard radio [HR] = 1.683, 95% confidence interval [CI] = 1.087–2.606, p = 0.020) and recurrence-free survival (HR = 2.496, 95% CI = 1.576–3.951, p < 0.001). Moreover, functional studies showed that overexpression of miR-1247-5p inhibited proliferation and induced apoptosis in breast cancer cells. Bioinformatics analysis and mechanistic investigations revealed that Dishevelled 1 (DVL1) was a direct target of miR-1247-5p. Inhibition of DVL1 by miR-1247-5p resulted in the suppression of Wnt/β-catenin signaling, whereas overexpression of DVL1 abrogated the miR-1247-5p-mediated effect. These data reveal that miR-1247-5p, as an oncosuppressor in breast cancer, may be a promising prognostic biomarker and therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Predicting concrete compressive strength using hybrid ensembling of surrogate machine learning models

This study aims to implement a hybrid ensemble surrogate machine learning technique in predicting the compressive strength (CS) of concrete, an important parameter used for durability design and service life prediction of concrete structures in civil engineering projects. For this purpose, an experimental database consisting of 1030 records has been compiled from the machine learning repository of the University of California, Irvine. The database was used to train and validate four conventional machine learning (CML) models, namely Artificial Neural Network (ANN), Linear and Non-Linear Multivariate Adaptive Regression Splines (MARS-L and MARS-C), Gaussian Process Regression (GPR), and Minimax Probability Machine Regression (MPMR). Subsequently, the predicted outputs of CML models were combined and trained using ANN to construct the Hybrid Ensemble Model (HENSM). It is observed that the proposed HENSM produces higher predictive accuracy compared to the CML models used in the present study. The predictive performance of all models for CS prediction was compared using the testing dataset and it is found that the HENSM model attained the highest predictive accuracy in both phases. Based on the experimental results, the newly constructed HENSM model is very potential to be a new alternative in handling the overfitting issues of CML models and hence, can be used to predict the concrete CS, including the design of less polluting and more sustainable concrete constructions.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Quantification of the REE 3+ aqua ions and chloride species in aqueous fluids by in situ Raman spectroscopy using perturbations of the water band

Acidic NaCl-rich aqueous fluids play a crucial role in forming hydrothermal rare earth elements (REE) mineral deposits. Aqueous REE mobility is mostly controlled by the stabilities of REE 3+ and REE chloride species. Our current knowledge of REE speciation is based on solubility data, thermodynamic models and in situ spectroscopic measurements, sometimes coupled with molecular simulations. Here, in this study, we investigate Nd and Yb speciation in pH2 Cl-bearing solutions at 25 °C and 0.1 MPa with variable Cl/REE ratios using Raman Spectroscopy in solutions with 0.1 to 0.6 mol/kg NdCl 3 or YbCl 3 and 0.2 to 3.2 mol/kg NaCl. Due to the challenges in resolving the REE-Cl band, we developed a new method using the water vibrational mode and multivariate curve resolution (MCR) analysis. The Raman spectra for the vibrational band of water (2700 to 3900 cm –1 ) were collected at 25 °C and fitted by three Gaussian sub-peaks, then quantified using MCR analysis to de-convolute the water band into bulk H 2 O and the perturbations caused by of Cl – , REE 3+ , and REE chloride species. REE speciation based on the perturbations of the water band indicates that REE 3+ aqua ions dominate acidic solutions at 25 °C, but up to ~20 mol% YbCl 2+ forms at high YbCl 3 concentrations. The new method is promising for quantifying in situ speciation of the REE 3+ aqua ions and REE chloride species in aqueous fluids while providing information on the hydration of ions. This method improves our molecular level understanding of REE aqueous species stability and their role in REE mobilization during fluid-rock interaction.

58 GEOSCIENCES↗
DOE OSTI2013

Cadmium exposure induces hematuria in Korean adults

Introduction: Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated. Methods: Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008–2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables. Results: Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019–1.777; P=0.037); 4th quartile, 1.52 (1.140–2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224–3.160; P{sub trend}=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses. Discussion: The present study shows that high cadmium exposure is associated with a risk of hematuria. -- Highlights: • A high level of blood cadmium is associated with a high risk of hematuria. • This correlation is independent of several confounding factors. • Blood levels of lead and mercury are not associated with risk of hematuria. • This is the first study on the correlation between cadmium exposure and hematuria risk.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Exposure to mercury among Spanish preschool children: Trend from birth to age four

The purpose of this study is to describe the total hair mercury concentrations and their determinants in preschool Spanish children, as well as to explore the trend in mercury exposure from birth to the age four. This evolution has been scarcely studied in other birth cohort studies. The study population was 580 four year old children participating in the INMA (i.e. Childhood and Environment) birth cohort study in Valencia (2008–2009). Total mercury concentration at age four was measured in hair samples by atomic absorption spectrometry. Fish consumption and other covariates were obtained by questionnaire. Multivariate linear regression models were conducted in order to explore the association between mercury exposure and fish consumption, socio-demographic characteristics and prenatal exposure to mercury. The geometric mean was 1.10 µg/g (95%CI: 1.02, 1.19). Nineteen percent of children had mercury concentrations above the equivalent to the Provisional Tolerable Weekly Intake proposed by WHO. Mercury concentration was associated with increasing maternal age, fish consumption and cord blood mercury levels, as well as decreasing parity. Children whose mothers worked had higher mercury levels than those with non working mothers. Swordfish, lean fish and canned fish were the fish categories most associated with hair mercury concentrations. We observed a decreasing trend in mercury concentrations between birth and age four. In conclusion, the children participating in this study had high hair mercury concentrations compared to reported studies on children from other European countries and similar to other countries with high fish consumption. The INMA study design allows the evaluation of the exposure to mercury longitudinally and enables this information to be used for biomonitoring purposes and dietary recommendations. - Highlights: • The geometric mean of hair Hg concentrations was 1.10 µg/g. • 19% of children had Hg concentrations above the RfD proposed by the WHO. • Hair Hg concentrations in children increased as a function of total fish intake. • Swordfish, lean fish and canned fish were the most related to Hg concentrations. • There was a decrease in Hg concentrations from birth to age four.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Distribution of chemical elements in soils and stream sediments in the area of abandoned Sb–As–Tl Allchar mine, Republic of Macedonia

The aim of this study was to investigate the distribution of some toxic elements in topsoil and subsoil, focusing on the identification of natural and anthropogenic element sources in the small region of rare As–Sb–Tl mineralization outcrop and abandoned mine Allchar known for the highest natural concentration of Tl in soil worldwide. The samples of soil and sediments after total digestion were analyzed by inductively coupled plasma–mass spectrometry (ICP–MS) and inductively coupled plasma–atomic emission spectrometry (ICP–AES). Factor analysis (FA) was used to identify and characterize element associations. Six associations of elements were determined by the method of multivariate statistics: Rb–Ta–K–Nb–Ga–Sn–Ba–Bi–Li–Be–(La–Eu)–Hf–Zr–Zn–In–Pd–Ag–Pt–Mg; Tl–As–Sb–Hg; Te–S–Ag–Pt–Al–Sc–(Gd–Lu)–Y; Fe–Cu–V–Ge–Co–In; Pd–Zr–Hf–W–Be and Ni–Mn–Co–Cr–Mg. The purpose of the assessment was to determine the nature and extent of potential contamination as well as to broadly assess possible impacts to human health and the environment. The results from the analysis of the collected samples in the vicinity of the mine revealed that As and Tl elements have the highest median values. Higher median values for Sb are obviously as a result of the past mining activities and as a result of area surface phenomena in the past. - Highlights: • Soil and river sediments were analyzed from Sb–As–Tl Allchar locality. • An increased content of certain toxic elements for environment was determined. • Highest As and Tl contents are obtained in the close vicinity of Allchar mine. • River sediments portray 160 times higher content of Sb than EU values. • The results classify Allchar as probably the highest natural Tl-deposit worldwide.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Cadmium exposure and neuropsychological development in school children in southwestern Spain

This study assessed the association between cadmium exposure and neuropsychological development in children from a region with high industrial and mining activities in southwestern Spain. We conducted a cross-sectional study with 261 children aged 6–9 years between January and March 2012. Cadmium exposure was measured in urine and hair of children, and neuropsychological development was assessed with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and with three computerized tests from the Behavioral Assessment and Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT). Multivariate linear regression models, adjusted for potential confounders, were used to estimate the association between neuropsychological development and cadmium exposure measured in urine and hair samples. Geometric means of urine and hair cadmium levels were 0.75 μg/g creatinine and 0.01 μg/g, respectively. We observed that doubling of levels of cadmium in urine was associated with a reduction of two points (95% CI: −3.8 to −0.4) in the Full-Scale intelligence quotient (IQ) in boys. By domains, association was statistically significant for Verbal Comprehension (β=−2.0; p=0.04) and close to the significance level for Perceptual Reasoning (β=−1.8; p=0.06). Among girls, only Verbal Comprehension showed suggestive associations with cadmium exposure (β=−1.7; p=0.06). Cadmium exposure is associated with cognitive delays in boys in our region. Our results provide additional evidence of the neurotoxic effect of low-level postnatal cadmium exposure among children, and support the hypothesis of differences between sexes in the neurotoxic effect of metals on children. - Highlights: • This study associates Cd exposure and neuropsychological development in children. • Cd exposure was associated with cognitive delay in boys, but not in girls. • Intellectual quotient of boys decreased two points for a doubling of urine Cd levels. • Verbal Comprehension and Perceptual Reasoning were the most affected domains in boys. • Results support the sex-related differences in the neurotoxicity of metals in children.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Modeling spatial effects of PM{sub 2.5} on term low birth weight in Los Angeles County

Air pollution epidemiological studies suggest that elevated exposure to fine particulate matter (PM{sub 2.5}) is associated with higher prevalence of term low birth weight (TLBW). Previous studies have generally assumed the exposure–response of PM{sub 2.5} on TLBW to be the same throughout a large geographical area. Health effects related to PM{sub 2.5} exposures, however, may not be uniformly distributed spatially, creating a need for studies that explicitly investigate the spatial distribution of the exposure–response relationship between individual-level exposure to PM{sub 2.5} and TLBW. Here, we examine the overall and spatially varying exposure–response relationship between PM{sub 2.5} and TLBW throughout urban Los Angeles (LA) County, California. We estimated PM{sub 2.5} from a combination of land use regression (LUR), aerosol optical depth from remote sensing, and atmospheric modeling techniques. Exposures were assigned to LA County individual pregnancies identified from electronic birth certificates between the years 1995-2006 (N=1,359,284) provided by the California Department of Public Health. We used a single pollutant multivariate logistic regression model, with multilevel spatially structured and unstructured random effects set in a Bayesian framework to estimate global and spatially varying pollutant effects on TLBW at the census tract level. Overall, increased PM{sub 2.5} level was associated with higher prevalence of TLBW county-wide. The spatial random effects model, however, demonstrated that the exposure–response for PM{sub 2.5} and TLBW was not uniform across urban LA County. Rather, the magnitude and certainty of the exposure–response estimates for PM{sub 2.5} on log odds of TLBW were greatest in the urban core of Central and Southern LA County census tracts. These results suggest that the effects may be spatially patterned, and that simply estimating global pollutant effects obscures disparities suggested by spatial patterns of effects. Studies that incorporate spatial multilevel modeling with random coefficients allow us to identify areas where air pollutant effects on adverse birth outcomes may be most severe and policies to further reduce air pollution might be most effective. - Highlights: • We model the spatial dependency of PM{sub 2.5} effects on term low birth weight (TLBW). • PM{sub 2.5} effects on TLBW are shown to vary spatially across urban LA County. • Modeling spatial dependency of PM{sub 2.5} health effects may identify effect 'hotspots'. • Birth outcomes studies should consider the spatial dependency of PM{sub 2.5} effects.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Circulating levels of perfluoroalkyl substances are associated with dietary patterns – A cross sectional study in elderly Swedish men and women

Background: In our daily life, we are exposed to perfluoroalkyl substances (PFAS) with possible health implications. The main exposure route for these substances is diet but comparative studies on how dietary habits influence exposure are lacking. Objectives: To examine the relations between blood levels of PFAS and adherence to three predefined dietary patterns (a WHO recommended diet, a Mediterranean-like diet, and a Low-Carbohydrate High-Protein (LCHP) diet) in an elderly Swedish population. Methods: Dietary data from 7-day food records and serum concentrations of PFAS were obtained from a 70-year-old Swedish population (n=844), the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The Healthy Diet Indicator score (based on WHO recommendations), the Mediterranean Diet Score and LCHP score were used to assess adherence. Multivariate linear regression was used to assess the associations between eight major PFAS and adherence to each dietary pattern. Results: The WHO recommended diet was positively associated with perfluorohexane sulfonic acid (PFHxS). The LCHP diet was positively related to four out of eight PFAS; namely, perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). The Mediterranean-like diet was positively associated with most PFAS; namely perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), PFHxS, PFNA, PFDA, and PFUnDA. Conclusions: All dietary patterns were positively associated with blood levels of PFAS. The highest body burden of PFAS was found in individuals with high adherence to a Mediterranean-like diet, whilst individuals who more closely followed the officially recommended diet displayed a lower body burden of these compounds. - Highlights: • Perfluoroalkyl substances (PFAS) quantified in blood of 70-y-old Swedish subjects. • Adherence to predefined dietary patterns was associated with circulating PFAS. • A Mediterranean-like diet was positively associated with most circulating PFAS. • A low-carbohydrate high-protein diet was positively related to some PFAS in blood. • A WHO-recommended diet was only related to higher circulating levels of PFHxS.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney injury in children.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Time-varying coefficient vector autoregressions model based on dynamic correlation with an application to crude oil and stock markets

This paper proposes a new time-varying coefficient vector autoregressions (VAR) model, in which the coefficient is a linear function of dynamic lagged correlation. The proposed model allows for flexibility in choices of dynamic correlation models (e.g. dynamic conditional correlation generalized autoregressive conditional heteroskedasticity (GARCH) models, Markov-switching GARCH models and multivariate stochastic volatility models), which indicates that it can describe many types of time-varying causal effects. Time-varying causal relations between West Texas Intermediate (WTI) crude oil and the US Standard and Poor’s 500 (S&P 500) stock markets are examined by the proposed model. The empirical results show that their causal relations evolve with time and display complex characters. Both positive and negative causal effects of the WTI on the S&P 500 in the subperiods have been found and confirmed by the traditional VAR models. Similar results have been obtained in the causal effects of S&P 500 on WTI. In addition, the proposed model outperforms the traditional VAR model.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Elemental content of the placenta: A comparison between two high-risk obstetrical populations, adult women carrying multiples and adolescents carrying singletons

Background: The placenta is responsible for the exchange of nutrients and for preventing harmful compounds from entering the fetal circulation. With increasing industrialization, exposures to commercial and toxic metals become a concern for both pregnant women and those planning a pregnancy. The understanding of transport mechanisms and pharmacokinetics for most inorganic elements is incomplete and limited to normal term deliveries. Objectives: To obtain novel data on 46 inorganic elements in placentae from two high-risk obstetric populations, women carrying multiples and adolescents carrying singletons, evaluating differences, if present, and identifying predictors of placental content. Methods: Placental tissue was collected from adolescents carrying singletons and adults carrying multiples. Elemental content was analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). Multivariate regression and factor analyses were used. Results: With the exception of Au and Pt, almost all placentae contained quantifiable concentrations of each element analyzed. All placentae contained the essential elements Ca, Fe, Mg, Se and Zn, which clustered together onto the same factor. Most elements were higher in placentae from women carrying multiples. Differences in placental content disappeared after adjusting for maternal age. Rare earth elements (REEs) clustered together and remained higher in the multiples even after adjusting for maternal age. Conclusion: Human placentae contain a wide range of elements, including REEs. Ranges differed considerably between cohorts. Elements with similar chemical properties, like REEs or nutritionally essential elements, clustered together. Maternal age, and therefore longer environmental exposure, was significantly associated with elevated element concentrations in the placenta. Placental concentrations of several metals that are known to be nutritionally essential (e.g., Fe, Ca, Mg, and Zn) did not differ significantly between cohorts, suggesting tight regulation, whereas concentrations of environmental contaminants differed significantly between groups, even after adjusting for maternal age. - Highlights: • Levels of 46 elements were measured in placentae from two high-risk cohorts. • Almost all placentae contained traces of the 46 elements, including REEs. • Maternal age was significantly associated with concentrations in the placenta. • Elements with similar properties and roles clustered together.

54 ENVIRONMENTAL SCIENCES↗