Grantee Research Project Results
2010 Progress Report: Arsenic and Maternal and Infant Immune Function
EPA Grant Number: R834599Center: Children's Environmental Health and Disease Prevention Center - Dartmouth College
Center Director: Karagas, Margaret Rita
Title: Arsenic and Maternal and Infant Immune Function
Investigators: Karagas, Margaret Rita , Korrick, Susan A. , Moeschler, John B. , Enelow, Richard I. , Robbins, David J , Folt, Carol L. , Cottingham, Kathryn L. , Onega, Tracy L. , Gui, Jiang , Rees, Judy , Punshon, Tracy , Shi, Xun
Current Investigators: Karagas, Margaret Rita , Purvis, Lisa A. , Korrick, Susan A. , Moeschler, John B. , Enelow, Richard I. , Robbins, David J , Folt, Carol L. , Cottingham, Kathryn L. , Onega, Tracy L. , Gui, Jiang , Rees, Judy , Madan, Juliette , Miller, Stephanie , Punshon, Tracy , Shi, Xun
Institution: University of Miami , Dartmouth Medical School , Dartmouth College
Current Institution: Dartmouth College , Dartmouth Medical School , University of Miami
EPA Project Officer: Callan, Richard
Project Period: February 15, 2010 through February 14, 2013 (Extended to February 14, 2014)
Project Period Covered by this Report: February 15, 2010 through February 14,2011
Project Amount: $1,079,663
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
There are four projects being conducted at the Children's Environmental Health and Disease Prevention Center. The objectives of these projects are described below.
Project 1: Arsenic and Maternal and Infant Immune Function
The primary objectives of the research are to: 1) test the hypothesis that prenatal and early life exposure to arsenic (i.e., via drinking water and food) is associated with an increased risk of infant infections during the first year of life; and 2) test the hypothesis that arsenic (As) exposure is related to an increased risk of maternal infection during pregnancy. A secondary/exploratory objective is to assess whether individual variation in arsenic (As) metabolism (based on maternal urinary As metabolites or As metabolism genes e.g., GSTO1, GSTO2, AS3T, PNP) and other factors (e.g., cigarette smoking, folate intake or polymorphisms in one carbon metabolism genes) modify the effects of arsenic on infant or maternal infection.
Project 2: Food Borne Exposure to Arsenic During the First Year of Life
We are studying dietary exposure to metals, especially arsenic, during pregnancy and the first year of life. Recent data suggest that both drinking water and food, especially rice and seafood, contribute to arsenic exposure. This is particularly true for infants and toddlers who often consume many different forms of rice during their transition to solid foods. Our goal is to understand how feeding and weaning habits influence arsenic exposure by measuring arsenic content of infant foods (breast milk, formula, cereals, and jarred foods) and quantifying dietary patterns via food frequency questionnaires and dietary records.
Project 3: An Integrated Geospatial and Epidemiological Study of Associations Between Birth Defects and Arsenic Exposure in New England
In this pilot project, our multidisciplinary team will: 1) establish a methodology integrating geospatial and epidemiological analyses to quantitatively and geographically monitor, characterize, and evaluate the associations between birth defects and arsenic exposure (i.e., inorganic arsenic) in New England; and 2) conduct a feasibility study for testing associations on an individual level. Epidemiologic studies indicate that birth defects relate to various environmental exposures and specifically suggest arsenic as a possible concern. Geospatial analyses in some regions have revealed considerable non-random spatial variation in the occurrence of birth defects, leading to the hypothesis that this may be due to spatial variation of environmental factors. The combination of geospatial and epidemiological analyses has the potential to create an economic, efficient, and effective procedure covering data preparation, spatial variation detection, case-control sampling, disease-environment relationship modeling, and finally risk mapping.
Project 4: Determining How Arsenic Modulates Hedgehog Signaling During Development
A number of limited studies have shown a statistically significant increase in birth defects of children exposed to arsenic (As) in utero. This number is probably an underestimate of the prevalence of As-induced birth defects, as the majority of early developmental abnormalities result in spontaneous abortion. Based on our unpublished results we hypothesize that As exerts some of its teratogenic effects through modulation of Sonic Hedgehog (Shh) signaling. This hypothesis is consistent with the pivotal role Shh plays in the development of numerous structures, including those that are consistently malformed in children exposed to As in utero. Our identification of As as a modulator of Shh signaling may be particularly relevant to human development, as humans are much more sensitive to modulation of Shh activity than various animal models. Interestingly, although As exhibits teratogenic activity in mice, the concentrations of As required to elicit these effects are higher than those that are relevant to human exposure. Thus, similar to the increased sensitivity of humans to Shh levels, it also has been argued that humans are more sensitive to the teratogenic effects of As. Here we propose to 1) determine the mechanism by which As modulates Shh signaling, and 2) begin to develop the reagents and protocols necessary to analyze human maternal and embryonic derived tissues for biomarkers of Shh activity. In future work, such reagents will be used to correlate in utero As exposure to modulation of Shh signaling, and ultimately to correlate this modulation of Shh signaling with various human developmental defects. This latter analysis of human samples will be particularly important because of the relative insensitivity of animal models to the in utero perturbation of Shh signaling.
There are separate progress reports for each of the four projects; see the progress reports for Grant Nos. R834599C001, R834599C002, R834599C003 and R834599C004.
Progress Summary:
Project 1:
This project extends the work of The New Hampshire Birth Cohort Study, an ongoing longitudinal study of women and infants who are residents of New Hampshire/Vermont and who obtain household water from wells that are a potential source of As exposure.
As part of Project 1, we are prospectively following infants enrolled in our cohort through: (1) interval interviews with the mothers at 4, 8 and 12 months of age; (2) screening infant pediatric records covering the first year of life; and 3) reviewing prenatal records for information on maternal infections and collecting data regarding infections on the post-partum questionnaire self-administered to women through the parent study.
Project 1 further collaborates with Pilot Project 2, Food Borne Exposure to Arsenic During the First Year of Life to obtain pilot feeding practices (e.g., breast or bottle feeding) and other dietary information and Pilot Project 4, entitled Determining How Arsenic Modulates Hedgehog Signaling During Development by providing placenta biopsies from our cohort. The additional protocols for Project 1 were approved by the Institutional Review Boards at Dartmouth College, Concord Hospital and the Environmental Protection Agency’s Human Subjects Review Official. The approval process was completed in June. In addition, we completed and submitted our EPA Quality Management Plan for all Center projects in February 2011.
While obtaining the necessary permissions to proceed with the research, we continued to refine the study protocols including the questionnaires for this aspect of the study (e.g., the 1 year interval interviews) and made necessay procedural modifications. The designed study forms and protocols integrate Project 1 and Pilot Project 2 objectives. To cost-effectively administer the interval interviews (by phone) and the mailed diet surveys for Pilot Project 2 at 12 months, we engaged the services of the University of New Hampshire (UNH) Survey Center. From September to December, we finalized contract details with the UNH Survey Center and completed the programming of the questionnaire for use with a Computer Assisted Telephone Inteviewing (CATI) instrument. This instrument tracks the data and progress of all phases of the 1 year follow-up activities for Project 1. The first subjects who have consented to the interval interviews turned 4 months old in October and we began the interview process.
Also in this reporting period, we enlisted the participation of one other prenatal clinic to bolster accrual, and refined our recruitment methods per recommendations of our Scientific Advisory Committee. Project 1 investigators have presented work related to the study at scientific conferences. and two manuscripts have been published. Two collborative publications with Pilot Project 2 currently are under review, and another is in preparation. We also submitted two collabortive grant applications to enhance the Center’s research (one in collaboration with Pilot Project 2).
Other preliminary work completed this first study year includes the development of data entry screens and data management tools and systems, and preliminary analysis of urinary arsenic metabolities in pregnant women in relation to diet and other factors. We continue to develop laboratory protocols for DNA extraction from placental tissue and meconium for our parent study.
Project 2:
To accomplish our primary aim of determining how infant consumption of breast milk and formula contributes to As exposure during the first 4 months of life, we have begun data collection on diet for infants at 4 months of age via telephone questionnaire (in coordination with Project 1). As of the end of this reporting period (February 2011), we have begun interviews with the parents and preliminary analyses of those data are under way. In addition, we have analyzed 11 common infant formulas at the Trace Elements Analysis Core at Dartmouth and will add to this database as we learn more about which formulas the infants in our study are eating.
Due to budgetary constraints, we have refocused secondary aim 1 (to begin evaluating how increased infant consumption of solid foods affects arsenic exposure for infants aged 4-12 months) to pilot test dietary assessment at 12 months. We are actively developing the instrument for this from existing tools, and expect to begin pilot testing it on 1-year-olds by early summer 2011. We anticipate beginning work on secondary aim 2 (to test the feasibility of measuring urinary metabolites of arsenic in infants at 4 months of age, and determine the relationships among urinary arsenic, arsenic ingestion estimated from food and water, and toenail arsenic levels) within the next reporting period.
Other related research conducted in this reporting period includes three preliminary studies that will help to inform this study. The results of these studies should be submitted for publication in peer-reviewed journals over the next few months. First, using data from case-control studies of adults, we evaluated associations between consumption of individual diet items and arsenic concentrations in toenail clippings for individuals with measured household tap water arsenic (Cottingham, et al., in preparation). Using the same dataset, we used general linear models to examine the associations between toenail arsenic and components of foods (e.g., proteins, lipids, vitamins and minerals), again taking into account the potentially confounding effects of variables such as sex, age, caloric intake, body mass index, smoking status, and water arsenic concentration. We also are completing work analyzing the associations between arsenic exposure via drinking water and diet (especially rice) and arsenic metabolites in the urine of pregnant women.
Project 3:
In the first several months we successfully acquired all the datasets as planned in the application for Aim 1. We went through the required IRB processes and proactively pursued the acquisition of data from various sources. The data we have acquired include:
• Birth defect data in the format of tabular records from the New Hampshire Birth Conditions Program (NHBCP);
• Data on all births in the format of tabular records from the New Hampshire Department of Human and Health Services (NH DHHS);
• LandScan data of population distribution from the Oak Ridge National Laboratory;
• Census data of demographics from the U.S Census;
• Arsenic exposure data from the USGS, containing the probabilities of water in bedrock wells exceeding 5 micrograms per liter; and
• Arsenic concentration values of 8,765 sampled wells in NH (both public and private wells) from the Dartmouth groundwater research program (Karagas).
We compiled these data into an integrated GIS database for quantitative spatial analysis. All the data layers have been cut to the spatial extent of New Hampshire and projected to the New Hampshire State Plane System for them to spatially match each other.
We then conducted an initial exploration of the data. We created GIS data layers of the birth defect records and all birth records at the town level. Using these two layers, we calculated a simple birth defect rate (number of birth defect babies over all births) for each town and created a map of it. Several data and scientific issues were identified through this exploration. For example, the data reveal that birth defects have strong association with the mother’s age, which confirms that age is a strong confounding factor in environmental health analysis of birth defects. We also find that there are quite a few cases in which one infant has multiple defects, or twins and triplets are involved, which should be given special considerations.
We then processed the data and sent them into the formal spatial statistical analysis to generate a risk map of birth defects based on existing cases. We first used identified unique infants, avoiding counting multiple defects on the same infant multiple times. We also exclude twins and triplets, which only account for a small proportion in the data, from analysis because there is no consensus on how to deal with them. To address the mother’s age factor, we divided the birth defect cases (infants) and all births into six age categories and analyzed each separately. We disaggregated the town level data (the birth defect cases and all birth data are only available to us at the town level) using a restricted and controlled randomization based on town boundaries and detailed demographic data generated through integrating the LandScan data and Census data. The disaggregated data were used to calculate the density of birth defect cases over the all-birth background. A Monte Carlo process was used to estimate the probability of the density at a location. The final risk map was created by integrating the probability maps created for individual age categories.
For Aim 2, we have been detailing the design of the epidemiologic part of this project by reviewing the details of the study design with various epidemiological experts regarding the best use of limited birth defects data to produce statistically significant and generalizable results. Specifically, we have been:
• Designing and preparing the collection kits for maternal and child buccal cell, fingernails, and drinking water samples.
• Developing the participant questionnaires.
• Developing and implementing a survey for subjects who decline participation (including reasons declined, demographics).
• Developing a study protocol and preparing an IRB application for the study.
Our participant survey is based on the Computer Aided Telephone Interview (CATI) Version 5 questionnaire that is used in the National Birth Defects Prevention Study, a Centers for Disease Control and Prevention (CDC) funded birth defects study. We have used this particular questionnaire because it already has been used for several years in the CDC study and has been thoroughly tested for reliability and validity. We are planning to add specific questions to the existing survey related to drinking water and arsenic exposures as well as to revise the daily food frequency section to be more specific to potential sources of arsenic in food. To date, we have obtained electronic versions of the CATI, informed consent, and biological sample collection kit fact sheets. In addition, the Project 3 team has discussed the use of saliva collection kits as opposed to the brush kit method for buccal cell collection. It has been decided that we will use the saliva collection method because of a much higher yield of DNA as compared to the check brush method. The Project 3 team also has reviewed the NBDPS survey in its entirety (85 pages) and revised it to be more specific to our needs for the proposed study.
Given the budget constraints that occurred in the first year of this project as well as the increase in cost for the saliva collection kits, it is likely that we will not be able to enlist as many maternal/child pairs as originally planned in New Hampshire. However, we will attempt to maximize enrollment in our study.
Expansion to Maine: We have continued communication with the state of Maine regarding this study and still plan to include this additional data source in our study by first obtaining Maine data to include in Aim 1 of our project. Further expansion to Maine, particularly for the epidemiological study, will be considered for the next grant.
Project 4:
We have discovered that As acts to activate HH signaling downstream of the GPCR Smoothened and upstream of the transcription factor GLI3. The ability of As to activate HH signaling also has directly led to our discovery that HH signaling plays a pivotal role in bladder cancer. A manuscript outlining this discovery has been submitted.
We now have optimized our ability to extract high quality RNA from human placenta samples. We also have optimized for Q-PCR Taqman probes to various relevant target genes.
Future Activities:
Project 1:
In the next year of support, we will continue to conduct the interval interviews (e.g., at 4, 8 and 12 months), continue medical record reviews, begin data and laboratory analyses and continue collaborations with Pilot Projects 2 and 4. We will continue to evaluate our new recruitment methods at the new study sites. We also will continue to conduct preliminary analyses, make scientific presentations and prepare manuscripts for publication. Additionally, we will continue to seek opportunity for building upon our project’s work and extend collaborations/interactions within our center, with centers at other institutions, agencies, organizations and the community.
Project 2:
We will continue to collect data on infant consumption of breast milk and formula as additional infants are enrolled in this study, and to analyze arsenic content of both breast milk and the formulas that the infants are consuming. A major goal for the next year is to quantify arsenic exposure from diet for these infants by combining diet information with information on the arsenic content of each diet item.
In addition, we will continue market basket studies of foods reported to be consumed by infants during the first 4 months of life. We anticipate that between now and December 2011, we will develop and implement the protocols for testing the feasibility of measuring urinary metabolites of arsenic in infants at 4 months of age to achieve secondary aim 2.
Project 3:
For Aim 1, we will perform sophisticated spatial analyses to detect the associations of birth outcomes, including birth defects and low birth weight births, to arsenic exposure through ground water. The outputs of those analyses are high-resolution raster maps with values at each pixel, i.e., they are not limited by subjectively defined polygons (e.g., towns or zip code). The analytic procedure was established in an earlier lung cancer study, but needs to be expanded and adjusted to adapt to the current study that features a narrower cohort and aggregated data.
For Aim 2, we will finish the preparation of the IRB protocol and all related study materials (fact sheets, biological sample collection kit instructions, etc.) for the study cohort in New Hampshire and submit it to the Dartmouth College Committee for the Protection of Human Subjects. Submission of a separate IRB application to the Maine Department of Health will occur following approval from the New Hampshire IRB. When the results from Aim 1 are available and the New Hampshire IRB protocol is approved, we will implement recruitment for the epidemiological study in New Hampshire.
Project 4:
We have a plan in place to convert expression data into a quantitative trait, which will subsequently be used to correlate with maternal As exposure.
Journal Articles: 29 Displayed | Download in RIS Format
Other center views: | All 76 publications | 29 publications in selected types | All 29 journal articles |
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Carey AM, Norton GJ, Deacon C, Scheckel KG, Lombi E, Punshon T, Guerinot ML, Lanzirotti A, Newville M, Choi Y, Price AH, Meharg AA. Phloem transport of arsenic species from flag leaf to grain during grain filling. New Phytologist 2011;192(1):87-98. |
R834599 (2012) R834599C002 (2012) |
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Carey A-M, Lombi E, Donner E, de Jonge MD, Punshon T, Jackson BP, Guerinot ML, Price AH, Meharg AA. A review of recent developments in the speciation and location of arsenic and selenium in rice grain. Analytical and Bioanalytical Chemistry 2012;402(10):3275-3286. |
R834599 (2012) R834599 (Final) R834599C002 (2012) R834599C002 (Final) |
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Cottingham KL, Karimi R, Gruber JF, Zens MS, Sayarath V, Folt CL, Punshon T, Morris JS, Karagas MR. Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water. Nutrition Journal 2013;12:149. |
R834599 (2011) R834599 (Final) R834599C001 (Final) R834599C002 (Final) R835442 (2014) R835442 (2015) R835442 (2016) |
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Davis MA, Mackenzie TA, Cottingham KL, Gilbert-Diamond D, Punshon T, Karagas MR. Rice consumption and urinary arsenic concentrations in U.S. children. Environmental Health Perspectives 2012;120(10):1418-1424. |
R834599 (2012) R834599 (Final) R834599C001 (2012) R834599C001 (Final) R834599C002 (2012) R834599C002 (Final) |
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Farzan SF, Karagas MR, Chen Y. In utero and early life arsenic exposure in relation to long-term health and disease. Toxicology and Applied Pharmacology 2013;272(2):384-390. |
R834599 (Final) R834599C001 (Final) |
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Farzan SF, Korrick S, Li Z, Enelow R, Gandolfi AJ, Madan J, Nadeau K, Karagas MR. In utero arsenic exposure and infant infection in a United States cohort: a prospective study. Environmental Research 2013;126:24-30. |
R834599 (Final) R834599C001 (Final) |
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Fei DL, Sanchez-Mejias A, Wang Z, Flaveny C, Long J, Singh S, Rodriguez-Blanco J, Tokhunts R, Giambelli C, Briegel KJ, Schulz WA, Gandolfi AJ, Karagas M, Zimmers TA, Jorda M, Bejarano P, Capobianco AJ, Robbins DJ. Hedgehog signaling regulates bladder cancer growth and tumorigenicity. Cancer Research 2012;72(17):4449-4458. |
R834599 (2012) R834599 (Final) R834599C004 (2012) R834599C004 (Final) |
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Fei DL, Koestler DC, Li Z, Giambelli C, Sanchez-Mejias A, Gosse JA, Marsit CJ, Karagas MR, Robbins DJ. Association between In Utero arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study. Environmental Health 2013;12:58 (8 pp.). |
R834599 (Final) R834599C001 (Final) R834599C004 (Final) R835442 (2014) R835442 (2015) R835442 (2016) |
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Gilbert-Diamond D, Cottingham KL, Gruber JF, Punshon T, Sayarath V, Gandolfi AJ, Baker ER, Jackson BP, Folt CL, Karagas MR. Rice consumption contributes to arsenic exposure in US women. Proceedings of the National Academy of Sciences of the United States of America 2011;108(51):20656-20660. |
R834599 (2011) R834599 (2012) R834599 (Final) R834599C001 (Final) R834599C002 (2012) R834599C002 (Final) |
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Gruber JF, Karagas MR, Gilbert-Diamond D, Bagley PJ, Zens MS, Sayarath V, Punshon T, Morris JS, Cottingham KL. Associations between toenail arsenic concentration and dietary factors in a New Hampshire population. Nutrition Journal 2012;11:45 (10 pp.). |
R834599 (2011) R834599 (2012) R834599 (Final) R834599C001 (2012) R834599C001 (Final) R834599C002 (2012) R834599C002 (Final) |
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Jackson BP, Taylor VF, Punshon T, Cottingham KL. Arsenic concentration and speciation in infant formulas and first foods. Pure and Applied Chemistry 2012;84(2):215-223. |
R834599 (2012) R834599 (Final) R834599C002 (2012) R834599C002 (Final) |
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Jackson BP, Taylor VF, Karagas MR, Punshon T, Cottingham KL. Arsenic, organic foods, and brown rice syrup. Environmental Health Perspectives 2012;120(5):623-626. |
R834599 (2011) R834599 (2012) R834599 (Final) R834599C001 (Final) R834599C002 (2012) R834599C002 (Final) |
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Karagas MR. Arsenic-related mortality in Bangladesh. The Lancet 2010;376(9737):213-214. |
R834599 (Final) R834599C001 (Final) |
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Karagas MR, Wasson JH. A World Wide Web-based survey of non-medical tattooing in the United States. Journal of the American Academy of Dermatology 2012;66(1):e13-e14. |
R834599 (2011) R834599 (Final) R834599C001 (Final) |
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Karagas MR, Choi AL, Oken E, Horvat M, Schoney R, Kamai E, Cowell W, Grandjean P, Korrick S. Evidence on the human health effects of low-level methylmercury exposure. Environmental Health Perspectives 2012;120(6):799-806. |
R834599 (2011) R834599 (2012) R834599 (Final) R834599C001 (2012) R834599C001 (Final) |
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Karagas MR, Andrew AS, Nelson HH, Li Z, Punshon T, Schned A, Marsit CJ, Morris JS, Moore JH, Tyler AL, Gilbert-Diamond D, Guerinot ML, Kelsey KT. SLC39A2 and FSIP1 polymorphisms as potential modifiers of arsenic-related bladder cancer. Human Genetics 2012;131(3):453-461. |
R834599 (2011) R834599 (Final) R834599C001 (Final) R834599C002 (Final) |
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Koestler DC, Christensen B, Karagas MR, Marsit CJ, Langevin SM, Kelsey KT, Wiencke JK, Houseman EA. Blood-based profiles of DNA methylation predict the underlying distribution of cell types: a validation analysis. Epigenetics 2013;8(8):816-826. |
R834599 (Final) R834599C001 (Final) |
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Koestler DC, Avissar-Whiting M, Houseman EA, Karagas MR, Marsit CJ. Differential DNA methylation in umbilical cord blood of infants exposed to low levels of arsenic in utero. Environmental Health Perspectives 2013;121(8):971-977. |
R834599 (2011) R834599 (Final) R834599C001 (Final) R835442 (2014) R835442 (2015) R835442 (2016) |
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Lesseur C, Gilbert-Diamond D, Andrew AS, Ekstrom RM, Li Z, Kelsey KT, Marsit CJ, Karagas MR. A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire. Toxicology Letters 2012;210(1):100-106. |
R834599 (2011) R834599 (Final) R834599C001 (Final) |
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Madan JC, Farzan SF, Hibberd PL, Karagas MR. Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Current Opinion in Pediatrics 2012;24(6):753-759. |
R834599 (2012) R834599 (Final) R834599C001 (2012) R834599C001 (Final) |
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Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, Moore JH, Guill MF, Morrison HG, Sogin ML, Hampton TH, Karagas MR, Palumbo PE, Foster JA, Hibberd PL, O'Toole GA. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. mBio 2012;3(4):e00251-12 (10 pp.). |
R834599 (2012) R834599 (Final) R834599C001 (2012) R834599C001 (Final) |
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Nadeau KC, Li Z, Farzan S, Koestler D, Robbins D, Fei DL, Malipatlolla M, Maecker H, Enelow R, Korrick S, Karagas MR. In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort. Clinical Immunology 2014;155(2):188-197. |
R834599 (2011) R835442 (2015) R835442 (2016) |
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Oken E, Choi AL, Karagas MR, Marien K, Rheinberger CM, Schoeny R, Sunderland E, Korrick S. Which fish should I eat? Perspectives influencing fish consumption choices. Environmental Health Perspectives 2012;120(6):790-798. |
R834599 (2011) R834599 (2012) R834599 (Final) R834599C001 (2012) R834599C001 (Final) |
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Punshon T, Tappero R, Ricachenevsky FK, Hirschi K, Nakata PA. Contrasting calcium localization and speciation in leaves of the Medicago truncatula mutant cod5 analyzed via synchrotron X-ray techniques. The Plant Journal 2013;76(4):627-633. |
R834599 (Final) R834599C002 (Final) |
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Punshon T, Ricachenevsky FK, Hindt MN, Socha AL, Zuber H. Methodological approaches for using synchrotron X-ray fluorescence (SXRF) imaging as a tool in ionomics: examples from Arabidopsis thaliana. Metallomics 2013;5(9):1133-1145. |
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Shi X, Miller S, Mwenda K, Onda A, Rees J, Onega T, Gui J, Karagas M, Demidenko E, Moeschler J. Mapping disease at an approximated individual level using aggregate data: a case study of mapping New Hampshire birth defects. International Journal of Environmental Research and Public Health 2013;10(9):4161-4174. |
R834599 (Final) R834599C001 (Final) R834599C003 (Final) |
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Sunderland EM, Amirbahman A, Burgess NM, Dalziel J, Harding G, Jones SH, Kamai E, Karagas MR, Shi X, Chen CY. Mercury sources and fate in the Gulf of Maine. Environmental Research 2012;119:27-41. |
R834599 (2011) R834599 (2012) R834599C001 (2012) |
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Wilhelm-Benartzi CS, Koestler DC, Karagas MR, Flanagan JM, Christensen BC, Kelsey KT, Marsit CJ, Houseman EA, Brown R. Review of processing and analysis methods for DNA methylation array data. British Journal of Cancer 2013;109(6):1394-1402. |
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Yang J, Punshon T, Guerinot ML, Hirschi KD. Plant calcium content: ready to remodel. Nutrients 2012;4(8):1120-1136. |
R834599 (2012) R834599C002 (2012) |
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Supplemental Keywords:
water, drinking water, ground water, exposure, risk, health effects, human health, vulnerability, sensitive populations, population, infants, children, susceptibility, metals, heavy metals, public policy, decision making, community-based, public good, environmental chemistry, biology, geography, epidemiology, immunology, analytical, surveys, measurement methods, Northeast, EPA Region 1, food processing, water safety, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Exposure, Environmental Chemistry, Biochemistry, Environmental Monitoring, Children's Health, Environmental Policy, Biology, Risk Assessment, birth defects, prenatal exposure, drinking water, perinatal exposure, children's vulnerablity, biological markers, arsenic exposure, dietary exposure, growth & development, developmental disordersRelevant Websites:
http://www.dartmouth.edu/~childrenshealth/index.html Exit
Progress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834599C001 Arsenic and Maternal and Infant Immune Function
R834599C002 Food Borne Exposure to Arsenic During the First Year of Life
R834599C003 An Integrated Geospatial and Epidemiological Study of Associations Between Birth Defects and Arsenic Exposure in New England
R834599C004 Determining How Arsenic (As) Modulates Sonic Hedgehog (Shh) Signaling During Development
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.