Grantee Research Project Results
2006 Progress Report: Center for Childhood Neurotoxicology and Assessment
EPA Grant Number: R829391Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Center for Childhood Neurotoxicology and Assessment
Investigators: Lambert, George H.
Current Investigators: Lambert, George H. , Wagner, George , Wilson, Daniel , Polunas, Marianne , Halladay, Alycia , DiCicco-Bloom, Emanuel , Burke, Kelly , Davidovics, Zev , Rossman, Ian , Ruehl, Kenneth R
Institution: University of Medicine and Dentistry of New Jersey
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2001 through October 31, 2006 (Extended to October 31, 2008)
Project Period Covered by this Report: November 1, 2005 through October 31, 2006
Project Amount: $6,751,466
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The unifying theme of the Center for Childhood Neurotoxicology and Assessment is to determine the influence of exposure to neurotoxicants on child neurological health and development, with autism and related learning disabilities as a focus. The objectives of the Center are to detect, understand, and prevent environmental health problems as they relate to children. These objectives are achieved by facilitating interdisciplinary research, enhancing community and advocacy group involvement, and disseminating results to the public through publications, conferences, and community outreach.
The multidisciplinary research of the Center is based on three main project areas. The Basic Sciences Projects examine facets of brain development, beginning with neurogenesis and proceeding through to behavior in the intact animal. The Clinical Sciences Projects are interactive with community groups representing children with learning disabilities and their families, with particular emphasis on autism. These projects explore the linkage between environmental neurotoxicants, clinical course of autism, regional brain growth, and a possible new gene-environment interaction with autism. The Exposure Assessment and Intervention Project (EAIP) will characterize the personal, residential, and general community of exposure of children selected by the Clinical Sciences Projects. The EAIP then will determine the need for interventions to reduce neurotoxicant exposure among learning-disabled children and assess the impact of such interventions. The Exposure Assessment Facility Core will provide innovative video techniques to assess the relationship between the behavior of the child with autism and his/her potential to contact with neurotoxicants. The overall mission of the Center is to improve environmental and public health of children through research, assessment, treatment, and outreach.
The objectives of the Administrative Core are to: (1) coordinate the individual studies so they are interactive; (2) recruit additional faculty whose research greatly compliments the five core projects, including supporting the Center’s new research faculty in environmental health; (3) assure collaborative relationships with the autism community of New Jersey and other states; (4) reach out to the federal government in various ways to educate and coordinate efforts regarding children and environmental health, particularly children with neurobehavioral issues; and (5) submit Center-related grants to the National Institute of Environmental Health Sciences (NIEHS).
Progress Summary:
The Center has flourished with exciting results that have led to clinically relevant findings regarding autism, gene environment interaction, and developing potential therapeutic/preventive measures through development and validation of neuroprotective agents. This research output is being developed and focused through the collaborative Translational Research Group that has been developed within the Center with basic and clinical scientists and key additional research faculty that have joined the Center and the Translational Research Group.
This Group and the Center consist of a core of multidisciplinary researchers and focus on improving the health of children with autism in at least ameliorating the clinical course of autism but eventually decreasing the incidence of autism. The research has begun to elucidate not only neurodevelopmental issues in children with autism but also will expand the knowledge base of neurodevelopmental and toxicological sciences in humans and animals.
Center’s Research Focus – Following the Direction of the Autism Research Findings
The Center’s main focus continues to be autism and gene environment interaction. The major findings of the Center are focused on the gene environment interaction, the apparent increased susceptibility of the child with autism to oxidative stress (see the 2006 Annual Report for R829391C005), and developing intervention strategies to provide increased antioxidative capacity to the child based on our animal models and the development of new knockout mice that mimic the human condition (see the 2006 Annual Report for R829391C005). As will be seen, this area holds great promise for understanding and hopefully prevention of autism and is the overriding focus of autism research in the future. This does not exclude related autism and environmental research.
In regards to current environmental chemical levels in the children with autism, our preliminary research is revealing that the child with autism does not have markedly exaggerated levels of environmental chemicals in their body, nor does the child with regression have markedly increased levels of at least the heavy metals. These data are from the first 50 children and may change as we finish recruiting the entire cohort of 100 children. Also, as some investigators have suggested, the children’s environmental levels may not be exaggerated greatly and may not be higher than the control population. Final determination of that will await completion of the cohort and comparison to statewide and national data sets such as the National Health and Nutrition Examination Survey (NHANES).
One-third of the homes, however, do have areas of environmental concern. We have demonstrated that with individually developed intervention strategies, the home levels of a wide variety of home environmental chemicals can be reduced remarkably. What we have learned is that the parents in our study have little information on how to reduce the amounts of environmental chemicals in the home and which interventional strategies are the most effective. The parents are very concerned and somewhat aggravated that they were not made aware of this information years before; this is clearly a public health need.
Other Known Autism Related Research – Relevant Output and Outcome of the Center
The presence of the Center has drawn other research collaboration into the area of children’s environmental health. These areas have included clinical studies with phthalates in newborns, polychlorinated biphenyl (PCB) exposure to human health and cytochrome P450 function, and the pharmacokinetic-pharmacodynamic (PKPD) properties of perchlorate. The outcome of at least one study is impacting how humans are exposed to plasticizers in hospitals. The phthalate study is being used in many hospital settings as a reason to change the type and manufacturing of plastic devices used in the hospital setting to no-phthalate plastics. The Center is entering into research agreements with selective manufacturers to develop new manufacturing processes of hospital plastic equipment and monitor plasticizer exposures. Several researchers are working to establish a linkage between phthalates and neurodevelopment, and the Center has entered an agreement with the Danish Institute of Technology to study phthalate gene interaction in children with asthma in Scandinavian countries.
This report presents the Administrative Core and overall Center activities; progress on each of the five projects is presented in the individual 2006 Annual Reports for R829391C001 through R829391C005.
Administrative Core
Center Membership. We have expanded the Center membership with additional faculty with special interests that complement current and future Center activities. The new faculty includes Dr. Peter Stein and his co-investigator Dr. Terry Sholz, who have a long history of National Institutes of Health (NIH) studies of human oxidative stress in the perinatal period and developmental outcome of the pregnancy and the child; Dr. Arnold Levine, who studies P53 and related genes; and Dr. Walter Zahorodny who is the principal investigator on the University of Medicine and Dentistry of New Jersey (UMDNJ) and Centers for Disease Control and Prevention health tracking of autism grant. Dr. Oleg Mirochnitchenko, who has great expertise in animal models and oxidative stress, will help characterize the new oxidative stress knockout mouse.
Center Research Meetings. Center meetings include weekly translational research meetings, weekly clinical research meetings, semiannual intramural director’s meetings, and the annual External Advisory Committee meeting. In addition, the Center has selectively invited guest speakers just for the Center’s core research group and the Center also co-sponsors several monthly research seminars.
A most productive and exciting meeting is the weekly translational research meeting. This meeting is held at the Center but on occasion is held by the Center faculty at the Newark Medical School of UMDNJ (Dr. Ming as host) and the Stratford, New Jersey, campus of the UMDNJ School of Osteopathic Medicine (Dr. Stein as host). The meeting is well attended primarily by the neurogenetics investigators, the oxidative stress groups, the pediatric environmental toxicology groups, and the animal pharmacology/animal modeling groups of Drs. Wagner and Ming. These are held weekly and focus on oxidative stress, preventive antioxidant therapies, animal modeling, and development of critical knockout mice. The synergistic, interactive, and cooperative atmosphere of this meeting is truly remarkable and exciting to all. This is demonstrated by the fact that many of the faculty travel several hours each from their laboratories to attend each meeting. One week per month there is a journal club based on neurogenetics and autism and oxidative stress. This also is well attended by faculty and graduate students.
The clinical studies groups meet weekly to discuss subject recruitment, subject tracking through studies, home intervention, retesting of subjects and homes, and family communications.
The intramural advisory group meets two or three times per year. This group has consisted of Drs. Lambert, Reuhl, and Lioy. Because the major focus of the research is expanding to encompass oxidative stress, this advisory group is being changed to include animal modelers and neurogenetics faculty.
The External Advisory Committee last met May 2004 at UMDNJ. This year, because of the need to competitively resubmit the Center application in response to the new Request for Applications (RFA), the External Advisory Committee will meet in September to mark the Center’s progress, advise on the resubmission strategy, and comment on P50 grants that will be submitted in mid-October. Because of the focus on animal modeling, stress, and clinical studies, Dr. Susan Schantz from the University of Illinois and the Director of the Friends Children’s Environmental Health Center has been added to the advisory group.
Center’s Outreach to the Autism Community. The Center and its investigators have become integrally involved with the autism community in various ways. The Center members and especially Dr. Lambert present information about the Center and the Center’s research and discuss the interaction between environmental chemicals and children, especially children with autism, on a regular basis to hospital-based families with autism and autism support advocacy groups such as The New Jersey Center for Outreach and Services for the Autism Community (COSAC), National Alliance for Autism Research (NAAR), and the Autism Society of America (ASA). The Center works with NAAR to raise funds for research and has won several awards from NAAR for its stellar fundraising. The attendance of the meetings where Center members present autism and environment issues is large: 1,450 parents and health care professionals attended this year’s COSAC annual meeting, 200 parents attended the NAAR Tri-State Support and Research Group meeting, and the ASA annual research meeting held in Indianapolis, Indiana, was attended by more than 600 parents and health care professionals. This year, Dr. Lambert talked to more than 3,000 parents about environmental pediatric health and autism. The Center has become an important part of the autism community in New Jersey and is very interactive with the national and the greater mental retardation community.
Center Outreach to the Scientific Community. The Center has published 25 papers this year and many abstracts. The Center members participated in the Children Centers’ Symposium held at the Meeting of the International Society of Environmental Epidemiology and other scientific meetings. Dr Lambert served on the National Academy of Sciences Committee on the Health Effects of Perchlorate with the findings published in January 2005. Dr Lambert currently serves on the Science Advisory Board (SAB) of the U.S. Environmental Protection Agency (EPA) and as the liaison from the SAB to the Board of Scientific Counselors (BOSC) of EPA’s Office of Research and Development. Dr. DiCicco-Bloom is a member of the scientific board of NAAR.
Center members, Drs. Johnson (neurogenetics), Ming (oxidative stress), and DiCicco-Bloom (neurogenesis) have received outside funding for their autism work of more than $1 million of direct costs this year from NIH and the New Jersey Governor’s Council on Autism. In addition, Dr. Lambert has received extramural funding to host an annual science and autism day just before the annual COSAC conference, which is the largest conference on autism in the country. The purpose of this event is to bring together the scientific and parent community in the Northeast and Central Atlantic regions to develop synergistic, cooperative, and translational research in autism. The Center has applied for a National Institute of Environmental Health Sciences (NIEHS) training grant.
Center Outreach to Government – The Impact. The investigators believe that a function of the Center should be to provide scientific information to governments at all levels so that the government can make public health decisions based on the best available science. Dr. Lambert has advised governors and state legislators on mercury, perchlorate, and the National Children’s Study. In fact, New Jersey passed the most rigid mercury emissions laws in the country primarily based on health concerns of children.
Dr. Lambert with Congressmen Saxton and Holt from New Jersey organized a Congressional Children’s Environmental Health Caucus (CEHC). The purpose of the Caucus is to provide Congress, on an as-needed and regular basis, scientific information on children’s environmental health. To date, the CEHC is 1 year old, has 30 members of Congress from 10 states and the Virgin Islands and held its first semiannual briefing and Congressional luncheon in May at the Capitol. Several members of Congress, including Congressional leaders Saxton and Holt, attended the briefing, along with 75-100 legislative assistants. The topic was the National Children’s Study. This is a scientific advisory caucus and not a lobbying caucus. Twenty to 30 other members of Congress have expressed interest in the CEHC, and the ultimate goal is to gather more than 200 members from both sides of Congress.
In addition, Dr. Lambert was asked by Congresswoman Solis to participate in her perchlorate briefing on the Hill. Dr. Lambert presented the Center’s Research at the NIEHS Executive Council in Research Triangle Park, North Carolina, and the BOSC 5-year Review of Extramural Human Health Research Program.
Center Awards. The Center and its members received several awards and honors. The Center received an award from NAAR indicating the Center was the third most successful group in raising funds for NAAR research. Dr. Lambert received the “Health Care Professional of the Year Award” from the COSAC at their annual convention. Other awards this year were from CNBC and the Governor of New Jersey. Dr. Lambert was appointed to the New Jersey Governor’s Council on the Prevention of Mental Retardation and gave a keynote address at the Council’s 20-year celebration.
The paper published on phthalates in newborns was selected to be considered for the Charles C. Shepard Science Award for the best scientific paper from the CDC for the year 2004 and is up for the best paper of the year award from the CDC.
Center Outreach to Government and Industry. The Center is partnering with the National Institute of Childhood Health and Human Development and the National Multi-Center MRI Study of brain development in normal children. We will compare the MRI images from our children with autism to their MRI volumetric assessment of regional brain growth in the normal child. This will allow us to have a comparison between the child with and without autism. We have implemented their MRI methods and our MRIs have passed their review for quality assurance allowing us to compare to their database and visa versa.
In addition, the Center’s research has lead to the development of collaborative efforts between the Center and several biotechnology leaders. The Center has begun working with Siemens Corporation Research Institute’s imaging and bioinformatics groups (Intelligent Vision and Reasoning Division) in Princeton, New Jersey. The Corporation has begun to develop enhanced integrative models for volumetric and regional specific measurements and mylinations. These measurements will be used to analyze our volumetric and functional MRI. They already have begun their developmental research using our MRIs. In addition, the collaborative group has agreed to try to develop mass spectral analysis of specific environmental chemicals from the spectral MRI we will collect.
The Center entered into a confidentiality agreement to work with Becton Dickerson and Company in the development and clinical assessment and exposure of no-phthalate containing medical supplies that are used in and around hospitals. Finally, the Centers’ Translational Research Group has begun to talk with the pharmaceutical companies in an effort to develop joint efforts in the development of interventional/preventive strategies to ameliorate or prevent autism using our Translational Research Group and animal and clinical studies. Center investigators have an approved patent for this approach to therapeutic intervention in autism.
Summary
The Center’s research, activities, and function have provided a focus of synergistic and interactive research for the autism community, scientists, and governments. There already have been tangible outputs and altered outcomes as a result of the research. More details on the individual research are provided in the individual 2006 Annual Reports for R829391C001 through R829391C005.
Publications/Presentations: See the list of publications/presentations included in the individual 2006 Annual Reports for R829391C001 through R829391C005.
Future Activities:
The investigators did not report any future activities.
Journal Articles: 85 Displayed | Download in RIS Format
| Other center views: | All 122 publications | 86 publications in selected types | All 85 journal articles |
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Akland GG, Pellizzari ED, Hu Y, Roberds M, Rohrer CA, Leckie JO, Berry MR. Factors influencing total dietary exposures of young children. Journal of Exposure Analysis and Environmental Epidemiology 2000;10(6 Pt 2):710-722. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2005) |
Exit Exit |
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Ayotte P, Dewailly E, Lambert GH, Perkins SL, Poon R, Feeley M, Larochelle C, Pereg D. Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines. Environmental Health Perspectives 2005;113(10):1318-1324. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C005 (2006) |
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Benayed R, Gharani N, Rossman I, Mancuso V, Lazar G, Kamdar S, Bruse SE, Tischfield S, Smith BJ, Zimmerman RA, DiCicco-Bloom E, Brzustowicz LM, Millonig JH. Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus. American Journal of Human Genetics 2005;77(5):851-868. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C001 (2006) |
Exit Exit |
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Black K, Shalat SL, Freeman NCG, Jimenez M, Donnelly KC, Calvin JA. Children's mouthing and food-handling behavior in an agricultural community on the US/Mexico border. Journal of Exposure Analysis and Environmental Epidemiology 2005;15(3):244-251. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2004) R829391C004 (2005) |
Exit Exit |
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Brenz Verca MS, Bahi A, Boyer F, Wagner GC, Dreyer J-L. Distribution of α- and γ-synucleins in the adult rat brain and their modification by high-dose cocaine treatment. European Journal of Neuroscience 2003;18(7):1923-1938. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2005) |
Exit |
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Burke K, Cheng Y, Li B, Petrov A, Joshi P, Berman RF, Reuhl KR, DiCicco-Bloom E. Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E. NeuroToxicology 2006;27(6):970-981. |
R829391 (2006) R829391 (Final) R829388 (2006) R829388 (Final) R829388C005 (2005) R833292 (2009) R833292 (Final) |
Exit Exit Exit |
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Buyske S, Williams TA, Mars AE, Stenroos ES, Ming SX, Wang R, Sreenath M, Factura MF, Reddy C, Lambert GH, Johnson WG. Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism. BMC Genetics 2006;7(1):8 (9 pp.). |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Calafat AM, Needham LL, Silva MJ, Lambert G. Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit. Pediatrics 2004;113(5):e429-e434. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C005 (2006) |
Exit Exit |
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Carlson KM, Wagner GC. Effects of phencyclidine on schedule-controlled responding following neurotoxic lesions of the striatum. Life Sciences 2005;77(4):372-385. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C003 (2006) |
Exit Exit |
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Carmody DP, Dunn SM, Boddie-Willis AS, DeMarco JK, Lewis M. A quantitative measure of myelination development in infants, using MR images. Neuroradiology 2004;46(9):781-786. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C005 (2006) |
Exit |
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Carmody DP, Moreno R, Mars AE, Seshadri K, Lambert GH, Lewis M. Brief report: brain activation to social words in a sedated child with autism. Journal of Autism and Developmental Disorders 2007;37(7):1381-1385. |
R829391 (2006) R829391 (Final) |
Exit |
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Cheh MA, Millonig JH, Roselli LM, Ming X, Jacobsen E, Kamdar S, Wagner GC. En2 knockout mice display neurobehavioral and neurochemical alterations relevant to autism spectrum disorder. Brain Research 2006;1116(1):166-176. |
R829391 (2006) |
Exit Exit |
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Chen T-F, Zhang Y-L, Xu W-L, Li Z-Q, Hou B, Wang C-L, Fan M, Qian L-J, Zhou R-P, Zhang C-G. Prokaryotic expression, polyclonal antibody preparation, and sub-cellular localization analysis of Na+, K+-ATPase β2 subunit. Protein Expression and Purification 2004;37(1):47-52. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C002 (2006) |
Exit Exit |
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Chen Z-Y, Sun C, Reuhl K, Bergemann A, Henkemeyer M, Zhou R. Abnormal hippocampal axon bundling in EphB receptor mutant mice. Journal of Neuroscience 2004;24(10):2366-2374. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C002 (2005) |
Exit Exit |
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Davidovics Z, DiCicco-Bloom E. Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture. Journal of Neuroscience Research 2005;80(6):817-825. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C001 (2006) |
Exit |
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Falluel-Morel A, Sokolowski K, Sisti HM, Zhou X, Shors TJ, Dicicco-Bloom E. Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty. Journal of Neurochemistry 2007;103(5):1968-1981. |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Fitzgerald EF, Hwang SA, Lambert G, Gomez M, Tarbell A. PCB exposure and in vivo CYP1A2 activity among Native Americans. Environmental Health Perspectives 2005;113(3):272-277. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C005 (2006) |
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Freeman NCG, Jimenez M, Reed KJ, Gurunathan S, Edwards RD, Roy A, Adgate JL, Pellizzari ED, Quackenboss J, Sexton K, Lioy PJ. Quantitative analysis of children's microactivity patterns: the Minnesota Children's Pesticide Exposure Study. Journal of Exposure Analysis and Environmental Epidemiology 2001;11(6):501-509. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2005) |
Exit Exit Exit |
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Freeman NCG, Sheldon L, Jimenez M, Melnyk L, Pellizzari E, Berry M. Contribution of children's activities to lead contamination of food. Journal of Exposure Analysis and Environmental Epidemiology 2001;11(5):407-413. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2005) |
Exit Exit |
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Freeman NCG, Shalat SL, Black K, Jimenez M, Donnelly KC, Calvin A, Ramirez J. Seasonal pesticide use in a rural community on the U.S./Mexico border. Journal of Exposure Analysis and Environmental Epidemiology 2004;14(6):473-478. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2004) |
Exit Exit |
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Georgopoulos PG, Wang S-W, Vyas VM, Sun Q, Burke J, Vedantham R, McCurdy T, Ozkaynak H. A source-to-dose assessment of population exposures to fine PM and ozone in Philadelphia, PA, during a summer 1999 episode.Journal of Exposure Analysis and Environmental Epidemiology 2005;15(5):439-457. |
R829391 (Final) R826768 (Final) |
Exit Exit Exit |
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Georgopoulos PG, Lioy PJ. From a theoretical framework of human exposure and dose assessment to computational system implementation: the Modeling ENvironment for TOtal Risk Studies (MENTOR). Journal of Toxicology and Environmental Health, Part B-Critical Reviews 2006;9(6):457-483. |
R829391 (2006) R829391 (Final) R826768 (Final) |
Exit |
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Halladay AK, Kusnecov A, Michna L, Kita T, Hara C, Wagner GC. Relationship between methamphetamine-induced dopamine release, hyperthermia, self-injurious behaviour and long term dopamine depletion in BALB/c and C57BL/6 mice. Pharmacology & Toxicology 2003;93(1):33-41. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2004) |
Exit Exit |
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Halladay AK, Tessarollo L, Zhou R, Wagner GC. Neurochemical and behavioral deficits consequent to expression of a dominant negative EphA5 receptor. Molecular Brain Research 2004;123(1-2):104-111. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2005) |
Exit Exit |
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Halladay AK, Wagner GC, Sekowski A, Rothman RB, Baumann MH, Fisher H. Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan. Synapse 2006;59(5):277-289. |
R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2006) |
Exit |
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Halladay AK, Wilson DT, Wagner GC, Reuhl KR. Trimethyltin-induced alterations in behavior are linked to changes in PSA-NCAM expression. NeuroToxicology 2006;27(2):137-146. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C002 (2005) |
Exit Exit |
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Hsu PC, Lai TJ, Guo NW, Lambert GH, Leon Guo Y. Serum hormones in boys prenatally exposed to polychlorinated biphenyls and dibenzofurans. Journal of Toxicology and Environmental Health-Part A 2005;68(17-18):1447-1456. |
R829391 (2006) R829391 (Final) |
Exit |
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Hsu P-C, Huang W, Yao W-J, Wu M-H, Guo YL, Lambert GH. Sperm changes in men exposed to polychlorinated biphenyls and dibenzofurans. Journal of the American Medical Association 2003;289(22):2943-2944. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C005 (2004) |
Exit Exit |
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Hu Z, Yue X, Shi G, Yue Y, Crockett DP, Blair-Flynn J, Reuhl K, Tessarollo L, Zhou R. Corpus callosum deficiency in transgenic mice expressing a truncated ephrin-A receptor. Journal of Neuroscience 2003;23(34):10963-10970. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C002 (2005) |
Exit Exit |
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Hu Z, Cooper M, Crockett DP, Zhou R. Differentiation of the midbrain dopaminergic pathways during mouse development. Journal of Comparative Neurology 2004;476(3):301-311. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C002 (2006) |
Exit |
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Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, Lopez J, Butz A, Mosley A, Coates L, Lambert G, Potito PA, Brenner B, Rivera M, Romero H, Thompson B, Coronado G, Halstead S. Community-based participatory research:lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1463-1471. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C005 (2006) R826710 (Final) R831709 (2005) R831709 (2007) R831709 (Final) R831709C003 (2005) R831709C003 (2006) R831710 (2004) R831710 (2005) R831710 (Final) R831710C001 (2006) R831710C002 (2006) R831710C004 (2006) R831711 (2005) R831711 (2006) R831711 (2007) R831711 (Final) R831711C001 (2006) R831711C002 (2006) R831711C003 (2006) R832139 (2006) |
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Johnson SK, Carlson KM, Lee J, Burr LE, Wagner GC. Effects of nicotine on target biting and resident-intruder attack. Life Sciences 2003;73(3):311-317. |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Johnson WG, Scholl TO, Spychala JR, Buyske S, Stenroos ES, Chen X. Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery. American Journal of Clinical Nutrition 2005;81(3):664-668. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C005 (2006) |
Exit Exit |
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Kita T, Wagner GC, Nakashima T. Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption. Journal of Pharmacological Sciences 2003;92(3):178-195. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2005) |
Exit Exit |
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Lioy PJ, Freeman NC, Millette JR. Dust: a metric for use in residential and building exposure assessment and source characterization. Environmental Health Perspectives 2002;110(10):969-983. |
R829391 (2006) R829391 (Final) |
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Lioy PJ. Employing dynamical and chemical processes for contaminant mixtures outdoors to the indoor environment: the implications for total human exposure analysis and prevention. Journal of Exposure Science & Environmental Epidemiology 2006;16(3):207-224. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2006) |
Exit Exit |
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Martin JV, Nolan B, Wagner GC, Fisher H. Effects of dietary caffeine and alcohol on liver carbohydrate and fat metabolism in rats. Medical Science Monitor 2004;10(12):BR455-BR461. |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins, Leukotrienes and Essential Fatty Acids 2005;73(5):379-384. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2006) |
Exit Exit |
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Prozialeck WC, Grunwald GB, Dey PM, Reuhl KR, Parrish AR. Cadherins and NCAM as potential targets in metal toxicity. Toxicology and Applied Pharmacology 2002;182(3):255-265. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C002 (2004) |
Exit Exit |
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Shalat SL, Donnelly KC, Freeman NCG, Calvin JA, Ramesh S, Jimenez M, Black K, Coutinho C, Needham LL, Barr DB, Ramirez J. Nondietary ingestion of pesticides by children in an agricultural community on the U.S./Mexico border: preliminary results. Journal of Exposure Analysis and Environmental Epidemiology 2003;13(1):42-50. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C004 (2004) R829391C004 (2005) |
Exit Exit |
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Turan VK, Sanchez RI, Li JJ, Li SA, Reuhl KR, Thomas PE, Conney AH, Gallo MA, Kauffman FC, Mesia-Vela S. The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17β-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16α-hydroxyestradiol, and 4-hydroxyestrone. Journal of Endocrinology 2004;183(1):91-99. |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Wagner GC, Avena N, Kita T, Nakashima T, Fisher H, Halladay AK. Risperidone reduction of amphetamine-induced self-injurious behavior in mice. Neuropharmacology 2004;46(5):700-708. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C003 (2004) |
Exit |
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Wagner GC, Reuhl KR, Cheh M, McRae P, Halladay AK. A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate. Journal of Autism and Developmental Disorders 2006;36(6):779-793. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C002 (2006) R829391C003 (2004) |
Exit |
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Wagner GC, Reuhl KR, Ming X, Halladay AK. Behavioral and neurochemical sensitization to amphetamine following early postnatal administration of methylmercury (MeHg). NeuroToxicology 2007;28(1):59-66. |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Williams TA, Mars AE, Buyske SG, Stenroos ES, Wang R, Factura-Santiago MF, Lambert GH, Johnson WG. Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Archives of Pediatric Adolescent Medicine 2007;161(4):356-361. |
R829391 (2006) R829391 (Final) |
Exit |
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Wilson DT, Polunas MA, Zhou R, Halladay AK, Lowndes HE, Reuhl KR. Methylmercury alters Eph and ephrin expression during neuronal differentiation of P19 embryonal carcinoma cells. NeuroToxicology 2005;26(4):661-674. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391 (Final) R829391C002 (2005) |
Exit Exit |
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Yang C-Y, Yu M-L, Guo H-R, Lai T-J, Hsu C-C, Lambert G, Guo YL. The endocrine and reproductive function of the female Yucheng adolescents prenatally exposed to PCBs/PCDFs. Chemosphere 2005;61(3):355-360. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C005 (2006) |
Exit Exit |
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Ye X, Fitzgerald EF, Gomez MI, Lambert GH, Longnecker MP. The ratio of specific polychlorinated biphenyls as a surrogate biomarker of cytochrome P4501A2 activity--a pharmaco-metabonomic study in humans. Cancer Epidemiology Biomarkers & Prevention 2008;17(4):1013-1025. |
R829391 (2006) R829391 (Final) |
Exit Exit |
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Yu CH, Yiin LM, Lioy PJ. The bioaccessibility of lead (Pb) from vacuumed house dust on carpets in urban residences. Risk Analysis 2006;26(1):125-134. |
R829391 (2006) R829391 (Final) |
Exit |
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Zhang C, Meng F, Wang C, Guo H, Fan M, Liu S, Zhou R, He F. Identification of a novel alternative splicing form of human netrin-4 and analyzing the expression patterns in adult rat brain. Molecular Brain Research 2004;130(1-2):68-80. |
R829391 (2004) R829391 (2005) R829391 (2006) R829391C002 (2006) |
Exit Exit |
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Hassett AL, Radvanski DC, Vaschillo EG, Vaschillo B, Sigal LH, Karavidas MK, Buyske S, Lehrer PM. A pilot study of the efficacy of heart rate variability (HRV) biofeedback in patients with fibromyalgia. Applied Psychophysiology and Biofeedback 2007;32:1-10. |
R829391 (Final) |
Exit |
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Matise TC, Chen F, Chen W, De La Vega FM, Hansen M, He C, Hyland FC, Kennedy GC, Kong X, Murray SS, Ziegle JS. A second-generation combined linkage–physical map of the human genome. Genome Research 2007;17(12):1783-1786. |
R829391 (Final) |
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Gernez Y, Tirouvanziam R, Nguyen KD, Herzenberg LA, Krensky AM, Nadeau KC. Altered phosphorylated signal transducer and activator of transcription profile of CD4+ CD161+ T cells in asthma:modulation by allergic status and oral corticosteroids. Journal of Allergy and Clinical Immunology 2007;120(6):1441-1448. |
R829391 (Final) |
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Goodin S, Shen F, Shih WJ, Dave N, Kane MP, Medina P, Lambert GH, Aisner J, Gallo M, DiPaola RS. Clinical and biological activity of soy protein powder supplementation in healthy male volunteers. Cancer Epidemiology Biomarkers & Prevention 2007;16(4):829-833. |
R829391 (Final) |
Exit |
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Mitchell CS, Zhang J, Sigsgaard T, Jantunen M, Lioy PJ, Samson R, Karol MH. Current state of the science:health effects and indoor environmental quality. Environmental Health Perspectives 2007;115(6):958-964. |
R829391 (Final) |
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Golbe LI, Iorio GD, Markopoulou K, Athanassiadou A, Papapetropoulos S, Watts RL, Vance JM, Bonifati V, Williams TA, Spychala JR, Stenroos ES. Glutathione S‐transferase polymorphisms and onset age in α‐synuclein A53T mutant Parkinson's disease. American Journal of Medical Genetics Part B:Neuropsychiatric Genetics 2007;144(2):254-258. |
R829391 (Final) |
Exit |
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Yin K, Gribbin E, Emanuel S, Orndorff R, Walker J, Weese J, Fallahnejad M. Histochemical alterations in one lung ventilation. Journal of Surgical Research 2007;137(1):16-20. |
R829391 (Final) |
Exit |
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Karavidas MK, Lehrer PM, Vaschillo E, Vaschillo B, Marin H, Buyske S, Malinovsky I, Radvanski D, Hassett A. Preliminary results of an open label study of heart rate variability biofeedback for the treatment of major depression. Applied Psychophysiology and Biofeedback 2007;32:19-30. |
R829391 (Final) |
Exit |
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Ming X, Brimacombe M, Wagner GC. Prevalence of motor impairment in autism spectrum disorders. Brain and Development 2007;29(9):565-570. |
R829391 (Final) |
Exit |
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McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, Harrington R, Svartengren M, Han IK, Ohman-Strickland P, Chung KF. Respiratory effects of exposure to diesel traffic in persons with asthma. New England Journal of Medicine 2007;357(23):2348-2358. |
R829391 (Final) |
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Han IK, Duan X, Zhang L, Yang H, Rhoads GG, Wei F, Zhang J. 1-Hydroxypyrene concentrations in first morning voids and 24-h composite urine:intra-and inter-individual comparisons. Journal of Exposure Science & Environmental Epidemiology 2008;18(5):477-485. |
R829391 (Final) |
Exit |
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Pahuja M, Tran C, Wang H, Yin K. Alveolar macrophage suppression in sepsis is associated with high mobility group box 1 transmigration. Shock 2008;29(6):754-760. |
R829391 (Final) |
Exit |
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Mamiya PC, Hennesy Z, Zhou R, Wagner GC. Changes in attack behavior and activity in EphA5 knockout mice. Brain Research 2008;1205:91-99. |
R829391 (Final) |
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Connors SL, Levitt P, Matthews SG, Slotkin TA, Johnston MV, Kinney HC, Johnson WG, Dailey RM, Zimmerman AW. Fetal mechanisms in neurodevelopmental disorders. Pediatric Neurology 2008;38(3):163-176. |
R829391 (Final) |
Exit |
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Nadeau KC, Callejas A, Wong WB, Joh JW, Cohen HJ, Jeng MR. Idiopathic neutropenia of childhood is associated with Fas/FasL expression. Clinical Immunology 2008;129(3):438-447. |
R829391 (Final) |
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Yue G, Shi G, Azaro MA, Yang Q, Hu G, Luo M, Yin K, Nagele RG, Fine DH, Yang JM, Li H. Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression. BMC Genomics 2008;9:1-3. |
R829391 (Final) |
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Buyske S. Maternal genotype effects can alias case genotype effects in case–control studies. European Journal of Human Genetics 2008;16(7):784-785. |
R829391 (Final) |
Exit |
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Han JF, He XY, Herrington JS, White LA, Zhang JF, Hong JY. Metabolism of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) by human CYP1B1 genetic variants. Drug Metabolism and Disposition 2008;36(4):745-752. |
R829391 (Final) |
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Peter Stein T, Scholl TO, Schluter MD, Leskiw MJ, Chen X, Spur BW, Rodriguez A. Oxidative stress early in pregnancy and pregnancy outcome. Free Radical Research 2008;42(10):841-848. |
R829391 (Final) |
Exit |
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Spokas EG, Harshman S, Cohen GM, Jiang C, Levine JM, Rodriguez AR, Foglein J, Spur BW. Release of the lipid peroxidation marker 8‐epi‐prostaglandin F2α from isolated gill pavement cells. Environmental Toxicology and Chemistry 2008;27(7):1569-1575. |
R829391 (Final) |
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Hassett AL, Radvanski DC, Buyske S, Savage SV, Gara M, Escobar JI, Sigal LH. Role of psychiatric comorbidity in chronic Lyme disease. Arthritis Care & Research 2008;59(12):1742-1749. |
R829391 (Final) |
Exit |
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Fiedler N, Kipen H, Ohman-Strickland P, Zhang J, Weisel C, Laumbach R, Kelly-McNeil K, Olejeme K, Lioy P. Sensory and cognitive effects of acute exposure to hydrogen sulfide. Environmental Health Perspectives 2008;116(1):78-85. |
R829391 (Final) |
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Nekrasova T, Jobes ML, Ting JH, Wagner GC, Minden A. Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion. Developmental Biology 2008;322(1):95-108. |
R829391 (Final) |
Exit |
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Hassett AL, Li T, Buyske S, Savage SV, Gignac MA. The multi-faceted assessment of independence in patients with rheumatoid arthritis:preliminary validation from the ATTAIN study. Current Medical Research and Opinion 2008;24(5):1443-1453. |
R829391 (Final) |
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Hassett AL, Simonelli LE, Radvanski DC, Buyske S, Savage SV, Sigal LH. The relationship between affect balance style and clinical outcomes in fibromyalgia. Arthritis Care & Research:Official Journal of the American College of Rheumatology 2008;59(6):833-840. |
R829391 (Final) |
Exit |
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Ming X, Gordon E, Kang N, Wagner GC. Use of clonidine in children with autism spectrum disorders. Brain and Development 2008;30(7):454-460. |
R829391 (Final) |
Exit |
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Ju J, Nolan B, Cheh M, Bose M, Lin Y, Wagner GC, Yang CS. Voluntary exercise inhibits intestinal tumorigenesis in Apc Min/+ mice and azoxymethane/dextran sulfate sodium-treated mice. BMC Cancer 2008;8:1-8. |
R829391 (Final) |
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Nguyen KD, Fohner A, Booker JD, Dong C, Krensky AM, Nadeau KC. XCL1 enhances regulatory activities of CD4+ CD25highCD127low/− T cells in human allergic asthma. The Journal of Immunology 2008;181(8):5386-5395. |
R829391 (Final) |
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Buyske S. Comment on the article “Heterogeneous dysregulation of microRNAs across the autism spectrum” by Abu-Elneel et al. Neurogenetics 2009;10(2):167. |
R829391 (Final) |
Exit |
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Wratten NS, Memoli H, Huang Y, Dulencin AM, Matteson PG, Cornacchia MA, Azaro MA, Messenger J, Hayter JE, Bassett AS, Buyske S. Identification of a schizophrenia-associated functional noncoding variant in NOS1AP. American Journal of Psychiatry 2009;166(4):434-441. |
R829391 (Final) |
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Gramatges MM, Fani P, Nadeau K, Pereira S, Jeng MR. Neonatal alloimmune thrombocytopenia and neutropenia associated with maternal human leukocyte antigen antibodies. Pediatric Blood & Cancer 2009;53(1):97-99. |
R829391 (Final) |
Exit |
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Nguyen KD, Vanichsarn C, Fohner A, Nadeau KC. Selective deregulation in chemokine signaling pathways of CD4+ CD25hiCD127lo/− regulatory T cells in human allergic asthma. Journal of Allergy and Clinical Immunology 2009;123(4):933-939. |
R829391 (Final) |
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Ming X, Johnson WG, Stenroos ES, Mars A, Lambert GH, Buyske S. Genetic variant of glutathione peroxidase 1 in autism. Brain and Development 2010;32(2):105-109. |
R829391 (Final) |
Exit |
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Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, Bienfait K, Dicke A. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology 2009;72(10):886-892. |
R829391 (Final) |
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Buyske S, Yang G, Matise TC, Gordon D. When a case is not a case:effects of phenotype misclassification on power and sample size requirements for the transmission disequilibrium test with affected child trios. Human Heredity 2009;67(4):287-292.. |
R829391 (Final) |
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Supplemental Keywords:
biology, chemistry, children’s health, disease and cumulative effects, ecological risk assessment, environmental chemistry, health risk assessment, risk assessments, susceptibility/sensitive population/genetic susceptibility, toxicology, genetic susceptibility, assessment of exposure, assessment technology, autism, behavioral assessment, behavioral deficits, childhood learning, children, developmental disorders, developmental effects, environmental health hazard, environmental toxicant, exposure assessment, gene-environment interaction, neurodevelopmental, neurological development, neuropathological damage, neurotoxic, neurotoxicity, outreach and education, public health,, RFA, Scientific Discipline, Health, Toxicology, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Ecological Risk Assessment, Children's Health, genetic susceptability, Biology, childhood learning, neurotoxic, behavioral assessment, gene-environment interaction, developmental effects, children, neurotoxicity, neurodevelopmental, assessment of exposure, public health, residential populations, behavioral deficits, environmental health hazard, environmental toxicant, autism, outreach and education, assessment technology, developmental disorders, exposure assessment, neurological developmentProgress 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).
R829391C001 Neurotoxicant Effects on Cell Cycle Regulation of Neurogenesis
R829391C002 Adhesion and Repulsion Molecules in Developmental Neurotoxic Injury
R829391C003 Disruption of Ontogenic Development of Cognitive and Sensory Motor Skills
R829391C004 Exposure Assessment and Intervention Project (EAIP)
R829391C005 Clinical Sciences Project
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.