Grantee Research Project Results
Metal Mixtures and Children’s Health
EPA Grant Number: R831725Center: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Metal Mixtures and Children’s Health
Investigators: Hu, Howard
Current Investigators: Hu, Howard , Brain, Joseph D. , Wright, Robert , Adams, Jeff , Cohen, Amy , Schaider, Laurel , Weisskopf, Marc , Bellinger, David , Hatley, Earl , Wright, Rosalind , Peterson, Karen E. , Shine, James P. , Wessling-Resnick, Marianne , Molina, Ramon , Maher, Tim , Spengler, John D. , Schwartz, Joel , Backus, Ann
Institution: Harvard University
EPA Project Officer: Callan, Richard
Project Period: June 1, 2004 through May 31, 2009 (Extended to May 31, 2011)
Project Amount: $7,894,185
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
We have proposed to establish a Center for Children’s Environmental Health and Disease Prevention Research that addresses the concerns of a community living in the Tar Creek Superfund site of Oklahoma – an area highly contaminated by metals (lead, cadmium, iron, manganese, and others) in mining waste and populated by many residents of Native American descent.
Approach:
Our overall goal is to take a highly innovative and integrated approach to addressing a “real world” problem, i.e., the potential of the mixtures of metals that are present in “chat” (mining waste) to interact with each other in terms of exposure, absorption, dose, and adverse effects on the development of children. Our Center will pursue four Research Projects with the support of four Cores. Project 1 will be a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions. Project 2 will assess the utility of size fractionation and sequential extraction studies for characterizing chat, conduct a nested case-control study of the determinants of high versus low burdens of metals amongst children participating in Project 1, and produce standardized “homogenized chat” for Projects 3 and 4. Project 3 will investigate the expression of binding and transporter molecules for metal transport and the corresponding pharmacokinetics of metals from the lung and gut to the blood, CNS and other organs as they relate to pregnant rats and their weanlings. Project 4 will examine the effect of pre- and neo-natal exposure to metals on neurochemical changes and neurobehavioral outcomes in rats. The effect of simple mixtures of metals will be compared with the effect of “homogenized chat” in both Projects 3 and 4. The potential effect of stress from living near toxic waste will be explored in Project 1 and the potential modifying effect of stress on metals neurotoxicity will also be explored in Project 4. Our Administrative, Analytical Chemistry, and Biostatistics Cores will enable us to fully integrate and support our research, and our Community Outreach and Translation Core will utilize an innovative portfolio of outreach activities developed in conjunction with a broadly-based Community Advisory Board to develop awareness and influence behaviors and health practices in order to prevent adverse health effects in children from exposure to metals in mining waste.
Expected Results:
We expect to better understand (1) the interaction between toxic metals in terms of migration from sources; absorption from the respiratory and gastrointestinal tracts; and neurotoxicity in both experimental animals and children participating in our community-based epidemiologic study; (2) the potential modifying effect of stress on the toxicity of metals; (3) the major environmental and lifestyle determinants of high metal burdens amongst community residents; and (4) periods of vulnerability to metals toxicity during pregnancy. We will also expect that (5) the nutritional and lifestyle intervention we develop and test in a quasi-experimental design in Project 1 will result in significant lowering of toxic metals exposure. Finally, we expect that (6) the activities of our Community Outreach and Translation Core will result in a public that is better-informed and prepared to mitigate the toxic effects of metals.
Journal Articles: 45 Displayed | Download in RIS Format
| Other center views: | All 63 publications | 46 publications in selected types | All 45 journal articles |
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Afeiche M, Peterson KE, Sanchez BN, Schnaas L, Cantonwine D, Ettinger AS, Solano-Gonzalez M, Hernandez-Avila M, Hu H, Tellez-Rojo MM. Windows of lead exposure sensitivity, attained height, and body mass index at 48 months. The Journal of Pediatrics 2012;160(6):1044-1049. |
R831725 (Final) R834800 (2012) R834800 (2013) |
Exit |
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Arora M, Weuve J, Schwartz J, Wright RO. Association of environmental cadmium exposure with pediatric dental caries. Environmental Health Perspectives 2008;116(6):821-825. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C001 (2008) R831725C003 (2007) R831725C004 (2007) |
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Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. American Journal of Respiratory Cell and Molecular Biology 2006;34(3):330-337. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Cantonwine D, Meeker JD, Hu H, Sanchez BN, Lamadrid-Figueroa H, Mercado-Garcia A, Fortenberry GZ, Calafat AM, Tellez-Rojo MM. Bisphenol A exposure in Mexico City and risk of prematurity:a pilot nested case control study. Environmental Health 2010;9:62. |
R831725 (Final) R834800 (2011) R834800 (2012) |
Exit Exit Exit |
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Chou K, Wright RO. Phthalates in food and medical devices. Journal of Medical Toxicology 2006;2(3):126-135. |
R831725 (Final) |
Exit |
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Heilig EA, Thompson KJ, Molina RM, Ivanov AR, Brain JD, Wessling-Resnick M. Manganese and iron transport across pulmonary epithelium. American Journal of Physiology–Lung Cellular and Molecular Physiology 2006;290(6):L1247-L1259. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Heilig E, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats. American Journal of Physiology–Lung Cellular and Molecular Physiology 2005;288(5):L887-L893. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C004 (2007) |
Exit Exit |
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Hopkins MR, Ettinger AS, Hernandez-Avila M, Schwartz J, Tellez-Rojo MM, Lamadrid-Figueroa H, Bellinger D, Hu H, Wright RO. Variants in iron metabolism genes predict higher blood lead levels in young children. Environmental Health Perspectives 2008;116(9):1261-1266. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
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Hu H, Tellez-Rojo MM, Bellinger D, Smith D, Ettinger AS, Lamadrid-Figueroa H, Schwartz J, Schnaas L, Mercado-Garcia A, Hernandez-Avila M. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environmental Health Perspectives 2006;114(11):1730-1735. |
R831725 (2007) R831725 (2009) R831725 (Final) |
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Hu H, Shine J, Wright RO. The challenge posed to children’s health by mixtures of toxic waste: the Tar Creek Superfund Site as a case-study. Pediatric Clinics of North America 2007;54(1):155-175. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C004 (2007) |
Exit |
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Lanphear BP, Wright RO, Dietrich KN. Environmental neurotoxins. Pediatrics in Review 2005;26(6):191-198. |
R831725 (2009) R831725 (Final) R831725C001 (2005) R829389 (2003) R829389 (2004) R829389 (2005) R829389 (Final) |
Exit |
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Oken E, Wright RO, Kleinman KP, Bellinger D, Amarasiriwardena CJ, Hu H, Rich-Edwards JW, Gillman MW. Maternal fish consumption, hair mercury, and infant cognition in a U.S. cohort. Environmental Health Perspectives 2005;113(10):1376-1380. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2005) |
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Ortega Garcia JA, Carrizo Gallardo D, Ferris i Tortajada J, Garcia MM, Grimalt JO. Meconium and neurotoxicants: searching for a prenatal exposure timing. Archives of Disease in Childhood 2006;91(8):642-646. |
R831725 (2009) |
Exit |
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Ostrea Jr EM, Morales V, Ngoumgna E, Prescilla R, Tan E, Hernandez E, Ramirez GB, Cifra HL, Manlapaz ML. Prevalence of fetal exposure to environmental toxins as determined by meconium analysis. NeuroToxicology 2002;23(3):329-339. |
R831725 (2009) |
Exit Exit |
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Schaider LA, Senn DB, Brabander DJ, McCarthy KD, Shine JP. Characterization of zinc, lead, and cadmium in mine waste: implications for transport, exposure, and bioavailability. Environmental Science and Technology 2007;41(11):4164-4171. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C004 (2007) |
Exit |
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Surkan PJ, Schnaas L, Wright RJ, Tellez-Rojo MM, Lamadrid-Figueroa H, Hu H, Hernandez-Avila EM, Bellinger DC, Schwartz J, Perroni E, Wright RO. Maternal self-esteem, exposure to lead, and child neurodevelopment. NeuroToxicology 2008;29(2):278-285. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C001 (2008) R831725C003 (2007) R831725C004 (2007) |
Exit Exit |
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Tellez-Rojo MM, Bellinger DC, Arroyo-Quiroz C, Lamadrid-Figueroa H, Mercado-Garcia A, Schnaas-Arrieta L, Wright RO, Hernandez-Avila M, Hu H. Longitudinal associations between blood lead concentrations lower than 10 μg/dL and neurobehavioral development in environmentally exposed children in Mexico City. Pediatrics 2006;118(2):e323-e330. |
R831725 (2007) R831725 (2009) R831725 (Final) R835441 (2017) |
Exit |
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Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. Journal of Nutrition 2006;136(12):3010-3014. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Thompson K, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. The influence of high iron diet on rat lung manganese absorption. Toxicology and Applied Pharmacology 2006;210(1-2):17-23. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Thompson K, Molina RM, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. FASEB Journal 2007;21(1):223-230. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit |
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Thompson K, Molina RM, Donaghey T, Brain JD, Wessling-Resnick M. Iron absorption by Belgrade rat pups during lactation. American Journal of Physiology-Gastrointestinal and Liver Physiology 2007;293(3):G640-G644. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Turker G, Ergen K, Karakoc Y, Arisoy AE, Barutcu UB. Concentrations of toxic metals and trace elements in the meconium of newborns from an industrial city. Biology of the Neonate 2006;89(4):244-250. |
R831725 (2009) |
Exit |
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Wright RO, Amarasiriwardena C, Woolf AD, Jim R, Bellinger DC. Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site. NeuroToxicology 2006;27(2):210-216. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2005) |
Exit Exit |
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Wright RO, Baccarelli A. Metals and neurotoxicology. The Journal of Nutrition 2007;137(12):2809-2813. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C004 (2007) |
Exit Exit |
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Wright RO, Fields N. Therapeutics and toxicology. Current Opinion in Pediatrics 2008;20(2):171. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
Exit Exit |
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Wright RO. Neurotoxicology: what can context teach us? Journal of Pediatrics 2008;152(2):155-157. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
Exit Exit |
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Wright RO. New morbidities: new challenges. Current Opinion in Pediatrics 2009;21(2):220-221. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
Exit Exit |
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Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, Wright RO. Maternal blood manganese levels and infant birth weight. Epidemiology 2009;20(3):367-373. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
Exit |
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Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of iron transport. The Journal of Nutrition 2008;138(11):2284-2288. |
R831725 (Final) |
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Zota AR, Willis R, Jim R, Norris GA, Shine JP, Duvall RM, Schaider LA, Spengler JD. Impact of mine waste on airborne respirable particulates in northeastern Oklahoma, United States. Journal of the Air & Waste Management Association 2009;59(11):1347-1357. |
R831725 (Final) |
Exit |
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Pilsner R, Hu H, Ettinger A, Sanchez B, Wright R, Cantonwine D, Lazarus A, Lamadrid-Figueroa H, Mercado-García A, Téllez-Rojo MM, Hernández-Avila M. Influence of prenatal lead exposure on genomic methylation of cord blood DNA. Epidemiology 2009;20(6):S84. |
R831725 (Final) |
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Ettinger AS, Zota AR, Amarasiriwardena CJ, Hopkins MR, Schwartz J, Hu H, Wright RO. Maternal arsenic exposure and impaired glucose tolerance during pregnancy. Environmental Health Perspectives 2009;117(7):1059-1064. |
R831725 (Final) |
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Deb S, Johnson EE, Robalinho-Teixeira RL, Wessling-Resnick M. Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction. Biometals 2009;22:855-862. |
R831725 (Final) |
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Sánchez BN, Hu H, Litman HJ, Téllez-Rojo MM. Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants. Environmental Health Perspectives 201;119(3):409-415. |
R831725 (Final) |
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Cantonwine D, Hu H, Sánchez BN, Lamadrid-Figueroa H, Smith D, Ettinger AS, Mercado-García A, Hernández-Avila M, Wright RO, Téllez-Rojo MM. Critical windows of fetal lead exposure:adverse impacts on length of gestation and risk of premature delivery. Journal of Occupational and Environmental Medicine 2010;52(11):1106-1111. |
R831725 (Final) |
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Cantonwine D, Hu H, Téllez-Rojo MM, Sánchez BN, Lamadrid-Figueroa H, Ettinger AS, Mercado-García A, Hernández-Avila M, Wright RO. HFE gene variants modify the association between maternal lead burden and infant birthweight:a prospective birth cohort study in Mexico City, Mexico. Environmental Health 2010;9:1-9. |
R831725 (Final) |
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Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annual Review of Nutrition 2010;30(1):105-122. |
R831725 (Final) |
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Pilsner JR, Hu H, Wright RO, Kordas K, Ettinger AS, Sanchez BN, Cantonwine D, Lazarus AL, Cantoral A, Schnaas L, Tellez-Rojo MM. Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City. The American Journal of Clinical Nutrition 2010;92(1):226-234. |
R831725 (Final) |
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Molina RM, Phattanarudee S, Kim J, Thompson K, Wessling-Resnick M, Maher TJ, Brain JD. Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring. Neurotoxicology 2011;32(4):413-422. |
R831725 (Final) |
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Thompson KJ, Molina RM, Donaghey T, Savaliya S, Schwob JE, Brain JD. Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia. Toxicological Sciences 2011;120(1):163-172. |
R831725 (Final) |
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Zota AR, Schaider LA, Ettinger AS, Wright RO, Shine JP, Spengler JD. Metal sources and exposures in the homes of young children living near a mining-impacted Superfund site. Journal of Exposure Science & Environmental Epidemiology 2011;21(5):495-505. |
R831725 (Final) |
not available |
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Adamkiewicz G, Zota AR, Fabian MP, Chahine T, Julien R, Spengler JD, Levy JI. Moving environmental justice indoors:understanding structural influences on residential exposure patterns in low-income communities. American Journal of Public Health 2011;101(S1):S238-245. |
R831725 (Final) |
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Afeiche M, Peterson KE, Sánchez BN, Cantonwine D, Lamadrid-Figueroa H, Schnaas L, Ettinger AS, Hernández-Avila M, Hu H, Téllez-Rojo MM. Prenatal lead exposure and weight of 0-to 5-year-old children in Mexico City. Environmental Health Perspectives 2011;119(10):1436-1441. |
R831725 (Final) |
not available |
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Sánchez BN, Kang S, Mukherjee B. A latent variable approach to study gene–environment interactions in the presence of multiple correlated exposures. Biometrics 2012;68(2):466-476. |
R831725 (Final) |
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Zhang A, Hu H, Sánchez BN, Ettinger AS, Park SK, Cantonwine D, Schnaas L, Wright RO, Lamadrid-Figueroa H, Tellez-Rojo MM. Association between prenatal lead exposure and blood pressure in children. Environmental Health Perspectives 2012;120(3):445-450. |
R831725 (Final) |
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Supplemental Keywords:
children, Native American, tribal, mixtures, lead, PBPK, community, Superfund, intervention,, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Epidemiology, Arsenic, Biochemistry, Children's Health, Immunology, Risk Assessment, community-based intervention, developmental toxicity, Human Health Risk Assessment, neurodevelopmental toxicity, children's environmental health, biological markers, mining wasteProgress and Final Reports:
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R831725C001 Metals, Nutrition, and Stress in Child Development
R831725C002 Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport, and Exposure Patterns
R831725C003 Manganese, Iron, Cadmium, and Lead Transport from the Environment to Critical Organs During Gestation and Early Development in a Rat Model
R831725C004 Metals Neurotoxicity Research 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.
Project Research Results
- Final Report
- 2009 Progress Report
- 2008
- 2007 Progress Report
- 2006
- 2005 Progress Report
- 2004 Progress Report
45 journal articles for this center