Grantee Research Project Results
2014 Progress Report: Southern California Children's Environmental Health Center
EPA Grant Number: R835441Center: Southern California Children's Environmental Health Center
Center Director: McConnell, Rob Scot
Title: Southern California Children's Environmental Health Center
Investigators: McConnell, Rob Scot , Sioutas, Constantinos , Gilliland, Frank D. , Berhane, Kiros , Hricko, Andrea M. , Goran, Michael , Nayak, Krishna S. , Sattler, Fred R , Allayee, Hooman , Bouret, Sebastien G. , Mittelman, Steven , Finch, Caleb E , Morgan, Todd
Current Investigators: McConnell, Rob Scot
Institution: University of Southern California
EPA Project Officer: Hahn, Intaek
Project Period: July 1, 2013 through June 30, 2018 (Extended to June 30, 2019)
Project Period Covered by this Report: July 1, 2013 through June 30,2014
Project Amount: $4,146,875
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Community Outreach and Translation Core
The COTC’s goal is to protect children’s health through educating new constituencies to understand the complex land use, public health and public policy dilemma between the need for increased outdoor physical activity to reduce obesity and the potential risks of active recreation near traffic pollution. The COTC is an integral part of the SC-CEHC, with the COTC director as a member of the Center’s executive committee, which meets monthly.
Aim 1. Develop new constituencies and new media outlets for dissemination of research findings on near-roadway air pollution (NRAP) and its adverse health effects on children, including (a) advocates of physical activity to reduce obesity; (b) advocates for new parks and outdoor exercise facilities and equitable access to green space in the city, including elected officials, urban planners, architects/landscape architects, land conservation and environmental justice (EJ) groups.
Aim 2. Build civic engagement in environmental health around the issues of air pollution and physical activity by using youth-based participatory engagement techniques, working with youth from two communities with significant NRAP and high obesity rates.
Aim 3. Enhance the capacity of current community partners, new constituencies, and youth to educate policymakers about the need to consider research findings on the adverse health effects of near-roadway air pollution, including obesity, when (a) siting new facilities to encourage physical activity; (b) expanding or building new highways or major roads close to where children play or exercise; and (c) considering new regulations to reduce air pollution to protect children’s health.
Aim 4. Evaluate COTC efforts and share successful strategies and models with others at the local and national level; meet with community advisors and a formal community advisory committee.
835441C001: Effects of Air Pollution on the Development of Obesity in Children
Obesity and its metabolic consequences are major public health issues. A growing body of evidence indicates that environmental exposures during the in utero, early-life and later childhood periods contribute to obesity and its metabolic consequences. In the Southern California Children’s Health Study (CHS), obesity, growth trajectory of body mass index (BMI) and attained BMI at age 18 years were associated with traffic density and near-roadway air pollution (NRAP) exposure during gestation and childhood, findings that were replicated for childhood exposures in a second independent cohort. Our preliminary data indicate that NRAP adversely affects body fat amount and distribution, systemic inflammation and pancreatic beta cell function. Recent experimental studies show that early-life air pollution exposures result in fat redistribution and contribute to systemic inflammatory responses and alterations of metabolic function, including insulin resistance (IR) and the metabolic syndrome (MetS). Studies in animal models have shown that early-life PM inhalation increases visceral adipose tissue (VAT), a fat depot that is associated with systemic inflammation and increased risk for later-life metabolic and cardiovascular diseases (CVD). The effects of air pollution on fat redistribution are reflected in increased hepatic fat fraction (HFF), which could contribute to the emergence of non-alcoholic fatty liver disease (NAFLD) in children. Taken together, these studies indicate that early-life traffic exposures have the potential to increase childhood obesity and contribute to fat redistribution, systemic inflammation and metabolic changes associated with increased risk for type 2 diabetes, NAFLD and CVD.
Although studies support the hypotheses that exposures to air pollution during developmental periods play a role in the trajectory toward childhood obesity, adipose tissue redistribution, inflammation and metabolic dysfunction, little is known about the responsible mechanisms or the causal components of air pollution that could be targets for prevention. We aim to fill critical gaps in the scientific knowledge base by investigating the effects of elevated NRAP exposures during the in utero and childhood periods on clinically important obesity phenotypes, obesity-related inflammation and adipokines, insulin sensitivity, pancreatic beta-cell function and components of the metabolic syndrome (MetS) at age 18 years. We have identified NRAP as the exposures of interest as traffic-related PM produce systemic oxidative stress and inflammation that may be responsible for adverse health effects.
Using newly assembled data, we will employ state-of-the-art spatio-temporal models to provide time-resolved (prenatal and childhood) EC2.5 and PM2.5 transition metals exposures to examine their effects during critical developmental periods on obesity among a subset of 4,560 Southern California-born CHS participants. This subset of subjects from the CHS has linked birth certificate data and extensive data on lifetime air pollution and tobacco smoke exposures, community contextual information, time-activity patterns, BMI trajectory, physical activity and health status. To investigate mechanism and mediation effects, we propose to examine adipose tissue distribution using advanced MRI imaging techniques, measures of inflammation, adipokines, insulin sensitivity and beta-cell function by frequently sampled intravenous glucose tolerance test (OGTT) and the prevalence of MetS and in a subsample of 200 overweight or obese CHS participants.
Specific Aim 1 will investigate the longitudinal effects of prenatal, early and later childhood exposure traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. We hypothesize that elevated exposure traffic-related air pollutant during the in utero and childhood periods are obesogenic and result in a steeper gender-specific trajectory of BMI increase with age and that cumulative exposures increase the prevalence of obesity at ages 5, 10 and 16 years.
Specific Aim 2 will examine the effects of lifetime traffic-related air pollutant exposures on the VAT, HFF, superficial adipose tissue (SAT), deep SAT (dSAT) and superficial SAT (sSAT) in 200 overweight or obese 18-years-old CHS participants sampled informatively based on EC2.5 exposure. We hypothesize that elevated exposure to EC2.5 will increase (1) the amount of VAT and dSAT relative to SAT and (2), HFF and the prevalence of non-alcoholic fatty liver disease (NAFLD).
Specific Aim 3 will investigate the effects of traffic-related air pollutant exposures on insulin sensitivity, pancreatic beta cell function, MetS and its components (blood pressure, glucose, lipid profile), adipokines and markers of inflammation (CRP, IL-6, TNF-α, MCP-1, leptin, resistin, adiponectin) in the 200 overweight or obese CHS 18-year-olds studied in Aim 2. We will assess VAT as a mediator for the chronic effects of exposure on adipokines, inflammatory markers, insulin sensitivity, pancreatic beta cell function and MetS using a novel quantile regression mediation approach. We hypothesize that after accounting for recent air pollution exposures, (1) chronic traffic-related air pollutant exposures will increase metabolic dysfunction and the risk for MetS; and (2) these adverse effects of chronic traffic exposures are mediated through VAT.
835441C002: Near-Roadway Air Pollution, Adipose Inflammation, and Metabolic Consequences
Animal toxicological studies suggest that adipose tissue inflammation plays a critical role in mediating the effects of air pollution on insulin resistance, systemic inflammation and the metabolic risk that is associated with obesity. These relationships have not previously been studied in humans. In Project 2, we will investigate specific toxicologically relevant pro-inflammatory components of the near-roadway particulate matter (PM) mixture. The specific aims are to:
- Investigate the effects of lifetime cumulative exposure to ambient NRAP EC and NOx on macrophage polarization in deep SAT from M2 to pro-inflammatory M1 subtypes. We hypothesize that exposure to markers of the NRAP mixture (EC and oxides of nitrogen [NOx]) will be associated with increased proportion of M1/M2 macrophages and with the presence of clusters of nectoric macrophates (crown-like structures [CLS]) in biopsy samples obtained from a novel deep subcutaneous adipose tissue (dSAT) biopsy.
- Investigate the effects of lifetime exposure to NRAP on adipose tissue function and cell-specific gene expression. We hypothesize that high lifetime exposure to EC and NOx will be associated with (Aim 2a) increased expression of NFĸB inflammatory and insulin signaling pathway genes in macrophages and adipocyte subfractions of SAT, and (Aim 2b) greater release of adipocytokines and biochemical markers of insulin resistance from SAT biopsies incubated ex vivo.
- Integrate information from P1 and P2 using a novel latent variable model to examine quantitatively the mechanisms underlying the entire pathway of NRAP effects on metabolic outcomes. The model will quantify the effects of exposure at different ages on a latent quantity such as underlying “adipose tissue inflammation.” This variable cannot be measured directly but can be informed by measures of surrogates like SAT inflammation (from n = 60 in P2) and abdominal visceral adipose tissue volume (from n = 200 in P1). Information on systemic metabolic outcomes from P1 and lifetime body mass index trajectory and other CHS covariates from the entire cohort effectively increases sample size. Understanding these mechanisms would strengthen our causal inference on NRAP health effects and identify new targets for intervention. We have modified the exposure aims based on the CSR comments to focus on NOx and EC as markers for NRAP exposure. Intracommunity variation in metals have proven difficult to model.
835441C003: Longitudinal Effects of Air Pollution on Obesity In Mice
The overall goals of Project 3 are to carry out comprehensive experiments in mice to determine the effect of NRAP on obesity and related metabolic traits. We will use a longitudinal study design and will focus on nanoscale particulate matter (nPM) as the pollutant of interest since these particles reflect the NRAP that is associated with obesity in the Children’s Health Study (CHS), as described in Project 1. Using the well-established C57BL/6 mouse model, we will induce obesity through combination of litter reduction at birth to promote over-nutrition during early life with high fat feeding at the time of weaning. Mice will be exposed to a novel near-roadway source of nPM (exposed group) or filtered air (control group) during prenatal, postnatal, or both pre- and postnatal development and will be characterized for obesity-related metabolic, molecular, biochemical and neurobiological phenotypes at 5 weeks of age (puberty period), 9 weeks of age (late adolescence) and 13 weeks of age (young adulthood). These proposed experiments are well-integrated with the overall focus of the Center and may provide causal information that could guide informed analyses in Projects 1 and 2 as analogous obesity-related parameters are collected in humans.
Specific Aim 1: We will determine the longitudinal effects of nPM exposure on the development of obesity and relevant physiological metabolic phenotypes. Mice in the control and exposed groups will undergo magnetic resonance imaging (MRI) to determine body composition (lean tissue mass and whole body fat) and fat distribution. We will also perform intraperitoneal glucose tolerance tests (IPGTTs) to assess glucose/insulin metabolism, measure a panel of adipocytokines in plasma, and determine hepatic lipid content.
Specific Aim 2: We will characterize adipose tissue from mice for molecular, histological, and biochemical phenotypes. Immunohistochemistry will be used to determine the presence of crown-like structures (CLS) in adipose tissue, which is indicative of macrophage infiltration and inflammation. Adipocytes will be separated from the stromal vascular fraction, which will be used to perform flow cytometry to determine macrophage subtypes (M1/M2). The effects of nPM exposure on inflammatory and metabolic gene expression will be investigated in both isolated adipocytes and macrophages. Explant incubation studies will be carried out to determine in vitro production of adipocytokines. We hypothesize that nPM exposure will have progressively adverse effects on adipose tissue homeostasis, with increased inflammation at the cellular, secretory and gene expression levels.
Specific Aim 3: We will investigate whether the effects of nPM exposure on obesity are mediated through neurobiological pathways involved in metabolic regulation. Immunohistochemical techniques and morphometric analyses will be used to characterize the hypothalamus from nPM-exposed and control mice with respect to the organization of neural projections involved in feeding regulation. Expression of metabolically relevant neuropeptide genes will also be investigated in a nucleus-specific manner by real-time PCR, and food intake will be assessed to determine whether nPM exposure results in altered feeding behavior.
Progress Summary:
Community Outreach and Translation Core
Studies and Results
During Year 1, the COTC developed new constituencies through sponsoring a 2.5-hour community forum on April 9, 2014, entitled “The Collision of Best Intentions: Public health, Smart Growth and Land Use Planning.” More than 100 participants attended the session, which included moderated posters by architecture students, housing and park advocates, environmental justice groups, and others. The meeting was cosponsored by the NIEHS Core Center, Southern California Environmental Health Sciences Center. Organizing this meeting provided an opportunity for the COTC and SC-CEHC Director Rob McConnell (who spoke at the meeting) to meet Los Angeles City commissioners of planning/housing/recreation and parks. It provided the attendees a chance to showcase the challenges they are facing when siting new parks and housing in light of evidence about the health effects of exposure to NRAP, including emerging evidence about obesity.
Los Angeles County Department of Public Health (LADPH) presentation: The COTC director presented research findings on near-roadway air pollution to 140 County environmental health inspectors as part of the LADPH’s efforts to inspire their health inspectors (many of whom inspect restaurants, pools and other facilities) to become more knowledgeable about environmental health issues in the communities where they conduct inspections.
National presentations: The COTC director had an opportunity to disseminate research findings about NRAP as an invited speaker at the EPA National Conversation on Ports webinar (February 2014, 400+ online attendees) and at the New Partnerships for Smart Growth meeting in Denver, CO (March 2014, 75 attendees). The latter meeting had an audience of urban planners, architects, city government agency staff, and leaders of community-based organizations.
The COTC is actively working with partner groups Asian/Pacific Islander Obesity Prevention Alliance (APIOPA) to plan youth workshops for summer 2014 that include training on environmental health and air pollution, tools for conducting audits of places where youth exercise, conducting community mapping, and creating digital story videos. In addition to APIOPA, the Social Justice Learning Institute and another group called From Lot to Spot are collaborating on the youth project. This collaboration will bring together Latino/African American/Tongan high school youth to participate in workshops, conducting air monitoring, producing a video of their findings and making presentations. These three organizations also participated in the Community Forum sponsored by the Center. As a pilot project, COTC staff worked with APIOPA at another high school in 2013 on an air pollution monitoring project.
Over the course of our first year, the COTC held monthly meetings with its community partners in THE Impact Project, at which it was able to obtain advice and feedback on the COTC’s work. In addition, a full Community Advisory Board meeting was held in 2013 at which the COTC received valuable advice about outreach to ethnic media and means of effective messaging on the obesity/NRAP issue.
We have begun to investigate the longitudinal effects of prenatal and early and later childhood exposure traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. The exposure assessment is being conducted from primary data, including review of residential address histories, geocoding with state-of-the-art methods and updated spatiotemporal land use regression models for exposure.
For aims 2 and 3, we have assembled the study team, developed study materials and questionnaires, obtained IRB approvals, designed and programmed study databases, tested our data collection protocols, defined our exposure-based sampling frame, and scheduled our first five study participants for study visits.
Significance
At the Los Angeles County and national conferences at which the COTC director spoke, many audience members were surprised to hear that research is being conducted to determine if NRAP may contribute to obesity and metabolic and inflammatory abnormalities that may increase the risk of type 2 diabetes. In conversation with park planners, they were also surprised to hear that NRAP might be something other than a respiratory problem for children. The work with APIOPA will reach a significantly impacted audience of youth. Below see a table of statistics about Lennox and West Carson, where APIOPA works:
Table 1.Statistics from Los Angeles County Department of Public Health, Rank in County Out of 128 (with 128 being the worst rank)
Community | Child obesity (%) | Rank in child obesity in Los Angeles County | Rank economic hardship in L.A. County | Park space, rank in Los Angeles County | Community partners |
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Lennox | 31.4 | 120/128 | 124/128 | 118/128 | APIOPA |
West Carson | 31.4 | 114/128 | 56/128 | 121/128 | APIOPA |
835441C001: Effects of Air Pollution on the Development of Obesity in Children
Studies and Results
We completed all administrative requirements to proceed, including preparation of a Project QAPP in accordance with the Center QMP. We have begun to investigate the longitudinal effects of prenatal, early and later childhood exposure traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. The exposure assessment is being conducted from primary data, including review of residential address histories, geocoding with state-of-the-art methods and updated spatiotemporal land use regression models for exposure.
For aims 2 and 3, we have assembled the study team, developed study materials and questionnaires, obtained IRB approvals, designed and programmed study databases, tested our data collection protocols, defined our exposure-based sampling frame and have completed the first 10 study participants.
Significance
The epidemiologic evidence is supported by experimental studies using animal models, which show particulate air pollutant increases visceral adiposity, adipose inflammation, systemic inflammation, metabolic dysfunction and atherosclerotic lesions. These data suggest that near roadway exposure to motor vehicle emissions are not only obesogenic, but increase the metabolic and inflammatory consequences of obesity. These obesogenic mobile source emissions are substantial in the Los Angeles region, and many of the 3 million children in Los Angeles are highly exposed because they reside, play and go to school in close proximity to major roads. These children may be at increased lifetime risk for chronic diseases from chronically elevated exposures occurring during critical developmental periods including the in utero, early childhood (ages 0–5 years) and later childhood (ages 5–18 years) periods.
835441C002: Near-Roadway Air Pollution, Adipose Inflammation, and Metabolic Consequences
Studies and Results
We completed all administrative requirements to proceed, including preparation of a Project QAPP in accordance with the Center QMP. In collaboration with Project 3, we have undertaken a small comparison study of methods for assessing selected adipocytokines (leptin, MCP-1 and TNFa) in fat lysate. We have successfully measured leptin and MCP-1 in lysate of human fat with good assay reproducibility, albeit at much lower levels than in serum. TNFa was measurable but with CV of replicate assays greater than 20%. Using a higher sensitivity assay, we anticipate that this will be an attractive alternative to measuring levels in ex vivo-cultured explants and will have equal or more physiological relevance. We have successfully recruited and completed our first subject for adipose tissue biopsy, and a second subject is pending. In collaboration with Project 1, we have examined the impact of NRAP on SAT in several existing data sets (results pending) and the joint impact of NRAP and secondhand smoke (SHS) exposure on the trajectory of BMI in adolescents (McConnell, in press). SHS and NRAP exposure were each positively and independently associated with BMI growth during an 8-year followup of a Children’s Health Study (CEHC) cohort, and there were synergistic effects of both exposures.
Significance
Strong, synergistic associations of two combustion sources (secondhand smoke and NRAP) with BMI in our upcoming paper, and the unambiguous temporal relationship, strengthen emerging evidence that exposure to tobacco smoke and NRP contribute to development of childhood obesity.
835441C003: Longitudinal Effects of Air Pollution on Obesity In Mice
Studies and Results
We completed all administrative requirements to proceed, including preparation of a Project QAPP in accordance with the Center QMP. As a first attempt to establish our exposure protocol, we carried out a pilot study to determine the effects of NRAP on obesity in mice. Male C57Bl/6J mice were put on a high-fat diet at 6 weeks of age and exposed to either 300 g nPM/m3 as a combination of gasoline and diesel exhaust (n = 8), or filtered air as a control (n = 8) for 7 weeks (7 day/week, 6 hr/day). Mice were then sacrificed at the end of the exposure period and characterized with respect to adiposity, plasma metabolic biomarkers, and adipose gene expression. While both groups of mice gained weight and had increased adiposity (data not shown), we did not observe differences in body weight, adipose tissue mass, or plasma metabolic markers between the nPM exposure and filtered air control at conclusion of the 7-week exposure period (see Figure below). We attribute this to several factors that we will address for the studies proposed (described below). First, we believe our high-fat diet had a very strong obesifying effect, which may have masked the metabolic effects of nPM exposure. For example, this diet contained 32% fat and 51% carbohydrate (in the form of sucrose). Based on this assumption, it is also possible that 7 weeks of exposure was not sufficient in duration to reveal an effect of nPM on obesity over and above the high-fat diet. Third, we only studied male mice, and it is possible that female mice exposed to nPM would exhibit alterations in metabolic phenotypes compared to the filtered air-exposed mice. Based on these observations, we have modified our exposure protocol, as described below.
Significance
The results from the pilot study described above, while negative, still yield important insights with respect to Project 3. Most importantly, it appears that the selection of an obesogenic diet must be carefully considered due to the apparent strong effect of a high-fat diet compared to nPM exposure on metabolic traits.
Future Activities:
Community Outreach and Translation Core
The COTC is actively working with partner groups such as APIOPA to plan youth workshops for summer 2014 that include training on environmental health and air pollution, tools for conducting audits of places where youth exercise, conducting community mapping, and creating digital story videos. In addition to APIOPA, the Social Justice Learning Institute and another group called From Lot to Spot are collaborating on the youth project. This collaboration will bring together Latino/African American/Tongan high school youth to participate in workshops, conducting air monitoring, producing a video of their findings and making presentations. From this work, a curriculum will be developed that can be used by others.
The COTC will be conducting key informant interviews with the professionals who attended the Collision of Best Intentions Community Forum. As noted, these include urban planners, landscape architects, architects, and planning/housing/recreation and parks commissioners. We will attempt to determine what information they gained from the forum and whether it sparked their interest in learning more about near-roadway air pollution. We will do a post-forum electronic evaluation of the community members and public attendees.
In Year 2, we will organize several van tours for urban planners and architects to discuss issues of concern with near-roadway air pollution, speak at community gatherings, continue evaluation through THE Impact Project and our advisory committee, and finalize the curriculum developed in Year 1 with APIOPA and other youth organizations.
835441C001: Effects of Air Pollution on the Development of Obesity in Children
We will continue to investigate the longitudinal effects of prenatal, early and later childhood exposure traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort. The exposure assessment will be completed. Analyses will be conducted to understand the longitudinal effects of prenatal, early and later childhood exposure to traffic-related air pollutant on BMI trajectory and obesity in the CHS cohort.
For aims 2 and 3, we will continue to assess study participants and conduct ongoing quality control and assurance activities.
835441C002: Near-Roadway Air Pollution, Adipose Inflammation, and Metabolic Consequences
The coming year will be focused on recruiting subjects.
835441C003: Longitudinal Effects of Air Pollution on Obesity In Mice
Based on our pilot study, we have revised our exposure protocol and are carrying out a second pilot study before performing the actual exposure experiments. The rationale for this strategy is because we would like to carry out the three arms of the mouse exposure studies at different stages of development simultaneously. First, we have eliminated litter restriction in combination with a high-fat diet since we believe this will further mask the effect of nPM exposure. We will also expose mice for a longer period (10 weeks) and use a different obesogenic diet that does not contain as high a fat and sucrose content. Third, we have elected to study both male and female mice. This second pilot is being carried out with mice being exposed during both pre- and postnatal development since we hypothesize that strongest effect of nPM will be in those mice exposed the longest. Having established an exposure protocol that shows a difference between FA and nPM groups, we will then move forward with exposing animals during prenatal, postnatal, or both pre- and postnatal development, as initially proposed. Mice will be characterized for obesity-related metabolic, molecular, biochemical and neurobiological phenotypes.
Journal Articles: 66 Displayed | Download in RIS Format
Other center views: | All 69 publications | 66 publications in selected types | All 66 journal articles |
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Alderete TL, Autran C, Brekke BE, Knight R, Bode L, Goran MI, Fields DA. Associations between human milk oligosaccharides and infant body composition in the first 6 mo of life. American Journal of Clinical Nutrition 2015;102(6):1381-1388. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Alderete TL, Habre R, Toledo-Corral CM, Berhane K, Chen Z, Lurmann FW, Weigensberg MJ, Goran MI, Gilliland FD. Longitudinal associations between ambient air pollution with insulin sensitivity, β-cell function, and adiposity in Los Angeles Latino children. Diabetes 2017;66(7):1789-1796. |
R835441 (2018) |
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Alderete TL, Jones RB, Chen Z, Kim JS, Habre R, Lurmann F, Gilliland FD, Goran MI. Exposure to traffic-related air pollution and the composition of the gut microbiota in overweight and obese adolescents. Environmental Research 2018;161:472-478. |
R835441 (2018) R835435 (Final) |
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Alderete TL, Song AY, Bastain T, Habre R, Toledo-Corral CM, Salam MT, Lurmann F, Gilliland FD, Breton CV. Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight. Pediatric Obesity 2018:13(6):348-356. |
R835441 (2018) R836158 (2017) R836158 (2018) R836158 (2019) R836158 (2020) |
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Allayee H, Hazen SL. Contribution of gut bacteria to lipid levels: another metabolic role for microbes? Circulation Research 2015;117(9):750-754. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Berger PK, Fields DA, Demerath EW, Fujiwara H, Goran MI. High-fructose corn-syrup-sweetened beverage intake increases 5-hour breast milk fructose concentrations in lactating women. Nutrients 2018;10(6):669 (9 pp.). |
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Bouret S, Levin BE, Ozanne SE. Gene-environment interactions controlling energy and glucose homeostasis and the developmental origins of obesity. Physiological Reviews 2015;95(1):47-82. |
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Breton CV, Mack WJ, Yao J, Berhane K, Amadeus M, Lurmann F, Gilliland F, McConnell R, Hodis HN, Kunzli N, Avol E. Prenatal air pollution exposure and early cardiovascular phenotypes in young adults. PLoS One 2016;11(3):e0150825 (12 pp.). |
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Burnor E, Cserbik D, Cotter D, Palmer C, Ahmad H, Eckel S, Berhane K, McConnell R, Chen J, Schwartz J, Jackson R, Hertling M. Association of Outdoor Ambient Fine Particulate Matter With Intracellular White Matter Microstructural Properties Among Children. JAMA NETWORK OPEN 2021;4(12). |
R835441 (Final) R835872 (2020) |
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Chen Z, Salam MT, Toledo-Corral C, Watanabe RM, Xiang AH, Buchanan TA, Habre R, Bastain TM, Lurmann F, Wilson JP, Trigo E, Gilliland FD. Ambient air pollutants have adverse effects on insulin and glucose homeostasis in Mexican Americans. Diabetes Care 2016;39(4):547-554. |
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Chen Z, Salam MT, Alderete TL, Habre R, Bastain TM, Berhane K, Gilliland FD. Effects of childhood asthma on the development of obesity among school-aged children. American Journal of Respiratory and Critical Care Medicine 2017;195(9):1181-1188. |
R835441 (2018) |
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Cheng H, Davis DA, Hasheminassab S, Sioutas C, Morgan TE, Finch CE. Urban traffic-derived nanoparticulate matter reduces neurite outgrowth via TNFα in vitro. Journal of Neuroinflammation 2016;13:19 (11 pp.). |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Cho J, Goldenson NI, Pester MS, Khoddam R, Bello MS, Dunton GF, Belcher BR, Leventhal AM. Longitudinal associations between anhedonia and body mass index trajectory groups among adolescents. Journal of Adolescent Health 2018;63(1):81-87. |
R835441 (2018) |
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Cotter D, Campbell C, Sukumaran K, McConnell R, Berhane K, Schwartz J, Hackman D, Ahmadi H, Chen J, Herting M. Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence. ENVIRONMENT INTERNATIONAL 2023;177(108001) |
R835441 (Final) |
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Cui X, Gong J, Han H, He L, Teng Y, Tetley T, Sinharay R, Chung KF, Islam T, Gilliland F, Grady S, Garshick E, Li Z, Zhang JJ. Relationship between free and total malondialdehyde, a well-established marker of oxidative stress, in various types of human biospecimens. Journal of Thoracic Disease 2018;10(5):3088-3097. |
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Dueker D, Taher M, Wilson J, McConnell R. Evaluating children's location using a personal GPS logging instrument: limitations and lessons learned. Journal of Exposure Science and Environmental Epidemiology 2014;24(3):244-252. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) |
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Dunton GF, O'Connor SG, Belcher BR, Maher JP, Schembre SM. Objectively-measured physical activity and sedentary time are differentially related to dietary fat and carbohydrate intake in children. Frontiers in Public Health 2018;6:198 (6 pp.). |
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Fruin S, Urman R, Lurmann F, McConnell R, Gauderman J, Rappaport E, Franklin M, Gilliland FD, Shafer M, Gorski P, Avol E. Spatial variation in particulate matter components over a large urban area. Atmospheric Environment 2014;83:211-219. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) R831845 (2005) |
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Ghazalpour A, Cespedes I, Bennett BJ, Allayee H. Expanding role of gut microbiota in lipid metabolism. Current Opinion in Lipidology 2016;27(2):141-147. |
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Ghosh R, Lurmann F, Perez L, Penfold B, Brandt S, Wilson J, Milet M, Kunzli N, McConnell R. Near-roadway air pollution and coronary heart disease: burden of disease and potential impact of a greenhouse gas reduction strategy in Southern California. Environmental Health Perspectives 2016;124(2):193-200. |
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Ghosh R, Gauderman WJ, Minor H, Youn HA, Lurmann F, Cromar KR, Chatzi L, Belcher B, Fielding CR, McConnell R. Air pollution, weight loss and metabolic benefits of bariatric surgery: a potential model for study of metabolic effects of environmental exposures. Pediatric Obesity 2018;13(5):312-320. |
R835441 (2017) R835441 (2018) |
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Goran MI, Martin AA, Alderete TL, Fujiwara H, Fields DA. Fructose in breast milk is positively associated with infant body composition at 6 months of age. Nutrients 2017;9(2)146 (11 pp.). |
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Habre R, Zhou H, Eckel SP, Enebish T, Fruin S, Bastain T, Rappaport E, Gilliland F. Short-term effects of airport-associated ultrafine particle exposure on lung function and inflammation in adults with asthma. Environment International 2018;118:48-59. |
R835441 (2018) |
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Hasson RE, Hsu YJ, Davis JN, Goran MI, Spruijt-Metz D. The influence of parental education on dietary intake in Latino youth. Journal of Immigrant and Minority Health 2018;20(1):250-254. |
R835441 (2018) |
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Hsieh S, Klassen AC, Curriero FC, Caulfield LE, Cheskin LJ, Davis JN, Goran MI, Weigensberg MJ, Spruijt-Metz D. Built environment associations with adiposity parameters among overweight and obese Hispanic youth. Preventive Medicine Reports 2015;2:406-412. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Hsieh S, Leaderer BP, Feldstein AE, Santoro N, McKay LA, Caprio S, McConnell R. Traffic-related air pollution associations with cytokeratin-18, a marker of hepatocellular apoptosis, in an overweight and obese paediatric population. Pediatric Obesity 2018;13(6):342-347. |
R835441 (2017) R835441 (2018) |
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Hsu TM, Konanur VR, Taing L, Usui R, Kayser BD, Goran MI, Kanoski SE. Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats. Hippocampus 2015;25(2):227-239. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Jerrett M, Shankardass K, Berhane K, Gauderman WJ, Künzli N, Avol E, Gilliland F, Lurmann F, Molitor JN, Molitor JT, Thomas DC, Peters J, McConnell R. Traffic-related air pollution and asthma onset in children: a prospective cohort study with individual exposure measurement. Environmental Health Perspectives 2008;116(10):1433-1438. |
R835441 (2017) R831861 (Final) R831861C001 (Final) R831861C002 (Final) R831861C003 (Final) |
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Jerrett M, McConnell R, Wolch J, Chang R, Lam C, Dunton G, Gilliland F, Lurmann F, Islam T, Berhane K. Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis. Environmental Health 2014;13:49 (9 pp.). |
R835441 (2015) R835441 (2016) R835441 (2018) |
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Johnston J, Juarez Z, Navarro S, Hernandez A, Hutschow W. Youth Engaged Participatory Air Monitoring:A 'Day in the Life' in Urban Environmental Justice Communities. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020;17(1):93. |
R835441 (Final) |
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Kayser BD, Goran MI, Bouret SG. Perinatal overnutrition exacerbates adipose tissue inflammation caused by high-fat feeding in C57BL/6J mice. PLoS One 2015;10(3):e0121954 (15 pp.). |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Kayser BD, Toledo-Corral CM, Alderete TL, Weigensberg MJ, Goran MI. Temporal relationships between adipocytokines and diabetes risk in Hispanic adolescents with obesity. Obesity 2015;23(7):1479-1485. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Kim JS, Alderete TL, Chen Z, Lurmann F, Rappaport E, Habre R, Berhane K, Gilliland FD. Longitudinal associations of in utero and early life near-roadway air pollution with trajectories of childhood body mass index. Environmental Health 2018;17(1):64 (10 pp.). |
R835441 (2018) |
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Kim JY, Goran MI, Toledo-Corral CM, Weigensberg MJ, Shaibi GQ. Comparing glycemic indicators of prediabetes: a prospective study of obese Latino Youth. Pediatric Diabetes 2015;16(8):640-643. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Li L, Lurmann F, Habre R, Urman R, Rappaport E, Ritz B, Chen JC, Gilliland FD, Wu J. Constrained mixed-effect models with ensemble learning for prediction of nitrogen oxides concentrations at high spatiotemporal resolution. Environmental Science & Technology 2017;51(17):9920-9929. |
R835441 (2018) |
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Liao J, Goodrich J, Walker D, Lin Y, Lurmann F, Qiu C, Hones D, Gilliland F, Chazi L, Chen Z. Metabolic pathways altered by air pollutant exposure in association with lipid profiles in young adults*. ENVIRONMENTAL POLLUTION 2023;327(121522) |
R835441 (Final) |
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Lopez NV, Schembre S, Belcher BR, O'Connor S, Maher JP, Arbel R, Margolin G, Dunton GF. Parenting styles, food-related parenting practices, and children's healthy eating: a mediation analysis to examine relationships between parenting and child diet. Appetite 2018;128:205-213. |
R835441 (2018) |
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Luo S, O'Connor SG, Belcher BR, Page KA. Effects of physical activity and sedentary behavior on brain response to high-calorie food cues in young adults. Obesity 2018;26(3):540-546. |
R835441 (2018) |
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Lurmann F, Avol E, Gilliland F. Emissions reduction policies and recent trends in Southern California's ambient air quality. Journal of the Air & Waste Management Association 2015;65(3):324-335. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Mahmodi G, Bafti R, Boroujeni N, Pradhan S, Danwal S, Sengupta B, Vatanpour V, Sorci M, Fathizadeh M, Bikkina P, Belfort G, Yu M, Kim S. Improving cellulose acetate mixed matrix membranes by incorporating hydrophilic MIL-101(Cr)-NH2 nanoparticles for treating dye/salt solution. CHEMICAL ENGINEERING JOURNAL 2023;477(146736) |
R835441 (Final) R835872 (Final) SU840147 (Final) |
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McConnell R, Shen E, Gilliland FD, Jerrett M, Wolch J, Chang C-C, Lurmann F, Berhane K. A longitudinal cohort study of body mass index and childhood exposure to secondhand tobacco smoke and air pollution: the Southern California Children's Health Study. Environmental Health Perspectives 2015;123(4):360-366. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) |
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McConnell R, Gilliland FD, Goran M, Allayee H, Hricko A, Mittelman S. Does near-roadway air pollution contribute to childhood obesity? Pediatric Obesity 2016;11(1):1-3. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) |
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Noble EE, Hsu TM, Jones RB, Fodor AA, Goran MI, Kanoski SE. Early-life sugar consumption affects the rat microbiome independently of obesity. The Journal of Nutrition 2017;147(1):20-28. |
R835441 (2018) |
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O'Connor SG, Ke W, Dzubur E, Schembre S, Dunton GF. Concordance and predictors of concordance of children's dietary intake as reported via ecological momentary assessment and 24 h recall. Public Health Nutrition 2018;21(6):1019-1027. |
R835441 (2018) |
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O'Reilly GA, Belcher BR, Davis JN, Martinez LT, Huh J, Antunez-Castillo L, Weigensberg M, Goran MI, Spruijt-Metz D. Effects of high-sugar and high-fiber meals on physical activity behaviors in Latino and African American adolescents. Obesity 2015;23(9):1886-1894. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Pomatto LCD, Cline M, Woodward N, Pakbin P, Sioutas C, Morgan TE, Finch CE, Forman HJ, Davies KJA. Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles ('vehicular smog'). Free Radical Biology and Medicine 2018;121:86-97. |
R835441 (2018) |
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Ritz B, Qiu J, Lee PC, Lurmann F, Penfold B, Erin Weiss R, McConnell R, Arora C, Hobel C, Wilhelm M. Prenatal air pollution exposure and ultrasound measures of fetal growth in Los Angeles, California. Environmental Research 2014;130:7-13. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) |
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Shankardass K, McConnell R, Jerrett M, Lam C, Wolch J, Milam J, Gilliland F, Berhane K. Parental stress increases body mass index trajectory in pre-adolescents. Pediatric Obesity 2014;9(6):435-442. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) R831845 (2005) |
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Smallwood T, Allayee H, Bennett BJ. Choline metabolites: gene by diet interactions. Current Opinion in Lipidology 2016;27(1):33-39. |
R835441 (2017) R835441 (2018) |
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Stratakis N, Conti D, Borras E, Sabido E, Roumeliotaki T, Papadopoulou E, Algier L, Basagana X, Bustamante M, Casas M, Farzan S, Fossati S, Gonzalez J, Grazuleviciene R, Heude B, Maitre L, McEachan R, Theologidis I, Urquiza J, Vafeiadi M, West J, Wright J, McConnell R, Brantsaeter A, Meltzer H, Vrijheid M, Chatzi L. Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children. JAMA NETWORK OPEN 2020;3(3):e201007. |
R835441 (Final) |
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Su JG, Jerrett M, McConnell R, Berhane K, Dunton G, Shankardass K, Reynolds K, Chang R, Wolch J. Factors influencing whether children walk to school. Health & Place 2013;22:153-161. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) R831845 (2005) |
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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. |
R835441 (2017) R831725 (2007) R831725 (2009) |
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Toledo-Corral CM, Alderete TL, Richey J, Sequeira P, Goran MI, Weigensberg MJ. Fasting, post-OGTT challenge, and nocturnal free fatty acids in prediabetic versus normal glucose tolerant overweight and obese Latino adolescents. Acta Diabetologica 2015;52(2):277-284. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Toledo-Corral CM, Alderete TL, Habre R, Berhane K, Lurmann FW, Weigensberg MJ, Goran MI, Gilliland FD. Effects of air pollution exposure on glucose metabolism in Los Angeles minority children. Pediatric Obesity 2018;13(1):54-62. |
R835441 (2018) |
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Urman R, Gauderman J, Fruin S, Lurmann F, Liu F, Hosseini R, Franklin M, Avol E, Penfold B, Gilliland F, Brunekreef B, McConnell R. Determinants of the spatial distributions of elemental carbon and particulate matter in eight Southern Californian communities. Atmospheric Environment 2014;86:84-92. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) |
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Urman R, McConnell R, Islam T, Avol EL, Lurmann FW, Vora H, Linn WS, Rappaport EB, Gilliland FD, Gauderman WJ. Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants. Thorax 2014;69(6):540-547. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) R831845 (2005) |
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Vos MB, Goran MI. Sugar, sugar ... not so sweet for the liver.Gastroenterology 2017;153(3):642-645. |
R835441 (2018) |
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Wang P, Tuvblad C, Younan D, Franklin M, Lurmann F, Wu J, Baker LA, Chen JC. Socioeconomic disparities and sexual dimorphism in neurotoxic effects of ambient fine particles on youth IQ: a longitudinal analysis. PLoS One 2017;12(12):e0188731 (15 pp.). |
R835441 (2018) |
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Wheelock K, Zhang JJ, McConnell R, Tang D, Volk HE, Wang Y, Herbstman JB, Wang S, Phillips DH, Camann D, Gong J, Perera F. A novel method for source-specific hemoglobin adducts of nitro-polycyclic aromatic hydrocarbons. Environmental Science: Processes & Impacts 2018;20(5):780-789. |
R835441 (2018) |
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Wu W, Muller R, Berhane K, Fruin S, Liu F, Jaspers I, Diaz-Sanchez D, Peden DB, McConnell R. Inflammatory response of monocytes to ambient particles varies by highway proximity. American Journal of Respiratory Cell and Molecular Biology 2014;51(6):802-809. |
R835441 (2015) R835441 (2016) R835441 (2017) R835441 (2018) R831845 (2005) |
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Younan D, Tuvblad C, Li L, Wu J, Lurmann F, Franklin M, Berhane K, McConnell R, Wu AH, Baker LA, Chen JC. Environmental determinants of aggression in adolescents: role of urban neighborhood greenspace. Journal of the American Academy of Child and Adolescent Psychiatry 2016;55(7):591-601. |
R835441 (2018) |
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Younan D, Tuvblad C, Franklin M, Lurmann F, Li L, Wu J, Berhane K, Baker LA, Chen JC. Longitudinal analysis of particulate air pollutants and adolescent delinquent behavior in Southern California. Journal of Abnormal Child Psychology 2018;46(6):1283-1293. |
R835441 (2018) |
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Zigman JM, Bouret SG, Andrews ZB. Obesity impairs the action of the neuroendocrine ghrelin system. Trends in Endocrinology and Metabolism 2016;27(1):54-63. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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Zink J, Belcher BR, Dzubur E, Ke W, O'Connor S, Huh J, Lopez N, Maher JP, Dunton GF. Association between self-reported and objective activity levels by demographic factors: ecological momentary assessment study in children. JMIR mHealth and uHealth 2018;6(6):e150 (12 pp.). |
R835441 (2018) |
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Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic related air pollution, particulate matter, and autism. JAMA Psychiatry 2013;70(1):71-77. |
R835441 (2017) R833292 (2012) |
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Cserbik D, Chen JC, McConnell R, Berhane K, Sowell ER, Schwartz J, Hackman DA, Kan E, Fan CC and Herting MM. Fine particulate matter exposure during childhood relates to hemispheric-specific differences in brain structure. Environ Int 2020; 143:105933. |
R835441 (Final) R835872 (2020) |
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Supplemental Keywords:
Children's health, children's environmental health, near-roadway air pollution, NRAP, air pollution, adverse health effects, obesity;Progress and Final Reports:
Original AbstractThe 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
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
- Original Abstract
66 journal articles for this center