Grantee Research Project Results
2015 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
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, 2014 through June 30,2015
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:
Project 1: 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 spatiotemporal 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.
Project 2: 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:
Specific Aim 1 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 near-roadway air pollutant (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 adipost tissue (dSAT) biopsy.
Specific Aim 2 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.
Specific Aim 3 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.
Project 3: The overall goals of Project 3 are to carry out comprehensive experiments in mice to determine the effect of near-roadway air pollution (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 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.
COTC: 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 a member of the Center’s executive committee which meets monthly.
Specific 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.
Specific 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.
Specific 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.
Specific 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.
Progress Summary:
All three projects have made substantial progress toward addressing Center goals. Recruitment of subjects is ongoing for Projects 1 and 2. Initial animal exposure has been completed for P3 and preliminary results show effects of air pollution on metabolic outcomes. COTC has developed good working relationships with community counterparts and several substantive outreach and translation activities have already been completed. Additional details are provided in the individual project and core reports.
The Center has made good progress toward aims in all 3 projects and in the cores. There were some administrative delays in obtaining IRB (P1) and Clinical Trials Unit approval (P2) in the first year, and slower accrual of subjects than expected in Year 2, but we have new recruitment procedures in place to address these issues. Additional details for each project are described in the corresponding progress report.
Project 1: We 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 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 recruited and tested 22 subjects. We had a slower start than anticipated but are now meeting our new recruiting target numbers after revising the protocol and increasing subject reimbursement. We anticipate meeting our targets by the end of year 4.
Project 2: We have fully developed procedures and are still in the data collection phase. Cell sorting is done at the time of adipose tissue biopsy and we have successfully counted M1 and M2 macrophages (Figure 1). We have in addition counted Treg and Teff cells. Tissue for other assays is archived until data collection is completed.
Figure 1
Recruitment has been slower than anticipated, in part because it is dependent on the recruitment from Project 1, which is improving rapidly with some changes to recruitment procedures (see report for P1). We have conducted exit interviews with subjects (from the P1 pool) who decline to participate in P2, and we are modifying procedures accordingly, including identifying a new coordinator/recruiter, more appropriate compensation for time and travel reimbursement, an intermediate step to asses physical activity assessment, compensated separately, allowing time to build a rapport between recruiter and subject. In addition, we have a plan to increase recruitment that we have developed with advice from members of our external advisory committee. We will use methods previously developed by Center deputy director and P2 co-investigator Michael Goran to recruit through advertising, restricting recruitment to lifetime southern California residents willing to have a fat biopsy. We are also exploring targeted advertising to the sample age group in CHS communities using commercial lists obtained from InfoUSA and Lexis Nexis. We will collect lifetime address histories from a broad pool willing to have a SAT biopsy, use this information to assign lifetime pollution exposure (using identical methods to those developed for P1 participants). We will select participants to maximize the exposure contrast (also using P1 procedures). This approach will provide complementary data to that from continued recruitment from the P1 pool and will allow us sufficient sample size to complete all major goals including the integrative modeling that will incorporate information from P2 and potentially also from the P3 animal study. We will conduct sensitivity analyses using the participants recruited through P1. We anticipate that using this approach we will be able to catch up and complete recruitment on the original time table. Among others, we have three particularly noteworthy publications, showing an association between near-roadway air pollution and BMI in a Children’s Health Study cohort1 and showing a synergistic effects of SHS and near-roadway pollution exposure in another cohort (publications developed across P1 and P2).2 Similar effects across multiple cohorts and strong, synergistic associations of two combustion sources (secondhand smoke and NRAP) with BMI, and the unambiguous temporal relationship, strengthen emerging evidence that air pollution contribute to development of childhood obesity. We also have a commentary in press in Pediatric Obesity (developed by investigators across the center) synthesizing the emerging evidence that air pollution causes obesity.
Project 3: To establish our experimental protocol, we first carried out a pilot study to determine the effects of NRAP on obesity in mice that had whole life exposures. At the time of pregnancy, female C57Bl/6J mice were exposed to either filtered air or 300 mcg/m3 nPM for 5 hours per day, 3 days per week. Subsequent to the birth of the pups, exposure was maintained in the same fashion until weaning at 4 weeks of age. Thereafter, male and female mice were put on either a regular chow diet (n = 8 males and n = 8 females) or a high fat diet (n = 8 males and n = 8 females) and exposure to filtered air or nPM was maintained in the same fashion for another 10 weeks. Exposures have just been completed and the mice are scheduled for sacrifice March 16 and 23, 2015. Currently, we have carried out several non-invasive measurements including body weight and glucose metabolism. We observed that there were no differences in the body weights of female mice in any of the exposed or dietary groups. Therefore, we will focus our efforts at the time of sacrifice on characterizing males with respect to adiposity, plasma metabolic biomarkers, and adipose gene expression. In preliminary analyses shown in Figure 2, male mice placed on the high fat (HF) had significantly increased body weight compared to mice on the chow (LF) diet (panel A). Within each dietary arm, there was also a trend towards higher body weight in mice exposed to nPM compared to controls, but these differences were suggestive and borderline significant (p = 0.08). Similar patterns between mice in the four groups were observed for fasting glucose levels (panel B). However, there were clear differences in glucose tolerance between the groups. As shown by the intraperitoneal glucose tolerance test profiles in panel C, mice placed on both a high fat and exposed to nPM had impaired glucose clearance compared to control exposed mice fed a high fat diet. These differences were even more apparent when compared to control and exposed mice on the control chow diet. Consistent with these results, the area under the glucose tolerance curve (AUC) was significantly higher for the nPM exposed mice on a high fat diet compared to control exposure and to mice on a chow diet (panel D).
Figure 2
COTC: The Community Outreach and Engagement Core (COTC) aims to serve as a bridge between the scientists in the Southern California Children’s Environmental Health Center (SC-CEHC) and the public, so that the public better understands concerns about near roadway air pollution, especially the potential impacts of air pollution, obesity and metabolic outcomes. We aim to engage a broad array of stakeholders, from health professionals to architects, urban planners and youth.
We had six major highlights this year: development of new social media resources; creation of a popular, easy to read and colorful infographic about near-roadway pollution and its health effects, including obesity; presentations to public health professionals on diabetes and the environment and on social determinants of health (including obesity, diabetes and the environment; a community forum on health concerns when building housing and parks near busy roads and freeways, and serving on a panel at an environmental justice conference to discuss that same issue; and a summer institute for high school youth.
- New Social Media Resources Developed: The COTC has introduced a new USC Environmental Health blog: http://USCEH.blogspot.com/ Exit to reach a wider audience. It is filled with current news, events, research projects and outreach activities of the Southern California Children's Environmental Health Center and other EH activities at USC. We have also created a new Twitter account, to promote stories on the blog, new resources on the website, and news stories on environmental health. View at https://twitter.com/USC_EH_Outreach Exit or follow @USC_EH_Outreach. A new Facebook page (Facebook.com/USCEHC) promotes stories on the blog, new resources on the website, and news stories on environmental health. The Facebook account is aimed at reaching wider community audiences with messages related to the health effects of near roadway air pollution and its impact on the health of children (and adults).
- New Infographic: The COTC staff created a new infographic titled “Living Near Busy Roads or Traffic Pollution” with information about health research in a visual format that is accessible for audiences of all reading levels. Online viewers can click on the text for more information: each health effect is linked to a scientific research article. Feedback from community partners has been very positive, with groups saying they will use the online and printed version to show this information to their members and across their communities. Spanish and Chinese versions are planned for next year. See the blog to view the infographic: http://USCEH.blogspot.com/. Exit Our infographic has generated 2,400 page views on our blog.
- Presentations to Public Health Professionals: The COTC worked with Dr. Stephen Mittelman to prepare a PowerPoint presentation on Diabetes and the Environment for the Asian Pacific Islander Health Summit sponsored by the Los Angeles County Department of Health and multiple community organizations in Los Angeles, held in January 2015. Members of the audience included health professionals, County Health Department leadership, and members of community organizations. Many were surprised to hear for the first time about potential links between obesity/diabetes and air pollution. In March 2015, the COTC director was the keynote speaker at a meeting for physicians and nurses who have volunteered to be advocates with Physicians for Social Responsibility - L.A. Her talk included some of the latest findings on obesity, diabetes, and impacts of both the social and physical environment. The presentation and a full list of citations were provided to attendees.
- Inserting “Environmental Health” into the Process when Developing Housing and Parks: Conflicts often arise between advocates for affordable housing, who may find that the least expensive and most readily available land for housing is near freeways, and the scientific community which raises questions about the health impacts of building residences or parks or schools near roadway pollution. Both sides have good intentions. The COTC organized an event titled “Community Forum: The Collision of Best Intentions.” It was held in the previous grant year, April 2014, but is included here because it occurred after the previous year’s report was turned in. This event was attended by approximately 150 individuals representing Los Angeles area community-based organizations (CBOs), NIEHS leadership and staff, students, and interested community members. It was sponsored by the SC-CEHC, Southern California Environmental Health Sciences Center and the National Institute of Environmental Health Sciences (NIEHS). The forum brought together stakeholders around environmental health issues, particularly the epidemic of childhood obesity. Through a series of presentations, including among others the Children’s Center director Rob McConnell, the COTC director and the director of NIEHS, a foundation was set for an open microphone session during which all attendees were given the opportunity to ask questions, give perspective and feedback and set the stage for continued dialogue, interaction and collaboration around three important issues: 1) the public health dilemma of incompatible land use decisions; 2) how we can achieve physical activity and other health benefits from building transit-oriented development (TOD) while also considering near roadway air pollution; and 3) the need for considering public health as we develop community gardens, urban parks, more walkable streets and new bicycle lanes. Presenters also included the president of East LA Community Corporation (an affordable housing developer) and a member of the Los Angeles City Recreation and Parks Commission. A highlight of the forum was a poster session in which community-based organizations showcased their work and questions were asked by environmental health scientists. At another event, this one an Environmental Justice Summit sponsored by the local Air Quality Management District (AQMD), the COTC director was on a panel of experts who addressed a scenario involving building housing and parks immediately adjacent to freeways. The panel consisted of multiple viewpoints, including a housing developer, an urban planner, a landscape architect, an environmental health scientist, and a legislator. The 300-person audience was equally diverse in terms of professions. This provided a significant opportunity to educate an audience with wide-ranging interests about the potential health effects, including diabetes and obesity, of building parks and homes near freeways.
Another highlight of the past year was our Environmental Justice Summer Institute (EJSI). The COTC and its community partners Asian and Pacific Islander Obesity Prevention Alliance (APIOPA), From Lot to Spot (FLTS), and Social Justice Learning Institute (SJLI) planned and implemented the new program. EJSI was created to engage a diverse group of local high school youth from disadvantaged communities in Los Angeles County around environmental health and environmental justice issues. The 14-session summer program was held June./July 2014. The EJSI curriculum focused on educating, engaging, and empowering the youth to be agents of change in their own neighborhoods. Youth learned about environmental health and justice through workshops, presentations, and community tours. The COTC presented research about possible links between air pollution and obesity. The curriculum covered: “researching EJ in our community”, and “becoming EJ youth leaders.” The youth developed hands-on experience by mapping polluted locations in their own neighborhoods, and used air and noise monitoring equipment to track pollution levels. With the help of two high school and college age interns, the participants added their plotted locations and data to an online map. The students also created videos, shooting and editing their own footage. A highlight of the summer was having the students present to the AQMD Governing Board. See the USC Environmental Health blog described below for links to the online map and videos (http://usceh.blogspot.com/p/blogpage_ 23.html Exit ). Other COTC Activities: The COTC also provided a training on the health effects of air pollution to Legacy L.A., a non-profit organization focused on youth and leadership development which offers academic support to students who live in a public housing complex near the USC Health Sciences campus. The youth used this information to help develop a plan for how they would like to showcase the issues in their community, and gave a presentation at a town hall meeting for key policy and decision makers in Los Angeles in June 2013. One issue that the students raised were concerns about air pollution at a relatively new park and playground on the housing complex grounds. The park/playground is located adjacent to a Metrolink rail line, a bus way, and a major freeway. Included in their proposed plan was the idea of asking government agencies to plant trees as a possible buffer between the park/playground and the adjacent mobile sources of pollution.
Other COTC Activities: The COTC also provided a training on the health effects of air pollution to Legacy L.A., a non-profit organization focused on youth and leadership development which offers academic support to students who live in a public housing complex near the USC Health Sciences campus. The youth used this information to help develop a plan for how they would like to showcase the issues in their community, and gave a presentation at a town hall meeting for key policy and decision makers in Los Angeles in June 2013. One issue that the students raised were concerns about air pollution at a relatively new park and playground on the housing complex grounds. The park/playground is located adjacent to a Metrolink rail line, a bus way, and a major freeway. Included in their proposed plan was the idea of asking government agencies to plant trees as a possible buffer between the park/playground and the adjacent mobile sources of pollution. The COTC spoke at the Environmental Health Work Group of the Long Beach Building Healthy Communities program, sharing our new infographic and demonstrating air monitoring equipment that is available for educational workshops about air pollution. The COTC has a longtime partnership with the Long Beach Alliance for Children with Asthma, whose “Neighborhood Assessment Teams” partner with the COTC to conduct community-based research on traffic pollution. COTC staff gave a presentation about USC’s health research studies, and trained new members on how to use the air monitoring equipment. COTC staff also assisted in a community gardening workshop of the Environmental Committee during the Empowerment Congress Summit on January 17, hosted annually by the Los Angeles County Second District Supervisor.
Future Activities:
Project 1: 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.
Project 2: The coming year will be focused on recruiting subjects, as described in the original timeline, using additional recruitment procedures described above.
Project 3: Our plans during the third year of Project 3 will be to carry out the two additional arms of the exposure studies. These are (1) exposing mice only during prenatal development and (2) exposing mice only during postnatal development. In combination with the results from the already completed whole life exposure study, we expect to obtain additional insight into the critical windows of susceptibility during development that are important for exposure to NRAP.
COTC: In the next reporting period, the COTC plans to continue to host events to engage urban planning, public policy, and community organizations around the issues of land use and near roadway air pollution. The COTC will continue to work with partner organizations in our target communities in 3 areas of Los Angeles (South Los Angeles, Long Beach, and East Los Angeles) to build youth engagement on environmental health issues. Youth workshops will include building skills on community mapping, taking pollution measurements, and creating videos. The COTC and Center researchers will make presentations to policymakers upon request, and highlight the need to consider health when making land use decisions, and reduce pollution to improve public health. Evaluation activities in the next reporting period include process evaluation, and meeting (as we do annually) with the Advisory Committee members for guidance on future programs and feedback on the past activities, and for assistance in measuring long-term outcomes. This year, we split our Advisory Committee into two groups, one focused on social media and ways to reach the public, and another with our other members. One meeting was in March and one in April. It is challenging to resolve the conflict between advocates for affordable housing and new parks (whose only option may be building near freeways) and those with public health concerns (who are concerned about near roadway air pollution). We have discussed approaches to dealing with this issue with our Advisory Committee members, who caution that we do not want to alienate allies in the important effort to build safe and affordable housing or who want more public parks in their communities. We plan to continue meeting and talking to housing and park advocates (as we did at the AQMD EJ Summit and at our own Community Forum) about this issue and ways to resolve the challenges.
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.). |
R835441 (2018) |
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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. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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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.). |
R835441 (2016) R835441 (2017) R835441 (2018) |
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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. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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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. |
R835441 (2018) |
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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.). |
R835441 (2018) |
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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. |
R835441 (2016) R835441 (2017) R835441 (2018) |
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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. |
R835441 (2016) |
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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.). |
R835441 (2018) |
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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
- 2014 Progress Report
- Original Abstract
66 journal articles for this center