Grantee Research Project Results
Final Report: UC Berkeley/Stanford Children's Environmental Health Center
EPA Grant Number: R835435Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: UC Berkeley/Stanford Children's Environmental Health Center
Investigators: Hammond, S. Katharine , Shaw, Gary M. , Balmes, John R.
Institution: University of California - Berkeley
EPA Project Officer: Hahn, Intaek
Project Period: July 1, 2013 through June 30, 2018 (Extended to June 30, 2019)
Project Amount: $4,765,843
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:
The Children's Health and Air Pollution Study (CHAPS) is a direct descendant of the University of California, Berkeley/Stanford Children's Environmental Health Pre-Center with the same name. The major goal of the UC Berkeley-Stanford Children's Environmental Health Center is to study the relationship between air pollution in the San Joaquin Valley of California and children's health.
Project 1: Exposures to Air Pollutants, Modifying Genes and Risk of Birth Defects and Preterm Birth
This project had the following 4 aims:
- To determine whether exposures to specific air pollutants (identified in our P20 research) are further modified by gene variants in biotransformation enzymes (e.g., NATs, GSTs, CYPH, or NOS3) for risk of selected birth defects.
- To determine whether ambient exposures to polycyclic aromatic hydrocarbons (PAHs), during critical periods of organogenesis, are associated with women delivering infants/fetuses with birth defects, and whether relationships are further modified by gene variants in Aim 1.
- To determine whether ambient exposures to PAHs, during critical periods of gestation, are associated with women delivering preterm.
- To determine whether the built environment is associated with preterm birth either directly or indirectly through a joint effect with ambient air pollution.
Project 2: Mechanisms of Polycyclic Aromatic Hydrocarbon-linked Immunopathogenesis in Atopy
This project had the following 3 aims:
- Determine the extent to which Treg functional impairment in children with asthma vs. without asthma is associated with high levels of PAH cumulative exposure.
- Determine the degree to which ambient PAH exposure alters Treg immunophenotypes leading to polarization of conventional CD4+ T cells towards a Tstrong phenotype in children with asthma vs. without asthma.
- Determine whether individual PAH exposures (short-term vs. long-term) are associated with increased DNA methylation of the FOXP3 genetic locus in Treg.
Project 3: Obesity and Glucose Dysregulation
Assess the association between exposure to air pollutants, especially ambient polycyclic aromatic hydrocarbons (PAHs), and markers of metabolic dysregulation in children.
Project 4: Transit Exposures During Pregnancy
To test the hypothesis that neighborhood characteristics have a direct and quantifiable relationship with an individual's transit patterns that affect personal exposures to traffic related air pollution (PAHs, PM2.5, and BC). This project had 4 aims:
Aim 1: Define neighborhoods within Fresno by using both secondary and primary data to characterize assets (e.g., bus stops/routes, sidewalks, food outlets) and liabilities (e.g., neighborhood foreclosure rate, density of condemned properties, Toxic Release Inventory sites, and high-speed surface street traffic) of the local built environment.
Aim 2: Estimate the indirect effects of neighborhood assets and liabilities on ambient air pollution by first assessing the impact of the built environment on transit use and then the impact of transit use on simulated personal exposures to PAHs, PM2.5, and BC.
Aim 3: Evaluate environmental exposures by different transit methods by measuring PM2.5, ultrafine particles, black carbon, and particle bound PAHs in 10 neighborhoods in Fresno California.
Aim 4: Evaluate what changes to neighborhood characteristics (i.e., interventions) would have the greatest potential to reduce transit-related exposures to PAHs, PM2.5, and BC in the population as a whole and in subgroups defined by geographic neighborhoods.
Core A: Administrative Core
The goals of the Administration Core include:
- To coordinate the work of the research Projects and Cores by holding biweekly meetings and semi-annual retreats of senior and junior investigators to plan CHAPS-SJV activities and discuss scientific issues.
- To manage the financial and personnel aspects of the overall CHAPS-SJV Center.
- To coordinate with the External Advisory Committee, support their efforts, set up meetings and make travel arrangements.
- To provide synergies in the field work in Fresno by establishing the CHAPS-SJV field office with colleagues at UCSF-Fresno and Clinica Sierra Vista
- To support the Children's Health Specialist, John Balmes
- To support the career development of Faculty Development Investigator and other creative junior faculty-level investigators at UCB, Stanford University, and CSU Fresno through direct mentorship with senior investigators and workshops presented by them to expose the junior investigators to the diversity in environmental health sciences, from basic sciences (mechanisms of immune-pathogenesis), through respiratory effects, field work (exposure assessment, subject recruitment), community engagement, epidemiology and data analysis.
- To support the data management and QA/QC operations of CHAPS-SJV
- To support and implement the data sharing plan
- To support the annual CEHC meetings and the travel of CHAPS-SJV investigators to these meetings.
Core B: Community Outreach Translation Core (COTC)
To provide communities in the San Joaquin Valley with information about the research findings of the Children's Health and Air Pollution Study (CHAPS).
Core C: Biostatistics/Epidemiology Core
The goals of the Biostatistics/Epidemiology Core include:
- Data Management, Quality Assurance and Oversight of Quality Control
- Develop structural framework for each project
- Statistical Analysis
- Service to UCB-Stanford and Other P01 Centers
Core D: Exposure Core
The primary goal of the Exposure Core is to assign individual exposures for relevant time-windows, from in utero to the time of last sample collection, for subjects in research projects 1-3. To do so, the core evaluates existing data, collects additional monitoring data and develops sophisticated models to assign weekly exposures to each study participant for criteria pollutants, as well as polycyclic aromatic hydrocarbons (PAH) and elemental carbon.
Summary/Accomplishments (Outputs/Outcomes):
Underlying all projects is the development of individual-level air pollution exposure estimates. To accomplish this, our exposure core collected air samples and air quality data to understand both temporal (on a weekly basis) and spatial variability of exposure. Using these data, we developed models to predict daily, individual-level exposures to traffic-related air pollutants for each of our study participants, with special focus on polycyclic aromatic hydrocarbons (PAHs) and other traffic-related air pollutants. The exposures generated allow for an examination of multiple exposure windows for each study participant throughout their lifetime, beginning within uteroexposures.
The health effects upon which we are focused include preterm birth, birth defects, allergic diseases, immunologic impacts, telomere length, pulmonary function, obesity and glucose dysregulation. To examine the effects of air pollution on preterm birth and birth defects, we obtained access to records for those who already have given birth. We used California birth records (State Vital Statistics Data) to examine preterm births and the California Birth Defects Monitoring Program (CBDMP)population-based registry to study birth defects. Alternatively, our studies of allergic diseases, immunologic impacts, telomere length, pulmonary function, obesity and glucose dysfunction rely on the following same three cohorts of children, which we have recruited over time in Fresno:
1. Pregnant women (N=220), recruited at ~20 weeks of pregnancy, and their children. Cord blood was collected at birth (n=53), and children were seen at 1 year (n=159) and 2 years (n=145) of age. Pregnant women are recruited through OB/Gyn clinics throughout Fresno and Clovis.
2. Children age 6 to 8 years (n=299), followed up two years after baseline, at ages 8-11 (n=218). Children were recruited through the Fresno Unified School District (schools were ranked by traffic density, and each month, two elementary schools were randomly selected for recruitment – one each from the upper and lower quartiles of traffic density).
3. Adolescents and young adults (N=100) who already have participated in our previous studies in Fresno (our pre-Center). Their follow-up visit was approximately 2 years after their previous visit. Most of these participants had 1 previous study visit (n=75), while a number actually had 2 previous study visits (n=25).
Throughout the study period, we built community support for our research, involved the Fresno community at large, and engaged our cohort participants in the research study and community building. Our Community Advisory Board, consisting of leaders from Fresno specializing in health, environment and children's development, has helped up shape our recruitment, retention, and communications strategies. Through our work with youth at the Center for Advanced Research and Technology (CART) and undergraduate students at Fresno State, we moved forward our goal of training the next generation of environmental public health scientists from within the Central Valley itself. We held numerous events to communicate the results of our research with the Central Valley medical, health education and environmental justice communities. An importantly, our fun family engagement events and periodic newsletters, social media posts and presentations engaged our study participants to share back to them the very research that they are making possible through their involvement in the study.
During the study period and using our various data sources, we have been able to demonstrate the negative consequences of traffic-related air pollution (PAH, NO2, PM2.5, and EC) on a wide range of children's health issues. These include adverse effects on numerous birth outcomes, including preterm birth and several birth defects; on the immune system throughout development and the promotion of allergic disease; and on metabolic dysregulation in children. Not only have we demonstrated the adverse effects of traffic-related air pollutants on children's health outcomes, we have also demonstrated the biological mechanisms underlying these relationships, including interactions between pollution and gene variants in biotransformation enzyme pathways and pollution-mediated epigenetic changes needed for healthy immune function.
We have also demonstrated that neighborhood conditions California's Central Valley can be characterized by a variety of data sources, including direct observations of social order/disorder and walkability, as well as using secondary data sources such as the US Census and California EPA's CalEnviroscreen. In turn, we've demonstrated that, not only are adverse neighborhood conditions related to higher levels of traffic-related air pollution in California's Central Valley, these neighborhood-level factors also are related to asthma and other respiratory conditions and adverse birth outcomes.
Throughout these projects, rigorous standards of quality control and assurance have been instituted. The collection and analysis of all air pollution data followed the quality assurance procedures according to EPA Requirements for Quality Assurance Projects Plans, EPA QA/R-5. All genotyping experiments were carried out by a highly experienced laboratory using state-of-the-art assays and by technicians blinded to case/control status. For laboratory analyses of immune function data, standardization of immune monitoring assays involved the use of quality-controlled reagents with minimal lot-to-lot variability; robust and optimized protocols that constrain all important performance variables; and reproducible instrumentation and instrument setup. For adipokine and isoprostane data, samples were stored at -80ºC and protocols on ELISA kits were followed, with the same internal controls included on each plate for quality assurance and reproducibility between each experimental run. All samples were run in duplicate in order to ensure accuracy of the results.
Vital statistics records and registrations of congenital birth defects by the California Birth Defects Monitoring Program have been well described previously for their completeness and quality. Cohort data collected with study participants in our field office are directly entered into computer-assisted interview software, which has the capacity for built in logic checks and question skip patterns. Further, all data collected in the field office are run through multiple rounds of data cleaning and management using statistical analysis software to verify the validity of responses and allow for the identification of any outliers or anomalies.
During the study period, our Center fostered the growth of many early stage investigators across four different academic institutions (UC Berkeley, Stanford University, UCSF, and Fresno State). During the time in which they were involved with the Center, junior faculty-level investigators were awarded numerous grants (including two Pathway to Independence (K99/R00) awards), one received academic tenure, and four accepted and started faculty positions at well-respected academic institutions.
Project 1: Exposures to Air Pollutants, Modifying Genes and Risk of Birth Defects and Preterm Birth
For Aim 1: For this aim, we identified ~1400 samples buccal cells (mother and infant) and bloodspots (infants only) from available birth defect cases and controls. Those samples have had the DNA extracted and genotyping for a broad panel of biotransformation enzymes has been completed. Epidemiologic analyses on this large amount of data have been made. We have published one manuscript that described the interrogation of these approximately 100 single nucleotide polymorphisms in conjunction with several air pollutant exposures for combinatorial risk on the birth defect, spina bifida. As a summary, in our previous study of air pollution exposures during the first two months of pregnancy, we found associations between high levels of CO and NO2and risk of spina bifida (ORCO= 2.00, 95% CI: 1.06, 3.75; ORNO2= 1.73, 95% CI: 1.01, 2.97). This newest work extends those findings and demonstrates a gene-environment interaction between each of the five criteria pollutants and several gene variants: NO (ABCC2), NO2(ABCC2, SLC01B1), PM10(ABCC2, CYP1A1, CYP2B6, CYP2C19, CYP2D6, NAT2, SLC01B1, SLC01B3),PM2.5(CYP1A1andCYP1A2). We view this investigation as exploratory even though some results showed sizable odds ratios (>4) and 95% confidence intervals excluding 1. Such caution seems prudent owing to sample sizes being relatively small, numerous comparisons being made, and a paucity of previous studies to corroborate these findings.
For Aim 2: We have geocoded all cases and controls and as indicated above have completed all of the genotyping. We have been investigating whether the original targeted geographic area of study (Fresno only) where we could assign PAH exposure can be expanded to the additional surrounding areas and therefore include additional cases and controls for investigation. Epidemiologic analyses are in progress with planned manuscripts to be developed.
For Aim 3: We have published the results of this aim. We applied the PAH exposure model to the study population within 20km of the central site in Fresno, CA. We analyzed the relationship between PAH during several periods during pregnancy (entire pregnancy, each trimester and last 6 weeks) with categories of gestational age at birth to determine the association between PAH and levels of preterm birth. We found associations between PAH during the last 6 weeks of pregnancy and birth at 20-27 weeks (OR=2.74; 95% CI: 2.24-3.34) comparing the highest quartile to the lower three quartiles. When examined for an exposure-response, the association increased across each quartile of PAH exposure. Inverse associations were also observed for exposure to PAH during the entire pregnancy and the first trimester and birth at 28-31 weeks and 20-27 weeks.
For Aim 4: We have conducted analyses on the effects of neighborhood factors and air pollution on preterm birth using causal inference methods (i.e., targeted maximum likelihood estimation). The effects of air pollution appear to be stronger in neighborhoods with greater deprivation. A manuscript is in preparation.
Project 2: Mechanisms of Polycyclic Aromatic Hydrocarbon-linked Immunopathogenesis in Atopy
For Aim 1: We showed that higher average PAH exposure was significantly associated with impaired regulatory T cell (Treg) function conditional on atopic status, suggesting that increased ambient PAH exposure is associated with impaired systemic immunity. In addition, the magnitude of the association increased as the length of the time-window of PAH exposure increased for both asthmatic and non-asthmatic subjects.
For Aim 2: Protein expression of immune cell markers was measured using mass cytometry in PBMCs. We used viSNE to visualize the cytof data, which showed a variety of cell populations.We expanded the aim and focused on the association of multiple types of pollutants with various cell types. Monocytes (e.g elemental carbon level at 1 week; est = -0.73;p=.01) and CD 4+ T cells (e.g. CO level 6 months; est = -0.51;p=.03) were associated with pollution levels at multiple exposure durations.In addition, systolic blood pressure was associated with the percentage of monocytes (est = 2.39;p=.02) and diastolic blood pressure was associated with the percentage of Th1 cells (est = -4.52;p= .04).
For Aim 3: We have found that FOXP3 methylation is associated with asthma status in the promoter region, but not in the enhancer region of FOXP3. We first found that increased PAH was associated with increased FOXP3 methylation. We then investigated other pollutants, such as O3, CO, NO2and PM2.5, and their association with methylation, and found that the strongest association of pollution with FOXP3 methylation is for 90 days post-exposure). Finally, we examined whether the methylation levels are sustained over time by comparing percentage levels across at least a 2-year time span and found that these methylation patterns were sustained across subjects.
Additionally, we found an inverse linear relationship between average PAH exposure and telomere length, as well as between age and telomere length. Asthmatics had shorter mean telomere length than non-asthmatics (1.13 vs. 1.29).
Project 3: Obesity and Glucose Dysregulation
· We confirmed that exposure to traffic-related air pollution is associated with metabolic dysregulation in young children.
· HbA1c is associated with exposure to the following air pollutants: nitrogen dioxide (NO2), fine particulate matter (PM2.5), elemental carbon (EC), and PAHs (4,5, and 6-ring).
· Systolic blood pressure is associated with exposure to NO2.
· Diastolic blood pressure is associated with exposure to traffic-related pollutants, especially EC.
· Waist-height ratio is associated with exposure to NO2.
Project 4: Transit Exposures During Pregnancy
In this exploratory study, we developed multiple ecological measures of neighborhood exposures, neighborhood design, and social-economic aspects of neighborhoods as potential predictors of public transit use, use of active transportation, and health outcomes. In multiple publications, we showed that public health undergraduate students could collect reliable data on neighborhood social conditions and walkability that supplement and extend analyses of transit use and health outcomes using other place-based measures. We also showed that students gained additional interest in research activities and understanding of environmental determinants if health. Importantly, we found that both primary and secondary place-based exposures, social conditions, and walkability measures were predictors of health outcomes in asthma and respiratory health, pregnancy and birth outcomes, survival among elders, and a range of other outcomes.
A manuscript in progress examines one of the key hypotheses raised by the set of published findings noted above. The built environment plays a large role in individuals' choices of modes of transportation. However, researchers do not fully understand the extent to which community-level social stressors play a role in the modes of transportation. This paper seeks to measure the extent to which community-level social and physical stressors impact choices in modes of transportation. To do this, we have collected primary data using a structured social observation tool to assess social and physical stressors in communities in Fresno, California. We gathered secondary data on socioeconomic status, demographic characteristics, time spent commuting to work, and Walk Score® at the census tract-level. The outcomes of interest are use of public transportation to work and driving alone to work. We used Poisson-based regression to estimate the rate of use. In comparison to the communities with both the lowest social and physical order, communities with higher social and physical order were associated with lower rates of public transportation (RR = 0.69 (0.58, 0.81) for social order, RR = 0.74 (0.61, 0.91) for physical order) even when controlling for neighborhood socioeconomic and demographic indicators. The social and physical context of a community need to be considered when assessing people's choices in modes of transportation.
Core A: Administrative Core
Project Coordination:
The CHAPS team established regular communications through bi-weekly meetings of the entire research group, weekly or bi-weekly meetings of the Center's three Principal Investigators, and semi-annual research retreats. The CHAPS External Advisory Committee was consulted throughout the project period, with several in-person meetings held.
Field Office:
Through our strong relationship with the UCSF-Fresno field office, we worked to recruit and retain over 600 study participants for the cohorts examined in Projects 2 and 3. The three cohorts were:
- 220 pregnant women (recruited at recruited at ~20 weeks of pregnancy) and their children. Cord blood was collected at birth (n=53), and children were seen at 1 year (n=159) and 2 years (n=145) of age.
- 299 children ages 6 to 8 years followed up two years after baseline, at ages 8-11 (n=218).
- Adolescents and young adults (N=100) who already have participated in our previous studies in Fresno (our pre-Center). Their follow-up visit was approximately 2 years after their previous visit. Most of these participants had 1 previous study visit (n=75), while a number actually had 2 previous study visits (n=25).
Daily or weekly email and phone communications between UC Berkeley Administrative Core staff and UCSF-Fresno field office staff provided a smooth mechanism for communicating protocol changes, troubleshooting, and equipment needs. Quarterly visits to the field office for purposes of trainings and refreshers provided excellent face-to-face time that strengthened the study.
In addition to collecting large amounts of information from our participants via questionnaire, we were also able gather many anthropometric measurements (e.g., height, weight, body fat percentage) and other clinical measures such as blood pressure. With their permission, we also obtained biological specimens (blood, urine and buccal swab) from most of our participants.
Children's Health Specialist:
Children's Health Specialist, John Balmes, MD. In addition to leading the Center Project on Obesity and Glucose Dysregulation and the COTC, Dr. Balmes has coordinated activities with the Pediatric Environmental Health Specialty Unit (PEHSU) at UCSF, of which he is the Principal Investigator, served as the Physician Member of the California Air Resources Board (CARB), and collaborated with the two other Children's Environmental Health Centers (CERCH, a former center that continues to be very active through other research support mechanisms, and CIRCLE, a current center) that are housed at UC Berkeley during the reporting period. Dr. Balmes collaborated with Dr. Miller in the latter's role as the Children's Health Specialist for CIRCLE. With the CERCH PI, Dr. Brenda Eskenazi, and co-investigators Drs. Bradman and Kim Harley, Dr. Balmes has been collaborating on research projects to assess the respiratory health impacts of organophosphate pesticides, agricultural fumigants, and triclosan. Two publications have resulted from this collaboration. In his role as Physician Member of CARB, Dr. Balmes continues to stress the importance of policy efforts to reduce exposure of children to air pollution, such as pushing for health co-benefits with climate change mitigation strategies, and he regularly briefs both the CHAPS investigators and the Community Advisory Board on the activities of CARB. One of the most important of these current activities is the implementation of a recent California legislation, "AB-617 Nonvehicular air pollution: criteria air pollutants and toxic air contaminants," which is considered a new frontier in air quality management.
Junior Investigators:
The goal was to support the career development of Faculty Development Investigator and other creative junior faculty-level investigators at UCB, Stanford University, and CSU Fresno through direct mentorship with senior investigators and workshops presented by them to expose the junior investigators to the diversity in environmental health sciences, from basic sciences (mechanisms of immune-pathogenesis), through respiratory effects, field work (exposure assessment, subject recruitment), community engagement, epidemiology and data analysis. During the course of the CHAPS P01 center the junior faculty-level investigators funded and included in development activities, led by Dr. Noth, were: Dr. Costello, Dr. Northcross, Dr. Hew, Dr. Liu, Ms. Minor, Dr. Neophytou, Dr. Noth, Dr. Padula, Dr. Prunicki, Prof. Zografos, and Prof. Kwon.
Junior investigators were included as full participants in bi-weekly Center meetings, and we convened junior investigator meetings on how to write successful grant applications to NIH and conducted peer editing.
Specific accomplishments during the project period relating to Faculty Development were:
- Prof Kwon received tenure at Fresno State
- Prof. Zografos became Director, Master of Public Health Program and also Chair of the Department of Public Health at Fresno State University
- Dr. Northcross accepted and started in a faculty position at George Washington University (she had been supported by the P20 and was our original Faculty Development Investigator)
- Dr. Liu accepted and started in a faculty position at Purdue University
- Dr. Neophytou accepted and started in a faculty position at Colorado State, Fort Collins
- Dr. Padula accepted and started a faculty position at University of California, San Francisco.
The junior investigators developed and submitted multiple grant proposals building off of the CHAPS cohorts, exposure data, or methodologies:
- Dr. Neophytou was awarded a K99/R00 award in 2017 by NIEHS titled, 'Air pollution exposures and children's health: mediation and interaction in a counterfactual framework'.
- Dr. Padula was awarded a K99/R00 award in 2013 by NIEHS titled, "Traffic-related air pollution, social factors and adverse birth outcomes."
- Dr. Padula was awarded a R03 award in 2018 by NIEHS titled, "Environmental, social and biological factors and disparities in preterm birth."
- Dr. Padula received the NIH Loan Repayment Program award in the Pediatric Research extramural category for contract years 2013-2015.
- Dr. Noth received the NIH Loan Repayment Program award in the Pediatric Research extramural category for contract years 2014-2018.
- Dr. Kwon received a $5000 award the2014-2015 Provost's Faculty Scholarship Support Programand $1,300 award fromCHHS 2014-2015 Faculty Research and Creative Activity Support Funds,both from California State University, Fresno.
- Dr. Noth was awarded a contract with the California Office of Environmental Health Hazard Assessment, "Pilot Air Quality Study for East Bay Diesel Exposure Project"to expand her work on polycyclic aromatic hydrocarbon monitoring in Richmond, using methodologies developed in this center.
Data Management and Sharing:
Throughout the Center's work, rigorous standards of quality control and assurance have been instituted. The Administrative Core ensured quality assurance in the collection and analysis of air pollution data, biospecimen data, and interview data.
Significant changes with the UC Berkeley IT structure resulted in major changes to the way in with the Center's data were stored, managed and shared mid-way through the funded project period. The CHAPS data manager worked closely with UC Berkeley's Information Services & Technology department and Research Data Management program to rebuild the server running the Center's computer-interview assisted program and associated database. The Center's data manager also established a new storage and sharing system for the data to ensure both data integrity and access to all CHAPS collaborators.
Core B: Community Outreach Translation Core (COTC)
· We convened a Community Advisory Board that met 2-3 times per year, and which included members from community-based organizations, local governmental agencies, and academia to advise CHAPS investigators about research priorities and how best to communicate research findings.
· We produced several newsletters and brochures describing the findings of our research.
· We were interviewed by local news media (Fresno Bee and Valley Public Radio) about our research findings.
· We held several community events to engage the families participating in our research.
· We supported student projects at The Center for Advanced Research and Technology (CART), a joint project of Clovis and Fresno USD, that provides STEM education for high school students (www.cart.org).
· We developed a website to inform community members about our researchhttps://www.chapssjv.org.
· We made multiple presentations about our research at San Joaquin Valley area venues.
Core C: Biostatistics/Epidemiology Core
Data Management and Quality Assurance/Control:
Throughout the project period, all data collection instruments and forms were developed in conjunction with multiple CHAPS collaborators. Pilot testing of instruments was performed, and any necessary adjustments were made. Once translated into Spanish, the data collection instruments are programmed into our Computer-Assisted Interview program called CASIC Builder, which our interviewers are employing for real-time data entry during interviews. Training on new protocols and data collection instruments was delivered in-person to the UCSF-Fresno field office staff during our quarterly visits. Following the administration of the first ~10 visits in the field, we engaged the interviewers and performed an extensive review of the data to identify and remedy any problematic issues with the instruments. This extensive review sometimes led to minor adjustments to the instruments and also sometimes highlighted needs for additional trainings.
Cohort data collected with study participants in our field office are entered directly into computer-assisted interview software, which has the capacity for built in logic checks and question skip patterns. Further, all data collected in the field office are run through multiple rounds of data cleaning and management using statistical analysis software to verify the validity of responses and allow for the identification of any outliers or anomalies. We have had had six data releases to Center collaborators over the project period and a final one is planned for Winter 2019.
Structural Framework:
We developed an overarching Directed Acyclic Graph (DAG) for center-level (integrated) key hypotheses (see Fig. 1). This DAG helps unite the different projects and cores and underscores the overarching biological hypothesis of molecular inflammation as central to all of our research questions. Molecular inflammation is the process by which air pollution leads to poorer birth outcomes (project 1) and obesity/dysregulation outcomes (project 3). Socioeconomic status variables, as measured in project 4 and by questionnaire, could influence air pollution exposure (exposure core) and have independent effects on methylation (project 2) and obesity/dysregulation outcomes (project 3). Air pollution can also have independent effects on methylation and obesity/dysregulation outcomes. And, lastly, methylation can lead to changes in obesity/dysregulation outcomes.
Figure 1: DAG for Center's work
Statistical Analysis and Service to the Center:
Throughout the period during which the Center was engaging in research, the Biostatistics/Epidemiology Core has provided support to investigators on all four projects in the form of consultations, sharing papers outlining innovative techniques, sharing coding, and reviewing papers for their statistical approach.
Core D: Exposure Core
During the project period and to achieve the objective of the research, we:
1. Acquired and analyzed historical air quality data for the San Joaquin Valley (SJV) in the 1997-2019 time period.
2. Estimated time series of PAH concentrations in the major SJV urban areas from 1997-2016
3. Collected hourly concentrations of important air pollutants for several years through the study. Augmented the existing air monitoring network in Fresno with speciated polycyclic aromatic hydrocarbon (PAH) measurements at two fixed sites and continuous measurements of combustion products, including aggregated particle phase-PAH (at four fixed sites), black carbon (BC), and brown carbon measurements (at two fixed sites). These fixed site measurements of PAH and carbon complemented on-going ozone, NO2, NO, CO, PM2.5, and PM10measurements at these sites, that together provided the ~6-year air quality database essential for the spatiotemporal model development and exposure assignments for the 2013-2019 time period.
4. Conducted multiple sampling campaigns to characterize the spatial patterns of individual PAH, BC, and NO2across Fresno and to analyze these field samples in our laboratory. The spatial saturation experiments were conducted in winter 2014-2015 at up to 50 locations concurrently to evaluate spatial patterns of air pollution in Fresno.
5. Developed spatiotemporal models of daily concentrations of PAHs and BC using the results of the sampling campaigns together with aggregated particle phase-PAH and other pollutant concentrations measured continuously at two fixed sites in Fresno, plus traffic, land use, meteorology, geophysical parameters, and demographic data.
6. Assigned individual participant exposures to PAH, BC, ozone, NO2, NO, CO, PM2.5, and PM10using individual participant data (e.g., residence history, school attendance), the spatiotemporal models developed in the study, and air pollution monitoring data from the two fixed sites.
Conclusions:
Overall, the work done by our Center during the period of funding has elucidated the detrimental effects of traffic-air pollution on wide-ranging aspects of the health and well-being of children, as well as the biological mechanisms by which these adverse effects occur. Further, we have demonstrated the role that the built environment plays in mediating the effects of traffic-related air pollutants on children's health. These scientifically robust findings can serve as the basis for the development and support of policies in California and beyond that move toward a reduction in vehicle miles travelled, reduced reliance on diesel- and gasoline burning vehicles, improvements in neighborhood quality, and empowerment of environmental justice communities. Project 1: Exposures to Air Pollutants, Modifying Genes and Risk of Birth Defects and Preterm Birth
The rich data generated in this Project will continue to be explored in the next few years despite the cessation of funding. We intend to: (a) continue to investigate the interaction of air pollution and gene variants with regard to additional specific birth defects. We plan to develop several draft manuscripts; (b) We plan to assign PAH exposures obtained from the Exposure Core to the birth defects data and conduct epidemiologic analyses for potential relationships between PAH, genes, and selected birth defects. A draft manuscript of this work will be developed; and (c) We will continue to evaluate the data we have on neighborhood deprivation and apply causal inference methods. We will also incorporate additional data on the built environment provided from Project 4.
Project 2: Mechanisms of Polycyclic Aromatic Hydrocarbon-linked Immunopathogenesis in Atopy
Collectively, these results will demonstrate the detrimental impact of AAP on the immune system throughout development and the role of air pollution exposure in allergic disease. Our overall objective is to determine the molecular mechanisms by which immune dysregulation leads to human disease, specifically the atopic diseases of food allergy, allergic rhinitis, allergic conjunctivitis and allergic asthma in the children exposed to high levels of ambient air pollutants. The rich data generated in this Project will continue to be explored in the next few years despite the cessation of funding, and manuscript writing will continue.
Project 3: Obesity and Glucose Dysregulation
Our data suggest that exposure to traffic-related air pollution during childhood may be a risk factor for the development of metabolic syndrome in adults.
Project 4: Transit Exposures During Pregnancy
Although the collection of neighborhood level exposure variables using portable air monitoring has not yet yielded publications, the engagement of Dr. Kwon and others on the team in learning to use and interpret data from individual monitors has been associated with an explosion in use of this equipment in the region since the study began in 2013. Focus group interviews with over 30 women (who were either new mothers, pregnant, or anticipating pregnancy) highlighted their beliefs around the need for collective action to increase neighborhood air quality and improve other health determinants. They cited the use of personal monitors and their intent to become engaged in air quality citizen science as a new factor in their lives.
Journal Articles: 44 Displayed | Download in RIS Format
Other center views: | All 126 publications | 45 publications in selected types | All 44 journal articles |
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Alcala E, Cisneros R, Capitman JA. Health care access, concentrated poverty, and pediatric asthma hospital care use in California's San Joaquin Valley: a multilevel approach. Journal of Asthma 2017:1-9. |
R835435 (2018) R835435 (Final) |
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Alcala E, Brown P, Capitman JA, Gonzalez M, Cisneros R. Cumulative impact of environmental pollution and population vulnerability on pediatric asthma hospitalizations:a multilevel analysis of CalEnviroScreen. International Journal of Environmental Research and Public Health. 2019;16(15):2683.. |
R835435 (Final) |
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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. |
R835435 (Final) R835441 (2018) |
Exit Exit Exit |
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Cossi M, Zuta S, Padula AM, Gould JB, Stevenson DK, Shaw GM. Role of infant sex in the association between air pollution and preterm birth. Annals of Epidemiology 2015;25(11):874-876. |
R835435 (2015) R835435 (2016) R835435 (2018) R835435 (Final) |
Exit Exit Exit |
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Gou P, Chang X, Ye Z, Yao Y, Nguyen PK, Hammond SK, Wang J, Liu S. A pilot study comparing T-regulatory cell function among healthy children in different areas of Gansu, China. Environmental Science and Pollution Research 2017;24(28):22579-22586. |
R835435 (Final) |
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Hew KM, Walker AI, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth EM, Mann JK, Pratt B, Balmes J, Hammond SK, Eisen EA, Nadeau KC. Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clinical & Experimental Allergy 2015;45(1):238-248. |
R835435 (2014) R835435 (2015) R835435 (2016) R835435 (Final) R834596 (2012) R834596 (Final) R834596C003 (Final) R834786 (Final) |
Exit Exit Exit |
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Kohli A, Garcia MA, Miller RL, Maher C, Humblet O, Hammond SK, Nadeau K. Secondhand smoke in combination with ambient air pollution exposure is associated with increased CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children. Clinical Epigenetics 2012;4(1):17 (16 pp.). |
R835435 (Final) R834596 (2011) R834596 (2012) R834596 (Final) R834596C003 (2011) R834596C003 (2012) R834596C003 (Final) R834786 (2012) |
Exit |
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Kwon J, Weisel CP, Morandi MT, Stock TH. Source proximity and meteorological effects on residential outdoor VOCs in urban areas: results from the Houston and Los Angeles RIOPA studies. Science of the Total Environment 2016;573:954-964. |
R835435 (2018) |
Exit Exit Exit |
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Lee EY, Lin J, Noth EM, Hammond SK, Nadeau KC, Eisen EA, Balmes JR. Traffic-related air pollution and telomere length in children and adolescents living in Fresno, CA: a pilot study. Journal of Occupational and Environmental Medicine 2017;59(5):446-452. |
R835435 (2018) R835435 (Final) |
Exit |
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Lessard LN, Alcala E, Capitman JA. Pollution, poverty, and potentially preventable childhood morbidity in central California. The Journal of Pediatrics 2016;168:198-204. |
R835435 (2014) R835435 (2016) R835435 (Final) |
Exit Exit Exit |
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Liu J, Zhang L, Winterroth LC, Garcia M, Weiman S, Wong JW, Sunwoo JB, Nadeau KC. Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells. Journal of Toxicology 2013;2013:967029. |
R835435 (Final) R834596 (2012) R834596 (Final) R834596C003 (2012) R834596C003 (Final) R834786 (2012) |
Exit |
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Mann JK, Balmes JR, Bruckner TA, Mortimer KM, Margolis HG, Pratt B, Hammond SK, Lurmann FW, Tager IB. Short-term effects of air pollution on wheeze in asthmatic children in Fresno, California. Environmental Health Perspectives 2010;118(10):1497-1502. |
R835435 (Final) R834596 (2010) R834596 (2011) R834596 (2012) R834596 (Final) |
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Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I. Ambient air pollution impairs regulatory T-cell function in asthma. Journal of Allergy and Clinical Immunology 2010;126(4):845-852.e10. |
R835435 (Final) R834596 (2010) R834596 (2011) R834596C003 (2010) R834596C003 (2011) R834786 (2011) |
Exit Exit |
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Noth EM, SK Hammond, GS Biging, and IB Tager. 2011. A spatial-temporal regression model to predict daily outdoor residential PAH concentrations in an epidemiologic study in Fresno, CA. Atmospheric Environment 2011;45(14):2394-2403. |
R835435 (Final) R828678C017 (Final) |
Exit Exit |
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Noth EM, Hammond SK, Biging GS, Tager IB. Mapping and modeling airborne urban phenanthrene distribution using vegetation biomonitoring. Atmospheric Environment 2013;77:518-524. |
R835435 (Final) R834596 (Final) |
Exit Exit Exit |
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Noth EM, Lurmann F, Northcross A, Perrino C, Vaughn D, Hammond SK. Spatial and temporal distribution of polycyclic aromatic hydrocarbons and elemental carbon in Bakersfield, California. Air Quality, Atmosphere & Health 2016;9(8):899-908. |
R835435 (2016) R835435 (2018) R835435 (Final) |
Exit Exit |
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Ortega Hinojosa AM, MacLeod K, Balmes JR, Jerrett M. Influence of school environments on childhood obesity in California. Environmental Research 2018;166:100-107. |
R835435 (2018) |
Exit Exit Exit |
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Padula AM, Mortimer K, Hubbard A, Lurmann F, Jerrett M, Tager IB. Exposure to traffic-related air pollution during pregnancy and term low birth weight:estimation of causal associations in a semiparametric model. American Journal of Epidemiology 2012;176(9):815. |
R835435 (Final) |
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Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann F, Shaw GM. Ambient air pollution and traffic exposures and congenital heart defects in the San Joaquin Valley of California. Paediatric and Perinatal Epidemiology 2013;27(4):329-339. |
R835435 (Final) R834596 (2011) R834596 (2012) R834596 (Final) R834596C002 (2011) R834596C002 (2012) R834596C002 (Final) |
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Padula AM, Tager IB, Carmichael SL, Hammond SK, Lurmann F, Shaw GM. The association of ambient air pollution and traffic exposures with selected congenital anomalies in the San Joaquin Valley of California. American Journal of Epidemiology 2013;177(10):1074-1085. |
R835435 (Final) R834596 (2011) R834596 (2012) R834596 (Final) R834596C002 (2011) R834596C002 (2012) R834596C002 (Final) |
Exit |
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Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann FW, Shaw GM. Traffic-related air pollution and selected birth defects in the San Joaquin Valley of California. Birth Defects Research, Part A: Clinical and Molecular Teratology 2013;97(11):730-735. |
R835435 (Final) R834596 (2012) R834596 (Final) R834596C002 (2012) R834596C002 (Final) |
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Padula AM, Mortimer KM, Tager IB, Hammond SK, Lurmann FW, Yang W, Stevenson DK, Shaw GM. Traffic-related air pollution and risk of preterm birth in the San Joaquin Valley of California. Annals of Epidemiology 2014;24(12):888-895e4. |
R835435 (2015) R835435 (2016) R835435 (2018) R835435 (Final) R834596 (2012) R834596 (Final) R834596C001 (2012) R834596C001 (Final) |
Exit Exit Exit |
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Padula AM, Noth EM, Hammond SK, Lurmann FW, Yang W, Tager IB, Shaw GM. Exposure to airborne polycyclic aromatic hydrocarbons during pregnancy and risk of preterm birth. Environmental Research 2014;135:221-226. |
R835435 (2014) R835435 (2015) R835435 (2016) R835435 (2018) R835435 (Final) |
Exit Exit Exit |
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Padula AM, Balmes JR, Eisen EA, Mann J, Noth EM, Lurmann FW, Pratt B, Tager IB, Nadeau K, Hammond SK. Ambient polycyclic aromatic hydrocarbons and pulmonary function in children. Journal of Exposure Science & Environmental Epidemiology 2015;25(3):295-302. |
R835435 (2014) R835435 (2015) R835435 (2016) R835435 (Final) R834596 (2012) R834596 (Final) |
Exit Exit |
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Padula AM, Yang W, Carmichael SL, Tager IB, Lurmann FW, Hammond SK, Shaw GM. Air pollution, neighbourhood socioeconomic factors, and neural tube defects in the San Joaquin Valley of California. Paediatric and Perinatal Epidemiology 2015;29(6):536-545. |
R835435 (2015) R835435 (2016) R835435 (2018) R835435 (Final) |
Exit Exit |
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Padula AM, Yang W, Schultz K, Tom L, Lin B, Carmichael SL, Lammer EJ, Shaw GM. Gene variants as risk factors for gastroschisis. American Journal of Medical Genetics Part A 2016;170(11):2788-2802. |
R835435 (2018) R835435 (Final) |
Exit Exit |
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Padula AM, Yang W, Carmichael SL, Lurmann F, Balmes J, Hammond K, Shaw GM. Air pollution, neighborhood acculturation factors and neural tube defects among Hispanic women in California. Birth Defects Research 2017;109(6):403-422. |
R835435 (2017) R835435 (2018) R835435 (Final) |
Exit Exit |
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Padula AM, Yang W, Schultz K, Lurmann F, Hammond SK, Shaw GM. Genetic variation in biotransformation enzymes, air pollution exposures, and risk of spina bifida. American Journal of Medical Genetics, Part A 2018 May;176(5):1055-1090. |
R835435 (2018) R835435 (Final) |
Exit Exit |
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Prunicki M, Stell L, Dinakarpandian D, de Planell-Saguer M, Lucas RW, Hammond SK, Balmes JR, Zhou X, Paglino T, Sabatti C, Miller RL, Nadeau KC. Exposure to NO2, CO, and PM2.5 is linked to regional DNA methylation differences in asthma. Clinical Epigenetics 2018;10:2. |
R835435 (2018) R835435 (Final) |
Exit Exit Exit |
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Prunicki, M., et al., Exposure to NO2, CO, and PM2.5 Is Linked to Regional DNA Methylation Differences in Asthma (submitted). |
R835435 (2017) |
not available |
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Tager IB, Lurmann FW, Haight T, Alcorn S, Penfold B, Hammond SK. Temporal and spatial patterns of ambient endotoxin concentrations in Fresno, California. Environmental Health Perspectives 2010;118(10):1490-1496. |
R835435 (Final) |
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Zografos K, Krenz V, Yarmo K, Alcala E. College students’ utilization of protective alcohol-use behaviors. Californian Journal of Health Promotion 201;13(1): 49-58. |
R835435 (Final) |
Exit |
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Gale SL, Noth EM, Mann J, Balmes J, Hammond SK, Tager IB. Polycyclic aromatic hydrocarbon exposure and wheeze in a cohort of children with asthma in Fresno, CA. Journal of Exposure Science and Environmental Epidemiology 2012;22(4):3 86. |
R835435 (Final) |
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Syed A, Hew K, Kohli A, Knowlton G, Nadeau KC. Air pollution and epigenetics. Journal of Environmental Protection 2013;4(08):114. |
R835435 (Final) |
not available |
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Sabounchi S, Bollyky J, Nadeau K. Review of environmental impact on the epigenetic regulation of atopic diseases. Current Allergy and Asthma Reports 2015;15(6):33. |
R835435 (Final) |
Exit |
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Quinn C, Miller-Lionberg DD, Klunder KJ, Kwon J, Noth EM, Mehaffy J, Leith D, Magzamen S, Hammond SK, Henry CS, Volckens J. Personal exposure to PM2.5 black carbon and aerosol oxidative potential using an automated microenvironmental aerosol sampler (AMAS). Environmental Science & Technology 2018;52(19):11267-11275. |
R835435 (Final) |
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Weber KA, Yang W, Carmichael SL, Padula AM, Shaw GM. A machine learning approach to investigate potential risk factors for gastroschisis in California. Birth Defects Research 2019;111(4):212-221. |
R835435 (Final) |
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Padula AM, Yang W, Lurmann FW, Balmes J, Hammond SK, Shaw GM. Prenatal exposure to air pollution, maternal diabetes and preterm birth. Environmental Research 2019;170:160-167. |
R835435 (Final) |
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Prunicki M, Zhou X, Nadeau K. The impact of a prescribed burn versus a wildfire on the immune and cardiovascular systems of children. Journal of Allergy and Clinical Immunology 2019;143(2):AB80. |
R835435 (Final) |
Exit Exit |
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Padula AM, Yang W, Schultz K, Lee C, Lurmann F, Hammond SK, Shaw GM. Gene–environment interactions between air pollution and biotransformation enzymes and risk of birth defects. Birth Defects Research 2021; 113(9):676-686. |
R835435 (Final) |
Exit |
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Prunicki, M and Nadeau, K. (2016) The Air We Breathe:How Extreme Weather Conditions Harm Us in Extreme Weather, Health, and Communities:Interdisciplinary Engagement, Springer Publishers. |
R835435 (2017) |
not available |
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Weber KA, Yang W, Lurmann F, Hammond SK, Shaw GM, Padula AM. Air pollution, maternal hypertensive disorders, and preterm birth. Environmental Epidemiology. 2019 Oct 1;3(5):e062. |
R835435 (Final) |
not available |
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Zografos, K; Alcala, E; & Capitman, J. Integrating Research Experiences into Public Health Curricula:Effects on Undergraduate Students’ Overall Educational Experience. To be submitted to:Pedagogy in Health Promotion. |
R835435 (2017) |
not available |
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Zografos K, Alcala E, Capitman J, Khang L. Integrating research experiences into public health curricula:effects on undergraduate students’ knowledge of neighborhood inequalities, perception of research, and motivation to talk about health issues. Pedagogy in Health Promotion 2019:2373379919881469. |
R835435 (Final) |
not available |
Relevant Websites:
Children's Health & Air Polution Study (CHAPS) Community Outreach Website Exit
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
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- Original Abstract
44 journal articles for this center