BACKGROUND: Children, especially those living near industry sites, are commonly exposed to multiple metals including lead and manganese. These metals are associated with adverse neurodevelopmental outcomes, with evidence of non-linear associations for essential metals. Metals target brain regions involved in cognition and motor function. However, there is a paucity of epidemiological studies focused on early-life exposure to metals, especially in association with less commonly studied neurodevelopmental domains like motor function. OBJECTIVE: To characterize exposure to multiple metals in early life, estimate associations with neurodevelopmental outcomes in adolescence, and examine susceptibility factors including exposure timing, co-exposures, and biological sex. METHODS: Research aims were addressed using data from the Assessing Children’s Environmental Exposures (ACHIEVE) study and the Public Health Impact of Metals Exposure (PHIME) study. The ACHIEVE study included 30 mother-child pairs from the town of Holliston, Massachusetts where naturally shed baby teeth were collected from children ages 5–13 years. In the first aim, we used multivariable linear mixed models to explore sociodemographic, dietary, and behavioral correlates of tooth metal concentrations for children in the ACHIEVE study (N=28). We estimated weekly prenatal and postnatal (up to one year of age) exposure to 12 metals. Tooth metal concentrations were quantified using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). For the second and third aims, we analyzed data from the PHIME study, comprised of 721 Italian adolescents living in proximity to steel production sites. Blood and hair samples were collected at the time of enrollment and analyzed for metals concentrations (manganese, lead, copper, and chromium) using ICP-MS. Teeth were collected for a subset of PHIME participants (N=195) and analyzed for manganese using LA-ICP-MS. A battery of neuropsychological assessments was administered to PHIME participants at enrollment by one of two trained neuropsychologists. In the second aim, we evaluated associations of prenatal, postnatal and childhood manganese levels in teeth with scores of adolescent verbal learning and memory, assessed using an Italian translation of the California Verbal Learning Test for Children (CVLT-C) (N=140). Associations were estimated using multivariable linear and logistic regression, generalized estimating equations and multiple informant models. In the third aim, we estimated associations of a metal mixture (lead, manganese, copper, and chromium) with multiple assessments of motor function (N=612). Statistical methods included generalized additive models, multivariable linear regression, quantile g-computation and Bayesian kernel machine regression. In the second and third aims, we also stratified analysis by sex to examine effect measure modification. Results: In the first aim, we found that temporal trends of tooth metal levels differed by metals and correlates of tooth metal levels included biological sex and primary source of milk during infancy. In the second aim, we estimated manganese-cognition associations that differed by exposure time window: prenatal manganese and childhood manganese for boys was beneficial but postnatal manganese associations were null. In the third aim, we observed sex-specific associations between a metal mixture with motor function scores. The metal mixture was associated with improved motor function scores among females (driven by copper and chromium) whereas the metal mixture was associated with worse motor function scores among males (driven by manganese and copper). CONCLUSION: The association between metal exposure in early life with neurodevelopment is dynamic and complex: associations between metals and neurodevelopment depend on exposure timing, biological sex, and co-exposures. This body of research can be used to inform future research by contributing to the understanding of metal neurotoxicity in critical windows of development and in relation to less studied neurodevelopmental domains, like motor function. / 2025-01-20T00:00:00Z

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Patterns of infectious disease in human populations result from complex interactions between the infectious agent, the disease host, and the environment in which host and agent interact. Many environmental factors influence infectious disease dynamics including characteristics of the natural and built environments and social systems. This dissertation focuses on key environmental factors associated with two timely infectious diseases in the United States (US): acute gastrointestinal illness (AGI) following overflow discharge from combined sewer systems (CSS) in Massachusetts (MA), and patterns of COVID-19 outcomes in relation to the spatial distribution of essential workers in MA. CSS exist in over 700 municipalities in the US as well as cities in Canada, Europe, Asia, and Australasia. When heavy rainfall or snowmelt occurs, CSS discharge untreated or undertreated wastewater into nearby waterways in combined sewer overflow (CSO) events. The association between CSO events and health has been understudied, and critical gaps in knowledge remain, including which exposure pathway(s) may be most relevant in communities downstream of CSO releases, whether CSO events and precipitation are independently associated with AGI, and which subpopulations may be at greatest risk of developing AGI following CSO events. The rapid spread and severity of COVID-19 disease led to widespread stay-at-home orders in the US beginning in March of 2020. In MA, only a designated set of essential businesses remained open during the stay-at-home orders (March through May 2020). During this period, essential workers who performed their duties in person were at higher risk of contracting COVID-19 than people who worked from home, but among essential workers, risk varied by industry- and worksite-specific factors. While differential risk of COVID-19 mortality and outbreaks are documented among essential workers, risk of COVID-19 infection among essential workers has been difficult to ascertain because occupation is frequently missing from state and federal COVID-19 surveillance efforts. The overall objective of this dissertation is to assess the associations between these two infectious diseases in MA and key environmental factors that influence how pathogens and susceptible hosts interact. The relationship between CSO events and AGI was investigated in a geographic region of MA where sewage discharges impact a river that is both a drinking water source and recreational destination for hundreds of thousands of people. Statewide patterns of COVID-19 cases and deaths were evaluated in relation to relative representation of categories of essential workers in MA census tracts. This dissertation relies on health outcome data from administrative and surveillance datasets, all analyses employ ecologic study designs with individual-level data aggregated to small areas, and methods incorporating geospatial and temporal data are included in each study. In Chapter 2, the association between extreme CSO events and AGI was assessed in MA municipalities bordering the CSO-impaired Merrimack River with a secondary analysis evaluating differences in the associations between CSO and AGI based on municipal drinking water source. In the 4-days following 95th percentile upstream CSO discharge events, the cumulative risk ratio (CRR) of AGI increased by 17% and CRR increased by 62% after 99th percentile CSO events. Stratification by drinking water source suggests that the association between CSO events and AGI is most pronounced among municipalities that do not have river-sourced drinking water, but there is elevated risk of AGI among all municipalities regardless of drinking water source following the largest CSO events. These findings suggest that CSO discharge volume is a critical factor in the association between CSO events and AGI, and that exposure to CSO discharge may occur through multiple pathways. Chapter 3 extends the work of Chapter 2 to an evaluation of the strength of the association between CSO events and AGI across subpopulations defined by age, sex, healthcare payer type, area-level social vulnerability, and drinking water source. The CRR of AGI was most pronounced among young people ages 5–19 and people living in areas of low social vulnerability relative to cumulative risk for the population as a whole. The results of this study suggest that the association between CSO events and AGI differs among subpopulations characterized by both physiological and social characteristics. In Chapter 4, categories of essential workers were defined from the broad set of essential occupations defined in the MA emergency response to COVID-19. The association between census-tract-resolution populations of essential worker categories and COVID-19 cases and deaths was evaluated, adjusting for multiple sociodemographic risk factors for COVID-19. Elevated COVID-19 case incidence was observed among census tracts with the highest populations of workers in construction, building maintenance, transportation, production, and public-facing sales and service occupations. Reduced case incidence was observed in tracts with the highest populations of essential workers able to work from home. These findings suggest that occupational composition of census tracts in MA may have influenced community-level COVID-19 transmission, possibly through spread from essential workers to those in their households and communities. Overall, the findings of this dissertation provide insight into the environmental factors associated AGI and COVID-19 in MA. In both cases, consideration of environmental factors provides opportunities to inform public health intervention measures for infectious diseases that are 1) influenced by climate change, and 2) symptomatic of globalization. / 2026-01-03T00:00:00Z

Our changing climate is intensifying the public health threat of extreme heat. Heat morbidity and mortality disproportionately burden those made most vulnerable by social, environmental, and structural factors manifesting heightened exposure and sensitivity as well as reduced adaptive capacity to heat. In order to address and prevent these negative impacts, cities are developing heat adaptation plans. There are several approaches by which researchers have positioned their work as informing decision-making, including vulnerability assessments and participatory action research. However, there remains a need to assess these approaches as applied to heat vulnerability and adaptation, with a lens towards the roles of researchers, decision-makers, and residents. This dissertation uses mixed-methods (qualitative and quantitative) to characterize heat vulnerability and understand perceptions and priorities of participants at multiple levels of assessment (individual, community, city, state). First, we assessed the decision-making implications of, and socio-spatial context for, developing HVIs for city- and state-levels. We found that the choices made in constructing an HVI, including those regarding geographic scale and presentation, influence its results and interpretation. The strong spatial association between HVI scores constructed for the Boston area and redlining maps reinforces the challenges in interpreting sociodemographic and land use covariates absent an historical context, and broadly, the challenges of developing nuanced interpretation from publicly available covariates. Moving from the state and city levels, we then focused in on the levels of community and individual, in the context of neighboring environmental justice and urban heat island communities: Chelsea and East Boston. We evaluated the responses of decision-makers to residents’ experiences, perspectives, and priorities around heat adaptation presented via photovoice. We engaged Chelsea and East Boston decision-makers through interviews with nineteen representatives of local government, public health, and policy organizations. Questions combined with viewing the photovoice exhibit and report elicited interviewees’ nuanced responses and valuable insights. Interviewees described how their work aligns with called-for actions by photovoice participants. They also identified barriers and challenges in taking action, gained insights from the photovoice project, and offered recommendations to expand and build on the called-for actions. Finally, we characterized and contextualized individual-level experiences of heat exposure, sensitivity, and adaptive capacity by integrating quantitative and qualitative data for a sample of ten Chelsea and East Boston residents. Across and within each of these participants’ data, we found high variability in exposures defined by time spent under thermal comfort thresholds, as well as in experiences of sensitivity and adaptive capacity. Participants described both taking on and trying to avoid a number of costs related to thermal comfort, in addition to the significant financial/economic costs, including impacts of heat on health and sleep disturbances, coping strategies around transportation, and other behaviors, including either leaving or staying at home on hot days. We demonstrated the value of mixed-methods analysis at an individual level and offer a framework that centers heat adaptation needs and accessibility in positioning interventions. This dissertation provides evidence for integrating qualitative and quantitative methods in community-engaged, participatory action research approaches that link heat vulnerability assessments to heat adaptation actions. / 2026-01-04T00:00:00Z

Urban environmental health challenges such as poor air quality and extreme heat disproportionately affect environmental justice communities, necessitating targeted interventions. Researchers have assessed these exposures through in-situ monitoring, statistical modeling, or a combination of both. However, there remains a need for data collection that better characterizes local-level exposures, including community-engaged approaches to ensure processes and interventions are appropriate and sustainable. This dissertation uses mixed-methods approaches to characterize local-level extreme heat and air pollution exposures in the urban environmental justice communities of Chelsea and East Boston, MA. First, we explored perceptions of air quality and heat, data resources, and barriers to information sharing through analysis of semi-structured interviews with community leaders serving Chelsea and East Boston. We found that community leaders face challenges conveying the risks associated with air pollution and extreme heat: information is often compartmentalized and complex, with difficulties in accessing and interpreting data for their community. Proposed solutions involved bolstering community participation, establishing portals for open data, and utilizing innovative approaches in science communication. Recommendations include enhanced collaborative partnerships across educational, governmental, and healthcare organizations. Next, we focus on air pollution through a pilot study assessing the use of portable air cleaners (PACs) to reduce indoor PM. We found that PACs were effective in reducing particulate matter when in use, though households varied in their use of the cleaners. Higher filtration levels correlated with more substantial PM reductions, though not uniformly across all homes. While this study suggested PAC efficacy, it also suggested the need for further exploration to reducing PAC implementation challenges in the homes. Finally, we describe an assessment of fine-scale ambient temperature variation within the City of Chelsea, MA, focusing on spatial disparities in heat exposure and implications for local climate planning and policy. Leveraging approximately 80 on-the-ground local temperature sensors, we found local sensors were significantly higher than National Weather Service readings. Through regression analyses and spatial mapping, we identified hot spots within Chelsea facing especially high temperatures during hotter weeks and heat waves. Broadly, this dissertation presents novel, local-level analyses on two important urban environmental exposures with a multitude of associated negative health impacts in the EJ communities of Chelsea and East Boston, MA. We provide evidence towards integrating mixed-methods, community-engaged approaches for strong, action-oriented outcomes. / 2026-05-10T00:00:00Z

Per and polyfluoroalkyl substances (PFAS) are a large class of human made fluorinated chemicals, some of which are persistent in the environment. The small number of PFAS studied have been shown to be mobile in the environment and are routinely measured in humans. For those PFAS, epidemiological and toxicological studies have demonstrated that low exposures are linked to negative health impacts. Understanding exposure to PFAS in human populations is critical to the evaluation of associated health effects and to parsing the relative sources of PFAS. This dissertation examines PFAS definitions, unidentified organofluorine in serum, and the contributions of drinking water and diet to exposure, enhancing our understanding of human PFAS exposures. Definitions of PFAS that group chemicals based on their structure have been proposed that range in their specificity and inclusion. These definitions have implications for the broader suite of organofluorine chemicals, yet little research has been done to evaluate what compounds are included under different definitions of PFAS. Naturally-occurring organofluorine compounds are rare, but organic fluorine is incorporated into many pharmaceuticals. Widely used organofluorine pharmaceuticals, including anti-depressants and cholesterol lowering medications, may commonly occur in human serum and in wastewater. It is not known how PFAS definitions used for categorizing, tracking, and regulating chemicals in commercial products, the environment, and humans vary in their inclusion of organofluorine pharmaceuticals. Thousands of PFAS exist, yet routine human biomonitoring is limited to 7–12 legacy compounds, and much less is known on the occurrence of other PFAS. Expanded testing shows additional PFAS in drinking water and food packaging beyond those that are routinely monitored. Studies using organofluorine mass balance have shown 30–70% of extractable organofluorine (EOF) in serum from China is not explained by targeted PFAS, and research into the identification of unexplained organofluorine is needed. Large amounts of unknown organofluorine have potentially important implications for human biomonitoring. Sources of unknown organofluorine may include replacement PFAS that are not yet measured, pesticides, or pharmaceuticals, the latter frequently used at relatively high doses. People can be exposed to PFAS from multiple and varied sources. Studies in highly exposed communities have shown associations with legacy PFAS in drinking water. While 99% of the U.S. population have detectable levels in serum, most people are not documented to live near large identifiable sources that may contaminate drinking water supplies, suggesting other sources are important. Studies in Europe have estimated the dominant source of exposure in general population to be diet, but regional differences in industry and unique dietary patterns make direct extrapolation to U.S. populations difficult. PFAS can enter foods via bioaccumulation from the environment or through contact with food packaging materials that are treated with PFAS for their grease-proofing properties. Many existing dietary studies in the U.S. use data from many years ago, but shifts in PFAS production over the last 20 years render older studies less reliable for explaining current exposure patterns. Water may also contribute to exposure in the general population, but few epidemiological studies consider contributions from diet and water together. Research on multiple exposure routes is needed in order to better characterize the extent to which sources contribute to exposure. The objectives of this dissertation were to 1) assess the implications of different PFAS definitions for inclusion of organofluorine pharmaceuticals, 2) determine to what extent organofluorine pharmaceuticals contribute to unknown organofluorine in commercial serum from U.S. blood donors, and 3) to examine associations between PFAS body burden and measures of exposure via diet and drinking water for participants in the California Regional Exposure Study. In Chapter 2, nine PFAS definitions were used to screen a comprehensive list of the 360 organofluorine pharmaceuticals approved and used globally between 1954–2021. Definitions ranged in their inclusion of organofluorine pharmaceuticals (1%–100%). The most inclusive definitions included several top prescribed pharmaceuticals, e.g., Prozac and Lipitor. Using pharmaceuticals as an example, we showed that the specificity of a given definition and its usefulness for its intended purpose depends on the context in which the definition is applied. Chapter 3 used combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assessed differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compared them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. For comparison, the geometric mean concentration of PFOS in U.S. adults from 2017–2018 as reported in NHANES was equivalent to 2.9 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) showed the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Compared to donors not taking pharmaceuticals, self-reported use of organofluorine pharmaceuticals was associated with a 0.36 ng F/mL (95% CL: −1.26 to 1.97) increase in UOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by methods of measuring EOF. Findings from this study suggested pharmaceuticals can contribute to EOF, but large amounts of EOF remain unexplained. Chapter 4 assessed contributions from drinking water and diet to levels of PFAS in serum collected from 700 adults living in southern and eastern California in 2018–2020. Using survey information on dietary consumption and levels of PFAS in drinking water measured in the U.S. Environmental Protection Agency’s third Unregulated Contaminant Monitoring Rule (UCMR 3), we used robust linear regression to examine the association between non-transformed serum concentrations, diet, and drinking water. Findings from this analysis suggest drinking and diet both contribute to exposure in this population. Fewer associations were observed for diet compared to epidemiological studies from many years ago. There are multiple possibilities for these unexpected results, including diminished levels in foods and corresponding reductions in serum concentrations, limitations of dietary assessment methods to measure patterns of diet, as well as potential confounding not adequately accounted for in our analysis. This dissertation illustrates the importance of clearly defining PFAS and provides recent data on the occurrence of known and unknown organofluorines in human serum, as well as potential exposure sources in the general population. These findings can guide future human biomonitoring studies and inform source reduction strategies. / 2026-08-23T00:00:00Z

Aircraft noise is a considerable environmental stressor for communities surrounding airports. There is also growing interest in the relationship between noise and health outcomes as exposure has been associated with physiological and psychological effects. Yet the extent to which aircraft noise influences cardiovascular health and cardiovascular disease (CVD) risk is still unclear. There is a shortage of noise-health studies in general, with very little noise characterization in the United States (U.S.) and few noise-health studies conducted using U.S. data. There is also a lack of attention to the inequitable burden of noise exposure on different communities. Most epidemiological studies evaluating the noise-CVD relationship have been unable to systematically incorporate spatially-resolved and time-dependent noise exposures, with few simultaneously examining multiple types of airports. This dissertation aimed to investigate the longitudinal cardiovascular effects of aircraft noise using modeled noise data from 1995–2015 in 5-year intervals for 90 U.S. airports. We first investigated the long-term trends of aircraft noise exposure and demographics of exposed populations in the U.S., then assessed the relationships between aircraft noise exposure and hypertension and CVD in the Women’s Health Initiative (WHI) study cohorts. WHI has followed over 160,000 post-menopausal women recruited from 1993–1998 across 24 U.S. states. Specifically, this dissertation addressed previous study limitations and expanded our understanding of the noise-health relationship by: (aim 1) characterizing spatiotemporal trends of aircraft noise exposure within the U.S. by investigating airport characteristics and demographics of populations exposed; (aim 2) investigating the effect of aircraft noise exposure on incident hypertension, a prominent CVD risk factor; and (aim 3) investigating the effect of aircraft noise exposure on CVD risk. Evaluations of temporal trends in noise exposure (aim 1) showed non-monotonic trends in noise contour areas over time among our sample of 90 U.S. airports. We found disparities in the demographics of exposed communities, where minority populations (e.g., Hispanics/Latinos, Blacks/African Americans) had greater proportions of exposure among their respective sub-populations compared to those who identified as non-Hispanic or White alone across all study years. In evaluating the association between aircraft noise exposure and incident hypertension (aim 2), we found a small yet non-significant association, with indications of elevated risk among post-menopausal women living in areas with lesser ambient noise. Finally, in evaluating the association between aircraft noise exposure and incident CVD (aim 3), we found significant positive risk among participants of the WHI Observational Studies cohort, but not the Clinical Trials. Aviation usage and interest in aircraft noise is continuously growing on both national and international scales. Study results may contribute to the overall scientific knowledge needed to inform policies and targeted interventions for reducing aircraft noise-associated health effects, particularly among vulnerable populations, while reinforcing the need for more large-scale cohort studies investigating the relationships between aircraft noise exposure and adverse health outcomes. / 2026-08-31T00:00:00Z