Global climate change is anticipated to raise the overall temperatures and is likely to increase future mortality attributable to heat. Predicting future health consequences of higher temperatures at the regional, national and global level based on historical temperature-mortality relationships can be challenging due in part to the uncertainties in the location-specific temperature-mortality relationship, the heat threshold, and how populations will adapt or acclimatize. This study reviews published estimates of the warm season temperature-mortality relationships around the world and explores the heterogeneity in terms of the magnitude of the relationship and the threshold. We also investigate the potential effects of adaptation and acclimatization on the estimates of excess heat-related deaths based on empirical evidence, and propose a method that can be used in future projections to address the uncertainties. This study contributes to the literature of projecting the future public health burden of heat-related effects, which provides valuable information to climate policy decision making.

The survival of three enteroviruses (polio 1, coxsackie B3 and echo 1) and a rotavirus (SA-11) was studied under laboratory conditions. The effects of temperature, dissolved oxygen, detention time, sludge source and virus type on virus inactivation were determined. Temperature was the single most important factor influencing the rate of virus inactivation. No significant differences were found for virus inactivation rates at dissolved oxygen levels between 0.9 and 5.8 mg/l. However, the inactivation rate of the viruses under aerobic conditions was found to be significantly greater than the inactivation rate under anaerobic conditions (−0.77log10/day vs −0.33 log10/day). Sludge source, detention time and virus type did not significantly influence the rate of virus inactivation.

This study assessed the usefulness of multivariate statistical tools to characterize watershed dynamics and prioritize streams for remediation. Three multiple regression models were developed using water quality data collected from Sinking Creek in the Watauga River watershed in Northeast Tennessee. Model 1 included all water quality parameters, model 2 included parameters identified by stepwise regression, and model 3 was developed using canonical discriminant analysis. Models were evaluated in seven creeks to determine if they correctly classified land use and level of fecal pollution. At the watershed level, the models were statistically significant (p < 0.001) but with low r2 values (Model 1 r2 = 0.02, Model 2 r2 = 0.01, Model 3 r2 = 0.35). Model 3 correctly classified land use in five of seven creeks. These results suggest this approach can be used to set priorities and identify pollution sources, but may be limited when applied across entire watersheds.

Determining the level of belief one has in themselves, or their self-efficacy, can be a key factor to improve certain dietary patterns and choices in the rural youth population. Sugar sweetened food and beverage consumption continues to rise and fruit and vegetable intake remains a struggle in rural areas; addressing both the food environment and adolescents’ self-efficacy could have a lasting impact on changing the nature of a generation of rural student’s food and beverage choices. This study measured self-efficacy levels of (n=425) adolescents in rural Kentucky and North Carolina using the Youth Impact Questionnaire and dietary intake using the NHANES Dietary Screener. Multiple linear regression analysis found that higher levels of self-efficacy resulted in a statistically significant ability to consume more vegetables. Further associations found that higher levels of self-efficacy resulted in increased fruit consumption, and improved added sugar food and beverage selections. These findings suggest that it could be beneficial to target adolescents’ self-efficacy as a way to modify certain health behaviors in a sparse food environment such as these rural Appalachian areas.

Uncontrolled growth of vascular stem cells as a result of endothelial-mesenchymal transition is considered to cause hyper-proliferative vascular remodeling in severe pulmonary arterial hypertension (PAH) patients. Hyperplastic intimal growth is one of the causes of closure of the lumen of pulmonary arterioles. This abnormal vessel remodeling leads to the progressive increase in pressure of the pulmonary arterioles causing severe PAH; and debilitating harm to patients resulting in mortality from right heart failure. Environmental factors, including polychlorinated biphenyls (PCBs), are considered to be involved in hyper-proliferative vascular remodeling because genetic makeup can only explain about 10% of severe PAH cases. PCB involvement in lung toxicity has received attention because (i) they have been reported to accumulate in the lung; (ii) PCBs produce pathological vascular remodeling in the experimental model; high levels of PCBs are found in human lung tissue; and (iii) epidemiological studies show the association between lung toxicity and PCBs; and prevalence of hypertension and elevated concentrations of particularly PCB153. Recent studies identify PCB153 as one of the largest contributors for total PCB body burden in humans. Our previous studies demonstrated PCB153 mediated vascular endothelial dysfunction and activated the inhibitor of differentiation protein 3 (ID3). ID3 is an important determinant of mitogen and reactive oxygen species-induced G1→S phase cell cycle progression. Although phosphorylation of ID3 increases cell growth by antagonizing the transcription of cell cycle inhibitors, still there is a critical gap in understanding the molecular mechanism(s) of pulmonary proliferative vascular remodeling associated with PCB exposure in humans and the role of the transcription regulator ID3. Our overall objective was to investigate ID3 mediated transcriptional reprogramming as a driver of PCB153-induced pathological proliferative vascular remodeling. Stable ectopic expression of ID3 in lung endothelial cells contributed to endothelial-mesenchymal transition (EndMT), cell proliferation, and cell migration. Using an endothelial spheroid assay, an established method to measure aberrant hyper-proliferation of endothelial cells in PAH patients, we show that stable ectopic expression of ID3 increased the number and size of vascular spheres. ID3 overexpressing cells exposed to environmentally relevant concentrations of PCB153 showed a two-fold increase in cell proliferation as determined by MTT, SRB, and BrdU assays. ID3 overexpressing cells showed the loss of VE-cadherin and gain of MMP9 and vimentin, which are markers of EndMT. PCB153 also increased phosphorylation of ID3 in lung endothelial cells. To determine the molecular mechanism by which ID3 contributes to hyper-proliferative endothelial cells, we investigated ID3 transcriptional reprogramming using ChIP-Seq and RNA-Seq technology. We show here for the first time that ID3 is part of a more general mechanism of transcriptional regulation. Our ChIP-Seq data show that ID3 binds to a subset of approximately 1200 target genes. Comprehensive motif analysis of ChIP-Seq data using the MEME Suite software toolkit revealed that ID3 bound to the GAGAGAGAGA motif sequence on genomic DNA. We also show a significant preference of ID3 binding to motifs associated with transcription factors IRF1, BC11A, IRF4, PRDM1, FOXJ3, SMAD4, ZBTB6, GATA1, and STAT2. Using an integrative approach of ChIP-Seq and RNA-Seq data, we identified 19 genes whose promoter region was bound by ID3 and RNA was differentially expressed in ID3 overexpressing cells. In summary, our data demonstrated that PCB153 and/or ID3 induces proliferation of lung endothelial cells via transcriptional reprogramming. Discoveries from these findings will lay the necessary groundbreaking work for testing the efficacy of ID3 antagonists for the prevention and treatment of pathological vascular remodeling as well as provide a new paradigm by which PCBs may contribute to lung vascular toxicity.

Spray Polyurethane Foam insulation (SPF) kits are currently being marketed and sold to do-it-yourselfers to meet various insulating needs. Like commercial SPF systems, the primary health concern with SPF kits is user overexposure to the isocyanates during product application. The potential health risk associated with SPF applications is driven by several factors including (but not limited to): the toxicity of isocyanates; the potentially high exposure intensity; the quantity of isocyanates used in the process; the enclosed nature of the environment in which the product could be applied; the potentially high exposure duration/frequency; and the limited availability of control measures to reduce agent intensity (e.g., personal protective equipment, dilution ventilation). To better understand the potential hazards associated with the use of SPF kits, the current study was designed to provide an initial characterization of user exposure to airborne particulate during the application process. Specifically, the study would aim to answer the following: * What is the particle size distribution of the aerosol a SPF kit user is exposed to during application? * What is the airborne particle mass concentration a SPF kit user is exposed to during application? To answer these questions, a single commercially available SPF kit was selected for use and a mock residential environment was constructed to support repeated applications of SPF. Size-selective and total dust air sampling were conducted during the applications to determine the particle size distribution and mass concentration of aerosols generated by the selected kit. The particle size distributions developed from the size selective sampling results showed the presence of airborne particulate capable of penetration to the gas exchange regions of the respiratory tract. The average mass median diameter and geometric standard deviation of the particle size distributions were 4.6 µm and 2.7 respectively. The total dust sampling results showed mean airborne concentrations of 10.40 mg/m3. Based on the sampling results the study, personal air monitoring is needed to assess the degree of user exposure to methylene diphenyl diisocyanate (MDI) and to provide information for the selection of exposure control methods.

The Multi-Agency Radiological Site Survey Investigation Manual (MARSSIM) is a regulatory guidance document regarding compliance evaluation of radiologically contaminated soils and buildings (USNRC, 2000). Compliance is determined by comparing radiological measurements to established limits using a combination of hypothesis testing and scanning measurements. Scanning allows investigators to identify localized pockets of contamination missed during sampling and allows investigators to assess radiological exposure at different spatial scales. Scale is important in radiological dose assessment as regulatory limits can vary with the size of the contaminated area and sites are often evaluated at more than one scale (USNRC, 2000). Unfortunately, scanning is not possible in the subsurface and direct application of MARSSIM breaks down. This dissertation develops a subsurface decision framework called the Geospatial Extension to MARSSIM (GEM) to provide multi-scale subsurface decision support in the absence of scanning technologies. Based on geostatistical simulations of radiological activity, the GEM recasts the decision rule as a multi-scale, geospatial decision rule called the regulatory limit rule (RLR). The RLR requires simultaneous compliance with all scales and depths of interest at every location throughout the site. The RLR is accompanied by a compliance test called the stochastic conceptual site model (SCSM). For those sites that fail compliance, a remedial design strategy is developed called the Multi-scale Remedial Design Model (MrDM) that spatially indicates volumes requiring remedial action. The MrDM is accompanied by a sample design strategy known as the Multi-scale Remedial Sample Design Model (MrsDM) that refines this remedial action volume through careful placement of new sample locations. Finally, a new sample design called “check and cover” is presented that can support early sampling efforts by directly using prior knowledge about where contamination may exist. This dissertation demonstrates how these tools are used within an environmental investigation and situates the GEM within existing regulatory methods with an emphasis on the Environmental Protection Agency’s Triad method which recognizes and encourages the use of advanced decision methods. The GEM is implemented within the Spatial Analysis and Decision Assistance (SADA) software and applied to a hypothetical radiologically contaminated site.

This thesis will use data derived from in-depth interviews, historical research, and environmental justice literature to examine the academic achievement of students living in the Community of Lennox. Specifically, this thesis will explore the intersectionality between social environments and academic resources to analyze how it supports or deters students from obtaining a higher degree education.

Multiple Sclerosis (MS) is a neurological autoimmune disease characterized by demyelination of central nervous system tissue and one way this is presented is in the demyelination of the retinal nerve, causing vision disturbance and loss (Munger et al., 2006). The thinning of the retinal nerve fiber layer (RNFL) can be measured and visualized using a noninvasive technique called Optical Coherence Tomography (OCT), which is also used to measure relative MS severity (Petzold et al., 2010). One environmental factor that has been found to have a relationship with MS is vitamin D; research findings suggest that sufficient levels of vitamin D may reduce the risk of developing MS, decrease MS severity, and may slow its progression (Ascherio et al., 2010; Munger et al., 2006; Muris et al., 2013). The mechanism by which vitamin D affects certain symptoms requires deeper investigation. This research examines the relationship between serum concentrations of 25-hydroxyvitamin D and retinal nerve fiber layer thicknesses in patients with MS. It was hypothesized that patients with sufficient vitamin D levels would have less demyelination of the retinal nerve caused by MS, and therefore would have a thicker RNFL in both eyes based on the proposed immunomodulatory role of vitamin D found in other studies. Blood samples were assayed to measure the concentration of 25-hydroxyvitamin D and OCT was used to measure RNFL thicknesses in patients with MS at the Harbor-UCLA Medical Center Neurology Clinic. Patients with sufficient levels of 25-hydroxyvitamin D had a greater mean global RNFL thickness in both eyes than in patients with insufficient levels of 25-hydroxyvitamin D; however the differences were not significant. Further research is necessary in order to determine whether or not there is a correlation between vitamin D and RNFL thickness and what role vitamin D plays in MS presentation.

Virus-specific cellular immune responses have been shown to be important in the control of viral replication in several animal and human virus models. Cells of both the CD8+ and CD4+T cell lineages have been shown to play protective roles during viral infections by exerting effector functions that can kill infected host cells or inhibit the production and spread of infectious virions. The continued spread of HIV-1 infection throughout the world, as well as the lack of a prophylactic HIV-1 vaccine have generated much interest in HIV-specific cellular immune responses. Recent technical advances have yielded a tremendous increase in our understanding of HIV-1-specific immunity, as well as HIV-1 replication dynamics and host cell factors that shape the course of acute and chronic infection. Unfortunately, due to small sample volumes and technological limitations, the study of HIV-1-specific T cell immunity in infants and children has been difficult. An improved understanding of the timing, specificity, and intensity of pediatric HIV-specific T cell responses would contribute to the development of a HIV-1 vaccine for use in regions of the developing world without access to antiretroviral therapeutics. In the small number of published studies investigating pediatric HIV-specific immunity, T cell responses were uncommonly detected in infants. It remains unclear, however, whether the lack of HIV-specific T cells is an accurate reflection of the in vivoimmune state in vertically-infected infants, or rather is a consequence of reagents and assays ill-suited to the detection of low-level and/or diverse T cell responses in pediatric subjects. In the present dissertation, several methodologies were used to investigate HIV-specific T cell responses in vertically-infected infants and children. HIV-specific CD8+ T cell responses were infrequently detected in a cohort of young infants, but are commonly detected in older infants and children. Interestingly, CMV-specific CD8+ T cell responses were detected in several young infants that lacked HIV-specific responses, suggesting a specific defect in the ability of some infants to generate HIV-specific CD8+ T cell responses. Further experiments characterizing detectable HIV-1-specific CD8+ T cell responses found that the HIV-1 accessory proteins may be important targets of the immune response during early vertical infection. The role of HLA class I genotype and viral sequence are also explored in a pair of vertically-infected twins with discordant CD8+T cell responses. Finally, viral isolates from an infant with a marked shift in gag-specific epitope usage during infancy are analyzed for the presence of escape mutations. Gag-specific CD4+ T cell responses were commonly detected in a large cohort of vertically-infected children. A linear relationship between HIV-1 replication and the presence and intensity of HIV-specific CD4+ T cell responses was found, but ongoing HIV-1 replication appeared to blunt CD4+T cell proliferation. The data presented in this dissertation describe pediatric T cell immune responses and how they relate to HIV-1 replication. This information may be useful to the design of a prophylactic or therapeutic HIV-1 vaccine for vertically-infected infants and children.