BACKGROUND: Military personnel are occupationally exposed to chemical mixtures at domestic locations and in theater. At military bases, a chemical hazard of concern is JP-8 jet fuel, the largest chemical exposure in the United States Air Force (USAF). We examined blood concentrations of JP-8 constituents as biomarkers of exposure and determined if workday exposure is associated with diminished balance control. Veterans of the 1990-1991 Gulf War (GW) were exposed to mixtures of chemicals in theater and about a third of GW veterans developed GW illness (GWI) on return from deployment. We identified health symptom profiles in the GWI literature and examined longitudinal exposure-symptom relationships in a subset of GW veterans. METHODS: In USAF personnel, personal air, urine, and blood samples were analyzed for components of JP-8. Separate multivariate linear regression analyses were conducted to examine relationships between personal air and post-shift blood volatile organic compounds (VOCs) and between JP-8 exposure and postural sway. Meta-analytic techniques were conducted to determine pooled prevalence and combined odds ratios of symptoms comparing GW and GW-era control veterans. Repeated logistic regression models stratified by sex examined the association of GW exposures and symptoms. RESULTS: Blood VOC concentrations were higher among participants with work-shift JP-8 exposure and breathing zone total hydrocarbons significantly predicted VOC blood levels. Postural sway outcomes were associated with personal variables and task difficulty but not JP-8 exposure. GW veterans had higher odds of reporting all analyzed symptoms compared to GW-era controls, with 20% excess prevalence for fatigue, memory problems, and joint pain. Men had more significant associations between GW exposures and symptoms compared to women. Specific exposures were significantly associated with higher symptom reporting over time. CONCLUSION: In USAF personnel, blood VOC concentrations reflected work-shift exposure to jet fuel, supporting their use as biomarkers of JP-8 exposure. Work-shift exposure to JP-8 did not diminish balance control. Health symptoms evaluated through meta-analysis with the largest summary odds ratios were consistent with the symptom clusters reported in case definitions of GWI. The associations between GW exposure and longitudinal symptom reporting differed between men and women. / 2019-11-08T00:00:00Z

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1975. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--New York University, Graduate School of Arts and Science, 2005. / Typescript. Includes bibliographical references (leaves 199-211). Also available in electronic format on the World Wide Web. Access restricted to users affiliated with the licensed institutions.

Biologists have traditionally studied adverse health effects of contaminants on wildlife, whereas public health researchers have independently studied effects of the same chemicals on humans. This siloed approach limits maximal progress towards understanding and managing pollution if relevant findings are not translated between fields. A new threat to human health, and potentially ecological health, is metabolic disruption. Metabolism disrupting chemicals (MDCs) are environmental chemicals that can act at systemic and molecular levels across the lifespan to interfere with normal adipose tissue development, lipid storage in the liver, and alter whole-body energetics. Using fish from New Bedford Harbor (NBH), Massachusetts, a marine Superfund site, this research demonstrates the benefit of using a holistic approach to examine exposures to and effects of contaminants in urban waterways. The overall goals of this dissertation were to investigate trends in polychlorinated biphenyl (PCB) contamination in NBH and to test the hypothesis that PCB and/or organotin exposure has resulted in metabolic disruption in Atlantic killifish (Fundulus heteroclitus) resident in New Bedford Harbor. First, trends in PCBs in seafood harvested throughout NBH since 2003 were characterized over time and space. PCBs declined in shellfish, but not finfish, over time. My risk assessment shows that human health risks associated with seafood consumption have decreased, but safe levels in seafood are not likely to be reached by the end of NBH sediment remediation, in the early 2020s. PCBs and tributyltin (TBT), a pollutant also commonly found in commercial harbors because of its use as an antifouling agent in marine paints, act as MDCs by distinct mechanisms. Dioxin-like PCBs act through the aryl hydrocarbon receptor. TBT acts through nuclear receptors, particularly PPARγ and RXR. In the second aim, using historical sediments and current sediments, I document the presence of tin in NBH above background levels. Biological investigations show that adult killifish two generations removed from NBH have more adipose tissue and higher levels of liver triglycerides than killifish from an uncontaminated location. Initial analyses show that changes in PPAR signaling may be particularly important in male killifish. In the third aim, I demonstrate that killifish embryos are minimally responsive to changes in PPARγ-regulated gene expression when treated with TBT or mammalian agonists. However, embryonic TBT exposure interferes with caudal fin development, likely through RXR activation and a reduction in bone formation signaling. Overall, these findings demonstrate metabolic disruption is occurring in a fish species resident to a highly polluted harbor and support the use of sentinel species not only for addressing potential human exposures but also potential adverse human health effects.

<p> Schistosomiasis control in sub-Saharan Africa is enacted primarily through mass drug administration, where predictive modeling plays an important role in filling knowledge gaps in the distribution of disease burden. Remote sensing (RS) satellite imagery is used to predictively model infectious disease transmission in schistosomiasis, since transmission requires environmental conditions to sustain specific freshwater snail species. Surveys are commonly used to obtain health outcome data, and while they provide accurate estimates of disease in a specific time and place, the resources required make performing surveys at large spatiotemporal scales impractical. Ongoing national surveillance data in the form of reported counts from health centers is conceptually better suited to utilizing the full spatiotemporal capabilities of publically available RS data, as most open source satellite products can be utilized as global continuous surfaces with historical (in some cases 40-year) timespans. In addition RS data is often in the public domain and takes at most a few days to order. Therefore, the use of surveillance data as an initial descriptive approach of mapping areas of high disease prevalence (often with large focal variation present) could then be followed up with more resource intensive methods such as health surveys paired with commercial, high spatial resolution imagery. Utilization of datasets and technologies more cost effectively would lead to sustainable control, a precursor to eradication (Rollinson et al. 2013). </p><p> In this study, environmental parameters were chosen for their historical use as proxies for climate. They were used as predictors and as inputs to a novel climate classification technique. This allowed for qualitative and quantitative analysis of broad climatic trends, and were regressed on 8 years of Ghanaian national surveillance health data. Mixed effect modeling was used to assess the relationship between reported disease counts and remote sensing data over space and time. A downward trend was observed in the reported disease rates (~1% per month). Seasonality was present, with two peaks (March and September) in the north of the country, a single peak (July) in the middle of the country, and lows consistently observed in December/January. Trend and seasonal patterns of the environmental variables and their associations with reported incidence varied across the defined climate zones. Environmental predictors explained little of the variance and did not improve model fit significantly, unlike district level effects which explained most of the variance. Use of climate zones showed potential and should be explored further. Overall, surveillance of neglected tropical diseases in low-income countries often suffers from incomplete records or missing observations. However, with systematic improvements, these data could potentially offer opportunities to more comprehensively analyze disease patterns by combining wide geographic coverage and varying levels of spatial and temporal aggregation. The approach can serve as a decision support tool and offers the potential for use with other climate-sensitive diseases in low-income settings.</p><p>

Background: The prenatal period is a critical window for neurodevelopment and is particularly sensitive to toxicant exposure. Traffic-related air pollution and per- and polyfluoroalkyl substances (PFASs) are two classes of potential developmental toxicants to which pregnant women are ubiquitously exposed. Objectives: In a cohort of children, characterize in utero exposure to traffic-related air pollution and PFASs and examine the effects of these exposures on childhood assessments of neurodevelopment. Methods: Analyses were conducted in Project Viva, a longitudinal Boston-area birth cohort enrolled during 1999‒2002. In mid-childhood (at age 6‒10), children completed assessments of cognitive function and mothers and classroom teachers assessed executive function and behavior problems in children using validated questionnaires. Estimates of traffic-related pollutant exposures, residential proximity to major roadways, and near-residence traffic density were generated for periods in pregnancy and childhood. Stored maternal plasma from pregnancy was analyzed for concentrations of four common PFASs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA). We modeled associations of exposures with neurodevelopmental assessment scores, adjusted for potential confounders. Results: Living within 50 meters of a major roadway at birth predicted lower non-verbal intelligence, verbal intelligence, and visual motor abilities in mid-childhood. Children with higher black carbon exposure during childhood had greater teacher-assessed problems with behavior regulation, but prenatal traffic exposures were not associated with greater problems. Children with higher prenatal exposure to PFOA scored lower on assessments of verbal IQ and visual motor abilities, but children with the highest levels of PFOS and PFNA exposure appeared to have better scores on some cognitive assessments (verbal IQ, non-verbal IQ and design memory for PFOS and verbal IQ, design memory and picture memory for PFNA). Conclusions: The influence of exposure to traffic-related pollution and PFASs on neurodevelopment varied across pollutants, exposure windows, and neurobehavioral domains. Results suggested that residential proximity to major roadways during gestation adversely affected cognitive development. Prenatal exposure to traffic-related pollution did not predict greater neurobehavioral problems, but childhood exposure appeared to influence behavioral regulation. Observed associations of prenatal PFAS exposure with childhood cognition differed across studied compounds and cognitive assessments, suggesting both deleterious and protective effects.

Motivation: Back pain is a major cause of absenteeism, lost work time and increased compensation and medical costs amongst workers and has been estimated to cost $20 billion annually in the United States. Back pain has long been associated with the driving of forklifts, and is a complex area of occupational health and safety, having many risk factors leading to musculo-skeletal injury. The health effects in this occupational group in South Africa, could be affecting upwards of 90 000 forklift drivers, and has a great direct and indirect influence on people's health at work as well as productivity and the economy. Purpose: To characterise the problem of back pain amongst forklift drivers with a view to reducing the morbidity from back pain, by evaluating the effectiveness or the use of back belts. Aim: To identify risk factors associated with back pain amongst forklift drivers at Portnet (handling wharf side cargo) in two cohorts of forklift drivers one using back belts and one control group, and to evaluate the relationship between back pain, the occupational environment (i.e.: forklift driving) and other associated factors, in order to establish the effectiveness of back belts in decreasing the severity and prevalence of back pain amongst forklift drivers. Objectives: 1.) To describe demographic and other relevant back pain risk factors in the two cohorts and to identify any significant differences between them. 2.) To characterise the compliance and frequency of use of the back belts by the user group. 3.) To measure vibration experienced in typical driving activities in the study population in order to characterise whole-body vibration exposures of the study subjects. 4.) To ascertain opinions and beliefs regarding back belts amongst users. 5.) To analyse, characterise and determine if any significant differences exist between the two groups as to the prevalence and severity of back pain, and what factors are associated with increased risk of back pain. Specifically to identify whether (a.) The frequency and/or intensity of use of back belts are associated with reduced risk for back pain, when controlling for all other risk factors, and (b.) Whether other factors modify this relationship. Study Design: Cross Sectional Study Design Subjects: Drivers of 3, 4, 4.5 and 5 ton forklifts in the permanent employment of Portnet, Durban, from the Point, Maydon Wharf (back belt group) and Combi-Terminal (control group) areas. Main Outcome Measures: Onset of back pain after starting driving, prevalence of regular back pain (ever), point prevalence (pain today), 1 year prevalence, severity of back pain, duration of pain, and treatment/medication sought for back pain. Results: The majority of forklift drivers (89%) in the study suffer from chronic back pain that is of a constant severity, and is significantly linked to the driving activities. The back belt wearers were more likely to suffer from back pain then the non-users (92% vs 80%). However, the belt wearers reported less severe pain than the control group, which could indicate the presence of a placebo effect related to the belt use. The belt users were more likely to suffer from pain of a longer duration, with less fluctuation in severity than the controls, and therefore a more constant type of pain (44% vs 41 %). The majority of bell wearers expressed the belief that the belts helped to reduce the back pain (81%). However, more objective measures do not bear out this conclusion when prevalence and severity of pain are compared to the control group. Drivers with back pain were more likely to wear the back belts and compliance was reduced as the prevalence of pain was reduced. These results may have been confounded by variations in the whole-body vibration exposure in the various test areas, and the inability to characterise individual whole-body vibration exposures and dose-response relationships. Conclusion: The prevalence of back pain in this study was high, with most drivers suffering from pain in the lower back region (79%), which was characterised as constant or chronic pain experienced either during or shortly after driving. Whole-body vibration levels were high in all test areas (1.9 m/s⁻², 1.3 m/s⁻² and 1.1 m/s⁻² predicted), and consistently exceeded the EEC machinery directive standards of 0.5 m/s⁻². Compliance with the use of back belts amongst drivers was high (90%), with most drivers (76%) wearing the belts on a regular basis whilst driving. The evidence for the effectiveness of back belts as a control measure against whole-body vibration remains obscure, and other more tested controls such as engineering, administrative and training of drivers should be implemented to address the problem following a holistic approach.

It is well recognized that the global increase in obesity and metabolic diseases over the last several decades cannot be solely attributed to aging and modern lifestyle trends (i.e., excess caloric intake and lack of physical activity). Metabolism disrupting chemicals (MDCs) are environmental and consumer product chemicals that act at the molecular level in multiple organs to affect systemic metabolic homeostasis and are hypothesized to increase the risk of obesity and metabolic diseases. The nuclear receptor peroxisome proliferator activated receptor γ (PPARγ) regulates insulin sensitivity, adipogenesis, and mature adipocyte maintenance, function and survival, which make it beneficial as a therapeutic target. However, PPARγ is also a target for structurally diverse MDCs that may not induce its health-promoting biological effects. One such PPARγ agonist is triphenyl phosphate (TPHP), an organophosphate ester commonly used in consumer products. Accumulating evidence from animal and in vitro studies demonstrates that MDCs act on multiple organs (e.g., liver, adipose, pancreas) to disrupt glucose and lipid homeostasis. Epidemiological studies have characterized human exposure to complex mixtures of MDCs and associated that exposure to obesity and metabolic diseases. However, not all suspected MDCs have been investigated in human epidemiological studies. Furthermore, these studies are complicated given the role of complex chemical mixtures. The objectives of this dissertation were: 1) to investigate the role of TPHP, a suspected MDC in animal studies, as a metabolic disruptor in humans, 2) to develop an improved biomarker of exposure to mixtures of environmental PPARγ ligands, the Serum PPARγ Activity Assay (SPAA), and 3) to investigate environmental exposures in a human cohort using the SPAA. In the first aim, we used publicly available data from the 2013-2014 National Health and Nutrition Examination Survey to investigate the association between urinary diphenyl phosphate (DPHP), a metabolite of TPHP and biomarker of exposure, and measures of body adiposity as well as markers of type 2 diabetes risk. In adjusted multivariate linear regression models, urinary DPHP was positively associated with increased waist circumference, body mass index, and sagittal abdominal diameter in adults aged 20-50 years, but not in older adults aged 51-79 years. In all adults, urinary DPHP was not associated with any marker of type 2 diabetes risk (fasting plasma glucose, hemoglobin A1c, homeostatic model assessment of insulin resistance, 2-hour oral glucose). In the second aim, we developed and optimized the SPAA as a tool to measure cumulative PPARγ ligand activity in human serum samples and then used the assay to assess exposure to PPARγ ligands in a human cohort. SPAA generates robust PPRE transcriptional activity using Cos-7 cells transfected with a human PPARγ1 expression vector along with a PPRE (DR1)-driven luciferase vector. With small volumes of serum, the SPAA reliably detected high PPRE transcriptional activity levels induced by rosiglitazone, a potent and efficacious therapeutic PPARγ agonist, in serum from experimentally exposed mice. The SPAA also detected significant differences in the PPRE transcriptional activity induced by U.S. based human commercial serum samples. The abrogation of the activity by a PPARγ antagonist, T0070907, confirmed the receptor-specificity of the human serum-induced activity. Finally, we investigated PPARγ agonist exposure in serum samples from a population of Danish women with extensive environmental chemical biomarker data using SPAA and used an additivity model to estimate the contribution of a subset of the chemicals towards measured activity. The serum samples from the Danish cohort induced PPRE transcriptional activity in the SPAA, but with an overall lower efficacy than a U.S. based serum samples. Modeling of the PPRE transcriptional activity induced by the perfluoroalkyl substances and a polybrominated diphenyl ether at concentrations measured in the Danish serum with effect summation demonstrated that these chemicals are unlikely to be the source of the serum activity. Together, these findings demonstrate that TPHP exposure is associated with metabolic disruption, specifically adiposity, in people, which supports toxicological research, and lay the foundation for future work using the SPAA as an exposure biomarker in human populations.

This study investigated single parent attitudes toward the sex education of their children. A questionnaire was devised to gather data about who should teach sex education to the children in a one- parent home and how it should be done. An open-ended question sought to determine specific problems which might be experienced. A majority of the single respondents agreed that sex education is a responsibility of the parent and school, but the family should remain the primary source of attitudes toward sex. Respondents expressed concern over their own sexuality, fears about the "freer" moods toward sex, and confidence that single parents have no more problems than two-parent families in teaching about sexuality.