Thesis (M.S.P.H.)--University of Michigan, 1932.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [117]-142).

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [127]-142).

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 69-98).

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

No Abstract Provided

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Estimation of exposure-specific risks (ESRs) using estimates of the overall risk and relative risk of disease given exposure has been performed in previous studies, but the performance of such an estimator has not been assessed nor has a variance for such an estimate been proposed. In this project I evaluated the performance of a simple product-based ESR and its variance derived using the delta method. I used the variance to estimate the 95% confidence interval. I found that this point estimate was biased and that the accompanying 95% confidence interval did not attain 95% coverage. I also proposed a revised product-based estimator and found that this estimator was unbiased. I used the delta method to derive a variance for this estimator and estimated the 95% confidence interval. The coverage of this interval attained 95% coverage in most situations. According to the CONSORT statement, subgroup analyses in randomized controlled trials (RCTs) should be pre-planned and accompanied with a formal test of interaction. I considered the interaction between treatment and a dichotomous prognostic factor with a continuous outcome. I examined the impact of misspecifying the distribution of the prognostic factor on power and sample size for interaction effects. I found that power for the interaction test was decreased when the misspecification of the distribution of the prognostic factor was away from a balanced design. I also proposed three methods for improving the power under misspecifications. Quota sampling maintained the power at 80%, but trial completion may be delayed under misspecifications. Modified quota sampling improved the power, but results were related to the proportion of trials switching to the quota sampling procedure. Sample size re-estimation improved the power, but did not always attain 80% power. All three methods maintained appropriate type I error. Lastly, I examined the impact of unplanned cross-over on power and sample size for interaction effects in RCTs. Unplanned cross-over is common in surgical trials and can diminish the magnitude of the interaction effect. Due to this, the sample size re-estimation procedure performed better than quota sampling and modified quota sampling in the presence of unplanned cross-over. / 2031-01-02

This study was carried out in order to investigate the human genetic effects of exposure to benzene in 66 male workers of a refinery population and the results compared with 33 control workers in the same refinery, not known to have had exposure to benzene. Questionnaires were used to determine various life style factors such as smoking, drinking and exposure to ionising radiation as examples of known confounding variables. In addition, experiments were designed to investigate the mechanism of benzene carcinogenicity using cell transformation techniques, together with a molecular dosimetry approach in an attempt to identify and quantify any interaction with benzene metabolites and DNA. The results from the human studies showed no difference between the groups when effects such as mitogen-induced blastogenesis, proliferative rate index, sister chromatid exchange and urine mutagenicity were measured. There was a suggestion of a decrease in mitogenic response with age in both exposed and control individuals in the mitogen induced blastogenesis experiments, which was consistent with other studies. Although no difference in the number of revertant colonies in strain TA 98 and 100 was demonstrated between the high and low urinary phenol groups there was a correlation between the number of revertants and the ages of the individuals as a whole. One statistical test used in the examination of the chromosome aberration data suggested a statistically significant increase in aberrations in the exposed group to the control groups, and this increase could be the result of benzene exposure. Cell transformation studies using C3H10T1/2 cell lines did not indicate that benzene had any initiating carcinogenic properties in vitro using the two stage model of carcinogenesis. Furthermore, molecular dosimetry studies using C[14]-labelled benzene in vivo demonstrated only a very weak interation between benzene metabolites and rat liver DNA. All the methods used in this study generated negative data except for that to detect chromosome damage. This method showed a slight increase in damage in exposed workers by comparison with the controls suggesting that benzene may be a weak clastogen at low doses.

Estimating the risk of polychlorinated biphenyls (PCBs) in aquatic systems requires evaluation of exposure, usually based on exhaustive chemical extraction of sediment and potentially exposed organisms and an assessment of toxicity. Remediation can then focus on areas where the exposure leads to the highest risk. Although effective, an approach that estimates exposure, which accounts for bioavailabilty, bioaccumulation, trophic transfer potential, and transport of materials within and out of the waterway, should serve as a more comprehensive environmental assessment. The current study examined exposure of PCBs in several different trophic levels within the Campus Lake ecosystem, Carbondale, Illinois. The source of contamination and the distribution of PCBs among ecosystem components demonstrated contamination within the aquatic portion of Campus Lake and transport out of the aquatic environment to the riparian area. Several media were collected including sediment, emergent insects, spiders, and three species of fish. Sediment extractions demonstrated that PCBs were localized to one small cove and this area served as the source for transfer of PCBs to both aquatic and terrestrial organisms. Single-point 24-h Tenax extractions formed the basis for evaluating the bioavailable component of the sediment-associated PCBs with strong correlations to laboratory-based bioaccumulation assays for oligochaetes and chironomid larvae. Stable isotope data suggested that the source of carbon to the food web was relatively constant. Food web samples of emerging insects, fish, and spiders revealed that the PCBs in Campus Lake were bioavailable and the pattern of the PCB signature among food web components followed typical food web processes. The PCB congener pattern was consistent between emergent midges and spiders demonstrating the transfer of PCBs from aquatic to terrestrial species. The PCB concentrations detected in emerging insects from the contaminated area were on average 25 times greater than those detected in emerging insects from reference sites outside the area of greatest sediment contamination. High PCB concentrations found in several species of fish suggested that despite the localized sediment contamination, fish throughout the lake were exposed. These levels also exceeded the fish consumption advisory criteria. The PCB pattern comparisons suggested that the contaminated sediment was the source of exposure throughout the food web. This approach identified the scope of exposure to organisms, demonstrated bioavailability, and provided a basis for future PCB remediation and subsequent monitoring of Campus Lake. In comparison to studies focused solely on limited sampling of fish for consumption advisory purposes, this approach demonstrated the importance of more comprehensive studies to examine the range of ecosystem exposure even from very limited contamination sources.