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Vinyl chloride (VC) is used as an example to demonstrate how biological information can be incorporated into quantitative risk assessment. The information included is the pharmacokinetics of VC in animals and humans and the data-generated hypothesis that VC primarily affects the initiation stage of the multistage carcinogenesis. The emphasis in this paper is on the improvement of risk assessment methodology rather than the risk assessment of VC per se.Sufficient data are available to construct physiologically-based pharmacokinetic models for both animals and humans. These models are used to calculate the metabolized dose corresponding to exposure scenarios in animals and in humans.On the basis of the data on liver angiosarcomas and carcinomas in rats, the cancer risk per unit of metabolized dose is comparable, irrespective of routes (oral or inhalation) of exposure. The tumor response from an intermittent/partial lifetime exposure is shown to be consistent with that from a lifetime exposure when VC is assumed to affect the first (initiation) stage of the multistage carcinogenic process. Furthermore, the risk estimates calculated on the basis of animal data are shown to be consistent with the human experience. 相似文献
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Eric J. Engstrom Ph. D. 《PSN》2003,1(1):53-61
Recent studies on Emil Kraepelin’s experimental work have focused on the relationship between the psychological experiment and his nosological delineation of dementia praecox and manic-depressive disorders. Interpreters have argued variously that the psychological experiment had either no influence on the nosology, or that it was the very precondition of the nosology, or that it biased the nosology in favor of organic disorders. This article calls into question this historiographic affiliation of experiment and nosology. It argues that by framing Kraepelin’s experimental research agenda solely in terms of his nosology, interpreters have overlooked other important personal, institutional, diagnostic, and professional motives governing that research. Kraepelin’s early career crisis, his frustrations working in overcrowded institutions, and his efforts to enhance the professional stature of psychiatry all influenced his experimental research agenda of amessende Individualpsychologie and the historical significance of that agenda in Kraepelinian psychiatry. 相似文献
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Using a slide culture technique, it was determined unequivocally that the chlamydospore of Candida albicans does germinate. The germination was by way of a multiple-budding process which was associated mostly with young spores following their transfer to a fresh environment. It is concluded the chlamydospore of C. albicans is a reproductive cell with a transient viability. 相似文献
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W. C. Louv Ph. D. 《Biometrical journal. Biometrische Zeitschrift》1987,29(1):81-92
The simultaneous estimation of individual growth curves and a mean growth curve is accomplished by weighted least squares. A polynomial curve is fitted for each individual and the polynomial parameters are linear functions of parameters corresponding to covariates. A simple, computationally efficient variance-covariance estimator is derived. The resultant estimate is used in the weighted least squares estimation. The results are compared to empirical Bayes estimation. 相似文献