Estimation of Metabolic Rate Constants in PBPK‐Models from Liver Slice Experiments: What Are the Experimental Needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.     

Modified cross-validation in density estimation

We propose a new modified (biased) cross-validation method for adaptively determining the bandwidth in a nonparametric density estimation setup. It is shown that the method provides consistent minimizers. Some simulation results are reported on which compare the small sample behavior of the new and the classical cross-validation selectors.     

Recurrent pain in college students.

The authors investigated the prevalence of recurrent pain in a college student sample. Of the 1,564 students surveyed, 467 (29%) indicated that they had experienced recurrent pain at an intensity that was mostly in the mild-to-moderate range. Students who reported having recurrent pain were significantly older and more depressed than students who did not indicate they suffered from recurrent pain. Pain intensity was positively correlated (r = .14) with depression among the students who reported having recurrent pain. Implications of the findings for future research, treatment, and health promotion efforts are discussed.     

Gender-specific changes in students' sexual behaviors and attitudes at a southeastern university between 1973 and 1988.

This study investigated the gender-specific, self-reported sexual behaviors and attitudes of never-married college students attending a southeastern university in 1973 and 1988. Data were collected by means of a mailed questionnaire that remained essentially unchanged for both years. The authors found that both men and women reported an increase in heterosexual relationships that included sexual intercourse and a decrease in nonsexual relationships with the other gender. The majority of the students perceived themselves as adequately informed about sexuality and satisfied with their relationships, although the proportion of men who reported being satisfied with their relationships declined over the 15 years. The students indicated that sexuality education should focus primarily on information about AIDS and on preparation for marriage.     

The effect of 1980s tort reform legislation on general liability and medical malpractice insurance

A large number of states adopted tort reforms in the mid-1980s to limit the dramatic surge in insurance losses and premiums. Evidence based on liability insurance data by state indicates that these reforms substantially influenced general liability insurance. The levels of losses, premiums, and loss ratios (a measure of insurance profitability) all reflected the impact of the reforms. The large-scale reform efforts in 1986 were particularly influential. Medical malpractice insurance was much less sensitive to the reform efforts.     

Procedures and tables for the construction and selection of chain sampling plans ChSP-4A(c1, c2,)r-Part 4

In this part of the series, the notion of average total inspection (ATI) is introduced to ChSP-4A(c1, c2)r plans, minimizing ATI at a given process average, while protection to the consumer is given in terms of average outgoing quality limit and limiting quality level. The procedure is similar to that of Dodge and Roming.     

A SCALE IN SEARCH OF A CONSTRUCT: COMMENTS ON GAVIN AND WAMBOLDT

The article examines some issues raised in Gavin and Wamboldt's (1992) recent study on the Family-of-Origin Scale (FOS) (Hovestadt, Anderson, Piercy, Cochran, & Fine, 1985). The discussion centers on unresolved concerns regarding the validity and utility of the FOS and on unsubstantiated and potentially misleading claims made in the Gavin and Wamboldt article. A case is made for conceptual and methodological precision in the study of family phenomena.     

A response to “the emotional consequences of physical child abuse” by Annaclare van Dalen

The author responds to the article by Annaclare van Dalen (1989), disputing her statement that there is little in the literature about the emotional consequences of child abuse. The author reviews the pertinent literature, which is abundant. The author disagrees with van Dalen's statement that the child experiences physical abuse outside the body, and with the statement that the child experiences sexual abuse as pleasurable. In addition the author disagrees with van Dalen's sharp differentiation between physical abuse and sexual abuse, and proposes that sexual abuse be regarded as a variant of physical abuse.     

What to Do at Low Doses: A Bounding Approach for Economic Analysis

To quantify the health benefits of environmental policies, economists generally require estimates of the reduced probability of illness or death. For policies that reduce exposure to carcinogenic substances, these estimates traditionally have been obtained through the linear extrapolation of experimental dose-response data to low-exposure scenarios as described in the U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment (1986). In response to evolving scientific knowledge, EPA proposed revisions to the guidelines in 1996. Under the proposed revisions, dose-response relationships would not be estimated for carcinogens thought to exhibit nonlinear modes of action. Such a change in cancer-risk assessment methods and outputs will likely have serious consequences for how benefit-cost analyses of policies aimed at reducing cancer risks are conducted. Any tendency for reduced quantification of effects in environmental risk assessments, such as those contemplated in the revisions to EPA's cancer-risk assessment guidelines, impedes the ability of economic analysts to respond to increasing calls for benefit-cost analysis. This article examines the implications for benefit-cost analysis of carcinogenic exposures of the proposed changes to the 1986 Guidelines and proposes an approach for bounding dose-response relationships when no biologically based models are available. In spite of the more limited quantitative information provided in a carcinogen risk assessment under the proposed revisions to the guidelines, we argue that reasonable bounds on dose-response relationships can be estimated for low-level exposures to nonlinear carcinogens. This approach yields estimates of reduced illness for use in a benefit-cost analysis while incorporating evidence of nonlinearities in the dose-response relationship. As an illustration, the bounding approach is applied to the case of chloroform exposure.