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.     

A screening system for tardive dyskinesia: development and implementation.

1. Most diagnosed cases of tardive dyskinesia (TD) are mildly inconvenient to the patient, but some can be severe or life-threatening. The primary goal of intervention should be early identification of abnormal movements related to TD and the prescribing of an appropriate medication regimen. 2. Unless specific training occurs and a specific monitoring system is in place, TD movements may be missed. However, not all movements are necessarily related to TD. 3. Although screening and monitoring are valuable, nothing is more important than prevention. New medications must be developed that do not carry the risk of TD, and other approaches to treat TD must be developed.     

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.     

Cognitive and interpersonal abilities related to the primary activities of R&D managers

This study attempted to identify the primary activities performed by R&D managers at different supervisory levels, and the cognitive and interpersonal ability requirements that underlie these activities. A task inventory containing 244 managerial tasks was completed by 117 R&D managers in nine organizations. The 48 tasks which managers rated as having spent the most time were factor analyzed, resulting in the identification of three primary activities: project management, personnel supervision, and strategic planning. Furthermore, these activities varied with supervisory level, with R&D managers performing a wider range of these activities with the progression from first-line to upper-level management.Thirty R&D managers later rated the degree to which 19 cognitive and interpersonal abilities were required for performing these primary activities. Strategic planning was rated as requiring significantly higher levels of oral expression, logical reasoning, originality, fluency of ideas, oral defense, and resistance to premature judgement than was required for the other two primary activities. Personnel supervision required a higher level of social sensitivity than was required for the other two activities. Project management required high levels of information ordering, oral fact- finding ability, problem sensitivity, and oral and written comprehension. Implications of the findings for understanding R&D managerial performance and personnel staffing functions are discussed.     

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.     

Determinants of housing quality: A comparison of white,African-American,and Hispanic single-parent women

This study examines housing quality among three groups of single-parent women: white, African-American, and Hispanic. Three indicators of housing quality—crowding, affordability, and satisfaction—are used to discover the extent to which these groups experience housing problems. This study also explores differences and similarities in the factors that precipitate problems in housing quality for these three groups of single parents. Findings suggest important differences and similarities in the nature of housing quality problems among white, African-American, and Hispanic single-parent women. The specified variables explained about 20% of the variance in crowding, housing affordability, and housing satisfaction. On measures of objective and subjective housing quality, white single mothers are better housed than their African-American or Hispanic counterparts. Hispanic single mothers have the largest housing cost burden and average more persons per household than the other groups. African-Americans are twice as likely as either group to live in low-quality housing and reported the lowest average satisfaction with their housing. Her research interests include housing and neighborhood assessment and women and public policy issues. She has recently published articles inUrban Affairs Quarterly andHousing and Society on housing and neighborhood assessment criteria among black urban households and the housing cost burden of various groups of female-headed households. She received her Ph.D. from Ohio State University. Her research interests include the housing adjustment behavior of women and public policy. She has recently completed her thesis on the role of noncustodial parents in determining the quality of life of their children. She is also the recipient of the Tessie Agan Award for research excellence from the American Association of Housing Educators for a paper titled “Unterstanding Constraints and Residential Satisfaction among Low-Income Single-Parent Families.”     

The Decline of Barriers to Immigrant Economic and Political Rights in the American States: 1977–20011

State governments exercise significant powers to regulate the economic and social activities of resident aliens. We review the laws of the six leading states of immigrant settlement regulating access of noncitizens to 23 occupations, updating existing studies from 1946–77. Citizenship requirements for these occupations have plummeted, a change we attribute to federal court decisions, advisory opinions of state attorneys general, and state legislative and administrative action. There are numerous additional citizenship requirements in the statutes of the six states, although these appear to be poorly enforced. The authority of states to regulate their political communities is the most important remaining constitutionally valid basis of citizenship requirements. States define their political community broadly, leading to questionable exclusions of noncitizens from important activities.