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.     

An Existential Approach to Risk Perception

Existential, or existential-phenomenological philosophical approaches to the social psychology of risk perception provide a novel framework for understanding issues that are common to all humanity, such as fear of death, freedom and responsibility, isolation and meaninglessness, as these anxieties are a function of existing, or being-in-the-world. These fundamental anxieties can be related theoretically to the ways people perceive risks within social and cultural milieus, and can also be used practically within case studies, as demonstrated in the three examples presented, which examine perceptions of climate change, food-related risks, and environmental awareness via a mixture of quantitative and qualitative techniques. The discussion focuses on the possible insights that can be gained from taking an existential perspective on risk perception, and relates notions of contemporary technologically-oriented societies to the existential challenges faced by individuals and societies in the contemporary world.     

PREDICTING MARITAL SUCCESS FOR PREMARITAL COUPLE TYPES BASED ON PREPARE

Recent studies have shown that group differences in marital stability and satisfaction can be predicted based on premarital relationship quality. There is also a growing literature indicating that there are distinct types of relationships, both premaritally and developmentally over time. This study examined the relationship between the four premarital types (Vitalized, Harmonious, Traditional, and Conflicted) identified by Fowers and Olson (1992) and relationship outcome over a 3-year period with 393 couples. A substantial relationship was found, with conflicted couples being the most likely to separate or divorce. Vitalized couples had the highest levels of satisfaction, followed by Harmonious, Traditional, and Conflicted couples. Traditional couples were less likely to have divorced than Harmonious couples, even though Harmonious couples had higher premarital relationship satisfaction scores.     

TESTAMENTARY BEHAVIOR:

Content analysis and qualitative analysis of all 319 last wills that were filed in Providence Probate Court, 1985, revealed that about ten percent of the testators used testamentary material, disinheritance or altruism to express their individuality. About 42 percent of the wills were personalized directly in other ways. Forty-eight percent displayed indirect influences of family, friends and community. Less that ten percent displayed primary influences of attorneys, banks, nursing homes, governments, religions or other organizations. In the light of these findings, while none of the three major theoretical positions on testamentary behavior prevails, the individualist position is manifested more often than is the family-community position. Both of these positions are manifested much more often than is the legalist position.
These findings are related to the work of Emile Durkheim and to contemporary sociological theories of the family, community and law.     

Scheduling Updates of Probabilistic Risk Assessments: The Arkansas Nuclear One-Unit 1 Experience

This paper presents the results of a study that identified how often a probabilistic risk assessment (PRA)should be updated to accommodate the changes that take place at nuclear power plants. Based on a 7-year analysis of design and procedural changes at one plant, we consider 5 years to be the maximum interval for updating PRAs. This conclusion is preliminary because it is based on the review of changes that occurred at a single plant, and it addresses only PRAs that involve a Level 1 analysis (i.e., a PRA including calculation of core damage frequency only). Nevertheless, this conclusion indicates that maintaining a useful PRA requires periodic updating efforts. However, the need for this periodic update stems only partly from the number of changes that can be expected to take place at nuclear power plants–changes that individually have only a moderate to minor impact on the PRA, but whose combined impact is substantial and necessitates a PRA update. Additionally, a comparison of two generations of PRAs performed about 5 years apart indicates that PRAs must be periodically updated to reflect the evolution of PRA methods. The most desirable updating interval depends on these two technical considerations as well as the cost of updating the PRA. (Cost considerations, however, were beyond the scope of this study.)     

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.     

Potential exposures and risks from beryllium-containing products.

Beryllium is the strongest of the lightweight metals. Used primarily in military applications prior to the end of the Cold War, beryllium is finding new applications in many commercial products, including computers, telecommunication equipment, and consumer and automotive electronics. The use of beryllium in nondefense consumer applications is of concern because beryllium is toxic. Inhalation of beryllium dust or vapor causes a chronic lung disease in some individuals at concentrations as low as 0.01 microg/m3 in air. As beryllium enters wider commerce, it is prudent to ask what risks this might present to the general public and to workers downstream of the beryllium materials industry. We address this question by evaluating the potential for beryllium exposure from the manufacturing, use, recycle, and disposal of beryllium-containing products. Combining a market study with a qualitative exposure analysis, we determine which beryllium applications and life cycle phases have the largest exposure potential. Our analysis suggests that use and maintenance of the most common types of beryllium-containing products do not result in any obvious exposures of concern, and that maintenance activities result in greater exposures than product use. Product disposal has potential to present significant individual risks, but uncertainties concerning current and future routes of product disposal make it difficult to be definitive. Overall, additional exposure and dose-response data are needed to evaluate both the health significance of many exposure scenarios, and the adequacy of existing regulations to protect workers and the public. Although public exposures to beryllium and public awareness and concern regarding beryllium risks are currently low, beryllium risks have psychometric qualities that may lead to rapidly heightened public concern.