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.     

Flipping and ex post aggregation

We show that Bayesian ex post aggregation is unstable with respect to refinements. Suppose a group of Bayesians use ex post aggregation. Since it is a joint problem, each agent's problem is captured by the same model, but probabilities and utilities may vary. If they analyze the same situation in more detail, their refined analysis should preserve their preferences among acts. However, ex post aggregation could bring about a preference reversal on the group level. Ex post aggregation thus depends on how much information is used and may keep oscillating (“flipping”) as one keeps adding more information. Received: 16 April 2002/Accepted: 27 May 2002     

On strategy-proofness and essentially single-valued cores: A converse result

In a general model of indivisible good allocation, S?nmez (1999) established that, whenever the core is nonempty for each preference profile, if an allocation rule is strategy-proof, individually rational and Pareto optimal, then the rule is a selection from the core correspondence, and the core correspondence must be essentially single-valued. This paper studies the converse claim of this result. I demonstrate that whenever the preference domain satisfies a certain condition of `richness', if the core correspondence is essentially single-valued, then any selection from the core correspondence is strategy-proof (even weakly coalition strategy-proof, in fact). In particular, on the domain of preferences in which each individual has strict preferences over his own assignments and there is no consumption externality, such an allocation rule is coalition strategy-proof. And on this domain, coalition strategy-proofness is equivalent to Maskin monotonicity, an important property in implementation theory. Received: 22 February 2000/Accepted: 22 January 2002 I am grateful to Ryo-ichi Nagahisa, Shinji Ohseto, Hiroshi Ono, Tomoichi Shinotsuka and Shigehiro Serizawa for valuable comments. And I am indebted to two anonymous referees for useful suggestions. Especially, I owe the present proof of Lemma 2 to one referee. I also thank Yukihiko Funaki, Atsushi Kajii, Mamoru Kaneko, Eiichi Miyagawa, Tatsuyoshi Saijo, Manimay Sengupta, Yves Sprumont, Yoshikatsu Tatamitani, Manabu Toda, Takashi Ui, Takehiko Yamato, Naoki Yoshihara and the participants of the seminars in Hokkaido University, Kansai University, ISER (Osaka University), Otaru University of Commerce and Tsukuba University. All errors are my own responsiblity.     

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.     

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.)     

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.