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.     

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.     

Internal and external determinants of persistent gambling: Problems in generalising from one form of gambling to another

Recent studies completed at the Australian National University focussing on poker machine players are reviewed and a speculative discussion attempts to link the various psychological processes that may contribute to the development of impaired control in regular poker machine players. On the assumption that there is some overlap between regular players and problem players in terms of their level of involvement in gambling, the theorising was extended to include problem players for whom an established habit was argued to be a necessary condition leading to impaired control. Two additional factors may be required for impaired control to be consistently present, negative emotions such as dysphoria and frustration, and indebtedness. Finally by drawing some limited contrasts with another popular, legal form of gambling, off-course betting, if was suggested that there may be different psychological processes causing impaired control in different forms of gambling.     

ACCOUNTING PRACTICES AND ORGANIZATIONAL DECISION MAKING

In this paper we argue for the importance of a sociologically informed study of organizational accounting practices. By making the nexus between accounting and decision making problematic, instead of given, we move issues of interpretation and hierarchical control to the center stage of understanding the social construction of accounting practices. We suggest that inductive case studies of the organizational setting is a promising methodological strategy for identifying how accounting operates as an organizational control system. We focus on debates and proceedings of the board of directors as an overlooked source of data on decision making and organizational practices. We show how accounting practices are part of the strategic control system that functions to interpret the environment and direct the adaptation of the organization in a manner particular to the substantive rationality of corporate decision makers. We illustrate these contentions with a case study of accounting practice changes over a six year period.     

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.     

The dilemma of recognition: Administrative categories and cultural diversity

Governments around the world combat inequality by means of group-specific redistribution. Some pursue redistribution that benefits groups, but also wish to avoid accentuating or even recognizing group distinctions. This poses a dilemma that they try to resolve by adjusting the category system used to target redistribution. There are three types of adjustment: accommodation (the multicultural approach), denial (the ideal-typical liberal solution), and replacement (a compromise). In replacement the targets of redistributive policies are constructed to avoid accentuation or recognition of inconvenient group distinctions, but still allow redistribution that benefits these groups. Replacement is increasingly in demand around the world because the disadvantages of multiculturalism are becoming apparent while denial is hard to sustain in the face of group inequality. The actual effect of replacement is little researched and less understood, however. Does it resolve the dilemma of recognition? Two examples–India and Nigeria–where replacement has been tried ever since the 1950s cast doubt on its viability.     

Uncertainty Analysis for Computer Model Projections of Hurricane Losses

Projecting losses associated with hurricanes is a complex and difficult undertaking that is wrought with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real-time estimates grew from 2 to 3 billion dollars in losses late on August 12 to a peak of 50 billion dollars for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm hit the resort areas of Charlotte Harbor near Punta Gorda and then went on to Orlando in the central part of the state, with early poststorm estimates converging on a damage estimate in the 28 to 31 billion dollars range. Comparable damage to central Florida had not been seen since Hurricane Donna in 1960. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has recognized the role of computer models in projecting losses from hurricanes. The FCHLPM established a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a Holland B parameter hurricane wind field model. Uncertainty analysis quantifies the expected percentage reduction in the uncertainty of wind speed and loss that is attributable to each of the input variables.