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.     

It takes two to tango: the integration of people with disabilities into society

The concept of integration is not well defined. It not known how people with disabilities experience integration. In this study qualitative methods were used. The aim of the article is to define a model of successful integration based on the perspectives of people with disabilities and people within their social environment. Integration consists of five elements: functioning ordinarily without receiving special attention, mixing with others that are not disabled, taking part in society, trying to realize one’s potential and directing one’s own life. Integration is obtained through a process of interaction between a person with a disability and society. This process is influenced by personal, societal and support factors. The individual with a disability and society have a mutual responsibility with respect to integration.     

The poverty of social control: explaining power in the historical sociology of the welfare state

The concept ‘social control’ has been criticised from a variety of quarters in recent years, particularly by historians and historical sociologists. However, it remains in common usage in sociological studies of welfare, deviance and social control. This paper shows, first, how this reliance on the concept of social control is rooted in a wider-ranging argument in social and political theory concerning the liberal-democratic fusion between the state and civil society, and that the lack of resolution of this argument is the foundation of the persistence of the concept social control in other areas of social inquiry, despite its repeated ‘falsification’. Second, the paper highlights the main arguments against the use of ‘social control’ in explaining social order, in particular the misunderstanding of class, culture and power which its use encourages, and the paper will conclude with a discussion of alternative ways of conceptualising the operation of power in contemporary societies.     

STTEPping in the right direction? Western classical music in an orchestral programme for disadvantaged African youth

This article looks at STTEP, an outreach project currently housed at the University of Pretoria, which concentrates on the teaching of western orchestral instruments, plus background areas such as music theory, to disadvantaged children and youth from a variety of townships around Pretoria, South Africa. STTEP’s direction can well be described as ‘right’ – pupils are already surrounded by all kinds of global phenomena, and their formal music studies in western classical music are not making them forget their roots. In fact, the contrary has been found to be the case and some interesting cultural fusions are already seen – always a sign of a living culture.     

Supervisory powers relating to foundations: A comparative analysis of foundation law

This paper compares legal approaches to foundations in six economically well-developed democracies (USA, England and Wales, Germany, Austria, France and the Netherlands). ‘Foundations’ refers to ‘non-governmental, non-membership, organisations, recognised as a legal category with a purpose in the general interest’. This covers the common field of the common law's charity and the civil law's foundation as a legal person. The countries organise public supervision of foundations in very different ways. Mostly there is governmental involvement or involvement of an independent body in the establishment and governmental supervision of foundations in action. In a few cases, the supervisory power—concerning the foundations' activities, not their establishment—is with judicial authorities. Access to information of foundations (registration) and possible requests for sanctions by interested parties are also rather different. Not all rules are in accordance with the freedom of organisation and some are less desirable. The conclusion is that a balance between the freedom of the foundation (board), the protection of the public order and the protection of the interests of others can be found in a system with systematic supervision at the establishment- and later practice—by governmental or independent authorities or in a system with good registration and incidental supervision by judicial authorities, also at the request of interested parties. Both have their advantages and disadvantages.     

Late fertility decline in the Netherlands: The influence of religious denomination,socioeconomic group and region

Both published results from the 1930, 1947, 1960 and 1971 censuses and unpublished ones are used to examine the influence that religious denomination, socio-economic group and region exerted on the fertility of marriages contracted between 1876 and 1959. A theory formulated by Lesthaeghe and Wilson on the relation between modes of production and secularization and the pace of fertility decline in Western Europe offers — in combination with van Heek's views on the special position of Dutch Roman Catholicism — a starting point for an explanation of why the fertility decline of Roman Catholics, self-employed and agricultural labourers lagged behind.     

Beggars can be choosers: Resource scarcity,dynamism, search activities,and their joint impact on performance

Research on firm search stresses the need for firms to adapt and align concurrently with their environment to optimize the ability to sense and seize opportunities for sustained performance. We postulate resource scarcity as an important contingency factor for the search-performance relationship, and assess its joint influence with high and low dynamism. Using a dataset spanning 23 years, we examine the performance implications of combinations of internal and external exploratory and exploitative search in resource-scarce environments, under conditions of high and low dynamism. We find that resource scarcity is an important condition for performance stemming from exploratory and exploitative search: even under conditions that involve low dynamism, but joined with resource scarcity, firms may benefit from pursuing exploratory and exploitative knowledge simultaneously.     

Axiomatizations of the normalized Banzhaf value and the Shapley value

A cooperative game with transferable utilities– or simply a TU-game – describes a situation in which players can obtain certain payoffs by cooperation. A solution concept for these games is a function which assigns to every such a game a distribution of payoffs over the players in the game. Famous solution concepts for TU-games are the Shapley value and the Banzhaf value. Both solution concepts have been axiomatized in various ways. An important difference between these two solution concepts is the fact that the Shapley value always distributes the payoff that can be obtained by the `grand coalition' consisting of all players cooperating together while the Banzhaf value does not satisfy this property, i.e., the Banzhaf value is not efficient. In this paper we consider the normalized Banzhaf value which distributes the payoff that can be obtained by the `grand coalition' proportional to the Banzhaf values of the players. This value does not satisfy certain axioms underlying the Banzhaf value. In this paper we introduce some new axioms that characterize the normalized Banzhaf value. We also provide an axiomatization of the Shapley value using similar axioms. Received: 10 April 1996 / Accepted: 2 June 1997     

Hospital-sponsored networks. The rush to consolidate and the future of medical practice

As the medical delivery system undergoes fundamental change, there is a growing pressure on hospitals to form networks with physicians. The prime motivation for these entities is to preserve market share and fill beds. There is likewise intense pressure on physicians to join them, even if these networks do not serve their best interests, or the goal of fostering physician-centered practice. A transformation is under way, however, that may well place doctors again in the central role of guiding the new modes of medical practice in the United States.