Physiologically Based Liver Modeling and Risk Assessment

Because of the inherent complexity of biological systems, there is often a choice between a number of apparently equally applicable physiologically based models to describe uptake and metabolism processes in toxicology or risk assessment. These models may fit the particular data sets of interest equally well, but may give quite different parameter estimates or predictions under different (extrapolated) conditions. Such competing models can be discriminated by a number of methods, including potential refutation by means of strategic experiments, and their ability to suitably incorporate all relevant physiological processes. For illustration, three currently used models for steady-state hepatic elimination--the venous equilibration model, the parallel tube model, and the distributed sinusoidal perfusion model--are reviewed and compared with particular reference to their application in the area of risk assessment. The ability of each of the models to describe and incorporate such physiological processes as protein binding, precursor-metabolite relations and hepatic zones of elimination, capillary recruitment, capillary heterogeneity, and intrahepatic shunting is discussed. Differences between the models in hepatic parameter estimation, extrapolation to different conditions, and interspecies scaling are discussed, and criteria for choosing one model over the others are presented. In this case, the distributed model provides the most general framework for describing physiological processes taking place in the liver, and has so far not been experimentally refuted, as have the other two models. These simpler models may, however, provide useful bounds on parameter estimates and on extrapolations and risk assessments.     

New Voices in Iceland. Parents and Adult Children: juggling supports and choices in time and space

This paper deals with parents' perspectives and experiences of bringing up children with a variety of impairments in Iceland, and how they impact the young disabled adults' approach to the status of adulthood. The paper is based on a qualitative study that explored perspectives and experiences of 36 young disabled adults (16-24 years old), their parents, friends and teachers. The purpose of this paper is to share themes related to patterns of parents' reactions and choices when coming to terms with parenting a disabled child, the support they found from their social network and professionals, and their sons or daughters' subsequent views of themselves and their prospects as young adults. The paper includes different perspectives on adulthood and the extent to which the young disabled people expect to reach that status or remain as 'eternal youth' enmeshed in segregated services. Findings show that the type and nature of early support for parents of disabled children is critical for the young adults' approaching adulthood in regular society or expecting to remain in the limbo of 'eternal youth' within segregated settings. Early 'betrayals' may, however, be revisited at each subsequent transition point. Furthermore, parents and their disabled children who struggled for social inclusion could obtain full active membership in society, even against social and physical barriers, and medically defined disability labels.     

Mining the Data: Analyzing the Economic Implications of Mining for Nonmetropolitan Regions

Extractive industries such as logging and mining are generally expected to bring significant economic benefits to rural regions, but a growing number of findings have now challenged that common expectation. Still, it is not clear whether the findings of less–than–desirable economic outcomes are isolated or representative. In this article, we assemble literally all of the relevant quantitative findings on mining that we have been able to identify in published and/or technical literature from the United States. In the interest of rigor, we limit the assessment to cases in which strictly nonmetropolitan mining regions are compared against other nonmetropolitan regions and/or against those regions’ own experiences over time. Overall, 301 findings meet the criteria for inclusion. Contrary to the long–established assumptions, but consistent with more recent critiques, roughly half of all published findings indicate negative economic outcomes in mining communities, with the remaining findings being split roughly evenly between favorable and neutral/indeterminate ones. Positive findings are more likely to be associated with incomes than with poverty or (especially) unemployment rates, and they are more likely to come from the western United States, where much of the mining involves relatively large, new coal strip mines. Over half of all positive findings come from the years prior to 1982. In virtually all other categories, the plurality or majority of findings have been negative. When the patterns of findings are subjected to one–sample means tests, the only way to produce a significantly positive outcome is by combining all neutral/indeterminate findings with the positive ones, while focusing exclusively on incomes; by contrast, in the case of poverty or unemployment rates—as well as for the overall body of findings—the results are consistently and significantly negative, whether the neutral/indeterminate findings are combined with negative ones or omitted from the equations altogether. Until or unless future studies produce dramatically different findings, there appears to be no scientific basis for accepting the widespread, “obvious” assumption that mining will lead to economic improvement.     

In Whose Backyard?: Concern About Siting a Nuclear Waste Facility*

Proponents of hazardous and nuclear waste depositories label opponents to local siting of such facilities “NIMBYs” (Not In My Backyard). This study assesses the extent to which the NIMBY label and the strategies of industry proponents to reduce opposition function on a reasonable set of assumptions. Using survey data and multiple regression techniques, the levels of concern of residents living in the county selected as the site of a low level radioactive waste disposal facility (imminent threat condition) are compared with a statewide sample (hypothetical threat condition). Consistent with proponents' theoretical assumptions, the levels of concern are greater for respondents under conditions of imminent threat than of hypothetical threat. However, within the host county, levels of concern are lowest, albeit most polarized, in the community closest to the proposed site. A conflict theory approach enhances an understanding of these findings by suggesting that within the most proximate community levels of concern are lowest for citizens who stand to gain the most economic benefits from the facility but highest for those citizens who are least likely to derive tangible gains.     

Aid, Relief, and Containment: The First Asylum Country and Beyond

A fundamental problem that confronts the European Union today is how it can maintain its commitment to the institution of asylum while checking irregular migration and the abuse of its asylum system. In order to explore a response to this dilemma the paper addresses the following questions: what role can relief and aid policies play in influencing migration patterns? What should be the appropriate approach to the granting of relief and aid to developing countries of first asylum? Should it be viewed as a part of the larger problem of development or be treated as a distinct issue? What kind of a relief/aid model will help refugees return to post–conflict societies and stop the conflict from reproducing itself? The paper examines two different approaches to address these questions: the alliance–containment approach and the distributive–developmental approach. It also looks at some empirical evidence, which reveals that at present it is a conservative alliance–containment approach that informs EU relief and aid practices. This approach, however, does not help achieve the stated objective of checking abuse of asylum and migration procedures while sustaining a commitment to a liberal asylum regime. The paper goes on to identify the gaps in EU policy and the lessons that can be drawn. It concludes by looking at different policy alternatives and suggesting the adoption of a reformist distributive–developmental model. The implementation of this model holds out the hope of reverting to a more liberal asylum regime while controlling irregular migration and “bogus” asylum seekers, for the reformist distributive developmental model takes a more long–term view of migration trends and also seeks to address the growing North–South divide.     

The Boston Area Diary Study and the Moral Citizenship of Care

This paper describes the theoretical foundations, empirical findings, and practical and philosophical implications of the Boston Area Diary Study (BADS), a study of the caring behavior of 44 participants over one calendar year. In particular, the paper presents an identification theory of care and discusses how it shaped the conceptualization, collection, and analysis of the data in a year-long diary study of daily voluntary assistance. The findings from the BADS (1) theoretically confirm the identification theory of care; (2) methodologically capture how individuals perceive and carry out caring behavior as a unity; and (3rpar; empirically document the existence of a moral citizenship in America that is substantially more vigorous than is implied by the usual indicators of civic and political citizenship.     

AN ALGORITHM FOR THE CONSTRUCTION OF OPTIMAL OR NEAR-OPTIMAL CHANGE-OVER DESIGNS

This paper presents an algorithm for the construction of optimal or near optimal change-over designs for arbitrary numbers of treatments, periods and units. Previous research on optimality has been either theoretical or has resulted in limited tabulations of small optimal designs. The algorithm consists of a number of steps:first find an optimal direct treatment effects design, ignoring residual effects, and then optimise this class of designs with respect to residual effects. Poor designs are avoided by judicious application of the (M, S)-optimality criterion, and modifications of it, to appropriate matrices. The performance of the algorithm is illustrated by examples.