Data and Model Management in a Generalized MCDM-DSS*

Drawing upon the choice models developed in the multiple criteria decision making (MCDM) area, this paper proposes an architecture for designing an intelligent decision support system (DSS) that is intended to aid in making choices among multiple alternatives along multiple dimensions. It argues that effective support can be provided to the decision maker when the knowledge-based DSS is capable of dynamically selecting choice models appropriate to the domain and context of a particular problem being specified by the decision maker, and of properly applying them to the problem solution. Development of a prototype intended to partially represent application of the architecture is described. The paper concludes with suggestions for research extensions.     

Incentives Policies to Site Hazardous Waste Facilities

This paper addresses the use of mitigation and compensation as incentives policies to stimulate agreement between parties interested in siting a hazardous waste facility and potential host communities. We develop a model of facility siting that distinguishes five key factors which influence the acceptability of a proposed facility when considered in relation to status quo conditions. This model then is used to examine the effectiveness of different incentives policies with regard to (a) mitigating the perceived risks and (b) compensating the adverse impacts of a hazardous waste facility.     

The Impact of Cytochrome P450 2E1-Dependent Metabolic Variance on a Risk-Relevant Pharmacokinetic Outcome in Humans

Risk assessments include assumptions about sensitive subpopulations, such as the fraction of the general population that is sensitive and the extent that biochemical or physiological attributes influence sensitivity. Uncertainty factors (UF) account for both pharmacokinetic (PK) and pharmacodynamic (PD) components, allowing the inclusion of risk-relevant information to replace default assumptions about PK and PD variance (uncertainty). Large numbers of human organ donor samples and recent advances in methods to extrapolate in vitro enzyme expression and activity data to the intact human enable the investigation of the impact of PK variability on human susceptibility. The hepatotoxicity of trichloroethylene (TCE) is mediated by acid metabolites formed by cytochrome P450 2E1 (CYP2E1) oxidation, and differences in the CYP2E1 expression are hypothesized to affect susceptibility to TCE's liver injury. This study was designed specifically to examine the contribution of statistically quantified variance in enzyme content and activity on the risk of hepatotoxic injury among adult humans. We combined data sets describing (1) the microsomal protein content of human liver, (2) the CYP2E1 content of human liver microsomal protein, and (3) the in vitro Vmax for TCE oxidation by humans. The 5th and 95th percentiles of the resulting distribution (TCE oxidized per minute per gram liver) differed by approximately sixfold. These values were converted to mg TCE oxidized/h/kg body mass and incorporated in a human PBPK model. Simulations of 8-hour inhalation exposure to 50 ppm and oral exposure to 5 micro g TCE/L in 2 L drinking water showed that the amount of TCE oxidized in the liver differs by 2% or less under extreme values of CYP2E1 expression and activity (here, selected as the 5th and 95th percentiles of the resulting distribution). This indicates that differences in enzyme expression and TCE oxidation among the central 90% of the adult human population account for approximately 2% of the difference in production of the risk-relevant PK outcome for TCE-mediated liver injury. Integration of in vitro metabolism information into physiological models may reduce the uncertainties associated with risk contributions of differences in enzyme expression and the UF that represent PK variability.     

Misdirection on the road to Shangri-La

Will life expectancy in the United States rise or fall in this century? The implications of either scenario are far reaching. We contend that the rise of childhood obesity in the United States in the past three decades has been so dramatic that it will soon lead to higher than expected death rates at middle ages and a possible decline in life expectancy by midcentury. The most detrimental health and longevity effects will not be seen for decades--a phenomenon that cannot be detected by current methods used to forecast life expectancy or estimate the number of deaths currently attributable to obesity. This scenario contrasts sharply with the views of mathematical demographers who generate forecasts by relying on the assumption that the U.S. pattern of longevity will follow that of other longer lived nations and on the extrapolation of historical trends in life expectancy into the future.     

Methods for Measuring Mechanisms of Contention

A substantial intellectual movement has been growing in the social sciences around the adoption of mechanism- and process-based explanations as complements to variable-based explanations, or even as substitutes for them. But once we have recognized the validity and dignity of studying mechanisms and processes, what is the next step? Recently, both political scientists’ and sociologists’ discussions have begun to turn away from correlation to mechanism-based approaches to causation. But there is still a widespread assumption that mechanisms are unobservable. We maintain that ways can be developed to observe the presence or absence of mechanisms either directly or indirectly. In this paper, by way of example, we put forward four methods—two direct and two indirect—for measuring mechanisms of contention.     

Science versus Human Welfare? Understanding Attitudes toward Animal Use

Scientists have been portrayed as having an uncaring attitude toward the use of animals and being inclined to reject the possibility of animal mind ( Baldwin, 1993 ; Blumberg & Wasserman, 1995 ), yet there is little empirical research to support these claims. We examined why disparate attitudes toward animal use are held. Scientists, animal welfarists, and laypersons (N = 372) were compared on questionnaire responses that measured attitudes toward four types of animal use, and factors that might underlie these views (including belief in animal mind). As expected, scientists and animal welfarists held polarized views on all measures, whereas laypersons fell between the two. Animal welfarists were consistently opposed to all types of animal use, whereas scientists expressed support for the use of animals for medical research, but not for dissection, personal decoration, and entertainment. Animal welfarists showed high levels of belief in animal mind for 13 animal types, and scientists believed some of the 13 animals to have at least a moderate capacity for cognition and most to have at least a moderate capacity for sentience. Hence, the negative image of the science community that is often portrayed was not supported by our data. Findings were discussed in relation to external (group membership) and internal (belief systems) factors, and it is concluded that some people hold fixed attitudes toward animal use, whereas others are more influenced by context.