Uncertainties in Pharmacokinetic Modeling for Perchloroethylene. I. Comparison of Model Structure, Parameters, and Predictions for Low-Dose Metabolism Rates for Models Derived by Different Authors

In recent years physiologically based pharmacokinetic models have come to play an increasingly important role in risk assessment for carcinogens. The hope is that they can help open the black box between external exposure and carcinogenic effects to experimental observations, and improve both high-dose to low-dose and interspecies projections of risk. However, to date, there have been only relatively preliminary efforts to assess the uncertainties in current modeling results. In this paper we compare the physiologically based pharmacokinetic models (and model predictions of risk-related overall metabolism) that have been produced by seven different sets of authors for perchloroethylene (tetrachloroethylene). The most striking conclusion from the data is that most of the differences in risk-related model predictions are attributable to the choice of the data sets used for calibrating the metabolic parameters. Second, it is clear that the bottom-line differences among the model predictions are appreciable. Overall, the ratios of low-dose human to bioassay rodent metabolism spanned a 30-fold range for the six available human/rat comparisons, and the seven predicted ratios of low-dose human to bioassay mouse metabolism spanned a 13-fold range. (The greater range for the rat/human comparison is attributable to a structural assumption by one author group of competing linear and saturable pathways, and their conclusion that the dangerous saturable pathway constitutes a minor fraction of metabolism in rats.) It is clear that there are a number of opportunities for modelers to make different choices of model structure, interpretive assumptions, and calibrating data in the process of constructing pharmacokinetic models for use in estimating "delivered" or "biologically effective" dose for carcinogenesis risk assessments. We believe that in presenting the results of such modeling studies, it is important for researchers to explore the results of alternative, reasonably likely approaches for interpreting the available data--and either show that any conclusions they make are relatively insensitive to particular interpretive choices, or to acknowledge the differences in conclusions that would result from plausible alternative views of the world.     

The Promise of Molecular Epidemiology for Quantitative Risk Assessment

In the long run, molecular epidemiological techniques can provide important insights for understanding a wide variety of important issues in current risk assessment and are applicable across a broad spectrum of adverse effects in addition to carcinogenesis. Unfortunately, current risk assessment practices make very little use of the kind of detailed mechanistic information that molecular epidemiology can provide. Eventually, there is reason to hope that the availability of mechanistic insights provided in part by molecular epidemiology can produce some of the "essential tension" required to reform paradigms for the formulation of quantitative risk assessment models in general.     

Marginal revenue and labor strife in major league baseball

An improved model of baseball player performance and revenue generation shows that, overall, major league players are paid more than the marginal revenue they generate from spectators at the ballpark. Broadcast revenue is shown to be a factor in player salaries, although this revenue is not sensitive to individual player output. Under the current bargaining procedure, collective action in baseball is therefore viewed as the only way to entice owners to pay players for the broadcast revenue they generate.     

Impact of Bereavement on the Self-Conceptions of Older Surviving Spouses

The purpose of this longitudinal study was to assess the extent to which the social anchorage dimension of the self-concept is impacted by the death of a spouse among a sample of older surviving spouses. Social anchorage was measured by the Twenty Statements Test (TST) in mailed questionnaires and consisted of self-statements that signify important social relationships and group memberships. As hypothesized, the 42 bereaved persons had lower social anchorage scores than the 72 nonbereaved controls. This significant effect was evident as early as three to four weeks following the death, and it persisted through five more measurement periods that covered the first two years of bereavement.     

What Should Be the Implications of Uncertainty,Variability, and Inherent “Biases”/“Conservatism” for Risk Management Decision-Making?

This paper is a challenge from a pair of lifelong technical specialists in risk assessment for the risk-management community to better define social decision criteria for risk acceptance vs. risk control in relation to the issues of variability and uncertainty. To stimulate discussion, we offer a variety of straw man proposals about where we think variability and uncertainty are likely to matter for different types of social policy considerations in the context of a few different kinds of decisions. In particular, we draw on recent presentations of uncertainty and variability data that have been offered by EPA in the context of the consideration of revised ambient air quality standards under the Clean Air Act.     

Aging as intracohort differentiation: Accentuation,the Matthew effect,and the life course

Recent contributions of sociologists and others have brought a new awareness and new theoretical understanding of the extent to which human aging and life-course patterns are shaped by social conditions and influenced by social change. Yet the potential of many social processes to account for individual aging patterns remains untapped, because research and theory have focused heavily upon comparisons between cohorts rather than the internal differentiation of cohorts. This paper shows that focusing upon intracohort differentiation over the life course leads to a mobilization of sociological findings whose age-related implications have not been exploited. Using the phenomenon of aged heterogeneity as an illustrative case, it is suggested that intracohort differentiation—operating through macro-level, organizational, and micro-level processes—can explain significant phenomena of aging previously neglected by theory, or else assumed to be psychological in origin. These processes specify Merton's Matthew effect. Implications for biological aging and for research are briefly discussed.     

The rise of developing Asia and the new economic order

This paper identifies emerging trends in the world economy during the next decade. The first is that China will overtake the U.S. in terms of gross domestic product (GDP), ending more than a century of U.S. leadership as the world's largest economy. The second is that Developing Asia, excluding Japan, will overtake the G7, a group of the seven largest industrialized economies established in 1975-76. Finally, India will overtake Japan, Russia will overtake Germany, and Brazil will overtake the U.K., leading to a New World Economic Order: China, the U.S., India, Japan, Russia, Germany, and Brazil.     

The Cost of Low Fertility in Europe

We analyze the effect of fertility on income per capita with a particular focus on the experience of Europe. For European countries with below-replacement fertility, the cost of continued low fertility will only be observed in the long run. We show that in the short run, a fall in the fertility rate will lower the youth dependency ratio and increase the working-age share, thus raising income per capita. In the long run, however, the burden of old-age dependency dominates the youth dependency decline, and continued low fertility will lead to small working-age shares in the absence of large migration inflows. We show that the currently very high working-age shares generated by the recent declines in fertility and migration inflows are not sustainable, and that significant drops in the relative size of the working-age population should be expected. Without substantial adjustments in labor force participation or migration policies, the potential negative repercussions on the European economy are large.     

Worker Turnover,Capital Dispersion,and Matching

Abstract. A model acknowledging technology and wage dispersion, search frictions, and costly worker turnover is used for testing the notion of random matching. Using a linked employer–employee data set on roughly 9,000 Norwegian establishments and 200,000 jobs during the period 1989–95, I show that establishments investing more in capital, pay more, and experience lower worker turnover rate. Strictly convex turnover costs are identified. High‐wage establishments post on average less intensively than low‐wage establishments. Positive relationships between wages and posting are observed for high‐tech industries and in the capital and surroundings. Thus, the notion of random matching is generally rejected.