Modeling Benzene Pharmacokinetics Across Three Sets of Animal Data: Parametric Sensitivity and Risk Implications

Typically, the uncertainty affecting the parameters of physiologically based pharmacokinetic (PBPK) models is ignored because it is not currently practical to adjust their values using classical parameter estimation techniques. This issue of parametric variability in a physiological model of benzene pharmacokinetics is addressed in this paper. Monte Carlo simulations were used to study the effects on the model output arising from variability in its parameters. The output was classified into two categories, depending on whether the output of the model on a particular run was judged to be generally consistent with published experimental data. Statistical techniques were used to examine sensitivity and interaction in the parameter space. The model was evaluated against the data from three different experiments in order to test for the structural adequacy of the model and the consistency of the experimental results. The regions of the parameter space associated with various inhalation and gavage experiments are distinct, and the model as presently structured cannot adequately represent the outcomes of all experiments. Our results suggest that further effort is required to discern between the structural adequacy of the model and the consistency of the experimental results. The impact of our results on the risk assessment process for benzene is also examined.     

Requirements for successful implementation of new manufacturing technologies

This paper addresses the issue of why many U.S. companies have had major problems implementing “programmable automation” technologies in a manner to exploit their full potential. Many competitors in Japan and Europe have been much more successful. The theme of the paper is that the real impediment to the effective use of this new manufacturing hardware lies in some deeply entrenched attitudes and ways of doing things that are incompatible with the requirements and unique capabilities of the new hardware. Barriers to successful implementation are explored and implications for managerial practice are discussed.     

Beyond the nature/society divide: Learning to think about a mountain

Sociological efforts to understand environment-society relationships fall primarily into four conceptual categories. The first three, involving analytical separation, analytical primacy, and balanced dualism, all draw distinctions between biophysical and social aspects of human experience, with subsequent analyses being based on thesea priori distinctions. The fourth or constructivist approach questions this naturalized dichotomy, calling attention instead to mutual contingency or conjoint constitution: What we take to be physical facts are likely to be strongly shaped by social construction processes, and at the same time, what we take to be strictly social will often have been shaped in part by taken-for-granted realities of the physical world. Technology offers important opportunities for tracing these interconnections, being an embodiment of both the physical and the social. The point is illustrated with a long-term historical analysis of a specific physiographic feature—a mountain—that has undergone little overtphysical change over the centuries, but has undergone repeated changes in its social meanings and uses. Few of the changes would have been possible in the absence of the mountain's physiographic characteristics; similarly, few would have occurred in the absence of changing sociocultural definitions and possibilities. The challenge for sociology is not just to recognize the importance of both the physical and the social factors, and certainly not to argue over the relative importance of the two, but to recognize the extent to which what we take to be physical and social factors can be conjointly constituted.The paper's subtitle is intended as a tribute to Aldo Leopold and to one of his most famous essays (1949).     

Some criteria for making decisions concerning the distribution of scarce medical resources

In this paper I proceed on the assumption that moral philosophers can and should contribute to the resolution of perplexing moral problems. The ones considered here relate to decisions concerning the distribution of scarce medical resources as between those in need of treatment. I draw on considerations of egalitarianism and concern for the maximization of the use of scarce resources in the task of satisfying basic human needs (such as for good health). I propose certain principles and offer some supporting suggestions as guidelines or rules for medical decisions with a view to providing a helpful decision procedure for the various persons (doctors, community panels and so on) whose task it is to make the life-or-death decisions involved in allocating certain scarce medical resources.     

Resource management schemes

Every large management organization undergoes the cyclic progress of planning, programming, budgeting, and rating of work tasks of projects to be accomplished by priority in the light of resource constraints controlling personnel strenghts and operating funds by fiscal periods. This is true, especially of governmental departments that are commodity oriented. There must be some ultimate goal of fine grain visibility that management can attempt to achieve or at least approach in order for the functional directors within the organization structure to relate and report most readily to provide required data for proficient resource management. Two essential requirements are visibility and integrated reporting as herein prescribed. Following the ascertainment of resource requirements in the light of projected work effort, some logical procedure should be employed in the rationale of resource adjustments. The Tolerance Box technique is herein described.     

Repeat abortion

A reanalysis of the repeat abortion experience of New York City residents during July 1, 1970 to June 30, 1972 is undertaken on the basis of a probability model that generates repeat abortion ratios as a function of assumptions about fecundity, contraceptive efficiency, and exposure lengths. Tested are three hypotheses put forward by Daily et al. in a 1973 analysis: (i) the low repeat abortion ratio of .0245 is attributable in part to underreporting of registered induced abortions as repeat ones; (ii) a major part of the rise in repeat abortion ratios, from virtually zero to six percent over four consecutive six-month intervals, is explainable in terms of the rising volume of exposure time to risk of repeat abortion relative to the stream of initial abortions; and (iii) the higher abortion ratios of women in their twenties compared to those of older or younger women is ascribable to “differences in fecundity and intercourse frequency.” Support is found for the first two hypotheses, and a mixed outcome for the third.     

Hot times,hot places. Youths’ risk perceptions and risk management in Chicago and Rotterdam

Many young people in low-income neighbourhoods are considered to be at risk of poor social outcomes and of becoming victims of violence and crime. This exploratory study focuses on how young people perceive risk and navigate their environment in two low-income, multi-ethnic neighbourhoods, one in Rotterdam and one in Chicago. We conducted in-depth interviews and mental mapping exercises with young people aged 14–19 in both sites. We found that neighbourhoods matter because they expose young people to certain kinds of risks, but also that their responses were shaped by their perceptions and interpretations of these risks. Moreover, we illustrate the dynamic and interactive nature of these processes of risk perception and management by discussing the ways in which different groups occupy and use, or travel through, public space at different times of the day. We argue that risk in disadvantaged neighbourhoods is not a static dimension in young people’s lives but rather emerges from an ongoing and complex interaction between perception, interpretation and response that can be seen as a kind of boundary work.     

Diagnosis of Pregnancy

Abstract

Contraceptive failure is a growing problem, especially on the college campus. Because of this, college health care providers are treating more and more college women not only for pregnancy-related problems, but women that present to the health center with other health complaints and are pregnant as well.

For these reasons, the diagnosis of pregnancy must always be entertained by all health care providers treating young women. Pregnancy must always be excluded before any tests or procedures are done that may be teratogenic. This is not only important for optimal health care, but also for medical-legal reasons.

This paper presents four unusual presentations of pregnancy and reviews the guidelines for diagnosis of pregnancy.