Horwitz's rule, transforming both sides and the design of experiments for mechanistic models

Summary. The paper develops methods for the design of experiments for mechanistic models when the response must be transformed to achieve symmetry and constant variance. The power transformation that is used is partially justified by a rule in analytical chemistry. Because of the nature of the relationship between the response and the mechanistic model, it is necessary to transform both sides of the model. Expressions are given for the parameter sensitivities in the transformed model and examples are given of optimum designs, not only for single-response models, but also for experiments in which multivariate responses are measured and for experiments in which the model is defined by a set of differential equations which cannot be solved analytically. The extension to designs for checking models is discussed.     

2½‐Year‐Old Children Use Animacy and Syntax to Learn a New Noun

We examine how attention to animacy information may contribute to children's developing knowledge of language. This research extends beyond prior research in that children were shown dynamic events with novel entities, and were asked not only to comprehend sentences but to use sentence structure to infer the meaning of a new word. In a 4 × 3 design, animacy status (e.g., animate agent, inanimate patient) and labeling syntax (agent, patient, nonlabel control) were varied. Across most events, 2 1/2‐year‐old participants responded as if they expected animate entities to be named. However, in a prototypical (animate agent‐inanimate patient) event condition, children responded differentially across different syntactic structures. Thus, the clearest evidence for attention to syntactic cues was found in the prototypical event condition. These results suggest that young children attend to the animacy status of unfamiliar entities, that they have expectations about animacy relations in events, and that these expectations support emerging syntactic knowledge.     

Direct and Indirect Causal Effects via Potential Outcomes*

Abstract. The use of the concept of ‘direct’ versus ‘indirect’ causal effects is common, not only in statistics but also in many areas of social and economic sciences. The related terms of ‘biomarkers’ and ‘surrogates’ are common in pharmacological and biomedical sciences. Sometimes this concept is represented by graphical displays of various kinds. The view here is that there is a great deal of imprecise discussion surrounding this topic and, moreover, that the most straightforward way to clarify the situation is by using potential outcomes to define causal effects. In particular, I suggest that the use of principal stratification is key to understanding the meaning of direct and indirect causal effects. A current study of anthrax vaccine will be used to illustrate ideas.     

Rural/Urban Differences in Child Growth and Survival in Bolivia

Abstract Using data from a national survey in Bolivia and from a regional sample of poor communities in two regions of Bolivia, we model the effects of community conditions, household characteristics, and social relations on child health as measured by child mortality and stunted growth. Based on national data, children in rural areas are twice as likely to die before the age of two than are children in large cities, and about one‐third of the children in rural areas are stunted. Including measures of community, household, and maternal characteristics accounts for at least two‐thirds of the urban/rural difference in child health. We conclude that expansion of health services, improvements in household and community sanitation, and socioeco‐nomic development are all needed to overcome the rural disadvantage in child health.     

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.     

A screening system for tardive dyskinesia: development and implementation.

1. Most diagnosed cases of tardive dyskinesia (TD) are mildly inconvenient to the patient, but some can be severe or life-threatening. The primary goal of intervention should be early identification of abnormal movements related to TD and the prescribing of an appropriate medication regimen. 2. Unless specific training occurs and a specific monitoring system is in place, TD movements may be missed. However, not all movements are necessarily related to TD. 3. Although screening and monitoring are valuable, nothing is more important than prevention. New medications must be developed that do not carry the risk of TD, and other approaches to treat TD must be developed.     

The Effects of ROTC Program Participation on Socioeconomic Status and Life Satisfaction*

Using mail survey data based on a stratified systematic sample [N = 686] of 1983–1988 graduates of a medium-sized state university, this research evaluates whether ROTC program participation constitutes an independent source of human capital in civilian labor markets by comparing postgraduate earnings (annual income), prestige and authority, and life satisfaction of ROTC program participants with those of nonparticipants. The results revealed no statistically significant ROTC program participation effects, independent of subsequent military status. ROTC program participation paid off in terms of occupational prestige and authority for those on active duty, but not for those in national guard or reserve units. Neither ROTC participation nor current military status affected income or life satisfaction levels.     

Recurrent pain in college students.

The authors investigated the prevalence of recurrent pain in a college student sample. Of the 1,564 students surveyed, 467 (29%) indicated that they had experienced recurrent pain at an intensity that was mostly in the mild-to-moderate range. Students who reported having recurrent pain were significantly older and more depressed than students who did not indicate they suffered from recurrent pain. Pain intensity was positively correlated (r = .14) with depression among the students who reported having recurrent pain. Implications of the findings for future research, treatment, and health promotion efforts are discussed.