Local information and the design of sequential hypothesis tests

Various results on sequential hypotheses testing are reviewed. Optimal stopping rules are related to a local measure of statistical information. In some cases, local information can be approximated by L-numbers discovered by Lorden, and simple rules based on these approximations are asymptotically optimal to better order than the cost for a single observation.     

An Adjustment Factor for Mode-of-Action Uncertainty with Dual-Mode Carcinogens: The Case of Naphthalene-Induced Nasal Tumors in Rats

The U.S. Environmental Protection Agency (USEPA) guidelines for cancer risk assessment recognize that some chemical carcinogens may have a site-specific mode of action (MOA) involving mutation and cell-killing-induced hyperplasia. The guidelines recommend that for such dual MOA (DMOA) carcinogens, judgment should be used to compare and assess results using separate "linear" (genotoxic) versus "nonlinear" (nongenotoxic) approaches to low-level risk extrapolation. Because the guidelines allow this only when evidence supports reliable risk extrapolation using a validated mechanistic model, they effectively prevent addressing MOA uncertainty when data do not fully validate such a model but otherwise clearly support a DMOA. An adjustment-factor approach is proposed to address this gap, analogous to reference-dose procedures used for classic toxicity endpoints. By this method, even when a "nonlinear" toxicokinetic model cannot be fully validated, the effect of DMOA uncertainty on low-dose risk can be addressed. Application of the proposed approach was illustrated for the case of risk extrapolation from bioassay data on rat nasal tumors induced by chronic lifetime exposure to naphthalene. Bioassay data, toxicokinetic data, and pharmacokinetic analyses were determined to indicate that naphthalene is almost certainly a DMOA carcinogen. Plausibility bounds on rat-tumor-type-specific DMOA-related uncertainty were obtained using a mechanistic two-stage cancer risk model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Bound-specific adjustment factors were then used to reduce naphthalene risk estimated by linear extrapolation (under the default genotoxic MOA assumption), to account for the DMOA exhibited by this compound.     

Comparing Estimates of the Effects of Air Pollution on Human Mortality Obtained Using Different Regression Methodologies

Studies using regression techniques report their results using a variety of statistics. Evaluation of the consistency of findings, such as in a metaanalysis, requires calculating the statistical estimates of the effect reported in each study in a comparable manner. In this paper, we consider multiple linear regression, multiple Poisson regression, and logistic regression estimates. We present results that are needed to calculate, on a common basis, the slope of the regression function at a specified value, the elasticity function of the regression function at a specified value, the relative risk at a specified value, and the odds ratio at a specified value. We apply these results to studies of the association of daily mortality in an area to the daily air pollution level of ozone and PM₁₀. We calculate the estimated slope of the number of deaths per billion population associated with an increase of 1 ppb of ozone level in studies of daily mortality in three urban areas. These studies, in Los Angeles, New York, and St. Louis, produced very comparable results on a common basis, especially when compared to the coefficients as reported. We also calculated the estimated elasticity function of the daily mortality and daily PM₁₀ level for eight areas and found that the elasticities varied within a factor of roughly two, much less than the variability in the coefficients as reported.     

Mixing patterns between age groups in social networks

We present a method for estimating transmission matrices that describe the mixing and the probability of infection between age groups. Transmission matrices can be used to estimate age-dependent forces of infection in age-structured, compartmental models for the study of infectious diseases. We analyze the social network generated by the synthetic population of Portland and extract mixing patterns. Our results show that the mixing within the population consists of two groups, children and adults. Children interact most frequently with other children close to their own age, while adults interact with a wider range of age groups and the durations of typical adult contacts are shorter than typical contacts between children. Furthermore, the transmission matrix shows that children are more likely to acquire infection than adults.     

ON A MULTIPLE THREE-DECISION PROCEDURE FOR COMPARING SEVERAL TREATMENTS WITH A CONTROL

For the two-sided comparisons of several treatments with a control, a common statistical problem is to decide which treatments are better than the control and which are worse than the control. This paper studies a multiple three-decision procedure for this purpose, proposed by Bohrer (1979) and Bohrer et al. (1981), and provides tables of critical points to facilitate the application of the procedure. The paper defines a power function of the procedure, and tabulates sample sizes necessary to guarantee a given power level. It addresses the problem of optimal sampling allocation in order to maximize the power for a given total sample size, and considers generalization to the situation where the treatments might have unequal numbers of observations.     

Development and Consideration of Global Policies for Managing the Future Risks of Poliovirus Outbreaks: Insights and Lessons Learned Through Modeling

The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes.     

Mental load and work stress as two types of energy mobilization

A conceptual framework is presented in which mental load and stress are regarded as two distinct biobehavioural states in the work environment that differ in energy mobilization, mood and coping strategy. The framework combines two types of theory that are based on human performance research using laboratory tasks on the one hand and applied research in the work environment on the other. A high workload is regarded as an important but not a critical factor in the development of stress symptoms. Even under unfavourable conditions it is possible to work intensively and to be highly activated without feelings of strain or psychosomatic complaints. In contrast, working conditions that provide few possibilities for control and little social support or are associated with reduced well-being and increased health risks. The two states differ in activation, coping style and mood. A proper distinction is important not only for theory building but also for the reconstruction of the work environment. It may lead to recommendations that aim to enhance the work efficiency of employees while reducing the probability that stress responses will occur.