Efficient designs for animal carcinogenicity experiments

In a typical carcinogenicity study, animals, usually rats or mice. are divided into a control and two to three dose groups of 50 or more by randomization. A chemical is administered at a constant daily dose rate for a major portion of the lifetime of the test animals, for example, two years. In general, such an experiment is expensive and time consuming In this paper, we propose an efficient design with reduced sample size and/or shortened study duration. An equal number of animals per dose group is considered in this study. A power study of the age-adjusted trend test, for the turnor incidence rate for single-sacrifice experiments proposed by Kodell et al. (Drug Information Journal, 1997) is conducted. A Monte Carlo simulation study is performed to compare the performance of the trend test for the standard design and various reduced designs. Based on the Kodell et al. test, the 21-month study duration with sample size 50 per group is recommended as the best, reduced design over the traditional 2-year study design with the same sample size.     

Model Uncertainty and Model Averaging in the Estimation of Infectious Doses for Microbial Pathogens

Food‐borne infection is caused by intake of foods or beverages contaminated with microbial pathogens. Dose‐response modeling is used to estimate exposure levels of pathogens associated with specific risks of infection or illness. When a single dose‐response model is used and confidence limits on infectious doses are calculated, only data uncertainty is captured. We propose a method to estimate the lower confidence limit on an infectious dose by including model uncertainty and separating it from data uncertainty. The infectious dose is estimated by a weighted average of effective dose estimates from a set of dose‐response models via a Kullback information criterion. The confidence interval for the infectious dose is constructed by the delta method, where data uncertainty is addressed by a bootstrap method. To evaluate the actual coverage probabilities of the lower confidence limit, a Monte Carlo simulation study is conducted under sublinear, linear, and superlinear dose‐response shapes that can be commonly found in real data sets. Our model‐averaging method achieves coverage close to nominal in almost all cases, thus providing a useful and efficient tool for accurate calculation of lower confidence limits on infectious doses.     

Revised Historical Viewpoints

The author describes the use of literature circles in a social studies methods course for elementary preservice teachers and analyzes their effectiveness in teaching powerful social studies ideas. Literature circles encourage students to take more of a leadership role in the classroom, expect their active involvement, and challenge them to think more deeply about social studies content within texts. Students can compare different perspectives on the same historical event, such as the encounter between Columbus and the Taino, and reasons for including and omitting important ideas. Students can also note similarities and differences among cultures and current and historical events through literature circle discussions. However, teachers must carefully select texts which focus on powerful social studies ideas, emphasize the goal of thoughtful discussions when introducing literature circles, and be ready to raise significant issues ignored in the literature circle discussions during follow-up class discussions.