Interspecies Extrapolation of Physiological Pharmacokinetic Parameter Distributions

Three methods (multiplicative, additive, and allometric) were developed to extrapolate physiological model parameter distributions across species, specifically from rats to humans. In the multiplicative approach, the rat model parameters are multiplied by the ratio of the mean values between humans and rats. Additive scaling of the distributions is denned by adding the difference between the average human value and the average rat value to each rat value. Finally, allometric scaling relies on established extrapolation relationships using power functions of body weight. A physiologically-based pharmacokinetic model was fitted independently to rat and human benzene disposition data. Human model parameters obtained by extrapolation and by fitting were used to predict the total bone marrow exposure to benzene and the quantity of metabolites produced in bone marrow. We found that extrapolations poorly predict the human data relative to the human model. In addition, the prediction performance depends largely on the quantity of interest. The extrapolated models underpredict bone marrow exposure to benzene relative to the human model. Yet, predictions of the quantity of metabolite produced in bone marrow are closer to the human model predictions. These results indicate that the multiplicative and allometric techniques were able to extrapolate the model parameter distributions, but also that rats do not provide a good kinetic model of benzene disposition in humans.     

An extended formulation of Arrow's theorem for k-social welfare functions

Past studies in social choice theory are generally based on the assumption that any two alternatives must be incompatible. We are concerned with the concept, k-social choice based on the assumption that just k alternatives out of p (1kp–1) are compatible. The purpose of this paper is to show an extended formulation of Arrow's theorem for k-social welfare functions.     

Do hours matter? The relationship between motivation and study intensity in learners of English in Scotland

This paper examines the impact of English language learners’ motivation on their choice of study intensity using data from a national survey of learners in publicly funded English for Speakers of Other Languages (ESOL) courses across Scotland. In particular, the motivation of learners attending only a few hours per week (i.e. very part-time learners) is compared with those attending for more hours. Our study found that there are differences in motivation and aspiration amongst very part-time and part-time or full-time learners but also that employment and child care may have as much influence as motivation in causing learners to enrol on very part-time English classes. The findings relating to these learners in our study present a particular challenge to ESOL providers which offer only very part-time courses.     

Yearlong physical activity and health-related quality of life in older Japanese adults: the Nakanojo Study

We hypothesized that the health-related quality of life (HRQOL) would be poorer in physically inactive older adults. This was tested in a sample of 73 male and 108 female free-living healthy Japanese participants, age 65-85 years. We measured accelerometer step counts and their metabolic equivalents (METs) throughout each 24-hr period for 1 year. At the end of the year, HRQOL was assessed. Physical activity was grouped into quartiles. HRQOL was poorer in the lowest quartiles of participants with respect to both step count and duration of activity >3 METs; however, our sample showed no better HRQOL in those participants exceeding minimum standards of daily physical activity, corresponding to counts of around 5,500 and 4,500 steps/day and durations of around 13 and 14 min/day in men and women, respectively. Causation cannot be demonstrated from this cross-sectional study, but nevertheless we suggest that elderly individuals should be encouraged to meet such standards of habitual physical activity.     

Manager-subordinate Relationship in Cross-cultural Organizations: The Case of Japanese Subsidiaries in the United States

Abstract  The paper examines the perceptions of Japanese expatriate management held by American employees, whilst isolating the factors influencing such perceptions. An analysis of the survey data from 388 American eniployees has revealed that they view Japanese co-workers as loyal to the organization, competent, trustworthy, somewhat friendly, patient and fair on the one hand; but as secretive, hard to understand, untrusting of others and somewhat indecisive on the other. It has been found that the local employees with higher ranks are likely to perceive the expatriate managers more negatively than the ones with lower ranks; and that the local employees who have worked longer tend to view the expatriate managers more negatively than those who have worked for shorter periods. Further, such perceptions are significantly affectd by position in the organization and the length of contact. These findings can have important implications for human resources management policies in Japanese multinational corporations.     

Sex, age, season, and habitual physical activity of older Japanese: the Nakanojo study

The interactions of sex, age, season, and habitual physical activity were examined in 41 male and 54 female Japanese age 65-83 yr, using a pedometer/accelerometer that determined step counts and amounts of physical activity (<3 and >3 metabolic equivalents [METs]) throughout each 24-hr period for an entire year. All 3 measures were greater in men than in women. In women, age was negatively correlated with step count and activity <3 METs, but in men, it was correlated with step count and activity >3 METs. Irrespective of sex or age, all 3 activity variables were low in the winter, peaking in spring or autumn. In the summer, step counts matched the annual average, but durations of activity <3 and >3 METs were, respectively, longer and shorter than in other seasons. These findings have practical implications for those promoting physical activity for older adults.     

Dose-response assessment for influenza A virus based on data sets of infection with its live attenuated reassortants

Reported data sets on infection of volunteers challenged with wild-type influenza A virus at graded doses are few. Alternatively, we aimed at developing a dose-response assessment for this virus based on the data sets for its live attenuated reassortants. Eleven data sets for live attenuated reassortants that were fit to beta-Poisson and exponential dose-response models. Dose-response relationships for those reassortants were characterized by pooling analysis of the data sets with respect to virus subtype (H1N1 or H3N2), attenuation method (cold-adapted or avian-human gene reassortment), and human age (adults or children). Furthermore, by comparing the above data sets to a limited number of reported data sets for wild-type virus, we quantified the degree of attenuation of wild-type virus with gene reassortment and estimated its infectivity. As a result, dose-response relationships of all reassortants were best described by a beta-Poisson model. Virus subtype and human age were significant factors determining the dose-response relationship, whereas attenuation method affected only the relationship of H1N1 virus infection to adults. The data sets for H3N2 wild-type virus could be pooled with those for its reassortants on the assumption that the gene reassortment attenuates wild-type virus by at least 63 times and most likely 1,070 times. Considering this most likely degree of attenuation, 10% infectious dose of H3N2 wild-type virus for adults was estimated at 18 TCID50 (95% CI = 8.8-35 TCID50). The infectivity of wild-type H1N1 virus remains unknown as the data set pooling was unsuccessful.