Statistical Modeling of Animal Bioassay Data with Variable Dosing Regimens: Example—Vinyl Chloride

We consider animal bioassay experiments with variable dosing regimens in which groups of animals are dosed beginning at different ages and for varying durations. Two response models are discussed and then applied to data from an experiment on vinyl chloride exposure of F-344 rats, B6C3F1 and Swiss CD-1 mice, and Syrian Golden hamsters. The multistage model of Armitage and Doll, as extended by Whittemore, Day and Brown, and Crump and Howe, is used to estimate the dose effect on the ordered stages of tumor development. The data for all endpoints and species/strains examined consistently indicate a predominant effect on the first stage, suggesting that vinyl chloride is primarily a tumor initiator. This is consistent with evidence from two-stage experiments on this chemical. The second response model, new to this article, adjusts for survival nonparametrically. It is used to test for an age difference in susceptibility, to evaluate alternative exposure durations, and to compare the effectiveness of alternative dosing regimens for detecting carcinogenicity.     

A Physiologically Based Pharmacokinetic Assessment of Tetrachloroethylene in Groundwater for a Bathing and Showering Determination

A two-step methodology is described to make a health-based determination for the bathing and showering use of the water from a private well contaminated with volatile organic chemicals. The chemical perchloroethylene (PERC) is utilized to illustrate the approach. First, a chemical-specific exposure model is used to predict the concentration of PERC in the shower air, shower water, and in the air above the bathtub. Second, a physiologically based pharmacokinetic (PBPK) model is used to predict the concentration of PERC delivered to the target tissue, the brain, since the focus is on neurological endpoints. The simulation exercise includes concurrent dermal and inhalation routes of exposure. A reference target tissue level (RTTL) in the brain is estimated using the PBPK model. A hazard index based on this benchmark guideline is used to make a regulatory determination for bathing and showering use of the contaminated water.     

A dose-response analysis of skin cancer from inorganic arsenic in drinking water

A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3] if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).     

Strategic assessment—A rational response to university cutbacks

Effective strategic assessment and planning is required if public higher education is to cope with the problems of the next two decades. This article suggests an approach that can be easily adapted to most public post-secondary institutions, based on a strategic plan devised to combat decline in enrolment and fiscal reduction in a State educational institution.     

No foot in the door: an experimental study of employment discrimination against older workers

Pairs of testers, one aged 57 and one aged 32, applied for 102 entry-level sales or management jobs in the Washington, DC, metropolitan area. Although their credentials described them as equally qualified, the older applicants received less favorable responses from employers 41.2% of the time. Three quarters of these differences occurred before older applicants could fully present their qualifications. The negative employer assumptions about older workers implied by these differences in outcome were seldom explicitly stated.     

Appraising financial performance for financial institutions

The author is an investment analyst whose area of specialization is financial shares, especially in banking. The prime responsibility of the investment analyst is to the investment institutions. However, the information available to the analyst is no more than that available to shareholders in the institution being monitored. The expertise of the analyst is in seeking out the information and interpreting it for the client. There has been a considerable improvement in investor relations in the U.K. in the past few years. The author suggests that more information could be provided by the U.K. Clearing Banks—information which is readily available within the banks—which would enable the investment analyst to make important comparisons from data which is not at present available to him.     

The medical device payment controversy rages on

Who will pay for investigational research? This seemingly endless debate assumes different guises as different aspects of the health care industry come under scrutiny. The latest wrinkle in the debate involves reimbursement for devices that are not FDA approved. My September column discussed the issue of funding investigational cancer therapies, specifically high-dose therapy and bone marrow transplant, as treatments for various malignancies. That controversy was centered on the use of FDA-approved drugs in settings beyond the labeled indications. However, the issue with medical devices is different. It involves implantable devices that the FDA says have not proven to be safe and effective.     

Patterns of employment among individuals with mental illness in vocational recovery

This article provides empirical evidence about the patterns of competitive employment among individuals with serious mental illness who are in vocational recovery. The findings are based on a 5-year longitudinal study on sustained employment, conducted with a national sample of 529 individuals with serious mental illness who were in vocational recovery at the time of study enrollment. Data analysis from the 328 participants who completed the study-from baseline through all five annual follow-up assessments-revealed three different postrecovery employment patterns: continuous, stable, and fluctuating. Although many participants demonstrated the capacity to sustain competitive employment during prolonged periods of time, others experienced employment interruptions. Work interruptions were most frequently attributed to exacerbation of psychiatric symptoms. Schizophrenia spectrum disorder, difficulties with daily functioning, and current receipt of disability benefits predicted the psychiatric-based work interruptions in this sample. Implications for clinical practice are also discussed.