Effects of the Mechanism of Receptor-Mediated Gene Expression on the Shape of the Dose-Response Curve

A mathematical model of receptor-mediated gene expression that includes receptor binding of natural and xenobiotic ligands, protein synthesis and degradation, and metabolism of the xenobiotic ligand was created to identify the determinants of the shape of the dose-response profile. Values of the model's parameters were varied to reflect alternative mechanisms of expression of the protein. These assumptions had dramatic effects on the computed response to a bolus dose of the xenobiotic ligand. If all processes in the model exhibit hyperbolic kinetics, the dose-response curves can appear sigmoidal but actually be linear with a positive slope at low doses. The slope of the curve only approached zero at low dose, indicative of a threshold for response, if binding of the xenobiotic ligand to the receptor exhibited positive cooperativity (ligand binding at one site increases the affinity for ligand at another binding site on the receptor). Positive cooperativity in the rate-limiting step of protein synthesis produced dose-response curves which were "U-shaped" at low doses, also indicative of a threshold. Positive cooperativity in the metabolism of the xenobiotic ligand produced dose-response curves that increased more rapidly than linearly with increasing dose. The model illustrates the fact that response cannot be predicted from qualitative mechanistic arguments alone; any assessment of risk to health from xenobiotic chemicals must be based on a detailed quantitative examination of the kinetic behavior of each chemical species individually.     

What Determines Trust in Information About Food-Related Risks? Underlying Psychological Constructs

Trust in risk information about food related-hazards may be an important determinant of public reactions to risk information. One of the central questions addressed by the risk communication literature is why some individuals and organizations are trusted as sources of risk information and others are not. Industry and government often lack public trust, whereas other sources (for example, consumer organizations, the quality media, medical doctors) are highly trusted. Problematically, previous surveys and questionnaire studies have utilized questions generated by the investigators themselves to assess public perceptions of trust in different sources. Furthermore, no account of the hazard domain was made. In the first study reported here, semistructured interviewing was used to elicit underpinning constructs determining trust and distrust in different sources providing food-related risk information ( n = 35). In the second study, the repertory grid method was used to elicit the terminology that respondents use to distinguish between different potential food-related information sources ( n = 35), the data being submitted to generalised Procrustes analysis. The results of the two studies were combined and validated in survey research ( n = 888) where factor analysis indicated that knowledge in itself does not lead to trust, but that trusted sources are seen to be characterised by multiple positive attributes. Contrary to previous research, complete freedom does not lead to trust—rather sources which possess moderate accountability are seen to be the most trusted.     

Mlonte Carlo Techniques for Quantitative Uncertainty Analysis in Public Health Risk Assessments

Most public health risk assessments assume and combine a series of average, conservative, and worst-case values to derive a conservative point estimate of risk. This procedure has major limitations. This paper demonstrates a new methodology for extended uncertainty analyses in public health risk assessments using Monte Carlo techniques. The extended method begins as do some conventional methods--with the preparation of a spreadsheet to estimate exposure and risk. This method, however, continues by modeling key inputs as random variables described by probability density functions (PDFs). Overall, the technique provides a quantitative way to estimate the probability distributions for exposure and health risks within the validity of the model used. As an example, this paper presents a simplified case study for children playing in soils contaminated with benzene and benzo(a)pyrene (BaP).     

A teaching model for work practice in occupational therapy

Given the global changes in how work is conceptualized, organized and performed [8], it is critical that graduating occupational therapists have an up-to-date knowledge of work and work practice. This article briefly explores the relative dearth of work practice courses in current occupational therapy curricula and presents the rationale for developing a model for teaching and learning about occupational therapy work practice. It introduces a client-centered and occupation-focused model developed for an undergraduate work practice course and describes the use of the model in a specific course. The model identifies eight common work-related areas of concern - values clarification, vocational exploration, vocational choice, job search, starting work, maintaining work, returning to work and leaving work. Occupational Therapy tools, techniques and programs which may be useful in addressing these concerns; and the environmental factors that influence therapist and client in addressing work issues are also part of the model. The article concludes with examples of topics and issues which could be explored using this teaching and learning model.     

Technology transfer concerns of college graduates with disabilities: Profiles in transition from higher education to competitive careers

The article describes the technology transfer concerns reported by a small sample (N=14) of recent college graduates with disabilities. In structured, in-depth interviews, researchers asked respondents to reflect on the extent to which they had utilized technology resources during their college years in preparation for the world of work. Results suggest that colleges and universities need to play a more active role in introducing students with disabilities to both generalized and assistive technology services.     

Banking on fewer children: financial intermediation,fertility and economic development

This paper shows that financial intermediation can influence fertility and labor allocation decisions by raising market wages. The increase in wages induces some households to abandon “traditional” labor intensive methods of production managed at the household level and supply labor to “modern” sector firms. Since it is optimal for households in the modern sector to have fewer children, the labor allocation decision leads to lower national fertility. A panel VAR using financial intermediation, fertility and industrial employment share data in 87 countries is estimated. The empirical results show that the data are consistent with the theoretical predictions. Received: 20 October 1997/Accepted: 31 August 1998     

Well siblings living with schizophrenia. Impact of associated behaviors.

As a result of the ongoing hallucinations and delusions, life at home became "anxious and chaotic" with "lots of stress." Because there was no on-site crisis intervention by professionals, well siblings were sometimes called upon to control the violent behavior and were vigilant and fearful regarding the potential for abuse. Negative symptoms were the most disturbing to well siblings. Siblings need help to understand that social isolation and lack of motivation are symptoms of the illness--not due to "laziness."     

What physician executives and health care organizations should expect from each other

Today, interest in defining the role of the physician executive and ensuring this individual is effectively integrated into the organization is high for good reason--the ranks of physician executives are growing. What attributes should health care organizations look for when hiring physician executives and what should they should expect of them once they are on the job? Physician executives should: (1) have demonstrated clinical and management skills; (2) have a comfort level with participatory decision-making; (3) have superb interpersonal skills; and (4) be a champion of the patient. Physician executives should expect the following support from their organizations: (1) varied roles and responsibilities; (2) mentoring by other senior executives; (3) lifelong learning opportunities; and (4) complete support of the management team.