Physiologically Based Liver Modeling and Risk Assessment

Because of the inherent complexity of biological systems, there is often a choice between a number of apparently equally applicable physiologically based models to describe uptake and metabolism processes in toxicology or risk assessment. These models may fit the particular data sets of interest equally well, but may give quite different parameter estimates or predictions under different (extrapolated) conditions. Such competing models can be discriminated by a number of methods, including potential refutation by means of strategic experiments, and their ability to suitably incorporate all relevant physiological processes. For illustration, three currently used models for steady-state hepatic elimination--the venous equilibration model, the parallel tube model, and the distributed sinusoidal perfusion model--are reviewed and compared with particular reference to their application in the area of risk assessment. The ability of each of the models to describe and incorporate such physiological processes as protein binding, precursor-metabolite relations and hepatic zones of elimination, capillary recruitment, capillary heterogeneity, and intrahepatic shunting is discussed. Differences between the models in hepatic parameter estimation, extrapolation to different conditions, and interspecies scaling are discussed, and criteria for choosing one model over the others are presented. In this case, the distributed model provides the most general framework for describing physiological processes taking place in the liver, and has so far not been experimentally refuted, as have the other two models. These simpler models may, however, provide useful bounds on parameter estimates and on extrapolations and risk assessments.     

人才测评及其功能和发展

人才测评的发展是经济建设和社会发展的必然要求 ,为此本文讨论了人才测评的功能、特性以及今后的发展方向 ,明确了人才测评在整体性人力资源开发和管理中的重要意义     

人才测评的内容、方法及存在的问题

讨论人才测评的内容、测评种类、测评工具和方法等 ,指出目前人才测评中存在的问题 ,提出对人机心理测评管理系统进行应用性开发研究     

Ranking Nuclear and Radiological Terrorism Scenarios: The Italian Case

A quantitative criterion for ranking the different scenarios of nuclear and radiological terrorism has been developed. The aim of the model is not to predict terroristic events but only to indicate which scenario has the higher utility from the point of view of a terroristic organization in terms of balance between factors favoring and discouraging the attack, respectively. All these factors were quantified according to a scoring system that takes into account the logarithmic relationship between perceptions and stimuli. The criterion was applied to several scenarios, each of which was modeled in a simple but not trivial way in order to estimate the expected damage in terms of probable life losses from both radiative and nonradiative effects. The outcome from the ranking method indicates that the attractive scenario appears to be the detonation of a low yield improvised nuclear device in the metropolitan area of a major city.     

PSC朗读评分中的语音缺陷问题

在2002年12月《普通话水平测试大纲》修订工作征求意见稿中,我们发现它增加了对短文朗读中语音缺陷扣分的规定。短文朗读中的"语音缺陷"在《普通话水平测试大纲》现行评分标准中一直处于被忽视的地位。笔者同意征求意见稿的观点,对短文朗读中存在的"语音缺陷"应该扣分。短文朗读中存在的"语音缺陷"不能归入语音错误,也不能把它们划入"方言语调"的范围,应该把它们并入"方言色彩"的测试中。为此,笔者提出了短文朗读里语音缺陷的评分办法。     

Bootstrap Estimation of Benchmark Doses and Confidence Limits with Clustered Quantal Data

The benchmark dose (BMD) is an exposure level that would induce a small risk increase (BMR level) above the background. The BMD approach to deriving a reference dose for risk assessment of noncancer effects is advantageous in that the estimate of BMD is not restricted to experimental doses and utilizes most available dose-response information. To quantify statistical uncertainty of a BMD estimate, we often calculate and report its lower confidence limit (i.e., BMDL), and may even consider it as a more conservative alternative to BMD itself. Computation of BMDL may involve normal confidence limits to BMD in conjunction with the delta method. Therefore, factors, such as small sample size and nonlinearity in model parameters, can affect the performance of the delta method BMDL, and alternative methods are useful. In this article, we propose a bootstrap method to estimate BMDL utilizing a scheme that consists of a resampling of residuals after model fitting and a one-step formula for parameter estimation. We illustrate the method with clustered binary data from developmental toxicity experiments. Our analysis shows that with moderately elevated dose-response data, the distribution of BMD estimator tends to be left-skewed and bootstrap BMDL s are smaller than the delta method BMDL s on average, hence quantifying risk more conservatively. Statistically, the bootstrap BMDL quantifies the uncertainty of the true BMD more honestly than the delta method BMDL as its coverage probability is closer to the nominal level than that of delta method BMDL. We find that BMD and BMDL estimates are generally insensitive to model choices provided that the models fit the data comparably well near the region of BMD. Our analysis also suggests that, in the presence of a significant and moderately strong dose-response relationship, the developmental toxicity experiments under the standard protocol support dose-response assessment at 5% BMR for BMD and 95% confidence level for BMDL.     

Summary of the Workshop on Issues in Risk Assessment: Quantitative Methods for Developmental Toxicology

This report summarizes the proceedings of a conference on quantitative methods for assessing the risks of developmental toxicants. The conference was planned by a subcommittee of the National Research Council's Committee on Risk Assessment Methodology ⁴ in conjunction with staff from several federal agencies, including the U.S. Environmental Protection Agency, U.S. Food and Drug Administration, U.S. Consumer Products Safety Commission, and Health and Welfare Canada. Issues discussed at the workshop included computerized techniques for hazard identification, use of human and animal data for defining risks in a clinical setting, relationships between end points in developmental toxicity testing, reference dose calculations for developmental toxicology, analysis of quantitative dose-response data, mechanisms of developmental toxicity, physiologically based pharmacokinetic models, and structure-activity relationships. Although a formal consensus was not sought, many participants favored the evolution of quantitative techniques for developmental toxicology risk assessment, including the replacement of lowest observed adverse effect levels (LOAELs) and no observed adverse effect levels (NOAELs) with the benchmark dose methodology.     

Intuitive Toxicology: Expert and Lay Judgments of Chemical Risks

Human beings have always been intuitive toxicologists, relying on their senses of sight, taste, and smell to detect harmful or unsafe food, water, and air. As we have come to recognize that our senses are not adequate to assess the dangers inherent in exposure to a chemical substance, we have created the sciences of toxicology and risk assessment to perform this function. Yet despite this great effort to overcome the limitations of intuitive toxicology, it has become evident that even our best scientific methods still depend heavily on extrapolations and judgments in order to infer human health risks from animal data. Many observers have acknowledged the inherent subjectivity in the assessment of chemical risks and have indicated a need to examine the subjective or intuitive elements of expert and lay risk judgments. We have begun such an examination by surveying members of the Society of Toxicology and the lay public about basic toxicological concepts, assumptions, and interpretations. Our results demonstrate large differences between toxicologists and laypeople, as well as differences between toxicologists working in industry, academia, and government. In addition, we find that toxicologists are sharply divided in their opinions about the ability to predict a chemical's effect on human health on the basis of animal studies. We argue that these results place the problems of risk communication in a new light. Although the survey identifies misconceptions that experts should clarify for the public, it also suggests that controversies over chemical risks may be fueled as much by limitations of the science of risk assessment and disagreements among experts as by public misconceptions.     

公益林补偿政策评价研究

论述了公益林补偿政策评价研究的现状,分析了补偿政策评价的特点和存在问题,提出了解决问题的对策,并借鉴了美国联邦政府项目评价体系,提出了补偿政策的定性评价内容。     

旅游市场开发中的旅游地评估研究

规范的旅游市场开发必须以明确的旅游地评估为前提。针对当前旅游开发热潮中的旅游地使用权益问题 ,本文就旅游地评估的实质、现实必要性、评估原则及评估方法等问题提出了看法 ,并以湖北省保康县野花谷为例进行评估