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.     

Empirical Bayes estimation in finite population sampling under functional measurement error models

The paper considers simultaneous estimation of finite population means for several strata. A model-based approach is taken, where the covariates in the super-population model are subject to measurement errors. Empirical Bayes (EB) estimators of the strata means are developed and an asymptotic expression for the MSE of the EB estimators is provided. It is shown that the proposed EB estimators are “first order optimal” in the sense of Robbins [1956. An empirical Bayes approach to statistics. In: Proceedings of the Third Berkeley Symposium on Mathematical Statistics and Probability, vol. 1, University of California Press, Berkeley, pp. 157–164], while the regular EB estimators which ignore the measurement error are not.     

A Process for Incorporating Comparative Risk into Environmental Policymaking in Louisiana

The goal of Louisiana's 1990–1991 comparative risk project, also called the Louisiana Environmental Action Plan (LEAP), was to incorporate risk assessment into state environmental planning and policymaking. Scientists, government officials, and citizens were brought together to estimate the relative risk to human health, natural resources, and quality of life posed by 33 selected environmental issues. The issues were then ranked according to their relative estimated risks. It was hoped that this ranking of "comparative risks" would enable state policymakers to target the most important environmental problems and allocate scarce public resources more rationally and efficiently. As a result of the project, the governor issued an Executive Order forming a permanent Public Advisory Committee to continue this type of comparative risk assessment in Louisiana.     

建设项目的专业技术 服务风险管理浅析

本文分析了建设项目中专业技术服务的潜在风险，探讨了风险管理的内容、途径和方法，简述了专业责任保险的特点和原则，指出了在我国开展专业责任保险的紧迫性。     

风险投资机构面临的融资风险及风险控制问题分析

本文认为,风险投资机构在设立之初及再融资过程中面临着融资风险,而拓宽融资渠道是降低这类风险的关键。本文首先介绍了风险投资机构的融资来源有哪些,以及影响风险投资机构融资的各种因素。在此基础上,笔者提出了目前扩大我国风险投资机构融资来源、控制转移融资风险的各种措施。     

商业银行跨营基金业务的风险与防范

作为混业经营的尝试,商业银行设立基金管理公司,在提升金融效益的同时,伴随而来的是巨大的金融风险。风险主要来自两方面:跨市场经营和分业监管体系.进一步完善资本市场,建立严密的业务隔离机制和联合监管新体制,将是我们防范和化解此类风险的必然选择。     

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.     

有错检验情况下标准型抽样方案的设计

本文给出了在有错检验情况下标准型抽样方案的设计方法，讨论了误检概率ｐ，ｐ′对抽样方案的影响，并给出抽样方案的实际应用。     

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.     

Professional Perspectives on Decision Making about the Long-term Care of Older People

With the increasing pressure on social and health care resources,professionals have to be more explicit in their decision makingregarding the long-term care of older people. This groundedtheory study used 19 focus groups and nine semi-structured interviews(99 staff in total) to explore professional perspectives onthis decision making. Focus group participants and intervieweescomprised care managers, social workers, consultant geriatricians,general medical practitioners, community nurses, home care managers,occupational therapists and hospital discharge support staff.The emerging themes spanned context, clients, families and services.Decisions were often prompted by a crisis, hindering professionalsseeking to make a measured assessment. Fear of burglary andassault, and the willingness and availability of family to helpwere major factors in decisions about living at home. Serviceavailability in terms of public funding for community care,the availability of home care workers and workload pressureson primary care services influenced decision ‘thresholds’regarding admission to institutional care. Assessment toolsdesigned to assist decision making about the long-term careof older people need to take into account the critical aspectsof individual fears and motivation, family support and the availabilityof publicly funded services as well as functional and medicalneeds.