Benchmark Analysis: Shopping with Proper Confidence

We discuss the issue of using benchmark doses for quantifying (excess) risk associated with exposure to environmental hazards. The paradigm of low-dose risk estimation in dose-response modeling is used as the primary application scenario. Emphasis is placed on making simultaneous inferences on benchmark doses when data are in the form of proportions, although the concepts translate easily to other forms of outcome data.     

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.     

Estimation of Benchmark Dose of Lifetime Cadmium Intake for Adverse Renal Effects Using Hybrid Approach in Inhabitants of an Environmentally Exposed River Basin in Japan

The aim of this study is to estimate the reference level of lifetime cadmium intake (LCd) as the benchmark doses (BMDs) and their 95% lower confidence limits (BMDLs) for various renal effects by applying a hybrid approach. The participants comprised 3,013 (1,362 men and 1,651 women) and 278 (129 men and 149 women) inhabitants of the Cd‐polluted and nonpolluted areas, respectively, in the environmentally exposed Kakehashi River basin. Glucose, protein, aminonitrogen, metallothionein, and β₂‐microglobulin in urine were measured as indicators of renal dysfunction. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at zero exposure set at 5%. The obtained BMDLs of LCd were 3.7 g (glucose), 3.2 g (protein), 3.7 g (aminonitrogen), 1.7 g (metallothionein), and 1.8 g (β₂‐microglobulin) in men and 2.9 g (glucose), 2.5 g (protein), 2.0 g (aminonitrogen), 1.6 g (metallothionein), and 1.3 g (β₂‐microglobulin) in women. The lowest BMDL was 1.7 g (metallothionein) and 1.3 g (β₂‐microglobulin) in men and women, respectively. The lowest BMDL of LCd (1.3 g) was somewhat lower than the representative threshold LCd (2.0 g) calculated in the previous studies. The obtained BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure.     

民族地区农村社会保障制度的实证分析

作者在分析民族地区农村社会保障制度建立的政策及经济发展背景和群众意愿的基础上,通过实证分析,提出农民的保障在一定时期内将是多元化的保障模式,民族地区农村社会保障制度建设主要应建立养老保险制度、最低生活保障制度、医疗保障制度和救济制度等四个方面的制度,同时,要发挥土地保障的主导作用,并继续挖掘各民族灿烂的历史文化资源,使其在新时期继续发挥作用。     

Benchmark Dose Analysis via Nonparametric Regression Modeling

Estimation of benchmark doses (BMDs) in quantitative risk assessment traditionally is based upon parametric dose‐response modeling. It is a well‐known concern, however, that if the chosen parametric model is uncertain and/or misspecified, inaccurate and possibly unsafe low‐dose inferences can result. We describe a nonparametric approach for estimating BMDs with quantal‐response data based on an isotonic regression method, and also study use of corresponding, nonparametric, bootstrap‐based confidence limits for the BMD. We explore the confidence limits’ small‐sample properties via a simulation study, and illustrate the calculations with an example from cancer risk assessment. It is seen that this nonparametric approach can provide a useful alternative for BMD estimation when faced with the problem of parametric model uncertainty.     

An International Pooled Analysis for Obtaining a Benchmark Dose for Environmental Lead Exposure in Children

Lead is a recognized neurotoxicant, but estimating effects at the lowest measurable levels is difficult. An international pooled analysis of data from seven cohort studies reported an inverse and supra‐linear relationship between blood lead concentrations and IQ scores in children. The lack of a clear threshold presents a challenge to the identification of an acceptable level of exposure. The benchmark dose (BMD) is defined as the dose that leads to a specific known loss. As an alternative to elusive thresholds, the BMD is being used increasingly by regulatory authorities. Using the pooled data, this article presents BMD results and applies different statistical techniques in the analysis of multistudy data. The calculations showed only a limited variation between studies in the steepness of the dose‐response functions. BMD results were quite robust to modeling assumptions with the best fitting models yielding lower confidence limits (BMDLs) of about 0.1–1.0 μ g/dL for the dose leading to a loss of one IQ point. We conclude that current allowable blood lead concentrations need to be lowered and further prevention efforts are needed to protect children from lead toxicity.     

运动动机在体操教学中的运用

根据体操运动的特点及学生个性心理特征,从能力知觉、内部动机需要及合理设置目标激发学生成就动机三方面阐述在体操教学中如何合理有效激发学生运动动机,以便高效、高质量完成体操教学任务。     

计算机辅助扩充频率法

本文基于Nyquest稳定性准则和扩充频率法,对含有滞后环节的被控对象的系统,提出一个能在微型计算机上实现的、能进行比例、比例加积分(和加微分)的整定参数计算的计算机辅助设计算法.本法使用了寻优技术,能快速求得结果.     

UNIX系统的性能评价

本文综述了一般计算机系统性能评价的基本方法,讨论了用基准检测模拟(BenchMark Modeling)的方法对操作系统进行评价。针对 UNIX 操作系统写出了不同的基准检测模拟程序,给出了它们在不同机器不同 UNIX 版本上的运行结果。     

落实“三三一八”工程 打造市场学系教学特色

以我院第二次教学工作会议的精神、孙广勇副院长的主题报告和"关于学院教学事业发展的几点思考"为指导思想,本文阐述了市场学系的学科建设和专业设置,提出了市场学系今后的工作重点和努力方向。