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.     

The use of GIS in informal settlement upgrading: its role and impact on the community and on local government

The Urban Geographical Information Systems (GIS) Group within the Department of Civil Engineering at the University of Cape Town has been coordinating a pilot informal settlement upgrading in Cape Town since 1998. The project objective has been the evolution of a model-based approach to informal settlement upgrading that is both structured and replicable. It was felt that the only way this could be achieved was through the use of a spatial data management system operated through a GIS system. The spatial database has been used for all facets of data collection and data process and forms the basis for all decision-making. Thus it covers all physical data pertaining to the site, cadastral and shack data, demographic and socio-economic data (with an in-depth review of every household) economic opportunities and physical planning and design data. The result is a comprehensive, integrated, settlement upgrading methodology that is built upon a GIS-based spatial data management framework. Such a framework is seen as the basic building block for large-scale informal settlement upgrading.     

Modeling for Risk Assessment of Neurotoxic Effects

The regulation of noncancer toxicants, including neurotoxicants, has usually been based upon a reference dose (allowable daily intake). A reference dose is obtained by dividing a no-observed-effect level by uncertainty (safety) factors to account for intraspecies and interspecies sensitivities to a chemical. It is assumed that the risk at the reference dose is negligible, but no attempt generally is made to estimate the risk at the reference dose. A procedure is outlined that provides estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect and the dose of a chemical. Knowledge of biological mechanisms and/or pharmacokinetics can assist in the choice of plausible mathematical models. The mathematical model provides estimates of average responses as a function of dose. Secondly, estimates of risk require selection of a distribution of individual responses about the average response given by the mathematical model. In the case of a normal or lognormal distribution, only an estimate of the standard deviation is needed. The third step is to define an adverse level for a response so that the probability (risk) of exceeding that level can be estimated as a function of dose. Because a firm response level often cannot be established at which adverse biological effects occur, it may be necessary to at least establish an abnormal response level that only a small proportion of individuals would exceed in an unexposed group. That is, if a normal range of responses can be established, then the probability (risk) of abnormal responses can be estimated. In order to illustrate this process, measures of the neurotransmitter serotonin and its metabolite 5-hydroxyindoleacetic acid in specific areas of the brain of rats and monkeys are analyzed after exposure to the neurotoxicant methylene-dioxymethamphetamine. These risk estimates are compared with risk estimates from the quantal approach in which animals are classified as either abnormal or not depending upon abnormal serotonin levels.     

Tree health mapping with multispectral remote sensing data at UC Davis, California

Tree health is a critical parameter for evaluating urban ecosystem health and sustainability. Traditionally, this parameter has been derived from field surveys. We used multispectral remote sensing data and GIS techniques to determine tree health at the University of California, Davis. The study area (363 ha) contained 8,962 trees of 215 species. Tree health conditions were mapped for each physiognomic type at two scales: pixel and whole tree. At the pixel scale, each tree pixel within the tree crown was classified as either healthy or unhealthy based on vegetation index values. At the whole tree scale, raster based statistical analysis was used to calculate tree health index which is the ratio of healthy pixels to entire tree pixels within the tree crown. The tree was classified as healthy if the index was greater than 70%. Accuracy was checked against a random sample of 1,186 trees. At the whole tree level, 86% of campus trees were classified as healthy with 88% mapping accuracy. At the pixel level, 86% of the campus tree cover was classified as healthy. This tree health evaluation approach allows managers to identify the location of unhealthy trees for further diagnosis and treatment. It can be used to track the spread of disease and monitor seasonal or annual changes in tree health. Also, it provides tree health information that is fundamental to modeling and analysis of the environmental, social, and economic services produced by urban forests.     

A modified false discovery rate multiple-comparisons procedure for discrete data, applied to human immunodeficiency virus genetics

Summary.  To help to design vaccines for acquired immune deficiency syndrome that protect broadly against many genetic variants of the human immunodeficiency virus, the mutation rates at 118 positions in HIV amino-acid sequences of subtype C versus those of subtype B were compared. The false discovery rate (FDR) multiple-comparisons procedure can be used to determine statistical significance. When the test statistics have discrete distributions, the FDR procedure can be made more powerful by a simple modification. The paper develops a modified FDR procedure for discrete data and applies it to the human immunodeficiency virus data. The new procedure detects 15 positions with significantly different mutation rates compared with 11 that are detected by the original FDR method. Simulations delineate conditions under which the modified FDR procedure confers large gains in power over the original technique. In general FDR adjustment methods can be improved for discrete data by incorporating the modification proposed.     

Book Reviews

Books reviewed:
R.J. Adler, R.E. Feldman & M.S. Taqqu, A Practical Guide to Heavy Tails: Statistical Techniques and Applications.
J.J. Foste, A Beginner's Guide to Data Analysis Using SPSS for Windows.
N. Limnios and G. Oprisan, Semi–Markov Processes and Reliability.     

Confidence Intervals for Current Status Data

Abstract.  The likelihood ratio statistic for testing pointwise hypotheses about the survival time distribution in the current status model can be inverted to yield confidence intervals (CIs). One advantage of this procedure is that CIs can be formed without estimating the unknown parameters that figure in the asymptotic distribution of the maximum likelihood estimator (MLE) of the distribution function. We discuss the likelihood ratio-based CIs for the distribution function and the quantile function and compare these intervals to several different intervals based on the MLE. The quantiles of the limiting distribution of the MLE are estimated using various methods including parametric fitting, kernel smoothing and subsampling techniques. Comparisons are carried out both for simulated data and on a data set involving time to immunization against rubella. The comparisons indicate that the likelihood ratio-based intervals are preferable from several perspectives.     

一个数据流查询系统的设计与实现

就目前大多数数据流查询处理过程中可能出现的一些问题，根据数据流处理的特点和要求，提出了新的查询处理结构，实现了数据共享及多流多查询环境下查询的处理．     

CCI与中国证券市场走势的实证分析

美英等国的消费者信心指数(CCI)对股市指数收益有很重要的影响力。为探讨CCI与中国证券市场走势的相关关系,通过两类模型对1999年10月~2004年8月间我国股市收益与CCI之间的关系进行了实证分析。结果表明:CCI对深沪五个指数的走势有显著的解释与预测效果,但对我国的B股市场似乎没有显著性。     

An evaluation of the childhood family structure measures from the sixth wave of the British Household Panel Survey

Summary.  The paper performs an evaluation of the data that were collected in the sixth wave of the British Household Panel Survey (BHPS) on childhood family structure. After comparing such data with a large number of studies by using external sources, we find that the BHPS data overestimate the proportion of people who report an experience of life in a non-intact family during childhood by about 10%. Although an explanation based on recall error that deteriorates with the age of the BHPS respondents is possible, the overestimation is likely to be accounted for by non-ignorable attrition that may affect most of the comparison studies based on longitudinal data. Conversely, comparisons with other independent measurements from the BHPS itself reveal that the wave 6 data underestimate the proportion of young people who have lived at least part of their childhood in a non-intact family by about 8%. The probability of disagreement between these two sets of measures is strongly associated with poor interview characteristics, which may affect the comparison measure more than the wave 6 measure. Despite such differences, there is therefore a substantial degree of similarity between the family structure information that was collected in the sixth wave of the BHPS and the host of highly diverse records against which it has been compared.