Comparing Experimental Designs for Benchmark Dose Calculations for Continuous Endpoints

The BMD (benchmark dose) method that is used in risk assessment of chemical compounds was introduced by Crump (1984) and is based on dose-response modeling. To take uncertainty in the data and model fitting into account, the lower confidence bound of the BMD estimate (BMDL) is suggested to be used as a point of departure in health risk assessments. In this article, we study how to design optimum experiments for applying the BMD method for continuous data. We exemplify our approach by considering the class of Hill models. The main aim is to study whether an increased number of dose groups and at the same time a decreased number of animals in each dose group improves conditions for estimating the benchmark dose. Since Hill models are nonlinear, the optimum design depends on the values of the unknown parameters. That is why we consider Bayesian designs and assume that the parameter vector has a prior distribution. A natural design criterion is to minimize the expected variance of the BMD estimator. We present an example where we calculate the value of the design criterion for several designs and try to find out how the number of dose groups, the number of animals in the dose groups, and the choice of doses affects this value for different Hill curves. It follows from our calculations that to avoid the risk of unfavorable dose placements, it is good to use designs with more than four dose groups. We can also conclude that any additional information about the expected dose-response curve, e.g., information obtained from studies made in the past, should be taken into account when planning a study because it can improve the design.     

Some New Residual Treatment Effects Designs for Comparing Test Treatments with a Control

Pigeon & Raghavarao (1987) introduced control balanced residual treatment effects designs for the situation where one treatment is a control or standard and is to be compared with the v test treatments, and they have also given methods of construction of control balanced residual treatment effects designs and have investigated their efficiencies. In this paper we have developed some new families of control balanced residual treatment effects designs, which are Schur-optimal.     

Optimal stated preference choice experiments when all choice sets contain a specific option

Stated preference choice experiments are routinely used in many areas from marketing to medicine. While results on the optimal choice sets to present for the forced choice setting have been determined in a variety of situations, no results have appeared to date on the optimal choice sets to use when either all choice sets are to contain a common base alternative or when all choice sets contain a “none of these” option. These problems are considered in this paper.     

Modifying a central composite design to model the process mean and variance when there are hard-to-change factors

Summary.  An important question within industrial statistics is how to find operating conditions that achieve some goal for the mean of a characteristic of interest while simultaneously minimizing the characteristic's process variance. Often, people refer to this kind of situation as the robust parameter design problem. The robust parameter design literature is rich with ways to create separate models for the mean and variance from this type of experiment. Many times time and/or cost constraints force certain factors of interest to be much more difficult to change than others. An appropriate approach to such an experiment restricts the randomization, which leads to a split-plot structure. The paper modifies the central composite design to allow the estimation of separate models for the characteristic's mean and variances under a split-plot structure. The paper goes on to discuss an appropriate analysis of the experimental results. It illustrates the methodology with an industrial experiment involving a chemical vapour deposition process for the manufacture of silicon wafers. The methodology was used to achieve a silicon layer thickness value of 485 Å while minimizing the process variation.     

Near-optimal designs for dual channel microarray studies

Summary.  Much biological and medical research employs microarray studies to monitor gene expression levels across a wide range of organisms and under many experimental conditions. Dual channel microarrays are a common platform and allow two samples to be measured simultaneously. A frequently used design uses a common reference sample to make conditions across different arrays comparable. Our aim is to formulate microarray experiments in the experimental design context and to use simulated annealing to search for near-optimal designs. We identify a subclass of designs, the so-called interwoven loop designs, that seems to have good optimality properties compared with the near-optimal designs that are found by simulated annealing. Commonly used reference designs and dye swap designs are shown to be highly inefficient.     

得意忘形——从《艺术的进化》和《原始分类》看符号的抽象化过程

《艺术的进化》一书,阿尔弗雷德?哈登（Alfred C.Haddon)对托雷斯海峡一代的巴布亚新几内亚人的艺术符号的发展过程进行了叙述,他使用了生物学和植物学的方法来研究艺术并提出了艺术符号是如何被赋予生命的过程。本文针对哈登提出的这一过程,联系《原始分类》一书,试看在原始文化中符号如何被抽象化,而形成的感官经验到抽象思维的转变过程。     

Long-term experiments and strip plot designs

In a long-term experiment usually the experimenter needs to know whether the effect of a treatment varies over time. But time usually has both a fixed and a random effects over the output and the difficulty in the analysis depends on the particular design considered and the availability of covariates. Actually, as shown in the paper, the presence of covariates can be very useful to model the random effect of time. In this paper a model to analyze data from a long-term strip plot design with covariates is proposed. Its effectiveness will be tested using both simulated and real data from a crop rotation experiment.     

Optimal and Robust Designs for Estimating the Concentration Curve and the AUC

The problem of interest is to estimate the concentration curve and the area under the curve (AUC) by estimating the parameters of a linear regression model with an autocorrelated error process. We introduce a simple linear unbiased estimator of the concentration curve and the AUC. We show that this estimator constructed from a sampling design generated by an appropriate density is asymptotically optimal in the sense that it has exactly the same asymptotic performance as the best linear unbiased estimator. Moreover, we prove that the optimal design is robust with respect to a minimax criterion. When repeated observations are available, this estimator is consistent and has an asymptotic normal distribution. Finally, a simulated annealing algorithm is applied to a pharmacokinetic model with correlated errors.     

On the unbiased estimation of fixed effects in a mixed model for growth curves

A mixed model for growth curves is introduced. A method of estimating the variance components is indicated. It is shown that the generalised least squares estimates of the fixed effects using estimates of variance components are unbiased and an expression is obtained for the increase in variance due to the substitution of the variances by their estimates. These results are directly applied to designs with two-way elimination of heterogeneity.     

A General Construction Method for Five-Level Second-Order Rotatable Designs

Response surface methodology is widely used for developing, improving, and optimizing processes in various fields. In this article, we present a method for constructing second-order rotatable designs in order to explore and optimize response surfaces based on an infinite class of supplementary difference sets. The produced designs achieve both properties of rotatability and estimation efficiency. Also, they possess good predictive properties.