Optimal designs for threshold-determining limiting dilution assays

In common with other non-linear models, the optimal design for a limiting dilution assay (LDA) depends on the value of the unknown parameter, θ$\theta$, in the model. Consequently optimal designs cannot be specified unless some assumptions are made about the possible values of θ$\theta$. If a prior distribution can be specified then a Bayesian approach can be adopted. A proper specification of the Bayesian approach requires the aim of the experiment to be described and quantified through an appropriate utility function. This paper addresses the problem of finding optimal designs for LDAs when the aim is to determine whether θ$\theta$ is above or below a specified threshold, _θ0${\theta }_0$.     

Cystatin C的检测及临床应用

Cystatin C(Cys C)是近年来研究发现的一种特异性高、准确性好、较肌酐清除率更为敏感的评价肾小球滤过率的新指标．Cys C能自由通过肾小球滤过膜，在近曲小管几乎被完全重吸收，然后完全分解代谢，不再重新回到血液循环中去，同时肾小管也不分泌，所以在血液中的浓度较为恒定，成为反映肾小球滤过率的灵敏指标．常用颗粒增强透射免疫比浊法(PETIA)和颗粒增强散射免疫比浊法(PENIA)检测Cys C，操作简单、速度快，在儿科疾病、糖尿病、心血管疾病、肿瘤化疗及肾移植后评估肾小球滤过率等方面具有很高的临床价值．     

A distribution-free approach to qdantal response assays

A nonparametric method is developed to estimate the minimum dosage level required to induce a given response rate in an experiment. The only assumption used about the response rate is that it is a nondecreasing function with respect to the dosage level. Let n_isubjects be independently tested at dosage level x_ix₁x₂x_k. This paper presents methodology for the estimation of the smallest i such that the response probability at x_i is no less than a required level p. A comparison with well-known nonparametric methods shows that this method is better in some cases. A design of minimum required sample size for a given accuracy is also developed.     

Designs for symmetrical parallel line assays obtainable through group divisible designs

A wide class of block designs for symmetrical parallel line assays with even number of doses, obtainable through group divisible designs is considered. Several new designs can thus be obtained using group divisibledesigns. Group divisible designs are also shown to provide a unification of many exisiting designs which follow as special cases.     

Simultaneous confidence interval for assessing non‐inferiority with assay sensitivity in a three‐arm trial with binary endpoints

A three‐arm trial including an experimental treatment, an active reference treatment and a placebo is often used to assess the non‐inferiority (NI) with assay sensitivity of an experimental treatment. Various hypothesis‐test‐based approaches via a fraction or pre‐specified margin have been proposed to assess the NI with assay sensitivity in a three‐arm trial. There is little work done on confidence interval in a three‐arm trial. This paper develops a hybrid approach to construct simultaneous confidence interval for assessing NI and assay sensitivity in a three‐arm trial. For comparison, we present normal‐approximation‐based and bootstrap‐resampling‐based simultaneous confidence intervals. Simulation studies evidence that the hybrid approach with the Wilson score statistic performs better than other approaches in terms of empirical coverage probability and mesial‐non‐coverage probability. An example is used to illustrate the proposed approaches.     

Assessing Overall Risk in Reproductive Experiments

Toxicologists are often interested in assessing the joint effect of an exposure on multiple reproductive endpoints, including early loss, fetal death, and malformation. Exposures that occur prior to mating or extremely early in development can adversely affect the number of implantation sites or fetuses that form within each dam and may even prevent pregnancy. A simple approach for assessing overall adverse effects in such studies is to consider fetuses or implants that fail to develop due to exposure as missing data. The missing data can be imputed, and standard methods for the analysis of quantal response data can then be used for quantitative risk assessment or testing. In this article, a new bias-corrected imputation procedure is proposed and evaluated. The procedure is straightforward to implement in standard statistical packages and has excellent operating characteristics when used in combination with a marginal model fit with generalized estimating equations. The methods are applied to data from a reproductive toxicity study of Nitrofurazone conducted by the National Toxicology Program.     

Comparative characteristics of estimators of the mean responding cell density in limiting dilution assays

The statistical problems associated with estimating the mean responding cell density in the limiting dilution assay (LDA) have largely been ignored. We evaluate techniques for analyzing LDA data from multiple biological samples, assumed to follow either a normal or gamma distribution. Simulated data is used to evaluate the performance of an unweighted mean, a log transform, and a weighted mean procedure described by Taswell (1987). In general, an unweighted mean with jackknife estimates will produce satisfactory results. In some cases, a log transform is more appropriate. Taswell's weighted mean algorithm is unable to estimate an accurate variance. We also show that methods which pool samples, or LDA data, are invalid. In addition, we show that optimization of the variance in multiple sample LDA's is dependent on the estimator, the between-organism variance, the replicate well size, and the numberof biological samples. However, this optimization is generally achieved by maximizing biological samples at the expense of well replicates.     

On the influence curve for quantal bioassay

Influence curves are defined for estimators of the ED50 in quantal bioassay, assuming a symmetic tolerance distribution. A definition of influence-curve robustness is suggested. Influence curves are obtained for L-,M- and R-estimators, and their robustness is investigated. The influence curve of the logistic maximum likelihood estimator is studied.     

A Comparison of the Predictive Validity of Procedures for Analyzing Binary Data

Some approaches for analyzing binary data are briefly described and compared. The results of two empirical investigations in the context of assessing consumer preferences and a simulation study yield some interesting findings. The article concludes with some directions for future research in this area.     

猪水肿毒素琼脂扩散沉淀反应方法的建立

采用滤膜除菌、生物大分子浓缩胶浓缩、戊二醛灭活的方法制备的EHEc水肿毒素抗原,可与其兔高免血清和鸡高免血清发生沉淀反应。对5株EHEc进行了分析,并与小白鼠毒性试验结果进行了比较,证明该沉淀反应具有高度的特异性。