Remove unwanted variation retrieves unknown experimental designs

Remove unwanted variation (RUV) is an estimation and normalization system in which the underlying correlation structure of a multivariate dataset is estimated from negative control measurements, typically gene expression values, which are assumed to stay constant across experimental conditions. In this paper we derive the weight matrix which is estimated and incorporated into the generalized least squares estimates of RUV-inverse, and show that this weight matrix estimates the average covariance matrix across negative control measurements. RUV-inverse can thus be viewed as an estimation method adjusting for an unknown experimental design. We show that for a balanced incomplete block design (BIBD), RUV-inverse recovers intra- and interblock estimates of the relevant parameters and combines them as a weighted sum just like the best linear unbiased estimator (BLUE), except that the weights are globally estimated from the negative control measurements instead of being individually optimized to each measurement as in the classical, single measurement BIBD BLUE.     

Web based resource for Statistical Consultants in the Pharmaceutical Industry

The intention of this article is to highlight sources of web-based reference material and software that will aid consulting statisticians when designing clinical trials. The article includes websites that provide links to explanation of statistical concepts for non-statisticians, regulatory guidelines, and free statistical study design software.     

Generalized phase I-II designs to increase long term therapeutic success rate

Designs for early phase dose finding clinical trials typically are either phase I based on toxicity, or phase I-II based on toxicity and efficacy. These designs rely on the implicit assumption that the dose of an experimental agent chosen using these short-term outcomes will maximize the agent's long-term therapeutic success rate. In many clinical settings, this assumption is not true. A dose selected in an early phase oncology trial may give suboptimal progression-free survival or overall survival time, often due to a high rate of relapse following response. To address this problem, a new family of Bayesian generalized phase I-II designs is proposed. First, a conventional phase I-II design based on short-term outcomes is used to identify a set of candidate doses, rather than selecting one dose. Additional patients then are randomized among the candidates, patients are followed for a predefined longer time period, and a final dose is selected to maximize the long-term therapeutic success rate, defined in terms of duration of response. Dose-specific sample sizes in the randomization are determined adaptively to obtain a desired level of selection reliability. The design was motivated by a phase I-II trial to find an optimal dose of natural killer cells as targeted immunotherapy for recurrent or treatment-resistant B-cell hematologic malignancies. A simulation study shows that, under a range of scenarios in the context of this trial, the proposed design has much better performance than two conventional phase I-II designs.     

Estimation of a Conditional Copula and Association Measures

Abstarct. This paper is concerned with studying the dependence structure between two random variables Y ₁ and Y ₂ conditionally upon a covariate X. The dependence structure is modelled via a copula function, which depends on the given value of the covariate in a general way. Gijbels et al. (Comput. Statist. Data Anal., 55, 2011, 1919) suggested two non‐parametric estimators of the ‘conditional’ copula and investigated their numerical performances. In this paper we establish the asymptotic properties of the proposed estimators as well as conditional association measures derived from them. Practical recommendations for their use are then discussed.     

Low-pass filter design using locally weighted polynomial regression and discrete prolate spheroidal sequences

The paper concerns the design of nonparametric low-pass filters that have the property of reproducing a polynomial of a given degree. Two approaches are considered. The first is locally weighted polynomial regression (LWPR), which leads to linear filters depending on three parameters: the bandwidth, the order of the fitting polynomial, and the kernel. We find a remarkable linear (hyperbolic) relationship between the cut-off period (frequency) and the bandwidth, conditional on the choices of the order and the kernel, upon which we build the design of a low-pass filter.The second hinges on a generalization of the maximum concentration approach, leading to filters related to discrete prolate spheroidal sequences (DPSS). In particular, we propose a new class of low-pass filters that maximize the concentration over a specified frequency range, subject to polynomial reproducing constraints. The design of generalized DPSS filters depends on three parameters: the bandwidth, the polynomial order, and the concentration frequency. We discuss the properties of the corresponding filters in relation to the LWPR filters, and illustrate their use for the design of low-pass filters by investigating how the three parameters are related to the cut-off frequency.     

Optimal designs for response functions with a downturn

In many toxicological assays, interactions between primary and secondary effects may cause a downturn in mean responses at high doses. In this situation, the typical monotonicity assumption is invalid and may be quite misleading. Prior literature addresses the analysis of response functions with a downturn, but so far as we know, this paper initiates the study of experimental design for this situation. A growth model is combined with a death model to allow for the downturn in mean doses. Several different objective functions are studied. When the number of treatments equals the number of parameters, Fisher information is found to be independent of the model of the treatment means and on the magnitudes of the treatments. In general, A- and D_A-optimal weights for estimating adjacent mean differences are found analytically for a simple model and numerically for a biologically motivated model. Results on c-optimality are also obtained for estimating the peak dose and the EC₅₀ (the treatment with response half way between the control and the peak response on the increasing portion of the response function). Finally, when interest lies only in the increasing portion of the response function, we propose composite D-optimal designs.     

Isomorphism check in fractional factorial designs via letter interaction pattern matrix

Two fractional factorial designs are considered isomorphic if one can be obtained from the other by relabeling the factors, reordering the runs, and/or switching the levels of factors. To identify the isomorphism of two designs is known as an NP hard problem. In this paper, we propose a three-dimensional matrix named the letter interaction pattern matrix (LIPM) to characterize the information contained in the defining contrast subgroup of a regular two-level design. We first show that an LIPM could uniquely determine a design under isomorphism and then propose a set of principles to rearrange an LIPM to a standard form. In this way, we can significantly reduce the computational complexity in isomorphism check, which could only take O(2^p)+O(3k³)+O(2^k) operations to check two 2^k−p designs in the worst case. We also find a sufficient condition for two designs being isomorphic to each other, which is very simple and easy to use. In the end, we list some designs with the maximum numbers of clear or strongly clear two-factor interactions which were not found before.     

Optimal U-type design for Bayesian nonparametric multiresponse prediction

This paper presents an extension of the work of Yue and Chatterjee (2010) about U-type designs for Bayesian nonparametric response prediction. We consider nonparametric Bayesian regression model with p responses. We use U-type designs with n runs, m factors and q levels for the nonparametric multiresponse prediction based on the asymptotic Bayesian criterion. A lower bound for the proposed criterion is established, and some optimal and nearly optimal designs for the illustrative models are given.     

Biosocial Influences on the Family: A Decade Review

The past decade brought a remarkable increase in the number and quality of biosocial studies of family processes. The current review summarizes recent advances in biosocial family research by providing key exemplars of emerging research paradigms. Research in the past decade has substantiated the claim in the previous Decade Review ( Booth, Carver, & Granger, 2000 ) that bidirectional influences between all levels of analysis are paramount. There is an emerging consensus that integrating factors at multiple biological and social levels is highly informative. Because ignoring biological factors often will underestimate mediating or moderating mechanisms, the review provides recommendations for biosocial family research. We also highlight the need for researchers who understand complex family environments to lend their expertise to biosocial studies.     

论宪政设计的可能性及其理论预设

人类社会可以通过政治设计来建立一个良好的政府,而宪政设计就是一个实现人间至善、建立美好现代社会的基本途径。人类具有主体性,政治具有向善性,这就使得宪政设计成为可能。进行宪政设计必须遵循一些理论预设,那就是关于人性的幽暗意识假定和关于权力的必要的恶的假定。