A semiparametric Bayesian model for repeatedly repeated binary outcomes

Summary.  We discuss the analysis of data from single-nucleotide polymorphism arrays comparing tumour and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes and single-nucleotide polymorphisms nested within regions. We propose to analyse these data by using a semiparametric model for multilevel repeated binary data. At the top level of the hierarchy we assume a sampling model for the observed binary LOH sequences that arises from a partial exchangeability argument. This implies a mixture of Markov chains model. The mixture is defined with respect to the Markov transition probabilities. We assume a non-parametric prior for the random-mixing measure. The resulting model takes the form of a semiparametric random-effects model with the matrix of transition probabilities being the random effects. The model includes appropriate dependence assumptions for the two remaining levels of the hierarchy, i.e. for regions within chromosomes and for chromosomes within patient. We use the model to identify regions of increased LOH in a data set coming from a study of treatment-related leukaemia in children with an initial cancer diagnostic. The model successfully identifies the desired regions and performs well compared with other available alternatives.     

Optimal sampling times in population pharmacokinetic studies

We propose a simulation-based approach to decision theoretic Bayesian optimal design. The underlying probability model is a population pharmacokinetic model which allows for correlated responses (drug concentrations) and patient-to-patient heterogeneity. We consider the problem of choosing sampling times for the anticancer agent paclitaxel, using criteria related to the total area under the curve, the time above a critical threshold and the sampling cost.     

Tourette's syndrome

1. Tourette's syndrome is a disorder with a multitude of complex behavioral problems with major implications for social impairment and emotional pain. 2. The generic care plan anticipates the predictable management problems in adolescent patients. It offers nursing interventions, particularly structure, which is important in managing symptoms. 3. The treatment process is slow. The successful implementation requires consistent efforts from the nursing staff, treatment team, and family.     

犹太人能成为基督徒吗?反思、挑战与困惑

本文从一名犹太基督徒的视角出发,阐述了在作者身上所发生的犹太教与基督教身份之间的张力,并从耶稣、保罗以及早期犹太基督徒身上寻找解决方案,进而消解基督教与犹太教之间历史上的误会与冲突,以及如何从基督教的角度去协同与犹太教的关系。最后,作者陈述了现代以色列国内巴勒斯坦人的现状,并提出作为一个基督徒的正当立场。     

Assessing discrimination of risk prediction rules in a clustered data setting

The AUC (area under ROC curve) is a commonly used metric to assess discrimination of risk prediction rules; however, standard errors of AUC are usually based on the Mann–Whitney U test that assumes independence of sampling units. For ophthalmologic applications, it is desirable to assess risk prediction rules based on eye-specific outcome variables which are generally highly, but not perfectly correlated in fellow eyes [e.g. progression of individual eyes to age-related macular degeneration (AMD)]. In this article, we use the extended Mann–Whitney U test (Rosner and Glynn, Biometrics 65:188–197, 2009) for the case where subunits within a cluster may have different progression status and assess discrimination of different prediction rules in this setting. Both data analyses based on progression of AMD and simulation studies show reasonable accuracy of this extended Mann–Whitney U test to assess discrimination of eye-specific risk prediction rules.     

A method for combining inference across related nonparametric Bayesian models

Summary.  We consider the problem of combining inference in related nonparametric Bayes models. Analogous to parametric hierarchical models, the hierarchical extension formalizes borrowing strength across the related submodels. In the nonparametric context, modelling is complicated by the fact that the random quantities over which we define the hierarchy are infinite dimensional. We discuss a formal definition of such a hierarchical model. The approach includes a regression at the level of the nonparametric model. For the special case of Dirichlet process mixtures, we develop a Markov chain Monte Carlo scheme to allow efficient implementation of full posterior inference in the given model.     

PARAMETER ESTIMATION FOR LOW-ORDER AUTO-REGRESSIVE MODELS WITH MISSING VALUES

Longitudinal data analysis in epidemiological settings is complicated by large multiplicities of short time series and the occurrence of missing observations. To handle such difficulties Rosner & Muñoz (1988) developed a weighted non-linear least squares algorithm for estimating parameters for first-order autoregressive (AR1) processes with time-varying covariates. This method proved efficient when compared to complete case procedures. Here that work is extended by (1) introducing a different estimation procedure based on the EM algorithm, and (2) formulating estimation techniques for second-order autoregressive models. The second development is important because some of the intended areas of application (adult pulmonary function decline, childhood blood pressure) have autocorrelation functions which decay more slowly than the geometric rate imposed by an AR1 model. Simulation studies are used to compare the three methodologies (non-linear, EM based and complete case) with respect to bias, efficiency and coverage both in the presence and in the absence of time-varying covariates. Differing degrees and mechanisms of missingness are examined. Preliminary results indicate the non-linear approach to be the method of choice: it has high efficiency and is easily implemented. An illustrative example concerning pulmonary function decline in the Netherlands is analyzed using this method.