MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Biostatistics' source. Mon, 06 Feb 2012 22:09:25 +0100 http://www.medworm.com/index.php?rid=5501854&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F193%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501854 Tue, 13 Dec 2011 05:00:00 +0100 5501854 http://www.medworm.com/index.php?rid=5501853&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F179%3Frss%3D1 Relative risks (RRs) are generally considered preferable to odds ratios in prospective studies. However, unlike logistic regression for odds ratios, the standard log-binomial model for RR regression does not respect the natural parameter constraints and is therefore often subject to numerical instability. In this paper, we develop a reliable and flexible method for fitting log-binomial models. We use an Expectation–Maximization (EM) algorithm where the multiplicative event probability is viewed as the joint probability for a collection of latent binary outcomes. This gives a simple iterative scheme that provides stable convergence to the maximum likelihood estimate. In addition to reliability, the method offers some flexible generalizations, including models with unspecified isotonic... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501853 Tue, 13 Dec 2011 05:00:00 +0100 5501853 http://www.medworm.com/index.php?rid=5501852&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F166%3Frss%3D1 It has recently been proposed that variation in DNA methylation at specific genomic locations may play an important role in the development of complex diseases such as cancer. Here, we develop 1- and 2-group multiple testing procedures for identifying and quantifying regions of DNA methylation variability. Our method is the first genome-wide statistical significance calculation for increased or differential variability, as opposed to the traditional approach of testing for mean changes. We apply these procedures to genome-wide methylation data obtained from biological and technical replicates and provide the first statistical proof that variably methylated regions exist and are due to interindividual variation. We also show that differentially variable regions in colon tumor and normal tis... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501852 Tue, 13 Dec 2011 05:00:00 +0100 5501852 http://www.medworm.com/index.php?rid=5501851&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F153%3Frss%3D1 We present a new method for Bayesian Markov Chain Monte Carlo–based inference in certain types of stochastic models, suitable for modeling noisy epidemic data. We apply the so-called uniformization representation of a Markov process, in order to efficiently generate appropriate conditional distributions in the Gibbs sampler algorithm. The approach is shown to work well in various data-poor settings, that is, when only partial information about the epidemic process is available, as illustrated on the synthetic data from SIR-type epidemics and the Center for Disease Control and Prevention data from the onset of the H1N1 pandemic in the United States. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501851 Tue, 13 Dec 2011 05:00:00 +0100 5501851 http://www.medworm.com/index.php?rid=5501850&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F142%3Frss%3D1 Clinical demand for individualized "adaptive" treatment policies in diverse fields has spawned development of clinical trial methodology for their experimental evaluation via multistage designs, building upon methods intended for the analysis of naturalistically observed strategies. Because often there is no need to parametrically smooth multistage trial data (in contrast to observational data for adaptive strategies), it is possible to establish direct connections among different methodological approaches. We show by algebraic proof that the maximum likelihood (ML) and optimal semiparametric (SP) estimators of the population mean of the outcome of a treatment policy and its standard error are equal under certain experimental conditions. This result is used to develop a unified and efficie... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501850 Tue, 13 Dec 2011 05:00:00 +0100 5501850 http://www.medworm.com/index.php?rid=5501849&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F129%3Frss%3D1 We present a flexible framework to incorporate the exchangeability into the representation of lists. The proposed framework supports straightforward comparison between any 2 lists. It can also be used to generate new more stable gene rankings incorporating more information from the experimental data. Using 2 microarray data sets, we show that the proposed method provides more robust gene rankings than existing methods with respect to sampling variations, without compromising the biological significance of the rankings. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501849 Tue, 13 Dec 2011 05:00:00 +0100 5501849 http://www.medworm.com/index.php?rid=5501848&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F113%3Frss%3D1 Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) is a powerful technique that is being used in a wide range of biological studies including genome-wide measurements of protein–DNA interactions, DNA methylation, and histone modifications. The vast amount of data and biases introduced by sequencing and/or genome mapping pose new challenges and call for effective methods and fast computer programs for statistical analysis. To systematically model ChIP-seq data, we build a dynamic signal profile for each chromosome and then model the profile using a fully Bayesian hidden Ising model. The proposed model naturally takes into account spatial dependency and global and local distributions of sequence tags. It can be used for one-sample and two-sample analyses. T... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501848 Tue, 13 Dec 2011 05:00:00 +0100 5501848 http://www.medworm.com/index.php?rid=5501847&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F101%3Frss%3D1 Peptide Microarray Immunoassay (PMI for brevity) is a novel technology that enables researchers to map a large number of proteomic measurements at a peptide level, providing information regarding the relationship between antibody response and clinical sensitivity. PMI studies aim at recognizing antigen-specific antibodies from serum samples and at detecting epitope regions of the protein antigen. PMI data present new challenges for statistical analysis mainly due to the structural dependence among peptides. A PMI is made of a complete library of consecutive peptides. They are synthesized by systematically shifting a window of a fixed number of amino acids through the finite sequence of amino acids of the antigen protein as ordered in the primary structure of the protein. This implies that ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501847 Tue, 13 Dec 2011 05:00:00 +0100 5501847 http://www.medworm.com/index.php?rid=5501846&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F89%3Frss%3D1 Nested case–control (NCC) design is used frequently in epidemiological studies as a cost-effective subcohort sampling strategy to conduct biomarker research. Sampling strategy, on the other hoand, creates challenges for data analysis because of outcome-dependent missingness in biomarker measurements. In this paper, we propose inverse probability weighted (IPW) methods for making inference about the prognostic accuracy of a novel biomarker for predicting future events with data from NCC studies. The consistency and asymptotic normality of these estimators are derived using the empirical process theory and convergence theorems for sequences of weakly dependent random variables. Simulation and analysis using Framingham Offspring Study data suggest that the proposed methods perform well ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501846 Tue, 13 Dec 2011 05:00:00 +0100 5501846 http://www.medworm.com/index.php?rid=5501845&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F74%3Frss%3D1 High-dimensional biomarker data are often collected in epidemiological studies when assessing the association between biomarkers and human disease is of interest. We develop a latent class modeling approach for joint analysis of high-dimensional semicontinuous biomarker data and a binary disease outcome. To model the relationship between complex biomarker expression patterns and disease risk, we use latent risk classes to link the 2 modeling components. We characterize complex biomarker-specific differences through biomarker-specific random effects, so that different biomarkers can have different baseline (low-risk) values as well as different between-class differences. The proposed approach also accommodates data features that are common in environmental toxicology and other biomarker exp... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501845 Tue, 13 Dec 2011 05:00:00 +0100 5501845 http://www.medworm.com/index.php?rid=5501844&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F61%3Frss%3D1 Mixed models are commonly used to represent longitudinal or repeated measures data. An additional complication arises when the response is censored, for example, due to limits of quantification of the assay used. While Gaussian random effects are routinely assumed, little work has characterized the consequences of misspecifying the random-effects distribution nor has a more flexible distribution been studied for censored longitudinal data. We show that, in general, maximum likelihood estimators will not be consistent when the random-effects density is misspecified, and the effect of misspecification is likely to be greatest when the true random-effects density deviates substantially from normality and the number of noncensored observations on each subject is small. We develop a mixed model... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501844 Tue, 13 Dec 2011 05:00:00 +0100 5501844 http://www.medworm.com/index.php?rid=5501843&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F48%3Frss%3D1 We present this paper as an illustration of the advantages of joint latent variable models and as an example of the applicability of these models for biomedical research. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501843 Tue, 13 Dec 2011 05:00:00 +0100 5501843 http://www.medworm.com/index.php?rid=5501842&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F32%3Frss%3D1 Sensitivity and specificity are common measures of the accuracy of a diagnostic test. The usual estimators of these quantities are unbiased if data on the diagnostic test result and the true disease status are obtained from all subjects in an appropriately selected sample. In some studies, verification of the true disease status is performed only for a subset of subjects, possibly depending on the result of the diagnostic test and other characteristics of the subjects. Estimators of sensitivity and specificity based on this subset of subjects are typically biased; this is known as verification bias. Methods have been proposed to correct verification bias under the assumption that the missing data on disease status are missing at random (MAR), that is, the probability of missingness depends... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501842 Tue, 13 Dec 2011 05:00:00 +0100 5501842 http://www.medworm.com/index.php?rid=5501841&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F18%3Frss%3D1 Semiparametric transformation models provide a very general framework for studying the effects of (possibly time-dependent) covariates on survival time and recurrent event times. Assessing the adequacy of these models is an important task because model misspecification affects the validity of inference and the accuracy of prediction. In this paper, we introduce appropriate time-dependent residuals for these models and consider the cumulative sums of the residuals. Under the assumed model, the cumulative sum processes converge weakly to zero-mean Gaussian processes whose distributions can be approximated through Monte Carlo simulation. These results enable one to assess, both graphically and numerically, how unusual the observed residual patterns are in reference to their null distributions... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501841 Tue, 13 Dec 2011 05:00:00 +0100 5501841 http://www.medworm.com/index.php?rid=5501840&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F4%3Frss%3D1 Understanding conception probabilities is important not only for helping couples to achieve pregnancy but also in identifying acute or chronic reproductive toxicants that affect the highly timed and interrelated processes underlying hormonal profiles, ovulation, libido, and conception during menstrual cycles. Currently, 2 statistical approaches are available for estimating conception probabilities depending upon the research question and extent of data collection during the menstrual cycle: a survival approach when interested in modeling time-to-pregnancy (TTP) in relation to women or couples' purported exposure(s), or a hierarchical Bayesian approach when one is interested in modeling day-specific conception probabilities during the estimated fertile window. We propose a biologically vali... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501840 Tue, 13 Dec 2011 05:00:00 +0100 5501840 http://www.medworm.com/index.php?rid=5501839&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F13%2F1%2F1%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5501839 Tue, 13 Dec 2011 05:00:00 +0100 5501839 http://www.medworm.com/index.php?rid=5204967&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F776%3Frss%3D1 Array-based comparative genomic hybridization (aCGH) enables the measurement of DNA copy number across thousands of locations in a genome. The main goals of analyzing aCGH data are to identify the regions of copy number variation (CNV) and to quantify the amount of CNV. Although there are many methods for analyzing single-sample aCGH data, the analysis of multi-sample aCGH data is a relatively new area of research. Further, many of the current approaches for analyzing multi-sample aCGH data do not appropriately utilize the additional information present in the multiple samples. We propose a procedure called the Fused Lasso Latent Feature Model (FLLat) that provides a statistical framework for modeling multi-sample aCGH data and identifying regions of CNV. The procedure involves modeling ea... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204967 Thu, 08 Sep 2011 04:00:00 +0100 5204967 http://www.medworm.com/index.php?rid=5204966&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F763%3Frss%3D1 In high-throughput -omics studies, markers identified from analysis of single data sets often suffer from a lack of reproducibility because of sample limitation. A cost-effective remedy is to pool data from multiple comparable studies and conduct integrative analysis. Integrative analysis of multiple -omics data sets is challenging because of the high dimensionality of data and heterogeneity among studies. In this article, for marker selection in integrative analysis of data from multiple heterogeneous studies, we propose a 2-norm group bridge penalization approach. This approach can effectively identify markers with consistent effects across multiple studies and accommodate the heterogeneity among studies. We propose an efficient computational algorithm and establish the asymptotic consis... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204966 Thu, 08 Sep 2011 04:00:00 +0100 5204966 http://www.medworm.com/index.php?rid=5204965&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F750%3Frss%3D1 Development of human immunodeficiency virus resistance mutations is a major cause of failure of antiretroviral treatment. We develop a recursive partitioning method to correlate high-dimensional viral sequences with repeatedly measured outcomes. The splitting criterion of this procedure is based on a class of U-type score statistics. The proposed method is flexible enough to apply to a broad range of problems involving longitudinal outcomes. Simulation studies are performed to explore the finite-sample properties of the proposed method, which is also illustrated through analysis of data collected in 3 phase II clinical trials testing the antiretroviral drug efavirenz. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204965 Thu, 08 Sep 2011 04:00:00 +0100 5204965 http://www.medworm.com/index.php?rid=5204964&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F737%3Frss%3D1 We investigate a change-point approach for modeling and estimating the regression effects caused by a concomitant intervention in a longitudinal study. Since a concomitant intervention is often introduced when a patient's health status exhibits undesirable trends, statistical models without properly incorporating the intervention and its starting time may lead to biased estimates of the intervention effects. We propose a shared parameter change-point model to evaluate the pre- and postintervention time trends of the response and develop a likelihood-based method for estimating the intervention effects and other parameters. Application and statistical properties of our method are demonstrated through a longitudinal clinical trial in depression and heart disease and a simulation study. (Sour... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204964 Thu, 08 Sep 2011 04:00:00 +0100 5204964 http://www.medworm.com/index.php?rid=5204963&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F723%3Frss%3D1 In many chronic diseases, the patient's health status is followed up by quantitative markers. The evolution is often characterized by a 2-phase degradation process, that is, a normal phase followed by a pathological degradation phase preceding the disease diagnosis. We propose a joint multistate model with latent state for the joint modeling of repeated measures of a quantitative marker, time-to-illness and time-to-death. Using data from the PAQUID cohort on cognitive aging, we jointly studied cognitive decline, dementia risk, and death risk. We estimated the mean evolution of cognitive scores given age at dementia for subjects alive and demented, the mean evolution of cognitive scores for subjects alive and nondemented, in addition to age at acceleration of cognitive decline and duration ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204963 Thu, 08 Sep 2011 04:00:00 +0100 5204963 http://www.medworm.com/index.php?rid=5204962&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F710%3Frss%3D1 We consider modeling the dependence of sensitivity and specificity on the disease prevalence in diagnostic accuracy studies. Many meta-analyses compare test accuracy across studies and fail to incorporate the possible connection between the accuracy measures and the prevalence. We propose a Pearson type correlation coefficient and an estimating equation–based regression framework to help understand such a practical dependence. The results we derive may then be used to better interpret the results from meta-analyses. In the biomedical examples analyzed in this paper, the diagnostic accuracy of biomarkers are shown to be associated with prevalence, providing insights into the utility of these biomarkers in low- and high-prevalence populations. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204962 Thu, 08 Sep 2011 04:00:00 +0100 5204962 http://www.medworm.com/index.php?rid=5204961&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F695%3Frss%3D1 We consider here the problem of classifying a macro-level object based on measurements of embedded (micro-level) observations within each object, for example, classifying a patient based on measurements on a collection of a random number of their cells. Classification problems with this hierarchical, nested structure have not received the same statistical understanding as the general classification problem. Some heuristic approaches have been developed and a few authors have proposed formal statistical models. We focus on the problem where heterogeneity exists between the macro-level objects within a class. We propose a model-based statistical methodology that models the log-odds of the macro-level object belonging to a class using a latent-class variable model to account for this heteroge... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204961 Thu, 08 Sep 2011 04:00:00 +0100 5204961 http://www.medworm.com/index.php?rid=5204960&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F682%3Frss%3D1 We propose a semiparametric Bayesian model, based on penalized splines, for the recovery of the time-invariant topology of a causal interaction network from longitudinal data. Our motivation is inference of gene regulatory networks from low-resolution microarray time series, where existence of nonlinear interactions is well known. Parenthood relations are mapped by augmenting the model with kinship indicators and providing these with either an overall or gene-wise hierarchical structure. Appropriate specification of the prior is crucial to control the flexibility of the splines, especially under circumstances of scarce data; thus, we provide an informative, proper prior. Substantive improvement in network inference over a linear model is demonstrated using synthetic data drawn from ordinar... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204960 Thu, 08 Sep 2011 04:00:00 +0100 5204960 http://www.medworm.com/index.php?rid=5204959&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F666%3Frss%3D1 Understanding infectious disease dynamics and the effect on prevalence and incidence is crucial for public health policies. Disease incidence and prevalence are typically not observed directly and increasingly are estimated through the synthesis of indirect information from multiple data sources. We demonstrate how an evidence synthesis approach to the estimation of human immunodeficiency virus (HIV) prevalence in England and Wales can be extended to infer the underlying HIV incidence. Diverse time series of data can be used to obtain yearly "snapshots" (with associated uncertainty) of the proportion of the population in 4 compartments: not at risk, susceptible, HIV positive but undiagnosed, and diagnosed HIV positive. A multistate model for the infection and diagnosis processes is then fo... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204959 Thu, 08 Sep 2011 04:00:00 +0100 5204959 http://www.medworm.com/index.php?rid=5204958&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F653%3Frss%3D1 There are copula-based statistical models in the literature for regression with dependent data such as clustered and longitudinal overdispersed counts, for which parameter estimation and inference are straightforward. For situations where the main interest is in the regression and other univariate parameters and not the dependence, we propose a "weighted scores method", which is based on weighting score functions of the univariate margins. The weight matrices are obtained initially fitting a discretized multivariate normal distribution, which admits a wide range of dependence. The general methodology is applied to negative binomial regression models. Asymptotic and small-sample efficiency calculations show that our method is robust and nearly as efficient as maximum likelihood for fully sp... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204958 Thu, 08 Sep 2011 04:00:00 +0100 5204958 http://www.medworm.com/index.php?rid=5204957&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F637%3Frss%3D1 In air pollution epidemiology, there is a growing interest in estimating the health effects of coarse particulate matter (PM) with aerodynamic diameter between 2.5 and 10 µm. Coarse PM concentrations can exhibit considerable spatial heterogeneity because the particles travel shorter distances and do not remain suspended in the atmosphere for an extended period of time. In this paper, we develop a modeling approach for estimating the short-term effects of air pollution in time series analysis when the ambient concentrations vary spatially within the study region. Specifically, our approach quantifies the error in the exposure variable by characterizing, on any given day, the disagreement in ambient concentrations measured across monitoring stations. This is accomplished by viewing mon... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204957 Thu, 08 Sep 2011 04:00:00 +0100 5204957 http://www.medworm.com/index.php?rid=5204956&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F624%3Frss%3D1 Food records, including 24-hour recalls and diet diaries, are considered to provide generally superior measures of long-term dietary intake relative to questionnaire-based methods. Despite the expense of processing food records, they are increasingly used as the main dietary measurement in nutritional epidemiology, in particular in sub-studies nested within prospective cohorts. Food records are, however, subject to excess reports of zero intake. Measurement error is a serious problem in nutritional epidemiology because of the lack of gold standard measurements and results in biased estimated diet–disease associations. In this paper, a 3-part measurement error model, which we call the never and episodic consumers (NEC) model, is outlined for food records. It allows for both real zeros... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204956 Thu, 08 Sep 2011 04:00:00 +0100 5204956 http://www.medworm.com/index.php?rid=5204955&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F610%3Frss%3D1 Association studies in environmental statistics often involve exposure and outcome data that are misaligned in space. A common strategy is to employ a spatial model such as universal kriging to predict exposures at locations with outcome data and then estimate a regression parameter of interest using the predicted exposures. This results in measurement error because the predicted exposures do not correspond exactly to the true values. We characterize the measurement error by decomposing it into Berkson-like and classical-like components. One correction approach is the parametric bootstrap, which is effective but computationally intensive since it requires solving a nonlinear optimization problem for the exposure model parameters in each bootstrap sample. We propose a less computationally i... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204955 Thu, 08 Sep 2011 04:00:00 +0100 5204955 http://www.medworm.com/index.php?rid=5204954&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F4%2F597%3Frss%3D1 Accurate risk prediction is an important step in developing optimal strategies for disease prevention and treatment. Based on the predicted risks, patients can be stratified to different risk categories where each category corresponds to a particular clinical intervention. Incorrect or suboptimal interventions are likely to result in unnecessary financial and medical consequences. It is thus essential to account for the costs associated with the clinical interventions when developing and evaluating risk stratification (RS) rules for clinical use. In this article, we propose to quantify the value of an RS rule based on the total expected cost attributed to incorrect assignment of risk groups due to the rule. We have established the relationship between cost parameters and optimal threshold ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=5204954 Thu, 08 Sep 2011 04:00:00 +0100 5204954 http://www.medworm.com/index.php?rid=4932966&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F594%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932966 Mon, 13 Jun 2011 23:00:00 +0100 4932966 http://www.medworm.com/index.php?rid=4932965&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F582%3Frss%3D1 The resampling-based test, which often relies on permutation or bootstrap procedures, has been widely used for statistical hypothesis testing when the asymptotic distribution of the test statistic is unavailable or unreliable. It requires repeated calculations of the test statistic on a large number of simulated data sets for its significance level assessment, and thus it could become very computationally intensive. Here, we propose an efficient p-value evaluation procedure by adapting the stochastic approximation Markov chain Monte Carlo algorithm. The new procedure can be used easily for estimating the p-value for any resampling-based test. We show through numeric simulations that the proposed procedure can be 100–500 000 times as efficient (in term of computing time) as the standa... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932965 Mon, 13 Jun 2011 23:00:00 +0100 4932965 http://www.medworm.com/index.php?rid=4932964&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F567%3Frss%3D1 Our research is motivated by 2 methodological problems in assessing diagnostic accuracy of traditional Chinese medicine (TCM) doctors in detecting a particular symptom whose true status has an ordinal scale and is unknown—imperfect gold standard bias and ordinal scale symptom status. In this paper, we proposed a nonparametric maximum likelihood method for estimating and comparing the accuracy of different doctors in detecting a particular symptom without a gold standard when the true symptom status had an ordered multiple class. In addition, we extended the concept of the area under the receiver operating characteristic curve to a hyper-dimensional overall accuracy for diagnostic accuracy and alternative graphs for displaying a visual result. The simulation studies showed that the pr... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932964 Mon, 13 Jun 2011 23:00:00 +0100 4932964 http://www.medworm.com/index.php?rid=4932963&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F548%3Frss%3D1 We argue that the time from the onset of infectiousness to infectious contact, which we call the "contact interval," is a better basis for inference in epidemic data than the generation or serial interval. Since contact intervals can be right censored, survival analysis is the natural approach to estimation. Estimates of the contact interval distribution can be used to estimate R0 in both mass-action and network-based models. We apply these methods to 2 data sets from the 2009 influenza A(H1N1) pandemic. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932963 Mon, 13 Jun 2011 23:00:00 +0100 4932963 http://www.medworm.com/index.php?rid=4932962&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F535%3Frss%3D1 Recurrent events are the natural outcome in many medical and epidemiology studies. To assess covariate effects on the gaps between consecutive recurrent events, the Cox proportional hazards model is frequently employed in data analysis. The validity of statistical inference, however, depends on the appropriateness of the Cox model. In this paper, we propose a class of graphical techniques and formal tests for checking the Cox model with recurrent gap time data. The building block of our model checking method is an averaged martingale-like process, based on which a class of multiparameter stochastic processes is proposed. This maneuver is very general and can be used to assess different aspects of model fit. Numerical simulations are conducted to examine finite-sample performance, and the p... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932962 Mon, 13 Jun 2011 23:00:00 +0100 4932962 http://www.medworm.com/index.php?rid=4932961&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F521%3Frss%3D1 Two-stage design has long been recognized to be a cost-effective way for conducting biomedical studies. In many trials, auxiliary covariate information may also be available, and it is of interest to exploit these auxiliary data to improve the efficiency of inferences. In this paper, we propose a 2-stage design with continuous outcome where the second-stage data is sampled with an "outcome-auxiliary-dependent sampling" (OADS) scheme. We propose an estimator which is the maximizer for an estimated likelihood function. We show that the proposed estimator is consistent and asymptotically normally distributed. The simulation study indicates that greater study efficiency gains can be achieved under the proposed 2-stage OADS design by utilizing the auxiliary covariate information when compared w... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932961 Mon, 13 Jun 2011 23:00:00 +0100 4932961 http://www.medworm.com/index.php?rid=4932960&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F506%3Frss%3D1 The outcome-dependent sampling (ODS) design, which allows observation of exposure variable to depend on the outcome, has been shown to be cost efficient. In this article, we propose a new statistical inference method, an estimated penalized likelihood method, for a partial linear model in the setting of a 2-stage ODS with a continuous outcome. We develop the asymptotic properties and conduct simulation studies to demonstrate the performance of the proposed estimator. A real environmental study data set is used to illustrate the proposed method. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932960 Mon, 13 Jun 2011 23:00:00 +0100 4932960 http://www.medworm.com/index.php?rid=4932959&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F493%3Frss%3D1 Longitudinal studies, in which individuals are measured repeatedly in time, are often incomplete. We model continuous-time longitudinal data from the Multicenter AIDS Cohort Study using a diffusion model in which the diffusion parameters are functions of the covariates. These data are jointly modeled with the process of time-to-death due to AIDS. We show that, even for large data sets with a large number of missing variables, a Bayesian analysis is feasible using Gibbs sampling and compare a complete case analysis with a Bayesian treatment of missing values. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932959 Mon, 13 Jun 2011 23:00:00 +0100 4932959 http://www.medworm.com/index.php?rid=4932958&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F478%3Frss%3D1 When the true end points (T) are difficult or costly to measure, surrogate markers (S) are often collected in clinical trials to help predict the effect of the treatment (Z). There is great interest in understanding the relationship among S, T, and Z. A principal stratification (PS) framework has been proposed by Frangakis and Rubin (2002) to study their causal associations. In this paper, we extend the framework to a multiple trial setting and propose a Bayesian hierarchical PS model to assess surrogacy. We apply the method to data from a large collection of colon cancer trials in which S and T are binary. We obtain the trial-specific causal measures among S, T, and Z, as well as their overall population-level counterparts that are invariant across trials. The method allows for informatio... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932958 Mon, 13 Jun 2011 23:00:00 +0100 4932958 http://www.medworm.com/index.php?rid=4932957&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F462%3Frss%3D1 Nucleosomes are units of chromatin structure, consisting of DNA sequence wrapped around proteins called "histones." Nucleosomes occur at variable intervals throughout genomic DNA and prevent transcription factor (TF) binding by blocking TF access to the DNA. A map of nucleosomal locations would enable researchers to detect TF binding sites with greater efficiency. Our objective is to construct an accurate genomic map of nucleosome-free regions (NFRs) based on data from high-throughput genomic tiling arrays in yeast. These high-volume data typically have a complex structure in the form of dependence on neighboring probes as well as underlying DNA sequence, variable-sized gaps, and missing data. We propose a novel continuous-index model appropriate for non-equispaced tiling array data that s... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932957 Mon, 13 Jun 2011 23:00:00 +0100 4932957 http://www.medworm.com/index.php?rid=4932956&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F445%3Frss%3D1 In the analysis of genome-wide association (GWA) data, the aim is to detect statistical associations between single nucleotide polymorphisms (SNPs) and the disease or trait of interest. These SNPs, or the particular regions of the genome they implicate, are then considered for further study. We demonstrate through a comprehensive simulation study that the inclusion of additional, biologically relevant information through a 2-level empirical Bayes hierachical model framework offers a more robust method of detecting associated SNPs. The empirical Bayes approach is an objective means of analyzing the data without the need for the setting of subjective parameter estimates. This framework gives more stable estimates of effects through a reduction of the variability in the usual effect estimates... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932956 Mon, 13 Jun 2011 23:00:00 +0100 4932956 http://www.medworm.com/index.php?rid=4932955&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F429%3Frss%3D1 In the analysis of high-throughput biological data, it is often believed that the biological units such as genes behave interactively by groups, that is, pathways in our context. It is conceivable that utilization of priorly available pathway knowledge would greatly facilitate both interpretation and estimation in statistical analysis of such high-dimensional biological data. In this article, we propose a 2-step procedure for the purpose of identifying pathways that are related to and influence the clinical phenotype. In the first step, a nonlinear dimension reduction method is proposed, which permits flexible within-pathway gene interactions as well as nonlinear pathway effects on the response. In the second step, a regularized model-based pathway ranking and selection procedure is develo... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932955 Mon, 13 Jun 2011 23:00:00 +0100 4932955 http://www.medworm.com/index.php?rid=4932954&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F413%3Frss%3D1 The statistical analysis of array comparative genomic hybridization (CGH) data has now shifted to the joint assessment of copy number variations at the cohort level. Considering multiple profiles gives the opportunity to correct for systematic biases observed on single profiles, such as probe GC content or the so-called "wave effect." In this article, we extend the segmentation model developed in the univariate case to the joint analysis of multiple CGH profiles. Our contribution is multiple: we propose an integrated model to perform joint segmentation, normalization, and calling for multiple array CGH profiles. This model shows great flexibility, especially in the modeling of the wave effect that gives a likelihood framework to approaches proposed by others. We propose a new dynamic progr... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932954 Mon, 13 Jun 2011 23:00:00 +0100 4932954 http://www.medworm.com/index.php?rid=4932953&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F3%2F399%3Frss%3D1 For medical classification problems, it is often desirable to have a probability associated with each class. Probabilistic classifiers have received relatively little attention for small n large p classification problems despite of their importance in medical decision making. In this paper, we introduce 2 criteria for assessment of probabilistic classifiers: well-calibratedness and refinement and develop corresponding evaluation measures. We evaluated several published high-dimensional probabilistic classifiers and developed 2 extensions of the Bayesian compound covariate classifier. Based on simulation studies and analysis of gene expression microarray data, we found that proper probabilistic classification is more difficult than deterministic classification. It is important to ensure tha... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4932953 Mon, 13 Jun 2011 23:00:00 +0100 4932953 http://www.medworm.com/index.php?rid=4621773&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F386%3Frss%3D1 This paper addresses the dose-finding problem in cancer trials in which we are concerned with the gradation of severe toxicities that are considered dose limiting. In order to differentiate the tolerance for different toxicity types and grades, we propose a novel extension of the continual reassessment method that explicitly accounts for multiple toxicity constraints. We apply the proposed methods to redesign a bortezomib trial in lymphoma patients and compare their performance with that of the existing methods. Based on simulations, our proposed methods achieve comparable accuracy in identifying the maximum tolerated dose but have better control of the erroneous allocation and recommendation of an overdose. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621773 Tue, 22 Mar 2011 00:00:00 +0100 4621773 http://www.medworm.com/index.php?rid=4621772&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F369%3Frss%3D1 Rather than viewing receiver operating characteristic (ROC) curves directly to compare the performances of diagnostic methods, the whole and the partial areas under the ROC curve (area under the ROC curve [AUC] and partial area under the ROC curve [pAUC]) are 2 of the most popularly used summaries of the curve. Moreover, when high specificity is a prerequisite, as in some medical diagnostics, pAUC is preferable. In this paper, we propose a wrapper-type algorithm to select the best linear combination of markers that has high sensitivity within a confined specificity range. The markers selected by the proposed algorithm are different from those selected by AUC-based algorithms and therefore provide different information for further studies. Most notably, for example, within the given range o... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621772 Tue, 22 Mar 2011 00:00:00 +0100 4621772 http://www.medworm.com/index.php?rid=4621771&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F354%3Frss%3D1 The hazard ratio provides a natural target for assessing a treatment effect with survival data, with the Cox proportional hazards model providing a widely used special case. In general, the hazard ratio is a function of time and provides a visual display of the temporal pattern of the treatment effect. A variety of nonproportional hazards models have been proposed in the literature. However, available methods for flexibly estimating a possibly time-dependent hazard ratio are limited. Here, we investigate a semiparametric model that allows a wide range of time-varying hazard ratio shapes. Point estimates as well as pointwise confidence intervals and simultaneous confidence bands of the hazard ratio function are established under this model. The average hazard ratio function is also studied ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621771 Tue, 22 Mar 2011 00:00:00 +0100 4621771 http://www.medworm.com/index.php?rid=4621770&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F341%3Frss%3D1 In functional linear models (FLMs), the relationship between the scalar response and the functional predictor process is often assumed to be identical for all subjects. Motivated by both practical and methodological considerations, we relax this assumption and propose a new class of functional regression models that allow the regression structure to vary for different groups of subjects. By projecting the predictor process onto its eigenspace, the new functional regression model is simplified to a framework that is similar to classical mixture regression models. This leads to the proposed approach named as functional mixture regression (FMR). The estimation of FMR can be readily carried out using existing software implemented for functional principal component analysis and mixture regressi... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621770 Tue, 22 Mar 2011 00:00:00 +0100 4621770 http://www.medworm.com/index.php?rid=4621769&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F327%3Frss%3D1 In medical studies, endpoints are often measured for each patient longitudinally. The mixed-effects model has been a useful tool for the analysis of such data. There are situations in which the parameters of the model are subject to some restrictions or constraints. For example, in hearing loss studies, we expect hearing to deteriorate with time. This means that hearing thresholds which reflect hearing acuity will, on average, increase over time. Therefore, the regression coefficients associated with the mean effect of time on hearing ability will be constrained. Such constraints should be accounted for in the analysis. We propose maximum likelihood estimation procedures, based on the expectation-conditional maximization either algorithm, to estimate the parameters of the model while accou... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621769 Tue, 22 Mar 2011 00:00:00 +0100 4621769 http://www.medworm.com/index.php?rid=4621768&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F313%3Frss%3D1 Encouragement design studies are particularly useful for estimating the effect of an intervention that cannot itself be randomly administered to some and not to others. They require a randomly selected group receive extra encouragement to undertake the treatment of interest, where the encouragement typically takes the form of additional information or incentives. We consider a "clustered encouragement design" (CED), where the randomization is at the level of the clusters (e.g. physicians), but the compliance with assignment is at the level of the units (e.g. patients) within clusters. Noncompliance and missing data are particular problems in encouragement design studies, where encouragement to take the treatment, rather than the treatment itself, is randomized. The motivating study looks a... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621768 Tue, 22 Mar 2011 00:00:00 +0100 4621768 http://www.medworm.com/index.php?rid=4621767&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F303%3Frss%3D1 The basic reproduction number is a key parameter determining whether an infectious disease will persist. Its counterpart over time, the effective reproduction number, is of value in assessing in real time whether interventions have brought an outbreak under control. In this paper, we use theoretical arguments and simulation to understand the relationship between estimation of the reproduction number based on a full continuous time epidemic model and 2 other recently developed estimators. All these methods make use of "epidemic curve" data and require assumptions about the generation time distribution. The 2 simplest estimators do not require information about the—often difficult to obtain—population size. The simplest estimator is shown to require further assumptions that are r... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621767 Tue, 22 Mar 2011 00:00:00 +0100 4621767 http://www.medworm.com/index.php?rid=4621766&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F283%3Frss%3D1 After a steep monotone rise with age, the seroprevalence profiles for human parvovirus B19 (PVB19) display a decrease or plateau between the ages of 20 and 40, in each of 5 European countries. We investigate whether this phenomenon is induced by waning antibodies for PVB19 and, if this is the case, whether secondary infections are plausible, or whether boosting may occur. Several immunological scenarios are tested for PVB19 by fitting different compartmental dynamic transmission models to serological data using data on social contact patterns. The social contact approach has already been shown informative to estimate transmission rates and the basic reproduction number for infections transmitted predominantly through nonsexual social contacts. Our results show that for 4 countries, model s... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621766 Tue, 22 Mar 2011 00:00:00 +0100 4621766 http://www.medworm.com/index.php?rid=4621765&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F270%3Frss%3D1 Suppose that under the conventional randomized clinical trial setting, a new therapy is compared with a standard treatment. In this article, we propose a systematic, 2-stage estimation procedure for the subject-level treatment differences for future patient's disease management and treatment selections. To construct this procedure, we first utilize a parametric or semiparametric method to estimate individual-level treatment differences, and use these estimates to create an index scoring system for grouping patients. We then consistently estimate the average treatment difference for each subgroup of subjects via a nonparametric function estimation method. Furthermore, pointwise and simultaneous interval estimates are constructed to make inferences about such subgroup-specific treatment diff... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621765 Tue, 22 Mar 2011 00:00:00 +0100 4621765 http://www.medworm.com/index.php?rid=4621764&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F258%3Frss%3D1 The Superior Yield of the New Strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) was a randomized, open-label, multicenter clinical trial comparing 2 anticoagulant drugs on the basis of time-to-event endpoints. In contrast to other studies of these agents, the primary, intent-to-treat analysis did not find evidence of a difference, leading to speculation that premature discontinuation of the study agents by some subjects may have attenuated the apparent treatment effect and thus to interest in inference on the difference in survival distributions were all subjects in the population to follow the assigned regimens, with no discontinuation. Such inference is often attempted via ad hoc analyses that are not based on a formal definition of this treatment ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621764 Tue, 22 Mar 2011 00:00:00 +0100 4621764 http://www.medworm.com/index.php?rid=4621763&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F247%3Frss%3D1 We propose a structural mean modeling approach to obtain compliance-adjusted estimates for treatment effects in a randomized-controlled trial comparing 2 active treatments. The model relates an individual's observed outcome to his or her counterfactual untreated outcome through the observed receipt of active treatments. Our proposed estimation procedure exploits baseline covariates that predict compliance levels on each arm. We give a closed-form estimator which allows for differential and unexplained selectivity (i.e. noncausal compliance-outcome association due to unobserved confounding) as well as a nonparametric error distribution. In a simple linear model for a 2-arm trial, we show that the distinct causal parameters are identified unless covariate-specific expected compliance levels ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621763 Tue, 22 Mar 2011 00:00:00 +0100 4621763 http://www.medworm.com/index.php?rid=4621762&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F234%3Frss%3D1 Methods for formally evaluating the clustering of events in space or time, notably the scan statistic, have been richly developed and widely applied. In order to utilize the scan statistic and related approaches, it is necessary to know the extent of the spatial or temporal domains wherein the events arise. Implicit in their usage is that these domains have no "holes"—hereafter "exclusion zones"—regions in which events a priori cannot occur. However, in many contexts, this requirement is not met. When the exclusion zones are known, it is straightforward to correct the scan statistic for their occurrence by simply adjusting the extent of the domain. Here, we tackle the more ambitious objective of formally evaluating clustering in the presence of "unknown" exclusion zones. We dev... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621762 Tue, 22 Mar 2011 00:00:00 +0100 4621762 http://www.medworm.com/index.php?rid=4621761&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F223%3Frss%3D1 In the development of molecular diagnostics, the main objective in high-dimensional genomic studies such as DNA microarray studies is to screen out genes strongly associated with clinical phenotypes to significantly improve diagnostic capabilities. The basic statistical task is thus estimation of the strengths of association or effect sizes for individual genes. We develop an empirical Bayes estimation method based on hierarchical mixture models for a gene-based statistic regarding effect size, without respect to the direction of differential expressions. A nonparametric prior is specified because of limited information on the distributional form of effect size in many genomic studies. Our methods provide some posterior indices useful for selecting candidate genes for further studies. We c... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621761 Tue, 22 Mar 2011 00:00:00 +0100 4621761 http://www.medworm.com/index.php?rid=4621760&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F211%3Frss%3D1 We present a new method that simultaneously detects multilocus interaction associations and imputes missing SNPs from a full Bayesian model. Our method treats both the case–control sample and the reference data as random observations. The output of our method is the posterior probabilities of SNPs for their marginal and interacting associations with the disease. Using simulations, we show that the method produces accurate and robust imputation with little overfitting problems. We further show that, with the type I error rate maintained at a common level, SNP imputation can consistently and sometimes substantially improve the power of detecting disease interaction associations. We use a data set of inflammatory bowel disease to demonstrate the application of our method. (Source: Biost... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621760 Tue, 22 Mar 2011 00:00:00 +0100 4621760 http://www.medworm.com/index.php?rid=4621759&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F2%2F197%3Frss%3D1 DNA methylation is a key regulator of gene function in a multitude of both normal and abnormal biological processes, but tools to elucidate its roles on a genome-wide scale are still in their infancy. Methylation sensitive restriction enzymes and microarrays provide a potential high-throughput, low-cost platform to allow methylation profiling. However, accurate absolute methylation estimates have been elusive due to systematic errors and unwanted variability. Previous microarray preprocessing procedures, mostly developed for expression arrays, fail to adequately normalize methylation-related data since they rely on key assumptions that are violated in the case of DNA methylation. We develop a normalization strategy tailored to DNA methylation data and an empirical Bayes percentage methylat... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4621759 Tue, 22 Mar 2011 00:00:00 +0100 4621759 http://www.medworm.com/index.php?rid=4277613&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F193%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277613 Tue, 21 Dec 2010 00:00:00 +0100 4277613 http://www.medworm.com/index.php?rid=4277612&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F192%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277612 Tue, 21 Dec 2010 00:00:00 +0100 4277612 http://www.medworm.com/index.php?rid=4277611&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F173%3Frss%3D1 A recurrent statistical problem in cell biology is to draw inference about cell kinetics from observations collected at discrete time points. We investigate this problem when multiple cell clones are observed longitudinally over time. The theory of age-dependent branching processes provides an appealing framework for the quantitative analysis of such data. Likelihood inference being difficult in this context, we propose an alternative composite likelihood approach, where the estimation function is defined from the marginal or conditional distributions of the number of cells of each observable cell type. These distributions have generally no closed-form expressions but they can be approximated using simulations. We construct a bias-corrected version of the estimating function, which also of... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277611 Tue, 21 Dec 2010 00:00:00 +0100 4277611 http://www.medworm.com/index.php?rid=4277610&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F156%3Frss%3D1 Rapid advancement in modern technology has allowed scientists to collect data of unprecedented size and complexity. This is particularly the case in genomics applications. One type of statistical problem in such applications is concerned with modeling an output variable as a function of a small subset of a large number of features based on relatively small sample sizes, which may even be coming from multiple subpopulations. As such, selecting the correct predictive features (variables) for each subpopulation is the key. To address this issue, we consider the problem of feature selection in finite mixture of sparse normal linear (FMSL) models in large feature spaces. We propose a 2-stage procedure to overcome computational difficulties and large false discovery rates caused by the large mod... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277610 Tue, 21 Dec 2010 00:00:00 +0100 4277610 http://www.medworm.com/index.php?rid=4277609&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F143%3Frss%3D1 In toxicological experiments with laboratory animals, there are usually many response variables of interest. When the response variables are continuous, parametric or nonparametric multivariate analysis of variance techniques can be applied to analyze the data. However, multivariate methods for dichotomous response variables are less developed in the statistical literature. An example of the need for such a method is a decompression sickness (DCS) study in which each animal subject is examined for the presence of multiple types of DCS. Two risk factors related to the outcomes are studied. Finding the range of these 2 risk factors for a fixed probability to develop DCS translates to the statistical question of estimating a 2D toxic dose corresponding to a fixed risk for multiple dichotomous... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277609 Tue, 21 Dec 2010 00:00:00 +0100 4277609 http://www.medworm.com/index.php?rid=4277608&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F122%3Frss%3D1 Statistical heterogeneity and small-study effects are 2 major issues affecting the validity of meta-analysis. In this article, we introduce the concept of a limit meta-analysis, which leads to shrunken, empirical Bayes estimates of study effects after allowing for small-study effects. This in turn leads to 3 model-based adjusted pooled treatment-effect estimators and associated confidence intervals. We show how visualizing our estimators using the radial plot indicates how they can be calculated using existing software. The concept of limit meta-analysis also gives rise to a new measure of heterogeneity, termed G2, for heterogeneity that remains after small-study effects are accounted for. In a simulation study with binary data and small-study effects, we compared our proposed estimators w... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277608 Tue, 21 Dec 2010 00:00:00 +0100 4277608 http://www.medworm.com/index.php?rid=4277607&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F112%3Frss%3D1 The attributable fraction (AF) is a widely used measure to assess the impact of an exposure on a disease. It is commonly estimated through maximum likelihood, which requires a regression model for the outcome. Recently, it was demonstrated that the AF can also be estimated through inverse probability weighting, which requires a model for the exposure. In this paper, we derive doubly robust estimators for the AF. These estimators require one model for the outcome and one model for the exposure and are consistent if either model is correct, not necessarily both. We consider both cohort/cross-sectional studies and case–control studies. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277607 Tue, 21 Dec 2010 00:00:00 +0100 4277607 http://www.medworm.com/index.php?rid=4277606&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F102%3Frss%3D1 Time-to-event and similar analyses can be problematic if the event of interest is operationally defined by some condition being true for a prolonged period of time. A particular example of this, remission in psoriatic arthritis, is considered in detail for illustration. A 3-state model is proposed for characterizing the transition rates into and out of remission. Remission is linked to an initial and subsequent state for the purpose of introducing the condition that remission must be of some duration to be clinically meaningful. The model is compared with alternative approaches that have been used in such situations. These involve 2-state models where the duration of remission is allowed for through different definitions for the time of entry into remission. Both definitions are linked to ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277606 Tue, 21 Dec 2010 00:00:00 +0100 4277606 http://www.medworm.com/index.php?rid=4277605&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F87%3Frss%3D1 The diagnostic likelihood ratio function, DLR, is a statistical measure used to evaluate risk prediction markers. The goal of this paper is to develop new methods to estimate the DLR function. Furthermore, we show how risk prediction markers can be compared using rank-invariant DLR functions. Various estimators are proposed that accommodate cohort or case–control study designs. Performances of the estimators are compared using simulation studies. The methods are illustrated by comparing a lung function measure and a nutritional status measure for predicting subsequent onset of major pulmonary infection in children suffering from cystic fibrosis. For continuous markers, the DLR function is mathematically related to the slope of the receiver operating characteristic (ROC) curve, an ent... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277605 Tue, 21 Dec 2010 00:00:00 +0100 4277605 http://www.medworm.com/index.php?rid=4277604&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F68%3Frss%3D1 We use the term "index predictor" to denote a score that consists of K binary rules such as "age > 60" or "blood pressure > 120 mm Hg." The index predictor is the sum of these binary scores, yielding a value from 0 to K. Such indices as often used in clinical studies to stratify population risk: They are usually derived from subject area considerations. In this paper, we propose a fast data-driven procedure for automatically constructing such indices for linear, logistic, and Cox regression models. We also extend the procedure to create indices for detecting treatment–marker interactions. The methods are illustrated on a study with protein biomarkers as well as a large microarray gene expression study. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277604 Tue, 21 Dec 2010 00:00:00 +0100 4277604 http://www.medworm.com/index.php?rid=4277603&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F51%3Frss%3D1 The analysis of large data sets of standardized mortality ratios (SMRs), obtained by collecting observed and expected disease counts in a map of contiguous regions, is a first step in descriptive epidemiology to detect potential environmental risk factors. A common situation arises when counts are collected in small areas, that is, where the expected count is very low, and disease risks underlying the map are spatially correlated. Traditional p-value–based methods, which control the false discovery rate (FDR) by means of Poisson p-values, might achieve small sensitivity in identifying risk in small areas. This problem is the focus of the present work, where a Bayesian approach which performs a test to evaluate the null hypothesis of no risk over each SMR and controls the posterior FD... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277603 Tue, 21 Dec 2010 00:00:00 +0100 4277603 http://www.medworm.com/index.php?rid=4277602&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F33%3Frss%3D1 Submicroscopic changes in chromosomal DNA copy number dosage are common and have been implicated in many heritable diseases and cancers. Recent high-throughput technologies have a resolution that permits the detection of segmental changes in DNA copy number that span thousands of base pairs in the genome. Genomewide association studies (GWAS) may simultaneously screen for copy number phenotype and single nucleotide polymorphism (SNP) phenotype associations as part of the analytic strategy. However, genomewide array analyses are particularly susceptible to batch effects as the logistics of preparing DNA and processing thousands of arrays often involves multiple laboratories and technicians, or changes over calendar time to the reagents and laboratory equipment. Failure to adjust for batch e... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277602 Tue, 21 Dec 2010 00:00:00 +0100 4277602 http://www.medworm.com/index.php?rid=4277601&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F18%3Frss%3D1 A major goal of genetic association studies concerned with single nucleotide polymorphisms (SNPs) is the detection of SNPs exhibiting an impact on the risk of developing a disease. Typically, this problem is approached by testing each of the SNPs individually. This, however, can lead to an inaccurate measurement of the influence of the SNPs on the disease risk, in particular, if SNPs only show an effect when interacting with other SNPs, as the multivariate structure of the data is ignored. In this article, we propose a testing procedure based on logic regression that takes this structure into account and therefore enables a more appropriate quantification of importance and ranking of the SNPs than marginal testing. Since even SNP interactions often exhibit only a moderate effect on the dis... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277601 Tue, 21 Dec 2010 00:00:00 +0100 4277601 http://www.medworm.com/index.php?rid=4277600&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F12%2F1%2F1%3Frss%3D1 Interpretability and power of genome-wide association studies can be increased by imputing unobserved genotypes, using a reference panel of individuals genotyped at higher marker density. For many markers, genotypes cannot be imputed with complete certainty, and the uncertainty needs to be taken into account when testing for association with a given phenotype. In this paper, we compare currently available methods for testing association between uncertain genotypes and quantitative traits. We show that some previously described methods offer poor control of the false-positive rate (FPR), and that satisfactory performance of these methods is obtained only by using ad hoc filtering rules or by using a harsh transformation of the trait under study. We propose new methods that are based on exac... Biostatistics journals http://www.medworm.com/rss/comments.php?id=4277600 Tue, 21 Dec 2010 00:00:00 +0100 4277600 http://www.medworm.com/index.php?rid=3902660&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F787%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902660 Wed, 25 Aug 2010 10:07:12 +0100 3902660 http://www.medworm.com/index.php?rid=3902659&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F771%3Frss%3D1 Generalized linear mixed models have become a frequently used tool for the analysis of non-Gaussian longitudinal data. Estimation is often based on maximum likelihood theory, which assumes that the underlying probability model is correctly specified. Recent research shows that the results obtained from these models are not always robust against departures from the assumptions on which they are based. Therefore, diagnostic tools for the detection of model misspecifications are of the utmost importance. In this paper, we propose 2 diagnostic tests that are based on 2 equivalent representations of the model information matrix. We evaluate the power of both tests using theoretical considerations as well as via simulation. In the simulations, the performance of the new tools is evaluated in man... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902659 Wed, 25 Aug 2010 10:07:12 +0100 3902659 http://www.medworm.com/index.php?rid=3902658&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F756%3Frss%3D1 Structural mean models (SMMs) were originally formulated to estimate causal effects among those selecting treatment in randomized controlled trials affected by nonignorable noncompliance. It has already been established that SMMs can identify these causal effects in randomized placebo-controlled trials under fairly weak assumptions. SMMs are now being used to analyze other types of study where identification depends on a no effect modification assumption. We highlight how this assumption depends crucially on the unknown causal model that generated the data, and so is difficult to justify. However, we also highlight that, if treatment selection is monotonic, additive and multiplicative SMMs do identify local (or complier) causal effects, but that the double-logistic SMM estimator does not w... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902658 Wed, 25 Aug 2010 10:07:12 +0100 3902658 http://www.medworm.com/index.php?rid=3902657&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F741%3Frss%3D1 Forecasting the length of the menstrual cycle and of its phases is an important problem in infertility management and natural family planning. Using repeated measurements of the length of the entire cycle and of the preovular phase provided by a large English database, we describe a Bayesian hierarchical dynamic approach to the problem. A state-space process is used to model the temporal behavior of the series of lengths for each woman. The individual processes are then embedded into a multivariate system through a Bayesian hierarchy in which model parameters are allowed to vary across subjects according to a specified probability distribution. The most interesting features of the suggested method are (a) it takes into account explicitly the temporal nature of the available data and (b) if... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902657 Wed, 25 Aug 2010 10:07:12 +0100 3902657 http://www.medworm.com/index.php?rid=3902656&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F720%3Frss%3D1 We present a spatial–temporal statistical model for quantifying spatial misalignment error and show how adjusted health risk estimates can be obtained using a regression calibration approach and a 2-stage Bayesian model. We apply our methods to a database containing information on hospital admissions, air pollution, and weather for 20 large urban counties in the United States. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902656 Wed, 25 Aug 2010 10:07:12 +0100 3902656 http://www.medworm.com/index.php?rid=3902655&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F707%3Frss%3D1 There are many more strategies for early detection of cancer than can be evaluated with randomized trials. Consequently, model-projected outcomes under different strategies can be useful for developing cancer control policy provided that the projections are representative of the population. To project population-representative disease progression outcomes and to demonstrate their value in assessing competing early detection strategies, we implement a model linking prostate-specific antigen (PSA) levels and prostate cancer progression and calibrate it to disease incidence in the US population. PSA growth is linear on the logarithmic scale with a higher slope after disease onset and with random effects on intercepts and slopes; parameters are estimated using data from the Prostate Cancer Pre... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902655 Wed, 25 Aug 2010 10:07:12 +0100 3902655 http://www.medworm.com/index.php?rid=3902654&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F693%3Frss%3D1 The nested case–control (NCC) design is a cost-effective sampling method to study the relationship between a disease and its risk factors in epidemiologic studies. NCC data are commonly analyzed using Thomas' partial likelihood approach under Cox's proportional hazards model with constant covariate effects. Here, we are interested in studying the potential time-varying effects of covariates in NCC studies and propose an estimation approach based on a kernel-weighted Thomas' partial likelihood. We establish asymptotic properties of the proposed estimator, propose a numerical approach to construct simultaneous confidence bands for time-varying coefficients, and develop a hypothesis testing procedure to detect time-varying coefficients. The proposed inference procedure is evaluated in s... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902654 Wed, 25 Aug 2010 10:07:12 +0100 3902654 http://www.medworm.com/index.php?rid=3902653&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F676%3Frss%3D1 While the commonly used log-rank test for survival times between 2 groups enjoys many desirable properties, sometimes the log-rank test and its related linear rank tests perform poorly when sample sizes are small. Similar concerns apply to interval estimates for treatment differences in this setting, though their properties are less well known. Standard permutation tests are one option, but these are not in general valid when the underlying censoring distributions in the comparison groups are unequal. We develop 2 methods for testing and interval estimation, for use with small samples and possibly unequal censoring, based on first imputing survival and censoring times and then applying permutation methods. One provides a heuristic justification for the approach proposed recently by Heinze ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902653 Wed, 25 Aug 2010 10:07:11 +0100 3902653 http://www.medworm.com/index.php?rid=3902652&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F674%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902652 Wed, 25 Aug 2010 10:07:11 +0100 3902652 http://www.medworm.com/index.php?rid=3902651&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F661%3Frss%3D1 Homer and others (2008. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genetics 4, e1000167) recently showed that, given allele frequency data for a large number of single nucleotide polymorphisms in a sample together with corresponding population "reference" frequencies, by typing an individual's DNA sample at the same set of loci it can be inferred whether or not the individual was a member of the sample. This observation has been responsible for precautionary removal of large amounts of summary data from public access. This and further work on the problem has followed a frequentist approach. This paper sets out a Bayesian analysis of this problem which clarifies the role of the reference frequencies ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902651 Wed, 25 Aug 2010 10:07:11 +0100 3902651 http://www.medworm.com/index.php?rid=3902650&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F644%3Frss%3D1 Missing data is a recurrent issue in epidemiology where the infection process may be partially observed. Approximate Bayesian computation (ABC), an alternative to data imputation methods such as Markov chain Monte Carlo (MCMC) integration, is proposed for making inference in epidemiological models. It is a likelihood-free method that relies exclusively on numerical simulations. ABC consists in computing a distance between simulated and observed summary statistics and weighting the simulations according to this distance. We propose an original extension of ABC to path-valued summary statistics, corresponding to the cumulated number of detections as a function of time. For a standard compartmental model with Suceptible, Infectious and Recovered individuals (SIR), we show that the posterior d... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902650 Wed, 25 Aug 2010 10:07:11 +0100 3902650 http://www.medworm.com/index.php?rid=3902649&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F631%3Frss%3D1 Neuron branching patterns can characterize neural cell types and act as markers for neurodegenerative disease and neural development. We develop a hybrid Markovian model for neural branching that extends previously published models by (i) using a discretized gamma model to account for underdispersion in primary branching, (ii) incorporating both bifurcation and trifurcation branching events to accommodate observed data, and (iii) only requiring branch counts and not branching topology as observations, allowing larger numbers of neurons to be sampled than in previous literature. Inference for primary branching is achieved through a gamma generalized linear model. Due to incomplete data, bifurcation and trifurcation probabilities are estimated using an expectation–maximization algorith... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902649 Wed, 25 Aug 2010 10:07:11 +0100 3902649 http://www.medworm.com/index.php?rid=3902648&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F609%3Frss%3D1 Some methods for the statistical analysis of surface shapes and asymmetry are introduced. We focus on a case study where magnetic resonance images of the brain are available from groups of 30 schizophrenia patients and 38 controls, and we investigate large-scale brain surface shape differences. Key aspects of shape analysis are to remove nuisance transformations by registration and to identify which parts of one object correspond with the parts of another object. We introduce maximum likelihood and Bayesian methods for registering brain images and providing large-scale correspondences of the brain surfaces. Brain surface size-and-shape analysis is considered using random field theory, and also dimension reduction is carried out using principal and independent components analysis. Some smal... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902648 Wed, 25 Aug 2010 10:07:11 +0100 3902648 http://www.medworm.com/index.php?rid=3902647&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F599%3Frss%3D1 In many high-dimensional microarray classification problems, an important task is to identify subsets of genes that best discriminate the classes. Nevertheless, existing gene selection methods for microarray classification cannot identify which classes are discriminable by these selected genes. In this paper, we propose an improved linear discriminant analysis (LDA) method that simultaneously selects important genes and identifies the discriminable classes. Specifically, a pairwise fusion penalty for LDA was used to shrink the differences of the class centroids in pairs for each variable and fuse the centroids of indiscriminable classes altogether. The numerical results in analyzing 2 gene expression profiles demonstrate the proposed approach help improve the interpretation of important ge... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902647 Wed, 25 Aug 2010 10:07:11 +0100 3902647 http://www.medworm.com/index.php?rid=3902646&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F4%2F583%3Frss%3D1 Missing data arise in genetic association studies when genotypes are unknown or when haplotypes are of direct interest. We provide a general likelihood-based framework for making inference on genetic effects and gene–environment interactions with such missing data. We allow genetic and environmental variables to be correlated while leaving the distribution of environmental variables completely unspecified. We consider 3 major study designs—cross-sectional, case–control, and cohort designs—and construct appropriate likelihood functions for all common phenotypes (e.g. case–control status, quantitative traits, and potentially censored ages at onset of disease). The likelihood functions involve both finite- and infinite-dimensional parameters. The maximum likeliho... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3902646 Wed, 25 Aug 2010 10:07:11 +0100 3902646 http://www.medworm.com/index.php?rid=3652057&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F572%3Frss%3D1 When estimating the association between an exposure and outcome, a simple approach to quantifying the amount of confounding by a factor, Z, is to compare estimates of the exposure–outcome association with and without adjustment for Z. This approach is widely believed to be problematic due to the nonlinearity of some exposure-effect measures. When the expected value of the outcome is modeled as a nonlinear function of the exposure, the adjusted and unadjusted exposure effects can differ even in the absence of confounding (Greenland , Robins, and Pearl, 1999); we call this the nonlinearity effect. In this paper, we propose a corrected measure of confounding that does not include the nonlinearity effect. The performances of the simple and corrected estimates of confounding are assessed ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652057 Thu, 10 Jun 2010 14:56:59 +0100 3652057 http://www.medworm.com/index.php?rid=3652056&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F559%3Frss%3D1 Human fecundability is defined as the probability of conception during a menstrual cycle among couples at risk for pregnancy. It is highly relevant for understanding human reproduction and represents a series of highly interrelated and timed processes. The statistical literature has recognized the need to incorporate both biological and behavioral factors (Barrett and Marshall, 1969; Dunson and Stanford, 2005) when modeling conception probabilities, given that intercourse during the fertile window is a necessary but not sufficient criterion for conception. The heterogeneity of behaviors such as the timing and frequency of intercourse in a menstrual cycle needs to be considered when estimating conception. Here we propose a joint model of intercourse behavior and human fecundability through ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652056 Thu, 10 Jun 2010 14:56:59 +0100 3652056 http://www.medworm.com/index.php?rid=3652055&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F546%3Frss%3D1 With clinical trials under pressure to produce more convincing results faster, we reexamine relative efficiencies for the semiparametric comparison of cause-specific rather than all-cause mortality events, observing that in many settings misclassification of cause of failure is not negligible. By incorporating known misclassification rates, we derive an adapted logrank test that optimizes power when the alternative treatment effect is confined to the cause-specific hazard. We derive sample size calculations for this test as well as for the corresponding all-cause mortality and naive cause-specific logrank test which ignores the misclassification. This may lead to new options at the design stage which we discuss. We reexamine a recently closed vaccine trial in this light and find the sample... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652055 Thu, 10 Jun 2010 14:56:59 +0100 3652055 http://www.medworm.com/index.php?rid=3652054&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F537%3Frss%3D1 We introduce a dose-finding algorithm to be used to identify a level of dose that corresponds to some given targeted response. Our motivation arises from problems where the response is a continuously measured quantity, typically some pharmacokinetic parameter. We consider the case where an agreed level of response has been determined from earlier studies on some population and the purpose of the current trial is to obtain the same, or a comparable, level of response in a new population. This relates to bridging studies. The example driving our interest comes from studies on drugs for HIV that have already been evaluated in adults and where the new studies are to be carried out in children. These drugs have the ability to produce some given mean pharmacokinetic response in the adult populat... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652054 Thu, 10 Jun 2010 14:56:59 +0100 3652054 http://www.medworm.com/index.php?rid=3652053&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F533%3Frss%3D1 The biological complexity of gene expression makes simulation of gene expression data difficult. We propose a spike-in simulation that adds a single simulated gene to the data set of interest. Features of this spike-in gene may be manipulated to observe how often the spiked-in gene appears in the list of differentially expressed genes. This approach provides insight into the data analysis method, the observed data, and the manner in which the method and data interact without relying on indefensible assumptions regarding gene coexpression. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652053 Thu, 10 Jun 2010 14:56:59 +0100 3652053 http://www.medworm.com/index.php?rid=3652052&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F519%3Frss%3D1 We propose a formal statistical inference framework for the evaluation of the penetrance of a rare genetic mutation using family data generated under a kin–cohort type of design, where phenotype and genotype information from first-degree relatives (sibs and/or offspring) of case probands carrying the targeted mutation are collected. Our approach is built upon a likelihood model with some minor assumptions, and it can be used for age-dependent penetrance estimation that permits adjustment for covariates. Furthermore, the derived likelihood allows unobserved risk factors that are correlated within family members. The validity of the approach is confirmed by simulation studies. We apply the proposed approach to estimating the age-dependent cancer risk among carriers of the MSH2 or MLH1 ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652052 Thu, 10 Jun 2010 14:56:59 +0100 3652052 http://www.medworm.com/index.php?rid=3652051&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F515%3Frss%3D1 Array comparative genomic hybridization (aCGH) is a microarray technology that allows one to detect and map genomic alterations. The standard workflow of the aCGH data analysis consists of 2 steps: detecting the boundaries of the regions of changed copy number by means of a segmentation algorithm (break point identification) and then labeling each region as loss, neutral, or gain with a probabilistic framework (calling procedure). In this paper, we introduce a novel calling procedure based on a mixture of truncated normal distributions, named FastCall, that aims to give aberration probabilities to segmented aCGH data in a very fast and accurate way. Both on synthetic and real aCGH data, FastCall obtains excellent performances in terms of classification accuracy and running time. (Source: B... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652051 Thu, 10 Jun 2010 14:56:59 +0100 3652051 http://www.medworm.com/index.php?rid=3652050&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F499%3Frss%3D1 The DNA of most vertebrates is depleted in CpG dinucleotide: a C followed by a G in the 5' to 3' direction. CpGs are the target for DNA methylation, a chemical modification of cytosine (C) heritable during cell division and the most well-characterized epigenetic mechanism. The remaining CpGs tend to cluster in regions referred to as CpG islands (CGI). Knowing CGI locations is important because they mark functionally relevant epigenetic loci in development and disease. For various mammals, including human, a readily available and widely used list of CGI is available from the UCSC Genome Browser. This list was derived using algorithms that search for regions satisfying a definition of CGI proposed by Gardiner-Garden and Frommer more than 20 years ago. Recent findings, enabled by advances in ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652050 Thu, 10 Jun 2010 14:56:59 +0100 3652050 http://www.medworm.com/index.php?rid=3652049&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F484%3Frss%3D1 Standard regression analyses are often plagued with problems encountered when one tries to make inference going beyond main effects using data sets that contain dozens of variables that are potentially correlated. This situation arises, for example, in epidemiology where surveys or study questionnaires consisting of a large number of questions yield a potentially unwieldy set of interrelated data from which teasing out the effect of multiple covariates is difficult. We propose a method that addresses these problems for categorical covariates by using, as its basic unit of inference, a profile formed from a sequence of covariate values. These covariate profiles are clustered into groups and associated via a regression model to a relevant outcome. The Bayesian clustering aspect of the propos... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652049 Thu, 10 Jun 2010 14:56:59 +0100 3652049 http://www.medworm.com/index.php?rid=3652048&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F473%3Frss%3D1 When testing multiple hypotheses simultaneously, there is a need to adjust the levels of the individual tests to effect control of the family-wise error rate (FWER). Standard frequentist adjustments control the error rate but are typically both conservative and oblivious to prior information. We propose a Bayesian testing approach—multiplicity-calibrated Bayesian hypothesis testing—that sets individual critical values to reflect prior information while controlling the FWER via the Bonferroni inequality. If the prior information is specified correctly, in the sense that those null hypotheses considered most likely to be false in fact are false, the power of our method is substantially greater than that of standard frequentist approaches. We illustrate our method using data from ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652048 Thu, 10 Jun 2010 14:56:59 +0100 3652048 http://www.medworm.com/index.php?rid=3652047&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F453%3Frss%3D1 Missing observations are commonplace in longitudinal data. We discuss how to model and analyze such data in a dynamic framework, that is, taking into consideration the time structure of the process and the influence of the past on the present and future responses. An autoregressive model is used as a special case of the linear increments model defined by Farewell (2006. Linear models for censored data, [PhD Thesis]. Lancaster University) and Diggle and others (2007. Analysis of longitudinal data with drop-out: objectives, assumptions and a proposal. Journal of the Royal Statistical Society, Series C (Applied Statistics, 56, 499–550). We wish to reconstruct responses for missing data and discuss the required assumptions needed for both monotone and nonmonotone missingness. The computa... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652047 Thu, 10 Jun 2010 14:56:59 +0100 3652047 http://www.medworm.com/index.php?rid=3652046&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F432%3Frss%3D1 Frequently, exposure data are measured over time on a grid of discrete values that collectively define a functional observation. In many applications, researchers are interested in using these measurements as covariates to predict a scalar response in a regression setting, with interest focusing on the most biologically relevant time window of exposure. One example is in panel studies of the health effects of particulate matter (PM), where particle levels are measured over time. In such studies, there are many more values of the functional data than observations in the data set so that regularization of the corresponding functional regression coefficient is necessary for estimation. Additional issues in this setting are the possibility of exposure measurement error and the need to incorpor... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652046 Thu, 10 Jun 2010 14:56:59 +0100 3652046 http://www.medworm.com/index.php?rid=3652045&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F419%3Frss%3D1 This article proposes a Bayesian nonparametric approach to this problem based on characterizing the conditional response density as a Gaussian mixture, with the locations of the Gaussian means varying flexibly with predictors subject to minimal constraints to ensure stochastic ordering. Theoretical properties are considered and Markov chain Monte Carlo methods are developed for posterior computation. The methods are illustrated using simulation examples and a reproductive epidemiology application. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652045 Thu, 10 Jun 2010 14:56:59 +0100 3652045 http://www.medworm.com/index.php?rid=3652044&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F413%3Frss%3D1 With the analysis of complex, messy data sets, the statistics community has recently focused attention on "reproducible research," namely research that can be readily replicated by others. One standard that has been proposed is the availability of data sets and computer code. However, in some situations, raw data cannot be disseminated for reasons of confidentiality or because the data are so messy as to make dissemination impractical. For one such situation, we propose 2 steps for reproducible research: (i) presentation of a table of data and (ii) presentation of a formula to estimate key quantities from the table of data. We illustrate this strategy in the analysis of data from the Prostate Cancer Prevention Trial, which investigated the effect of the drug finasteride versus placebo on t... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652044 Thu, 10 Jun 2010 14:56:59 +0100 3652044 http://www.medworm.com/index.php?rid=3652043&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F397%3Frss%3D1 Generalized linear mixed models (GLMMs) continue to grow in popularity due to their ability to directly acknowledge multiple levels of dependency and model different data types. For small sample sizes especially, likelihood-based inference can be unreliable with variance components being particularly difficult to estimate. A Bayesian approach is appealing but has been hampered by the lack of a fast implementation, and the difficulty in specifying prior distributions with variance components again being particularly problematic. Here, we briefly review previous approaches to computation in Bayesian implementations of GLMMs and illustrate in detail, the use of integrated nested Laplace approximations in this context. We consider a number of examples, carefully specifying prior distributions ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652043 Thu, 10 Jun 2010 14:56:59 +0100 3652043 http://www.medworm.com/index.php?rid=3652042&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F395%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652042 Thu, 10 Jun 2010 14:56:59 +0100 3652042 http://www.medworm.com/index.php?rid=3652041&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F393%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652041 Thu, 10 Jun 2010 14:56:59 +0100 3652041 http://www.medworm.com/index.php?rid=3652040&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F391%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652040 Thu, 10 Jun 2010 14:56:58 +0100 3652040 http://www.medworm.com/index.php?rid=3652039&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F389%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652039 Thu, 10 Jun 2010 14:56:58 +0100 3652039 http://www.medworm.com/index.php?rid=3652038&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F385%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652038 Thu, 10 Jun 2010 14:56:58 +0100 3652038 http://www.medworm.com/index.php?rid=3652037&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F383%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652037 Thu, 10 Jun 2010 14:56:58 +0100 3652037 http://www.medworm.com/index.php?rid=3652036&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F381%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652036 Thu, 10 Jun 2010 14:56:58 +0100 3652036 http://www.medworm.com/index.php?rid=3652034&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F376%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652034 Thu, 10 Jun 2010 14:56:58 +0100 3652034 http://www.medworm.com/index.php?rid=3652033&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F3%2F375%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3652033 Thu, 10 Jun 2010 14:56:58 +0100 3652033 http://www.medworm.com/index.php?rid=3321942&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F373%3Frss%3D1 When analyzing a 2 x 2 table, the two-sided Fisher's exact test and the usual exact confidence interval (CI) for the odds ratio may give conflicting inferences; for example, the test rejects but the associated CI contains an odds ratio of 1. The problem is that the usual exact CI is the inversion of the test that rejects if either of the one-sided Fisher's exact tests rejects at half the nominal significance level. Further, the confidence set that is the inversion of the usual two-sided Fisher's exact test may not be an interval, so following Blaker (2000, Confidence curves and improved exact confidence intervals for discrete distributions. Canadian Journal of Statistics 28, 783–798), we define the "matching" interval as the smallest interval that contains the confidence set. We expl... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321942 Tue, 02 Mar 2010 08:05:32 +0100 3321942 http://www.medworm.com/index.php?rid=3321941&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F353%3Frss%3D1 Most investigations in the social and health sciences aim to understand the directional or causal relationship between a treatment or risk factor and outcome. Given the multitude of pathways through which the treatment or risk factor may affect the outcome, there is also an interest in decomposing the effect of a treatment of risk factor into "direct" and "mediated" effects. For example, child's socioeconomic status (risk factor) may have a direct effect on the risk of death (outcome) and an effect that may be mediated through the adulthood socioeconomic status (mediator). Building on the potential outcome framework for causal inference, we develop a Bayesian approach for estimating direct and mediated effects in the context of a dichotomous mediator and dichotomous outcome, which is chall... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321941 Tue, 02 Mar 2010 08:05:32 +0100 3321941 http://www.medworm.com/index.php?rid=3321940&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F337%3Frss%3D1 Quantile regression has emerged as a useful supplement to ordinary mean regression. Traditional frequentist quantile regression makes very minimal assumptions on the form of the error distribution and thus is able to accommodate nonnormal errors, which are common in many applications. However, inference for these models is challenging, particularly for clustered or censored data. A Bayesian approach enables exact inference and is well suited to incorporate clustered, missing, or censored data. In this paper, we propose a flexible Bayesian quantile regression model. We assume that the error distribution is an infinite mixture of Gaussian densities subject to a stochastic constraint that enables inference on the quantile of interest. This method outperforms the traditional frequentist method... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321940 Tue, 02 Mar 2010 08:05:32 +0100 3321940 http://www.medworm.com/index.php?rid=3321939&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F317%3Frss%3D1 Skew-normal and skew-t distributions have proved to be useful for capturing skewness and kurtosis in data directly without transformation. Recently, finite mixtures of such distributions have been considered as a more general tool for handling heterogeneous data involving asymmetric behaviors across subpopulations. We consider such mixture models for both univariate as well as multivariate data. This allows robust modeling of high-dimensional multimodal and asymmetric data generated by popular biotechnological platforms such as flow cytometry. We develop Bayesian inference based on data augmentation and Markov chain Monte Carlo (MCMC) sampling. In addition to the latent allocations, data augmentation is based on a stochastic representation of the skew-normal distribution in terms of a rand... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321939 Tue, 02 Mar 2010 08:05:32 +0100 3321939 http://www.medworm.com/index.php?rid=3321938&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F304%3Frss%3D1 Continuous-time Markov processes are frequently used to describe the evolution of a disease over different phases. Such modeling can provide estimates for important parameters that are defined on the paths of the process. A simple example is the mean first hitting time to a set of states. However, more interesting events are defined by several time points such as the first time the process stays in state j for at least time units. These kinds of events are very important in relapsing–remitting diseases such as in multiple sclerosis (MS) where the focus is on a sustained worsening that lasts 6 months or longer. The current paper considers data on independent continuous Markov processes that are only observed intermittently. It reviews modeling and estimation, presents a new general co... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321938 Tue, 02 Mar 2010 08:05:32 +0100 3321938 http://www.medworm.com/index.php?rid=3321937&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F290%3Frss%3D1 The competing risks illness–death model describes the dynamics of healthy subjects who may move to an "illness" state before entering into one of several competing terminal states. A motivating example concerns patients in a hospital who may acquire infections during their stay, where the competing terminal states are discharged alive and death in the hospital. We consider a cross-sectional sampling of independent competing risks illness–death processes in which data are subject to length bias and censoring and develop estimators for functionals of the underlying distribution such as the joint probability of the terminal state and illness (infection) and cumulative incidence functions. We apply the methodology to infection data obtained in a cross-sectional study of patients ho... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321937 Tue, 02 Mar 2010 08:05:32 +0100 3321937 http://www.medworm.com/index.php?rid=3321936&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F281%3Frss%3D1 The main purpose of microarray studies is screening to identify differentially expressed genes as candidates for further investigation. Because of limited resources in this stage, prioritizing or ranking genes is a relevant statistical task in microarray studies. In this article, we develop 3 empirical Bayes methods for gene ranking on the basis of differential expression, using hierarchical mixture models. These methods are based on (i) minimizing mean squared errors of estimation for parameters, (ii) minimizing mean squared errors of estimation for ranks of parameters, and (iii) maximizing sensitivity in selecting prespecified numbers of differential genes, with the largest effect. Our methods incorporate the mixture structures of differential and nondifferential components in empirical ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321936 Tue, 02 Mar 2010 08:05:32 +0100 3321936 http://www.medworm.com/index.php?rid=3321935&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F265%3Frss%3D1 Array comparative genomic hybridization (aCGH) is a microarray technology that allows one to detect and map genomic alterations. The goal of aCGH analysis is to identify the boundaries of the regions where the number of DNA copies changes (breakpoint identification) and then to label each region as loss, neutral, or gain (calling). In this paper, we introduce a new algorithm, based on the shifting level model (SLM), with the aim of locating regions with different means of the log2 ratio in genomic profiles obtained from aCGH data. We combine the SLM algorithm with the CGHcall calling procedure and compare their performances with 5 state-of-the-art methods. When dealing with synthetic data, our method outperforms the other 5 algorithms in detecting the change in the number of DNA copies in ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321935 Tue, 02 Mar 2010 08:05:32 +0100 3321935 http://www.medworm.com/index.php?rid=3321934&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F254%3Frss%3D1 Microarray experiments provide data on the expression levels of thousands of genes and, therefore, statistical methods applicable to the analysis of such high-dimensional data are needed. In this paper, we propose robust nonparametric tools for the description and analysis of microarray data based on the concept of functional depth, which measures the centrality of an observation within a sample. We show that this concept can be easily adapted to high-dimensional observations and, in particular, to gene expression data. This allows the development of the following depth-based inference tools: (1) a scale curve for measuring and visualizing the dispersion of a set of points, (2) a rank test for deciding if 2 groups of multidimensional observations come from the same population, and (3) supe... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321934 Tue, 02 Mar 2010 08:05:32 +0100 3321934 http://www.medworm.com/index.php?rid=3321933&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F242%3Frss%3D1 Robust multiarray analysis (RMA) is the most widely used preprocessing algorithm for Affymetrix and Nimblegen gene expression microarrays. RMA performs background correction, normalization, and summarization in a modular way. The last 2 steps require multiple arrays to be analyzed simultaneously. The ability to borrow information across samples provides RMA various advantages. For example, the summarization step fits a parametric model that accounts for probe effects, assumed to be fixed across arrays, and improves outlier detection. Residuals, obtained from the fitted model, permit the creation of useful quality metrics. However, the dependence on multiple arrays has 2 drawbacks: (1) RMA cannot be used in clinical settings where samples must be processed individually or in small batches a... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321933 Tue, 02 Mar 2010 08:05:32 +0100 3321933 http://www.medworm.com/index.php?rid=3321932&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F226%3Frss%3D1 Accurate knowledge of the null distribution of hypothesis tests is important for valid application of the tests. In previous papers and software, the asymptotic null distribution of likelihood ratio tests for detecting genetic linkage in multivariate variance components models has been stated to be a mixture of chi-square distributions with binomial mixing probabilities. For variance components models under the complete pleiotropy assumption, we show by simulation and by theoretical arguments based on the geometry of the parameter space that all aspects of the previously stated asymptotic null distribution are incorrect—both the binomial mixing probabilities and the chi-square components. Correcting the null distribution gives more conservative critical values than previously stated,... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321932 Tue, 02 Mar 2010 08:05:32 +0100 3321932 http://www.medworm.com/index.php?rid=3321931&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F213%3Frss%3D1 We develop a locally efficient test for (multiplicative) gene–environment interaction in family studies that collect genotypic information and environmental exposures for affected offspring along with genotypic information for their parents or relatives. The proposed test does not require modeling the effects of environmental exposures and is doubly robust in the sense of being valid if either a model for the main genetic effect holds or a model for the expected environmental exposure (given the offspring affection status and parental mating types) but not necessarily both. It extends the FBAT-I to allow for missing parental mating types and families of arbitrary size. Simulation studies and the analysis of an Alzheimer's disease study confirm the adequate performance of the proposed... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321931 Tue, 02 Mar 2010 08:05:32 +0100 3321931 http://www.medworm.com/index.php?rid=3321930&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F195%3Frss%3D1 Boosting is an important tool in classification methodology. It combines the performance of many weak classifiers to produce a powerful committee, and its validity can be explained by additive modeling and maximum likelihood. The method has very general applications, especially for high-dimensional predictors. For example, it can be applied to distinguish cancer samples from healthy control samples by using antibody microarray data. Microarray data are often high-dimensional and many of them are incomplete. One natural idea is to impute a missing variable based on the observed predictors. However, the calculation of imputation for high-dimensional predictors with missing data may be rather tedious. In this paper, we propose 2 conditional mean imputation methods. They can be applied to the ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321930 Tue, 02 Mar 2010 08:05:32 +0100 3321930 http://www.medworm.com/index.php?rid=3321929&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F2%2F177%3Frss%3D1 We propose a new methodological framework for the analysis of hierarchical functional data when the functions at the lowest level of the hierarchy are correlated. For small data sets, our methodology leads to a computational algorithm that is orders of magnitude more efficient than its closest competitor (seconds versus hours). For large data sets, our algorithm remains fast and has no current competitors. Thus, in contrast to published methods, we can now conduct routine simulations, leave-one-out analyses, and nonparametric bootstrap sampling. Our methods are inspired by and applied to data obtained from a state-of-the-art colon carcinogenesis scientific experiment. However, our models are general and will be relevant to many new data sets where the object of inference are functions or i... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3321929 Tue, 02 Mar 2010 08:05:32 +0100 3321929 http://www.medworm.com/index.php?rid=3100236&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F176%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100236 Thu, 17 Dec 2009 17:19:24 +0100 3100236 http://www.medworm.com/index.php?rid=3100235&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F164%3Frss%3D1 High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell line... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100235 Thu, 17 Dec 2009 17:19:24 +0100 3100235 http://www.medworm.com/index.php?rid=3100234&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F151%3Frss%3D1 Before a comparative diagnostic trial is carried out, maximum sample sizes for the diseased group and the nondiseased group need to be obtained to achieve a nominal power to detect a meaningful difference in diagnostic accuracy. Sample size calculation depends on the variance of the statistic of interest, which is the difference between receiver operating characteristic summary measures of 2 medical diagnostic tests. To obtain an appropriate value for the variance, one often has to assume an arbitrary parametric model and the associated parameter values for the 2 groups of subjects under 2 tests to be compared. It becomes more tedious to do so when the same subject undergoes 2 different tests because the correlation is then involved in modeling the test outcomes. The calculated variance ba... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100234 Thu, 17 Dec 2009 17:19:24 +0100 3100234 http://www.medworm.com/index.php?rid=3100233&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F139%3Frss%3D1 Genome-wide association studies (GWAS) are increasingly utilized for identifying novel susceptible genetic variants for complex traits, but there is little consensus on analysis methods for such data. Most commonly used methods include single single nucleotide polymorphism (SNP) analysis or haplotype analysis with Bonferroni correction for multiple comparisons. Since the SNPs in typical GWAS are often in linkage disequilibrium (LD), at least locally, Bonferroni correction of multiple comparisons often leads to conservative error control and therefore lower statistical power. In this paper, we propose a hidden Markov random field model (HMRF) for GWAS analysis based on a weighted LD graph built from the prior LD information among the SNPs and an efficient iterative conditional mode algorith... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100233 Thu, 17 Dec 2009 17:19:24 +0100 3100233 http://www.medworm.com/index.php?rid=3100232&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F127%3Frss%3D1 Longitudinal data with binary and ordinal outcomes routinely appear in medical applications. Existing methods are typically designed to deal with short measurement series. In contrast, modern longitudinal data can result in large numbers of subject-specific serial observations. In this framework, we consider multivariate probit models with random effects to capture heterogeneity and autoregressive terms for describing the serial dependence. Since likelihood inference for the proposed class of models is computationally burdensome because of high-dimensional intractable integrals, a pseudolikelihood approach is followed. The methodology is motivated by the analysis of a large longitudinal study on the determinants of migraine severity. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100232 Thu, 17 Dec 2009 17:19:24 +0100 3100232 http://www.medworm.com/index.php?rid=3100231&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F111%3Frss%3D1 In epidemiological and clinical studies, time-to-event data often violate the assumptions of Cox regression due to the presence of time-dependent covariate effects and unmeasured risk factors. An alternative approach, which does not require proportional hazards, is to use a first hitting time model which treats a subject's health status as a latent stochastic process that fails when it reaches a threshold value. Although more flexible than Cox regression, existing methods do not account for unmeasured covariates in both the initial state and the rate of the process. To address this issue, we propose a Bayesian methodology that models an individual's health status as a Wiener process with subject-specific initial state and drift. Posterior inference proceeds via a Markov chain Monte Carlo m... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100231 Thu, 17 Dec 2009 17:19:23 +0100 3100231 http://www.medworm.com/index.php?rid=3100230&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F93%3Frss%3D1 Dropout is a common occurrence in longitudinal studies. Building upon the pattern-mixture modeling approach within the Bayesian paradigm, we propose a general framework of varying-coefficient models for longitudinal data with informative dropout, where measurement times can be irregular and dropout can occur at any point in continuous time (not just at observation times) together with administrative censoring. Specifically, we assume that the longitudinal outcome process depends on the dropout process through its model parameters. The unconditional distribution of the repeated measures is a mixture over the dropout (administrative censoring) time distribution, and the continuous dropout time distribution with administrative censoring is left completely unspecified. We use Markov chain Mont... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100230 Thu, 17 Dec 2009 17:19:23 +0100 3100230 http://www.medworm.com/index.php?rid=3100229&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F82%3Frss%3D1 Bandeen-Roche and Liang (2002, Modelling multivariate failure time associations in the presence of a competing risk. Biometrika 89, 299–314.) tailored Oakes (1989, Bivariate survival models induced by frailties. Journal of the American Statistical Association 84, 487–493.)'s conditional hazard ratio to evaluate cause-specific associations in bivariate competing risks data. In many population-based family studies, one observes complex multivariate competing risks data, where the family sizes may be > 2, certain marginals may be exchangeable, and there may be multiple correlated relative pairs having a given pairwise association. Methods for bivariate competing risks data are inadequate in these settings. We show that the rank correlation estimator of Bandeen-Roche and Liang (... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100229 Thu, 17 Dec 2009 17:19:23 +0100 3100229 http://www.medworm.com/index.php?rid=3100228&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F70%3Frss%3D1 Genome-wide association studies (GWAS) have become the method of choice for investigating the genetic basis of common diseases and complex traits. The immense scale of these experiments is unprecedented, involving thousands of samples and up to a million variables. The careful execution of exploratory data analysis (EDA) prior to the actual genotype–phenotype association analysis is crucial as this identifies problematic samples and poorly assayed genetic polymorphisms that, if undetected, can compromise the outcome of the experiment. EDA of such large-scale genetic data sets thus requires specialized numerical and graphical strategies, and this article provides a review of the current exploratory tools commonly used in GWAS. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100228 Thu, 17 Dec 2009 17:19:23 +0100 3100228 http://www.medworm.com/index.php?rid=3100227&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F57%3Frss%3D1 Age–period–cohort (APC) models are frequently used to analyze mortality or morbidity rates stratified by age group and period. For the case in which rates are given in different strata, multivariate APC models have been considered only recently. Such models share a set of parameters, for example, the age effects, while the other parameters may vary across strata. We show that differences of strata-specific effects are identifiable. We then propose a Bayesian approach based on smoothing priors to estimate multivariate APC models. This provides an alternative to maximum likelihood (ML) estimates of relative risk in the case of equal intervals and gives useful results even in the case of unequal intervals, where ML estimates have severe artifacts. This is illustrated with data on ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100227 Thu, 17 Dec 2009 17:19:23 +0100 3100227 http://www.medworm.com/index.php?rid=3100226&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F48%3Frss%3D1 Genetic data collected from surveys such as the Third National Health and Nutrition Examination Survey (NHANES III) enable researchers to investigate the association between wide varieties of health factors and genetic variation for the US population. Tests for trend in disease with increasing number of alleles have been developed for simple random samples. However, surveys such as the NHANES III have complex sample designs involving multistage cluster sampling and sample weighting. These types of sample designs can affect Type I error and power properties of statistical tests based on simple random samples. In order to address these issues, we have derived tests of trend based on Wald and quasi-score statistics, with and without assuming a genetic model, that account for the complex sampl... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100226 Thu, 17 Dec 2009 17:19:23 +0100 3100226 http://www.medworm.com/index.php?rid=3100225&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F34%3Frss%3D1 In the past decade, several principal stratification–based statistical methods have been developed for testing and estimation of a treatment effect on an outcome measured after a postrandomization event. Two examples are the evaluation of the effect of a cancer treatment on quality of life in subjects who remain alive and the evaluation of the effect of an HIV vaccine on viral load in subjects who acquire HIV infection. However, in general the developed methods have not addressed the issue of missing outcome data, and hence their validity relies on a missing completely at random (MCAR) assumption. Because in many applications the MCAR assumption is untenable, while a missing at random (MAR) assumption is defensible, we extend the semiparametric likelihood sensitivity analysis approac... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100225 Thu, 17 Dec 2009 17:19:23 +0100 3100225 http://www.medworm.com/index.php?rid=3100224&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F18%3Frss%3D1 This article is focused on discovering the functional diversification within a protein family. A Bayesian mixture approach is proposed to model a protein family as a mixture of profile hidden Markov models. For a given mixture size, a hybrid Markov chain Monte Carlo sampler comprising both Gibbs sampling steps and hierarchical clustering–based split/merge proposals is used to obtain posterior inference. Inference for mixture size concentrates on comparing the integrated likelihoods. The choice of priors is critical with respect to the performance of the procedure. Through simulation studies, we show that 2 priors that are based on independent data sets allow correct identification of the mixture size, both when the data are homogeneous and when the data are generated from a mixture. ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100224 Thu, 17 Dec 2009 17:19:23 +0100 3100224 http://www.medworm.com/index.php?rid=3100223&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F11%2F1%2F1%3Frss%3D1 It is our experience that in many settings, crossover trials that have within-period baseline measurements are analyzed wrongly. A "conventional" analysis of covariance in this setting uses each baseline as a covariate for the following outcome variable in the same period but not for any other outcome. If used with random subject effects such an analysis leads to biased treatment comparisons; this is an example of cross-level bias. Using a postulated covariance structure that reflects the symmetry of the crossover setting, we quantify such bias and, at the same time, investigate potential gains and losses in efficiency through the use of the baselines. We then describe alternative methods of analysis that avoid the cross-level bias. The development is illustrated throughout with 2 example ... Biostatistics journals http://www.medworm.com/rss/comments.php?id=3100223 Thu, 17 Dec 2009 17:19:23 +0100 3100223 http://www.medworm.com/index.php?rid=2788379&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F808%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788379 Thu, 10 Sep 2009 23:00:00 +0100 2788379 http://www.medworm.com/index.php?rid=2788378&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F806%3Frss%3D1 (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788378 Thu, 10 Sep 2009 23:00:00 +0100 2788378 http://www.medworm.com/index.php?rid=2788377&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F792%3Frss%3D1 In mixed treatment comparison (MTC) meta-analysis, modeling the heterogeneity in between-trial variances across studies is a difficult problem because of the constraints on the variances inherited from the MTC structure. Starting from a consistent Bayesian hierarchical model for the mean treatment effects, we represent the variance configuration by a set of triangle inequalities on the standard deviations. We take the separation strategy (Barnard and others, 2000) to specify prior distributions for standard deviations and correlations separately. The covariance matrix of the latent treatment arm effects can be employed as a vehicle to load the triangular constraints, which in addition allows incorporation of prior beliefs about the correlations between treatment effects. The spherical para... Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788377 Thu, 10 Sep 2009 23:00:00 +0100 2788377 http://www.medworm.com/index.php?rid=2788376&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F779%3Frss%3D1 The objective is to make inference for the infection rate parameters in the underlying model of disease transmission. The principal challenge is that the required likelihood of the data is intractable in all but the simplest cases. Demiris and O'Neill (2005b) used data augmentation methods involving a certain random graph in a Markov chain Monte Carlo setting to address this situation in the special case where the sample is the same as the entire population. Here, we take an approach relying on broadly similar principles, but for which the implementation details are markedly different. Specifically, to cover the general case of sample data, we use an alternative data augmentation scheme and employ noncentering methods. The methods are illustrated using data from an influenza outbreak. (Sou... Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788376 Thu, 10 Sep 2009 23:00:00 +0100 2788376 http://www.medworm.com/index.php?rid=2788375&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F773%3Frss%3D1 The number of copies of DNA in human cells can be measured using array comparative genomic hybridization (aCGH), which provides intensity ratios of sample to reference DNA at genomic locations corresponding to probes on a microarray. In the present paper, we devise a statistical model, based on a latent continuous-index Markov jump process, that is aimed to capture certain features of aCGH data, including probes that are unevenly long, unevenly spaced, and overlapping. The model has a continuous state space, with 1 state representing a normal copy number of 2, and the rest of the states being either amplifications or deletions. We adopt a Bayesian approach and apply Markov chain Monte Carlo (MCMC) methods for estimating the parameters and the Markov process. The model can be applied to dat... Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788375 Thu, 10 Sep 2009 23:00:00 +0100 2788375 http://www.medworm.com/index.php?rid=2788374&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F756%3Frss%3D1 We present methods of estimating the baseline marginal distributions, covariate effects, and association parameters for clustered current status data based on second-order generalized estimating equations. We examine the efficiency gains realized from using second-order estimating equations compared with first-order equations, issues of copula misspecification, and apply the methods to motivating studies including one on the incidence of joint damage in patients with psoriatic arthritis. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788374 Thu, 10 Sep 2009 23:00:00 +0100 2788374 http://www.medworm.com/index.php?rid=2788373&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F744%3Frss%3D1 A mixed model framework is presented to model the characteristic multivariate binary anomaly data as provided in some teratology studies. The key features of the model are the incorporation of covariate effects, a flexible random effects distribution by means of a finite mixture, and the application of copula functions to better account for the relation structure of the anomalies. The framework is motivated by data of the Boston Anticonvulsant Teratogenesis study and offers an integrated approach to investigate substantive questions, concerning general and anomaly-specific exposure effects of covariates, interrelations between anomalies, and objective diagnostic measurement. (Source: Biostatistics) Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788373 Thu, 10 Sep 2009 23:00:00 +0100 2788373 http://www.medworm.com/index.php?rid=2788372&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F729%3Frss%3D1 Interval-censored longitudinal data taken from a Norwegian study of individuals with Parkinson's disease are investigated with respect to the onset of dementia. Of interest are risk factors for dementia and the subdivision of total life expectancy (LE) into LE with and without dementia. To estimate LEs using extrapolation, a parametric continuous-time 3-state illness–death Markov model is presented in a Bayesian framework. The framework is well suited to allow for heterogeneity via random effects and to investigate additional computation using model parameters. In the estimation of LEs, microsimulation is used to take into account random effects. Intensities of moving between the states are allowed to change in a piecewise-constant fashion by linking them to age as a time-dependent c... Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788372 Thu, 10 Sep 2009 23:00:00 +0100 2788372 http://www.medworm.com/index.php?rid=2788371&cid=s_31987_79_f&fid=31987&url=http%3A%2F%2Fbiostatistics.oxfordjournals.org%2Fcgi%2Fcontent%2Fshort%2F10%2F4%2F719%3Frss%3D1 Leptospirosis is the most widespread zoonosis throughout the world and human mortality from severe disease forms is high even when optimal treatment is provided. Leptospirosis is also one of the most common causes of reproductive losses in cattle worldwide and is associated with significant economic costs to the dairy farming industry. Herds are tested for exposure to the causal organism either through serum testing of individual animals or through testing bulk milk samples. Using serum results from a commonly used enzyme-linked immunosorbent assay (ELISA) test for Leptospira interrogans serovar Hardjo (L. hardjo) on samples from 979 animals across 12 Scottish dairy herds and the corresponding bulk milk results, we develop a model that predicts the mean proportion of exposed animals in a h... Biostatistics journals http://www.medworm.com/rss/comments.php?id=2788371 Thu, 10 Sep 2009 23:00:00 +0100 2788371