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Clustered data are a special type of correlated data where units within a cluster are correlated while units between different clusters are independent. The number of units in a cluster can be associated with that cluster's outcome. This is called the informative cluster size (ICS), which is known to impact clustered data inference. However, when comparing the outcomes from multiple groups of units in clustered data, investigating ICS may not be enough. This is because the number of units belonging to a particular group in a cluster can be associated with the outcome from that group in that cluster, leading to an informative intra-cluster group size or IICGS. This phenomenon of IICGS can exist even in the absence of ICS. Ignoring the existence of IICGS can result in a biased inference for group-based outcome comparisons in clustered data. In this article, we mathematically formulate the concept of IICGS while distinguishing it from ICS and propose a nonparametric bootstrap-based statistical hypothesis-testing mechanism for testing any claim of IICGS in a clustered data setting. Through simulations and real data applications, we demonstrate that our proposed statistical testing method can accurately identify IICGS, with substantial power, in clustered data. [ABSTRACT FROM AUTHOR]

When integrating data from multiple sources, a common challenge is block-wise missing. Most existing methods address this issue only in cross-sectional studies. In this paper, we propose a method for variable selection when combining datasets from multiple sources in longitudinal studies. To account for block-wise missing in covariates, we impute the missing values multiple times based on combinations of samples from different missing pattern and predictors from different data sources. We then use these imputed data to construct estimating equations, and aggregate the information across subjects and sources with the generalized method of moments. We employ the smoothly clipped absolute deviation penalty in variable selection and use the extended Bayesian Information Criterion criteria for tuning parameter selection. We establish the asymptotic properties of the proposed estimator, and demonstrate the superior performance of the proposed method through numerical experiments. Furthermore, we apply the proposed method in the Alzheimer's Disease Neuroimaging Initiative study to identify sensitive early-stage biomarkers of Alzheimer's Disease, which is crucial for early disease detection and personalized treatment. [ABSTRACT FROM AUTHOR]

Entropy is widely used in ecological and environmental studies, where data often present complex interactions. Difficulties arise in linking entropy to available covariates or data dependence structures, thus, all existing entropy estimators assume independence. To overcome this limit, we take a Bayesian model-based approach which focuses on estimating the probabilities that compose the index, accounting for any data dependence and correlation. An estimate of entropy can be constructed from the model fitted values, returning an observation-specific measure of entropy rather than an overall index. This way, the latent heterogeneity of the system can be represented by a curve in time or a surface in space, according to the characteristics of the survey study at hand. An empirical study illustrates the flexibility and interpretability of our results over temporally and spatially correlated data. An application is presented about the biodiversity of spatially structured rainforest tree data. [ABSTRACT FROM AUTHOR]

The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods. This manuscript presents an extension of this approach so that inference for the AUC may be performed in a three-level hierarchical data setting (e.g., eyes nested within persons and persons nested within families). A method that accounts for the effect of tied prediction scores on inference is also described. The performance of 95% confidence intervals around the AUC was assessed through the simulation of three-level clustered data in multiple settings, including ones with tied data and variable cluster sizes. Across all settings, the actual 95% confidence interval coverage varied from 0.943 to 0.958, and the ratio of the theoretical variance to the empirical variance of the AUC varied from 0.920 to 1.013. The results are better than those from existing methods. Two examples of applying the proposed methodology are presented.

The area under the true ROC curve (AUC) is routinely used to determine how strongly a given model discriminates between the levels of a binary outcome. Standard inference with the AUC requires that outcomes be independent of each other. To overcome this limitation, a method was developed for the estimation of the variance of the AUC in the setting of two-level hierarchical data using probit-transformed prediction scores generated from generalized estimating equation models, thereby allowing for the application of inferential methods. This manuscript presents an extension of this approach so that inference for the AUC may be performed in a three-level hierarchical data setting (e.g., eyes nested within persons and persons nested within families). A method that accounts for the effect of tied prediction scores on inference is also described. The performance of 95% confidence intervals around the AUC was assessed through the simulation of three-level clustered data in multiple settings, including ones with tied data and variable cluster sizes. Across all settings, the actual 95% confidence interval coverage varied from 0.943 to 0.958, and the ratio of the theoretical variance to the empirical variance of the AUC varied from 0.920 to 1.013. The results are better than those from existing methods. Two examples of applying the proposed methodology are presented. [ABSTRACT FROM AUTHOR]

Abstract Background Studies that utilize RNA Sequencing (RNA-Seq) in conjunction with designs that introduce dependence between observations (e.g. longitudinal sampling) require specialized analysis tools to accommodate this additional complexity. This R package contains a set of utilities to fit linear mixed effects models to transformed RNA-Seq counts that properly account for this dependence when performing statistical analyses. Results In a simulation study comparing lmerSeq and two existing methodologies that also work with transformed RNA-Seq counts, we found that lmerSeq was comprehensively better in terms of nominal error rate control and statistical power. Conclusions Existing R packages for analyzing transformed RNA-Seq data with linear mixed models are limited in the variance structures they allow and/or the transformation methods they support. The lmerSeq package offers more flexibility in both of these areas and gave substantially better results in our simulations.

In recent decades, the use of regression models with random effects has made great progress. Among these models' attractions is the flexibility to analyze correlated data. In various situations, the distribution of the response variable presents asymmetry or bimodality. In these cases, it is possible to use the normal regression with random effect at the intercept. In light of these contexts, i.e. the desire to analyze correlated data in the presence of bimodality or asymmetry, in this paper we propose a regression model with random effect at the intercept based onthe generalized inverse Gaussian distribution model with correlated data. The maximum likelihood is adopted to estimate the parameters and various simulations are performed for correlated data. A type of residuals for the new regression is proposed whose empirical distribution is close to normal. The versatility of the new regression is demonstrated by estimating the average price per hectare of bare land in 10 municipalities in the state of São Paulo (Brazil). In this context, various databases are constantly emerging, requiring flexible modeling. Thus, it is likely to be of interest to data analysts, and can make a good contribution to the statistical literature. [ABSTRACT FROM AUTHOR]

Despite major advances in research and treatment, identifying important genotype risk factors for high blood pressure remains challenging. Traditional genome-wide association studies (GWAS) focus on one single nucleotide polymorphism (SNP) at a time. We aim to select among over half a million SNPs along with time-varying phenotype variables via simultaneous modeling and variable selection, focusing on the most dangerous blood pressure levels at high quantiles. Taking advantage of rich data from a large-scale public health study, we develop and apply a novel quantile penalized generalized estimating equations (GEE) approach, incorporating several key aspects including ultra-high dimensional genetic SNPs, the longitudinal nature of blood pressure measurements, time-varying covariates, and conditional high quantiles of blood pressure. Importantly, we identify interesting new SNPs for high blood pressure. Besides, we find blood pressure levels are likely heterogeneous, where the important risk factors identified differ among quantiles. This comprehensive picture of conditional quantiles of blood pressure can allow more insights and targeted treatments. We provide an efficient computational algorithm and prove consistency, asymptotic normality, and the oracle property for the quantile penalized GEE estimators with ultra-high dimensional predictors. Moreover, we establish model-selection consistency for high-dimensional BIC. Simulation studies show the promise of the proposed approach. for this article are available online. [ABSTRACT FROM AUTHOR]

This article demonstrates how data from a biology paper, which analyzes the relationship between mass and metabolic rate for two species of marine bryozoan, can be used to teach a variety of regression topics to both introductory and advanced students. A thorough analysis requires intelligent data wrangling, variable transformations, and accounting for correlation between observations. The bryozoan data can be used as a valuable class example throughout the semester, or as a dataset for extended homework assignments and class projects. Supplementary materials for this article are available online.

Abstract Background As the cost of RNA-sequencing decreases, complex study designs, including paired, longitudinal, and other correlated designs, become increasingly feasible. These studies often include multiple hypotheses and thus multiple degree of freedom tests, or tests that evaluate multiple hypotheses jointly, are often useful for filtering the gene list to a set of interesting features for further exploration while controlling the false discovery rate. Though there are several methods which have been proposed for analyzing correlated RNA-sequencing data, there has been little research evaluating and comparing the performance of multiple degree of freedom tests across methods. Methods We evaluated 11 different methods for modelling correlated RNA-sequencing data by performing a simulation study to compare the false discovery rate, power, and model convergence rate across several hypothesis tests and sample size scenarios. We also applied each method to a real longitudinal RNA-sequencing dataset. Results Linear mixed modelling using transformed data had the best false discovery rate control while maintaining relatively high power. However, this method had high model non-convergence, particularly at small sample sizes. No method had high power at the lowest sample size. We found a mix of conservative and anti-conservative behavior across the other methods, which was influenced by the sample size and the hypothesis being evaluated. The patterns observed in the simulation study were largely replicated in the analysis of a longitudinal study including data from intensive care unit patients experiencing cardiogenic or septic shock. Conclusions Multiple degree of freedom testing is a valuable tool in longitudinal and other correlated RNA-sequencing experiments. Of the methods that we investigated, linear mixed modelling had the best overall combination of power and false discovery rate control. Other methods may also be appropriate in some scenarios.

Modern approaches to supervised learning like deep neural networks (DNNs) typically implicitly assume that observed responses are statistically independent. In contrast, correlated data are prevalent in real-life large-scale applications, with typical sources of correlation including spatial, temporal and clustering structures. These correlations are either ignored by DNNs, or ad-hoc solutions are developed for specific use cases. We propose to use the mixed models framework to handle correlated data in DNNs. By treating the effects underlying the correlation structure as random effects, mixed models are able to avoid overfitted parameter estimates and ultimately yield better predictive performance. The key to combining mixed models and DNNs is using the Gaussian negative log-likelihood (NLL) as a natural loss function that is minimized with DNN machinery including stochastic gradient descent (SGD). Since NLL does not decompose like standard DNN loss functions, the use of SGD with NLL presents some theoretical and implementation challenges, which we address. Our approach which we call LMMNN is demonstrated to improve performance over natural competitors in various correlation scenarios on diverse simulated and real datasets. Our focus is on a regression setting and tabular datasets, but we also show some results for classification. Our code is available at https://github.com/gsimchoni/lmmnn. [ABSTRACT FROM AUTHOR]

In many situations, it is common to have more than one observation per experimental unit, thus generating the experiments with repeated measures. In the modeling of such experiments, it is necessary to consider and model the intra-unit dependency structure. In the literature, there are several proposals to model positive continuous data with repeated measures. In this paper, we propose one more with the generalization of the beta prime regression model. We consider the possibility of dependence between observations of the same unit. Residuals and diagnostic tools also are discussed. To evaluate the finite-sample performance of the estimators, using different correlation matrices and distributions, we conducted a Monte Carlo simulation study. The methodology proposed is illustrated with an analysis of a real data set. Finally, we create an R package for easy access to publicly available the methodology described in this paper. [ABSTRACT FROM AUTHOR]

We introduce Gaussian orthogonal latent factor processes for modeling and predicting large correlated data. To handle the computational challenge, we first decompose the likelihood function of the Gaussian random field with a multi-dimensional input domain into a product of densities at the orthogonal components with lower-dimensional inputs. The continuous-time Kalman filter is implemented to compute the likelihood function efficiently without making approximations. We also show that the posterior distribution of the factor processes is independent, as a consequence of prior independence of factor processes and orthogonal factor loading matrix. For studies with large sample sizes, we propose a flexible way to model the mean, and we derive the marginal posterior distribution to solve identifiability issues in sampling these parameters. Both simulated and real data applications confirm the outstanding performance of this method. [ABSTRACT FROM AUTHOR]

Background: Studies that utilize RNA Sequencing (RNA-Seq) in conjunction with designs that introduce dependence between observations (e.g. longitudinal sampling) require specialized analysis tools to accommodate this additional complexity. This R package contains a set of utilities to fit linear mixed effects models to transformed RNA-Seq counts that properly account for this dependence when performing statistical analyses. Results: In a simulation study comparing lmerSeq and two existing methodologies that also work with transformed RNA-Seq counts, we found that lmerSeq was comprehensively better in terms of nominal error rate control and statistical power. Conclusions: Existing R packages for analyzing transformed RNA-Seq data with linear mixed models are limited in the variance structures they allow and/or the transformation methods they support. The lmerSeq package offers more flexibility in both of these areas and gave substantially better results in our simulations. [ABSTRACT FROM AUTHOR]

Many statistical models currently used in ecology and evolution account for covariances among random errors. Here, I address five points: (i) correlated random errors unite many types of statistical models, including spatial, phylogenetic and time‐series models; (ii) random errors are neither unpredictable nor mistakes; (iii) diagnostics for correlated random errors are not useful, but simulations are; (iv) model predictions can be made with random errors; and (v) can random errors be causal?These five points are illustrated by applying statistical models to analyse simulated spatial, phylogenetic and time‐series data. These three simulation studies are paired with three types of predictions that can be made using information from covariances among random errors: predictions for goodness‐of‐fit, interpolation, and forecasting.In the simulation studies, models incorporating covariances among random errors improve inference about the relationship between dependent and independent variables. They also imply the existence of unmeasured variables that generate the covariances among random errors. Understanding the covariances among random errors gives information about possible processes underlying the data.Random errors are caused by something. Therefore, to extract full information from data, covariances among random errors should not just be included in statistical models; they should also be studied in their own right. Data are hard won, and appropriate statistical analyses can make the most of them. [ABSTRACT FROM AUTHOR]

Performing a genome-wide association study (GWAS) with a binary phenotype using family data is a challenging task. Using linear mixed effects models is typically unsuitable for binary traits, and numerical approximations of the likelihood function may not work well with rare genetic variants with small counts. Additionally, imbalance in the case-control ratios poses challenges as traditional statistical methods such as the Score test or Wald test perform poorly in this setting. In the last couple of years, several methods have been proposed to better approximate the likelihood function of a mixed effects logistic regression model that uses Saddle Point Approximation (SPA). SPA adjustment has recently been implemented in multiple software, including GENESIS, SAIGE, REGENIE and fastGWA-GLMM: four increasingly popular tools to perform GWAS of binary traits. We compare Score and SPA tests using real family data to evaluate computational efficiency and the agreement of the results. Additionally, we compare various ways to adjust for family relatedness, such as sparse and full genetic relationship matrices (GRM) and polygenic effect estimates. We use the New England Centenarian Study imputed genotype data and the Long Life Family Study whole-genome sequencing data and the binary phenotype of human extreme longevity to compare the agreement of the results and tools' computational performance. The evaluation suggests that REGENIE might not be a good choice when analyzing correlated data of a small size. fastGWA-GLMM is the most computationally efficient compared to the other three tools, but it appears to be overly conservative when applied to family-based data. GENESIS, SAIGE and fastGWA-GLMM produced similar, although not identical, results, with SPA adjustment performing better than Score tests. Our evaluation also demonstrates the importance of adjusting by full GRM in highly correlated datasets when using GENESIS or SAIGE. [ABSTRACT FROM AUTHOR]

Performing a genome-wide association study (GWAS) with a binary phenotype using family data is a challenging task. Using linear mixed effects models is typically unsuitable for binary traits, and numerical approximations of the likelihood function may not work well with rare genetic variants with small counts. Additionally, imbalance in the case-control ratios poses challenges as traditional statistical methods such as the Score test or Wald test perform poorly in this setting. In the last couple of years, several methods have been proposed to better approximate the likelihood function of a mixed effects logistic regression model that uses Saddle Point Approximation (SPA). SPA adjustment has recently been implemented in multiple software, including GENESIS, SAIGE, REGENIE and fastGWA-GLMM: four increasingly popular tools to perform GWAS of binary traits. We compare Score and SPA tests using real family data to evaluate computational efficiency and the agreement of the results. Additionally, we compare various ways to adjust for family relatedness, such as sparse and full genetic relationship matrices (GRM) and polygenic effect estimates. We use the New England Centenarian Study imputed genotype data and the Long Life Family Study whole-genome sequencing data and the binary phenotype of human extreme longevity to compare the agreement of the results and tools’ computational performance. The evaluation suggests that REGENIE might not be a good choice when analyzing correlated data of a small size. fastGWA-GLMM is the most computationally efficient compared to the other three tools, but it appears to be overly conservative when applied to family-based data. GENESIS, SAIGE and fastGWA-GLMM produced similar, although not identical, results, with SPA adjustment performing better than Score tests. Our evaluation also demonstrates the importance of adjusting by full GRM in highly correlated datasets when using GENESIS or SAIGE.

Background: As the cost of RNA-sequencing decreases, complex study designs, including paired, longitudinal, and other correlated designs, become increasingly feasible. These studies often include multiple hypotheses and thus multiple degree of freedom tests, or tests that evaluate multiple hypotheses jointly, are often useful for filtering the gene list to a set of interesting features for further exploration while controlling the false discovery rate. Though there are several methods which have been proposed for analyzing correlated RNA-sequencing data, there has been little research evaluating and comparing the performance of multiple degree of freedom tests across methods.Methods: We evaluated 11 different methods for modelling correlated RNA-sequencing data by performing a simulation study to compare the false discovery rate, power, and model convergence rate across several hypothesis tests and sample size scenarios. We also applied each method to a real longitudinal RNA-sequencing dataset.Results: Linear mixed modelling using transformed data had the best false discovery rate control while maintaining relatively high power. However, this method had high model non-convergence, particularly at small sample sizes. No method had high power at the lowest sample size. We found a mix of conservative and anti-conservative behavior across the other methods, which was influenced by the sample size and the hypothesis being evaluated. The patterns observed in the simulation study were largely replicated in the analysis of a longitudinal study including data from intensive care unit patients experiencing cardiogenic or septic shock.Conclusions: Multiple degree of freedom testing is a valuable tool in longitudinal and other correlated RNA-sequencing experiments. Of the methods that we investigated, linear mixed modelling had the best overall combination of power and false discovery rate control. Other methods may also be appropriate in some scenarios. [ABSTRACT FROM AUTHOR]

This article demonstrates how data from a biology paper, which analyzes the relationship between mass and metabolic rate for two species of marine bryozoan, can be used to teach a variety of regression topics to both introductory and advanced students. A thorough analysis requires intelligent data wrangling, variable transformations, and accounting for correlation between observations. The bryozoan data can be used as a valuable class example throughout the semester, or as a dataset for extended homework assignments and class projects. for this article are available online. [ABSTRACT FROM AUTHOR]

Abstract Background There is high rate of under-five mortality in West Africa with little effort made to study determinants that significantly increase or decrease its risk across the West African sub-region. This is important since it will help in the design of effective intervention programs for each country or the entire region. The overall objective of this research evaluates the determinants of under-five mortality prior to the end of the 2015 Millennium Development Goals, to guide West African countries implement strategies that will aid them achieve the Sustainable Development Goal 3 by 2030. Method This study used the Demographic and Health Survey (DHS) data from twelve (12) out of the eighteen West African countries; Ghana, Benin, Cote d’ Ivoire, Guinea, Liberia, Mali, Niger, Nigeria, Sierra Leone, Burkina Faso, Gambia and Togo. Data were extracted from the children and women of reproductive age files as provided in the DHS report. The response or outcome variable of interest is under-five mortality rate. A Bayesian exponential, Weibull and Gompertz regression models via a gamma shared frailty model were used for the analysis. The deviance information criteria and Bayes factors were used to discriminate between models. These analyses were carried out using Stata version 15 software. Results The study recorded 101 (95% CI: 98.6–103.5) deaths per 1000 live births occurring among the twelve countries. Burkina Faso (124.4), Cote D’lvoire (110.1), Guinea (116.4), Nigeria (120.6) and Niger (118.3) recorded the highest child under-5 mortality rate. Gambia (48.1), Ghana (60.1) and Benin (70.4) recorded the least unde-5 mortality rate per 1000 livebirths. Multiple birth children were about two times more likely to die compared to singleton birth, in all except Gambia, Nigeria and Sierra Leone. We observed significantly higher hazard rates for male compared to female children in the combined data analysis (HR: 1.14, 95% CI: [1.10–1.18]). The country specific analysis in Benin, Cote D’lvoire, Guinea, Liberia, Mali and Nigeria showed higher under-5 mortality hazard rates among male children compared to female children whilst Niger was the only country to report significantly lower hazard rate of males compared to females. Conclusion There is still quite a substantial amount of work to be done in order to meet the Sustainable Development Goal 3 in 2030 in West Africa. There exist variant differences among some of the countries with respect to mortality rates and determinants which require different interventions and policy decisions.

Abstract Background Event-related potentials (ERP) data are widely used in brain studies that measure brain responses to specific stimuli using electroencephalogram (EEG) with multiple electrodes. Previous ERP data analyses haven’t accounted for the structured correlation among observations in ERP data from multiple electrodes, and therefore ignored the electrode-specific information and variation among the electrodes on the scalp. Our objective was to evaluate the impact of early adversity on brain connectivity by identifying risk factors and early-stage biomarkers associated with the ERP responses while properly accounting for structured correlation. Methods In this study, we extend a penalized generalized estimating equation (PGEE) method to accommodate structured correlation of ERPs that accounts for electrode-specific data and to enable group selection, such that grouped covariates can be evaluated together for their association with brain development in a birth cohort of urban-dwelling Bangladeshi children. The primary ERP responses of interest in our study are N290 amplitude and the difference in N290 amplitude. Results The selected early-stage biomarkers associated with the N290 responses are representatives of enteric inflammation (days of diarrhea, MIP1b, retinol binding protein (RBP), Zinc, myeloperoxidase (MPO), calprotectin, and neopterin), systemic inflammation (IL-5, IL-10, ferritin, C Reactive Protein (CRP)), socioeconomic status (household expenditure), maternal health (mother height) and sanitation (water treatment). Conclusions Our proposed group penalized GEE estimator with structured correlation matrix can properly model the complex ERP data and simultaneously identify informative biomarkers associated with such brain connectivity. The selected early-stage biomarkers offer a potential explanation for the adversity of neurocognitive development in low-income countries and facilitate early identification of infants at risk, as well as potential pathways for intervention. Trial registration The related clinical study was retrospectively registered with https://doi.org/ClinicalTrials.gov , identifier NCT01375647, on June 3, 2011.

Abstract Background As the barriers to incorporating RNA sequencing (RNA-Seq) into biomedical studies continue to decrease, the complexity and size of RNA-Seq experiments are rapidly growing. Paired, longitudinal, and other correlated designs are becoming commonplace, and these studies offer immense potential for understanding how transcriptional changes within an individual over time differ depending on treatment or environmental conditions. While several methods have been proposed for dealing with repeated measures within RNA-Seq analyses, they are either restricted to handling only paired measurements, can only test for differences between two groups, and/or have issues with maintaining nominal false positive and false discovery rates. In this work, we propose a Bayesian hierarchical negative binomial generalized linear mixed model framework that can flexibly model RNA-Seq counts from studies with arbitrarily many repeated observations, can include covariates, and also maintains nominal false positive and false discovery rates in its posterior inference. Results In simulation studies, we showed that our proposed method (MCMSeq) best combines high statistical power (i.e. sensitivity or recall) with maintenance of nominal false positive and false discovery rates compared the other available strategies, especially at the smaller sample sizes investigated. This behavior was then replicated in an application to real RNA-Seq data where MCMSeq was able to find previously reported genes associated with tuberculosis infection in a cohort with longitudinal measurements. Conclusions Failing to account for repeated measurements when analyzing RNA-Seq experiments can result in significantly inflated false positive and false discovery rates. Of the methods we investigated, whether they model RNA-Seq counts directly or worked on transformed values, the Bayesian hierarchical model implemented in the mcmseq R package (available at https://github.com/stop-pre16/mcmseq ) best combined sensitivity and nominal error rate control.

This paper proposes a new classification of correlated data types based upon the relative number of direct connections among observations, producing a family of correlated observations embracing seven categories, one whose empirical counterpart currently is unknown, and ranging from independent (i.e., no links) to approaching near-complete linkage (i.e., n(n − 1)/2 links). Analysis of specimen datasets from publicly available data sources furnishes empirical illustrations for these various categories. Their descriptions also include their historical context and calculation of their effective sample sizes (i.e., an equivalent number of independent observations). Concluding comments contain some state-of-the-art future research topics.

Abstract Background Elderly population’s health is a major concern for most industrial nations. National health surveys provide a measure of the state of elderly health. One such survey is the Chinese Longitudinal Healthy Longevity Survey. It collects data on risk factors and outcomes on the elderly. We examine these longitudinal survey data to determine the changes in health and to identify risk factors as they impact health outcomes including the elderly’s ability to do a physical check. Methods We use a Partitioned GMM logistic regression model to identify risk factors. The model also accounts for the correlation between lagged time-dependent covariates and the outcomes. It addresses present and past measures of time-dependent covariates on simultaneous outcomes. The relation produces additional regression coefficients as byproduct of the Partitioned model, identifying the immediate, delayed effects (lag − 1), further delayed (lag-2), etc. Therefore, the model presents the opportunity for decision makers to monitor the covariate over time. This technique is particularly useful in healthcare and health related research. We use the Chinese Longitudinal Health Longevity Survey data to identify those risk factors and to display the utility of the model. Results We found that one’s ability to make own decisions, frequently consuming vegetables, exercise frequently, one’s ability to transfer without assistance, having visual difficulties and being able to pick book from floor while standing had varying effects of significance on one’s health and ability to complete physical checks as they get older. Conclusions The partitioning of the covariates as immediate effect, delayed effect or further delayed effect are important measures in a declining population.

Collinearity can be a problem in regression models. When examining the effects of an exposure at different time points, constrained distributed lag models can alleviate some of the problems caused by collinearity. Still, some consequences of collinearity may remain and they are often unexplored. We aimed to illustrate the effects of collinearity in the context of distributed lag models, and to provide a tool to assess whether the results of a study could be influenced by collinearity. We used simulations under different scenarios of hypothesized effects of an exposure to visualize the resulting curves of lagged effects. We analysed three real datasets: a cohort study looking for windows of vulnerability to air pollution, a time series study examining the linear association of air pollution with hospital admissions, and a time series study examining the non-linear association between temperature and mortality. We showed that collinearity could be the explanation for some unexpected results, e.g. for statistically significant associations in the opposite direction from that expected, or for wrongly suggesting that some periods are more important than others. We implemented the collin R package to explore the potential consequences of collinearity in the context of distributed lag models. Our visual tool can be a useful way to assess if the results of an analysis may be influenced by collinearity. [ABSTRACT FROM AUTHOR]

In a cluster randomized trial (CRT), groups of people are randomly assigned to different interventions. Existing parametric and semiparametric methods for CRTs rely on distributional assumptions or a large number of clusters to maintain nominal confidence interval (CI) coverage. Randomization-based inference is an alternative approach that is distribution-free and does not require a large number of clusters to be valid. Although it is well-known that a CI can be obtained by inverting a randomization test, this requires testing a non-zero null hypothesis, which is challenging with non-continuous and survival outcomes. In this article, we propose a general method for randomization-based CIs using individual-level data from a CRT. This approach accommodates various outcome types, can account for design features such as matching or stratification, and employs a computationally efficient algorithm. We evaluate this method's performance through simulations and apply it to the Botswana Combination Prevention Project, a large HIV prevention trial with an interval-censored time-to-event outcome. [ABSTRACT FROM AUTHOR]

New technologies have produced increasingly complex and massive datasets, such as next generation sequencing and microarray data in biology, dynamic treatment regimes in clinical trials and long-term wide-scale studies in the social sciences. Each study exhibits its unique data structure within individuals, clusters and possibly across time and space. In order to draw valid conclusion from such large dimensional data, we must account for intracluster correlations, varying cluster sizes, and outliers in response and/or covariate domains to achieve valid and efficient inferences. A weighted rank-based method is proposed for selecting variables and estimating parameters simultaneously. The main contribution of the proposed method is four fold: (1) variable selection using adaptive lasso is extended to robust rank regression so that protection against outliers in both response and predictor variables is obtained; (2) within-subject correlations are incorporated so that efficiency of parameter estimation is improved; (3) the computation is convenient via the existing function in statistical software R. (4) the proposed method is proved to have desirable asymptotic properties for fixed number of covariates (p). Simulation studies are carried out to evaluate the proposed method for a number of scenarios including the cases when p equals to the number of subjects. The simulation results indicate that the proposed method is efficient and robust. A hormone dataset is analyzed for illustration. By adding additional redundant variables as covariates, the penalty approach and weighting schemes are proven to be effective. [ABSTRACT FROM AUTHOR]

Count data have emerged in many applied research areas. In recent years, there has been a considerable interest in models for count data. In modelling such data, it is common to face a large frequency of zeroes. The data are regarded as zero-inflated when the frequency of observed zeroes is larger than what is expected from a theoretical distribution such as Poisson distribution, as a standard model for analysing count data. Data analysis, using the simple Poisson model, may lead to over-dispersion. Several classes of different mixture models were proposed for handling zero-inflated data. But they do not apply to cases when inflated counts happen at some other points, in addition to zero. In these cases, a doubly-inflated Poisson model has been suggested which only be used for cross-sectional data and cannot consider correlations between observations. However, correlated count data have a large application, especially in the health and medical fields. The present study aims to introduce a Doubly-Inflated Poisson models with random effect for correlated doubly-inflated data. Then, the best performance of the proposed method is shown via different simulation scenarios. Finally, the proposed model is applied to a dental study. [ABSTRACT FROM AUTHOR]

Background: There is high rate of under-five mortality in West Africa with little effort made to study determinants that significantly increase or decrease its risk across the West African sub-region. This is important since it will help in the design of effective intervention programs for each country or the entire region. The overall objective of this research evaluates the determinants of under-five mortality prior to the end of the 2015 Millennium Development Goals, to guide West African countries implement strategies that will aid them achieve the Sustainable Development Goal 3 by 2030. Method: This study used the Demographic and Health Survey (DHS) data from twelve (12) out of the eighteen West African countries; Ghana, Benin, Cote d' Ivoire, Guinea, Liberia, Mali, Niger, Nigeria, Sierra Leone, Burkina Faso, Gambia and Togo. Data were extracted from the children and women of reproductive age files as provided in the DHS report. The response or outcome variable of interest is under-five mortality rate. A Bayesian exponential, Weibull and Gompertz regression models via a gamma shared frailty model were used for the analysis. The deviance information criteria and Bayes factors were used to discriminate between models. These analyses were carried out using Stata version 15 software. Results: The study recorded 101 (95% CI: 98.6–103.5) deaths per 1000 live births occurring among the twelve countries. Burkina Faso (124.4), Cote D'lvoire (110.1), Guinea (116.4), Nigeria (120.6) and Niger (118.3) recorded the highest child under-5 mortality rate. Gambia (48.1), Ghana (60.1) and Benin (70.4) recorded the least unde-5 mortality rate per 1000 livebirths. Multiple birth children were about two times more likely to die compared to singleton birth, in all except Gambia, Nigeria and Sierra Leone. We observed significantly higher hazard rates for male compared to female children in the combined data analysis (HR: 1.14, 95% CI: [1.10–1.18]). The country specific analysis in Benin, Cote D'lvoire, Guinea, Liberia, Mali and Nigeria showed higher under-5 mortality hazard rates among male children compared to female children whilst Niger was the only country to report significantly lower hazard rate of males compared to females. Conclusion: There is still quite a substantial amount of work to be done in order to meet the Sustainable Development Goal 3 in 2030 in West Africa. There exist variant differences among some of the countries with respect to mortality rates and determinants which require different interventions and policy decisions. [ABSTRACT FROM AUTHOR]

Background: A recently proposed method for estimating qPCR amplification efficiency E analyzes fluorescence intensity ratios from pairs of points deemed to lie in the exponential growth region on the amplification curves for all reactions in a dilution series. This method suffers from a serious problem: The resulting ratios are highly correlated, as they involve multiple use of the raw data, for example, yielding ~ 250 E estimates from ~ 25 intensity readings. The resulting statistics for such estimates are falsely optimistic in their assessment of the estimation precision. Results: Monte Carlo simulations confirm that the correlated pairs method yields precision estimates that are better than actual by a factor of two or more. This result is further supported by estimating E by both pairwise and Cq calibration methods for the 16 replicate datasets from the critiqued work, and then comparing the ensemble statistics for these methods. Conclusion: Contrary to assertions in the proposing work, the pairwise method does not yield E estimates a factor of 2 more precise than estimates from Cq calibration fitting (the standard curve method). On the other hand, the statistically correct direct fit of the data to the model behind the pairwise method can yield E estimates of comparable precision. Ways in which the approach might be improved are discussed briefly. [ABSTRACT FROM AUTHOR]

Much recent research focuses on how to make disease detection more accurate as well as "slimmer", i.e., allowing analysis with smaller datasets. Explanatory models are a hot research topic because they explain how the data are generated. We propose a spatial explanatory modelling approach that combines Optical Coherence Tomography (OCT) retinal imaging data with clinical information. Our model consists of a spatial linear mixed effects inference framework, which innovatively models the spatial topography of key information via mixed effects and spatial error structures, thus effectively modelling the shape of the thickness map. We show that our spatial linear mixed effects (SLME) model outperforms traditional analysis-of-variance approaches in the analysis of Heidelberg OCT retinal thickness data from a prospective observational study, involving 300 participants with diabetes and 50 age-matched controls. Our SLME model has a higher power for detecting the difference between disease groups, and it shows where the shape of retinal thickness profiles differs between the eyes of participants with diabetes and the eyes of healthy controls. In simulated data, the SLME model demonstrates how incorporating spatial correlations can increase the accuracy of the statistical inferences. This model is crucial in the understanding of the progression of retinal thickness changes in diabetic maculopathy to aid clinicians for early planning of effective treatment. It can be extended to disease monitoring and prognosis in other diseases and with other imaging technologies. [ABSTRACT FROM AUTHOR]

Background: Elderly population's health is a major concern for most industrial nations. National health surveys provide a measure of the state of elderly health. One such survey is the Chinese Longitudinal Healthy Longevity Survey. It collects data on risk factors and outcomes on the elderly. We examine these longitudinal survey data to determine the changes in health and to identify risk factors as they impact health outcomes including the elderly's ability to do a physical check.Methods: We use a Partitioned GMM logistic regression model to identify risk factors. The model also accounts for the correlation between lagged time-dependent covariates and the outcomes. It addresses present and past measures of time-dependent covariates on simultaneous outcomes. The relation produces additional regression coefficients as byproduct of the Partitioned model, identifying the immediate, delayed effects (lag - 1), further delayed (lag-2), etc. Therefore, the model presents the opportunity for decision makers to monitor the covariate over time. This technique is particularly useful in healthcare and health related research. We use the Chinese Longitudinal Health Longevity Survey data to identify those risk factors and to display the utility of the model.Results: We found that one's ability to make own decisions, frequently consuming vegetables, exercise frequently, one's ability to transfer without assistance, having visual difficulties and being able to pick book from floor while standing had varying effects of significance on one's health and ability to complete physical checks as they get older.Conclusions: The partitioning of the covariates as immediate effect, delayed effect or further delayed effect are important measures in a declining population. [ABSTRACT FROM AUTHOR]

Experimental designs such as matched-pair or longitudinal studies yield mRNA sequencing (mRNA-Seq) counts that are correlated across samples. Most of the approaches for the analysis of correlated mRNA-Seq data are restricted to a specific design and/or balanced data only (with the same number of samples in each group). We propose a model that is applicable to the analysis of correlated mRNA-Seq data of different types: paired, clustered, longitudinal, or others. Any combination of explanatory variables, as well as unbalanced data, can be processed within the proposed modeling framework. The model assumes that exon counts of a particular gene of an individual sample jointly follow a multivariate negative-binomial distribution. Additional correlation between exon counts obtained for, for example, individual samples within the same pair or cluster, is taken into account by including into the model a cluster-level normally distributed random effect. An interesting feature of the model is that it provides explicit expression for marginal correlation between exon counts at different levels. The performance of the model is evaluated by using a simulation study and an analysis of two real-life data sets: a paired mRNA-Seq experiment for 24 patients with clear-cell renal-cell carcinoma and a longitudinal mRNA-Seq experiment for 29 patients with Lyme disease. [ABSTRACT FROM AUTHOR]

Traditional cluster analysis methods used in ordinal data, for instance k-means and hierarchical clustering, are mostly heuristic and lack statistical inference tools to compare among competing models. To address this we propose a latent transitional model, a finite mixture model that includes both observed and latent covariates and apply it for the first time to the case of longitudinal ordinal data. This model-based clustering model is an extension of the proportional odds model and includes a first-order transitional term, occasion effects and interactions which provide flexible ways to capture different time patterns by cluster as well as time-heterogeneous transitions. We estimate model parameters within a Bayesian setting using a Markov chain Monte Carlo scheme and block-wise Metropolis–Hastings sampling. We illustrate the model using 2001–2011 self-reported health status (SRHS) from the Household, Income and Labour Dynamics in Australia survey. SRHS is recorded as an ordinal variable with five levels: poor, fair, good, very good and excellent. Using the Widely Applicable Information Criterion for model comparison, we find evidence for six latent groups. Transitions in the original data and the estimated groups are visualized using heatmaps. [ABSTRACT FROM AUTHOR]

Differential Privacy (DP) has received increasing attention as a rigorous privacy framework. Many existing studies employ traditional DP mechanisms (e.g., the Laplace mechanism) as primitives to continuously release private data for protecting privacy at each time point (i.e., event-level privacy), which assume that the data at different time points are independent, or that adversaries do not have knowledge of correlation between data. However, continuously generated data tend to be temporally correlated, and such correlations can be acquired by adversaries. In this paper, we investigate the potential privacy loss of a traditional DP mechanism under temporal correlations. First, we analyze the privacy leakage of a DP mechanism under temporal correlation that can be modeled using Markov Chain. Our analysis reveals that, the event-level privacy loss of a DP mechanism may increase over time. We call the unexpected privacy loss temporal privacy leakage (TPL). Although TPL may increase over time, we find that its supremum may exist in some cases. Second, we design efficient algorithms for calculating TPL. Third, we propose data releasing mechanisms that convert any existing DP mechanism into one against TPL. Experiments confirm that our approach is efficient and effective. [ABSTRACT FROM AUTHOR]

Analysis of longitudinal count data has, for long, been done using a generalized linear mixed model (GLMM), in its Poisson-normal version, to account for correlation by specifying normal random effects. Univariate counts are often handled with the negativebinomial (NEGBIN) model taking into account overdispersion by use of gamma random effects. Inherently though, longitudinal count data commonly exhibit both features of correlation and overdispersion simultaneously, necessitating analysis methodology that can account for both. The introduction of the combined model (CM) by Molenberghs, Verbeke, and Demétrio (2007) and Molenberghs, Verbeke, Demétrio, and Vieira (2010) serves this purpose, not only for count data but for the general exponential family of distributions. Here, a Poisson model is specified as the parent distribution of the data with a normally distributed random effect at the subject or cluster level and/or a gamma distribution at observation level. The GLMM and NEGBIN model are special cases. Data can be simulated from (1) the general CM, with random effects, or, (2) its marginal version directly. This paper discusses an implementation of (1) in SAS software (SAS Inc. 2011). One needs to reflect on the mean of both the combined (hierarchical) and marginal models in order to generate correlated and/or overdispersed counts. A pre-specification of the desired marginal mean (in terms of covariates and marginal parameters), a marginal variance-covariance structure and the hierarchical mean (in terms of covariates and regression parameters) is required. The implied hierarchical parameters, the variance-covariance matrix of the random effects, and the variance-covariance matrix of the overdispersion part are then derived from which correlated Poisson data are generated. Sample calls of the SAS macro are presented as well as output.

Abstract Background Incomplete data often arise in various clinical trials such as crossover trials, equivalence trials, and pre and post-test comparative studies. Various methods have been developed to construct confidence interval (CI) of risk difference or risk ratio for incomplete paired binary data. But, there is little works done on incomplete continuous correlated data. To this end, this manuscript aims to develop several approaches to construct CI of the difference of two means for incomplete continuous correlated data. Methods Large sample method, hybrid method, simple Bootstrap-resampling method based on the maximum likelihood estimates (B 1) and Ekbohm’s unbiased estimator (B 2), and percentile Bootstrap-resampling method based on the maximum likelihood estimates (B 3) and Ekbohm’s unbiased estimator (B 4) are presented to construct CI of the difference of two means for incomplete continuous correlated data. Simulation studies are conducted to evaluate the performance of the proposed CIs in terms of empirical coverage probability, expected interval width, and mesial and distal non-coverage probabilities. Results Empirical results show that the Bootstrap-resampling-based CIs B 1, B 2, B 4 behave satisfactorily for small to moderate sample sizes in the sense that their coverage probabilities could be well controlled around the pre-specified nominal confidence level and the ratio of their mesial non-coverage probabilities to the non-coverage probabilities could be well controlled in the interval [0.4, 0.6]. Conclusions If one would like a CI with the shortest interval width, the Bootstrap-resampling-based CIs B 1 is the optimal choice.

In the information industry there is a huge amount of data which can be used to obtain relevant information necessary for them to be processed, cleaned and analyzed. This survey paper presents different data extraction research that can be applied in various areas. The main point is to determine a new approach and to be the starting point for new experiments in agriculture predictions. The collaborative data mining approach assumes that correlated units or devices will have similar behavior that can be determined with an acceptable approximation. [ABSTRACT FROM AUTHOR]

Large-scale surveys, such as national forest inventories and vegetation monitoring programs, usually have complex sampling designs that include geographical stratification and units organized in clusters. When models are developed using data from such programs, a key question is whether or not to utilize design information when analyzing the relationship between a response variable and a set of covariates. Standard statistical regression methods often fail to account for complex sampling designs, which may lead to severely biased estimators of model coefficients. Furthermore, ignoring that data are spatially correlated within clusters may underestimate the standard errors of regression coefficient estimates, with a risk for drawing wrong conclusions. We first review general approaches that account for complex sampling designs, e.g. methods using probability weighting, and stress the need to explore the effects of the sampling design when applying logistic regression models. We then use Monte Carlo simulation to compare the performance of the standard logistic regression model with two approaches to model correlated binary responses, i.e. cluster-specific and population-averaged logistic regression models. As an example, we analyze the occurrence of epiphytic hair lichens in the genus Bryoria ; an indicator of forest ecosystem integrity. Based on data from the National Forest Inventory (NFI) for the period 1993–2014 we generated a data set on hair lichen occurrence on >100,000 Picea abies trees distributed throughout Sweden. The NFI data included ten covariates representing forest structure and climate variables potentially affecting lichen occurrence. Our analyses show the importance of taking complex sampling designs and correlated binary responses into account in logistic regression modeling to avoid the risk of obtaining notably biased parameter estimators and standard errors, and erroneous interpretations about factors affecting e.g. hair lichen occurrence. We recommend comparisons of unweighted and weighted logistic regression analyses as an essential step in development of models based on data from large-scale surveys. [ABSTRACT FROM AUTHOR]

In this article I develop a wild bootstrap procedure for cluster-robust inference in linear quantile regression models. I show that the bootstrap leads to asymptotically valid inference on the entire quantile regression process in a setting with a large number of small, heterogeneous clusters and provides consistent estimates of the asymptotic covariance function of that process. The proposed bootstrap procedure is easy to implement and performs well even when the number of clusters is much smaller than the sample size. An application to Project STAR data is provided. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

The estimation of parameters is a key component in statistical modelling and inference. However, parametrization of certain likelihood functions could lead to highly correlated estimates, causing numerical problems, mathematical complexities and difficulty in estimation or erroneous interpretation and subsequently inference. In statistical estimation, the concept of orthogonalization is familiar as a simplifying technique that allows parameters to be estimated independently and thus separates information from each other. We introduce a Fisher scoring iterative process that incorporates the Gram-Schmidt orthogonalization technique for maximum likelihood estimation. A finite mixture model for correlated binary data is used to illustrate the implementation of the method with discussion of application to oesophageal cancer data. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the efficiency of spatial statistical analysis in the selection of genotypes in a plant breeding program and, particularly, to demonstrate the benefits of the approach when experimental observations are not spatially independent. The basic material of this study was a yield trial of soybean lines, with five check varieties (of fixed effect) and 110 test lines (of random effects), in an augmented block design. The spatial analysis used a random field linear model (RFML), with a covariance function estimated from the residuals of the analysis considering independent errors. Results showed a residual autocorrelation of significant magnitude and extension (range), which allowed a better discrimination among genotypes (increase of the power of statistical tests, reduction in the standard errors of estimates and predictors, and a greater amplitude of predictor values) when the spatial analysis was applied. Furthermore, the spatial analysis led to a different ranking of the genetic materials, in comparison with the non-spatial analysis, and a selection less influenced by local variation effects was obtained.O objetivo deste trabalho foi avaliar a eficiência da análise estatística espacial na seleção de genótipos de plantas num programa de melhoramento. Buscou-se demonstrar os benefícios potenciais dessa abordagem quando as observações experimentais não são espacialmente independentes. O material consistiu de um ensaio de competição de linhagens de soja, com cinco cultivares testemunhas (de efeitos fixos) e 110 novos genótipos (de efeitos aleatórios), delineado em blocos aumentados. O ajuste espacial foi feito pelo modelo linear de campo aleatório (RFLM), com função de autocovariância estimada a partir dos resíduos da análise sob erros independentes. Os resultados apontaram uma autocorrelação residual de magnitude e alcance significativos, o que garantiu à abordagem espacial uma melhoria considerável na discriminação dos tratamentos genéticos - aumento do poder dos testes estatísticos, redução nos erros padrão de estimativas e de preditores e alargamento na amplitude das predições genotípicas. A análise espacial levou a um diferente ordenamento das linhagens em relação à análise não espacial e, finalmente, a uma seleção menos influenciada por efeitos da variação local.