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In medical studies, time-to-event outcomes such as time to death or relapse of a disease are routinely recorded along with longitudinal data that are observed intermittently during the follow-up period. For various reasons, marginal approaches to model the event time, corresponding to separate approaches for survival data/longitudinal data, tend to induce bias and lose efficiency. Instead, a joint modeling approach that brings the two types of data together can reduce or eliminate the bias and yield a more efficient estimation procedure. A well-established avenue for joint modeling is the joint likelihood approach that often produces semiparametric efficient estimators for the finite-dimensional parameter vectors in both models. Through a transformation survival model with an unspecified baseline hazard function, this review introduces joint modeling that accommodates both baseline covariates and time-varying covariates. The focus is on the major challenges faced by joint modeling and how they can be overcome. A review of available software implementations and a brief discussion of future directions of the field are also included. 

Abstract With the advance of science and technology, more and more data are collected in the form of functions. A fundamental question for a pair of random functions is to test whether they are independent. This problem becomes quite challenging when the random trajectories are sampled irregularly and sparsely for each subject. In other words, each random function is only sampled at a few time-points, and these time-points vary with subjects. Furthermore, the observed data may contain noise. To the best of our knowledge, there exists no consistent test in the literature to test the independence of sparsely observed functional data. We show in this work that testing pointwise independence simultaneously is feasible. The test statistics are constructed by integrating pointwise distance covariances (Székely et al., 2007) and are shown to converge, at a certain rate, to their corresponding population counterparts, which characterize the simultaneous pointwise independence of two random functions. The performance of the proposed methods is further verified by Monte Carlo simulations and analysis of real data. 

Abstract The maturation of regional brain volumes from birth to preadolescence is a critical developmental process that underlies emerging brain structural connectivity and function. Regulated by genes and environment, the coordinated growth of different brain regions plays an important role in cognitive development. Current knowledge about structural network evolution is limited, partly due to the sparse and irregular nature of most longitudinal neuroimaging data. In particular, it is unknown how factors such as mother’s education or sex of the child impact the structural network evolution. To address this issue, we propose a method to construct evolving structural networks and study how the evolving connections among brain regions as reflected at the network level are related to maternal education and biological sex of the child and also how they are associated with cognitive development. Our methodology is based on applying local Fréchet regression to longitudinal neuroimaging data acquired from the RESONANCE cohort, a cohort of healthy children (245 females and 309 males) ranging in age from 9 weeks to 10 years. Our findings reveal that sustained highly coordinated volume growth across brain regions is associated with lower maternal education and lower cognitive development. This suggests that higher neurocognitive performance levels in children are associated with increased variability of regional growth patterns as children age. 

Abstract Quantifying the association between components of multivariate random curves is of general interest and is a ubiquitous and basic problem that can be addressed with functional data analysis. An important application is the problem of assessing functional connectivity based on functional magnetic resonance imaging (fMRI), where one aims to determine the similarity of fMRI time courses that are recorded on anatomically separated brain regions. In the functional brain connectivity literature, the static temporal Pearson correlation has been the prevailing measure for functional connectivity. However, recent research has revealed temporally changing patterns of functional connectivity, leading to the study of dynamic functional connectivity. This motivates new similarity measures for pairs of random curves that reflect the dynamic features of functional similarity. Specifically, we introduce gradient synchronization measures in a general setting. These similarity measures are based on the concordance and discordance of the gradients between paired smooth random functions. Asymptotic normality of the proposed estimates is obtained under regularity conditions. We illustrate the proposed synchronization measures via simulations and an application to resting-state fMRI signals from the Alzheimer’s Disease Neuroimaging Initiative and they are found to improve discrimination between subjects with different disease status. 

Abstract Testing the homogeneity between two samples of functional data is an important task. While this is feasible for intensely measured functional data, we explain why it is challenging for sparsely measured functional data and show what can be done for such data. In particular, we show that testing the marginal homogeneity based on point-wise distributions is feasible under some mild constraints and propose a new two-sample statistic that works well with both intensively and sparsely measured functional data. The proposed test statistic is formulated upon energy distance, and the convergence rate of the test statistic to its population version is derived along with the consistency of the associated permutation test. The aptness of our method is demonstrated on both synthetic and real data sets.