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It is of substantial scientific interest to detect mediators that lie in the causal pathway from an exposure to a survival outcome. However, with high-dimensional mediators, as often encountered in modern genomic data settings, there is a lack of powerful methods that can provide valid post-selection inference for the identified marginal mediation effect. To resolve this challenge, we develop a post-selection inference procedure for the maximally selected natural indirect effect using a semiparametric efficient influence function approach. To this end, we establish the asymptotic normality of a stabilized one-step estimator that takes the selection of the mediator into account. Simulation studies show that our proposed method has good empirical performance. We further apply our proposed approach to a lung cancer dataset and find multiple DNA methylation CpG sites that might mediate the effect of cigarette smoking on lung cancer survival., Comment: 32 pages, 8 figures

This paper develops a new approach to post-selection inference for screening high-dimensional predictors of survival outcomes. Post-selection inference for right-censored outcome data has been investigated in the literature, but much remains to be done to make the methods both reliable and computationally-scalable in high-dimensions. Machine learning tools are commonly used to provide {\it predictions} of survival outcomes, but the estimated effect of a selected predictor suffers from confirmation bias unless the selection is taken into account. The new approach involves construction of semi-parametrically efficient estimators of the linear association between the predictors and the survival outcome, which are used to build a test statistic for detecting the presence of an association between any of the predictors and the outcome. Further, a stabilization technique reminiscent of bagging allows a normal calibration for the resulting test statistic, which enables the construction of confidence intervals for the maximal association between predictors and the outcome and also greatly reduces computational cost. Theoretical results show that this testing procedure is valid even when the number of predictors grows superpolynomially with sample size, and our simulations support that this asymptotic guarantee is indicative the performance of the test at moderate sample sizes. The new approach is applied to the problem of identifying patterns in viral gene expression associated with the potency of an antiviral drug., Comment: 102 pages, 7 figures, 4 tables

Stein's method is used to study discrete representations of multidimensional distributions that arise as approximations of states of quantum harmonic oscillators. These representations model how quantum effects result from the interaction of finitely many classical "worlds," with the role of sample size played by the number of worlds. Each approximation arises as the ground state of a Hamiltonian involving a particular interworld potential function. Such approximations have previously been studied for one-dimensional quantum harmonic oscillators, but the multidimensional case has remained unresolved. Our approach, framed in terms of spherical coordinates, provides the rate of convergence of the discrete approximation to the ground state in terms of Wasserstein distance. The fastest rate of convergence to the ground state is found to occur in three dimensions. This result is obtained using a discrete density approach to Stein's method applied to the radial component of the ground state solution., Comment: Main text is 22 pages; the rest of the paper consists of (i) supplementary material (including some additional proofs) of 17 pages; (ii) Mathematica and R code

We consider the problem of testing for the presence of linear relationships between large sets of random variables based on a post-selection inference approach to canonical correlation analysis. The challenge is to adjust for the selection of subsets of variables having linear combinations with maximal sample correlation. To this end, we construct a stabilized one-step estimator of the euclidean-norm of the canonical correlations maximized over subsets of variables of pre-specified cardinality. This estimator is shown to be consistent for its target parameter and asymptotically normal provided the dimensions of the variables do not grow too quickly with sample size. We also develop a greedy search algorithm to accurately compute the estimator, leading to a computationally tractable omnibus test for the global null hypothesis that there are no linear relationships between any subsets of variables having the pre-specified cardinality. Further, we develop a confidence interval for the target parameter that takes the variable selection into account.

Hall, Deckert and Wiseman (2014) recently proposed that quantum theory can be understood as the continuum limit of a deterministic theory in which there is a large, but finite, number of classical "worlds." A resulting Gaussian limit theorem for particle positions in the ground state, agreeing with quantum theory, was conjectured in Hall, Deckert and Wiseman (2014) and proven by McKeague and Levin (2016) using Stein's method. In this article we propose new connections between Stein's method and Many Interacting Worlds (MIW) theory. In particular, we show that quantum position probability densities for higher energy levels beyond the ground state arise as distributional fixed points in a new generalization of Stein's method. These are then used to obtain a rate of distributional convergence for conjectured particle positions in the first energy level above the ground state to the (two-sided) Maxwell distribution; new techniques must be developed for this setting where the usual "density approach" Stein solution (see Chatterjee and Shao (2011)) has a singularity., Comment: 17 pages

From its beginning, there have been attempts by physicists to formulate quantum mechanics without requiring the use of wave functions. An interesting recent approach takes the point of view that quantum effects arise solely from the interaction of finitely many classical "worlds." The wave function is then recovered (as a secondary object) from observations of particles in these worlds, without knowing the world from which any particular observation originates. Hall, Deckert and Wiseman [Physical Review X 4 (2014) 041013] have introduced an explicit many-interacting-worlds harmonic oscillator model to provide support for this approach. In this note we provide a proof of their claim that the particle configuration is asymptotically Gaussian, thus matching the stationary ground-state solution of Schroedinger's equation when the number of worlds goes to infinity. We also construct a Markov chain based on resampling from the particle configuration and show that it converges to an Ornstein-Uhlenbeck process, matching the time-dependent solution as well.

This paper develops an empirical likelihood approach to testing for the presence of stochastic ordering among univariate distributions based on independent random samples from each distribution. The proposed test statistic is formed by integrating a localized empirical likelihood statistic with respect to the empirical distribution of the pooled sample. The asymptotic null distribution of this test statistic is found to have a simple distribution-free representation in terms of standard Brownian bridge processes. The approach is used to compare the lengths of rule of Roman Emperors over various historical periods, including the "decline and fall" phase of the empire. In a simulation study, the power of the proposed test is found to improve substantially upon that of a competing test due to El Barmi and Mukerjee., Comment: Published in at http://dx.doi.org/10.3150/11-BEJ393 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm)

This paper develops a point impact linear regression model in which the trajectory of a continuous stochastic process, when evaluated at a sensitive time point, is associated with a scalar response. The proposed model complements and is more interpretable than the functional linear regression approach that has become popular in recent years. The trajectories are assumed to have fractal (self-similar) properties in common with a fractional Brownian motion with an unknown Hurst exponent. Bootstrap confidence intervals based on the least-squares estimator of the sensitive time point are developed. Misspecification of the point impact model by a functional linear model is also investigated. Non-Gaussian limit distributions and rates of convergence determined by the Hurst exponent play an important role., Comment: Published in at http://dx.doi.org/10.1214/10-AOS791 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org)

This article extends the scope of empirical likelihood methodology in three directions: to allow for plug-in estimates of nuisance parameters in estimating equations, slower than $\sqrt{n}$-rates of convergence, and settings in which there are a relatively large number of estimating equations compared to the sample size. Calibrating empirical likelihood confidence regions with plug-in is sometimes intractable due to the complexity of the asymptotics, so we introduce a bootstrap approximation that can be used in such situations. We provide a range of examples from survival analysis and nonparametric statistics to illustrate the main results., Comment: Published in at http://dx.doi.org/10.1214/07-AOS555 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org)

For time-to-event data with finitely many competing risks, the proportional hazards model has been a popular tool for relating the cause-specific outcomes to covariates [Prentice et al. Biometrics 34 (1978) 541--554]. This article studies an extension of this approach to allow a continuum of competing risks, in which the cause of failure is replaced by a continuous mark only observed at the failure time. We develop inference for the proportional hazards model in which the regression parameters depend nonparametrically on the mark and the baseline hazard depends nonparametrically on both time and mark. This work is motivated by the need to assess HIV vaccine efficacy, while taking into account the genetic divergence of infecting HIV viruses in trial participants from the HIV strain that is contained in the vaccine, and adjusting for covariate effects. Mark-specific vaccine efficacy is expressed in terms of one of the regression functions in the mark-specific proportional hazards model. The new approach is evaluated in simulations and applied to the first HIV vaccine efficacy trial., Comment: Published in at http://dx.doi.org/10.1214/07-AOS554 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org)

We investigate the problem of finding confidence sets for split points in decision trees (CART). Our main results establish the asymptotic distribution of the least squares estimators and some associated residual sum of squares statistics in a binary decision tree approximation to a smooth regression curve. Cube-root asymptotics with nonnormal limit distributions are involved. We study various confidence sets for the split point, one calibrated using the subsampling bootstrap, and others calibrated using plug-in estimates of some nuisance parameters. The performance of the confidence sets is assessed in a simulation study. A motivation for developing such confidence sets comes from the problem of phosphorus pollution in the Everglades. Ecologists have suggested that split points provide a phosphorus threshold at which biological imbalance occurs, and the lower endpoint of the confidence set may be interpreted as a level that is protective of the ecosystem. This is illustrated using data from a Duke University Wetlands Center phosphorus dosing study in the Everglades., Comment: Published at http://dx.doi.org/10.1214/009053606000001415 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org)