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Linear Mixed-Effects (LME) models are a fundamental tool for modeling correlated data, including cohort studies, longitudinal data analysis, and meta-analysis. Design and analysis of variable selection methods for LMEs is more difficult than for linear regression because LME models are nonlinear. In this article we propose a novel optimization strategy that enables a wide range of variable selection methods for LMEs using both convex and nonconvex regularizers, including 𝓁1, Adaptive-𝓁1, SCAD, and 𝓁0. The computational framework only requires the proximal operator for each regularizer to be readily computable, and the implementation is available in an open source python package pysr3, consistent with the sklearn standard. The numerical results on simulated data sets indicate that the proposed strategy improves on the state of the art for both accuracy and compute time. The variable selection techniques are also validated on a real example using a data set on bullying victimization. Supplementary materials for this article are available online. 

In this paper, we provide a full conjugacy and subdifferential calculus for convex convex-composite functions in finite-dimensional space. Our approach, based on infimal convolution and cone convexity, is straightforward. The results are established under a verifiable Slater-type condition, with relaxed monotonicity and without lower semicontinuity assumptions on the functions in play. The versatility of our findings is illustrated by a series of applications in optimization and matrix analysis, including conic programming, matrix-fractional, variational Gram, and spectral functions. 

We study a class of real robust phase retrieval problems under a Gaussian assumption on the coding matrix when the received signal is sparsely corrupted by noise. The goal is to establish conditions on the sparsity under which the input vector can be exactly recovered. The recovery problem is formulated as residual minimization in the l1-norm. The main contribution is a robust phase retrieval counterpart to the seminal paper by Candes and Tao on compressed sensing (l1 regression) [``Decoding by linear programming''. IEEE Transactions on Information Theory, 51(12):4203–4215, 2005]. The analysis depends on a key new property of the coding matrix called the Absolute Range Property (ARP) which is the analogue to the Null Space Property (NSP) in compressed sensing. When the residuals are computed using squared magnitudes, we show that ARP follows from a standard Restricted Isometry Property (RIP). However, when the residuals are computed using absolute magnitudes, a different kind of RIP or growth property is required. We conclude by showing that the robust phase retrieval objectives are sharp with respect to their minimizers with high probability. 

This work concerns the local convergence theory of Newton and quasi-Newton methods for convex-composite optimization: where one minimizes an objective that can be written as the composition of a convex function with one that is continuiously differentiable. We focus on the case in which the convex function is a potentially infinite-valued piecewise linear-quadratic function. Such problems include nonlinear programming, mini-max optimization, and estimation of nonlinear dynamics with non-Gaussian noise as well as many modern approaches to large-scale data analysis and machine learning. Our approach embeds the optimality conditions for convex-composite optimization problems into a generalized equation. We establish conditions for strong metric subregularity and strong metric regularity of the corresponding set-valued mappings. This allows us to extend classical convergence of Newton and quasi-Newton methods to the broader class of nonfinite valued piecewise linear-quadratic convex-composite optimization problems. In particular, we establish local quadratic convergence of the Newton method under conditions that parallel those in nonlinear programming. 

Block tridiagonal systems appear in classic Kalman smoothing problems, as well in generalized Kalman smoothing, where problems may have nonsmooth terms, singular covariance, constraints, nonlinear models, and unknown parameters. In this paper, first we interpret all the classic smoothing algorithms as different approaches to solve positive definite block tridiagonal linear systems. Then, we obtain new results on their numerical stability. Our outcomes apply to all systems with dynamic structure, informing both classic and modern inference for generalized Kalman smoothing.Elsevier 

This paper focuses on the design of sequential quadratic optimization (commonly known as SQP) methods for solving large-scale nonlinear optimization problems. The most computationally demanding aspect of such an approach is the computation of the search direction during each iteration, for which we consider the use of matrix-free methods. In particular, we develop a method that requires an inexact solve of a single QP subproblem to establish the convergence of the overall SQP method. It is known that SQP methods can be plagued by poor behavior of the global convergence mechanism. To confront this issue, we propose the use of an exact penalty function with a dynamic penalty parameter updating strategy to be employed within the subproblem solver in such a way that the resulting search direction predicts progress toward both feasibility and optimality. We present our parameter updating strategy and prove that, under reasonable assumptions, the strategy does not modify the penalty parameter unnecessarily. We close the paper with a discussion of the results of numerical experiments that illustrate the benefits of our proposed techniques. 

Population pharmacokinetic (PK) modeling has become a cornerstone of drug development and optimal patient dosing. This approach offers great benefits for datasets with sparse sampling, such as in pediatric patients, and can describe between-patient variability. While most current algorithms assume normal or log-normal distributions for PK parameters, we present a mathematically consistent nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions without any assumption about the shape of the distribution. This approach can handle distributions with any shape for all PK parameters. It is shown in convexity theory that the NPML estimator is discrete, meaning that it has finite number of points with nonzero probability. In fact, there are at most N points where N is the number of observed subjects. The original infinite NPML problem then becomes the finite dimensional problem of finding the location and probability of the support points. In the simplest case, each point essentially represents the set of PK parameters for one patient. The probability of the points is found by a primal-dual interior-point method; the location of the support points is found by an adaptive grid method. Our method is able to handle high-dimensional and complex multivariate mixture models. An important application is discussed for the problem of population pharmacokinetics and a nontrivial example is treated. Our algorithm has been successfully applied in hundreds of published pharmacometric studies. In addition to population pharmacokinetics, this research also applies to empirical Bayes estimation and many other areas of applied mathematics. Thereby, this approach presents an important addition to the pharmacometric toolbox for drug development and optimal patient dosing.