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Though platform trials have been touted for their flexibility and streamlined use of trial resources, their statistical efficiency is not well understood. We fill this gap by establishing their greater efficiency for comparing the relative efficacy of multiple interventions over using several separate, two-arm trials, where the relative efficacy of an arbitrary pair of interventions is evaluated by contrasting their relative risks as compared to control. In theoretical and numerical studies, we demonstrate that the inference of such a contrast using data from a platform trial enjoys identical or better precision than using data from separate trials, even when the former enrolls substantially fewer participants. This benefit is attributed to the sharing of controls among interventions under contemporaneous randomization, which is a key feature of platform trials. We further provide a novel procedure for establishing the non-inferiority of a given intervention relative to the most efficacious of the other interventions under evaluation, where this procedure is adaptive in the sense that it need not be \textit{a priori} known which of these other interventions is most efficacious. Our numerical studies show that this testing procedure can attain substantially better power when the data arise from a platform trial rather than multiple separate trials. Our results are illustrated using data from two monoclonal antibody trials for the prevention of HIV., Comment: 60 pages, 7 figures, 4 tables

We aim to make inferences about a smooth, finite-dimensional parameter by fusing data from multiple sources together. Previous works have studied the estimation of a variety of parameters in similar data fusion settings, including in the estimation of the average treatment effect and average reward under a policy, with the majority of them merging one historical data source with covariates, actions, and rewards and one data source of the same covariates. In this work, we consider the general case where one or more data sources align with each part of the distribution of the target population, for example, the conditional distribution of the reward given actions and covariates. We describe potential gains in efficiency that can arise from fusing these data sources together in a single analysis, which we characterize by a reduction in the semiparametric efficiency bound. We also provide a general means to construct estimators that achieve these bounds. In numerical experiments, we illustrate marked improvements in efficiency from using our proposed estimators rather than their natural alternatives. Finally, we illustrate the magnitude of efficiency gains that can be realized in vaccine immunogenicity studies by fusing data from two HIV vaccine trials.

We propose a new method for separating valid inequalities for the epigraph of a function of binary variables. The proposed inequalities are disjunctive cuts defined by disjunctive terms obtained by enumerating a subset $I$ of the binary variables. We show that by restricting the support of the cut to the same set of variables $I$, a cut can be obtained by solving a linear program with $2^{|I|}$ constraints. While this limits the size of the set $I$ used to define the multi-term disjunction, the procedure enables generation of multi-term disjunctive cuts using far more terms than existing approaches. We present two approaches for choosing the subset of variables. Experience on three MILP problems with block diagonal structure using $|I|$ up to size 10 indicates the sparse cuts can often close nearly as much gap as the multi-term disjunctive cuts without this restriction and in a fraction of the time. We also find that including these cuts within a cut-and-branch solution method for these MILP problems leads to significant reductions in solution time or ending optimality gap for instances that were not solved within the time limit. Finally, we describe how the proposed approach can be adapted to optimally "tilt" a given valid inequality by modifying the coefficients of a sparse subset of the variables.

We consider human activity recognition (HAR) from wearable sensor data in manual-work processes, like warehouse order-picking. Such structured domains can often be partitioned into distinct process steps, e.g., packaging or transporting. Each process step can have a different prior distribution over activity classes, e.g., standing or walking, and different system dynamics. Here, we show how such context information can be integrated systematically into a deep neural network-based HAR system. Specifically, we propose a hybrid architecture that combines a deep neural network-that estimates high-level movement descriptors, attributes, from the raw-sensor data-and a shallow classifier, which predicts activity classes from the estimated attributes and (optional) context information, like the currently executed process step. We empirically show that our proposed architecture increases HAR performance, compared to state-of-the-art methods. Additionally, we show that HAR performance can be further increased when information about process steps is incorporated, even when that information is only partially correct., Comment: 3rd International Workshop on Deep Learning for Human Activity Recognition

Sum-Product Networks (SPNs) are expressive probabilistic models that provide exact, tractable inference. They achieve this efficiency by making use of local independence. On the other hand, mixtures of exchangeable variable models (MEVMs) are a class of tractable probabilistic models that make use of exchangeability of discrete random variables to render inference tractable. Exchangeability, which arises naturally in relational domains, has not been considered for efficient representation and inference in SPNs yet. The contribution of this paper is a novel probabilistic model which we call Exchangeability-Aware Sum-Product Networks (XSPNs). It contains both SPNs and MEVMs as special cases, and combines the ability of SPNs to efficiently learn deep probabilistic models with the ability of MEVMs to efficiently handle exchangeable random variables. We introduce a structure learning algorithm for XSPNs and empirically show that they can be more accurate than conventional SPNs when the data contains repeated, interchangeable parts., Comment: accepted at IJCAI 2022

We study the performance of shape-constrained methods for evaluating immune response profiles from early-phase vaccine trials. The motivating problem for this work involves quantifying and comparing the IgG binding immune responses to the first and second variable loops (V1V2 region) arising in HVTN 097 and HVTN 100 HIV vaccine trials. We consider unimodal and log-concave shape-constrained methods to compare the immune profiles of the two vaccines, which is reasonable because the data support that the underlying densities of the immune responses could have these shapes. To this end, we develop novel shape-constrained tests of stochastic dominance and shape-constrained plug-in estimators of the Hellinger distance between two densities. Our techniques are either tuning parameter free, or rely on only one tuning parameter, but their performance is either better (the tests of stochastic dominance) or comparable with the nonparametric methods (the estimators of Hellinger distance). The minimal dependence on tuning parameters is especially desirable in clinical contexts where analyses must be prespecified and reproducible. Our methods are supported by theoretical results and simulation studies.

In [Kim05], Kim gave a new proof of Siegel's Theorem that there are only finitely many $S$-integral points on $\mathbb P^1_{\mathbb Z}\setminus\{0,1,\infty\}$. One advantage of Kim's method is that it in principle allows one to actually find these points, but the calculations grow vastly more complicated as the size of $S$ increases. In this paper, we implement a refinement of Kim's method to explicitly compute various examples where $S$ has size $2$ which has been introduced in [BD19]. In so doing, we exhibit new examples of a natural generalisation of a conjecture of Kim., Comment: 35 pages, comments welcome

In the absence of data from a randomized trial, researchers often aim to use observational data to draw causal inference about the effect of a treatment on a time-to-event outcome. In this context, interest often focuses on the treatment-specific survival curves; that is, the survival curves were the entire population under study to be assigned to receive the treatment or not. Under certain causal conditions, including that all confounders of the treatment-outcome relationship are observed, the treatment-specific survival can be identified with a covariate-adjusted survival function. Several estimators of this function have been proposed, including estimators based on outcome regression, inverse probability weighting, and doubly robust estimators. In this article, we propose a new cross-fitted doubly-robust estimator that incorporates data-adaptive (e.g. machine learning) estimators of the conditional survival functions. We establish conditions on the nuisance estimators under which our estimator is consistent and asymptotically linear, both pointwise and uniformly in time. We also propose a novel ensemble learner for combining multiple candidate estimators of the conditional survival estimators. Notably, our methods and results accommodate events occurring in discrete or continuous time (or both). We investigate the practical performance of our methods using numerical studies and an application to the effect of a surgical treatment to prevent metastases of parotid carcinoma on mortality.

We investigate new methods for generating Lagrangian cuts to solve two-stage stochastic integer programs. Lagrangian cuts can be added to a Benders reformulation, and are derived from solving single scenario integer programming subproblems identical to those used in the nonanticipative Lagrangian dual of a stochastic integer program. While Lagrangian cuts have the potential to significantly strengthen the Benders relaxation, generating Lagrangian cuts can be computationally demanding. We investigate new techniques for generating Lagrangian cuts with the goal of obtaining methods that provide significant improvements to the Benders relaxation quickly. Computational results demonstrate that our proposed method improves the Benders relaxation significantly faster than previous methods for generating Lagrangian cuts and, when used within a branch-and-cut algorithm, significantly reduces the size of the search tree for three classes of test problems.

We present an improved Standard-Model (SM) prediction for the dilepton decay of the neutral pion. The loop amplitude is determined by the pion transition form factor for $\pi^0\to\gamma^*\gamma^*$, for which we employ a dispersive representation that incorporates both space-like and time-like data as well as short-distance constraints. The resulting SM branching fraction, $\text{BR}[\pi^0\to e^+e^-]=6.25(3)\times 10^{-8}$ , sharpens constraints on physics beyond the SM, including pseudoscalar and axial-vector mediators., Comment: 9 pages, 3 figures; journal version

We present a general framework for using existing data to estimate the efficiency gain from using a covariate-adjusted estimator of a marginal treatment effect in a future randomized trial. We describe conditions under which it is possible to define a mapping from the distribution that generated the existing external data to the relative efficiency of a covariate-adjusted estimator compared to an unadjusted estimator. Under conditions, these relative efficiencies approximate the ratio of sample size needed to achieve a desired power. We consider two situations where the outcome is either fully or partially observed and several treatment effect estimands that are of particular interest in most trials. For each such estimand, we develop a semiparametrically efficient estimator of the relative efficiency that allows for the application of flexible statistical learning tools to estimate the nuisance functions and an analytic form of a corresponding Wald-type confidence interval. We also propose a double bootstrap scheme for constructing confidence intervals. We demonstrate the performance of the proposed methods through simulation studies and apply these methods to data to estimate the relative efficiency of using covariate adjustment in Covid-19 therapeutic trials.

VPIC is a general purpose Particle-in-Cell simulation code for modeling plasma phenomena such as magnetic reconnection, fusion, solar weather, and laser-plasma interaction in three dimensions using large numbers of particles. VPIC's capacity in both fidelity and scale makes it particularly well-suited for plasma research on pre-exascale and exascale platforms. In this paper we demonstrate the unique challenges involved in preparing the VPIC code for operation at exascale, outlining important optimizations to make VPIC efficient on accelerators. Specifically, we show the work undertaken in adapting VPIC to exploit the portability-enabling framework Kokkos and highlight the enhancements to VPIC's modeling capabilities to achieve performance at exascale. We assess the achieved performance-portability trade-off through a suite of studies on nine different varieties of modern pre-exascale hardware. Our performance-portability study includes weak-scaling runs on three of the top ten TOP500 supercomputers, as well as a comparison of low-level system performance of hardware from four different vendors.

The optimal dynamic treatment rule (ODTR) framework offers an approach for understanding which kinds of patients respond best to specific treatments -- in other words, treatment effect heterogeneity. Recently, there has been a proliferation of methods for estimating the ODTR. One such method is an extension of the SuperLearner algorithm -- an ensemble method to optimally combine candidate algorithms extensively used in prediction problems -- to ODTRs. Following the "causal roadmap," we causally and statistically define the ODTR and provide an introduction to estimating it using the ODTR SuperLearner. Additionally, we highlight practical choices when implementing the algorithm, including choice of candidate algorithms, metalearners to combine the candidates, and risk functions to select the best combination of algorithms. Using simulations, we illustrate how estimating the ODTR using this SuperLearner approach can uncover treatment effect heterogeneity more effectively than traditional approaches based on fitting a parametric regression of the outcome on the treatment, covariates and treatment-covariate interactions. We investigate the implications of choices in implementing an ODTR SuperLearner at various sample sizes. Our results show the advantages of: (1) including a combination of both flexible machine learning algorithms and simple parametric estimators in the library of candidate algorithms; (2) using an ensemble metalearner to combine candidates rather than selecting only the best-performing candidate; (3) using the mean outcome under the rule as a risk function. Finally, we apply the ODTR SuperLearner to the "Interventions" study, an ongoing randomized controlled trial, to identify which justice-involved adults with mental illness benefit most from cognitive behavioral therapy (CBT) to reduce criminal re-offending.

We explore generalizations of some integrated learning and optimization frameworks for data-driven contextual stochastic optimization that can adapt to heteroscedasticity. We identify conditions on the stochastic program, data generation process, and the prediction setup under which these generalizations possess asymptotic and finite sample guarantees for a class of stochastic programs, including two-stage stochastic mixed-integer programs with continuous recourse. We verify that our assumptions hold for popular parametric and nonparametric regression methods.

Bose-Einstein condensates (BECs) in free fall constitute a promising source for space-borne matter-wave interferometry. Indeed, BECs enjoy a slowly expanding wave function, display a large spatial coherence and can be engineered and probed by optical techniques. On a sounding rocket, we explore matter-wave fringes of multiple spinor components of a BEC released in free fall employing light-pulses to drive Bragg processes and induce phase imprinting. The prevailing microgravity played a crucial role in the observation of these interferences which not only reveal the spatial coherence of the condensates but also allow us to measure differential forces. Our work establishes matter-wave interferometry in space with future applications in fundamental physics, navigation and Earth observation., Comment: 7 pages, 3 figures

Bayes estimators are well known to provide a means to incorporate prior knowledge that can be expressed in terms of a single prior distribution. However, when this knowledge is too vague to express with a single prior, an alternative approach is needed. Gamma-minimax estimators provide such an approach. These estimators minimize the worst-case Bayes risk over a set $\Gamma$ of prior distributions that are compatible with the available knowledge. Traditionally, Gamma-minimaxity is defined for parametric models. In this work, we define Gamma-minimax estimators for general models and propose adversarial meta-learning algorithms to compute them when the set of prior distributions is constrained by generalized moments. Accompanying convergence guarantees are also provided. We also introduce a neural network class that provides a rich, but finite-dimensional, class of estimators from which a Gamma-minimax estimator can be selected. We illustrate our method in two settings, namely entropy estimation and a prediction problem that arises in biodiversity studies., Comment: add funder

We consider data-driven approaches that integrate a machine learning prediction model within distributionally robust optimization (DRO) given limited joint observations of uncertain parameters and covariates. Our framework is flexible in the sense that it can accommodate a variety of regression setups and DRO ambiguity sets. We investigate asymptotic and finite sample properties of solutions obtained using Wasserstein, sample robust optimization, and phi-divergence-based ambiguity sets within our DRO formulations, and explore cross-validation approaches for sizing these ambiguity sets. Through numerical experiments, we validate our theoretical results, study the effectiveness of our approaches for sizing ambiguity sets, and illustrate the benefits of our DRO formulations in the limited data regime even when the prediction model is misspecified.

We discuss the thought-provoking new objective functions for policy learning that were proposed in "More efficient policy learning via optimal retargeting" by Nathan Kallus and "Learning optimal distributionally robust individualized treatment rules" by Weibin Mo, Zhengling Qi, and Yufeng Liu. We show that it is important to take the curvature of the value function into account when working within the retargeting framework, and we introduce two ways to do so. We also describe more efficient approaches for leveraging calibration data when learning distributionally robust policies., Comment: Submitted to the Journal of the American Statistical Association as an invited discussion

We study the stochastic convergence of the Ces\`{a}ro mean of a sequence of random variables. These arise naturally in statistical problems that have a sequential component, where the sequence of random variables is typically derived from a sequence of estimators computed on data. We show that establishing a rate of convergence in probability for a sequence is not sufficient in general to establish a rate in probability for its Ces\`{a}ro mean. We also present several sets of conditions on the sequence of random variables that are sufficient to guarantee a rate of convergence for its Ces\`{a}ro mean. We identify common settings in which these sets of conditions hold.