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Covariate adjustment is desired by both practitioners and regulators of randomized clinical trials because it improves precision for estimating treatment effects. However, covariate adjustment presents a particular challenge in time-to-event analysis. We propose to apply covariate adjusted pseudovalue regression to estimate between-treatment difference in restricted mean survival times (RMST). Our proposed method incorporates a prognostic covariate to increase precision of treatment effect estimate, maintaining strict type I error control without introducing bias. In addition, the amount of increase in precision can be quantified and taken into account in sample size calculation at the study design stage. Consequently, our proposed method provides the ability to design smaller randomized studies at no expense to statistical power.

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Next Point-of-Interest (POI) recommendation is a critical task in location-based services that aim to provide personalized suggestions for the user's next destination. Previous works on POI recommendation have laid focused on modeling the user's spatial preference. However, existing works that leverage spatial information are only based on the aggregation of users' previous visited positions, which discourages the model from recommending POIs in novel areas. This trait of position-based methods will harm the model's performance in many situations. Additionally, incorporating sequential information into the user's spatial preference remains a challenge. In this paper, we propose Diff-POI: a Diffusion-based model that samples the user's spatial preference for the next POI recommendation. Inspired by the wide application of diffusion algorithm in sampling from distributions, Diff-POI encodes the user's visiting sequence and spatial character with two tailor-designed graph encoding modules, followed by a diffusion-based sampling strategy to explore the user's spatial visiting trends. We leverage the diffusion process and its reversed form to sample from the posterior distribution and optimized the corresponding score function. We design a joint training and inference framework to optimize and evaluate the proposed Diff-POI. Extensive experiments on four real-world POI recommendation datasets demonstrate the superiority of our Diff-POI over state-of-the-art baseline methods. Further ablation and parameter studies on Diff-POI reveal the functionality and effectiveness of the proposed diffusion-based sampling strategy for addressing the limitations of existing methods.

Permutation tests are widely recognized as robust alternatives to tests based on the normal theory. Random permutation tests have been frequently employed to assess the significance of variables in linear models. Despite their widespread use, existing random permutation tests lack finite-sample and assumption-free guarantees for controlling type I error in partial correlation tests. To address this standing challenge, we develop a conformal test through permutation-augmented regressions, which we refer to as PALMRT. PALMRT not only achieves power competitive with conventional methods but also provides reliable control of type I errors at no more than $2\alpha$ given any targeted level $\alpha$, for arbitrary fixed-designs and error distributions. We confirmed this through extensive simulations. Compared to the cyclic permutation test (CPT), which also offers theoretical guarantees, PALMRT does not significantly compromise power or set stringent requirements on the sample size, making it suitable for diverse biomedical applications. We further illustrate their differences in a long-Covid study where PALMRT validated key findings previously identified using the t-test, while CPT suffered from a drastic loss of power. We endorse PALMRT as a robust and practical hypothesis test in scientific research for its superior error control, power preservation, and simplicity.

In general, high order splitting methods suffer from an order reduction phenomena when applied to the time integration of partial differential equations with non-periodic boundary conditions. In the last decade, there were introduced several modifications to prevent the second order Strang Splitting method from such a phenomena. In this article, inspired by these recent corrector techniques, we introduce a splitting method of order three for a class of semilinear parabolic problems that avoids order reduction in the context of non-periodic boundary conditions. We give a proof for the third order convergence of the method in a simplified linear setting and confirm the result by numerical experiments. Moreover, we show numerically that the high order convergence persists for an order four variant of a splitting method, and also for a nonlinear source term.

With the increasing availability of large scale datasets, computational power and tools like automatic differentiation and expressive neural network architectures, sequential data are now often treated in a data-driven way, with a dynamical model trained from the observation data. While neural networks are often seen as uninterpretable black-box architectures, they can still benefit from physical priors on the data and from mathematical knowledge. In this paper, we use a neural network architecture which leverages the long-known Koopman operator theory to embed dynamical systems in latent spaces where their dynamics can be described linearly, enabling a number of appealing features. We introduce methods that enable to train such a model for long-term continuous reconstruction, even in difficult contexts where the data comes in irregularly-sampled time series. The potential for self-supervised learning is also demonstrated, as we show the promising use of trained dynamical models as priors for variational data assimilation techniques, with applications to e.g. time series interpolation and forecasting.

Marginal structural models (MSMs) are often used to estimate causal effects of treatments on survival time outcomes from observational data when time-dependent confounding may be present. They can be fitted using, e.g., inverse probability of treatment weighting (IPTW). It is important to evaluate the performance of statistical methods in different scenarios, and simulation studies are a key tool for such evaluations. In such simulation studies, it is common to generate data in such a way that the model of interest is correctly specified, but this is not always straightforward when the model of interest is for potential outcomes, as is an MSM. Methods have been proposed for simulating from MSMs for a survival outcome, but these methods impose restrictions on the data-generating mechanism. Here we propose a method that overcomes these restrictions. The MSM can be a marginal structural logistic model for a discrete survival time or a Cox or additive hazards MSM for a continuous survival time. The hazard of the potential survival time can be conditional on baseline covariates, and the treatment variable can be discrete or continuous. We illustrate the use of the proposed simulation algorithm by carrying out a brief simulation study. This study compares the coverage of confidence intervals calculated in two different ways for causal effect estimates obtained by fitting an MSM via IPTW.

Besov priors are nonparametric priors that can model spatially inhomogeneous functions. They are routinely used in inverse problems and imaging, where they exhibit attractive sparsity-promoting and edge-preserving features. A recent line of work has initiated the study of their asymptotic frequentist convergence properties. In the present paper, we consider the theoretical recovery performance of the posterior distributions associated to Besov-Laplace priors in the density estimation model, under the assumption that the observations are generated by a possibly spatially inhomogeneous true density belonging to a Besov space. We improve on existing results and show that carefully tuned Besov-Laplace priors attain optimal posterior contraction rates. Furthermore, we show that hierarchical procedures involving a hyper-prior on the regularity parameter lead to adaptation to any smoothness level.

Early warnings for dynamical transitions in complex systems or high-dimensional observation data are essential in many real world applications, such as gene mutation, brain diseases, natural disasters, financial crises, and engineering reliability. To effectively extract early warning signals, we develop a novel approach: the directed anisotropic diffusion map that captures the latent evolutionary dynamics in low-dimensional manifold. Applying the methodology to authentic electroencephalogram (EEG) data, we successfully find the appropriate effective coordinates, and derive early warning signals capable of detecting the tipping point during the state transition. Our method bridges the latent dynamics with the original dataset. The framework is validated to be accurate and effective through numerical experiments, in terms of density and transition probability. It is shown that the second coordinate holds meaningful information for critical transition in various evaluation metrics.

A general class of the almost instantaneous fixed-to-variable-length (AIFV) codes is proposed, which contains every possible binary code we can make when allowing finite bits of decoding delay. The contribution of the paper lies in the following. (i) Introducing $N$-bit-delay AIFV codes, constructed by multiple code trees with higher flexibility than the conventional AIFV codes. (ii) Proving that the proposed codes can represent any uniquely-encodable and uniquely-decodable variable-to-variable length codes. (iii) Showing how to express codes as multiple code trees with minimum decoding delay. (iv) Formulating the constraints of decodability as the comparison of intervals in the real number line. The theoretical results in this paper are expected to be useful for further study on AIFV codes.

Spinal cord stimulation (SCS) is a therapeutic approach used for the management of chronic pain. It involves the delivery of electrical impulses to the spinal cord via an implanted device, which when given suitable stimulus parameters can mask or block pain signals. Selection of optimal stimulation parameters usually happens in the clinic under the care of a provider whereas at-home SCS optimization is managed by the patient. In this paper, we propose a recommender system for the management of pain in chronic pain patients undergoing SCS. In particular, we use a contextual multi-armed bandit (CMAB) approach to develop a system that recommends SCS settings to patients with the aim of improving their condition. These recommendations, sent directly to patients though a digital health ecosystem, combined with a patient monitoring system closes the therapeutic loop around a chronic pain patient over their entire patient journey. We evaluated the system in a cohort of SCS-implanted ENVISION study subjects (Clinicaltrials.gov ID: NCT03240588) using a combination of quality of life metrics and Patient States (PS), a novel measure of holistic outcomes. SCS recommendations provided statistically significant improvement in clinical outcomes (pain and/or QoL) in 85\% of all subjects (N=21). Among subjects in moderate PS (N=7) prior to receiving recommendations, 100\% showed statistically significant improvements and 5/7 had improved PS dwell time. This analysis suggests SCS patients may benefit from SCS recommendations, resulting in additional clinical improvement on top of benefits already received from SCS therapy.

In this paper, two novel classes of implicit exponential Runge-Kutta (ERK) methods are studied for solving highly oscillatory systems. Firstly, we analyze the symplectic conditions for two kinds of exponential integrators and obtain the symplectic method. In order to effectively solve highly oscillatory problems, we try to design the highly accurate implicit ERK integrators. By comparing the Taylor series expansion of numerical solution with exact solution, it can be verified that the order conditions of two new kinds of exponential methods are identical to classical Runge-Kutta (RK) methods, which implies that using the coefficients of RK methods, some highly accurate numerical methods are directly formulated. Furthermore, we also investigate the linear stability properties for these exponential methods. Finally, numerical results not only display the long time energy preservation of the symplectic method, but also present the accuracy and efficiency of these formulated methods in comparison with standard ERK methods.

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