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.
The prevailing statistical approach to analyzing persistence diagrams is concerned with filtering out topological noise. In this paper, we adopt a different viewpoint and aim at estimating the actual distribution of a random persistence diagram, which captures both topological signal and noise. To that effect, Chazel and Divol (2019) proved that, under general conditions, the expected value of a random persistence diagram is a measure admitting a Lebesgue density, called the persistence intensity function. In this paper, we are concerned with estimating the persistence intensity function and a novel, normalized version of it -- called the persistence density function. We present a class of kernel-based estimators based on an i.i.d. sample of persistence diagrams and derive estimation rates in the supremum norm. As a direct corollary, we obtain uniform consistency rates for estimating linear representations of persistence diagrams, including Betti numbers and persistence surfaces. Interestingly, the persistence density function delivers stronger statistical guarantees.
We study the multiplicative hazards model with intermittently observed longitudinal covariates and time-varying coefficients. For such models, the existing {\it ad hoc} approach, such as the last value carried forward, is biased. We propose a kernel weighting approach to get an unbiased estimation of the non-parametric coefficient function and establish asymptotic normality for any fixed time point. Furthermore, we construct the simultaneous confidence band to examine the overall magnitude of the variation. Simulation studies support our theoretical predictions and show favorable performance of the proposed method. A data set from cerebral infarction is used to illustrate our methodology.
This work focuses on accelerating the multiplication of a dense random matrix with a (fixed) sparse matrix, which is frequently used in sketching algorithms. We develop a novel scheme that takes advantage of blocking and recomputation (on-the-fly random number generation) to accelerate this operation. The techniques we propose decrease memory movement, thereby increasing the algorithm's parallel scalability in shared memory architectures. On the Intel Frontera architecture, our algorithm can achieve 2x speedups over libraries such as Eigen and Intel MKL on some examples. In addition, with 32 threads, we can obtain a parallel efficiency of up to approximately 45%. We also present a theoretical analysis for the memory movement lower bound of our algorithm, showing that under mild assumptions, it's possible to beat the data movement lower bound of general matrix-matrix multiply (GEMM) by a factor of $\sqrt M$, where $M$ is the cache size. Finally, we incorporate our sketching algorithm into a randomized least squares solver. For extremely over-determined sparse input matrices, we show that our results are competitive with SuiteSparse; in some cases, we obtain a speedup of 10x over SuiteSparse.
Spinal cord segmentation is clinically relevant and is notably used to compute spinal cord cross-sectional area (CSA) for the diagnosis and monitoring of cord compression or neurodegenerative diseases such as multiple sclerosis. While several semi and automatic methods exist, one key limitation remains: the segmentation depends on the MRI contrast, resulting in different CSA across contrasts. This is partly due to the varying appearance of the boundary between the spinal cord and the cerebrospinal fluid that depends on the sequence and acquisition parameters. This contrast-sensitive CSA adds variability in multi-center studies where protocols can vary, reducing the sensitivity to detect subtle atrophies. Moreover, existing methods enhance the CSA variability by training one model per contrast, while also producing binary masks that do not account for partial volume effects. In this work, we present a deep learning-based method that produces soft segmentations of the spinal cord. Using the Spine Generic Public Database of healthy participants ($\text{n}=267$; $\text{contrasts}=6$), we first generated participant-wise soft ground truth (GT) by averaging the binary segmentations across all 6 contrasts. These soft GT, along with a regression-based loss function, were then used to train a UNet model for spinal cord segmentation. We evaluated our model against state-of-the-art methods and performed ablation studies involving different GT mask types, loss functions, and contrast-specific models. Our results show that using the soft average segmentations along with a regression loss function reduces CSA variability ($p < 0.05$, Wilcoxon signed-rank test). The proposed spinal cord segmentation model generalizes better than the state-of-the-art contrast-specific methods amongst unseen datasets, vendors, contrasts, and pathologies (compression, lesions), while accounting for partial volume effects.
Bidirectional typing is a discipline in which the typing judgment is decomposed explicitly into inference and checking modes, allowing to control the flow of type information in typing rules and to specify algorithmically how they should be used. Bidirectional typing has been fruitfully studied and bidirectional systems have been developed for many type theories. However, the formal development of bidirectional typing has until now been kept confined to specific theories, with general guidelines remaining informal. In this work, we give a generic account of bidirectional typing for a general class of dependent type theories. This is done by first giving a general definition of type theories (or equivalently, a logical framework), for which we define declarative and bidirectional type systems. We then show, in a theory-independent fashion, that the two systems are equivalent. This equivalence is then explored to establish the decidability of typing for weak normalizing theories, yielding a generic type-checking algorithm that has been implemented in a prototype and used in practice with many theories.
We develop a provably efficient importance sampling scheme that estimates exit probabilities of solutions to small-noise stochastic reaction-diffusion equations from scaled neighborhoods of a stable equilibrium. The moderate deviation scaling allows for a local approximation of the nonlinear dynamics by their linearized version. In addition, we identify a finite-dimensional subspace where exits take place with high probability. Using stochastic control and variational methods we show that our scheme performs well both in the zero noise limit and pre-asymptotically. Simulation studies for stochastically perturbed bistable dynamics illustrate the theoretical results.
An important strategy for identifying principal causal effects, which are often used in settings with noncompliance, is to invoke the principal ignorability (PI) assumption. As PI is untestable, it is important to gauge how sensitive effect estimates are to its violation. We focus on this task for the common one-sided noncompliance setting where there are two principal strata, compliers and noncompliers. Under PI, compliers and noncompliers share the same outcome-mean-given-covariates function under the control condition. For sensitivity analysis, we allow this function to differ between compliers and noncompliers in several ways, indexed by an odds ratio, a generalized odds ratio, a mean ratio, or a standardized mean difference sensitivity parameter. We tailor sensitivity analysis techniques (with any sensitivity parameter choice) to several types of PI-based main analysis methods, including outcome regression, influence function (IF) based and weighting methods. We illustrate the proposed sensitivity analyses using several outcome types from the JOBS II study. This application estimates nuisance functions parametrically -- for simplicity and accessibility. In addition, we establish rate conditions on nonparametric nuisance estimation for IF-based estimators to be asymptotically normal -- with a view to inform nonparametric inference.
Increasing individuals' awareness of their own body signals can lead to improved interoception, enabling the brain to estimate current body states more accurately and in a timely manner. However, certain body signals, such as eye movements, often go unnoticed by individuals themselves. This study aimed to test the hypothesis that providing eye-movement-correlated tactile feedback on the body enhances individuals' awareness of their attentive states, subsequently improving attention. Our results demonstrate the effectiveness of such feedback in redirecting and enhancing attention, particularly in the presence of distractions during long-duration tasks. Additionally, we observed that people's gaze behaviors changed in response to the tactile feedback, suggesting an increased self-awareness of current eye movements and attentive states. Ultimately, these changes in gaze behaviors contribute to the modulation of attentive states. Our findings highlight the potential of eye-movement-correlated bodily tactile feedback to increase individuals' self-awareness of their eye movements and attentive states. By providing real-time feedback through tactile stimuli, we can actively engage individuals in regulating their attention and enhancing their overall performance.
Agent-based models are widely used to predict infectious disease spread. For these predictions, one needs to understand how each input parameter affects the result. Here, some parameters may affect the sensitivities of others, requiring the analysis of higher order coefficients through e.g. Sobol sensitivity analysis. The geographical structures of real-world regions are distinct in that they are difficult to reduce to single parameter values, making a unified sensitivity analysis intractable. Yet analyzing the importance of geographical structure on the sensitivity of other input parameters is important because a strong effect would justify the use of models with real-world geographical representations, as opposed to stylized ones. Here we perform a grouped Sobol's sensitivity analysis on COVID-19 spread simulations across a set of three diverse real-world geographical representations. We study the differences in both results and the sensitivity of non-geographical parameters across these geographies. By comparing Sobol indices of parameters across geographies, we find evidence that infection rate could have more sensitivity in regions where the population is segregated, while parameters like recovery period of mild cases are more sensitive in regions with mixed populations. We also show how geographical structure affects parameter sensitivity changes over time.
We introduce an efficient first-order primal-dual method for the solution of nonsmooth PDE-constrained optimization problems. We achieve this efficiency through not solving the PDE or its linearisation on each iteration of the optimization method. Instead, we run the method interwoven with a simple conventional linear system solver (Jacobi, Gauss-Seidel, conjugate gradients), always taking only one step of the linear system solver for each step of the optimization method. The control parameter is updated on each iteration as determined by the optimization method. We prove linear convergence under a second-order growth condition, and numerically demonstrate the performance on a variety of PDEs related to inverse problems involving boundary measurements.