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Introduction: Heterogeneity of the progression of neurodegenerative diseases is one of the main challenges faced in developing effective therapies. With the increasing number of large clinical databases, disease progression models have led to a better understanding of this heterogeneity. Nevertheless, these diseases may have no clear onset and biological underlying processes may start before the first symptoms. Such an ill-defined disease reference time is an issue for current joint models, which have proven their effectiveness by combining longitudinal and survival data. Objective In this work, we propose a joint non-linear mixed effect model with a latent disease age, to overcome this need for a precise reference time. Method: To do so, we utilized an existing longitudinal model with a latent disease age as a longitudinal sub-model and associated it with a survival sub-model that estimates a Weibull distribution from the latent disease age. We then validated our model on different simulated scenarios. Finally, we benchmarked our model with a state-of-the-art joint model and reference survival and longitudinal models on simulated and real data in the context of Amyotrophic Lateral Sclerosis (ALS). Results: On real data, our model got significantly better results than the state-of-the-art joint model for absolute bias (4.21(4.41) versus 4.24(4.14)(p-value=1.4e-17)), and mean cumulative AUC for right censored events (0.67(0.07) versus 0.61(0.09)(p-value=1.7e-03)). Conclusion: We showed that our approach is better suited than the state-of-the-art in the context where the reference time is not reliable. This work opens up the perspective to design predictive and personalized therapeutic strategies.

This paper is focused on the study of entropic regularization in optimal transport as a smoothing method for Wasserstein estimators, through the prism of the classical tradeoff between approximation and estimation errors in statistics. Wasserstein estimators are defined as solutions of variational problems whose objective function involves the use of an optimal transport cost between probability measures. Such estimators can be regularized by replacing the optimal transport cost by its regularized version using an entropy penalty on the transport plan. The use of such a regularization has a potentially significant smoothing effect on the resulting estimators. In this work, we investigate its potential benefits on the approximation and estimation properties of regularized Wasserstein estimators. Our main contribution is to discuss how entropic regularization may reach, at a lower computational cost, statistical performances that are comparable to those of un-regularized Wasserstein estimators in statistical learning problems involving distributional data analysis. To this end, we present new theoretical results on the convergence of regularized Wasserstein estimators. We also study their numerical performances using simulated and real data in the supervised learning problem of proportions estimation in mixture models using optimal transport.

A popular method for variance reduction in observational causal inference is propensity-based trimming, the practice of removing units with extreme propensities from the sample. This practice has theoretical grounding when the data are homoscedastic and the propensity model is parametric (Yang and Ding, 2018; Crump et al. 2009), but in modern settings where heteroscedastic data are analyzed with non-parametric models, existing theory fails to support current practice. In this work, we address this challenge by developing new methods and theory for sample trimming. Our contributions are three-fold: first, we describe novel procedures for selecting which units to trim. Our procedures differ from previous work in that we trim not only units with small propensities, but also units with extreme conditional variances. Second, we give new theoretical guarantees for inference after trimming. In particular, we show how to perform inference on the trimmed subpopulation without requiring that our regressions converge at parametric rates. Instead, we make only fourth-root rate assumptions like those in the double machine learning literature. This result applies to conventional propensity-based trimming as well and thus may be of independent interest. Finally, we propose a bootstrap-based method for constructing simultaneously valid confidence intervals for multiple trimmed sub-populations, which are valuable for navigating the trade-off between sample size and variance reduction inherent in trimming. We validate our methods in simulation, on the 2007-2008 National Health and Nutrition Examination Survey, and on a semi-synthetic Medicare dataset and find promising results in all settings.

Faithfully summarizing the knowledge encoded by a deep neural network (DNN) into a few symbolic primitive patterns without losing much information represents a core challenge in explainable AI. To this end, Ren et al. (2023c) have derived a series of theorems to prove that the inference score of a DNN can be explained as a small set of interactions between input variables. However, the lack of generalization power makes it still hard to consider such interactions as faithful primitive patterns encoded by the DNN. Therefore, given different DNNs trained for the same task, we develop a new method to extract interactions that are shared by these DNNs. Experiments show that the extracted interactions can better reflect common knowledge shared by different DNNs.

Treatment approaches for colorectal cancer (CRC) are highly dependent on the molecular subtype, as immunotherapy has shown efficacy in cases with microsatellite instability (MSI) but is ineffective for the microsatellite stable (MSS) subtype. There is promising potential in utilizing deep neural networks (DNNs) to automate the differentiation of CRC subtypes by analyzing Hematoxylin and Eosin (H\&E) stained whole-slide images (WSIs). Due to the extensive size of WSIs, Multiple Instance Learning (MIL) techniques are typically explored. However, existing MIL methods focus on identifying the most representative image patches for classification, which may result in the loss of critical information. Additionally, these methods often overlook clinically relevant information, like the tendency for MSI class tumors to predominantly occur on the proximal (right side) colon. We introduce `CIMIL-CRC', a DNN framework that: 1) solves the MSI/MSS MIL problem by efficiently combining a pre-trained feature extraction model with principal component analysis (PCA) to aggregate information from all patches, and 2) integrates clinical priors, particularly the tumor location within the colon, into the model to enhance patient-level classification accuracy. We assessed our CIMIL-CRC method using the average area under the curve (AUC) from a 5-fold cross-validation experimental setup for model development on the TCGA-CRC-DX cohort, contrasting it with a baseline patch-level classification, MIL-only approach, and Clinically-informed patch-level classification approach. Our CIMIL-CRC outperformed all methods (AUROC: $0.92\pm0.002$ (95\% CI 0.91-0.92), vs. $0.79\pm0.02$ (95\% CI 0.76-0.82), $0.86\pm0.01$ (95\% CI 0.85-0.88), and $0.87\pm0.01$ (95\% CI 0.86-0.88), respectively). The improvement was statistically significant.

Accurate and automated gland segmentation on pathological images can assist pathologists in diagnosing the malignancy of colorectal adenocarcinoma. However, due to various gland shapes, severe deformation of malignant glands, and overlapping adhesions between glands. Gland segmentation has always been very challenging. To address these problems, we propose a DEA model. This model consists of two branches: the backbone encoding and decoding network and the local semantic extraction network. The backbone encoding and decoding network extracts advanced Semantic features, uses the proposed feature decoder to restore feature space information, and then enhances the boundary features of the gland through boundary enhancement attention. The local semantic extraction network uses the pre-trained DeepLabv3+ as a Local semantic-guided encoder to realize the extraction of edge features. Experimental results on two public datasets, GlaS and CRAG, confirm that the performance of our method is better than other gland segmentation methods.

Physiological fatigue, a state of reduced cognitive and physical performance resulting from prolonged mental or physical exertion, poses significant challenges in various domains, including healthcare, aviation, transportation, and industrial sectors. As the understanding of fatigue's impact on human performance grows, there is a growing interest in developing effective fatigue monitoring techniques. Among these techniques, electroencephalography (EEG) has emerged as a promising tool for objectively assessing physiological fatigue due to its non-invasiveness, high temporal resolution, and sensitivity to neural activity. This paper aims to provide a comprehensive analysis of the current state of the use of EEG for monitoring physiological fatigue.

The ultimate goal of any numerical scheme for partial differential equations (PDEs) is to compute an approximation of user-prescribed accuracy at quasi-minimal computational time. To this end, algorithmically, the standard adaptive finite element method (AFEM) integrates an inexact solver and nested iterations with discerning stopping criteria balancing the different error components. The analysis ensuring optimal convergence order of AFEM with respect to the overall computational cost critically hinges on the concept of R-linear convergence of a suitable quasi-error quantity. This work tackles several shortcomings of previous approaches by introducing a new proof strategy. First, the algorithm requires several fine-tuned parameters in order to make the underlying analysis work. A redesign of the standard line of reasoning and the introduction of a summability criterion for R-linear convergence allows us to remove restrictions on those parameters. Second, the usual assumption of a (quasi-)Pythagorean identity is replaced by the generalized notion of quasi-orthogonality from [Feischl, Math. Comp., 91 (2022)]. Importantly, this paves the way towards extending the analysis to general inf-sup stable problems beyond the energy minimization setting. Numerical experiments investigate the choice of the adaptivity parameters.

We present efficient MATLAB implementations of the lowest-order primal hybrid finite element method (FEM) for linear second-order elliptic and parabolic problems with mixed boundary conditions in two spatial dimensions. We employ the Crank-Nicolson finite difference scheme for the complete discrete setup of the parabolic problem. All the codes presented are fully vectorized using matrix-wise array operations. Numerical experiments are conducted to show the performance of the software.

Languages have long been described according to their perceived rhythmic attributes. The associated typologies are of interest in psycholinguistics as they partly predict newborns' abilities to discriminate between languages and provide insights into how adult listeners process non-native languages. Despite the relative success of rhythm metrics in supporting the existence of linguistic rhythmic classes, quantitative studies have yet to capture the full complexity of temporal regularities associated with speech rhythm. We argue that deep learning offers a powerful pattern-recognition approach to advance the characterization of the acoustic bases of speech rhythm. To explore this hypothesis, we trained a medium-sized recurrent neural network on a language identification task over a large database of speech recordings in 21 languages. The network had access to the amplitude envelopes and a variable identifying the voiced segments, assuming that this signal would poorly convey phonetic information but preserve prosodic features. The network was able to identify the language of 10-second recordings in 40% of the cases, and the language was in the top-3 guesses in two-thirds of the cases. Visualization methods show that representations built from the network activations are consistent with speech rhythm typologies, although the resulting maps are more complex than two separated clusters between stress and syllable-timed languages. We further analyzed the model by identifying correlations between network activations and known speech rhythm metrics. The findings illustrate the potential of deep learning tools to advance our understanding of speech rhythm through the identification and exploration of linguistically relevant acoustic feature spaces.