Agglomerative hierarchical clustering is one of the most widely used approaches for exploring how observations in a dataset relate to each other. However, its greedy nature makes it highly sensitive to small perturbations in the data, often producing different clustering results and making it difficult to separate genuine structure from spurious patterns. In this paper, we show how randomizing hierarchical clustering can be useful not just for measuring stability but also for designing valid hypothesis testing procedures based on the clustering results. We propose a simple randomization scheme together with a method for constructing a valid p-value at each node of the hierarchical clustering dendrogram that quantifies evidence against performing the greedy merge. Our test controls the Type I error rate, works with any hierarchical linkage without case-specific derivations, and simulations show it is substantially more powerful than existing selective inference approaches. To demonstrate the practical utility of our p-values, we develop an adaptive $α$-spending procedure that estimates the number of clusters, with a probabilistic guarantee on overestimation. Experiments on simulated and real data show that this estimate yields powerful clustering and can be used, for example, to assess clustering stability across multiple runs of the randomized algorithm.

Heterogeneous data are now ubiquitous in many applications in which correctly identifying the subgroups from a heterogeneous population is critical. Although there is an increasing body of literature on subgroup detection, existing methods mainly focus on the univariate response setting. In this paper, we propose a joint heterogeneity and reduced-rank learning framework to simultaneously identify the subgroup structure and estimate the covariate effects for heterogeneous multivariate response regression. In particular, our approach uses rank-constrained pairwise fusion penalization and conducts the subgroup analysis without requiring prior knowledge regarding the individual subgroup memberships. We implement the proposed approach by an alternating direction method of multipliers (ADMM) algorithm and show its convergence. We also establish the asymptotic properties for the resulting estimators under mild and interpretable conditions. A predictive information criterion is proposed to select the rank of the coefficient matrix with theoretical support. The effectiveness of the proposed approach is demonstrated through simulation studies and a real data application.

We develop a novel characterization of extremal dependence between two cortical regions of the brain when its signals display extremely large amplitudes. We show that connectivity in the tails of the distribution reveals unique features of extreme events (e.g., seizures) that can help to identify their occurrence. Numerous studies have established that connectivity-based features are effective for discriminating brain states. Here, we demonstrate the advantage of the proposed approach: that tail connectivity provides additional discriminatory power, enabling more accurate identification of extreme-related events and improved seizure risk management. Common approaches in tail dependence modeling use pairwise summary measures or parametric models. However, these approaches do not identify channels that drive the maximal tail dependence between two groups of signals -- an information that is useful when analyzing electroencephalography of epileptic patients where specific channels are responsible for seizure occurrences. A familiar approach in traditional signal processing is canonical correlation, which we extend to the tails to develop a visualization of extremal channel-contributions. Through the tail pairwise dependence matrix (TPDM), we develop a computationally-efficient estimator for our canonical tail dependence measure. Our method is then used for accurate frequency-based soft clustering of neonates, distinguishing those with seizures from those without.

Extreme weather events are widely studied in fields such as agriculture, ecology, and meteorology. The spatio-temporal co-occurrence of extreme events can strengthen or weaken under changing climate conditions. In this paper, we propose a novel approach to model spatio-temporal extremes by integrating climate indices via a conditional variational autoencoder (cXVAE). A convolutional neural network (CNN) is embedded in the decoder to convolve climatological indices with the spatial dependence within the latent space, thereby allowing the decoder to be dependent on the climate variables. There are three main contributions here. First, we demonstrate through extensive simulations that the proposed conditional XVAE accurately emulates spatial fields and recovers spatially and temporally varying extremal dependence with very low computational cost post training. Second, we provide a simple, scalable approach to detecting condition-driven shifts and whether the dependence structure is invariant to the conditioning variable. Third, when dependence is found to be condition-sensitive, the conditional XVAE supports counterfactual experiments allowing intervention on the climate covariate and propagating the associated change through the learned decoder to quantify differences in joint tail risk, co-occurrence ranges, and return metrics. To demonstrate the practical utility and performance of the model in real-world scenarios, we apply our method to analyze the monthly maximum Fire Weather Index (FWI) over eastern Australia from 2014 to 2024 conditioned on the El Niño/Southern Oscillation (ENSO) index.

We theoretically demonstrate that the generalization error of interpolators for machine learning models under teacher-student settings becomes 0 once the number of training samples exceeds a certain threshold. Understanding the high generalization ability of large-scale models such as deep neural networks (DNNs) remains one of the central open problems in machine learning theory. While recent theoretical studies have attributed this phenomenon to the implicit bias of stochastic gradient descent (SGD) toward well-generalizing solutions, empirical evidences indicate that it primarily stems from properties of the model itself. Specifically, even randomly sampled interpolators, which are parameters that achieve zero training error, have been observed to generalize effectively. In this study, under a teacher-student framework, we prove that the generalization error of randomly sampled interpolators becomes exactly zero once the number of training samples exceeds a threshold determined by the geometric structure of the interpolator set in parameter space. As a proof technique, we leverage tools from algebraic geometry to mathematically characterize this geometric structure.

Stochastic Reaction Networks (SRNs) are a fundamental modeling framework for systems ranging from chemical kinetics and epidemiology to ecological and synthetic biological processes. A central computational challenge is the estimation of expected outputs across initial conditions and times, a task that is rarely solvable analytically and becomes computationally prohibitive with current methods such as Finite State Projection or the Stochastic Simulation Algorithm. Existing deep learning approaches offer empirical scalability, but provide neither interpretability nor reliability guarantees, limiting their use in scientific analysis and in applications where model outputs inform real-world decisions. Here we introduce DeepSKA, a neural framework that jointly achieves interpretability, guaranteed reliability, and substantial computational gains. DeepSKA yields mathematically transparent representations that generalise across states, times, and output functions, and it integrates this structure with a small number of stochastic simulations to produce unbiased, provably convergent, and dramatically lower-variance estimates than classical Monte Carlo. We demonstrate these capabilities across nine SRNs, including nonlinear and non-mass-action models with up to ten species, where DeepSKA delivers accurate predictions and orders-of-magnitude efficiency improvements. This interpretable and reliable neural framework offers a principled foundation for developing analogous methods for other Markovian systems, including stochastic differential equations.

Semi-supervised learning (SSL) constructs classifiers from datasets in which only a subset of observations is labelled, a situation that naturally arises because obtaining labels often requires expert judgement or costly manual effort. This motivates methods that integrate labelled and unlabelled data within a learning framework. Most SSL approaches assume that label absence is harmless, typically treated as missing completely at random or ignored, but in practice, the missingness process can be informative, as the chances of an observation being unlabelled may depend on the ambiguity of its feature vector. In such cases, the missingness indicators themselves provide additional information that, if properly modelled, may improve estimation efficiency. The \textbf{SSLfmm} package for R is designed to capture this behaviour by estimating the Bayes' classifier under a finite mixture model in which each component corresponding to a class follows a multivariate normal distribution. It incorporates a mixed-missingness mechanism that combines a missing completely at random (MCAR) component with a (non-ignorable) missing at random (MAR) component, the latter modelling the probability of label missingness as a logistic function of the entropy based on the features. Parameters are estimated via an Expectation--Conditional Maximisation algorithm. In the two-class Gaussian setting with arbitrary covariance matrices, the resulting classifier trained on partially labelled data may, in some cases, achieve a lower misclassification rate than the supervised version in the case where all the labels are known. The package includes a practical tool for modelling and illustrates its performance through simulated examples.

Clustering in stationary and nonstationary settings, where data distributions remain static or evolve over time, requires models that can adapt to distributional shifts while preserving previously learned cluster structures. This paper proposes an Adaptive Resonance Theory (ART)-based topological clustering algorithm that autonomously adjusts its recalculation interval and vigilance threshold through a diversity-driven adaptation mechanism. This mechanism enables hyperparameter-free learning that maintains cluster stability and continuity in dynamic environments. Experiments on 24 real-world datasets demonstrate that the proposed algorithm outperforms state-of-the-art methods in both clustering performance and continual learning capability. These results highlight the effectiveness of the proposed parameter adaptation in mitigating catastrophic forgetting and maintaining consistent clustering in evolving data streams. Source code is available at https://github.com/Masuyama-lab/IDAT

The application of Vision-Language Models (VLMs) in medicine is critically hampered by the scarcity of high-quality, expert-annotated data. Supervised Fine-Tuning (SFT) on existing datasets often leads to poor generalization on unseen modalities and tasks, while Reinforcement Learning (RL), a promising alternative, is stymied by the lack of reliable reward signals in this data-scarce domain. To break this impasse, we introduce Generative Reward Learning for Medical Reasoning (MedGR$^2$), a novel framework that creates a self-improving virtuous cycle. MedGR$^2$ co-develops a data generator and a reward model, enabling the automated, continuous creation of high-quality, multi-modal medical data that serves as both a superior training source for SFT and RL. Our experiments demonstrate that SFT with MedGR$^2$-produced data already surpasses baselines trained on large-scale, human-curated datasets. Crucially, when leveraging this data for RL via Group Relative Policy Optimization (GRPO), our model achieves state-of-the-art cross-modality and cross-task generalization, significantly outperforming specialized RL-based methods. Furthermore, our compact model, empowered by MedGR$^2$, achieves performance competitive with foundation models possessing over 10 times more parameters. MedGR$^2$ presents a new paradigm for data-efficient learning in high-stakes domains, transforming the problem from data scarcity to data generation and unlocking the full potential of RL for building truly generalizable medical AI.

Magnetic resonance imaging (MRI) inpainting supports numerous clinical and research applications. We introduce the first generative model that conditions on voxel-level, continuous tumor concentrations to synthesize high-fidelity brain tumor MRIs. For the BraTS 2025 Inpainting Challenge, we adapt this architecture to the complementary task of healthy tissue restoration by setting the tumor concentrations to zero. Our latent diffusion model conditioned on both tissue segmentations and the tumor concentrations generates 3D spatially coherent and anatomically consistent images for both tumor synthesis and healthy tissue inpainting. For healthy inpainting, we achieve a PSNR of 18.5, and for tumor inpainting, we achieve 17.4. Our code is available at: https://github.com/valentin-biller/ldm.git