Electronic health records (EHR) pose large-scale multi-disease modeling problems in which many outcomes are rare and strongly influenced by shared risk factors. While modern approaches achieve strong predictive performance, they often treat diseases independently or rely on black-box architectures, offering limited insight into how risk factors organize disease risk and little principled uncertainty quantification. We introduce a Bayesian hypergraph inference framework that reframes multi-disease modeling around latent, risk-factor-modulated disease pathways. Risk factors act on hyperedges, latent disease subsets with shared risk patterns, allowing diseases to participate in multiple distinct pathways and enabling interpretable, higher-order structure beyond pairwise associations. A repulsion prior encourages parsimonious and identifiable structure, while posterior inference provides calibrated uncertainty over both disease groupings and risk-factor influence. To enable scalable inference on large EHR datasets, we develop a structured variational inference algorithm that preserves logical dependencies among hyperedge existence, disease membership, and pathway-level effects. Experiments on simulated data and UK Biobank demonstrate stable and interpretable disease pathway structure, well-calibrated uncertainty, improved estimation for rare diseases, and competitive predictive performance.

Gaussian graphical models in the spectral domain offer a principled approach for recovering conditional dependence structures in stationary high-dimensional time series. Inference on the spectral precision matrix at a fixed frequency enables tests of frequency-specific conditional associations among time series components. The problem is challenging because finite-sample discrete Fourier transforms induce truncation and smoothing biases, while the complex-valued nature of the spectral precision matrix complicates high-dimensional variance estimation, rendering methods for i.i.d. samples not directly applicable. Existing approaches do not provide full likelihood-based inference for the discrete Fourier transforms. We propose a high-dimensional inference framework for sparse spectral precision matrices using the full likelihood of neighboring discrete Fourier transforms. We construct a debiased complex graphical lasso estimator at any fixed frequency. Using asymptotic theory for quadratic forms of multivariate time series, we establish its asymptotic normality and construct entry-wise consistent covariance estimators by aggregating information across neighboring frequencies. The key theoretical contribution is the simultaneous control of regularization, finite-sample truncation, and smoothing biases, enabling valid inference. Simulation studies show reliable coverage away from zero frequency and improved detection power over the benchmark, with false discovery rates near the desired level.

Agentic reinforcement learning (RL) enables LLM agents to improve continuously from environment rewards, yet the resulting policies do not systematically accumulate reusable strategies that generalize across tasks. Modular skills can provide such reusable strategies, yet existing skill-augmented RL methods decouple skill creation from policy optimization, risking adopting skills that conflict with the evolving policy. Inspired by Anthropic's Skill Creator, we introduce RESKILL, an RL-in-the-loop skill creation framework that reconciles skill evolution with policy learning. RESKILL exploits the group-wise structure of GRPO to naturally embed three mechanisms with only marginal additional overhead: (1) an assertion-driven skill creator that diagnoses failures from past experience and proposes conditional, trigger-based skill revisions; (2) within-group rollout sampling that enables controlled comparison of skill versions, capturing which version best supports the policy's ongoing learning; and (3) Thompson Sampling with adaptive discounting to balance exploration and exploitation in skill version selection as the policy evolves. Across several domains, RESKILL consistently outperforms existing memory and skill-based RL methods, with the largest gains on unseen tasks. Analysis of the skill lifecycle shows skills being automatically created, tested, refined, and pruned as the policy improves, demonstrating reconciled skill-policy co-evolution.

Recurrent neural networks maintain a hidden state $h_t$, but its probabilistic meaning is often unclear. We study hidden-state stability through \emph{backward coherence}: the extent to which $h_t$ can be reconstructed from $h_{t+1}$ by a learned backward projector $g_ϕ$. Under contraction and summable backward drift, the hidden-state sequence forms a quasi-reverse-martingale. This yields almost-sure convergence, rates under mixing, an interpretable limiting representation, finite pathwise stopping times, and a theoretical framework for time-uniform confidence sequences. Simulations support the theory. Backward-coherence regularisation reduces the empirical quasi-martingale total $\hat Q$ by $43$--$58%$, reaches stability $28$--$44%$ earlier than an unregularised RNN, and gives tracking-error recovery consistent with geometric bounds. Additional tests confirm echo-state forgetting rates bounded by $ρ$ and verify the increment-sum tube $R_t$ with $100%$ simultaneous coverage, although $R_t$ is conservative; in practice, the defect-tail proxy $\hat Q_t$ is the more useful monitor. The backward-coherence loss is also equivalent to minimising a Kullback--Leibler divergence in a Gaussian backward model, linking the method to variational inference. Extensions cover $ϕ$-mixing inputs, change-point tracking, and finite-sample concentration. Three real-data studies further validate the approach. On PhysioNet 2012 ICU data, the Reverse Martingale RNN (RMRNN) matches RNN mortality-prediction AUC while reaching stable representations 13 hours earlier. On FRED-MD, it reduces one-month-ahead forecast error by about fourfold under concept drift. On UCI Human Activity Recognition, it maintains lower post-transition tracking error with geometric decay. The guarantees apply under the stated assumptions; universality is not claimed.

Undirected graphical models provide a fundamental framework for representing conditional independence structures among high-dimensional random variables. While undirected graphical model selection has become a central problem in high-dimensional statistics, most existing methods are restricted to parametric settings. In this paper, we develop a nonparametric approach to undirected graphical model selection based on diffusion models. Recent work has shown that diffusion models can adapt to the unknown graph structure of the underlying distribution, yet utilizing these models for explicit graph estimation remains unexplored. To bridge this gap, we introduce a novel diffusion-based method for nonparametric undirected graphical model selection. We establish the model selection consistency of the proposed method and demonstrate its empirical performance through extensive simulations and two real data analyses.

We study component recovery and mixing-matrix estimation from unlabeled finite mixtures whose observable distributions share the same latent components but have unknown mixing weights. The main identifying signal is marginal independence: each component is assumed to be independent on at least one coordinate pair, but no labels, clean component samples, or mixing weights are observed. We first prove a structural result for product components: under linear independence of the univariate marginals, any independent affine combination of the components must coincide with a single component. We then extend this principle to observable mixtures and show that, under full-rank and no-cancellation conditions, marginally independent affine combinations recover the corresponding latent components. When every component is independent on some coordinate pair, all components are identifiable, and the mixing matrix is recoverable under the stated completion conditions. Finally, we propose a Product-Marginal Maximum Mean Discrepancy (PM-MMD) estimator over affine combinations of the observable mixtures and prove uniform convergence and stability under approximate marginal independence. This framework also separates the empirical roles of the assumptions: irreducibility is, in general, not directly testable from the unlabeled mixtures alone, whereas marginal independence yields a candidate-level diagnostic through held-out PM-MMD. Controlled and flow-cytometry experiments show when marginal independence provides a useful recovery signal. In the reported multi-component comparisons, condition-aware representative selection stabilizes PM-MMD and improves recovery relative to clustering, factorization, and pairwise mixture-proportion baselines using the same unlabeled mixtures.

Scientific machine learning is limited less by model size than by the data it is trained on. Observational data records what happened but not why; template synthetic data has a known generating process but only for the simulator's template, not the case a user faces. We argue a third option is now operationally feasible: instrumented data, in which every datum carries the mechanistic model that produced it, an explicit uncertainty over that model, and an executable family of counterfactuals. Verification-and-validation (V&V) instrumented image-to-simulation pipelines are one realisation: a sensor observation becomes a fully specified, solver-backed simulation with explicit, editable parameters and a propagated aleatoric/epistemic uncertainty. The substrate is case-specific, mechanistically supervised, and supports causal interventions through Pearl's do-operator.

In regression modelling, the primary objective is to approximate the true conditional mean of a response given a set of features. To this end, various statistical models are used to fit a regression function that provides a mean estimate for each single set of features. This function is said to be calibrated if the resulting mean estimates match the true conditional means for almost all features. Aiming for calibration seems not achievable in practice as models are fitted on finite samples of noisy observations. A weaker notion of calibration is auto-calibration (sometimes also called mean-calibration or well-calibration); see, for example, Kr uger-Ziegel [22] and Denuit et al. [7]. This notion goes back to earlier works on the reliability of probabilistic forecasts in meteorology; we refer to Bross [2], Sanders [26] and Murphy-Winkler [23]. It means that when responses are grouped according to their mean estimates, the average of the responses within each group matches this estimate. This property is important in various applications where sums of mean estimates have to match sums of responses at a global and local level. This is, for example, the case in insurance pricing as an auto-calibrated pricing system avoids systematic cross-subsidy between different price cohorts; we refer the reader to Pohle [24], Denuit et al. [6], Fissler et al. [9] and W uthrich-Merz [30].

Externally controlled survival trials are increasingly used when concurrent randomized controls are infeasible, particularly in oncology and rare-disease settings with time-to-event endpoints. We target an average-treatment-effect-on-the-treated (ATT)-type marginal hazard-ratio estimand, comparing treatment with counterfactual control in the treated trial population, and estimate it using inverse-probability-weighted (IPW) Cox regression. Valid inference is challenging because IPW Cox regression depends on the weights through both event contributions and risk-set averages, making flexible machine-learning nuisance estimation difficult to incorporate directly. Building on machine-learning-assisted generalized entropy calibration (MEC) by Lee and Kim (2026), we propose MEC-Cox for ATT-weighted IPW Cox regression. The method begins with normalized source-propensity-score odds weights for external controls and then applies Bregman calibration to balance cross-fitted prognostic summaries between external controls and treated trial patients. The calibration basis may include control-survival predictions, Cox linear predictors, penalized-survival-model predictions, or other prognostic-score summaries. MEC-updated weights therefore play a dual role as source-transport and prognostic-score balancing weights. We establish consistency, characterize a calibration-induced efficiency gain, and develop a stacked sandwich variance estimator. Simulations show that MEC-Cox can reduce bias, increase efficiency, and improve coverage through flexible machine-learning-assisted adjustment.

Black-box variational inference (BBVI) is a methodology for posterior approximation that relies on stochastic optimization. In practice, the stochastic optimizers underpinning BBVI generally require extensive problem-specific tuning, which undermines its promise as a truly "black box" inference algorithm. However, over the past decade, many new adaptive stochastic optimization algorithms have been developed that reduce or remove entirely the need for tuning. In this work, we investigate this new collection of adaptive methods in the context of BBVI, with the goal of establishing the current state of the art in tuning-free optimization-based inference. In particular, we present a large-scale empirical evaluation of 56 stochastic gradient-based optimization algorithms applied to 1092 Bayesian inference optimization problems, involving over 550,000 individual optimization runs and 15 core-years of compute. The optimization algorithms we evaluate are chosen to represent a wide spectrum of recent approaches and the benchmark problems are chosen to span a range of difficulty, with posterior target dimension 1-10^4, condition number 1-10^8, and a range of variational families. Our results show that no single method dominates, but running a selection of 5 algorithms suffices to reliably get close to the best-possible observed performance. We thus provide a strong baseline for applications where expert tuning is not possible and for comparison when developing new stochastic optimization algorithms.