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01.
medRxiv (Medicine) 2026-06-22

Starting, stopping and restarting. Patterns of Methylphenidate Use over 14 years in a large public health system

Background Persistence with stimulant medication is poor in children and adolescents with ADHD, and the evidence base is derived predominantly from high-income countries. We describe methylphenidate utilisation patterns and predictors of 12-month retention across 14 years in a large South African public health service. Methods Retrospective cohort study using routine pharmacy data from the Western Cape provincial health service (2011-2024). Children aged 5-18 at first prescription were included. Treatment episodes were defined as continuous prescription sequences with no gap exceeding 90 days and classified as initiations or restarts. Logistic regression modelled 12-month retention against early visit frequency and formulation type as pre-specified exposures. Findings 421,925 prescription events for 23,243 children across 115 facilities generated 65,885 treatment episodes. Median age at first prescription was 10 years (IQR 8-12); 77.6% were male. Kaplan-Meier 12-month survival was 28.2% for initiations and 15.4% for restarts, substantially below high-income country comparators. A quarter of all initiating prescriptions were not followed by a subsequent dispensing event; nearly 40% of patients had three or more treatment episodes. Early visit frequency was the strongest predictor of 12-month retention (high vs low: OR 2.85, 95% CI 2.65-3.06). The sustained-release formulation effect was present but attenuated on multivariable adjustment. Treatment re-initiations showed a marked seasonal pattern consistent with the South African school calendar. Interpretation Twelve-month retention was markedly lower than high-income country rates. Against a backdrop of high attrition, both early visit frequency and sustained-release formulation access predicted persistence; clinical engagement and reducing structural barriers to access are modifiable factors in this setting. Funding None.

02.
arXiv (CS.LG) 2026-06-19

Variational Consensus Monte Carlo for Bayesian Mixture

arXiv:2606.19643v1 Announce Type: cross Abstract: Motivated by the privacy, sensitivity and sharing limitations of health data, we present a comprehensive pipeline for inference of Bayesian mixture models within a federated learning setting, i.e. when data cannot be fully shared or pooled across compute nodes. We adopt a Consensus Monte Carlo (CMC) approach, in which an MCMC algorithm is run independently within each data silo to estimate local posterior distributions, which are then aggregated to approximate the posterior over the full data. The variational CMC approach of Rabinovich, Angelino and Jordan (2015) [1] frames the aggregation step as a variational inference problem, but their application to mixtures assumes the number of clusters and key mixture parameters to be known. Our main methodological contributions are: (i) an extension of variational CMC to over-fitted Bayesian mixture models that infer the number of clusters and all model parameters, without requiring conjugacy; (ii) novel cluster-matching algorithms suitable for cross-silo settings in which not every cluster appears in each local dataset; (iii) a number of inference strategies for the aggregation step, matched to different federated learning constraints; and (iv) guidelines for choosing among these in practice. A comprehensive simulation study validates the framework and allows us to compare to state-of-the-art federated learning alternatives. Notably, we show that when the composition of local datasets reflects the underlying clustering structure in the data, our approach can recover small clusters with greater accuracy than standard MCMC applied to the pooled data. We illustrate the framework on large-scale electronic health record data, identifying multi-morbidity patterns in a British geriatric population.

03.
arXiv (CS.CV) 2026-06-18

Reference-Driven Multi-Speaker Audio Scene Generation from In-the-Wild Priors

Existing multi-speaker dialogue systems bind speakers to utterances through structured supervision: per-turn tags, multi-stream transcriptions, or learnable speaker embeddings. These systems operate within speech-only pipelines that produce clean vocal sequences without the ambient texture of real conversations. We take a different approach. Our method, ScenA, conditions a text-to-audio flow-matching foundation model, pretrained on large-scale in-the-wild data, directly on multiple reference voices and a free-form natural language prompt that describes an entire multi-speaker audio scene. Leveraging such a foundational model allows us to inherit its capacity for natural, non-studio audio: background noise, room acoustics, overlapping dialogue, and spontaneous paralinguistic events, while adding multi-speaker control without any per-turn structure. Concretely, reference latents are concatenated into the model's token sequence and distinguished by lightweight identity-aware positional encodings. However, we identify a critical obstacle to this approach: the Reference Shortcut. During training under standard noise schedules, the model can identify the matching reference by acoustic similarity to the noisy target, bypassing the text prompt entirely. We address this with a high-noise-biased timestep distribution that forces the model to rely on the text prompt for speaker assignment. We evaluate ScenA on the CoVoMix2-Dialogue benchmark, showing that it outperforms existing multi-speaker systems on speaker-binding metrics while generating rich conversational audio with overlapping speech, emotional vocalizations, and ambient sound. Our results demonstrate the advantage of using a general-purpose audio model conditioned on a free-form scene description, rather than passing structured dialog scripts through a speech-only pipeline.

04.
arXiv (quant-ph) 2026-06-17

Quantum Resources and Wigner Symmetry in Nucleon-Nucleon Scattering from Effective Field Theory

arXiv:2606.17148v1 Announce Type: cross Abstract: We study quantum resources in the spin degrees of freedom, such as entanglement, stabilizer magic, and non-local magic, in low-energy nucleon-nucleon scattering through next-to-leading order in pionless effective field theory. Treating each nucleon spin as a qubit, we calculate the corresponding resource-generating powers of the scattering operator at generic center-of-mass momentum and scattering angle $\Theta$. The analysis retains $S$- and $P$-wave channels generated by two-derivative contact interactions. When the microscopic physics exhibits Wigner's $SU(4)$ spin-flavor symmetry, the neutron-proton amplitude becomes proportional to the spin-space identity operator and therefore generates no new resources after scattering, extending an observation previously made for leading-order $S$-wave scattering. The same-nucleon channel remains resource-generating because constraints from identical particles project out part of the Hilbert space. These results show how enhanced symmetries, partial-wave structure, and resource generation are intertwined in low-energy two-body scattering.

05.
medRxiv (Medicine) 2026-06-17

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

Despite recent advances in next-generation sequencing, genetic diagnostic rates for dilated cardiomyopathy (DCM) remain low. Among paediatric DCM, causes are often heritable, with a greater frequency of de novo, recessive and syndromic causes of disease. Novel diagnostic methods are therefore required to solve monogenic cases. To assess the value of proteomics as a diagnostic tool for paediatric DCM, we obtained left ventricle myocardial samples from paediatric patients undergoing heart transplantation at the Royal Children's Hospital, Melbourne. We performed genome sequencing and proteomics and leveraged this multi-omics dataset to uncover the molecular cause of disease in a gene elusive proband. The proband carried a heterozygous JPH2 frameshift variant identified on clinical exome sequencing. However, proteomic analysis showed a pronounced downregulation of JPH2, suggestive of biallelic loss-of-function. Closer inspection of the genomic data revealed a large inversion (~8.34 Mb) with a breakpoint falling within intron 5 of JPH2 that displaces the 3'UTR from the coding transcript. The two variants were confirmed to be in trans using long read DNA sequencing, consistent with a diagnosis of JPH2 autosomal recessive DCM. Finally, we applied RNA sequencing with total RNA library preparation to show that transcripts containing a 3'UTR were reduced to ~10% relative to controls. As a proof-of-principle, we present the first reported use of proteomics from explanted cardiac tissue to provide a genetic diagnosis. Our methodology has broad relevance to patients with genetically unsolved Mendelian diseases, who might undergo organ transplantation as part of clinical management.

06.
arXiv (math.PR) 2026-06-16

Stein's method for the matrix normal distribution

arXiv:2601.11422v2 Announce Type: replace-cross Abstract: This work presents the first systematic development of Stein's method for matrix distributions. We establish the basic essential ingredients of Stein's method for matrix normal approximation: we derive an extended-generator-based Stein identity from a matrix Ornstein-Uhlenbeck diffusion with two-sided scales, provide an explicit semigroup representation for the solution of the Stein equation, and obtain regularity estimates for the solution. The new methodology is demonstrated in three examples: (i) smooth Wasserstein distance bounds to quantify the matrix central limit theorem (a didactic example), (ii) a Wasserstein distance bound for the matrix normal approximation of the centered matrix $T$ distribution, and (iii) a Stein's method-of-moments approach to estimating the row and column covariance factors of the matrix normal, yielding a flexible class of weighted flip-flop Stein estimators that generalize Dutilleul's classical flip-flop algorithm and naturally accommodate row/column importance weights, systematic missingness, and projection onto structured covariance families. The latter two examples are intrinsically matrix-valued and cannot be treated using naive vectorization.

07.
arXiv (CS.AI) 2026-06-16

Optimising Temporary Accommodation Placement Across London with AI-Powered SaaS in E-Governance Systems

arXiv:2606.16652v1 Announce Type: cross Abstract: Temporary accommodation has become a major fiscal and administrative pressure for English local authorities, particularly in London, where demand and costs have risen sharply. This paper documents the creation and use of DOMUS, a cloud-based, AI-enabled decision-support system built from scratch at the University of East London and customised for the needs of London Borough of Newham to support statutory Temporary accommodation placement. DOMUS integrates household case records, policy-constrained affordability and suitability rules, and live private-rental listings within a single governance-aligned workflow. The system combines transparent, rule-based filtering with large language model-assisted search to standardise the application of bedroom need, affordability thresholds, geographic preferences, and accessibility requirements, while preserving officer discretion and audibility. Household and property attributes are encoded into policy-consistent representations prior to AI-assisted ranking and explanation. A pilot deployment in Newham's secure environment evaluated operational performance relative to manual workflows. Results indicate substantial reductions in search time, improved adherence to key placement constraints, and high staff satisfaction, while maintaining statutory compliance and role-based accountability. Beyond TA, the paper frames DOMUS as replicable digital public infrastructure: a modular, cloud-native Software-as-a-Service architecture that can be deployed across other UK boroughs and adapted to other public administration tasks characterised by scarcity, rule-bound eligibility, and high stakes. The findings demonstrate the feasibility of scalable, ethically governed AI deployment in local government and contribute to debates on AI-enabled public value creation in e-governance.

08.
medRxiv (Medicine) 2026-06-15

Prevalence and Clinical Impact of Pathogenic Variants in Cardiomyopathy Genes Among Individuals with Cardiac Conduction Disorders

Importance: Cardiac conduction disorders have traditionally been regarded as a secondary manifestation of underlying structural heart diseases. However, isolated conduction disorders may precede the onset of heart failure (HF) suggesting shared mechanisms. Objective: To evaluate the prevalence and clinical significance of pathogenic/likely pathogenic (P/LP) rare variants in cardiomyopathy genes among individuals with conduction disorders. Design, Setting, and Participants: Biobank analysis of 192,834 participants with whole genome sequence data from Vanderbilt's BioVU and 353,092 participants from the All of Us Research Program (AoU). Participants with primary conduction disorder (left bundle branch block [LBBB], right bundle branch block [RBBB], high-grade atrioventricular block [AVB]) were identified after excluding secondary causes. Exposures: P/LP variants in cardiomyopathy genes. Main Outcomes and Measures: Primary outcome was P/LP carrier status by age and HF status. Secondary outcomes included incident HF and composite ventricular arrhythmias/sudden cardiac death/mortality (VA/SCD/mortality). Results: Among 16,959 participants with conduction disorders in BioVU and 13,442 in AoU, 432 (2.6%) and 206 (1.5%) were P/LP carriers, respectively. Conduction disorder was independently associated with carrier status (BioVU p

09.
arXiv (CS.CL) 2026-06-12

Operadic consistency: a label-free signal for compositional reasoning failures in LLMs

Detecting LLM reasoning failures at inference time without ground-truth labels has motivated a wide range of confidence baselines, including self-consistency, semantic entropy, and P(True), built on within-question sampling and self-evaluation. Operad theory, the formalism for systems built by iterated substitution, suggests a complementary diagnostic: a model's direct answer to a compositional query should agree with the answer it produces by composing a stated decomposition of the same query. We instantiate this idea as operadic consistency (OC), a per-question signal. Across twelve instruction-tuned LLMs (4B to 671B parameters, open-weights and closed-source) on four multi-hop QA datasets, OC is strongly correlated with accuracy on every dataset (Pearson $r \in [0.86, 0.94]$, all $p \leq 0.0004$), and is the only signal we evaluate with $r \geq 0.85$ uniformly across all four datasets. Chain-of-thought self-consistency (CoT-SC; Wang et al., 2023) matches OC on HotpotQA and DROP ($r = 0.93, 0.87$) but drops to $r \approx 0.45$ on MuSiQue and StrategyQA. At the per-question level, OC contributes information beyond CoT-SC and semantic entropy on every dataset (cluster-robust $p \leq 10^{-16}$ for the OC coefficient), and the conclusion is robust to additionally controlling for constructed decomposition-aware baselines ($p \leq 10^{-13}$). The same signal yields selective-prediction improvements (accuracy at fixed coverage) over a tuned CoT-SC baseline at the equal-cost $K = 3$ budget (AUARC lifts of +0.086 to +0.096 and AUROC lifts of +0.092 to +0.164; 95% CIs exclude zero on every cell). On five frontier thinking models, where the decomposition is extracted from the model's own chain of thought, the same equal-cost comparison gives positive selective-prediction point-estimate lift on all 16 (dataset, budget, metric) cells tested, with 95% CIs excluding zero on 12 of the 16.

10.
arXiv (CS.CL) 2026-06-12

Operads for compositional reasoning in LLMs

Question decomposition, i.e. breaking a complex query into simpler sub-queries whose answers are composed to produce a final answer, is a widely used strategy for improving LLM reasoning, yet it currently lacks a rigorous mathematical foundation. In this paper, we propose operads, mathematical structures that model many-in, one-out operations and compositions thereof, as a natural framework for describing question decomposition. We define the questions operad $Q$, in which operations correspond to question templates and composition corresponds to substitution of sub-answers, and show how QA models can be interpreted as algebras over $Q$. Beyond reframing existing practice, this operadic perspective points toward new methods, in particular a notion of operadic consistency, which measures whether a QA model's answers agree across the partial collapses of a question decomposition tree. Empirical evaluation of operadic consistency is reported in our companion paper (Bottman, Liu, and Richardson, 2026), which finds it strongly correlated with accuracy across twelve LLMs and four multi-hop QA datasets and outperforming standard temperature-based self-consistency baselines. We argue that operads are the natural mathematical home for question decomposition, and that invariants such as operadic consistency open new directions for analyzing and improving the reliability of multi-step reasoning.

11.
arXiv (CS.CL) 2026-06-11

When Probing Accuracy Saturates, Fragility Resolves: A Complementary Metric for LLM Pre-Training Analysis

Standard linear probing declares a property "encoded" when a classifier on hidden states achieves high accuracy. The protocol works well on a snapshot but breaks across pre-training: probe accuracy saturates within the first few thousand steps, leaving most of training invisible to the instrument. We introduce fragility, a complementary per-layer metric defined as the activation-noise level at which probe accuracy collapses. Fragility is sensitive to both the margin of separability and the redundancy of representation, both of which keep evolving long after accuracy plateaus. Applied to open-checkpoint language models, fragility recovers structure that accuracy alone cannot see. Moralized representations emerge along a lexical $\to$ compositional gradient: lexical moral detection first, compositional moral encoding later. Because probe accuracy on its own tracks how lexically separable a dataset is, we establish the compositional encoding directly, by showing it transfers across construction types that share no contrast tokens. A layer-depth robustness gradient develops monotonically across training while accuracy stays flat. And matched fine-tuning corpora that produce identical probing accuracy leave distinct fragility fingerprints, showing that data curation reshapes probe robustness without changing probe accuracy. In every comparison we test, where probing accuracy returns a flat answer, fragility returns a structured one.

12.
arXiv (CS.CV) 2026-06-11

Task-Aligned Stability Analysis of Vision-Language Models for Autonomous Driving Hazard Detection

Vision-language models (VLMs) are increasingly used for scene understanding in autonomous driving, but robustness analysis often relies on task-agnostic embedding stability alone. We study whether corruption-induced embedding drift predicts changes in a task-aligned hazard score derived from CLIP image-text similarities. Using controlled corruptions on BDD100K road scenes, we compare embedding drift against margin drift, defined as the change in hazard score under perturbation. The relationship is highly corruption-dependent: some families exhibit strong coupling between representation drift and decision drift, while others induce hazardous decision instability despite relatively modest embedding change. Furthermore, corruption families differ in failure direction: most suppress hazard detections via false negatives, while occlusion instead triggers false alarms, suggesting that benchmark design should account for asymmetric failure modes, not just overall instability rates. These results suggest that robustness benchmarks should include task-aligned stability measures in addition to embedding-level perturbation statistics.