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01.
medRxiv (Medicine) 2026-06-16

Cross-sectional study of the association between depressive symptoms and attentional bias to emotional stimuli in patients with acute stroke: Study protocol

Post-stroke depression affects approximately 30% of patients after stroke and is associated with delayed recovery in activities of daily living, reduced rehabilitation effectiveness, and poorer quality of life. Attentional bias modification may provide a low-burden, nonpharmacological approach for patients in the acute phase of stroke. However, before such an intervention can be implemented in clinical practice, it is necessary to clarify whether attentional bias is present in patients with acute stroke and depressive symptoms, whether cognitive function influences the manifestation of this bias, and which task and stimulus formats are most appropriate for assessment. This multicenter, cross-sectional observational study will enroll patients with acute stroke between 7-30 days after stroke onset. Depressive symptoms will be assessed using the depression subscale of the Hospital Anxiety and Depression Scale. Attentional bias will be measured under four task conditions based on the dot-probe task and the cue-target task, using face and word stimuli. Secondary assessments will include cognitive function, anxiety symptoms, activities of daily living, health-related quality of life, and clinical background variables. The aims of this study are to investigate the association between depressive symptoms and attentional bias in patients with acute stroke, compare attentional bias characteristics across task and stimulus types, and examine the potential influence of cognitive function on this association. The findings are expected to provide an empirical basis for designing future attentional bias modification protocols targeting post-stroke depression in the acute phase. This study has been registered with the UMIN Clinical Trials Registry (UMIN000059166).

02.
medRxiv (Medicine) 2026-06-15

Primary care practitioners preconception health literacy and information-seeking: A cross-sectional survey.

Background Parental health before pregnancy influences maternal and child outcomes. Primary care professionals, including general practitioners [GPs], midwives, and naturopaths, can provide preconception care, yet many report limited knowledge and difficulty accessing relevant information. This study described Australian GPs, midwives, and naturopaths preconception health literacy, including knowledge and ability to access information. Methods Between July and September 2022, Australian GPs, midwives, and naturopaths completed a 32-item online cross-sectional survey. Participants were recruited through professional associations, and data were analysed using descriptive and inferential statistics Results Participants (N=373) included naturopaths (40.7%), GPs (32.4%), and midwives (26.8%). Reported barriers to clinician health literacy including lack of preconception care resources (25.5%), and limited clinician knowledge (23.6%). The proportion identifying limited clinician knowledge differed significantly between professions (GP: 31.4%; midwives: 23.0%; naturopaths: 17.8%; p=0.030). The highest level of accurate knowledge regarding preconception exposures was for pre-pregnancy obesity (82.7%), while low birth weight was the most accurately identified preconception outcomes (83.7%). Incorrect responses were most common for maternal multivitamin use as an exposure (28.3%) and childhood leukaemia as an outcome (26.3%). Differences between professions were strongest for infant outcomes, with moderate associations observed for shoulder dystocia (V=.2355), precipitous labour (V=.2173), macrosomia (V=.2060), labour dystocia (V=.2018) and cryptorchidism (V=.2018). Discussion Preconception health literacy varies across primary care professions. Clinicians require greater access to targeted resources and education tailored to their differing scopes of practice and experience. Improving clinician preconception health literacy may strengthen consistent evidence-based care and support better maternal, child, and long-term family health outcomes.

03.
arXiv (math.PR) 2026-06-19

Asymptotic properties for fully coupled delayed forward-backward stochastic differential equations

arXiv:2606.19925v1 Announce Type: new Abstract: We investigate the asymptotic behavior of solutions to a class of fully coupled forward-backward stochastic differential equations with time-delayed generators. Such systems arise naturally in stochastic models with memory effects and constitute a significant extension of the classical fully coupled FBSDE framework. The presence of delay introduces additional analytical difficulties due to the dependence of the coefficients on the past trajectories of the solution processes and the resulting non-Markovian structure. Under suitable assumptions on the coefficients, we study the asymptotic properties of a perturbed delayed FBSDE driven by a small noise parameter. We first establish the convergence in distribution of the associated solution processes as the perturbation parameter tends to zero. We then prove almost sure convergence towards the solution of the corresponding deterministic limiting system. As a consequence of these asymptotic results, we derive a large deviation principle for the solution processes. Our results extend the asymptotic analysis of Cruzeiro, Gomes and Zhang (2014) from the classical fully coupled FBSDE setting to the delayed framework, and complement existing works on weakly coupled delayed forward-backward systems. They provide, to the best of our knowledge, the first large deviation principle for fully coupled forward-backward stochastic differential equations with delayed generators.

04.
arXiv (CS.AI) 2026-06-19

SleepMaMi: A Universal Sleep Foundation Model for Integrating Macro- and Micro-structures

arXiv:2602.07628v2 Announce Type: replace Abstract: While the shift toward unified foundation models has revolutionized many deep learning domains, sleep medicine remains largely restricted to task-specific models that focus on localized micro-structure features. These approaches often neglect the rich, multi-modal context of Polysomnography (PSG) and fail to capture the global macro-structure of a full night's sleep. To address this, we introduce SleepMaMi , a Sleep Foundation Model engineered to master both hour-long sleep architectures and fine-grained signal morphologies. Our framework utilizes a hierarchical dual-encoder design: a Macro-Encoder to model full-night temporal dependencies and a Micro-Encoder to capture short-term characteristics from biosignals. Macro-Encoder is trained via Demographic-Guided Contrastive Learning, which aligns overnight sleep patterns with objective subject metadata, such as age, sex and BMI to refine global representations. Micro-Encoder is optimized via a hybrid Masked Autoencoder (MAE) and multi-modal contrastive objective. Pre-trained on a massive corpus of $>$20,000 PSG recordings (158K hours),SleepMaMi outperforms or matches state-of-the-art existing foundation models across a diverse suite of downstream tasks, demonstrating superior generalizability and label-efficient adaptation for clinical sleep analysis.

05.
arXiv (CS.LG) 2026-06-12

Smarter Saboteurs, Better Fixers: Scaling & Security in Linear Multi-Agent Workflows

arXiv:2606.12709v1 Announce Type: cross Abstract: As LLM-based multi-agent systems (MAS) are deployed in the wild, the resilience of their collaboration structures against adversarial compromise becomes a critical safety concern. Attackers may leverage prompt-injection or jailbreaking to sabotage individual agents within MAS workflows, but the interaction between model scaling and system-level resilience remains poorly understood. This paper investigates how model scale affects the security of linear multi-agent workflows. Our experiments across scales of two open-weight model families on the HumanEval benchmark reveal a compliance-correction symmetry: larger models are far more likely to faithfully execute malicious instructions, with the control-to-malicious performance drop reaching 53.7pp at 27B in uncorrected pipelines. However, appending a lightweight terminal Fixer stage collapses this to 0.6pp and restores statistical parity with control-level performance, demonstrating that strictly linear collaboration structures can be viable and resilient to adversaries at this scale, and suggesting that the brittleness previously attributed to linear topology may stem from a lack of correction.

06.
arXiv (CS.AI) 2026-06-12

Multi-Agent Reinforcement Learning from Delayed Marketplace Feedback for Objective-Weight Adaptation in Three-Sided Dispatch

arXiv:2606.13604v1 Announce Type: new Abstract: Dispatch in three-sided marketplaces provides a natural setting for reinforcement learning from world feedback: decisions are evaluated by delayed operational outcomes such as delivery speed, courier utilization, and merchant congestion. We present a deployed reinforcement learning system at DoorDash that adapts dispatch objective weights in a large-scale food-delivery marketplace using delayed signals. Rather than replacing the combinatorial assignment optimizer, a store-level policy learned from logged marketplace data selects a discrete multiplier that shifts the dispatch optimizer's tradeoff between delivery quality and batching efficiency. This interface enables offline policy learning under noisy, delayed, and coupled feedback while preserving production feasibility constraints and operational safeguards. We train a shared value function using centralized offline data and decentralized store-level execution, with Double Q-learning targets and a conservative regularizer to reduce out-of-distribution value overestimation. In a production switchback experiment, the offline-trained policy increases batching and reduces courier-side time costs without degrading customer-facing delivery quality. Results illustrate how world feedback from a live economic and logistics system can be used to safely adapt decision policies online.

07.
arXiv (quant-ph) 2026-06-12

Experiment-compatible measurement–feedback quantum state preparation with reinforcement learning

arXiv:2606.13005v1 Announce Type: new Abstract: Ground-state preparation is a critical task in quantum simulation and quantum computing, as it enables the study of correlated phases and the generation of entangled resource states. While measurement–feedback control has emerged as a promising route to state preparation, existing schemes either rely on handcrafted, task-specific policies or are designed using full quantum-state information that is unavailable in real experiments and becomes impractical for large many-body systems. Here we develop an adaptive measurement–feedback protocol based on reinforcement learning under partial observability. The controller uses only the history of experimentally accessible measurement outcomes to choose both the measurement operator and the feedback action in real time. To make training compatible with experiments, we introduce a stochastic terminal reward built from one-shot measurements of randomly sampled Hamiltonian components, avoiding unphysical full-state reconstruction while remaining an unbiased estimator of the target energy. We demonstrate the method by preparing ground states of the Bose–Hubbard model and by generating GHZ states, establishing a scalable and hardware-compatible route to quantum state preparation.

08.
arXiv (CS.LG) 2026-06-19

Comparing Linear Probes with Mahalanobis Cosine Similarity

arXiv:2606.19603v1 Announce Type: new Abstract: Linear probes are widely used in interpretability research and often compared by cosine similarity. The Mahalanobis cosine similarity (MCS) between two directions, which reweights the inner product by test data covariance, is a natural task-aware refinement. Ying et al. (2026) report that a probe's MCS to a reference probe trained on the out-of-distribution (OOD) data near-perfectly linearly predicts the probe's OOD AUROC (R^2 = 0.98). Here, we extend this empirical finding across models, layers, and concept domains, and prove this general phenomenon in closed form: For balanced classes whose projections are Gaussian, OOD AUROC and MCS to the reference probe are linear because both are sigmoid-shaped functions of the probe's signal-to-noise ratio (SNR) on the test data. The theory also predicts when this linearity fails, which we verify empirically. MCS offers a theoretically grounded and empirically effective alternative to Euclidean cosine similarity for comparing linear probes.

09.
arXiv (quant-ph) 2026-06-12

Coarse-grained quantum thermodynamics: Observation-dependent quantities, observation-independent laws

arXiv:2507.15918v2 Announce Type: replace Abstract: In both classical and quantum thermodynamics, physical quantities are typically assigned objective values defined independently of our observations. We then refer to the 'work performed by a gas', or the 'entropy of the gas', regardless of how they are evaluated. Here, we question this conception in the context of quantum thermodynamics, estimating how the definition of pivotal thermodynamic quantities is affected by experimental instruments of limited precision. We find that the coarse-grained thermodynamic quantities frequently lead to different conclusions from those drawn in fine-grained scenarios. For instance, the irreversibility of a process, or its work payoff, can significantly vary with the instrument precision. We show nonetheless that coarse-grained thermodynamic quantities satisfy the same relations (i.e., the second law inequality, the relation between dissipation and distinguishability of a process from its time-reverse, and the quantum work fluctuation theorems) as their fine-grained counterparts. These results highlight the observation-independence of relations linking thermodynamic quantities which are themselves observation-dependent.

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

Rarity-Gated Context Conditioning for Offline Imitation Learning-Based Maritime Anomaly Detection

arXiv:2606.13311v1 Announce Type: cross Abstract: Contextual anomaly detection aims to identify abnormal behavior conditional on context variables, but practical deployments often face highly imbalanced context distributions where rare regimes can be critical information. Under such frequency bias, context-conditioned models can produce unstable decisions and excessive false alarms in rare contexts. We propose Rarity-Gated Feature-wise Linear Modulation (RGFiLM), a rarity-aware conditioning module that combines feature-wise modulation (i.e., context-conditioned scaling and shifting of hidden features) with a gate controlled by a data-driven rarity score. The rarity score is estimated from the empirical distribution of context variables and regulates how strongly context modulates intermediate representations: the gate becomes more decisive under rare contexts while remaining conservative under frequent contexts. We evaluate RGFiLM on maritime trajectory anomaly detection using AIS motion sequences with ERA5 environmental context in an environment-sensitive detour scenario. When instantiated in a sequential anomaly scoring pipeline, RGFiLM achieves the best mean F1–False Positive Rate (FPR) trade-off among the compared context-agnostic and context-conditioned methods. These results suggest that explicitly accounting for context rarity is an effective approach for reducing false alarms in context-sensitive anomaly detection.

11.
bioRxiv (Bioinfo) 2026-06-15

Maternal BMI and Placental Transcriptomic Changes: A Meta-Analysis of Gene Expression at the Maternal-Fetal Interface

Objective: Maternal body mass index (BMI) is often used as a measure of metabolic status and increased or decreased maternal BMI is associated with a heightened risk of cardiometabolic diseases across generations. The placenta mediates these maternal metabolic cues; however, its genome wide transcriptional adaptations in response to maternal BMI remain incompletely defined. Methods: To delineate placental genes, pathways, and interaction clusters whose transcript abundance varies with maternal prepregnancy BMI through a genome wide meta analysis of human placental RNA sequencing datasets. Placental RNA seq reads from four publicly available cohorts (n=146) were mapped to the GRCh38 reference genome and differentially expressed genes were identified. An independent microarray cohort (n=19) was reanalysed separately to facilitate cross platform comparison. Functional enrichment employed GO, KEGG, and STRING protein interaction resources. Results: Meta-analysis of 146 RNA seq samples identified eight genes with genome-wide significance in placentae from underweight pregnancies including inflammatory signaling gene MAP4K1 and metabolic enzyme PSPH, while overweight and obese categories revealed nominally significant differential expression. KEGG analysis demonstrated significant downregulation of oxidative phosphorylation with increasing maternal BMI, and protein-protein interaction networks revealed inflammatory mediators as central nodes in overweight and obese groups. Independent microarray validation corroborated key findings, including consistent downregulation of oxidative phosphorylation in obesity. Conclusion: Maternal BMI is associated with placental transcriptomic signatures involving inflammatory, metabolic, and hormonal pathways, with consistent downregulation of oxidative phosphorylation across platforms. This genome-wide meta-analysis provides a reproducible catalogue of BMI-responsive placental transcripts that may contribute to developmental programming of offspring health.

12.
arXiv (CS.CV) 2026-06-17

MLLMs Get It Right, Then Get It Wrong: Tracing and Correcting Late-Layer Textual Bias

When vision contradicts text, multimodal large language models (MLLMs) consistently favor text, even when images provide clear evidence otherwise. This bias poses risks for applications requiring visual grounding, yet its cause remains unclear. In this paper, we uncover a surprising finding: models often get it right initially, forming correct vision-based predictions in their intermediate layers, before changing their minds and favoring text in the final output. We call this "late-layer textual override". The visual information is encoded, it simply does not survive to the output. More intriguingly, we find that how predictions change reveals whether they're correct: 85% of failures shift toward text, while 89% of successes shift toward vision. This directional signature enables a simple but powerful intervention: when we detect a confident visual prediction being suppressed, we restore it. We propose CALRD (Conflict-Aware Layer Reference Decoding), a training-free method that recovers overridden predictions at inference time. Experiments across five MLLMs of varying architectures demonstrate up to 9.4% absolute improvements on conflict benchmarks while largely preserving standard performance, without training or external knowledge. It recovers what the model already knew but failed to preserve.

13.
PLOS Medicine 2026-05-13

Contribution of nosocomial transmission to <i>Klebsiella pneumoniae</i> neonatal sepsis in Africa and South Asia: An observational study of infection clusters inferred from pathogen genomics and temporal data

by Erkison Ewomazino Odih, Jabir A. Abdulahi, Anne V. Amulele, Matthew Bates, Eva Heinz, Weiming Hu, Kajal Jain, Rindidzani Magobo, Courtney P. Olwagen, John M. Tembo, Tolbert Sonda, Jonathan Strysko, Caroline C. Tigoi, Kyle Bittinger, Jennifer Cornick, Ebenezer Foster-Nyarko, Wilson Gumbi, Steven M. Jones, Chileshe L. Musyani, Carolyn M. McGann, Ahmed M. Moustafa, Patrick Musicha, James C. L. Mwansa, Moreka L. Ndumba, Thomas D. Stanton, Donwilliams O. Omuoyo, Oliver Pearse, Laura T. Phillips, Paul J. Planet, Charlene M. C. Rodrigues, Fatou Secka, Kirsty Sands, Erin Theiller, Allan M. Zuza, Sulagna Basu, Grace J. Chan, Kenneth C. Iregbu, Jean-Baptiste Mazarati, Semaria Solomon Alemayehu, Timothy R. Walsh, Rabaab Zahra, Angela Dramowski, Sombo Fwoloshi, Appiah-Korang Labi, Lola Madrid, Noah Obeng-Nkrumah, David Ojok, Boaz D. Wadugu, Andrew C. Whitelaw, Anudita Bhargava, Atul Jindal, Ramesh K. Agarwal, Alexander M. Aiken, James A. Berkley, Susan E. Coffin, Nicholas A. Feasey, Nelesh P. Govender, Davidson H. Hamer, Shabir A. Madhi, Mari Jeeva Sankar, Kelly L. Wyres, Kathryn E. Holt Background Klebsiella pneumoniae is the leading cause of sepsis among neonates in low- and middle-income countries (LMICs) in Africa and Asia, contributing substantially to the overall burden of antimicrobial-resistant infections and mortality among neonates globally. Pathogen sequencing has been used to investigate case clusters and confirm nosocomial transmission in a small number of neonatal units. Here we utilise pathogen sequence data to estimate the fraction of K. pneumoniae neonatal sepsis attributable to nosocomial transmission in African and South Asian countries. Methods and findings We estimated the proportion of invasive K. pneumoniae disease involved in nosocomial transmission clusters in a given neonatal unit, using single-linkage clustering based on pairwise temporal and genetic distances estimated from bacterial whole-genome sequences aggregated from 10 contributing studies. Analysing 1,523 K. pneumoniae isolates from 27 units in 13 countries in Africa and South Asia between 2013 and 2023, we inferred 156 nosocomial transmission clusters, ranging from 2 to 188 neonates each (83 of the clusters comprised ≥3 cases). Overall, we estimated that 1,035 neonatal infections (68.0%) were part of nosocomial transmission clusters. Excluding the first infection in each cluster as a potential index case, we estimate at least 879 (57.7%) infections were acquired via nosocomial transmission. Sensitivity analyses showed that results were robust to the choice of genetic distance estimation methods and thresholds used to define clusters, and cluster estimates were stable over temporal distance thresholds ranging from 2 to 8 weeks. Isolates were mostly extended-spectrum beta-lactamase (ESBL) producers (90.9%) and included 172 multi-locus sequence types (STs). Fourteen STs, including several globally recognised multidrug-resistant lineages, were associated with transmission clusters at multiple units, and these were collectively responsible for two-thirds of all infections. Carriage of carbapenemase genes (adjusted odds ratio, aOR = 2.08 [95% confidence interval, CI: 1.04, 4.14]; p = 0.04) and ESBL genes (aOR = 2.48 [95% CI: 1.26, 4.90]; p = 0.006) were significantly positively associated with transmission in a logistic regression model with site as a covariate. Limitations of this study include the lack of sufficient clinical data to allow high-resolution investigation of transmission dynamics and lack of facility-level data to investigate contributors to the observed differences in transmission burden across sites. Conclusions Nosocomial transmission contributes to a substantial proportion of K. pneumoniae sepsis in neonatal care units in Africa and South Asia. Reducing transmission within these settings through improved infection prevention and control and other measures could substantially reduce the neonatal sepsis burden. A high burden of transmission clusters is associated with the same drug-resistant lineages that are recognised as high-risk clones associated with hospital outbreaks in high-income countries, indicating global connectivity of the antimicrobial-resistant pathogen population.

14.
arXiv (CS.AI) 2026-06-16

CrossMaps: Confidence-Aware Open-Vocabulary Semantic Mapping for Rover Navigation

arXiv:2606.16935v1 Announce Type: cross Abstract: Rovers rely on perception to maintain spatial maps that encode both objects and sensor quality (e.g., range reliability, lighting artifacts, data density), guiding data fusion, embedding updates, and navigation under partial observability. To study these coupled perception-navigation processes, we present CrossMaps, a real-time confidence-aware open-vocabulary semantic mapping pipeline that constructs language-queryable maps from RGB-D data. Building on VLMaps-style approaches, CrossMaps integrates multi-scale CLIP embeddings with confidence-aware fusion and a dual-memory architecture consisting of Short-Term Memory (STM) and Long-Term Memory (LTM). The STM aggregates noisy visual observations using geometric, semantic, and temporal confidence cues, while confident and coherent cells are promoted to the LTM as persistent semantic landmarks. Designed for deployment with a Jetson Orin-powered UGV alongside SLAM, CrossMaps runs in real time and produces semantic heatmaps that can be queried with natural language to guide rover navigation.

15.
arXiv (CS.LG) 2026-06-16

Your Privacy My Cloak: Backdoor Attacks on Differentially Private Federated Learning

arXiv:2606.17035v1 Announce Type: new Abstract: Prior research suggests that differential privacy (DP) inherently enhances the robustness of federated learning (FL) against backdoor attacks. In this paper, we challenge this assumption. Through an empirical analysis of two baseline attack strategies, we uncover a fundamental tension in DP-FL: while bypassing DP allows state-of-the-art defenses to detect and filter malicious updates, complying with DP inadvertently masks their distinguishing statistical characteristics. Consequently, existing defenses become ineffective as DP reduces the raw backdoor signal. Building on this masking effect, we propose RING, a novel attack that explicitly exploits DP to conceal malicious contributions while maximizing attack impact. By collaboratively crafting adversarial perturbations, compromised clients reconstruct a strong backdoor signal during aggregation without triggering anomaly detection. RING operates as a perturbation layer that is agnostic to the underlying backdoor technique, making it broadly applicable and composable with existing attacks – a property that significantly amplifies the threat it poses to DP-FL. Extensive evaluations across four image and text datasets under non-iid distributions show that RING achieves an average attack success rate of 90.3% against six state-of-the-art defenses under a moderate privacy budget, an improvement of up to 26.08x over baseline strategies. Finally, we evaluate potential countermeasures and find that mitigating this threat incurs significant utility trade-offs, exposing a fundamental security gap in the deployment of differentially private FL.

16.
arXiv (CS.LG) 2026-06-16

In-Context Learning Is Provably Bayesian Inference: A Generalization Theory for Meta-Learning

arXiv:2510.10981v3 Announce Type: replace-cross Abstract: This paper develops a finite-sample statistical theory for in-context learning (ICL), analyzed within a meta-learning framework that accommodates mixtures of diverse task types. We introduce a principled risk decomposition that separates the total ICL risk into two orthogonal components: Bayes Gap and Posterior Variance. The Bayes Gap quantifies how well the trained model approximates the Bayes-optimal in-context predictor. For a uniform-attention Transformer, we derive a non-asymptotic upper bound on this gap, which explicitly clarifies the dependence on the number of pretraining prompts and their context length. The Posterior Variance is a model-independent risk representing the intrinsic task uncertainty. Our key finding is that this term is determined solely by the difficulty of the true underlying task, while the uncertainty arising from the task mixture vanishes exponentially fast with only a few in-context examples. Together, these results provide a unified view of ICL: the Transformer selects the optimal meta-algorithm during pretraining and rapidly converges to the optimal algorithm for the true task at test time.

17.
arXiv (CS.LG) 2026-06-18

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.

18.
medRxiv (Medicine) 2026-06-16

Optimal Clinical Trials Platform for Progressive Multiple Sclerosis (OCTOPUS): protocol for an international, multi-arm, multi-stage, platform, randomized controlled, double-blind, phase 3 clinical trial.

Introduction Current treatments for multiple sclerosis (MS) do not address the pathological processes of neurodegeneration and chronic demyelination. This, coupled with the significant challenges of translating promising phase 2 results to phase 3 trial success, highlights the need for more efficient trial designs, such as platform multi-arm multi-stage (MAMS) trial approaches. MAMS trials have demonstrated success in areas such as oncology and infectious diseases. They are typified by a statistically robust core trial design that allows the addition of further treatment arms and utilisation of interim outcome analyses at pre-defined timepoints, to determine whether to terminate a treatment arm early or proceed to the final outcome analysis. To address the challenges in progressive multiple sclerosis (PMS) treatment discovery, the Optimal Clinical Trials Platform for PMS (OCTOPUS) trial was developed. It currently utilises MRI whole-brain atrophy as its interim outcome measure and the clinically relevant composite Expanded Disability Status Scale Plus (EDSS-Plus) as its final outcome measure. A rigorous and systematic drug selection process that assessed preclinical in vitro and animal model evidence, along with additional human data, led to the prioritisation of R/S-alpha lipoic acid (R/S-ALA) and metformin for testing against placebo, targeting pathobiological mechanisms relevant to PMS. All participants will be eligible to receive the current standard of care, including disease-modifying treatments (DMTs). Method and analysis OCTOPUS will be a multi-centre, randomised, placebo-controlled, double-blind, phase 3, MAMS trial of participants aged 25 to 70 years (inclusive) with PMS and an EDSS score of 4.0 to 8.0 (inclusive). Steady progression must be the major cause of increasing disability rather than relapse in the preceding 2 years. In the trial s first candidate drug cycle, participants will be allocated to R/S-ALA, metformin, or placebo in a 1:1:1 ratio. Cycle 1 active treatments will start as R/S-ALA 600 mg once daily, increased after 4 weeks to 600 mg twice daily, or metformin 1 g once daily, increased after 4 weeks to 1 g twice daily. The trial will be multinational, with participation from 28 hospitals across the UK and 10 hospitals in Australia. Clinician-reported measures will include: the EDSS-Plus and the individual components: EDSS, Timed 25 Foot Walk (T25FW); 9 Hole Peg Test (9HPT); Symbol Digit Modalities Test (SDMT); Sloan Low Contrast Visual Acuity (SLCVA); and Relapse assessment. Patient-reported outcomes include MS specific walking, fatigue, pain, and impact scales. We will include a health economic analysis. Analysis stage 1 will require randomisation of 125 participants per arm and utilise MRI percentage brain volume change (PBVC) with the Structural Image Evaluation using Normalisation of Atrophy (SIENA) technique from baseline to 78 weeks. A positive outcome in analysis stage 1 will detect a 0.15% per year whole brain atrophy difference with a one-sided alpha of 0.35 and power of 95%, ensuring a low probability of erroneously rejecting a treatment arm at this stage. Any arms that show a positive effect will proceed to final analysis stage 2. Analysis stage 2 will require 600 participants per arm. Participants included in stage 1 will also be included in the stage 2. Analysis stage 2 will evaluate time to 6-month confirmed disability progression in the EDSS-Plus, in order to detect a 25% hazard ratio reduction with 90% power and an alpha of 0.05. Assuming one treatment arm proceeds to analysis stage 2, the trial will recruit approximately 1,200 participants and last about 6 years. This is approximately two-thirds the size and half the duration of separately conducted two-arm phase 2 and 3 trials. Ethics and dissemination The protocol was approved by the London Hampstead REC (22/LO/0622). This manuscript is based on protocol version 8.0, 28th August 2025. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations. There will be a close communication strategy developed with the UK MS Society (MSS) and full patient and public involvement and engagement (PPIE). Trial registration ISRCTN: 14048364 EudraCT number: 2021-003034-37 CTA 20363/0445 IRAS number: 1003943 Secondary identifying numbers: ND001, CPMS 54274 Strengths and limitations - The OCTOPUS trial will be the first platform multi-arm multi-stage phase 3 trial in PMS, offering the potential to significantly expedite clinical trial processes with advantages in cost- and time-efficiency, focusing specifically on the poorly treated pathobiological processes of chronic neurodegeneration and demyelination - It will begin by assessing two promising drug candidates, immediate-release metformin and R/S-ALA, and will expand over the duration of the trial to include more drug arms under the same trial master protocol - The flexible and statistically robust trial design means that several components of the design (such as the early analysis stage 1 interim outcome) can be updated in line with evolving scientific knowledge - It will ultimately be the largest ever investigator-initiated phase 3 trial in PMS - It will include a range of national and international trial sites, including neuroscience centres and district general hospitals - It will have a high inclusion limit for age (up to 70 years) and disability (up to EDSS 8.0) - Several components (the telephone EDSS and virtual patient-reported outcome measures) will be amenable to remote collection increasing inclusivity and thus addressing public and participant suggestions, while minimising the risk of missing data - The main challenges in this trial design are the statistical and methodological complexity involved in design and implementation, and interpretation of interim trial results. Conclusion The trial launched cycle 1 in January 2023. Analysis stage 1 recruitment of 375 participants was achieved in November 2024, enabling planned interim analysis stage 1 to be conducted by late 2026 (Figure 1). On the 1st of June 2026, in the UK, 24 sites are active with a further 4 in set-up as part of stage 2, and in the Australian extension, Platform Adaptive Trial for Remyelination and Neuroprotection in Multiple Sclerosis (PLATYPUS), 1 site is active, with 9 additional sites in set-up.

19.
arXiv (quant-ph) 2026-06-16

Benchmarking Quantum Extreme Learning based on Gaussian Boson Sampling

arXiv:2606.15230v1 Announce Type: new Abstract: Reservoir models offer a hardware-efficient learning paradigm for noisy intermediate-scale quantum devices by exploiting untrained quantum dynamics as a fixed feature map and restricting optimization to a simple classical readout layer. We propose a quantum extreme learning machine implemented using gaussian boson sampling and an encoding strategy that achieves high classification accuracy while reducing optical resource requirements. Classical inputs are jointly encoded in the squeezing parameters and in the interferometer unitary, enabling sampling-based, highly nonlinear feature maps while leveraging large-scale GBS output statistics, which are conjectured to be classically intractable. We systematically compare multiple families of quantum features accessible in the same setup and find that photon-number sampling probabilities provide the best performance, consistent with their higher effective feature dimensionality. Finally, we benchmark against classical nonlinear baselines and analyse robustness under noisy scenarios, showing competitive performance with fewer trainable parameters and indicating practical promise for near-term photonic implementations.

20.
arXiv (CS.AI) 2026-06-19

Beyond Entropy: Learning from Token-Level Distributional Deviations for LLM Reasoning

arXiv:2606.19771v1 Announce Type: new Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) has significantly advanced Large Language Model (LLM) reasoning; however, it faces a fundamental optimization instability: uniform token updates precipitate entropy collapse, leading to premature convergence to suboptimal strategies, whereas excessive Shannon Entropy maximization can cause entropy explosion, driving blind exploration toward incoherent reasoning chains. To resolve this dichotomy, we introduce the Independent Combinatorial Tokens (ICT) framework, which shifts the optimization focus from scalar uncertainty to the distributional properties of token logits. By leveraging the Jensen-Shannon (JS) divergence between token logits distributions, ICT identifies tokens with distinctive distributional patterns as critical branching points for guiding effective exploration in LLM reasoning. Our theoretical analysis, grounded in both Shannon and second-order Rényi entropy, proves that selectively updating on these tokens regulates policy concentration: it reduces the overall distribution uncertainty measured by Shannon entropy, while controlling probability concentration captured by second-order Rényi entropy. This dual effect prevents over-concentrated token generation from weakening exploration and effectively stabilizes the training landscape. Empirical results demonstrate that updating only the top 10% of unique tokens on Qwen2.5 (0.5B/1.5B/7B) models yields an average pass@4 improvement of 4.58%, with a maximum gain of 14.9%, over GRPO, 20-Entropy, and STAPO baselines across seven benchmarks spanning math, commonsense, and Olympiad-level problems.

21.
arXiv (CS.AI) 2026-06-16

Frame-Conditioned Moral Computation in LLaMA 3.1-8B-Instruct: A Mechanistic Interpretability Audit of Ethical Reasoning

arXiv:2606.15507v1 Announce Type: new Abstract: Behavioral audits of Large Language Models on moral prompts measure what the model says, not the internal computation producing it. We use Transluce, an AI-driven mechanistic-interpretability platform, to examine LLaMA 3.1-8B-Instruct on 54 moral prompts in four batteries: 17 dilemmas, policy, and meta-ethical questions (B1); 6 role-playing scenarios (B3); and a controlled trolley contrast varying the switching mechanism with people fixed (B4, 15 prompts) or identity attributes with mechanism fixed (B5, 16 prompts). Two complementary metric families, five cluster-level metrics and a six-metric neuron-level panel, converge on a Situational Anchor Effect: domain-specific representations dominate the top of the activation list across every battery. The model's ethics-labeled capacity stays essentially constant; its salience (rank, priority, top-of-list presence) is highly sensitive to the interpretive frame the prompt selects. The B4-vs-B5 contrast confirms the model attends to whichever surface feature varies: aggregate ethics metrics are indistinguishable, but the dominant non-ethics distractor mirrors the design. A multi-temperature audit identifies a candidate ethics neuron (L16/N3837) stable across temperatures; a cross-model behavioral proxy on two frontier models yields preliminary evidence of divergence in self-reported moral focus, consistent with an Alignment Wrapper in which RLHF re-orders surface text without removing underlying domain-first frames. We unify these as Frame-Conditioned Moral Computation: the prompt's surface vocabulary selects a feature manifold, and the moral conclusion is downstream of that selection. Behavioral alignment must be supplemented by Mechanistic Alignment: a research program asking whether ethics-related features can be shown causally privileged under controlled frame variation, not merely loud in the explanation.

22.
arXiv (CS.AI) 2026-06-17

L-Proto: Language-Aware Episodic Prototypical Training for Multilingual Speaker Verification

arXiv:2606.17416v1 Announce Type: cross Abstract: Multilingual speaker verification remains challenging because language-dependent acoustic variability causes speaker identity to become entangled with linguistic characteristics, degrading generalization across languages. In multilingual training, embeddings often encode language cues with speaker identity, causing speakers to form language-specific clusters. We propose L-Proto, a language-aware episodic prototypical training strategy that constructs language-consistent episodes. By sampling speakers from a single language per episode, L-Proto reduces language-driven variation during training and encourages embeddings to focus more directly on speaker identity. Experiments on the TidyVoice Challenge benchmark demonstrate consistent performance improvements over conventional fine-tuning and random episodic sampling across multiple backbone architectures.

23.
arXiv (CS.CL) 2026-06-11

Fine-tuning Multi-modal LLMs with ART: Art-based Reinforcement Training

There are two main Parameter-Efficient Fine-Tuning (PEFT) techniques for Large Language Models (LLMs). While Low-Rank Adaptation (LoRA) introduces additional weights between the LLM layers, Soft Prompting introduces additional fine-tuning-specific raw tokens to an LLM input. However, both require modification to the computational graphs of precompiled, preoptimized LLMs. As a result, neither is fully supported in high-throughput engines like vLLM. We propose fine-tuning with ART (Art-based Reinforcement Training). The method injects information into a frozen Multimodal Large Language Model (MLLM) by optimizing only its raw visual input, thus enabling the soft-token approach on pre-compiled computational graphs. It relies on backpropagation of gradients back into a plain pixel array and thus supports any fine-tuning objective. Moreover, the optimized visual input can be stylized as task-relevant computational artworks. The approach's effectiveness is confirmed for different sizes of a popular open Qwen architecture and for several textual benchmarks. Specifically, ART reaches accuracy competitive with LoRA across mathematics and structured-tool-use benchmarks.

24.
arXiv (quant-ph) 2026-06-12

Toward Entanglement Bootstrap for Conformal Field Theory in Any Dimension

arXiv:2606.12540v1 Announce Type: cross Abstract: Given a quantum critical wavefunction in any dimension, we propose a reconstructed Hamiltonian, analogous to the ones previously found for 1+1d CFT and for 2+1d bosonic liquid topologically-ordered states. We test numerically that, for known regularized approximate CFT groundstates (on the icosahedron and the fuzzy sphere), (1) they are close to the groundstate of their reconstructed Hamiltonian, and (2) the spectrum of their reconstructed Hamiltonian on the unit sphere has CFT properties (integer spacing of descendants) and matches known low-lying energies. We show that this provides an automated method to improve the finite-size effects in a fixed Hilbert space.

25.
arXiv (CS.CL) 2026-06-12

C-QUERI: Congressional Questions, Exchanges, and Responses in Institutions Dataset

Questions in political interviews and hearings serve strategic purposes beyond information gathering including advancing partisan narratives and shaping public perceptions. However, these strategic aspects remain understudied due to the lack of large-scale datasets for studying such discourse. Congressional hearings provide an especially rich and tractable site for studying political questioning: Interactions are structured by formal rules, witnesses are obliged to respond, and members with different political affiliations are guaranteed opportunities to ask questions, enabling comparisons of behaviors across the political spectrum. We develop a pipeline to extract question-answer pairs from unstructured hearing transcripts and construct a novel dataset of committee hearings from the 108th–117th Congress. Our analysis reveals systematic differences in questioning strategies across parties, by showing the party affiliation of questioners can be predicted from their questions alone. Our dataset and methods not only advance the study of congressional politics, but also provide a general framework for analyzing question-answering across interview-like settings.