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01.
medRxiv (Medicine) 2026-06-16

Utilising Artificial Intelligence to Identify Ventricular Tachycardia Ablation Targets in Sinus Rhythm

Background and Aims: Machine learning has shown potential in predicting ablation targets for ventricular tachycardia (VT) in an animal model. This study progresses to externally validating deep learning approaches for human data. Methods: The development and external validation dataset included 21 and 13 patients, respectively, with structural VT undergoing catheter ablation. In the development datasets, electrophysiological studies were conducted using the AdvisorTM HD grid (EnsiteTM X), while both CARTO and Ensite Precision were used in the validation dataset. In each patient, VT ablation targets were defined as mapping points within 8 mm of VT isthmuses. Three advanced machine learning models were trained using cardiac mapping data acquired in both omnipolar and unipolar configurations during sinus rhythm and ventricular pacing. Discrimination was evaluated using nested leave-one-out cross-validation at patient level. Results: Overall, graph convolutional networks (GCNs), which integrate intracardiac signal waveforms with three-dimensional electroanatomical geometries, achieved the highest performance, with optimal results obtained from unipolar electrograms acquired in sinus rhythm (median AUC 0.793, sensitivity 83.6%, specificity 69.0%). This may be partly explained by the inclusion of repolarization dynamics in unipolar electrograms and the higher point density of sinus rhythm maps. Comparable performance was observed in the external dataset. Conclusion: This study demonstrates that graph convolutional networks applied to sinus rhythm EGM waveforms collected during substrate mapping can localise critical components of VT re-entry circuits. This approach has potential to provide fast and accurate ablation guidance without the need to induce and map VT, improving safety and efficacy of VT catheter ablation.

02.
arXiv (CS.AI) 2026-06-15

A Temporal Planning Framework for Disruption Aware Dynamic Route Optimization in Heterogeneous Railway Systems

arXiv:2606.14582v1 Announce Type: new Abstract: Efficient route optimization play a vital role in ensuring both safety and punctuality in railway operations. It is very crucial particularly in heterogeneous multi-gauge railway networks with varying train speed, stopping pattern, infrastructure compatibility constraints increase coordination complexity. In single-track systems these challenges are further intensify due to all trains to share the same track and requires frequent track switching.Stochastic disruptions events including blocked tracks, blocked trains, engine failure and speed slowdowns introduces additional unpredictability in operations and deviate the timetable. However, existing studies predominantly focuses on high-level timetabling, omitting operational details such as track switching coordination. As a result leaving decision to human operators, increasing safety risks into railway operations. This study proposes a framework based on temporal planning for dynamic route optimization and disruption management in heterogeneous railway systems. The framework formulates railway operations as a temporal planning problem using PDDL 2.1 with explicitly modeling gauge compatibility constraints and diverse disruption scenarios. It generates conflict-free timestamped operational plans specifying both optimized schedules and executable action sequences. To evaluate the proposed framework, we developed a benchmark problem set with 200 instances using up to 1,000 track points and 120 trains. Two state-of-the-art temporal planners and a plan validator were employed to assessed the framework. The experimental results demonstrate that the framework effectively generates temporal operational plans for heterogeneous railway systems and handles multi-gauge constraints, disruptions, and reduces dependence on manual decision making.

03.
arXiv (CS.AI) 2026-06-16

Unifying Post-hoc Explanations of Knowledge Graph Completions

arXiv:2507.22951v2 Announce Type: replace Abstract: Knowledge Graphs organize information as entity-relation-entity triples, enabling machine learning models to predict plausible missing triples in a task known as Knowledge Graph Completion (KGC). Post-hoc explainability for KGC addresses the problem of identifying which triples most influence the predictions of machine learning models. Currently, the field lacks formalization and consistent evaluations, hindering reproducibility and cross-study comparisons. This paper argues for a unified taxonomy for post-hoc explainability in KGC. First, we propose a characterization of post-hoc explanations via multi-objective optimization that unifies existing post-hoc explainability algorithms in KGC and the explanations they produce, balancing explanation effectiveness and conciseness. Next, we examine improved evaluation protocols based on popular metrics, such as Mean Reciprocal Rank and Hits@k, through illustrative experiments. Finally, we stress the importance of interpretability as the ability of explanations to address queries meaningful to end users. By unifying methods and discussing evaluation standards, this work puts forward a case for more reproducible and impactful research in KGC explainability.

04.
arXiv (CS.LG) 2026-06-16

Towards CONUS-Wide ML-Augmented Conceptually-Interpretable Modeling of Catchment-Scale Precipitation-Storage-Runoff Dynamics

arXiv:2510.02605v2 Announce Type: replace Abstract: While many modern studies are dedicated to ML-based large-sample hydrologic modeling, these efforts have not necessarily translated into predictive improvements that are grounded in enhanced physical-conceptual understanding. Here, we report on a CONUS-wide large-sample study (spanning diverse hydro-geo-climatic conditions) using ML-augmented physically-interpretable catchment-scale models of varying complexity based in the Mass-Conserving Perceptron (MCP). Results were evaluated using attribute masks such as snow regime, forest cover, and climate zone. Our results indicate the importance of selecting model architectures of appropriate model complexity based on how process dominance varies with hydrological regime. Benchmark comparisons show that physically-interpretable mass-conserving MCP-based models can achieve performance comparable to data-based models based in the Long Short-Term Memory network (LSTM) architecture. Overall, this study highlights the potential of a theory-informed, physically grounded approach to large-sample hydrology, with emphasis on mechanistic understanding and the development of parsimonious and interpretable model architectures, thereby laying the foundation for future models of everywhere that architecturally encode information about spatially- and temporally-varying process dominance.

05.
bioRxiv (Bioinfo) 2026-06-10

GEOAgent: An AI-driven Autonomous Framework for Intelligent GEO Data Retrieval and Standardized Preprocessing

Datasets in the Gene Expression Omnibus (GEO) remain difficult to reuse at scale because sample annotations are heterogeneous and raw sequencing data require assay-specific preprocessing. We present GEOAgent, an AI-driven autonomous framework designed for intelligent dataset retrieval and standardized preprocessing by coupling autonomous semantic governance with an automated Nextflow pipeline named bioStream. Metadata from 181,760 sequencing series and 84,756 associated PubMed records were organized in a relational database and semantic index to support natural-language dataset retrieval. The framework automatically determines assay modalities, resolves experimental design pairings, and standardizes sample naming to minimize manual curation overhead. Based on these parsed attributes, the framework generates deployment-ready manifests to automatically execute containerized workflows across bulk and single-cell omics modalities. In expert-curated benchmarks, the workflow achieved 96% retrieval precision alongside 100% accuracy in assay classification and sample relationship resolution. The web platform is publicly accessible, while the source code and associated databases are openly available via GitHub and Zenodo.

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

Who Pays the Price? Stakeholder-Centric Prompt Injection Benchmarking for Real-world Web Agents

arXiv:2606.13385v1 Announce Type: cross Abstract: Web agents driven by large language models (LLMs) are increasingly deployed in real-world environments, where they operate over untrusted web content and execute actions with direct consequences. This makes them vulnerable to prompt-injection attacks, in which seemingly benign content embeds adversarial instructions that manipulate agent behaviour. Existing security benchmarks adopt an attack-centric perspective, focusing on the technical feasibility of injections while overlooking the nuanced distribution of resulting harms. In practice, however, prompt-injection risk is victim-dependent: a single exploit can produce asymmetric consequences for different stakeholders, and the same attack pattern may exhibit substantially different effectiveness depending on whom it targets. To capture these properties, we introduce \sysname, a stakeholder-centric benchmark to systematically categorize and attribute harm in real-world web agent systems. It distinguishes between affected entities (e.g., user, seller, platform), decomposes the attacks into concrete objectives, and evaluates each case with complementary outcome- and process-level metrics. Our results reveal substantial and heterogeneous vulnerabilities: not a single attack objective is reliably resisted by current agents, and failures distribute across qualitatively distinct modes ranging from stealthy parasitism (attack succeeds without disrupting the user's delegated task) to misaligned disruption (task disrupted without attack success) and compounded failure (both adversarial objective and task integrity simultaneously violated). These patterns are missed by conventional evaluation, highlighting the need for stakeholder-aware assessment of LLM-based agents in real-world deployments. Benchmark is available at https://github.com/StakeBench/SBC.

07.
arXiv (CS.LG) 2026-06-17

Maximin Relative Improvement: Fair Learning as a Bargaining Problem

arXiv:2602.04155v2 Announce Type: replace-cross Abstract: When deploying a single predictor across multiple subpopulations, we propose a fundamentally different approach: interpreting group fairness as a bargaining problem among subpopulations. This game-theoretic perspective reveals that existing robust optimization methods such as minimizing worst-group loss or regret correspond to classical bargaining solutions and embody different fairness principles. We propose relative improvement, the ratio of actual risk reduction to potential reduction from a baseline predictor, which recovers the Kalai-Smorodinsky solution. Unlike absolute-scale methods that may not be comparable when groups have different potential predictability, relative improvement provides axiomatic justification including scale invariance and individual monotonicity. We establish finite-sample convergence guarantees under mild conditions.

08.
medRxiv (Medicine) 2026-06-11

Neighborhood socioeconomic status associated with post-stroke cognitive impairment: a retrospective cohort study

Background: Late complications after stroke (LCAS), including cognitive symptoms, impact quality of life and recovery. It is not known if neighborhood-level measures of socioeconomic status (SES) influence LCAS. This study assessed associations between SES measures, including neighborhood income inequality (Gini) and area deprivation index (ADI), and cognitive symptoms after acute ischemic stroke (AIS) in a hospital leveraging active surveillance of LCAS. Methods: This retrospective cohort study included 512 patients hospitalized with AIS at Tufts Medical Center with subsequent follow-up (between zero and three months or between three and twelve months) in the Stroke Clinic from 1/1/2018 - 12/31/2022. Using ZIP code data, patients were characterized as low Gini (low inequality) and high ADI (high deprivation) (Gini = 5) by state medians. These variables were combined, indicating patients who were living in both a low Gini and high ADI neighborhood to evaluate the effects of living in a homogeneously deprived area. There were 206 and 281 patients in the low Gini and high ADI groups respectively. 140 patients lived in a low Gini and high ADI neighborhood. The multivariable logistic analysis assessed the likelihood of cognitive symptoms, adjusting for age, race, ethnicity, sex, NIH Stroke Scale (NIHSS), thrombolysis, active LCAS surveillance, poverty, and ADI-Gini combination. Results: There were no associations between high ADI (OR: 1.03, 95% CI: 0.67 ? 1.57) or low Gini (OR: 1.74, 95% CI: 0.98 ? 3.07) alone and cognitive symptoms after AIS. However, the combined variable demonstrated increased likelihood of cognitive symptoms in the high ADI-low Gini group (OR: 1.82, 95% CI: 1.08 ? 3.06). Conclusions: This study suggests that individuals living in homogeneously deprived neighborhoods report higher likelihood of cognitive symptoms after AIS. Further studies with increased power are needed to investigate the underlying causes of these disparities and to develop interventions to reduce these complications.

09.
arXiv (CS.LG) 2026-06-16

PromptShift-CRC: Drift-Aware Conformal Risk Control for Foundation Models Under Prompt and Domain Shift

arXiv:2606.15964v1 Announce Type: cross Abstract: Foundation models are now used in settings where the prompts they receive can change quickly. Users change, topics change, policies change, and the model may suddenly face a kind of request that was rare in the calibration data. This makes fixed calibration risky. Conformal prediction and conformal risk control give model-agnostic ways to control error, but they work best when the calibration data still look like the future data. This paper develops PromptShift CRC, a drift-aware conformal risk control method for foundation-model outputs under prompt and domain shift. The method embeds prompts and responses, measures how far the current prompt stream has moved from the calibration pool, gives more weight to relevant or recent calibration examples, and updates the risk level online after observed violations. It reports three practical diagnostics: realized risk error, prompt drift, and effective calibration size. We give conditions under which the method controls risk up to terms for distribution mismatch and weighted quantile uncertainty. In a synthetic prompt-shift benchmark, static conformal risk control fails sharply after drift, while PromptShift-CRC gives the best coverage among the adaptive baselines considered. We then evaluate the same calibration layer on public benchmark derived streams for question answering, toxicity, summarization factuality, and long-context hallucination risk

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

An End-to-End Hybrid Framework for Rumour Detection in Low-Resources Algerian Dialect

The rapid growth of social media has intensified the spread of rumours. This issue is more challenging in the Algerian context due to the informal and code-switched nature of dialectal content, the scarcity of annotated resources, and the limited effectiveness of standard Arabic NLP tools on dialect text. This paper presents an end-to-end rumour detection hybrid framework for Algerian dialect social media content. We build a domain-specific annotated dataset by combining real social media posts, synthetic data, and the FASSILA corpus, with automatic labeling based on a similarity-based annotation process. A transliteration pipeline is also introduced to generate parallel datasets in Arabic script and Arabizi. We evaluate multiple approaches, including classical machine learning, deep learning, transformers, and hybrid models. Experimental results show that a hybrid approach combining transformer embeddings with a classical classifier achieves the best performance, reaching an F1-score of 0.84. We also find that domain-specific pre-training is more important than model size, with social media-trained models outperforming larger models trained on formal Arabic corpora. These results demonstrate the feasibility of rumour detection in low-resource Algerian dialect settings.

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

Beyond Uniform Tokens: Adaptive Compression for Time Series Language Models

Large language models (LLMs) have enabled time series (TS) analysis by jointly modeling numerical observations and textual context through a shared token interface. However, TS tokens and prompt tokens exhibit fundamentally different information structures, making uniform token processing inefficient. In this paper, we study token efficiency in TS language modeling from an asymmetric-token perspective. We show that TS tokens have highly uneven spectral contributions, where many tokens share redundant frequency patterns while a small subset preserves critical temporal evidence. We also observe that prompt-token influence attenuates with model depth, suggesting that full prompt retention across all layers is unnecessary. Based on these findings, we develop an adaptive token budgeting framework that compresses TS tokens via frequency-domain structure and progressively reduces prompt tokens across layers. Experiments across forecasting, classification, imputation, and anomaly detection demonstrate up to 7.68$\times$ inference acceleration and performance gains in 78\% of evaluated settings, showing the effectiveness of asymmetric token compression for scalable TS foundation models.

12.
bioRxiv (Bioinfo) 2026-06-11

HalluDesign-NA: Extending HalluDesign for De Novo Nucleic Acid Design

AlphaFold3 has revolutionized the prediction of biomolecular structures and interactions, including atomic-level modeling of nucleic acids. However, the de novo design of structured and functional nucleic acids remains a significant challenge. Here, we extend our HalluDesign framework to nucleic acid design by integrating NA-MPNN for nucleic acid sequence optimization and design. This new framework, HalluDesign-NA, enables iterative sequence-structure co-optimization, facilitating the de novo design of nucleic acids. Computational benchmarking across ssDNA, ssRNA, and aptamer design tasks demonstrates consistent improvements in confidence scores (pLDDT, ipTM), supporting the feasibility of de novo nucleic acid design under various constraints, such as sequence length, symmetry, and protein structure context. We anticipate that HalluDesign-NA will accelerate the de novo design of functional nucleic acids for applications in biotechnology and medicine. The source code for HalluDesign-NA is available at https://github.com/MinchaoFang/HalluDesign_NA.

13.
Nature (Science) 2026-06-10

Light slows down carbon nanotubes in water

Water-suspended carbon nanotubes move more slowly in green light, suggesting that excited electrons in the tubes couple to the water through ‘quantum friction’. Water-suspended carbon nanotubes move more slowly in green light, suggesting that excited electrons in the tubes couple to the water through ‘quantum friction’.

14.
arXiv (CS.LG) 2026-06-17

Evaluating Uplift Modeling under Structural Biases: Insights into Metric Stability and Model Robustness

arXiv:2603.20775v2 Announce Type: replace Abstract: In personalized marketing, uplift models estimate the incremental effect of an intervention by modeling how customer behavior would change under alternative treatments using counterfactual analysis. However, real-world marketing data often exhibit various biases, such as selection bias, spillover effects, measurement error, and unobserved confounding. These biases can adversely affect both the accuracy of uplift estimation and the validity of evaluation metrics. Despite the importance of bias-aware assessment, there remains a lack of systematic studies evaluating how different models and metrics perform under such biased conditions. To bridge this gap, we design a systematic benchmarking framework. Unlike standard predictive tasks, real-world uplift datasets inherently lack counterfactual ground truth. This limitation renders the direct validation of evaluation metrics infeasible and prevents the precise quantification of biases. Therefore, a semi-synthetic approach serves as a critical enabler for systematic benchmarking. This approach effectively bridges the gap by retaining real-world feature dependencies while providing the ground truth needed to isolate structural biases. Our investigations reveal that (i) uplift targeting and prediction can manifest as distinct objectives, where proficiency in one does not ensure efficacy in the other; (ii) while many models exhibit inconsistent performance under diverse biases, TARNet shows notable robustness, providing insights for subsequent model design; (iii) the stability of evaluation metrics is linked to their mathematical alignment with the ATE, suggesting that ATE-approximating metrics yield more consistent model rankings under structural data imperfections. These findings suggest the need for more robust uplift models and evaluation metrics under real-world data imperfections.

15.
arXiv (CS.AI) 2026-06-17

Learn to Quantify Social Interaction with Constraints for Pedestrian Walking

Authors:

arXiv:2606.17897v1 Announce Type: new Abstract: Long-term human path forecasting in crowds is critical for autonomous moving platforms (like autonomous driving cars and social robots) to avoid collision and make high-quality planning. Although the current research take into account social interactions for prediction, they don't reveal the exact kinds of social interactions happened among people and how the social interactions affect the decision-making process of pedestrians, which further limits its robustness. Social interactions in pedestrian walking are intuitively massive and hard to label and quantify. In this paper, we explore creatively to quantify and interpret how pedestrians interact with others by proposing Learn to Cluster. Our clustering social interactions is probabilistic latent variable generative, learning directly from sequential trajectory observations, scalable to arbitrary number of pedestrians. Learn to cluster is label-free and can be naturally integrated into the training process of the prediction model. The latent variables will then serve as 'labels' to categorize social interactions. Extensive experiments over several trajectory prediction benchmarks demonstrate that our method is able to learn the patterns of social interactions and effectively integrate the patterns to pedestrian trajectory prediction.

16.
arXiv (CS.LG) 2026-06-11

MPK: A Compiler and Runtime for Mega-Kernelizing Tensor Programs

arXiv:2512.22219v2 Announce Type: replace-cross Abstract: We introduce Mirage Persistent Kernel (MPK), the first compiler and runtime system that automatically transforms multi-GPU model inference into a single high-performance mega-kernel. MPK introduces an SM-level graph representation that captures data dependencies at the granularity of individual streaming multiprocessors (SMs), enabling cross-operator software pipelining, \rev{fine-grained overlap of computation and communication, and other optimizations that are infeasible under the conventional kernel-per-operator execution model}. The MPK compiler lowers tensor programs into optimized SM-level task graphs and generates fast CUDA implementations for each task, while the MPK in-kernel parallel runtime executes these tasks within a single persistent mega-kernel using decentralized scheduling across SMs. Together, these components provide end-to-end kernel fusion with minimal developer effort, while preserving the flexibility of existing programming models. Our evaluation shows that MPK significantly outperforms existing kernel-per-operator LLM serving systems, achieving up to 1.7$\times$ lower end-to-end inference latency and pushing LLM inference performance close to the limits of the underlying hardware. MPK is publicly available at https://github.com/mirage-project/mirage.

17.
arXiv (CS.CL) 2026-06-19

Reliability without Validity: A Systematic, Large-Scale Evaluation of LLM-as-a-Judge Models Across Agreement, Consistency, and Bias

LLM-as-a-Judge has become the dominant evaluation paradigm for language models, but judge validation in practice relies on exact-match agreement, a metric that does not correct for chance and systematically overstates discriminative ability. We present the largest systematic evaluation of LLM-as-a-Judge to date: 21 judges from nine providers across MT-Bench, JudgeBench, and RewardBench, evaluated under three protocols (agreement, consistency, bias audit) over 118 runs and approximately 541,000 individual judgments. Four findings emerge, consistent across the full cohort, including the April 2026 frontier: kappa deflation between exact match and Cohen's kappa is universal (33–41 pp on MT-Bench), judge rankings shift by up to 14 positions across benchmarks, high test–retest reliability (>0.95) coexists with severe position bias (>0.10) in two production-deployed judges (instantiating a consistency–bias paradox), and verbosity bias is small (

18.
arXiv (CS.CV) 2026-06-15

Pano3D: Unified 3D Reconstruction and Panoptic Segmentation

Recent advances in 3D feedforward reconstruction neural networks have achieved remarkable success in dense reconstruction from images without any camera parameters. Yet, equipping these models with robust semantic understanding remains an open problem. Here we introduce an approach that performs 3D reconstruction and 3D panoptic segmentation in a unified framework. We build on existing 3D reconstruction models and augment them with a set-based mask decoder. The approach is jointly trained with a geometric and semantic loss, which are shown to be mutually beneficial. More precisely, the features are initialized from the geometric information and then finetuned to capture jointly geometry and semantics. We demonstrate the generality of our approach by successfully applying our framework both to online and all-to-all attention reconstruction backbones. Our method achieves state-of-the-art performance in 3D panoptic segmentation across ScanNet, ScanNet200, and ScanNet++ datasets. Ablation studies show that such joint training of a unified model equips 3D feedforward reconstruction neural networks with panoptic segmentation and yields mutually beneficial improvements.

19.
Science (Express) 2026-06-18

Indium-free perovskite/silicon tandem solar cells with tin oxide recombination layer and electrodes | Science

Authors: Unknown Author

Indium-based transparent conductive oxides are widely used as electrodes and recombination layers in perovskite/silicon tandem solar cells, yet their scalability is constrained by indium scarcity and sputtering-induced damage. Here we report high efficiency and stable indium-free perovskite/silicon tandem solar cells enabled by reactive plasma deposited tin oxide (RPD-SnO x ). For RPD-SnO x as the recombination layer, a certified efficiency of 33.6% is achieved. Fully indium-free tandems that used RPD-SnO x as both recombination layer and electrodes delivering a champion PCE of 33.2% (1 cm 2 ) and a mini-module with a certified efficiency of 31.0% (207.9 cm 2 ). Dense and uniform self-assembled monolayer anchoring enabled by RPD-SnO x suppressed non-radiative recombination and reduced halide migration. Indium-free mini-modules exhibited high thermal, damp-heat, and outdoor operational stability and retained 65% of their maximum initial efficiency after 105 days of outdoor operation.

20.
arXiv (CS.CL) 2026-06-16

Stop When Further Reasoning Won't Help: Attention-State Adaptive Generation in Reasoning Models

By incorporating test-time compute scaling, large reasoning models (LRMs) can solve complex problems through explicit chain-of-thought (CoT) reasoning processes. However, they often suffer from overthinking, resulting in redundant token outputs and degraded accuracy. Current methods to mitigate this issue remain limited: training-based approaches require substantial computational resources, while training-free methods rely on well-crafted prompts or unreliable confidence signals. In this work, we investigate early stopping from the perspective of attention distributions and propose a simple method, ASAG, which infers the model's reasoning state and adaptively adjusts the generation strategy. The proposed framework is training-free and plug-and-play, enabling seamless integration into existing LRMs. Extensive experiments on nine benchmarks demonstrate consistent improvements across mainstream LRMs with varying parameter scales, including the DeepSeek-R1-Distill and Qwen3 series. Specifically, ASAG improves average accuracy by 3.2% while reducing the number of generated tokens by nearly 40% across all reasoning tasks on Qwen3-8B.

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

DYNA-PRUNER: Input-Adaptive Data-Model Co-Pruning for Efficient and Scalable Spatio-Temporal Media Prediction

Spatio-temporal prediction supports radar/satellite nowcasting and city-scale traffic monitoring, but modern models are often too expensive for real-time deployment. This stems from a mismatch between dense computation and strong input-dependent redundancy (e.g., calm seas or clear skies). To enable automated, resource-aware architecture optimization in scalable media analysis, we propose Dyna-Pruner, an end-to-end framework for input-dependent co-pruning of data and model structure. A shared-importance synchronization mechanism generates coupled masks that prune redundant regions and their corresponding computational units (e.g., convolutional filters), yielding per-sample sparse sub-networks at inference time. Experiments on WeatherBench, SEVIR, and TaxiBJ show seamless integration with CNN, RNN, and Transformer backbones, reducing FLOPs by up to $70\%$ and achieving a $2.5\times$ speedup on NVIDIA Jetson AGX Orin with negligible accuracy loss ($

22.
medRxiv (Medicine) 2026-06-22

A Controlled Human Malaria Infection model for relapsing Plasmodium vivax

Background Plasmodium vivax malaria relapses are a major source of morbidity and onward transmission of infection. The underlying mechanisms are poorly understood and current therapies sub-optimal. We examined the safety and feasibility of a controlled human malaria infection (CHMI) model for relapsing P. vivax. Methods We conducted an open-label, proof-of-concept, CHMI study of relapsing P. vivax. Healthy, malaria-naive, Duffy-positive adults aged 18-45 years with extensive CYP2D6 metaboliser phenotype and normal blood glucose-6-phosphate dehydrogenase (G6PD) levels were recruited in Oxford, UK. Mosquito-bite CHMI was performed in Nijmegen, The Netherlands, using Anopheles stephensi mosquitoes infected with PvW1, a clonal isolate of P. vivax from Thailand. All follow-up visits were conducted in Oxford, UK. Primary P. vivax infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine (80mg/480mg at 8, 24, 36, 48 and 60 hours). From Day 28 following CHMI, participants attended a fortnightly clinic for clinical review and qPCR blood sampling, with additional assessments performed for any reported symptoms. P. vivax relapse infections (qPCR > 500 genome copies/mL) were treated with artemether-lumefantrine as per primary infection. Definitive anti-malarial treatment with atovaquone-proguanil (1000mg/400mg once daily for three days) and primaquine (0{middle dot}5 mg/kg/day for 14 days) was administered six months following CHMI, regardless of parasitaemia or symptoms. The primary objective was to assess the safety, feasibility and frequency of relapsing P. vivax after CHMI. Remote follow-up (5 years) is ongoing. The study is registered with ISRCTN registry (ISRCTN48625883). Findings 20 participants were screened for eligibility from 21 January 2025. Five participants (median age 22 years) underwent CHMI (five infected mosquitoes per participant) on 15 April 2025. All participants developed primary P. vivax infection and experienced at least one relapse infection. Two participants experienced a second relapse. Overall incidence rate was 3{middle dot}6 relapse infections per person-year. Solicited adverse events were mild or moderate and there were no serious adverse events. Definitive anti-malarial treatment was administered to all participants. One participant experienced primaquine-induced methaemoglobinaemia, resolving with early discontinuation of treatment (total dose 5{middle dot}3 mg/kg). To date, more than six months after primaquine treatment, no further relapses have been recorded. Interpretation CHMI of relapsing P. vivax is safe and feasible, allowing exploration of the mechanisms underlying relapse infections and providing a platform for future anti-relapse efficacy studies. Funding European Union Horizon Europe programme and UK Research and Innovation (UKRI) via OptiVivax consortium; UK National Institute for Health and Care Research Biomedical Research Centre: Oxford; and UK Medical Research Council.

23.
arXiv (CS.LG) 2026-06-17

Data augmented bootstrap: Unifying confidence interval construction by approximate invariance

arXiv:2606.09049v2 Announce Type: replace-cross Abstract: We propose the data augmented bootstrap (DAB), a framework for constructing confidence intervals from approximately invariant transformations of the data. As special cases, DAB recovers popular methods that rely on exact group symmetries, such as conformal prediction, wild bootstrap for Maximum Mean Discrepancy U-statistics and the recently proposed SymmPI. Meanwhile, DAB also recovers the classical bootstrap method, which exploits the dataset's approximate invariance under uniform sampling of data indices as the dataset size grows. For all DAB methods, we establish theoretical coverage results that interpolate between finite-sample and asymptotic guarantees according to the strength of the invariance, and without assuming a group structure. The approximate invariance is measured in the Kolmogorov distance and, for statistics that satisfy Gaussian universality, reduces to conditional mean and variance matching. This allows us to incorporate data augmentation (DA), a widely used machine learning heuristic based on approximate invariances, into known statistical methods. We empirically test the performance of incorporating DA into bootstrap, wild bootstrap and conformal prediction for simulated settings as well as for image, language and scientific data.

24.
arXiv (CS.LG) 2026-06-16

When Does q-error Predict Plan Regret? Three Regimes of Cardinality-Estimation Error

arXiv:2606.15600v1 Announce Type: cross Abstract: Cardinality-estimation (CE) research ranks estimators by q-error, yet it is well known that q-error is an imperfect proxy for query-plan quality. We give a measurement-driven account of when it is a good proxy and when it is not, and why. Modeling plan selection as an argmin over a piecewise-linear cost landscape, we find that plan regret (the cost of the chosen plan relative to the optimal, under true cardinalities) is governed by plan-cost geometry in a regime-dependent way. (i) For small errors, a true-point condition number kappa predicts regret and out-predicts q-error; its predictive power decays to zero as error grows, as a local linearization must. (ii) For large errors – where deployed learned estimators operate – an estimator-independent average-case sub-optimality measure ACS-infinity predicts which queries are regret-prone (Spearman rho ~ 0.54 on STATS-CEB), while q-error is nearly uninformative at the query level (rho ~ 0.05). (iii) The worst case is Haritsa's maximum sub-optimality (MSO). The three are one cost-ratio spectrum under three weightings. We prove a limit law ACS-infinity = sum_k r_k pi_k with cardinality-independent combinatorial weights, and validate every claim on STATS-CEB and JOB-light with four released estimators under pre-registered decision rules, and confirm on real PostgreSQL runtime that ACS-infinity predicts regret where q-error does not. The contribution is conceptual and empirical – an average-case companion to worst-case robust query optimization, and a characterization of when an accuracy metric tracks plan quality – rather than a new estimator. Code and the full pre-registration are public.

25.
arXiv (CS.LG) 2026-06-18

KANEL\'E: Kolmogorov-Arnold Networks for Efficient LUT-based Evaluation

arXiv:2512.12850v3 Announce Type: replace-cross Abstract: Low-latency, resource-efficient neural network inference on FPGAs is essential for applications demanding real-time capability and low power. Lookup table (LUT)-based neural networks are a common solution, combining strong representational power with efficient FPGA implementation. In this work, we introduce KANEL\'E, a framework that exploits the unique properties of Kolmogorov-Arnold Networks (KANs) for FPGA deployment. Unlike traditional multilayer perceptrons (MLPs), KANs employ learnable one-dimensional splines with fixed domains as edge activations, a structure naturally suited to discretization and efficient LUT mapping. We present the first systematic design flow for implementing KANs on FPGAs, co-optimizing training with quantization and pruning to enable compact, high-throughput, and low-latency KAN architectures. Our results demonstrate up to a 2700x speedup and orders of magnitude resource savings compared to prior KAN-on-FPGA approaches. Moreover, KANEL\'E matches or surpasses other LUT-based architectures on widely used benchmarks, particularly for tasks involving symbolic or physical formulas, while balancing resource usage across FPGA hardware. Finally, we showcase the versatility of the framework by extending it to real-time, power-efficient control systems.