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01.
arXiv (CS.LG) 2026-06-12

Clipping Makes Distributed and Federated Asynchronous SGD Robust to Stragglers

arXiv:2606.13287v1 Announce Type: new Abstract: In modern machine learning, parallelization of training is an important strategy for increasing scale. Asynchronous stochastic gradient descent (ASGD), which maximizes the utilization of available hardware by avoiding waiting for slow workers. However, with constant step sizes, the convergence of ASGD is nonetheless affected negatively by slow workers due to large delays in updates. At the same time, it has been empirically observed in asynchronous training of deep learning models that gradient clipping "stabilizes" training. In this work, we provide a theoretical justification for this behavior, as we show that clipping removes the dependence of the maximum delay in the oracle complexity. We employ a sub-Weibull model of gradient noise which generalizes sub-Gaussian and sub-exponential distributions to more heavy-tailed distributions, motivated by empirical observations in deep learning. We show convergence in expectation, and the first time in asynchronous optimization, convergence with high probability.

02.
arXiv (quant-ph) 2026-06-11

The quantum harmonic oscillator and the real Hilbert space

arXiv:2606.12060v1 Announce Type: new Abstract: The harmonic oscillator is considered within generalized frameworks using complex and quaternionic numbers. The classical oscillator is considered in terms of a complex position function, and quantum oscillators are examined in terms of complex wave functions, and in terms of quaternionic wave functions as well. Both of the quantum solutions are obtained within the real Hilbert space formalism. The results reveal the complex and quaternionic descriptions as suitable frameworks for non-stationary processes, including damped oscillations, forced oscillations, and additionally self-interacting processes that cannot be appropriately described otherwise.

03.
arXiv (CS.CV) 2026-06-12

MAMVI: 3D Test-Time Adaptation via Masked Multi-View Point Clouds

3D point cloud models suffer significant performance degradation under distribution shifts caused by sensor noise, occlusions, and environmental changes. Test-time adaptation (TTA) has emerged as a practical paradigm for mitigating this issue during inference. Recently, leveraging multi-view augmentation has shown promise in improving 3D TTA performance. However, existing multi-view approaches are often constrained by sequential optimization that treats each view independently. This sequential optimization leads to substantial inference latency due to repetitive optimization steps, making real-time adaptation impractical. To address this, we propose Masked Multi-View Test-Time Adaptation (MAMVI), which replaces sequential optimization with a unified single-step adaptation. Specifically, MAMVI utilizes a hybrid masking strategy that combines fixed ratios for stability with Beta-distributed sampling for diversity. By aggregating losses across multiple views, MAMVI performs adaptation through a single backward pass based on multi-view consensus. Additionally, a confidence-based adaptive learning rate is used to dynamically adjust the adaptation intensity for each sample. Extensive experiments on ModelNet-40C, ShapeNet-C, and ScanObjectNN-C demonstrate that MAMVI achieves state-of-the-art accuracy on ShapeNet-C and ScanObjectNN-C. Moreover, it remains competitive on ModelNet-40C while delivering 4.9-8.9 times faster inference, making it highly suitable for real-time applications. Our code is available at https://github.com/Inseok-kong/MAMVI

04.
arXiv (quant-ph) 2026-06-19

Subsystem Quantum Error Correction for Noisy Quantum Metrology

arXiv:2606.19628v1 Announce Type: new Abstract: Quantum error correction has been successfully applied to enhance the precision of parameter estimation in the presence of noise. Nonetheless, existing methods require a number of noiseless, controllable ancillae and lack efficient encoding and decoding procedures. In this Letter, we demonstrate that subsystem error correction provides a new direction that can substantially simplify the metrological protocol. We derive general conditions under which subsystem stabilizer codes achieve the Heisenberg limit and show that, for broad classes of noise, this can be realized by syndrome-free protocols using at most a single ancilla qubit. Furthermore, we extend this framework to dynamical error correction and show that Floquet codes can protect time-dependent metrological signals in reaching the Heisenberg limit.

05.
arXiv (CS.CV) 2026-06-18

AMALIA-VL: A Native European Portuguese Open-Source Vision and Language Model

Large Vision and Language Models (LVLMs) have advanced rapidly, yet European Portuguese (pt-PT) remains systematically underserved by existing open-source multimodal models, which either conflate it with Brazilian Portuguese or severely under-represent it in their training data mixes. We introduce AMALIA-VL, the first open-source instruction-tuned LVLM built natively for pt-PT, pairing a high-resolution vision encoder with dynamic image tiling and a fully open pt-PT-optimized language model via a learned connector. We contribute with a purposefully designed three-stage training process - vision-language alignment, general visual instruction tuning, and preference optimization - together with a pt-PT-centric multimodal data mix combining curated and translated public datasets with novel datasets that address the near-total absence of European Portuguese multimodal resources. Our evaluation shows that AMALIA-VL establishes a strong baseline for open-source pt-PT LVLMs.We will release model weights, training data, and construction pipelines along with machine-translated pt-PT evaluation benchmarks to help democratize pt-PT LVLM development.

06.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.

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

LentiAvatar: Pseudo-Multiview Reconstruction and Subpixel Prism Rendering for Real-Time Stereoscopic Communication

Real-time stereoscopic video communication has long been a goal of immersive telepresence, yet practical systems still require specialized capture rigs or reduce remote users to a single portrait view. We present LentiAvatar, a Gaussian head-avatar system that connects monocular avatar capture with subpixel-encoded glasses-free lenticular display for real-time autostereoscopic communication. From a monocular portrait video, LentiAvatar reconstructs a controllable head avatar and optimizes it for the lateral viewing zones induced by the display. The method uses natural head turns as pseudo-multiview (PMV) supervision to constrain regions that are otherwise weakly observed in monocular training, including hair, ears, jaw contours, and neck boundaries. Reliable side frames are yaw-binned, aligned to virtual cameras, and supervised within a strict head-and-hair domain; contour-aware losses and staged regularization further suppress ghosting, alpha leakage, and depth instability while preserving lateral detail. At runtime, LentiAvatar renders 32 virtual views and encodes them into a 4K lenticular raster with calibrated subpixel-routing masks. The live-tracker prototype sustains 10.65 FPS, and a subject-specific distilled driver raises the same display pipeline to 38.49 FPS.

08.
arXiv (math.PR) 2026-06-12

Voronoi Percolation: Topological Stability and Giant Cycles

arXiv:2601.00793v2 Announce Type: replace Abstract: We study the topological stability of Voronoi percolation in higher dimensions. We show that slightly increasing p allows a discretization that preserves increasing topological properties with high probability. This strengthens a theorem of Bollobás and Riordan and generalizes it to higher dimensions. As a consequence, we prove a sharp phase transition for the emergence of i-dimensional giant cycles in Voronoi percolation on the 2i-dimensional torus.

09.
arXiv (CS.AI) 2026-06-15

A Fixed-Point Neural Operator for Size- and Functional-Transferable Hamiltonian Prediction

arXiv:2606.14498v1 Announce Type: cross Abstract: Predicting the Kohn-Sham Hamiltonian with machine learning can accelerate density functional theory while retaining access to molecular orbitals, energy levels, and electronic-structure observables that energy-only surrogates cannot resolve. Yet element-wise agreement with the converged Hamiltonian, an implicit fixed point of the self-consistent field iteration, does not determine the occupied subspace that governs orbital energies and densities. Here we present HamEvo, a neural operator that learns the single-step self-consistent update and returns the converged Hamiltonian as its fixed point. HamEvo is pre-trained on intermediate self-consistent trajectories and calibrated at equilibrium with density-matrix supervision. Across benchmarks from MD17 to drug-like QMugs, HamEvo lowers Hamiltonian errors by 35-49% over direct-regression and deep-equilibrium baselines, and predicts QMugs HOMO and LUMO energies with mean absolute errors of 0.036 and 0.053 eV, near the 1 kcal/mol chemical-accuracy scale. Few-shot fine-tuning with only 20 reference conformations extends HamEvo to molecules of up to 122 atoms, well beyond the size range covered by pre-training. With thermal molecular-dynamics sampling, HamEvo captures temperature-dependent HOMO-LUMO gap renormalization beyond the harmonic approximation. Inference is up to 242 times faster than conventional DFT.

10.
arXiv (CS.CL) 2026-06-15

TA-RAG: Tone-Aware Retrieval-Augmented Generation for Peer-Support Health Communication

Retrieval-augmented generation (RAG) successfully grounds large language model (LLM) outputs in trusted documents, but factual grounding alone is insufficient for sensitive peer-support health communication. In domains such as HIV peer support, responses must also be accessible, stigma-free, empathetic, and tailored to the recipient. This paper presents TA-RAG, a lightweight, prompt-based tone-aware RAG framework that embeds explicit tone control into a RAG pipeline without requiring model fine-tuning. We operationalise tone across four core components: stigma-free rewriting, readability adjustment, recipient adaptation, and empathy rephrasing. We evaluate TA-RAG through component-level tests using questions derived from HIV Online Learning Australia (HOLA), UNAIDS terminology guidance, readability metrics, peer-support standards from National Association of People with HIV Australia (NAPWHA), and a public empathy dataset. Results show that the TA-RAG's components improve their targeted communication quality while preserving key content. These findings emphasise that prompt-based tone control is a potential direction for making RAG outputs suitable for sensitive peer-support health communication.

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

Probing Low Frame Rate Degradation in Neural Audio Codecs

arXiv:2606.16969v1 Announce Type: cross Abstract: Low frame rates in neural audio codecs are attractive for autoregressive speech synthesis, where the generation cost scales linearly with the sequence length. Recent work has demonstrated that codecs can operate at 12.5 Hz and below, but the mechanisms underlying low frame rate degradation remain insufficiently understood. We investigate these mechanisms through a controlled frame rate ablation. We reproduce a quality cliff at 6.25 Hz reported in previous works and evaluate candidate explanations: phonemic collisions and codebook saturation, neither of which shows evidence of a fundamental barrier. The cliff is instead caused by suboptimal training configuration: fixed clip duration during training yields too few tokens at low frame rates, starving the decoder of inter-token context. Once corrected, WER degrades smoothly with phonemic load down to 3.1 Hz and 1.6 Hz, suggesting the inference-time efficiency gains of low frame rate codecs are more accessible than previously assumed.

12.
arXiv (CS.AI) 2026-06-16

LabOSBench: Benchmarking Computer Use Agents for Scientific Instrument Control

arXiv:2606.16802v1 Announce Type: new Abstract: Current computer-use benchmarks primarily focus on software operation tasks in virtualized systems, whereas scientific instrumentation scenarios require coordinated control over complex interfaces, and feedback-driven parameter adjustment. However, directly evaluating agents on physical high-precision instruments is impractical due to high cost, safety risks, limited accessibility, and difficulty in ensuring reproducible evaluation. This motivates the need for a simulated yet realistic testbed that preserves the operational challenges of scientific instruments while enabling scalable and safe benchmarking. To this end, we introduce LabOSBench, a challenging benchmark for multimodal GUI agents built on a suite of web-based scientific-instrument simulators. Operating directly via a browser, LabOSBench avoids resource-heavy OS virtualization while supporting flexible task configuration and execution-based evaluation. Specifically, LabOSBench constructs 96 subtasks across eight instrument simulators, covering workflows from sample loading, alignment, parameter tuning, and data acquisition to result inspection. We evaluate general-purpose vision-language models, specialized GUI agent models, and advanced agentic frameworks at both subtask and end-to-end levels. Our experiments reveal that while existing agents can complete many structured GUI subtasks, they still struggle with feedback-driven operations and long-horizon workflow execution. Overall, LabOSBench provides a reproducible, low-cost testbed for advancing computer-using agents toward scientific-instrument control.

13.
arXiv (CS.CV) 2026-06-17

Phenotyping TPF via Self-Supervised Learning: A Label-Agnostic Framework with Expert Validation

The full potential of artificial intelligence in tibial plateau fracture characterisation remains unrealised, constrained by a fundamental dependency on labelled datasets whose consistency cannot be guaranteed: conventional classification schemes such as Schatzker and AO/OTA suffer from inter-observer variability, causing supervised models to learn human disagreement rather than stable fracture morphology. We design, implement, and validate a label-agnostic framework that eliminates this constraint by learning fracture representations directly from imaging data without observer-assigned labels. A RadImageNet-pretrained ResNet-50 encoder is fine-tuned on 154 cleaned knee radiographs using the SimCLR contrastive objective, preceded by a data cleaning protocol and followed by UMAP dimensionality reduction and k-means clustering to discover four imaging-derived phenotypes. Phenotype validity is assessed through a blinded expert review protocol administered to two independent clinicians. The four phenotypes demonstrate robust stability (bootstrap ARI = 0.319 +/- 0.041), strong internal cohesion (silhouette = 0.511), and coherence ratings of 3-5/5 from both reviewers under blinded conditions; one phenotype was unanimously identified as exhibiting comminution – a high-complexity feature isolated without any supervisory signal. Inter-partition comparison against Schatzker labels yields ARI = 0.013, confirming orthogonality to conventional classification boundaries. Notably, expert reviewers anchored to established classification vocabularies perceived imaging-derived groups as heterogeneous precisely where Schatzker alignment was lowest, suggesting that Schatzker-trained perception and label-agnostic embedding geometry measure orthogonal dimensions. These findings establish label-agnostic SSL phenotyping as a reproducible and clinically interpretable complement to conventional classification.

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

GRASP: Gradient-Aligned Sequential Parameter Transfer for Memory-Efficient Multi-Source Learning

arXiv:2606.14900v1 Announce Type: new Abstract: Multi-source transfer learning faces a fundamental scalability bottleneck: existing approaches require either loading all K source models into memory simultaneously during parameter fusion, requiring O(K) memory, or deploying all models at inference time, making production deployment infeasible. We propose GRASP (Gradient-Aligned Sequential Parameter Transfer), which achieves superior knowledge integration while maintaining O(1) memory consumption through three key innovations: (1) sequential processing that merges one source at a time into an evolving target model, (2) parameter-wise gradient alignment that selectively transfers only parameters whose optimization directions align with the target domain, avoiding negative transfer, and (3) iterative fine-tuning that adapts transferred knowledge before integrating the next source. Extensive experiments across three continual learning benchmarks (Yearbook, CLEAR-10, CLEAR-100) spanning 10 to 108-year temporal distribution shifts and four architectures (1.3M to 25.6M parameters) demonstrate that GRASP achieves 93.5% mean accuracy over all datasets and architectures compared to ensemble method's 71.7% accuracy while requiring only constant memory versus K models for standard multi-source fusion. Critically, GRASP's sequential previously merged models and scales to arbitrarily many sources without memory growth, making it uniquely suitable for resource-constrained deployment and continually evolving source domains.

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

HAMON: Passive Optical Sequence Mixing for Long-Horizon Forecasting

arXiv:2606.17028v1 Announce Type: cross Abstract: Simple linear and frequency-domain models remain surprisingly competitive in long-horizon time-series forecasting, and recent mechanistic evidence suggests that standard forecasting benchmarks may not require the dense superposed representations that make transformers powerful in other domains. This raises a substrate-level question: if the core forecasting operator is often low-complexity and approximately linear, does it need to be implemented as learned digital temporal mixing? We introduce HAMON, a passive diffractive optical forecasting core in which historical values are encoded onto an optical aperture, future positions are left dark, and cascaded trainable phase masks with free-space diffraction shape the forecast directly in the output field. At inference, prediction is performed by a single passive optical propagation pass with no trainable digital sequence-mixing layer. Across standard benchmarks, HAMON outperforms the strongest digital baselines considered on ETTm2 at all horizons and on ETTh2 at all but the longest horizon, improving MSE by up to 14\% and doing so consistently across horizons rather than at isolated points. It is competitive on Weather and trails the strongest baselines on the remaining ETT settings and on the high-channel-count Traffic and Electricity datasets. Phase encoding, intensity-compatible readout, and phase-scrambling ablations, together with a TorchOptics cross-simulator check, indicate that the forecasts arise from the data-bearing optical field rather than from a digital forecasting head. Because the passive core uses standard Fourier optics, HAMON defines a concrete target for optical hardware and for passive physical sequence mixing.

16.
arXiv (quant-ph) 2026-06-17

Impact of Network Constraints on Fault-Tolerant Distributed Quantum Computing

arXiv:2606.17495v1 Announce Type: new Abstract: As we move towards scalable and modular quantum computing, quantum data centres become imperative. Existing analyses typically treat network constraints in isolation or through simplified models, leaving the interplay between error correction operations and communication resources underexplored. In this work, we present an end-to-end simulation framework that jointly models surface-code operations, internal QPU connectivity, and realistic network constraints including finite entanglement generation rates, limited communication qubits, and bandwidth contention, producing execution latency, from which logical error rate estimates are obtained. The framework is modular by design, allowing individual components such as routing heuristics, scheduling policies, and network topologies to be independently replaced. Numerical evaluation reveals distinct operating regimes in which the optimal resource allocation and code distance selection shift depending on the network characteristics. These results point to tradeoffs in the design of distributed quantum computing architectures that are not visible when computation and communication are modeled separately.

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

MassSpecGym in the Wild: Uncovering and Correcting Evaluation Pitfalls in AI-Driven Molecule Discovery

arXiv:2606.19624v1 Announce Type: new Abstract: Reliable benchmarking is critical for developing machine learning models for tandem mass spectrometry (MS/MS) based molecule discovery. Subtle issues in experimental design and model evaluation procedures can degrade the trustworthiness of such benchmarks and lead to erroneous conclusions. We conduct a thorough review of model evaluation issues in the recent MS/MS machine learning literature, using the standard MassSpecGym benchmark suite as a case study to illustrate the impact of these issues. We find evaluation issues in at least 17 of 26 papers reporting MassSpecGym benchmark results in the first year of its adoption. We isolate three classes of failures: (i) data leakage, (ii) shortcut learning, and (iii) implementation bugs and metric divergence. Through extensive experimentation and code replication, we quantify the impact of these issues and show how they corrupt the evaluation standards MassSpecGym was designed to enforce. We distill our findings into recommendations generalizable to MS/MS challenges, benchmarks, and custom evaluation setups. We also release MassSpecGym v1.5, an implementation of our recommendations in the MassSpecGym benchmarking suite which addresses the failure modes identified in this audit. MassSpecGym v1.5 is publicly available at https://github.com/pluskal-lab/MassSpecGym.

18.
arXiv (quant-ph) 2026-06-16

Nonlinear cascaded quantum network with giant emitters

arXiv:2404.09829v2 Announce Type: replace Abstract: Chiral quantum optics is central to developing scalable quantum networks, yet existing approaches rely predominantly on linear single-photon regimes. It remains unclear how to generate directional multiphotons. Here we show that giant emitters coupled to nonlinear quantum optical baths enable tunable directional correlated photons, revealing a mechanism for multiphoton directional emission. We demonstrate that the propagation phases of correlated photons, together with the coupling phases of giant emitters, can generate destructive interference in one direction while enhancing emission in the opposite direction, making directionality fully tunable. Building on this mechanism, we introduce a nonlinear cascaded quantum network paradigm mediated by correlated flying qubits, providing a configurable building block enabling distinct many-body applications beyond linear unidirectional setups. These results reveal a rich landscape for engineering multiphoton propagation and correlations through interference in giant emitter-nonlinear bath architectures, offering pathways for quantum networks and strongly correlated light-matter platforms.

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

HypOProto: Hyperbolic Ordinal Prototypes for Left Ventricular Filling Pressure Classification

Echocardiography (echo) is a widely used imaging modality for assessing cardiac function, with Left Ventricular Filling Pressure (LVFP) serving as a critical physiological marker for conditions such as heart failure. Standard LVFP classification into normal vs elevated categories relies on the Doppler-derived $E/e'$ ratio, which is operator-dependent and often unavailable in resource-limited settings, motivating methods that infer LVFP directly from B-mode echo. Existing deep learning approaches achieve high performance but remain largely black-box, limiting clinical interpretability. We propose HypOProto, a hyperbolic, ordinal prototype-based framework for interpretable LVFP classification using a frozen, explainable foundation model backbone. HypOProto arranges prototypes along the physiological $E/e'$ scale, placing borderline cases near the hyperboloid root where small angular differences separate similar cases, while normal and elevated cases occupy outward positions reflecting increasing diagnostic certainty. This hyperbolic geometry encodes clinically meaningful ordinal relationships and improves interpretability. We also introduce a novel Hyperbolic Prototype Angular Separation (HyperPAS) loss, enforcing inter-class prototype separation in hyperbolic space. HypOProto achieves SOTA performance while maintaining transparency, and highlights clinically relevant regions in visualizations. This work represents the first prototype-based framework for LVFP classification in echo. Our code can be found at https://github.com/DeepRCL/HypOProto.

21.
arXiv (CS.AI) 2026-06-11

MLaGA: Multimodal Large Language and Graph Assistant

arXiv:2506.02568v2 Announce Type: replace Abstract: Large Language Models (LLMs) have demonstrated substantial efficacy in advancing graph-structured data analysis. Prevailing LLM-based graph methods excel in adapting LLMs to text-rich graphs, wherein node attributes are text descriptions. However, their applications to multimodal graphs–where nodes are associated with diverse attribute types, such as texts and images–remain underexplored, despite their ubiquity in real-world scenarios. To bridge the gap, we introduce the Multimodal Large Language and Graph Assistant (MLaGA), an innovative model that adeptly extends LLM capabilities to facilitate reasoning over complex graph structures and multimodal attributes. We first design a structure-aware multimodal encoder to align textual and visual attributes within a unified space through a joint graph pre-training objective. Subsequently, we implement a multimodal instruction-tuning approach to seamlessly integrate multimodal features and graph structures into the LLM through lightweight projectors. Extensive experiments across multiple datasets demonstrate the effectiveness of MLaGA compared to leading baseline methods, achieving superior performance in diverse graph learning tasks under both supervised and transfer learning scenarios.

22.
arXiv (quant-ph) 2026-06-17

Quantum Information Processing: A brief overview on Quantum Teleportation

作者:

arXiv:1604.00852v3 Announce Type: replace Abstract: Quantum Information Processing (QIP) exploits the principles of quantum mechanics to perform information storage, communication, and computation in ways that are fundamentally impossible within classical frameworks. This article presents a pedagogical overview of the mathematical foundations of quantum information theory, including qubits, Hilbert spaces, linear operators, quantum measurements, tensor products, density operators, and quantum entanglement. Building upon these concepts, we provide a detailed introduction to quantum teleportation, one of the most remarkable protocols in quantum communication. The discussion covers the no cloning theorem, the original teleportation protocol by Bennett et al., experimental realisations of quantum teleportation, and extensions involving probabilistic and multiqubit teleportation schemes. Particular emphasis is placed on the role of entanglement as a communication resource, together with the study of teleportation channels based on bipartite and multipartite quantum states. Various quantitative measures of entanglement, including concurrence, negativity, entanglement of formation, and relative entropy of entanglement, are reviewed alongside teleportation fidelity as a performance metric. Furthermore, the interplay between Bell nonlocality, mixed state entanglement, and teleportation efficiency is examined, followed by a survey of advanced developments such as controlled teleportation, bidirectional teleportation, cluster state teleportation, and recent advances in the Quantum 2.0 era. This review aims to provide students, researchers, and engineers with a coherent introduction to the theoretical foundations and practical significance of quantum teleportation in emerging quantum technologies.

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

Finite Resources False Discovery Rate Control in Structured Hypothesis Spaces

arXiv:2606.15393v1 Announce Type: cross Abstract: Scientific discovery relies on large-scale hypothesis testing. However, the capacity to identify true discoveries while controlling false discovery faces major challenges: obtaining relevant reference data (the null distribution) is resource-intensive, leaving finite-data uncertainty, and the procedure should account for the inherent structure in the hypothesis space, when such structure exists. Here, we present a framework for controlling the false discovery rate both when each hypothesis is evidenced only by a finite count of null draws, leaving its p-value uncertain, and when the hypothesis space carries arbitrary structure, requiring only that the structure be represented through a suitable reproducing kernel. We present two decision rules that are both robust to structural mis-specification, yet offer a distinct trade-off between exact FDR control and statistical power. The first rule guarantees exact FDR control; the second maximizes power by adapting mirror-statistic control into count space, utilizing an analytical framework to assess FDR control when exact mirror symmetry is relaxed. Furthermore, the tractability gained by the RKHS framework allows us to directly investigate finite-data uncertainties, which we leverage to suggest a policy for the efficient allocation of null distribution samples.

25.
medRxiv (Medicine) 2026-06-15

Investigation of Intra-Fraction Stability and Inter-Fraction Reproducibility of Deep Inspiration Breath-Hold Across Two Hypofractionated Radiotherapy Regimens in the HYPORT Adjuvant Study.

Background: Deep Inspiration Breath Hold (DIBH) is a widely used respiratory motion management technique for minimizing cardiac dose in left-sided breast radiotherapy. In the Breast HYPORT Adjuvant study, DIBH was employed for cardiac sparing in patients without nodal irradiation using a standardized institutional protocol with the Varian Real-time Position Management (RPM) system. Both moderate-hypofractionation (control arm - 40Gy in 15 fractions) and one-week hypofractionation (experimental arm - 26 Gy in 5 fractions) regimens were delivered using this protocol. This study aimed to evaluate the robustness of DIBH by analyzing intra-fraction stability and inter-fraction reproducibility of breath-hold amplitude across the two treatment regimens. Methods: Respiratory waveforms acquired during each treatment session were analyzed to determine the median breath-hold amplitude and its standard deviation during beam delivery. Intra-fraction stability was assessed from vari- ations within individual treatment sessions, while inter-fraction reproducibility was evaluated relative to the simula- tion waveform amplitude across all treatment sessions. These parameters were compared between the two HYPORT regimens to examine breath-hold consistency during treatment delivery. Moreover, an additional comparison was made between the one-week hypofractionation regimen and the first five fractions of the moderate-hypofractionation regimen to evaluate the effect of treatment duration . Lung volumes from free-breathing and DIBH CT scans were analyzed to assess the effectiveness of patient breath-hold training. Results: Both arms demonstrated an average 1.7-fold increase of air volume in lung during the breath-hold position, confirming the effective implementation of DIBH during treatment planning and delivery. Structured training resulted in increased breath-hold amplitudes, with gains of 22.87% and 24.16% with respect to the first trial session in the experimental and control arms, respectively. Both regimens receive equivalent doses for approximately the same air volume in lung . Despite the different prescription doses in the two arms (26 Gy vs. 40 Gy), the experimental arm achieved an equivalent mean heart dose of 2.91% (75.6 cGy) compared with 2.95% (118.51 cGy) in the control arm, suggesting a similar cardiac preservation protocol adopted during treatment planning. Intra-fraction stability was similar between the control arm and the experimental arm, with median amplitude variations of 1.006 mm (95% CI: [0.998-1.015]) and 1.079 mm (95% CI: [1.067-1.097]), respectively. In contrast, inter-fraction reproducibility improved in the experimental arm, with lower deviation from simulation amplitude (0.44 {+/-} 0.24 mm vs. 0.66 {+/-} 0.25 mm) for the entire treatment schedule. The stability and reproducibility of experimental arm were further compared with the first five fractions of the control arm. The results were similar to those of the experimental arm. Conclusion: In this study, we compared two treatment regimens in terms of intra-fraction stability and inter-fraction reproducibility during DIBH radiotherapy. Both regimens demonstrated comparable intra-fraction stability, indicating effective motion management irrespective of treatment duration. However, the experimental arm showed better inter- fraction reproducibility, suggesting more consistent breath-hold performance throughout the treatment course. Based on stability and reproducibility, a reasonable narrowing of the DIBH gating window may be implemented with minor changes to the institutional protocol. The observed trend highlights the potential for improved consistency with the experimental approach and supports further investigation to better understand the underlying factors and strengthen these findings in future studies.