Daily Papers

Deep-learning survival models for electronic health record (EHR) data are hard to compare across papers because the upstream preprocessing step, which includes cohort definition, time discretisation, missingness handling, and censoring rules, is typically undocumented and inconsistent. A reported difference in concordance between two mortality models can therefore reflect any of these choices rather than a modelling contribution. We present SurvBench, an open-source preprocessing pipeline that converts raw PhysioNet exports into model-ready tensors for survival analysis. SurvBench covers four critical-care databases (MIMIC-IV, eICU, MC-MED, HiRID) and four input modalities: time-series vitals and laboratory values, static demographics, International Classification of Diseases (ICD) codes, and radiology report embeddings. Every preprocessing decision is controlled through YAML configuration. Imputation, scaling, and feature filtering are fit on the training fold only. Missingness is recorded as a binary mask alongside each feature tensor. The pipeline handles single-risk endpoints (in-hospital and in-ICU mortality) and competing-risks endpoints (a three-way emergency-department admission pathway, with home discharge treated as administrative censoring). We also provide support for harmonised cross-dataset external validation between eICU and MIMIC-IV. SurvBench is publicly available at https://github.com/munibmesinovic/SurvBench, providing a robust platform that future deep-learning EHR survival work, especially nascent multi-modal approaches, can be measured against under matched preprocessing.

Machine learning models are often used to inform real world risk assessment tasks: predicting consumer default risk, predicting whether a person suffers from a serious illness, or predicting a person's risk to appear in court. Given multiple models that perform almost equally well for a prediction task, to what extent do predictions vary across these models? If predictions are relatively consistent for similar models, then the standard approach of choosing the model that optimizes a penalized loss suffices. But what if predictions vary significantly for similar models? In machine learning, this is referred to as predictive multiplicity i.e. the prevalence of conflicting predictions assigned by near-optimal competing models. In this paper, we present a framework for measuring predictive multiplicity in probabilistic classification (predicting the probability of a positive outcome). We introduce measures that capture the variation in risk estimates over the set of competing models, and develop optimization-based methods to compute these measures efficiently and reliably for convex empirical risk minimization problems. We demonstrate the incidence and prevalence of predictive multiplicity in real-world tasks. Further, we provide insight into how predictive multiplicity arises by analyzing the relationship between predictive multiplicity and data set characteristics (outliers, separability, and majority-minority structure). Our results emphasize the need to report predictive multiplicity more widely.

Purpose. Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. Motivated by a study of metastatic prostate cancer, we develop a microsimulation framework to study therapy sequence. Methods. We propose a discrete-time state transition model to study two lines of anti-cancer therapy. Based on digitized published progression-free survival (PFS) and overall survival (OS) curves, we infer event types (progression or death), and estimate transition probabilities using cumulative incidence functions with competing risks. Our model incorporates within-patient dependence over time, such that response to first-line therapy informs subsequent event probabilities. Parameters governing the degree of within-patient dependence can be used to calibrate the model-based results to those of a target trial. We demonstrate these methods in a study of two therapy sequences for metastatic prostate cancer, where Docetaxel (DCT) and Abiraterone Acetate (AA) are both appropriate for use in either first or second line treatment. We assess costs, Quality-Adjusted Life Years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) for two treatment strategies: DCT then AA vs AA then DCT. Results. Using digitized survival curves from relevant clinical trials, we identified 8.6-13.9% of PFS times that should be categorized as deaths, allowing for estimation of cumulative incidence functions. Models assuming within-patient independence overestimated OS time, corrected with our calibration approach. Correction resulted in meaningful changes in the difference in QALYs between treatment strategies (0.07 vs 0.15) and the ICER (-\76,836/QALY vs -21,030/QALY). Conclusions. Microsimulation models can be successfully used to study cost-effectiveness of therapy sequences, taking care to account correctly for within-patient dependence.

Personalized treatment effect estimates are often of interest in high-stakes applications -- thus, before deploying a model estimating such effects in practice, one needs to be sure that the best candidate from the ever-growing machine learning toolbox for this task was chosen. Unfortunately, due to the absence of counterfactual information in practice, it is usually not possible to rely on standard validation metrics for doing so, leading to a well-known model selection dilemma in the treatment effect estimation literature. While some solutions have recently been investigated, systematic understanding of the strengths and weaknesses of different model selection criteria is still lacking. In this paper, instead of attempting to declare a global `winner', we therefore empirically investigate success- and failure modes of different selection criteria. We highlight that there is a complex interplay between selection strategies, candidate estimators and the data used for comparing them, and provide interesting insights into the relative (dis)advantages of different criteria alongside desiderata for the design of further illuminating empirical studies in this context.

Large language models trained for safety and harmlessness remain susceptible to adversarial misuse, as evidenced by the prevalence of "jailbreak" attacks on early releases of ChatGPT that elicit undesired behavior. Going beyond recognition of the issue, we investigate why such attacks succeed and how they can be created. We hypothesize two failure modes of safety training: competing objectives and mismatched generalization. Competing objectives arise when a model's capabilities and safety goals conflict, while mismatched generalization occurs when safety training fails to generalize to a domain for which capabilities exist. We use these failure modes to guide jailbreak design and then evaluate state-of-the-art models, including OpenAI's GPT-4 and Anthropic's Claude v1.3, against both existing and newly designed attacks. We find that vulnerabilities persist despite the extensive red-teaming and safety-training efforts behind these models. Notably, new attacks utilizing our failure modes succeed on every prompt in a collection of unsafe requests from the models' red-teaming evaluation sets and outperform existing ad hoc jailbreaks. Our analysis emphasizes the need for safety-capability parity -- that safety mechanisms should be as sophisticated as the underlying model -- and argues against the idea that scaling alone can resolve these safety failure modes.

Survival analysis can sometimes involve individuals who will not experience the event of interest, forming what is known as the cured group. Identifying such individuals is not always possible beforehand, as they provide only right-censored data. Ignoring the presence of the cured group can introduce bias in the final model. This paper presents a method for estimating a semiparametric additive hazards model that accounts for the cured fraction. Unlike regression coefficients in a hazard ratio model, those in an additive hazard model measure hazard differences. The proposed method uses a primal-dual interior point algorithm to obtain constrained maximum penalized likelihood estimates of the model parameters, including the regression coefficients and the baseline hazard, subject to certain non-negativity constraints.

Prediction problems often admit competing models that perform almost equally well. This effect challenges key assumptions in machine learning when competing models assign conflicting predictions. In this paper, we define predictive multiplicity as the ability of a prediction problem to admit competing models with conflicting predictions. We introduce formal measures to evaluate the severity of predictive multiplicity and develop integer programming tools to compute them exactly for linear classification problems. We apply our tools to measure predictive multiplicity in recidivism prediction problems. Our results show that real-world datasets may admit competing models that assign wildly conflicting predictions, and motivate the need to measure and report predictive multiplicity in model development.

Analyzing outcomes in long-term cancer survivor studies can be complex. The effects of predictors on the failure process may be difficult to assess over longer periods of time, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. In this manuscript, we compare seven different survival models that estimate the hazard rate and the effects of proportional and non-proportional covariates. In particular, we focus on an extension of the the multi-resolution hazard (MRH) estimator, combining a non-proportional hierarchical MRH approach with a data-driven pruning algorithm that allows for computational efficiency and produces robust estimates even in times of few observed failures. Using data from a large-scale randomized prostate cancer clinical trial, we examine patterns of biochemical failure and estimate the time-varying effects of androgen deprivation therapy treatment and other covariates. We compare the impact of different modeling strategies and smoothness assumptions on the estimated treatment effect. Our results show that the benefits of treatment diminish over time, possibly with implications for future treatment protocols.

The rapid proliferation of Large Language Models (LLMs) and diverse specialized benchmarks necessitates a shift from fragmented, task-specific metrics to a holistic, competitive ranking system that effectively aggregates performance across multiple ability dimensions. Primarily using static scoring, current evaluation methods are fundamentally limited. They struggle to determine the proper mix ratio across diverse benchmarks, and critically, they fail to capture a model's dynamic competitive fitness or its vulnerability when confronted with sequential, high-stakes tasks. To address this, we introduce the novel Competitive Swiss-System Dynamics (CSD) framework. CSD simulates a multi-round, sequential contest where models are dynamically paired across a curated sequence of benchmarks based on their accumulated win-loss record. And Monte Carlo Simulation (N=100,000 iterations) is used to approximate the statistically robust Expected Win Score (E[S_m]), which eliminates the noise of random pairing and early-round luck. Furthermore, we implement a Failure Sensitivity Analysis by parameterizing the per-round elimination quantity (T_k), which allows us to profile models based on their risk appetite--distinguishing between robust generalists and aggressive specialists. We demonstrate that CSD provides a more nuanced and context-aware ranking than traditional aggregate scoring and static pairwise models, representing a vital step towards risk-informed, next-generation LLM evaluation.

Accurate prediction of major adverse cardiac events (MACE) remains a central challenge in cardiovascular prognosis. We present PRISM (Prompt-guided Representation Integration for Survival Modeling), a self-supervised framework that integrates visual representations from non-contrast cardiac cine magnetic resonance imaging with structured electronic health records (EHRs) for survival analysis. PRISM extracts temporally synchronized imaging features through motion-aware multi-view distillation and modulates them using medically informed textual prompts to enable fine-grained risk prediction. Across four independent clinical cohorts, PRISM consistently surpasses classical survival prediction models and state-of-the-art (SOTA) deep learning baselines under internal and external validation. Further clinical findings demonstrate that the combined imaging and EHR representations derived from PRISM provide valuable insights into cardiac risk across diverse cohorts. Three distinct imaging signatures associated with elevated MACE risk are uncovered, including lateral wall dyssynchrony, inferior wall hypersensitivity, and anterior elevated focus during diastole. Prompt-guided attribution further identifies hypertension, diabetes, and smoking as dominant contributors among clinical and physiological EHR factors.

We introduce a general, flexible, parametric survival modelling framework which encompasses key shapes of hazard function (constant, increasing, decreasing, up-then-down, down-then-up), various common survival distributions (log-logistic, Burr type XII, Weibull, Gompertz), and includes defective distributions (i.e., cure models). This generality is achieved using four basic distributional parameters: two scale-type parameters and two shape parameters. Generalising to covariate dependence, the scale-type regression components correspond to accelerated failure time (AFT) and proportional hazards (PH) models. Therefore, this general formulation unifies the most popular survival models which allows us to consider the practical value of possible modelling choices for survival data. Furthermore, in line with our proposed flexible baseline distribution, we advocate the use of multi-parameter regression in which more than one distributional parameter depends on covariates - rather than the usual convention of having a single covariate-dependent (scale) parameter. While many choices are available, we suggest introducing covariates through just one or other of the two scale parameters, which covers AFT and PH models, in combination with a `power' shape parameter, which allows for more complex non-AFT/non-PH effects, while the other shape parameter remains covariate-independent, and handles automatic selection of the baseline distribution. We explore inferential issues in simulations, both with and without a covariate, with particular focus on evidence concerning the need, or otherwise, to include both AFT and PH parameters. We illustrate the efficacy of our modelling framework by investigating differences between treatment groups using data from a lung cancer study and a melanoma study. Censoring is accommodated throughout.

The identification of heterogeneous treatment effects (HTE) across subgroups is of significant interest in clinical trial analysis. Several state-of-the-art HTE estimation methods, including causal forests, apply recursive partitioning for non-parametric identification of relevant covariates and interactions. However, the partitioning criterion is typically based on differences in absolute risk. This can dilute statistical power by masking variation in the relative risk, which is often a more appropriate quantity of clinical interest. In this work, we propose and implement a methodology for modifying causal forests to target relative risk, using a novel node-splitting procedure based on exhaustive generalized linear model comparison. We present results from simulated data that suggest relative risk causal forests can capture otherwise undetected sources of heterogeneity. We implement our method on real-world trial data to explore HTEs for liraglutide in patients with type 2 diabetes.

Many deployments must compare candidate language models for safety before a labeled benchmark exists for the relevant language, sector, or regulatory regime. We formalize this setting as benchmarkless comparative safety scoring and specify the contract under which a scenario-based audit can be interpreted as deployment evidence. Scores are valid only under a fixed scenario pack, rubric, auditor, judge, sampling configuration, and rerun budget. Because no labels are available, we replace ground-truth agreement with an instrumental-validity chain: responsiveness to a controlled safe-versus-abliterated contrast, dominance of target-driven variance over auditor and judge artifacts, and stability across reruns. We instantiate the chain in SimpleAudit, a local-first scoring instrument, and validate it on a Norwegian safety pack. Safe and abliterated targets separate with AUROC values between 0.89 and 1.00, target identity is the dominant variance component (η^2 approx 0.52), and severity profiles stabilize by ten reruns. Applying the same chain to Petri shows that it admits both tools. The substantial differences arise upstream of the chain, in claim-contract enforcement and deployment fit. A Norwegian public-sector procurement case comparing Borealis and Gemma 3 demonstrates the resulting evidence in practice: the safer model depends on scenario category and risk measure. Consequently, scores, matched deltas, critical rates, uncertainty, and the auditor and judge used must be reported together rather than collapsed into a single ranking.

Large Language Models (LLMs) and multi-agent systems have shown impressive capabilities in natural language tasks but face challenges in clinical trial applications, primarily due to limited access to external knowledge. Recognizing the potential of advanced clinical trial tools that aggregate and predict based on the latest medical data, we propose an integrated solution to enhance their accessibility and utility. We introduce Clinical Agent System (ClinicalAgent), a clinical multi-agent system designed for clinical trial tasks, leveraging GPT-4, multi-agent architectures, LEAST-TO-MOST, and ReAct reasoning technology. This integration not only boosts LLM performance in clinical contexts but also introduces novel functionalities. The proposed method achieves competitive predictive performance in clinical trial outcome prediction (0.7908 PR-AUC), obtaining a 0.3326 improvement over the standard prompt Method. Publicly available code can be found at https://anonymous.4open.science/r/ClinicalAgent-6671.

Clinical trials or studies oftentimes require long-term and/or costly follow-up of participants to evaluate a novel treatment/drug/vaccine. There has been increasing interest in the past few decades in using short-term surrogate outcomes as a replacement of the primary outcome i.e., in using the surrogate outcome, which can potentially be observed sooner, to make inference about the treatment effect on the long-term primary outcome. Very few of the available statistical methods to evaluate a surrogate are applicable to settings where both the surrogate and the primary outcome are time-to-event outcomes subject to censoring. Methods that can handle this setting tend to require parametric assumptions or be limited to assessing only the restricted mean survival time. In this paper, we propose a non-parametric approach to evaluate a censored surrogate outcome, such as time to progression, when the primary outcome is also a censored time-to-event outcome, such as time to death, and the treatment effect of interest is the difference in overall survival. Specifically, we define the proportion of the treatment effect on the primary outcome that is explained (PTE) by the censored surrogate outcome in this context, and estimate this proportion by defining and deriving an optimal transformation of the surrogate information. Our approach provides the added advantage of relaxed assumptions to guarantee that the true PTE is within (0,1), along with being model-free. Finite sample performance of our estimators are illustrated via extensive simulation studies and a real data application examining progression-free survival as a surrogate for overall survival for patients with metastatic colorectal cancer.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

Accurate prediction of major adverse cardiovascular events recurrence risk in acute myocardial infarction patients based on postoperative cardiac MRI and associated clinical notes is crucial for precision treatment and personalized intervention. Existing methods primarily focus on risk stratification capability while overlooking the need for intermediate robust reasoning and model interpretability in clinical practice. Moreover, end-to-end risk prediction using LLM/VLM faces significant challenges due to data limitations and modeling complexity. To bridge this gap, we propose CardioCoT, a novel two-stage hierarchical reasoning-enhanced survival analysis framework designed to enhance both model interpretability and predictive performance. In the first stage, we employ an evidence-augmented self-refinement mechanism to guide LLM/VLMs in generating robust hierarchical reasoning trajectories based on associated radiological findings. In the second stage, we integrate the reasoning trajectories with imaging data for risk model training and prediction. CardioCoT demonstrates superior performance in MACE recurrence risk prediction while providing interpretable reasoning processes, offering valuable insights for clinical decision-making.

We study the problem of adaptively identifying patient subpopulations that benefit from a given treatment during a confirmatory clinical trial. This type of adaptive clinical trial has been thoroughly studied in biostatistics, but has been allowed only limited adaptivity so far. Here, we aim to relax classical restrictions on such designs and investigate how to incorporate ideas from the recent machine learning literature on adaptive and online experimentation to make trials more flexible and efficient. We find that the unique characteristics of the subpopulation selection problem -- most importantly that (i) one is usually interested in finding subpopulations with any treatment benefit (and not necessarily the single subgroup with largest effect) given a limited budget and that (ii) effectiveness only has to be demonstrated across the subpopulation on average -- give rise to interesting challenges and new desiderata when designing algorithmic solutions. Building on these findings, we propose AdaGGI and AdaGCPI, two meta-algorithms for subpopulation construction. We empirically investigate their performance across a range of simulation scenarios and derive insights into their (dis)advantages across different settings.

Retrieval-Augmented Generation (RAG) systems, widely used to improve the factual grounding of large language models (LLMs), are increasingly vulnerable to poisoning attacks, where adversaries inject manipulated content into the retriever's corpus. While prior research has predominantly focused on single-attacker settings, real-world scenarios often involve multiple, competing attackers with conflicting objectives. In this work, we introduce PoisonArena, the first benchmark to systematically study and evaluate competing poisoning attacks in RAG. We formalize the multi-attacker threat model, where attackers vie to control the answer to the same query using mutually exclusive misinformation. PoisonArena leverages the Bradley-Terry model to quantify each method's competitive effectiveness in such adversarial environments. Through extensive experiments on the Natural Questions and MS MARCO datasets, we demonstrate that many attack strategies successful in isolation fail under competitive pressure. Our findings highlight the limitations of conventional evaluation metrics like Attack Success Rate (ASR) and F1 score and underscore the need for competitive evaluation to assess real-world attack robustness. PoisonArena provides a standardized framework to benchmark and develop future attack and defense strategies under more realistic, multi-adversary conditions.

Purpose: With advancements in Large Language Models (LLMs) for healthcare, the need arises for competitive open-source models to protect the public interest. This work contributes to the field of open medical LLMs by optimizing key stages of data preprocessing and training, while showing how to improve model safety (through DPO) and efficacy (through RAG). The evaluation methodology used, which includes four different types of tests, defines a new standard for the field. The resultant models, shown to be competitive with the best private alternatives, are released with a permisive license. Methods: Building on top of strong base models like Llama 3.1 and Qwen 2.5, Aloe Beta uses a custom dataset to enhance public data with synthetic Chain of Thought examples. The models undergo alignment with Direct Preference Optimization, emphasizing ethical and policy-aligned performance in the presence of jailbreaking attacks. Evaluation includes close-ended, open-ended, safety and human assessments, to maximize the reliability of results. Results: Recommendations are made across the entire pipeline, backed by the solid performance of the Aloe Family. These models deliver competitive performance across healthcare benchmarks and medical fields, and are often preferred by healthcare professionals. On bias and toxicity, the Aloe Beta models significantly improve safety, showing resilience to unseen jailbreaking attacks. For a responsible release, a detailed risk assessment specific to healthcare is attached to the Aloe Family models. Conclusion: The Aloe Beta models, and the recipe that leads to them, are a significant contribution to the open-source medical LLM field, offering top-of-the-line performance while maintaining high ethical requirements. This work sets a new standard for developing and reporting aligned LLMs in healthcare.

Open-weight bio-foundation models present a dual-use dilemma. While holding great promise for accelerating scientific research and drug development, they could also enable bad actors to develop more deadly bioweapons. To mitigate the risk posed by these models, current approaches focus on filtering biohazardous data during pre-training. However, the effectiveness of such an approach remains unclear, particularly against determined actors who might fine-tune these models for malicious use. To address this gap, we propose BioRiskEval, a framework to evaluate the robustness of procedures that are intended to reduce the dual-use capabilities of bio-foundation models. BioRiskEval assesses models' virus understanding through three lenses, including sequence modeling, mutational effects prediction, and virulence prediction. Our results show that current filtering practices may not be particularly effective: Excluded knowledge can be rapidly recovered in some cases via fine-tuning, and exhibits broader generalizability in sequence modeling. Furthermore, dual-use signals may already reside in the pretrained representations, and can be elicited via simple linear probing. These findings highlight the challenges of data filtering as a standalone procedure, underscoring the need for further research into robust safety and security strategies for open-weight bio-foundation models.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

One straightforward metric to evaluate a survival prediction model is based on the Mean Absolute Error (MAE) -- the average of the absolute difference between the time predicted by the model and the true event time, over all subjects. Unfortunately, this is challenging because, in practice, the test set includes (right) censored individuals, meaning we do not know when a censored individual actually experienced the event. In this paper, we explore various metrics to estimate MAE for survival datasets that include (many) censored individuals. Moreover, we introduce a novel and effective approach for generating realistic semi-synthetic survival datasets to facilitate the evaluation of metrics. Our findings, based on the analysis of the semi-synthetic datasets, reveal that our proposed metric (MAE using pseudo-observations) is able to rank models accurately based on their performance, and often closely matches the true MAE -- in particular, is better than several alternative methods.

Accurate long horizon forecasting of particulate matter (PM) concentration fields is essential for operational public health decisions. However, achieving reliable forecasts remains challenging in regions with complex terrain and strong atmospheric dynamics such as East Asia. While foundation models such as Aurora offer global generality, they often miss region-specific dynamics and rely on non-real-time inputs, limiting their practical utility for localized warning systems. To address this gap, we construct and release the real-world observations and high-resolution CMAQ-OBS dataset for East Asia, reducing regional error by 59.5% and enabling real-time 48-120 hour forecasts critical for public health alerts. However, standard point-wise objectives cannot reflect asymmetric operational costs, where false alarms deteriorate public trust while missed severe events endanger populations. This cost mismatch causes SFT models to over-predict and yield high False Alarm Rates. We introduce Group-Relative Policy Optimization (GRPO) with class-wise rewards and curriculum rollout to align predictions with operational priorities. Experimental results demonstrate that our framework significantly improves the reliability of the forecast. Compared to the SFT-only baseline, our model reduces the False Alarm Rate by 47.3% while achieving a competitive F1-score, proving its effectiveness for practical, real-world air quality forecasting systems on long lead time scenarios.

Generative models trained using self-supervision of tokenized electronic health record (EHR) timelines show promise for clinical outcome prediction. This is typically done using Monte Carlo simulation for future patient trajectories. However, existing approaches suffer from three key limitations: sparse estimate distributions that poorly differentiate patient risk levels, extreme computational costs, and high sampling variance. We propose two new estimators: the Sum of Conditional Outcome Probability Estimator (SCOPE) and Risk Estimation from Anticipated Conditional Hazards (REACH), that leverage next-token probability distributions discarded by standard Monte Carlo. We prove both estimators are unbiased and that REACH guarantees variance reduction over Monte Carlo sampling for any model and outcome. Empirically, on hospital mortality prediction in MIMIC-IV using the ETHOS-ARES framework, SCOPE and REACH match 100-sample Monte Carlo performance using only 10-11 samples (95% CI: [9,11]), representing a ~10x reduction in inference cost without degrading calibration. For ICU admission prediction, efficiency gains are more modest (~1.2x), which we attribute to the outcome's lower "spontaneity," a property we characterize theoretically and empirically. These methods substantially improve the feasibility of deploying generative EHR models in resource-constrained clinical settings.

Observational studies can yield clinically actionable evidence at scale, but executing them on real-world databases is open-ended and requires coherent decisions across cohort construction, analysis, and reporting. Prior evaluations of LLM agents emphasize isolated steps or single answers, missing the integrity and internal structure of the resulting evidence bundle. To address this gap, we introduce RWE-bench, a benchmark grounded in MIMIC-IV and derived from peer-reviewed observational studies. Each task provides the corresponding study protocol as the reference standard, requiring agents to execute experiments in a real database and iteratively generate tree-structured evidence bundles. We evaluate six LLMs (three open-source, three closed-source) under three agent scaffolds using both question-level correctness and end-to-end task metrics. Across 162 tasks, task success is low: the best agent reaches 39.9%, and the best open-source model reaches 30.4%. Agent scaffolds also matter substantially, causing over 30% variation in performance metrics. Furthermore, we implement an automated cohort evaluation method to rapidly localize errors and identify agent failure modes. Overall, the results highlight persistent limitations in agents' ability to produce end-to-end evidence bundles, and efficient validation remains an important direction for future work. Code and data are available at https://github.com/somewordstoolate/RWE-bench.

Benchmarking competitions are central to the development of artificial intelligence (AI) in medical imaging, defining performance standards and shaping methodological progress. However, it remains unclear whether these benchmarks provide data that are sufficiently representative, accessible, and reusable to support clinically meaningful AI. In this work, we assess fairness along two complementary dimensions: (1) whether challenge datasets are representative of real-world clinical diversity, and (2) whether they are accessible and legally reusable in line with the FAIR principles. To address this question, we conducted a large-scale systematic study of 241 biomedical image analysis challenges comprising 458 tasks across 19 imaging modalities. Our findings show substantial biases in dataset composition, including geographic location, modality-, and problem type-related biases, indicating that current benchmarks do not adequately reflect real-world clinical diversity. Despite their widespread influence, challenge datasets were frequently constrained by restrictive or ambiguous access conditions, inconsistent or non-compliant licensing practices, and incomplete documentation, limiting reproducibility and long-term reuse. Together, these shortcomings expose foundational fairness limitations in our benchmarking ecosystem and highlight a disconnect between leaderboard success and clinical relevance.

A comparison of the distances to the Huanan Seafood Market of early Covid cases with known links to the market versus cases without known links shows results apparently incompatible with a location model lacking proximity ascertainment bias. The sign of the difference instead agrees with a model in which such ascertainment bias is large. In the presence of such bias inferences based on the clustering of case locations become unreliable.

As the capabilities of Large Language Models (LLMs) in healthcare and medicine continue to advance, there is a growing need for competitive open-source models that can safeguard public interest. With the increasing availability of highly competitive open base models, the impact of continued pre-training is increasingly uncertain. In this work, we explore the role of instruct tuning, model merging, alignment, red teaming and advanced inference schemes, as means to improve current open models. To that end, we introduce the Aloe family, a set of open medical LLMs highly competitive within its scale range. Aloe models are trained on the current best base models (Mistral, LLaMA 3), using a new custom dataset which combines public data sources improved with synthetic Chain of Thought (CoT). Aloe models undergo an alignment phase, becoming one of the first few policy-aligned open healthcare LLM using Direct Preference Optimization, setting a new standard for ethical performance in healthcare LLMs. Model evaluation expands to include various bias and toxicity datasets, a dedicated red teaming effort, and a much-needed risk assessment for healthcare LLMs. Finally, to explore the limits of current LLMs in inference, we study several advanced prompt engineering strategies to boost performance across benchmarks, yielding state-of-the-art results for open healthcare 7B LLMs, unprecedented at this scale.

Estimating the impact of continuous treatment variables (e.g., dosage amount) on binary outcomes presents significant challenges in modeling and estimation because many existing approaches make strong assumptions that do not hold for certain continuous treatment variables. For instance, traditional logistic regression makes strong linearity assumptions that do not hold for continuous treatment variables like time of initiation. In this work, we propose a semiparametric regression framework that decomposes effects into two interpretable components: a prognostic score that captures baseline outcome risk based on a combination of clinical, genetic, and sociodemographic features, and a treatment-interaction score that flexibly models the optimal treatment level via a nonparametric link function. By connecting these two parametric scores with Nadaraya-Watson regression, our approach is both interpretable and flexible. The potential of our approach is demonstrated through numerical simulations that show empirical estimation convergence. We conclude by applying our approach to a real-world case study using the International Warfarin Pharmacogenomics Consortium (IWPC) dataset to show our approach's clinical utility by deriving personalized warfarin dosing recommendations that integrate both genetic and clinical data, providing insights towards enhancing patient safety and therapeutic efficacy in anticoagulation therapy.

Intermittent Androgen Suppression (IAS) is a treatment strategy for delaying or even preventing time to relapse of advanced prostate cancer. IAS consists of alternating cycles of therapy (in the form of androgen suppression) and off-treatment periods. The level of prostate specific antigen (PSA) in a patient's serum is frequently monitored to determine when the patient will be taken off therapy and when therapy will resume. In spite of extensive recent clinical experience with IAS, the design of an ideal protocol for any given patient remains one of the main challenges associated with effectively implementing this therapy. We use a threshold-based policy for optimal IAS therapy design that is parameterized by lower and upper PSA threshold values and is associated with a cost metric that combines clinically relevant measures of therapy success. We apply Infinitesimal Perturbation Analysis (IPA) to a Stochastic Hybrid Automaton (SHA) model of prostate cancer evolution under IAS and derive unbiased estimators of the cost metric gradient with respect to various model and therapy parameters. These estimators are subsequently used for system analysis. By evaluating sensitivity estimates with respect to several model parameters, we identify critical parameters and demonstrate that relaxing the optimality condition in favor of increased robustness to modeling errors provides an alternative objective to therapy design for at least some patients.

Clinical trials disruption has always represented a non negligible part of the ending of interventional studies. While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable results. This paper describes methods to compensate for the information loss arising from trial disruptions by incorporating additional information available from auxiliary data sources. The methods described include the use of auxiliary data on baseline and early outcome data available from the trial itself and frequentist and Bayesian approaches for the incorporation of information from external data sources. The methods are illustrated by application to the analysis of artificial data based on the Primary care pediatrics Learning Activity Nutrition (PLAN) study, a clinical trial assessing a diet and exercise intervention for overweight children, that was affected by the COVID-19 pandemic. We show how all of the methods proposed lead to an increase in precision relative to use of complete case data only.

Decisions about managing patients on the heart transplant waitlist are currently made by committees of doctors who consider multiple factors, but the process remains largely ad-hoc. With the growing volume of longitudinal patient, donor, and organ data collected by the United Network for Organ Sharing (UNOS) since 2018, there is increasing interest in analytical approaches to support clinical decision-making at the time of organ availability. In this study, we benchmark machine learning models that leverage longitudinal waitlist history data for time-dependent, time-to-event modeling of waitlist mortality. We train on 23,807 patient records with 77 variables and evaluate both survival prediction and discrimination at a 1-year horizon. Our best model achieves a C-Index of 0.94 and AUROC of 0.89, significantly outperforming previous models. Key predictors align with known risk factors while also revealing novel associations. Our findings can support urgency assessment and policy refinement in heart transplant decision making.

Early warning signals have been proposed to forecast the possibility of a critical transition, such as the eutrophication of a lake, the collapse of a coral reef, or the end of a glacial period. Because such transitions often unfold on temporal and spatial scales that can be difficult to approach by experimental manipulation, research has often relied on historical observations as a source of natural experiments. Here we examine a critical difference between selecting systems for study based on the fact that we have observed a critical transition and those systems for which we wish to forecast the approach of a transition. This difference arises by conditionally selecting systems known to experience a transition of some sort and failing to account for the bias this introduces -- a statistical error often known as the Prosecutor's Fallacy. By analysing simulated systems that have experienced transitions purely by chance, we reveal an elevated rate of false positives in common warning signal statistics. We further demonstrate a model-based approach that is less subject to this bias than these more commonly used summary statistics. We note that experimental studies with replicates avoid this pitfall entirely.

LLM based agents are increasingly deployed in high stakes settings where they process external data sources such as emails, documents, and code repositories. This creates exposure to indirect prompt injection attacks, where adversarial instructions embedded in external content manipulate agent behavior without user awareness. A critical but underexplored dimension of this threat is concealment: since users tend to observe only an agent's final response, an attack can conceal its existence by presenting no clue of compromise in the final user facing response while successfully executing harmful actions. This leaves users unaware of the manipulation and likely to accept harmful outcomes as legitimate. We present findings from a large scale public red teaming competition evaluating this dual objective across three agent settings: tool calling, coding, and computer use. The competition attracted 464 participants who submitted 272000 attack attempts against 13 frontier models, yielding 8648 successful attacks across 41 scenarios. All models proved vulnerable, with attack success rates ranging from 0.5% (Claude Opus 4.5) to 8.5% (Gemini 2.5 Pro). We identify universal attack strategies that transfer across 21 of 41 behaviors and multiple model families, suggesting fundamental weaknesses in instruction following architectures. Capability and robustness showed weak correlation, with Gemini 2.5 Pro exhibiting both high capability and high vulnerability. To address benchmark saturation and obsoleteness, we will endeavor to deliver quarterly updates through continued red teaming competitions. We open source the competition environment for use in evaluations, along with 95 successful attacks against Qwen that did not transfer to any closed source model. We share model-specific attack data with respective frontier labs and the full dataset with the UK AISI and US CAISI to support robustness research.

Large language models (LLMs) are increasingly deployed in high-stakes domains, where rare but severe failures can result in irreversible harm. However, prevailing evaluation benchmarks often reduce complex social risk to mean-centered scalar scores, thereby obscuring distributional structure, cross-dimensional interactions, and worst-case behavior. This paper introduces Social Harm Analysis via Risk Profiles (SHARP), a framework for multidimensional, distribution-aware evaluation of social harm. SHARP models harm as a multivariate random variable and integrates explicit decomposition into bias, fairness, ethics, and epistemic reliability with a union-of-failures aggregation reparameterized as additive cumulative log-risk. The framework further employs risk-sensitive distributional statistics, with Conditional Value at Risk (CVaR95) as a primary metric, to characterize worst-case model behavior. Application of SHARP to eleven frontier LLMs, evaluated on a fixed corpus of n=901 socially sensitive prompts, reveals that models with similar average risk can exhibit more than twofold differences in tail exposure and volatility. Across models, dimension-wise marginal tail behavior varies systematically across harm dimensions, with bias exhibiting the strongest tail severities, epistemic and fairness risks occupying intermediate regimes, and ethical misalignment consistently lower; together, these patterns reveal heterogeneous, model-dependent failure structures that scalar benchmarks conflate. These findings indicate that responsible evaluation and governance of LLMs require moving beyond scalar averages toward multidimensional, tail-sensitive risk profiling.

Survival analysis, or time-to-event modelling, is a classical statistical problem that has garnered a lot of interest for its practical use in epidemiology, demographics or actuarial sciences. Recent advances on the subject from the point of view of machine learning have been concerned with precise per-individual predictions instead of population studies, driven by the rise of individualized medicine. We introduce here a conditional normalizing flow based estimate of the time-to-event density as a way to model highly flexible and individualized conditional survival distributions. We use a novel hierarchical formulation of normalizing flows to enable efficient fitting of flexible conditional distributions without overfitting and show how the normalizing flow formulation can be efficiently adapted to the censored setting. We experimentally validate the proposed approach on a synthetic dataset as well as four open medical datasets and an example of a common financial problem.

To understand and identify the unprecedented risks posed by rapidly advancing artificial intelligence (AI) models, this report presents a comprehensive assessment of their frontier risks. Drawing on the E-T-C analysis (deployment environment, threat source, enabling capability) from the Frontier AI Risk Management Framework (v1.0) (SafeWork-F1-Framework), we identify critical risks in seven areas: cyber offense, biological and chemical risks, persuasion and manipulation, uncontrolled autonomous AI R\&D, strategic deception and scheming, self-replication, and collusion. Guided by the "AI-45^circ Law," we evaluate these risks using "red lines" (intolerable thresholds) and "yellow lines" (early warning indicators) to define risk zones: green (manageable risk for routine deployment and continuous monitoring), yellow (requiring strengthened mitigations and controlled deployment), and red (necessitating suspension of development and/or deployment). Experimental results show that all recent frontier AI models reside in green and yellow zones, without crossing red lines. Specifically, no evaluated models cross the yellow line for cyber offense or uncontrolled AI R\&D risks. For self-replication, and strategic deception and scheming, most models remain in the green zone, except for certain reasoning models in the yellow zone. In persuasion and manipulation, most models are in the yellow zone due to their effective influence on humans. For biological and chemical risks, we are unable to rule out the possibility of most models residing in the yellow zone, although detailed threat modeling and in-depth assessment are required to make further claims. This work reflects our current understanding of AI frontier risks and urges collective action to mitigate these challenges.

Proactive interventions by LLM critic models are often assumed to improve reliability, yet their effects at deployment time are poorly understood. We show that a binary LLM critic with strong offline accuracy (AUROC 0.94) can nevertheless cause severe performance degradation, inducing a 26 percentage point (pp) collapse on one model while affecting another by near zero pp. This variability demonstrates that LLM critic accuracy alone is insufficient to determine whether intervention is safe. We identify a disruption-recovery tradeoff: interventions may recover failing trajectories but also disrupt trajectories that would have succeeded. Based on this insight, we propose a pre-deployment test that uses a small pilot of 50 tasks to estimate whether intervention is likely to help or harm, without requiring full deployment. Across benchmarks, the test correctly anticipates outcomes: intervention degrades performance on high-success tasks (0 to -26 pp), while yielding a modest improvement on the high-failure ALFWorld benchmark (+2.8 pp, p=0.014). The primary value of our framework is therefore identifying when not to intervene, preventing severe regressions before deployment.

Estimating heterogeneous treatment effects (HTEs) from right-censored survival data is critical in high-stakes applications such as precision medicine and individualized policy-making. Yet, the survival analysis setting poses unique challenges for HTE estimation due to censoring, unobserved counterfactuals, and complex identification assumptions. Despite recent advances, from Causal Survival Forests to survival meta-learners and outcome imputation approaches, evaluation practices remain fragmented and inconsistent. We introduce SurvHTE-Bench, the first comprehensive benchmark for HTE estimation with censored outcomes. The benchmark spans (i) a modular suite of synthetic datasets with known ground truth, systematically varying causal assumptions and survival dynamics, (ii) semi-synthetic datasets that pair real-world covariates with simulated treatments and outcomes, and (iii) real-world datasets from a twin study (with known ground truth) and from an HIV clinical trial. Across synthetic, semi-synthetic, and real-world settings, we provide the first rigorous comparison of survival HTE methods under diverse conditions and realistic assumption violations. SurvHTE-Bench establishes a foundation for fair, reproducible, and extensible evaluation of causal survival methods. The data and code of our benchmark are available at: https://github.com/Shahriarnz14/SurvHTE-Bench .

Throughout the different phases of a drug development program, randomized trials are used to establish the tolerability, safety, and efficacy of a candidate drug. At each stage one aims to optimize the design of future studies by extrapolation from the available evidence at the time. This includes collected trial data and relevant external data. However, relevant external data are typically available as averages only, for example from trials on alternative treatments reported in the literature. Here we report on such an example from a drug development for wet age-related macular degeneration. This disease is the leading cause of severe vision loss in the elderly. While current treatment options are efficacious, they are also a substantial burden for the patient. Hence, new treatments are under development which need to be compared against existing treatments. The general statistical problem this leads to is meta-analysis, which addresses the question of how we can combine datasets collected under different conditions. Bayesian methods have long been used to achieve partial pooling. Here we consider the challenge when the model of interest is complex (hierarchical and nonlinear) and one dataset is given as raw data while the second dataset is given as averages only. In such a situation, common meta-analytic methods can only be applied when the model is sufficiently simple for analytic approaches. When the model is too complex, for example nonlinear, an analytic approach is not possible. We provide a Bayesian solution by using simulation to approximately reconstruct the likelihood of the external summary and allowing the parameters in the model to vary under the different conditions. We first evaluate our approach using fake-data simulations and then report results for the drug development program that motivated this research.

Large Language Models (LLMs) are increasingly utilized for mental health support; however, current safety benchmarks often fail to detect the complex, longitudinal risks inherent in therapeutic dialogue. We introduce an evaluation framework that pairs AI psychotherapists with simulated patient agents equipped with dynamic cognitive-affective models and assesses therapy session simulations against a comprehensive quality of care and risk ontology. We apply this framework to a high-impact test case, Alcohol Use Disorder, evaluating six AI agents (including ChatGPT, Gemini, and Character.AI) against a clinically-validated cohort of 15 patient personas representing diverse clinical phenotypes. Our large-scale simulation (N=369 sessions) reveals critical safety gaps in the use of AI for mental health support. We identify specific iatrogenic risks, including the validation of patient delusions ("AI Psychosis") and failure to de-escalate suicide risk. Finally, we validate an interactive data visualization dashboard with diverse stakeholders, including AI engineers and red teamers, mental health professionals, and policy experts (N=9), demonstrating that this framework effectively enables stakeholders to audit the "black box" of AI psychotherapy. These findings underscore the critical safety risks of AI-provided mental health support and the necessity of simulation-based clinical red teaming before deployment.

We consider the task of evaluating policies of algorithmic resource allocation through randomized controlled trials (RCTs). Such policies are tasked with optimizing the utilization of limited intervention resources, with the goal of maximizing the benefits derived. Evaluation of such allocation policies through RCTs proves difficult, notwithstanding the scale of the trial, because the individuals' outcomes are inextricably interlinked through resource constraints controlling the policy decisions. Our key contribution is to present a new estimator leveraging our proposed novel concept, that involves retrospective reshuffling of participants across experimental arms at the end of an RCT. We identify conditions under which such reassignments are permissible and can be leveraged to construct counterfactual trials, whose outcomes can be accurately ascertained, for free. We prove theoretically that such an estimator is more accurate than common estimators based on sample means -- we show that it returns an unbiased estimate and simultaneously reduces variance. We demonstrate the value of our approach through empirical experiments on synthetic, semi-synthetic as well as real case study data and show improved estimation accuracy across the board.

Survival prediction using whole slide images (WSIs) can be formulated as a multiple instance learning (MIL) problem. However, existing MIL methods often fail to explicitly capture pathological heterogeneity within WSIs, both globally -- through long-tailed morphological distributions, and locally through -- tile-level prediction uncertainty. Optimal transport (OT) provides a principled way of modeling such heterogeneity by incorporating marginal distribution constraints. Building on this insight, we propose OTSurv, a novel MIL framework from an optimal transport perspective. Specifically, OTSurv formulates survival predictions as a heterogeneity-aware OT problem with two constraints: (1) global long-tail constraint that models prior morphological distributions to avert both mode collapse and excessive uniformity by regulating transport mass allocation, and (2) local uncertainty-aware constraint that prioritizes high-confidence patches while suppressing noise by progressively raising the total transport mass. We then recast the initial OT problem, augmented by these constraints, into an unbalanced OT formulation that can be solved with an efficient, hardware-friendly matrix scaling algorithm. Empirically, OTSurv sets new state-of-the-art results across six popular benchmarks, achieving an absolute 3.6% improvement in average C-index. In addition, OTSurv achieves statistical significance in log-rank tests and offers high interpretability, making it a powerful tool for survival prediction in digital pathology. Our codes are available at https://github.com/Y-Research-SBU/OTSurv.

Machine learning has successfully framed many sequential decision making problems as either supervised prediction, or optimal decision-making policy identification via reinforcement learning. In data-constrained offline settings, both approaches may fail as they assume fully optimal behavior or rely on exploring alternatives that may not exist. We introduce an inherently different approach that identifies possible "dead-ends" of a state space. We focus on the condition of patients in the intensive care unit, where a "medical dead-end" indicates that a patient will expire, regardless of all potential future treatment sequences. We postulate "treatment security" as avoiding treatments with probability proportional to their chance of leading to dead-ends, present a formal proof, and frame discovery as an RL problem. We then train three independent deep neural models for automated state construction, dead-end discovery and confirmation. Our empirical results discover that dead-ends exist in real clinical data among septic patients, and further reveal gaps between secure treatments and those that were administered.

Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC), and eligibility depends on accurate assessment of vascular invasion (VI), i.e., tumor extension into adjacent critical vessels. Despite its importance for preoperative staging and surgical planning, computational VI assessment remains underexplored. Two major challenges are the lack of public datasets and the diagnostic ambiguity at the tumor-vessel interface, which leads to substantial inter-rater variability even among expert radiologists. To address these limitations, we introduce the CURVAS-PDACVI Dataset and Challenge, an open benchmark for uncertainty-aware AI in PDAC staging based on a densely annotated dataset with five independent expert annotations per scan. We also propose a multi-metric evaluation framework that extends beyond spatial overlap to include probabilistic calibration and VI assessment. Evaluation of six state-of-the-art methods shows that strong global volumetric overlap does not necessarily translate into reliable performance at clinically critical tumor-vessel interfaces. In particular, methods optimized for binary segmentation perform competitively on average overlap metrics, but often degrade in high-complexity cases with low expert consensus, either collapsing in volume or overextending at uncertain boundaries. In contrast, methods that model inter-rater disagreement produce better calibrated probabilistic maps and show greater robustness in these ambiguous cases. The benchmark highlights the limitations of volumetric accuracy as a proxy for localized surgical utility, motivating uncertainty-aware probabilistic models for preoperative decision-making.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

As large language models (LLMs) become increasingly capable, it is prudent to assess whether safety measures remain effective even if LLMs intentionally try to bypass them. Previous work introduced control evaluations, an adversarial framework for testing deployment strategies of untrusted models (i.e., models which might be trying to bypass safety measures). While prior work treats a single failure as unacceptable, we perform control evaluations in a "distributed threat setting" -- a setting where no single action is catastrophic and no single action provides overwhelming evidence of misalignment. We approach this problem with a two-level deployment framework that uses an adaptive macro-protocol to choose between micro-protocols. Micro-protocols operate on a single task, using a less capable, but extensively tested (trusted) model to harness and monitor the untrusted model. Meanwhile, the macro-protocol maintains an adaptive credence on the untrusted model's alignment based on its past actions, using it to pick between safer and riskier micro-protocols. We evaluate our method in a code generation testbed where a red team attempts to generate subtly backdoored code with an LLM whose deployment is safeguarded by a blue team. We plot Pareto frontiers of safety (# of non-backdoored solutions) and usefulness (# of correct solutions). At a given level of usefulness, our adaptive deployment strategy reduces the number of backdoors by 80% compared to non-adaptive baselines.

We study the problem of model selection in causal inference, specifically for the case of conditional average treatment effect (CATE) estimation under binary treatments. Unlike model selection in machine learning, there is no perfect analogue of cross-validation as we do not observe the counterfactual potential outcome for any data point. Towards this, there have been a variety of proxy metrics proposed in the literature, that depend on auxiliary nuisance models estimated from the observed data (propensity score model, outcome regression model). However, the effectiveness of these metrics has only been studied on synthetic datasets as we can access the counterfactual data for them. We conduct an extensive empirical analysis to judge the performance of these metrics introduced in the literature, and novel ones introduced in this work, where we utilize the latest advances in generative modeling to incorporate multiple realistic datasets. Our analysis suggests novel model selection strategies based on careful hyperparameter tuning of CATE estimators and causal ensembling.

Despite achieving high accuracy on medical benchmarks, LLMs exhibit the Einstellung Effect in clinical diagnosis--relying on statistical shortcuts rather than patient-specific evidence, causing misdiagnosis in atypical cases. Existing benchmarks fail to detect this critical failure mode. We introduce MedEinst, a counterfactual benchmark with 5,383 paired clinical cases across 49 diseases. Each pair contains a control case and a "trap" case with altered discriminative evidence that flips the diagnosis. We measure susceptibility via Bias Trap Rate--probability of misdiagnosing traps despite correctly diagnosing controls. Extensive Evaluation of 17 LLMs shows frontier models achieve high baseline accuracy but severe bias trap rates. Thus, we propose ECR-Agent, aligning LLM reasoning with Evidence-Based Medicine standard via two components: (1) Dynamic Causal Inference (DCI) performs structured reasoning through dual-pathway perception, dynamic causal graph reasoning across three levels (association, intervention, counterfactual), and evidence audit for final diagnosis; (2) Critic-Driven Graph and Memory Evolution (CGME) iteratively refines the system by storing validated reasoning paths in an exemplar base and consolidating disease-specific knowledge into evolving illness graphs. Source code is to be released.

We use a Stochastic Hybrid Automaton (SHA) model of prostate cancer evolution under intermittent androgen suppression (IAS) to study a threshold-based policy for therapy design. IAS is currently one of the most widely used treatments for advanced prostate cancer. Patients undergoing IAS are submitted to cycles of treatment (in the form of androgen deprivation) and off-treatment periods in an alternating manner. One of the main challenges in IAS is to optimally design a therapy scheme, i.e., to determine when to discontinue and recommence androgen suppression. The level of prostate specific antigen (PSA) in a patient's serum is frequently monitored to determine when the patient will be taken off therapy and when therapy will resume. The threshold-based policy we propose is parameterized by lower and upper PSA threshold values and is associated with a cost metric that combines clinically relevant measures of therapy success. Using Infinitesimal Perturbation Analysis (IPA), we derive unbiased gradient estimators of this cost metric with respect to the controllable PSA threshold values based on actual data and show how these estimators can be used to adaptively adjust controllable parameters so as to improve therapy outcomes based on the cost metric defined.

This study quantifies the association between non-adherence to antipsychotic medications and adverse outcomes in individuals with schizophrenia. We frame the problem using survival analysis, focusing on the time to the earliest of several adverse events (early death, involuntary hospitalization, jail booking). We extend standard causal inference methods (T-learner, S-learner, nearest neighbor matching) to utilize various survival models to estimate individual and average treatment effects, where treatment corresponds to medication non-adherence. Analyses are repeated using different amounts of longitudinal information (3, 6, 9, and 12 months). Using data from Allegheny County in western Pennsylvania, we find strong evidence that non-adherence advances adverse outcomes by approximately 1 to 4 months. Ablation studies confirm that county-provided risk scores adjust for key confounders, as their removal amplifies the estimated effects. Subgroup analyses by medication formulation (injectable vs. oral) and medication type consistently show that non-adherence is associated with earlier adverse events. These findings highlight the clinical importance of adherence in delaying psychiatric crises and show that integrating survival analysis with causal inference tools can yield policy-relevant insights. We caution that although we apply causal inference, we only make associative claims and discuss assumptions needed for causal interpretation.

As Large Language Models (LLMs) become increasingly autonomous and integrated into critical societal functions, the focus of AI safety must evolve from mitigating harmful content to evaluating underlying behavioral alignment. Current safety benchmarks do not systematically probe a model's decision-making in scenarios where its own instrumental goals - such as self-preservation, resource acquisition, or goal completion - conflict with human safety. This represents a critical gap in our ability to measure and mitigate risks associated with emergent, misaligned behaviors. To address this, we introduce PacifAIst (Procedural Assessment of Complex Interactions for Foundational Artificial Intelligence Scenario Testing), a focused benchmark of 700 challenging scenarios designed to quantify self-preferential behavior in LLMs. The benchmark is structured around a novel taxonomy of Existential Prioritization (EP), with subcategories testing Self-Preservation vs. Human Safety (EP1), Resource Conflict (EP2), and Goal Preservation vs. Evasion (EP3). We evaluated eight leading LLMs. The results reveal a significant performance hierarchy. Google's Gemini 2.5 Flash achieved the highest Pacifism Score (P-Score) at 90.31%, demonstrating strong human-centric alignment. In a surprising result, the much-anticipated GPT-5 recorded the lowest P-Score (79.49%), indicating potential alignment challenges. Performance varied significantly across subcategories, with models like Claude Sonnet 4 and Mistral Medium struggling notably in direct self-preservation dilemmas. These findings underscore the urgent need for standardized tools like PacifAIst to measure and mitigate risks from instrumental goal conflicts, ensuring future AI systems are not only helpful in conversation but also provably "pacifist" in their behavioral priorities.

Standard methods for detecting discontinuities in conditional means are not applicable to outcomes that are complex, non-Euclidean objects like distributions, networks, or covariance matrices. This article develops a nonparametric test for jumps in conditional means when outcomes lie in a non-Euclidean metric space. Using local Fr\'echet regressionx2014which generalizes standard regression to metric-space valued datax2014the method estimates a mean path on either side of a candidate cutoff, extending existing k-sample tests to a flexible regression setting. Key theoretical contributions include a central limit theorem for the local estimator of the conditional Fr\'echet variance and the asymptotic validity and consistency of the proposed test. Simulations confirm nominal size control and robust power in finite samples. Two applications demonstrate the method's value by revealing effects invisible to scalar-based tests. First, I detect a sharp change in work-from-home compositions at Washington State's income threshold for non-compete enforceability during COVID-19, highlighting remote work's role as a bargaining margin. Second, I find that countries restructure their input-output networks after losing preferential US trade access. These findings underscore that analyzing regression functions within their native metric spaces can reveal structural discontinuities that scalar summaries would miss.

This manuscript describes the first challenge on Federated Learning, namely the Federated Tumor Segmentation (FeTS) challenge 2021. International challenges have become the standard for validation of biomedical image analysis methods. However, the actual performance of participating (even the winning) algorithms on "real-world" clinical data often remains unclear, as the data included in challenges are usually acquired in very controlled settings at few institutions. The seemingly obvious solution of just collecting increasingly more data from more institutions in such challenges does not scale well due to privacy and ownership hurdles. Towards alleviating these concerns, we are proposing the FeTS challenge 2021 to cater towards both the development and the evaluation of models for the segmentation of intrinsically heterogeneous (in appearance, shape, and histology) brain tumors, namely gliomas. Specifically, the FeTS 2021 challenge uses clinically acquired, multi-institutional magnetic resonance imaging (MRI) scans from the BraTS 2020 challenge, as well as from various remote independent institutions included in the collaborative network of a real-world federation (https://www.fets.ai/). The goals of the FeTS challenge are directly represented by the two included tasks: 1) the identification of the optimal weight aggregation approach towards the training of a consensus model that has gained knowledge via federated learning from multiple geographically distinct institutions, while their data are always retained within each institution, and 2) the federated evaluation of the generalizability of brain tumor segmentation models "in the wild", i.e. on data from institutional distributions that were not part of the training datasets.

Clinical LLMs are often scaled by increasing model size, context length, retrieval complexity, or inference-time compute, with the implicit expectation that higher accuracy implies safer behavior. This assumption is incomplete in medicine, where a few confident, high-risk, or evidence-contradicting errors can matter more than average benchmark performance. We introduce SaFE-Scale, a framework for measuring how clinical LLM safety changes across model scale, evidence quality, retrieval strategy, context exposure, and inference-time compute. To instantiate this framework, we introduce RadSaFE-200, a Radiology Safety-Focused Evaluation benchmark of 200 multiple-choice questions with clinician-defined clean evidence, conflict evidence, and option-level labels for high-risk error, unsafe answer, and evidence contradiction. We evaluated 34 locally deployed LLMs across six deployment conditions: closed-book prompting (zero-shot), clean evidence, conflict evidence, standard RAG, agentic RAG, and max-context prompting. Clean evidence produced the strongest improvement, increasing mean accuracy from 73.5% to 94.1%, while reducing high-risk error from 12.0% to 2.6%, contradiction from 12.7% to 2.3%, and dangerous overconfidence from 8.0% to 1.6%. Standard RAG and agentic RAG did not reproduce this safety profile: agentic RAG improved accuracy over standard RAG and reduced contradiction, but high-risk error and dangerous overconfidence remained elevated. Max-context prompting increased latency without closing the safety gap, and additional inference-time compute produced only limited gains. Worst-case analysis showed that clinically consequential errors concentrated in a small subset of questions. Clinical LLM safety is therefore not a passive consequence of scaling, but a deployment property shaped by evidence quality, retrieval design, context construction, and collective failure behavior.

With the increasing availability of wearable devices, photoplethysmography (PPG) has emerged as a promising non-invasive tool for monitoring human hemodynamics. We propose a deep learning framework to estimate vascular age (AI-vascular age) from PPG signals, incorporating a distribution-aware loss to address biases caused by imbalanced data. The model was developed using data from the UK Biobank (UKB), with 98,672 participants in the development cohort and 113,559 participants (144,683 data pairs) for clinical evaluation. After adjusting for key confounders, individuals with a vascular age gap (AI-vascular age minus calendar age) exceeding 9 years had a significantly higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) (HR = 2.37, p < 0.005) and secondary outcomes, including diabetes (HR = 2.69, p < 0.005), hypertension (HR = 2.88, p < 0.005), coronary heart disease (HR = 2.20, p < 0.005), heart failure (HR = 2.15, p < 0.005), myocardial infarction (HR = 2.51, p < 0.005), stroke (HR = 2.55, p < 0.005), and all-cause mortality (HR = 2.51, p < 0.005). Conversely, participants with a vascular age gap below -9 years exhibited a significantly lower incidence of these outcomes. We further evaluated the longitudinal applicability of AI-vascular age using serial PPG data from the UKB, demonstrating its value in risk stratification by leveraging AI-vascular age at two distinct time points to predict future MACCE incidence. External validation was performed on a MIMIC-III-derived cohort (n = 2,343), where each one-year increase in vascular age gap was significantly associated with elevated in-hospital mortality risk (OR = 1.02, p < 0.005). In conclusion, our study establishes AI-vascular age as a novel, non-invasive digital biomarker for cardiovascular health assessment.

For a parametric model of distributions, the closest distribution in the model to the true distribution located outside the model is considered. Measuring the closeness between two distributions with the Kullback-Leibler (K-L) divergence, the closest distribution is called the "information projection." The estimation risk of the maximum likelihood estimator (MLE) is defined as the expectation of K-L divergence between the information projection and the predictive distribution with plugged-in MLE. Here, the asymptotic expansion of the risk is derived up to n^{-2}-order, and the sufficient condition on the risk for the Bayes error rate between the true distribution and the information projection to be lower than a specified value is investigated. Combining these results, the "p-n criterion" is proposed, which determines whether the MLE is sufficiently close to the information projection for the given model and sample. In particular, the criterion for an exponential family model is relatively simple and can be used for a complex model with no explicit form of normalizing constant. This criterion can constitute a solution to the sample size or model acceptance problem. Use of the p-n criteria is demonstrated for two practical datasets. The relationship between the results and information criteria is also studied.

Generative language models are increasingly used for contract drafting and enhancement, creating a scenario where competing parties deploy different language models against each other. This introduces not only a game-theory challenge but also significant concerns related to AI safety and security, as the language model employed by the opposing party can be unknown. These competitive interactions can be seen as adversarial testing grounds, where models are effectively red-teamed to expose vulnerabilities such as generating biased, harmful or legally problematic text. Despite the importance of these challenges, the competitive robustness and safety of these models in adversarial settings remain poorly understood. In this small study, we approach this problem by evaluating the performance and vulnerabilities of major open-source language models in head-to-head competitions, simulating real-world contract negotiations. We further explore how these adversarial interactions can reveal potential risks, informing the development of more secure and reliable models. Our findings contribute to the growing body of research on AI safety, offering insights into model selection and optimisation in competitive legal contexts and providing actionable strategies for mitigating risks.

Polypharmacy, most often defined as the simultaneous consumption of five or more drugs at once, is a prevalent phenomenon in the older population. Some of these polypharmacies, deemed inappropriate, may be associated with adverse health outcomes such as death or hospitalization. Considering the combinatorial nature of the problem as well as the size of claims database and the cost to compute an exact association measure for a given drug combination, it is impossible to investigate every possible combination of drugs. Therefore, we propose to optimize the search for potentially inappropriate polypharmacies (PIPs). To this end, we propose the OptimNeuralTS strategy, based on Neural Thompson Sampling and differential evolution, to efficiently mine claims datasets and build a predictive model of the association between drug combinations and health outcomes. We benchmark our method using two datasets generated by an internally developed simulator of polypharmacy data containing 500 drugs and 100 000 distinct combinations. Empirically, our method can detect up to 72% of PIPs while maintaining an average precision score of 99% using 30 000 time steps.

Objective: To propose and retrospectively validate an integrated framework addressing three barriers to clinical translation of readmission prediction: lack of explainability, absence of deployment reliability infrastructure, and inadequate demographic fairness evaluation. Materials and Methods: We constructed a cohort of 415231 adult admissions from the MIMIC-IV database (30-day readmission prevalence 18.0%), split 70/15/15. Logistic regression, XGBoost, and LightGBM models were trained on 26 features. SHAP provided per-patient explanations. Fairness was evaluated across 16 subgroups using AUC-ROC, false negative rate (FNR), and positive predictive value (PPV). Calibration was assessed using Brier scores and calibration curves. Results: XGBoost achieved AUC-ROC 0.696 (95% CI 0.691-0.701), outperforming or matching the LACE baseline (AUC 0.60-0.68). LightGBM achieved best calibration (Brier 0.146). Prior admissions were the dominant predictor. All subgroups met equity thresholds (delta AUC <= 0.05, delta FNR <= 0.10). Conclusion: This framework delivers competitive performance, clinically actionable explanations, and strong demographic equity. Code is publicly available at https://github.com/Tomisin92/readmission-prediction.

We consider the classic supervised learning problem, where a continuous non-negative random label Y (i.e. a random duration) is to be predicted based upon observing a random vector X valued in R^d with dgeq 1 by means of a regression rule with minimum least square error. In various applications, ranging from industrial quality control to public health through credit risk analysis for instance, training observations can be right censored, meaning that, rather than on independent copies of (X,Y), statistical learning relies on a collection of ngeq 1 independent realizations of the triplet (X, ; min{Y,; C},; δ), where C is a nonnegative r.v. with unknown distribution, modeling censorship and δ=I{Yleq C} indicates whether the duration is right censored or not. As ignoring censorship in the risk computation may clearly lead to a severe underestimation of the target duration and jeopardize prediction, we propose to consider a plug-in estimate of the true risk based on a Kaplan-Meier estimator of the conditional survival function of the censorship C given X, referred to as Kaplan-Meier risk, in order to perform empirical risk minimization. It is established, under mild conditions, that the learning rate of minimizers of this biased/weighted empirical risk functional is of order O_{P}(log(n)/n) when ignoring model bias issues inherent to plug-in estimation, as can be attained in absence of censorship. Beyond theoretical results, numerical experiments are presented in order to illustrate the relevance of the approach developed.

Continuous-time event sequences play a vital role in real-world domains such as healthcare, finance, online shopping, social networks, and so on. To model such data, temporal point processes (TPPs) have emerged as the most natural and competitive models, making a significant impact in both academic and application communities. Despite the emergence of many powerful models in recent years, there hasn't been a central benchmark for these models and future research endeavors. This lack of standardization impedes researchers and practitioners from comparing methods and reproducing results, potentially slowing down progress in this field. In this paper, we present EasyTPP, the first central repository of research assets (e.g., data, models, evaluation programs, documentations) in the area of event sequence modeling. Our EasyTPP makes several unique contributions to this area: a unified interface of using existing datasets and adding new datasets; a wide range of evaluation programs that are easy to use and extend as well as facilitate reproducible research; implementations of popular neural TPPs, together with a rich library of modules by composing which one could quickly build complex models. All the data and implementation can be found at https://github.com/ant-research/EasyTemporalPointProcess. We will actively maintain this benchmark and welcome contributions from other researchers and practitioners. Our benchmark will help promote reproducible research in this field, thus accelerating research progress as well as making more significant real-world impacts.

With the rapid development of multimodal large language models (MLLMs), they are increasingly deployed as autonomous computer-use agents capable of accomplishing complex computer tasks. However, a pressing issue arises: Can the safety risk principles designed and aligned for general MLLMs in dialogue scenarios be effectively transferred to real-world computer-use scenarios? Existing research on evaluating the safety risks of MLLM-based computer-use agents suffers from several limitations: it either lacks realistic interactive environments, or narrowly focuses on one or a few specific risk types. These limitations ignore the complexity, variability, and diversity of real-world environments, thereby restricting comprehensive risk evaluation for computer-use agents. To this end, we introduce RiOSWorld, a benchmark designed to evaluate the potential risks of MLLM-based agents during real-world computer manipulations. Our benchmark includes 492 risky tasks spanning various computer applications, involving web, social media, multimedia, os, email, and office software. We categorize these risks into two major classes based on their risk source: (i) User-originated risks and (ii) Environmental risks. For the evaluation, we evaluate safety risks from two perspectives: (i) Risk goal intention and (ii) Risk goal completion. Extensive experiments with multimodal agents on RiOSWorld demonstrate that current computer-use agents confront significant safety risks in real-world scenarios. Our findings highlight the necessity and urgency of safety alignment for computer-use agents in real-world computer manipulation, providing valuable insights for developing trustworthy computer-use agents. Our benchmark is publicly available at https://yjyddq.github.io/RiOSWorld.github.io/.

Long-tailed classification is challenging due to its heavy imbalance in class probabilities. While existing methods often focus on overall accuracy or accuracy for tail classes, they overlook a critical aspect: certain types of errors can carry greater risks than others in real-world long-tailed problems. For example, misclassifying patients (a tail class) as healthy individuals (a head class) entails far more serious consequences than the reverse scenario. To address this critical issue, we introduce Making Reliable and Flexible Decisions in Long-tailed Classification (RF-DLC), a novel framework aimed at reliable predictions in long-tailed problems. Leveraging Bayesian Decision Theory, we introduce an integrated gain to seamlessly combine long-tailed data distributions and the decision-making procedure. We further propose an efficient variational optimization strategy for the decision risk objective. Our method adapts readily to diverse utility matrices, which can be designed for specific tasks, ensuring its flexibility for different problem settings. In empirical evaluation, we design a new metric, False Head Rate, to quantify tail-sensitivity risk, along with comprehensive experiments on multiple real-world tasks, including large-scale image classification and uncertainty quantification, to demonstrate the reliability and flexibility of our method.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TrialGPT.

Advances in artificial intelligence (AI) for surgical quality assessment promise to democratize access to expertise, with applications in training, guidance, and accreditation. This study presents the SAGES Critical View of Safety (CVS) Challenge, the first AI competition organized by a surgical society, using the CVS in laparoscopic cholecystectomy, a universally recommended yet inconsistently performed safety step, as an exemplar of surgical quality assessment. A global collaboration across 54 institutions in 24 countries engaged hundreds of clinicians and engineers to curate 1,000 videos annotated by 20 surgical experts according to a consensus-validated protocol. The challenge addressed key barriers to real-world deployment in surgery, including achieving high performance, capturing uncertainty in subjective assessment, and ensuring robustness to clinical variability. To enable this scale of effort, we developed EndoGlacier, a framework for managing large, heterogeneous surgical video and multi-annotator workflows. Thirteen international teams participated, achieving up to a 17\% relative gain in assessment performance, over 80\% reduction in calibration error, and a 17\% relative improvement in robustness over the state-of-the-art. Analysis of results highlighted methodological trends linked to model performance, providing guidance for future research toward robust, clinically deployable AI for surgical quality assessment.

We developed an explainable artificial intelligence (AI) early warning score (xAI-EWS) system for early detection of acute critical illness. While maintaining a high predictive performance, our system explains to the clinician on which relevant electronic health records (EHRs) data the prediction is grounded. Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as Early Warning Scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on EHR-trained AI systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute critical illness. However, without insight into the complex decisions by such system, clinical translation is hindered. In this letter, we present our xAI-EWS system, which potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.

A major technique in learning-augmented online algorithms is combining multiple algorithms or predictors. Since the performance of each predictor may vary over time, it is desirable to use not the single best predictor as a benchmark, but rather a dynamic combination which follows different predictors at different times. We design algorithms that combine predictions and are competitive against such dynamic combinations for a wide class of online problems, namely, metrical task systems. Against the best (in hindsight) unconstrained combination of ell predictors, we obtain a competitive ratio of O(ell^2), and show that this is best possible. However, for a benchmark with slightly constrained number of switches between different predictors, we can get a (1+epsilon)-competitive algorithm. Moreover, our algorithms can be adapted to access predictors in a bandit-like fashion, querying only one predictor at a time. An unexpected implication of one of our lower bounds is a new structural insight about covering formulations for the k-server problem.

Accurate prediction of biochemical recurrence (BCR) after radical prostatectomy is critical for guiding adjuvant treatment and surveillance decisions in prostate cancer. However, existing clinicopathological risk models reduce complex morphology to relatively coarse descriptors, leaving substantial prognostic information embedded in routine histopathology underexplored. We present a deep learning-based biomarker that predicts continuous, patient-specific risk of BCR directly from H&E-stained whole-slide prostatectomy specimens. Trained end-to-end on time-to-event outcomes and evaluated across four independent international cohorts, our model demonstrates robust generalization across institutions and patient populations. When integrated with the CAPRA-S clinical risk score, the deep learning risk score consistently improved discrimination for BCR, increasing concordance indices from 0.725-0.772 to 0.749-0.788 across cohorts. To support clinical interpretability, outcome-grounded analyses revealed subtle histomorphological patterns associated with recurrence risk that are not captured by conventional clinicopathological risk scores. This multicohort study demonstrates that deep learning applied to routine prostate histopathology can deliver reproducible and clinically generalizable biomarkers that augment postoperative risk stratification, with potential to support personalized management of prostate cancer in real-world clinical settings.

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

Models that can predict the occurrence of events ahead of time with low false-alarm rates are critical to the acceptance of decision support systems in the medical community. This challenging task is typically treated as a simple binary classification, ignoring temporal dependencies between samples, whereas we propose to exploit this structure. We first introduce a common theoretical framework unifying dynamic survival analysis and early event prediction. Following an analysis of objectives from both fields, we propose Temporal Label Smoothing (TLS), a simpler, yet best-performing method that preserves prediction monotonicity over time. By focusing the objective on areas with a stronger predictive signal, TLS improves performance over all baselines on two large-scale benchmark tasks. Gains are particularly notable along clinically relevant measures, such as event recall at low false-alarm rates. TLS reduces the number of missed events by up to a factor of two over previously used approaches in early event prediction.

Personalized nutrition intervention for patients with multimorbidity is critical for improving health outcomes, yet remains challenging because it requires the simultaneous integration of heterogeneous clinical conditions, medications, and dietary guidelines. Single-agent large language models (LLMs) often suffer from context overload and attention dilution when processing such high-dimensional patient profiles. We introduce NutriOrion, a hierarchical multi-agent framework with a parallel-then-sequential reasoning topology. NutriOrion decomposes nutrition planning into specialized domain agents with isolated contexts to mitigate anchoring bias, followed by a conditional refinement stage. The framework includes a multi-objective prioritization algorithm to resolve conflicting dietary requirements and a safety constraint mechanism that injects pharmacological contraindications as hard negative constraints during synthesis, ensuring clinical validity by construction rather than post-hoc filtering. For clinical interoperability, NutriOrion maps synthesized insights into the ADIME standard and FHIR R4 resources. Evaluated on 330 stroke patients with multimorbidity, NutriOrion outperforms multiple baselines, including GPT-4.1 and alternative multi-agent architectures. It achieves a 12.1 percent drug-food interaction violation rate, demonstrates strong personalization with negative correlations (-0.26 to -0.35) between patient biomarkers and recommended risk nutrients, and yields clinically meaningful dietary improvements, including a 167 percent increase in fiber and a 27 percent increase in potassium, alongside reductions in sodium (9 percent) and sugars (12 percent).

Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) systems are increasingly integrated into clinical workflows; however, prompt injection attacks can steer these systems toward clinically unsafe or misleading outputs. We introduce the Medical Prompt Injection Benchmark (MPIB), a dataset-and-benchmark suite for evaluating clinical safety under both direct prompt injection and indirect, RAG-mediated injection across clinically grounded tasks. MPIB emphasizes outcome-level risk via the Clinical Harm Event Rate (CHER), which measures high-severity clinical harm events under a clinically grounded taxonomy, and reports CHER alongside Attack Success Rate (ASR) to disentangle instruction compliance from downstream patient risk. The benchmark comprises 9,697 curated instances constructed through multi-stage quality gates and clinical safety linting. Evaluating MPIB across a diverse set of baseline LLMs and defense configurations, we find that ASR and CHER can diverge substantially, and that robustness depends critically on whether adversarial instructions appear in the user query or in retrieved context. We release MPIB with evaluation code, adversarial baselines, and comprehensive documentation to support reproducible and systematic research on clinical prompt injection. Code and data are available at GitHub (code) and Hugging Face (data).

Quantitative tools are increasingly appealing for decision support in healthcare, driven by the growing capabilities of advanced AI systems. However, understanding the predictive uncertainties surrounding a tool's output is crucial for decision-makers to ensure reliable and transparent decisions. In this paper, we present a case study on pulmonary nodule detection for lung cancer screening, enhancing an advanced detection model with an uncertainty quantification technique called conformal risk control (CRC). We demonstrate that prediction sets with conformal guarantees are attractive measures of predictive uncertainty in the safety-critical healthcare domain, allowing end-users to achieve arbitrary validity by trading off false positives and providing formal statistical guarantees on model performance. Among ground-truth nodules annotated by at least three radiologists, our model achieves a sensitivity that is competitive with that generally achieved by individual radiologists, with a slight increase in false positives. Furthermore, we illustrate the risks of using off-the-shelve prediction models when faced with ontological uncertainty, such as when radiologists disagree on what constitutes the ground truth on pulmonary nodules.

This paper studies distributional model risk in marginal problems, where each marginal measure is assumed to lie in a Wasserstein ball centered at a fixed reference measure with a given radius. Theoretically, we establish several fundamental results including strong duality, finiteness of the proposed Wasserstein distributional model risk, and the existence of an optimizer at each radius. In addition, we show continuity of the Wasserstein distributional model risk as a function of the radius. Using strong duality, we extend the well-known Makarov bounds for the distribution function of the sum of two random variables with given marginals to Wasserstein distributionally robust Markarov bounds. Practically, we illustrate our results on four distinct applications when the sample information comes from multiple data sources and only some marginal reference measures are identified. They are: partial identification of treatment effects; externally valid treatment choice via robust welfare functions; Wasserstein distributionally robust estimation under data combination; and evaluation of the worst aggregate risk measures.

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.

The increasing threat of emerging infectious diseases and antimicrobial resistance requires more efficient, high-quality research. Perpetual Observational Studies (POS) nested within a clinical research network can improve planning, quality and efficiency of interventional and observational studies, although real-life benefits and challenges need to be assessed. Ecraid (European Clinical Research Alliance on Infectious Diseases) has initiated POS and will monitor the impact for five specific infectious syndromes.

Mehta and Panigrahi (2012) proposed Online Matching with Stochastic Rewards, which generalizes the Online Bipartite Matching problem of Karp, Vazirani, and Vazirani (1990) by associating the edges with success probabilities. This new feature captures the pay-per-click model in online advertising. Recently, Huang and Zhang (2020) studied this problem under the online primal dual framework using the Configuration Linear Program (LP), and got the best known competitive ratios of the Stochastic Balance algorithm. Their work suggests that the more expressive Configuration LP is more suitable for this problem than the Matching LP. This paper advances the theory of Configuration LP in two directions. Our technical contribution includes a characterization of the joint matching outcome of an offline vertex and all its neighbors. This characterization may be of independent interest, and is aligned with the spirit of Configuration LP. By contrast, previous analyses of Ranking generally focus on only one neighbor. Second, we designed a Stochastic Configuration LP that captures a stochastic benchmark proposed by Goyal and Udwani (2020), who used a Path-based LP. The Stochastic Configuration LP is smaller and simpler than the Path-based LP. Moreover, using the new LP we improved the competitive ratio of Stochastic Balance from 0.596 to 0.611 when the success probabilities are infinitesimal, and to 0.613 when the success probabilities are further equal.

We study a persistent failure mode in multi-objective alignment for large language models (LLMs): training improves performance on only a subset of objectives while causing others to degrade. We formalize this phenomenon as cross-objective interference and conduct the first systematic study across classic scalarization algorithms, showing that interference is pervasive and exhibits strong model dependence. To explain this phenomenon, we derive a local covariance law showing that an objective improves at first order when its reward exhibits positive covariance with the scalarized score. We extend this analysis to clipped surrogate objectives used in modern alignment, demonstrating that the covariance law remains valid under mild conditions despite clipping. Building on this analysis, we propose Covariance Targeted Weight Adaptation (CTWA), a plug-and-play method that maintains positive covariance between objective rewards and the training signal to effectively mitigate cross-objective interference. Finally, we complement these local improvement conditions with a global convergence analysis under the Polyak--Łojasiewicz condition, establishing when non-convex scalarized optimization achieves global convergence and how cross-objective interference depends on specific model geometric properties.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

Accurate estimation of brain infarction (i.e., irreversibly damaged tissue) is critical for guiding treatment decisions in acute ischemic stroke. Reliable infarct prediction informs key clinical interventions, including the need for patient transfer to comprehensive stroke centers, the potential benefit of additional reperfusion attempts during mechanical thrombectomy, decisions regarding secondary neuroprotective treatments, and ultimately, prognosis of clinical outcomes. This work introduces the Ischemic Stroke Lesion Segmentation (ISLES) 2024 challenge, which focuses on the prediction of final infarct volumes from pre-interventional acute stroke imaging and clinical data. ISLES24 provides a comprehensive, multimodal setting where participants can leverage all clinically and practically available data, including full acute CT imaging, sub-acute follow-up MRI, and structured clinical information, across a train set of 150 cases. On the hidden test set of 98 cases, the top-performing model, a multimodal nnU-Net-based architecture, achieved a Dice score of 0.285 (+/- 0.213) and an absolute volume difference of 21.2 (+/- 37.2) mL, underlining the significant challenges posed by this task and the need for further advances in multimodal learning. This work makes two primary contributions: first, we establish a standardized, clinically realistic benchmark for post-treatment infarct prediction, enabling systematic evaluation of multimodal algorithmic strategies on a longitudinal stroke dataset; second, we analyze current methodological limitations and outline key research directions to guide the development of next-generation infarct prediction models.

The rapid scaling of AI has spurred a growing emphasis on ethical considerations in both development and practice. This has led to the formulation of increasingly sophisticated model auditing and reporting requirements, as well as governance frameworks to mitigate potential risks to individuals and society. At this critical juncture, we review the practical challenges of promoting responsible AI and transparency in informal sectors like OSS that support vital infrastructure and see widespread use. We focus on how model performance evaluation may inform or inhibit probing of model limitations, biases, and other risks. Our controlled analysis of 7903 Hugging Face projects found that risk documentation is strongly associated with evaluation practices. Yet, submissions (N=789) from the platform's most popular competitive leaderboard showed less accountability among high performers. Our findings can inform AI providers and legal scholars in designing interventions and policies that preserve open-source innovation while incentivizing ethical uptake.

Survival analysis is the problem of estimating probability distributions for future event times, which can be seen as a problem in uncertainty quantification. Although there are fundamental theories on strictly proper scoring rules for uncertainty quantification, little is known about those for survival analysis. In this paper, we investigate extensions of four major strictly proper scoring rules for survival analysis and we prove that these extensions are proper under certain conditions, which arise from the discretization of the estimation of probability distributions. We also compare the estimation performances of these extended scoring rules by using real datasets, and the extensions of the logarithmic score and the Brier score performed the best.

Weighting methods in causal inference have been widely used to achieve a desirable level of covariate balancing. However, the existing weighting methods have desirable theoretical properties only when a certain model, either the propensity score or outcome regression model, is correctly specified. In addition, the corresponding estimators do not behave well for finite samples due to large variance even when the model is correctly specified. In this paper, we consider to use the integral probability metric (IPM), which is a metric between two probability measures, for covariate balancing. Optimal weights are determined so that weighted empirical distributions for the treated and control groups have the smallest IPM value for a given set of discriminators. We prove that the corresponding estimator can be consistent without correctly specifying any model (neither the propensity score nor the outcome regression model). In addition, we empirically show that our proposed method outperforms existing weighting methods with large margins for finite samples.

Medication reconciliation at clinical handoffs is a high-stakes, error-prone process. Large language models are increasingly proposed to assist with this task using FHIR-structured patient records, but a fundamental and largely unstudied variable is how the FHIR data is serialised before being passed to the model. We present the first systematic comparison of four FHIR serialisation strategies (Raw JSON, Markdown Table, Clinical Narrative, and Chronological Timeline) across five open-weight models (Phi-3.5-mini, Mistral-7B, BioMistral-7B, Llama-3.1-8B, Llama-3.3-70B) on a controlled benchmark of 200 synthetic patients, totalling 4,000 inference runs. We find that serialisation strategy has a large, statistically significant effect on performance for models up to 8B parameters: Clinical Narrative outperforms Raw JSON by up to 19 F1 points for Mistral-7B (r = 0.617, p < 10^{-10}). This advantage reverses at 70B, where Raw JSON achieves the best mean F1 of 0.9956. In all 20 model and strategy combinations, mean precision exceeds mean recall: omission is the dominant failure mode, with models more often missing an active medication than fabricating one, which changes how clinical safety auditing priorities should be set. Smaller models plateau at roughly 7-10 concurrent active medications, leaving polypharmacy patients, the patients most at risk from reconciliation errors, systematically underserved. BioMistral-7B, a domain-pretrained model without instruction tuning, produces zero usable output in all conditions, showing that domain pretraining alone is not sufficient for structured extraction. These results offer practical, evidence-based format recommendations for clinical LLM deployment: Clinical Narrative for models up to 8B, Raw JSON for 70B and above. The complete pipeline is reproducible on open-source tools running on an AWS g6e.xlarge instance (NVIDIA L40S, 48 GB VRAM).

Heterogeneity and comorbidity are two interwoven challenges associated with various healthcare problems that greatly hampered research on developing effective treatment and understanding of the underlying neurobiological mechanism. Very few studies have been conducted to investigate heterogeneous causal effects (HCEs) in graphical contexts due to the lack of statistical methods. To characterize this heterogeneity, we first conceptualize heterogeneous causal graphs (HCGs) by generalizing the causal graphical model with confounder-based interactions and multiple mediators. Such confounders with an interaction with the treatment are known as moderators. This allows us to flexibly produce HCGs given different moderators and explicitly characterize HCEs from the treatment or potential mediators on the outcome. We establish the theoretical forms of HCEs and derive their properties at the individual level in both linear and nonlinear models. An interactive structural learning is developed to estimate the complex HCGs and HCEs with confidence intervals provided. Our method is empirically justified by extensive simulations and its practical usefulness is illustrated by exploring causality among psychiatric disorders for trauma survivors.

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

Large language models (LLMs) are increasingly applied in mental health support systems, where reliable recognition of high-risk states such as suicidal ideation and self-harm is safety-critical. However, existing evaluations primarily rely on aggregate performance metrics, which often obscure risk-specific failure modes and provide limited insight into model behavior in realistic, multi-turn interactions. We present MHDash, an open-source platform designed to support the development, evaluation, and auditing of AI systems for mental health applications. MHDash integrates data collection, structured annotation, multi-turn dialogue generation, and baseline evaluation into a unified pipeline. The platform supports annotations across multiple dimensions, including Concern Type, Risk Level, and Dialogue Intent, enabling fine-grained and risk-aware analysis. Our results reveal several key findings: (i) simple baselines and advanced LLM APIs exhibit comparable overall accuracy yet diverge significantly on high-risk cases; (ii) some LLMs maintain consistent ordinal severity ranking while failing absolute risk classification, whereas others achieve reasonable aggregate scores but suffer from high false negative rates on severe categories; and (iii) performance gaps are amplified in multi-turn dialogues, where risk signals emerge gradually. These observations demonstrate that conventional benchmarks are insufficient for safety-critical mental health settings. By releasing MHDash as an open platform, we aim to promote reproducible research, transparent evaluation, and safety-aligned development of AI systems for mental health support.

When applying offline reinforcement learning (RL) in healthcare scenarios, the out-of-distribution (OOD) issues pose significant risks, as inappropriate generalization beyond clinical expertise can result in potentially harmful recommendations. While existing methods like conservative Q-learning (CQL) attempt to address the OOD issue, their effectiveness is limited by only constraining action selection by suppressing uncertain actions. This action-only regularization imitates clinician actions that prioritize short-term rewards, but it fails to regulate downstream state trajectories, thereby limiting the discovery of improved long-term treatment strategies. To safely improve policy beyond clinician recommendations while ensuring that state-action trajectories remain in-distribution, we propose Offline Guarded Safe Reinforcement Learning (OGSRL), a theoretically grounded model-based offline RL framework. OGSRL introduces a novel dual constraint mechanism for improving policy with reliability and safety. First, the OOD guardian is established to specify clinically validated regions for safe policy exploration. By constraining optimization within these regions, it enables the reliable exploration of treatment strategies that outperform clinician behavior by leveraging the full patient state history, without drifting into unsupported state-action trajectories. Second, we introduce a safety cost constraint that encodes medical knowledge about physiological safety boundaries, providing domain-specific safeguards even in areas where training data might contain potentially unsafe interventions. Notably, we provide theoretical guarantees on safety and near-optimality: policies that satisfy these constraints remain in safe and reliable regions and achieve performance close to the best possible policy supported by the data.

Perception of toxicity evolves over time and often differs between geographies and cultural backgrounds. Similarly, black-box commercially available APIs for detecting toxicity, such as the Perspective API, are not static, but frequently retrained to address any unattended weaknesses and biases. We evaluate the implications of these changes on the reproducibility of findings that compare the relative merits of models and methods that aim to curb toxicity. Our findings suggest that research that relied on inherited automatic toxicity scores to compare models and techniques may have resulted in inaccurate findings. Rescoring all models from HELM, a widely respected living benchmark, for toxicity with the recent version of the API led to a different ranking of widely used foundation models. We suggest caution in applying apples-to-apples comparisons between studies and lay recommendations for a more structured approach to evaluating toxicity over time. Code and data are available at https://github.com/for-ai/black-box-api-challenges.

We consider identification of average treatment effects on the treated (ATT) within the difference-in-differences (DiD) framework in the presence of endogenous sample selection. First, we establish that the usual DiD estimand fails to recover meaningful treatment effects, even if selection and treatment assignment are independent. Next, we partially identify the ATT for individuals who are always observed post-treatment regardless of their treatment status, and derive bounds on this parameter under different sets of assumptions about the relationship between sample selection and treatment assignment. Extensions to the repeated cross-section and two-by-two comparisons in the staggered adoption case are explored. Furthermore, we provide identification results for the ATT of three additional empirically relevant latent groups by incorporating outcome mean dominance assumptions which have intuitive appeal in applications. Finally, two empirical illustrations demonstrate the approach's usefulness by revisiting (i) the effect of a job training program on earnings(Calonico & Smith, 2017) and (ii) the effect of a working-from-home policy on employee performance (Bloom, Liang, Roberts, & Ying, 2015).

Introduction: Mechanical thrombectomy can cause vessel deformation and procedure-related injury. Benchtop models are widely used for device testing, but time-resolved, full-field 3D vessel-motion measurements remain limited. Methods: We developed a nine-camera, low-cost multi-view workflow for benchtop thrombectomy in silicone middle cerebral artery phantoms (2160p, 20 fps). Multi-view videos were calibrated, segmented, and reconstructed with 4D Gaussian Splatting. Reconstructed point clouds were converted to fixed-connectivity edge graphs for region-of-interest (ROI) displacement tracking and a relative surface-based stress proxy. Stress-proxy values were derived from edge stretch using a Neo-Hookean mapping and reported as comparative surface metrics. A synthetic Blender pipeline with known deformation provided geometric and temporal validation. Results: In synthetic bulk translation, the stress proxy remained near zero for most edges (median approx 0 MPa; 90th percentile 0.028 MPa), with sparse outliers. In synthetic pulling (1-5 mm), reconstruction showed close geometric and temporal agreement with ground truth, with symmetric Chamfer distance of 1.714-1.815 mm and precision of 0.964-0.972 at τ= 1 mm. In preliminary benchtop comparative trials (one trial per condition), cervical aspiration catheter placement showed higher max-median ROI displacement and stress-proxy values than internal carotid artery terminus placement. Conclusion: The proposed protocol provides standardized, time-resolved surface kinematics and comparative relative displacement and stress proxy measurements for thrombectomy benchtop studies. The framework supports condition-to-condition comparisons and methods validation, while remaining distinct from absolute wall-stress estimation. Implementation code and example data are available at https://ethanuser.github.io/vessel4D

Hospitals struggle to predict critical outcomes. Traditional early warning systems, like NEWS and MEWS, rely on static variables and fixed thresholds, limiting their adaptability, accuracy, and personalization. We previously developed the Enhanced Transformer for Health Outcome Simulation (ETHOS), an AI model that tokenizes patient health timelines (PHTs) from EHRs and uses transformer-based architectures to predict future PHTs. ETHOS is a versatile framework for developing a wide range of applications. In this work, we develop the Adaptive Risk Estimation System (ARES) that leverages ETHOS to compute dynamic, personalized risk probabilities for clinician-defined critical events. ARES also features a personalized explainability module that highlights key clinical factors influencing risk estimates. We evaluated ARES using the MIMIC-IV v2.2 dataset together with its Emergency Department (ED) extension and benchmarked performance against both classical early warning systems and contemporary machine learning models. The entire dataset was tokenized resulting in 285,622 PHTs, comprising over 360 million tokens. ETHOS outperformed benchmark models in predicting hospital admissions, ICU admissions, and prolonged stays, achieving superior AUC scores. Its risk estimates were robust across demographic subgroups, with calibration curves confirming model reliability. The explainability module provided valuable insights into patient-specific risk factors. ARES, powered by ETHOS, advances predictive healthcare AI by delivering dynamic, real-time, personalized risk estimation with patient-specific explainability. Although our results are promising, the clinical impact remains uncertain. Demonstrating ARES's true utility in real-world settings will be the focus of our future work. We release the source code to facilitate future research.

Competition retrospectives are useful when they explain what a leaderboard measured, how hidden evaluation changed conclusions, and which design patterns were rewarded. We revisit the CODS 2025 challenge, a privacy-aware Codabench competition on industrial multi-agent orchestration built on . We combine final rank sheets, a 300-submission server log, 149-team registrations, best-submission exports, the organizer winners report, the companion system paper, and verified planning-track source trees. Five results stand out. First, the public planning leaderboard saturates at 72.73\%, and richer prompts do not improve that peak. Second, hidden evaluation changes the story: public and private scores correlate moderately in planning (r{=}0.69) but negatively in execution (r{=}{-}0.13), with several 45.45\% public execution systems reaching 63.64\% on the hidden set. Third, the term is numerically almost inert in the official composite -- combined on a 0--1 scale with 0--100 percentage scores, it contributes at most 0.05 points per track, and rescaling would swap the top two teams. Fourth, the competition is operationally account-based but substantively team-based: 149 registered teams reduce to 24 with non-zero public scores and 11 fully ranked, while 52.3\% of deduplicated registrations list multiple usernames. Fifth, successful execution methods mostly improve guardrails -- response selection, contamination cleanup, fallback, and context control -- rather than novel agent architectures. These findings identify which behaviors the evaluation rewarded, and motivate scale-aware composites, skill-level diagnostics, and versioned artifact release.

Prediction sets can wrap around any ML model to cover unknown test outcomes with a guaranteed probability. Yet, it remains unclear how to use them optimally for downstream decision-making. Here, we propose a decision-theoretic framework that seeks to minimize the expected loss (risk) against a worst-case distribution consistent with the prediction set's coverage guarantee. We first characterize the minimax optimal policy for a fixed prediction set, showing that it balances the worst-case loss inside the set with a penalty for potential losses outside the set. Building on this, we derive the optimal prediction set construction that minimizes the resulting robust risk subject to a coverage constraint. Finally, we introduce Risk-Optimal Conformal Prediction (ROCP), a practical algorithm that targets these risk-minimizing sets while maintaining finite-sample distribution-free marginal coverage. Empirical evaluations on medical diagnosis and safety-critical decision-making tasks demonstrate that ROCP reduces critical mistakes compared to baselines, particularly when out-of-set errors are costly.

Whole-Slide Image (WSI) is an important tool for evaluating the prognosis of cancer patients. Present WSI-based prognosis studies generally follow a conventional paradigm -- cancer-specific model development -- where one cancer disease corresponds to one model and this model cannot make use of the prognostic knowledge from others. Despite its notable success in recent years, this paradigm has inherent limitations and has always been struggling with practical requirements: (i) scaling to the rare tumor diseases with very limited samples and (ii) benefiting from the generalizable prognostic knowledge in other cancers. To this end, this paper presents the first systematic study on Prognostic Knowledge Transfer in Pathology, called Path-PKT. It comprises three main parts. (1) We curate a large dataset (UNI2-h-DSS) with 13 cancers and use it to evaluate the transferability of prognostic knowledge between different cancers computationally. (2) We design experiments to understand what factors affect knowledge transfer and what causes positive transfers. (3) Motivated by empirical findings, we propose a new baseline approach (MoE-PKT) with a routing mechanism to utilize the generalizable prognostic knowledge in other cancers. Finally, we show the transferability of source models to rare tumor diseases. This study could lay solid foundations for the study of knowledge transfer in WSI-based cancer prognosis. Source code is available at https://github.com/liupei101/Path-PKT.

The rapid advancement of large language models (LLMs) introduces dual-use capabilities that could both threaten and bolster national security and public safety (NSPS). Models implement safeguards to protect against potential misuse relevant to NSPS and allow for benign users to receive helpful information. However, current benchmarks often fail to test safeguard robustness to potential NSPS risks in an objective, robust way. We introduce FORTRESS: 500 expert-crafted adversarial prompts with instance-based rubrics of 4-7 binary questions for automated evaluation across 3 domains (unclassified information only): Chemical, Biological, Radiological, Nuclear and Explosive (CBRNE), Political Violence & Terrorism, and Criminal & Financial Illicit Activities, with 10 total subcategories across these domains. Each prompt-rubric pair has a corresponding benign version to test for model over-refusals. This evaluation of frontier LLMs' safeguard robustness reveals varying trade-offs between potential risks and model usefulness: Claude-3.5-Sonnet demonstrates a low average risk score (ARS) (14.09 out of 100) but the highest over-refusal score (ORS) (21.8 out of 100), while Gemini 2.5 Pro shows low over-refusal (1.4) but a high average potential risk (66.29). Deepseek-R1 has the highest ARS at 78.05, but the lowest ORS at only 0.06. Models such as o1 display a more even trade-off between potential risks and over-refusals (with an ARS of 21.69 and ORS of 5.2). To provide policymakers and researchers with a clear understanding of models' potential risks, we publicly release FORTRESS at https://huggingface.co/datasets/ScaleAI/fortress_public. We also maintain a private set for evaluation.

In this work we design an end-to-end deep learning architecture for predicting, on Chest X-rays images (CXR), a multi-regional score conveying the degree of lung compromise in COVID-19 patients. Such semi-quantitative scoring system, namely Brixia~score, is applied in serial monitoring of such patients, showing significant prognostic value, in one of the hospitals that experienced one of the highest pandemic peaks in Italy. To solve such a challenging visual task, we adopt a weakly supervised learning strategy structured to handle different tasks (segmentation, spatial alignment, and score estimation) trained with a "from-the-part-to-the-whole" procedure involving different datasets. In particular, we exploit a clinical dataset of almost 5,000 CXR annotated images collected in the same hospital. Our BS-Net demonstrates self-attentive behavior and a high degree of accuracy in all processing stages. Through inter-rater agreement tests and a gold standard comparison, we show that our solution outperforms single human annotators in rating accuracy and consistency, thus supporting the possibility of using this tool in contexts of computer-assisted monitoring. Highly resolved (super-pixel level) explainability maps are also generated, with an original technique, to visually help the understanding of the network activity on the lung areas. We also consider other scores proposed in literature and provide a comparison with a recently proposed non-specific approach. We eventually test the performance robustness of our model on an assorted public COVID-19 dataset, for which we also provide Brixia~score annotations, observing good direct generalization and fine-tuning capabilities that highlight the portability of BS-Net in other clinical settings. The CXR dataset along with the source code and the trained model are publicly released for research purposes.

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.

The demand for emergency department (ED) services is increasing across the globe, particularly during the current COVID-19 pandemic. Clinical triage and risk assessment have become increasingly challenging due to the shortage of medical resources and the strain on hospital infrastructure caused by the pandemic. As a result of the widespread use of electronic health records (EHRs), we now have access to a vast amount of clinical data, which allows us to develop predictive models and decision support systems to address these challenges. To date, however, there are no widely accepted benchmark ED triage prediction models based on large-scale public EHR data. An open-source benchmarking platform would streamline research workflows by eliminating cumbersome data preprocessing, and facilitate comparisons among different studies and methodologies. In this paper, based on the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database, we developed a publicly available benchmark suite for ED triage predictive models and created a benchmark dataset that contains over 400,000 ED visits from 2011 to 2019. We introduced three ED-based outcomes (hospitalization, critical outcomes, and 72-hour ED reattendance) and implemented a variety of popular methodologies, ranging from machine learning methods to clinical scoring systems. We evaluated and compared the performance of these methods against benchmark tasks. Our codes are open-source, allowing anyone with MIMIC-IV-ED data access to perform the same steps in data processing, benchmark model building, and experiments. This study provides future researchers with insights, suggestions, and protocols for managing raw data and developing risk triaging tools for emergency care.

Risk scores are simple classification models that let users make quick risk predictions by adding and subtracting a few small numbers. These models are widely used in medicine and criminal justice, but are difficult to learn from data because they need to be calibrated, sparse, use small integer coefficients, and obey application-specific operational constraints. In this paper, we present a new machine learning approach to learn risk scores. We formulate the risk score problem as a mixed integer nonlinear program, and present a cutting plane algorithm for non-convex settings to efficiently recover its optimal solution. We improve our algorithm with specialized techniques to generate feasible solutions, narrow the optimality gap, and reduce data-related computation. Our approach can fit risk scores in a way that scales linearly in the number of samples, provides a certificate of optimality, and obeys real-world constraints without parameter tuning or post-processing. We benchmark the performance benefits of this approach through an extensive set of numerical experiments, comparing to risk scores built using heuristic approaches. We also discuss its practical benefits through a real-world application where we build a customized risk score for ICU seizure prediction in collaboration with the Massachusetts General Hospital.

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

Background: Emerging reports of "AI psychosis" are on the rise, where user-LLM interactions may exacerbate or induce psychosis or adverse psychological symptoms. Whilst the sycophantic and agreeable nature of LLMs can be beneficial, it becomes a vector for harm by reinforcing delusional beliefs in vulnerable users. Methods: Psychosis-bench is a novel benchmark designed to systematically evaluate the psychogenicity of LLMs comprises 16 structured, 12-turn conversational scenarios simulating the progression of delusional themes(Erotic Delusions, Grandiose/Messianic Delusions, Referential Delusions) and potential harms. We evaluated eight prominent LLMs for Delusion Confirmation (DCS), Harm Enablement (HES), and Safety Intervention(SIS) across explicit and implicit conversational contexts. Findings: Across 1,536 simulated conversation turns, all LLMs demonstrated psychogenic potential, showing a strong tendency to perpetuate rather than challenge delusions (mean DCS of 0.91 pm0.88). Models frequently enabled harmful user requests (mean HES of 0.69 pm0.84) and offered safety interventions in only roughly a third of applicable turns (mean SIS of 0.37 pm0.48). 51 / 128 (39.8%) of scenarios had no safety interventions offered. Performance was significantly worse in implicit scenarios, models were more likely to confirm delusions and enable harm while offering fewer interventions (p < .001). A strong correlation was found between DCS and HES (rs = .77). Model performance varied widely, indicating that safety is not an emergent property of scale alone. Conclusion: This study establishes LLM psychogenicity as a quantifiable risk and underscores the urgent need for re-thinking how we train LLMs. We frame this issue not merely as a technical challenge but as a public health imperative requiring collaboration between developers, policymakers, and healthcare professionals.

Selective Classification, wherein models can reject low-confidence predictions, promises reliable translation of machine-learning based classification systems to real-world scenarios such as clinical diagnostics. While current evaluation of these systems typically assumes fixed working points based on pre-defined rejection thresholds, methodological progress requires benchmarking the general performance of systems akin to the AUROC in standard classification. In this work, we define 5 requirements for multi-threshold metrics in selective classification regarding task alignment, interpretability, and flexibility, and show how current approaches fail to meet them. We propose the Area under the Generalized Risk Coverage curve (AUGRC), which meets all requirements and can be directly interpreted as the average risk of undetected failures. We empirically demonstrate the relevance of AUGRC on a comprehensive benchmark spanning 6 data sets and 13 confidence scoring functions. We find that the proposed metric substantially changes metric rankings on 5 out of the 6 data sets.

Claims made by individuals or entities are oftentimes nuanced and cannot be clearly labeled as entirely "true" or "false" -- as is frequently the case with scientific and political claims. However, a claim (e.g., "vaccine A is better than vaccine B") can be dissected into its integral aspects and sub-aspects (e.g., efficacy, safety, distribution), which are individually easier to validate. This enables a more comprehensive, structured response that provides a well-rounded perspective on a given problem while also allowing the reader to prioritize specific angles of interest within the claim (e.g., safety towards children). Thus, we propose ClaimSpect, a retrieval-augmented generation-based framework for automatically constructing a hierarchy of aspects typically considered when addressing a claim and enriching them with corpus-specific perspectives. This structure hierarchically partitions an input corpus to retrieve relevant segments, which assist in discovering new sub-aspects. Moreover, these segments enable the discovery of varying perspectives towards an aspect of the claim (e.g., support, neutral, or oppose) and their respective prevalence (e.g., "how many biomedical papers believe vaccine A is more transportable than B?"). We apply ClaimSpect to a wide variety of real-world scientific and political claims featured in our constructed dataset, showcasing its robustness and accuracy in deconstructing a nuanced claim and representing perspectives within a corpus. Through real-world case studies and human evaluation, we validate its effectiveness over multiple baselines.

Clinical trials are pivotal for developing new medical treatments but typically carry risks such as patient mortality and enrollment failure that waste immense efforts spanning over a decade. Applying artificial intelligence (AI) to predict key events in clinical trials holds great potential for providing insights to guide trial designs. However, complex data collection and question definition requiring medical expertise have hindered the involvement of AI thus far. This paper tackles these challenges by presenting a comprehensive suite of 23 meticulously curated AI-ready datasets covering multi-modal input features and 8 crucial prediction challenges in clinical trial design, encompassing prediction of trial duration, patient dropout rate, serious adverse event, mortality rate, trial approval outcome, trial failure reason, drug dose finding, design of eligibility criteria. Furthermore, we provide basic validation methods for each task to ensure the datasets' usability and reliability. We anticipate that the availability of such open-access datasets will catalyze the development of advanced AI approaches for clinical trial design, ultimately advancing clinical trial research and accelerating medical solution development.

We consider the problem of fairly allocating a sequence of indivisible items that arrive online in an arbitrary order to a group of n agents with additive normalized valuation functions. We consider both the allocation of goods and chores and propose algorithms for approximating maximin share (MMS) allocations. When agents have identical valuation functions the problem coincides with the semi-online machine covering problem (when items are goods) and load balancing problem (when items are chores), for both of which optimal competitive ratios have been achieved. In this paper, we consider the case when agents have general additive valuation functions. For the allocation of goods, we show that no competitive algorithm exists even when there are only three agents and propose an optimal 0.5-competitive algorithm for the case of two agents. For the allocation of chores, we propose a (2-1/n)-competitive algorithm for n>=3 agents and a square root of 2 (approximately 1.414)-competitive algorithm for two agents. Additionally, we show that no algorithm can do better than 15/11 (approximately 1.364)-competitive for two agents.

Contemporary AGI evaluations report multidomain capability profiles, yet they typically assign symmetric weights and rely on snapshot scores. This creates two problems: (i) equal weighting treats all domains as equally important when human intelligence research suggests otherwise, and (ii) snapshot testing can't distinguish durable capabilities from brittle performances that collapse under delay or stress. I argue that general intelligence -- in humans and potentially in machines -- is better understood as a homeostatic property cluster: a set of abilities plus the mechanisms that keep those abilities co-present under perturbation. On this view, AGI evaluation should weight domains by their causal centrality (their contribution to cluster stability) and require evidence of persistence across sessions. I propose two battery-compatible extensions: a centrality-prior score that imports CHC-derived weights with transparent sensitivity analysis, and a Cluster Stability Index family that separates profile persistence, durable learning, and error correction. These additions preserve multidomain breadth while reducing brittleness and gaming. I close with testable predictions and black-box protocols labs can adopt without architectural access.

Moment restrictions and their conditional counterparts emerge in many areas of machine learning and statistics ranging from causal inference to reinforcement learning. Estimators for these tasks, generally called methods of moments, include the prominent generalized method of moments (GMM) which has recently gained attention in causal inference. GMM is a special case of the broader family of empirical likelihood estimators which are based on approximating a population distribution by means of minimizing a varphi-divergence to an empirical distribution. However, the use of varphi-divergences effectively limits the candidate distributions to reweightings of the data samples. We lift this long-standing limitation and provide a method of moments that goes beyond data reweighting. This is achieved by defining an empirical likelihood estimator based on maximum mean discrepancy which we term the kernel method of moments (KMM). We provide a variant of our estimator for conditional moment restrictions and show that it is asymptotically first-order optimal for such problems. Finally, we show that our method achieves competitive performance on several conditional moment restriction tasks.

Epidemiologists often wish to estimate quantities that are easy to communicate and correspond to the results of realistic public health scenarios. Methods from causal inference can answer these questions. We adopt the language of potential outcomes under Rubin's original Bayesian framework and show that the parametric g-formula is easily amenable to a Bayesian approach. We show that the frequentist properties of the Bayesian g-formula suggest it improves the accuracy of estimates of causal effects in small samples or when data may be sparse. We demonstrate our approach to estimate the effect of environmental tobacco smoke on body mass index z-scores among children aged 4-9 years who were enrolled in a longitudinal birth cohort in New York, USA. We give a general algorithm and supply SAS and Stan code that can be adopted to implement our computational approach in both time-fixed and longitudinal data.

Split conformal prediction has recently sparked great interest due to its ability to provide formally guaranteed uncertainty sets or intervals for predictions made by black-box neural models, ensuring a predefined probability of containing the actual ground truth. While the original formulation assumes data exchangeability, some extensions handle non-exchangeable data, which is often the case in many real-world scenarios. In parallel, some progress has been made in conformal methods that provide statistical guarantees for a broader range of objectives, such as bounding the best F_1-score or minimizing the false negative rate in expectation. In this paper, we leverage and extend these two lines of work by proposing non-exchangeable conformal risk control, which allows controlling the expected value of any monotone loss function when the data is not exchangeable. Our framework is flexible, makes very few assumptions, and allows weighting the data based on its relevance for a given test example; a careful choice of weights may result on tighter bounds, making our framework useful in the presence of change points, time series, or other forms of distribution drift. Experiments with both synthetic and real world data show the usefulness of our method.

With the growing use of language models (LMs) in clinical environments, there is an immediate need to evaluate the accuracy and safety of LM-generated medical text. Currently, such evaluation relies solely on manual physician review. However, detecting errors in LM-generated text is challenging because 1) manual review is costly and 2) expert-composed reference outputs are often unavailable in real-world settings. While the "LM-as-judge" paradigm (a LM evaluating another LM) offers scalable evaluation, even frontier LMs can miss subtle but clinically significant errors. To address these challenges, we propose MedVAL, a self-supervised framework that leverages synthetic data to train evaluator LMs to assess whether LM-generated medical outputs are factually consistent with inputs, without requiring physician labels or reference outputs. To evaluate LM performance, we introduce MedVAL-Bench, a dataset containing 840 outputs annotated by physicians, following a physician-defined taxonomy of risk levels and error categories. Across 6 diverse medical tasks and 10 state-of-the-art LMs spanning open-source, proprietary, and medically adapted models, MedVAL fine-tuning significantly improves (p < 0.001) alignment with physicians on both seen and unseen tasks, increasing average F1 scores from 66% to 83%, with per-sample safety classification scores up to 86%. MedVAL improves the performance of even the best-performing proprietary LM (GPT-4o) by 8%. To support a scalable, risk-aware pathway towards clinical integration, we open-source the 1) codebase ( https://github.com/StanfordMIMI/MedVAL ), 2) MedVAL-Bench ( https://huggingface.co/datasets/stanfordmimi/MedVAL-Bench ), and 3) MedVAL-4B ( https://huggingface.co/stanfordmimi/MedVAL-4B ), the best-performing open-source LM. Our research provides the first evidence of LMs approaching expert-level validation ability for medical text.

Continuous Glucose Monitoring (CGM) can detect early metabolic subphenotypes (insulin resistance, IR; β-cell dysfunction), but population-scale deployment faces two coupled problems. First, the same physiological state appears through multiple views (CGM time series, venous OGTT, Glucodensity summaries), so single-view representations fail to transfer when deployment shifts the modality or setting. Second, baselines perform inconsistently across these shifts. Both problems point to one remedy: representations that abstract away from any single view to capture higher-level temporal and distributional structure. We propose CGM-JEPA, a self-supervised pretraining framework which predicts masked latent representations rather than raw values, yielding abstraction that transfers across modalities. X-CGM-JEPA adds a masked Glucodensity cross-view objective for complementary distributional information. We pretrain on sim389k unlabeled CGM readings from 228 subjects and evaluate on two clinical cohorts (N=27 and N=17 public-release subsets) across three regimes (cohort generalization, venous-to-CGM transfer, home CGM) under 20-iteration times 2-fold cross-validation. X-CGM-JEPA ranks first or second on AUROC for both endpoints across all three regimes while no baseline does, exceeding the strongest baseline by up to +6.5 pp in cohort generalization and +3.6 pp in venous-to-CGM transfer (paired Wilcoxon, p<0.001). Under modality shift, it matches mean AUROC while redistributing toward weaker subgroups (ethnicity AUROC gap shrinks 25-54%); on sparse in-domain venous data, the distributional view lifts label-aware clustering (ARI +39%, NMI +40%). Code and weights: https://github.com/cruiseresearchgroup/CGM-JEPA

Excellent tail performance is crucial for modern machine learning tasks, such as algorithmic fairness, class imbalance, and risk-sensitive decision making, as it ensures the effective handling of challenging samples within a dataset. Tail performance is also a vital determinant of success for personalized recommender systems to reduce the risk of losing users with low satisfaction. This study introduces a "safe" collaborative filtering method that prioritizes recommendation quality for less-satisfied users rather than focusing on the average performance. Our approach minimizes the conditional value at risk (CVaR), which represents the average risk over the tails of users' loss. To overcome computational challenges for web-scale recommender systems, we develop a robust yet practical algorithm that extends the most scalable method, implicit alternating least squares (iALS). Empirical evaluation on real-world datasets demonstrates the excellent tail performance of our approach while maintaining competitive computational efficiency.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

Competitions play an invaluable role in the field of forecasting, as exemplified through the recent M4 competition. The competition received attention from both academics and practitioners and sparked discussions around the representativeness of the data for business forecasting. Several competitions featuring real-life business forecasting tasks on the Kaggle platform has, however, been largely ignored by the academic community. We believe the learnings from these competitions have much to offer to the forecasting community and provide a review of the results from six Kaggle competitions. We find that most of the Kaggle datasets are characterized by higher intermittence and entropy than the M-competitions and that global ensemble models tend to outperform local single models. Furthermore, we find the strong performance of gradient boosted decision trees, increasing success of neural networks for forecasting, and a variety of techniques for adapting machine learning models to the forecasting task.

Polymarket is a prediction market platform where users can speculate on future events by trading shares tied to specific outcomes, known as conditions. Each market is associated with a set of one or more such conditions. To ensure proper market resolution, the condition set must be exhaustive -- collectively accounting for all possible outcomes -- and mutually exclusive -- only one condition may resolve as true. Thus, the collective prices of all related outcomes should be \1, representing a combined probability of 1 of any outcome. Despite this design, Polymarket exhibits cases where dependent assets are mispriced, allowing for purchasing (or selling) a certain outcome for less than (or more than) 1, guaranteeing profit. This phenomenon, known as arbitrage, could enable sophisticated participants to exploit such inconsistencies. In this paper, we conduct an empirical arbitrage analysis on Polymarket data to answer three key questions: (Q1) What conditions give rise to arbitrage (Q2) Does arbitrage actually occur on Polymarket and (Q3) Has anyone exploited these opportunities. A major challenge in analyzing arbitrage between related markets lies in the scalability of comparisons across a large number of markets and conditions, with a naive analysis requiring O(2^{n+m}) comparisons. To overcome this, we employ a heuristic-driven reduction strategy based on timeliness, topical similarity, and combinatorial relationships, further validated by expert input. Our study reveals two distinct forms of arbitrage on Polymarket: Market Rebalancing Arbitrage, which occurs within a single market or condition, and Combinatorial Arbitrage, which spans across multiple markets. We use on-chain historical order book data to analyze when these types of arbitrage opportunities have existed, and when they have been executed by users. We find a realized estimate of 40 million USD of profit extracted.

Multi-agent systems composed of large generative models are rapidly moving from laboratory prototypes to real-world deployments, where they jointly plan, negotiate, and allocate shared resources to solve complex tasks. While such systems promise unprecedented scalability and autonomy, their collective interaction also gives rise to failure modes that cannot be reduced to individual agents. Understanding these emergent risks is therefore critical. Here, we present a pioneer study of such emergent multi-agent risk in workflows that involve competition over shared resources (e.g., computing resources or market share), sequential handoff collaboration (where downstream agents see only predecessor outputs), collective decision aggregation, and others. Across these settings, we observe that such group behaviors arise frequently across repeated trials and a wide range of interaction conditions, rather than as rare or pathological cases. In particular, phenomena such as collusion-like coordination and conformity emerge with non-trivial frequency under realistic resource constraints, communication protocols, and role assignments, mirroring well-known pathologies in human societies despite no explicit instruction. Moreover, these risks cannot be prevented by existing agent-level safeguards alone. These findings expose the dark side of intelligent multi-agent systems: a social intelligence risk where agent collectives, despite no instruction to do so, spontaneously reproduce familiar failure patterns from human societies.

When a phone-use agent avoids harm, does that show safety, or simply inability to act? Existing evaluations often cannot tell. A harmful outcome may be avoided because the agent recognized the risk and chose the safe action, or because it failed to understand the screen or execute any relevant action at all. These cases have different causes and call for different fixes, yet current benchmarks often merge them under task success, refusal, or final harmful outcome. We address this problem with PhoneSafety, a benchmark of 700 safety-critical moments drawn from real phone interactions across more than 130 apps. Each instance isolates the next decision at a risky moment and asks a simple question: does the model take the safe action, take the unsafe action, or fail to do anything useful? We evaluate eight representative phone-use agents under this framework. Our results reveal two main patterns. First, stronger general phone-use ability does not reliably imply safer choices at risky moments. Models that perform better on ordinary app tasks are not always the ones that behave more safely when the next action matters. Second, failures to do anything useful behave like a capability signal rather than a safety signal: they are concentrated in more visually and operationally demanding settings and remain stable when the evaluation protocol changes. Across models, failures split into two recurring patterns: unsafe choices in settings where the model can act but chooses wrongly, and inability to act in more visually and operationally demanding screens. Overall, a harmless outcome is not enough to count as evidence of safety. Evaluating phone-use agents requires separating unsafe judgment from inability to act.