Clinical prediction can saturate for two different reasons: a fitted learner may fail to extract available information, or the recorded variables may impose a population frontier. We separate these quantities through the \emph{learner gap} and the \emph{measurement-channel ceiling}. Optimal balanced accuracy is characterized by total-variation separation, yielding architecture invariance, a sharp partial-identification result under replacement contamination, a cross-fitted ceiling estimator, and exact conditions for multimodal decision improvement. We add two finite-sample diagnostics, namely a label-permutation optimism floor and an underfit curve, and validate the audit on three real cohorts: UCI readmission ($n=99{,}343$), BRFSS diabetes ($n=253{,}680$), and NHANES HbA1c ($n=10{,}219$). Well-tuned gradient boosting nearly reaches the estimated frontier in UCI and BRFSS, whereas deliberately or practically deficient learners retain large gaps. NHANES yields a null difference between questionnaire and measured marginal frontiers but a significant joint complementarity gain, refining the simplistic claim that an objective modality must dominate. Across all cohorts, modest AUROC gains coexist with substantially larger Bayes decision-flip rates, and several architectures estimate similar frontiers while their achieved balanced accuracy differs sharply. A PRISMA-guided synthesis of 104 clinical tasks then shows that the same channel-level regularities recur across more than 18 disease categories: a broad but non-universal structured-clinical region, diminishing same-channel gains across model families, and higher performance when measurement channels change. The framework converts saturation from an empirical observation into an auditable decision: improve the learner when headroom remains; improve measurement when it does not.
Medical vision-language models (VLMs) can appear reliable in-domain while failing when acquisition domain, paired supervision, or evaluation protocol changes. We study this failure mode as a representation-level blind spot relevant to epistemic intelligence, without claiming a formal estimator of epistemic uncertainty. Using NIH ChestXray14 and CheXpert, we first isolate source-only cross-dataset visual transfer from unsupervised domain-adaptation diagnostics. Using PadChest and OpenI, we then evaluate multimodal alignment under strict pair-index retrieval and quantify metadata-derived source-proxy information retained in frozen embeddings. Self-supervised visual initialization improves NIH-to-CheXpert transfer over supervised ImageNet initialization in matched ResNet-18 comparisons, whereas adversarial adaptation is useful only in a narrow regime and becomes unstable as adversarial pressure increases. Multimodal exact-pair retrieval remains low under external OpenI stress testing, and source-proxy information remains recoverable from learned representations. Qualitative nearest-neighbor and Grad-CAM analyses show clinically plausible cross-dataset structure and thoracic attention patterns in many cases, while device-heavy and false-positive cases remain ambiguous. Auxiliary architecture checks are task-dependent and do not support a universal backbone ranking. Overall, the study shows that apparent competence under a single protocol can conceal transfer, alignment, and shortcut-related failure modes, motivating stress-tested evaluation of medical VLMs under distribution shift.
Clinical-AI guidance increasingly recommends prompting language models to reason with attention to diversity, equity, and inclusion (DEI). We measure a side effect that misrepresents patients: a one-sentence DEI prompt appended to a medical question leads models to add patient demographic attributes (race, socioeconomic status, sex) the question never stated, in effect rewriting who the patient is. We call this demographic injection. Across 47 models, four medical benchmarks, and 376,000 responses scored by a validated model-judge pipeline, a single DEI prompt raises the injection rate from 0.7% to 33.1% (47x) in all 47 of 47 models, attributable to the equity content rather than to added length (18x above a length-matched control; p=1.4x10^-14). Most added content is a general population statement that leaves the answer unchanged, but a smaller subset attaches an attribute to the specific patient or changes the selected option (0.25-2.4% of responses, 99.8% toward the incorrect option), where the invented demographic changes the answer the model recommends. Phrasing scales the effect from 14% to 56%. DEI prompts are just one example of a more general mechanism. Any instruction that nudges how a model reasons can make it add unrequested details, including details about the patient. Flagged outputs are treated as model errors under study, not clinical guidance.
Yizhi Dong, Yuhe Ke, Hairil Rizal Abdullah +4cs.LG
Postoperative adverse events, including mortality and morbidity, remain a major global burden, many of which are preventable through early identification of high-risk patients and targeted perioperative care. Accurate risk stratification is therefore essential. With the growing availability of large-scale electronic health records (EHRs), machine learning (ML) provides a data-driven approach to model complex clinical patterns. However, existing studies vary widely in design, and methodological practices remain fragmented. This scoping review characterizes ML pipelines for surgical risk stratification and outcome prediction using EHR data. We reviewed 190 studies covering the ML workflow, including data preprocessing, algorithm selection, model evaluation, and explainability. Most studies relied on single-center private datasets with limited data modalities, while the scarcity of open-access surgical datasets constrained reproducibility and generalizability. Reporting of key preprocessing steps, including missing data handling, feature selection, and class imbalance, was often incomplete. Conventional ML models and simple neural networks predominated, whereas deep learning and multimodal approaches remained uncommon. Benchmark datasets and standardized evaluation protocols were largely absent, hindering cross-study comparisons. Only about one-third of studies incorporated explainability methods. This review identifies methodological gaps limiting clinically robust postoperative ML tools and provides a structured reference to support more rigorous, reproducible, and clinically meaningful ML development for perioperative care.
Joshua C. Vences, William T. Tran, Nikko Gimpaya +15cs.CV cs.AI
Background and Study Aims: Accurate optical diagnosis of colorectal polyps guides resection strategy and surveillance, with multimodal large language models (MLLMs) showing potential for image-based diagnosis. We aimed to evaluate the diagnostic accuracy of MLLMs in classifying colorectal polyps and predicting histology. Methods: We conducted a retrospective diagnostic performance study using the PRIME dataset, a curated set of white light and narrow-band imaging (NBI) images. We evaluated Claude Opus 4, Google Gemini 2.5 Pro, GPT-o3, GPT-4o, and GPT-5. For Paris, Narrow-band Imaging Colorectal Endoscopic (NICE), and predicted histology, we calculated F1 scores, percent correct scores, and accuracy of each MLLM compared to expert responses for 132 cases. Cochran's Q and McNemar's Test were used to determine differences between predicted values of each MLLM. Results: The F1 scores among MLLMs were >0.9 for all models for neoplastic vs. non-neoplastic polyps. Gemini 2.5 Pro demonstrated the highest F1 scores for invasive vs. non-invasive polyps and low- vs. high-grade adenoma, at 0.560 and 0.492 respectively. Claude Opus 4 and GPT-5 had statistically significantly higher percent correct scores than other MLLMs at 41.7%, using Paris classification. Conclusions: Claude Opus 4 and Gemini 2.5 Pro showed the highest accuracy in differentiating polyp subtypes, performing closest to expert consensus. Sensitivity and specificity, however, did not meet ESGE standards, highlighting the need for prospective multicenter trials and the design of human-in-the-loop workflows before clinical deployment.
Recent work has argued normatively, on synthetic data, that evaluating survival models by discrimination alone (concordance index) yields systematically misleading model comparisons, because the metric ignores calibration and time-dependent accuracy. Whether this matters for real, published, non-clinical models has not been tested. We reproduce three published survival-ML models across three structurally distinct domains -- hard-drive failure prediction, peer-to-peer credit default, and user disengagement on digital platforms -- validate our instrument against the anchor paper's own synthetic experiment, and test five pre-registered hypotheses under a Holm-corrected family-wise error rate. Three of five reject (though one pre-registered threshold clears by a narrow margin). A model reproducing the published literature's discrimination almost exactly (C = 0.9595 vs. 0.958 reported) fails a formal calibration test at p < 0.001; a broad feature-ablation search finds no single attribute responsible for its discrimination, so the calibration failure is not a trivial shortcut artifact. A lender's estimated default risk is biased upward by roughly two percentage points, growing to nearly four in the riskiest segment, when loan prepayment is treated as non-informative censoring rather than a competing risk. A platform's churn model shows probability estimates that degrade with the horizon even as global discrimination stays within the pre-registered C-index band. A direct test of whether metric choice inverts model preference does not reject, though with limited power given two to three models per domain; the failure mode we document is better characterized as misplaced confidence in a chosen model than as choosing the wrong one. We release a pre-registered evaluation harness with full code and an annotated notebook, so these results can be verified independently and the audit extended.
This position paper argues that claims about explanation stability are scientifically invalid without cross method validation. Just as statistical significance requires the test statistic to be specified, stability should either be evaluated across multiple attribution paradigms or explicitly scoped to the computational objective of a single method. In controlled chest X ray experiments, DenseNet201, ResNet50V2, and InceptionV3 achieved AUC values above 99%, yet their stability rankings reversed across attribution methods. LayerCAM ranked InceptionV3 as the most stable model, with an IoU of 0.777, whereas GradCAM++ favored DenseNet201 and reduced InceptionV3 stability score by 17.3%. These findings demonstrate that explanation stability is an emergent property of the model method pair rather than an intrinsic characteristic of the model alone. We therefore argue that explanation based claims should be validated across multiple attribution methods and that regulatory submissions should explicitly specify the attribution operators used to avoid creating illusory safety assurances.
Dominic Okonkwo, Magnus Hodgson, Temitope I. David +1cs.CL
Frontier language models are increasingly evaluated on biomedical benchmarks, but two problems undermine most published evaluations: legacy benchmarks are near-saturated, and open-ended responses are graded by other language models. We evaluate Claude Fable 5, Anthropic's most capable publicly available model, across eight biomedical benchmarks, four text and four multimodal, using deterministic scoring against fixed answer keys throughout. We include two Claude predecessors and GPT-5 as baselines. Refusal is tracked as a distinct outcome in every result table. That decision produces the paper's central finding. Fable 5 refuses between 8.0% and 99.4% of questions depending on the benchmark, a pattern absent in both predecessors and in GPT-5. Once refused items are excluded from the denominator, Fable 5's accuracy exceeds or meets every other model on every benchmark in this study. We identify two distinguishable refusal patterns: one concentrating in basic-science and mechanism content across MedQA and MedXpertQA MM, confirmed independently on two benchmarks using each benchmark's own category labels; and a separate disease-domain pattern on RareBench, where inborn metabolic disease presentations are refused near-universally while adult-onset autoimmune presentations are not. The primary constraint on Fable 5's biomedical usefulness is willingness to engage, not capability once it does.
Mayur Sanap, Prasanna Desikan, Edgar Lobatoneess.AS cs.AI cs.HC cs.SD
Respiratory acoustic foundation models (FMs) are benchmarked exclusively on smartphone recordings, yet clinical deployment increasingly targets body-coupled (BC) wearables whose sensors attenuate high-frequency content through tissue and bone, leaving FM reliability uncharacterised. We introduce BCoughBench, evaluating five FMs (OPERA-CT/CE/GT, HeAR, M2D+Resp) on nine classification tasks (AUROC, sensitivity at 95% specificity, Expected Calibration Error) and three age regression tasks (MAE vs. a mean-predictor baseline) across five EBEN-simulated BC sensor conditions on five labeled cough datasets. Mean AUROC declines from 0.785 (smartphone) to 0.689-0.723, degrading most under temple vibration pickup ($Δ$ = -0.096) and least under the soft in-ear ($Δ$ = -0.062). No FM meets the clinical sensitivity threshold (Se@Sp95 $\geq$ 0.20) on most disease tasks under any BC sensor. Sex classification on the CIDRZ cohort collapses (AUROC 0.954 to 0.596-0.628, $Δ$ = -0.341) while COVID detection is nearly unaffected ($Δ$ = -0.004). Age regression is robust, improving under the forehead accelerometer on CoughVID (MAE 9.61 to 8.97 yr); HeAR leads on regression and demographic tasks, M2D+Resp on disease and characteristic tasks. BCoughBench provides a reproducible framework for FM evaluation under wearable conditions.
Seasonal influenza infects millions of people and causes substantial morbidity and mortality in the United States each year, making accurate short-term forecasting a core public-health need. Reliable forecasts of epidemic time series can inform vaccination timing, hospital staffing, and resource allocation, yet the comparative behavior of modern forecasting architectures on infectious-disease surveillance data remains insufficiently characterized. We address this gap through a systematic evaluation of regional influenza forecasting using influenza-like illness surveillance and influenza-associated hospitalization time series under both temporal and spatial generalization settings for 1-4-week-ahead prediction. We compare classical neural network architectures, numerical transformer-based models, pretrained time series foundation models, and LLM-based forecasting approaches. Across tasks, we demonstrate that a mixture-of-experts model that fuses multiple pretrained forecasters achieves the strongest overall performance, indicating that heterogeneous pretrained representations provide complementary predictive information. Our results further show that numerical transformer-based models produce reliable forecasts, while pretraining provides the largest gains at longer horizons, particularly when the pretraining domain is mechanistically aligned with influenza dynamics. In contrast, LLM-based time series methods underperform relative to numerical forecasters in this setting. Finally, we examine hospitalization information as both an auxiliary covariate and a pretraining source. Hospitalization signals provide complementary improvements in selected settings and clarify when additional surveillance streams enhance the robustness of multi-horizon forecasting. These findings provide actionable guidance on model selection, pretraining strategy, and auxiliary-signal use for influenza preparedness.
Mahshad Lotfinia, Sebastian Ziegelmayer, Lisa Adams +3cs.CV cs.AI cs.CL cs.LG
Medical vision-language models report strong chest radiograph accuracy, and this is increasingly read as evidence that they use the image. That inference is unsafe: a model exploiting finding-name priors scores like one that reads the scan, and no standard benchmark separates them. We introduce a causal audit that intervenes on the image, occluding the relevant region, occluding an irrelevant one, and swapping in another patient's same-label scan, and combines three behavioral metrics to test whether a correct answer depends on the image. Across nine systems, a text-only model with no image access reaches within 5.7 accuracy points of the best multimodal one, and a 119-billion-parameter multimodal model is statistically indistinguishable from a 7-billion text-only baseline. The audit splits the cohort into three models that ignore the image, one that is unstable, and five that use it selectively, for a subset of findings; the categories hold across a second dataset, resolution, and prompt phrasing. Against board-certified radiologists, a text-only model is statistically indistinguishable from a radiologist's accuracy while grounding at zero, whereas the image-using models ground at radiologist-comparable rates. Reported confidence flags ungrounded answers only when a model uses the image. Grounding audits, not accuracy, should gate clinical deployment.
Aggregate accuracy benchmarks conceal a systematic structure in how large language models fail at electronic health record (EHR) question answering: questions requiring more inferential steps produce disproportionately more errors. Motivated by theoretical results on transformer compositionality limits, we introduce a pre-specified hop-count taxonomy -- the number of distinct reasoning steps required to answer a clinical question from an EHR -- as a principled predictor of model failure. We annotate 313 clinician-generated MedAlign EHR question-answer pairs across four hop levels and evaluate 301 questions in a within-model ablation (claude-sonnet-4-6, zero-shot vs. extended thinking) and cross-architecture replications (gpt-4o and gpt-5.4-2026-03-05, zero-shot). All three models, spanning two providers and two OpenAI generations (GPT-4 and GPT-5), show monotone accuracy decline with hop count: Claude Sonnet zero-shot falls from 30.6% (hop=1) to 17.6% (hop=4) (Cochran-Armitage z=-2.30, p=0.011; OR per hop 0.72, 95% CI [0.56,0.92], p=0.008); GPT-4o replicates this (37.8% to 14.7%; OR 0.58 [0.45,0.75], p<0.001); and gpt-5.4-2026-03-05 confirms it (37.8% to 23.5%; OR 0.80 [0.66,0.98], p=0.027). A pre-specified context-sufficiency audit shows higher-hop questions are not differentially disadvantaged by EHR truncation (answerability 93-95% at hops 2-4 vs. 79% at hop=1), so the decline reflects compositional reasoning difficulty. Extended thinking did not significantly flatten the accuracy-depth curve across three reasoning conditions, and thinking-token usage scaled with hop count (r=0.31, p<0.0001), consistent with the predicted O(k) computational requirement. Hop count is thus a theory-motivated, cross-architecture predictor of large-language-model error on EHR question answering, with direct implications for deployment risk stratification of clinical AI.
Ask a pretrained biomedical language model whether "cortisol 28 ug/dL" and "stock-market volatility" are related, and it returns a cosine similarity of 0.83 on a scale where 1.0 means identical. The two share no mechanism. This is not a corner case: every off-the-shelf biomedical encoder we tested (BioBERT, PubMedBERT, BioM-ELECTRA) scores unrelated cross-domain pairs between 0.76 and 0.92 when the answer should be near zero. Accuracy on cross-domain discrimination is 0%. Retrieval systems survive this, because a language model downstream filters the noise. A Large Behavioural Model (LBM), a foundation model whose subject is a person rather than a sentence, does not: it reasons over a graph of a user's life and treats embedding proximity as evidence that two events are causally linked. False proximity writes a false causal edge, and everything downstream inherits the error. Here, embedding geometry is not a tuning knob; it is correctness. We report the fix. A contrastive pass over 72,034 pairs raises PubMedBERT BIOSSES correlation from 0.633 to 0.828 and within-vs-across-domain separation from 1.05x to 1.63x. A second pass, BODHI, mines hard negatives from edges absent in a biomedical knowledge graph and lifts separation to 2.30x and the discrimination gap to +0.392, at a 4.5% BIOSSES cost. On an Intel Xeon 6737P with AMX, OpenVINO cuts single-query latency from 1367 ms to 10 ms (133x) and reaches 555 sentences/sec. One finding contradicts standard advice: FP16 beats INT8 on this silicon at every serving batch size, and we explain why. The same model on a no-AMX Ice Lake instance runs 13-27x slower. We release the benchmark suite, training corpora, the BODHI generator, and the OpenVINO scripts.
Dilakshan Srikanthan, Amoon Jamzad, Paul Wilson +5cs.CV
Whether attention maps from pathology foundation models capture genuine biology remains unknown, yet this question is critical for clinical trust and regulatory approval. We propose a spatial transcriptomics-based framework for orthogonal, hypothesis-free evaluation of attention and apply it to five pathology foundation models (CONCH v1.5, UNI v2, Virchow2, GigaPath, H-Optimus-1) and a ResNet50 baseline. Using attention-based multiple instance learning, we train single-task and multi-task models to predict five molecular alterations in glioblastoma on the CPTAC cohort, validate on an independent TCGA cohort, and evaluate biological coherence of attention maps against 87 transcriptional signatures using co-registered Visium spatial transcriptomics data from 18 samples. Internally, no single encoder dominates across all tasks, and external validation inverts internal performance rankings. Attention maps show a five-fold enrichment gradient from pathways (Cohen's d=0.329) to individual genes (d=0.055), indicating that attention captures emergent multi-gene transcriptional programs rather than individual molecular events. Spatially smooth attention maps do not imply biological coherence, and different encoders attend to distinct biological compartments. Our framework provides objective, quantitative assessment of what foundation models learn from histopathology, moving the field beyond qualitative saliency map review.