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Oct 16

Enhancing Fluorescence Lifetime Parameter Estimation Accuracy with Differential Transformer Based Deep Learning Model Incorporating Pixelwise Instrument Response Function

Fluorescence Lifetime Imaging (FLI) is a critical molecular imaging modality that provides unique information about the tissue microenvironment, which is invaluable for biomedical applications. FLI operates by acquiring and analyzing photon time-of-arrival histograms to extract quantitative parameters associated with temporal fluorescence decay. These histograms are influenced by the intrinsic properties of the fluorophore, instrument parameters, time-of-flight distributions associated with pixel-wise variations in the topographic and optical characteristics of the sample. Recent advancements in Deep Learning (DL) have enabled improved fluorescence lifetime parameter estimation. However, existing models are primarily designed for planar surface samples, limiting their applicability in translational scenarios involving complex surface profiles, such as in-vivo whole-animal or imaged guided surgical applications. To address this limitation, we present MFliNet (Macroscopic FLI Network), a novel DL architecture that integrates the Instrument Response Function (IRF) as an additional input alongside experimental photon time-of-arrival histograms. Leveraging the capabilities of a Differential Transformer encoder-decoder architecture, MFliNet effectively focuses on critical input features, such as variations in photon time-of-arrival distributions. We evaluate MFliNet using rigorously designed tissue-mimicking phantoms and preclinical in-vivo cancer xenograft models. Our results demonstrate the model's robustness and suitability for complex macroscopic FLI applications, offering new opportunities for advanced biomedical imaging in diverse and challenging settings.

  • 7 authors
·
Nov 25, 2024

Marginal Fidelity Does Not Establish User Simulation in Demographic Synthetic Survey Panels: Response Contracts, Support Collapse and Conditioning Failure

Demographic synthetic survey panels are often validated by matching aggregate answers to published surveys. We test what that certificate establishes across six multiselect batteries from four survey organisations in three countries. The headline analysis is restricted to three instruments whose synthetic cohort and human target share the stated population frame; three other batteries remain sensitivity analyses. The response contract dominates measured fidelity. In the aligned instruments, committed sets leave 66 of 128 model-battery option slots empty in panels of up to 500 respondents, versus 0 of 128 under per-option probability elicitation. Across eight uncapped model-instrument comparisons, probabilities reduce option-marginal MAE by 4.53 to 7.30 points. The capped instrument reverses on two models until the vectors are projected onto its stated maximum. These are measurement effects: human targets are realised check-all responses, whereas the vectors are latent inclusion propensities. Published marginal agreement also fails to discriminate respondent simulation from direct population estimation. On nine aligned model-battery pairs, a no-persona population-prevalence query averages 6.27 MAE versus 12.39 for committed panels and wins all nine comparisons. Constraint-aware probability vectors average 5.34 and beat the query on four of nine, so the baseline challenges the validation criterion rather than proving direct estimation uniformly best. On three unpublished demographic cells, neither approach beats reciting the national distribution. Population-marginal agreement is therefore evidence about an elicitation contract and an estimand obtainable without simulated respondents, not evidence of individual simulation.

  • 1 authors
·
Sep 6

Rubric Rewards from Item Response Theory

Many language tasks have no single answer that can be checked automatically. Rubrics provide criteria for judging responses to these tasks. For reinforcement learning, the resulting verdicts must be combined into a scalar reward. A common approach sums the points assigned to satisfied criteria. Distinct verdict patterns can thus receive the same reward, and the fixed points encode how much each criterion should count, not how strongly its verdict distinguishes the current rollouts. Beyond this aggregation problem, judging the full rubric needs more judge requests as the criterion count grows. To address these limitations, Rubric Response Theory (RRT) measures quality and selects criteria when rubric criteria are monotone indicators of a shared target. Rather than adding assigned points, RRT uses a two parameter item response model that treats the verdict pattern as evidence about scalar quality specific to the rubric. Under this model, its likelihood score maximizes the local signal-to-noise ratio for quality. Its Response Parameter Network (RPN) reads the prompt and criterion text to predict criterion difficulty and discrimination. As the policy distribution changes during training, RRT uses online expectation maximization to update the RPN from current rollout verdicts. With Qwen3.5-4B as the policy, RRT's macro criterion score across Medical, Science, Rubrics as Rewards Science, and RubricBench is 1.7 points above that of group relative policy optimization (GRPO). On hard and very hard criteria in Medical and Science, RRT gains 2.8 to 5.6 points over GRPO. At half the criterion budget, adaptive Fisher selection with a frozen RPN keeps the macro criterion score across four datasets within 0.1 points of GRPO with full judging. These results show RRT can reduce judge requests while remaining competitive with GRPO.

microsoft Microsoft
·
Sep 27 2

Beyond Perturbation Magnitude: Direction-Dependent Responses in Multimodal Geometric Representations

Geometric alignment scores based on Gram determinants provide a compact way to model higher-order consistency among modalities, yet how such scores respond to modality degradation is poorly understood. This paper asks whether the response of a multimodal geometric score is determined primarily by the magnitude of the perturbation-induced displacement. Using frozen cohorts from MSR-VTT (N=878) and DiDeMo (N=980), we apply controlled video blur and audio noise and analyze the response in the relational geometry on which the score is defined. Displacement magnitude explains at most 15% of the out-of-sample variance in the absolute response, and magnitude-matched pairs respond systematically differently, so scalar magnitude does not organize the response. The closed-form first-order expansion of the Gramian volume yields the Directional Geometric Response (DGR): the projection of the displacement onto the local volume gradient, which jointly captures the clean operating point, displacement magnitude, and displacement direction. The absolute first-order DGR term explains the observed response with out-of-sample R^2 of 0.838-0.969, matched-magnitude ranking accuracies of 0.864-0.963, and response-sign accuracies of 0.909-0.989, whereas the tested direction-free alternatives remain weak or unstable under the corresponding evaluation protocols. A pre-specified gain-normalization candidate, V/(g_V+eps), fails its predictability and clean-order gates. DGR uses the observed degraded-state displacement and is therefore an explanatory quantity, not a deployment-time predictor: geometric response depends on where the representation operates, how far degradation moves the relational geometry, and in which direction it moves.

  • 5 authors
·
Oct 5

Incompressible Knowledge Probes: Estimating Black-Box LLM Parameter Counts via Factual Capacity

Closed-source frontier labs do not disclose parameter counts. Storing F facts requires at least F/(bits per parameter) weights, so factual recall lower-bounds parameter count--an intrinsic, serving-independent signal, though (as we show) a coarse one. We introduce Incompressible Knowledge Probes (IKPs), a benchmark of 1,400 factual questions spanning 7 tiers of obscurity, designed to isolate knowledge that cannot be derived by reasoning or compressed by architectural improvements. We score with no hallucination penalty (lambda = 0: IKP accuracy is simply the fraction of probed facts answered correctly), which removes both the penalty hyperparameter and the per-tier flooring choice; a full lambda x flooring ablation shows the calibration is robust across scoring choices while individual estimates are not, motivating the no-penalty default. We calibrate a log-linear mapping from IKP accuracy to parameter count on 93 open-weight models (135M-1,600B) spanning 19 vendors, achieving R^2 = 0.910; leave-one-out cross-validation confirms generalization (median fold error 1.48x, 72% within 2x, 86% within 3x). The instrument is deliberately coarse--its 90% prediction interval spans ~3x in either direction, wider than inference economics--so IKP recovers order-of-magnitude effective capacity and relative rankings, not precise parameter counts. For Mixture-of-Experts models, total parameters predict knowledge (R^2 = 0.67) better than active parameters (R^2 = 0.41). We evaluate 201 models from 27 vendors on a curated probe set (1,311 of 1,400 probes surviving name-collision and label-ambiguity filters) and report effective knowledge capacity for all major proprietary frontier models as prediction bands rather than point estimates; for heavily safety-tuned models these are lower bounds, since refusal policy can suppress tens of percentage points of otherwise-answerable capacity.

  • 1 authors
·
Jul 4

Constructing interval variables via faceted Rasch measurement and multitask deep learning: a hate speech application

We propose a general method for measuring complex variables on a continuous, interval spectrum by combining supervised deep learning with the Constructing Measures approach to faceted Rasch item response theory (IRT). We decompose the target construct, hate speech in our case, into multiple constituent components that are labeled as ordinal survey items. Those survey responses are transformed via IRT into a debiased, continuous outcome measure. Our method estimates the survey interpretation bias of the human labelers and eliminates that influence on the generated continuous measure. We further estimate the response quality of each labeler using faceted IRT, allowing responses from low-quality labelers to be removed. Our faceted Rasch scaling procedure integrates naturally with a multitask deep learning architecture for automated prediction on new data. The ratings on the theorized components of the target outcome are used as supervised, ordinal variables for the neural networks' internal concept learning. We test the use of an activation function (ordinal softmax) and loss function (ordinal cross-entropy) designed to exploit the structure of ordinal outcome variables. Our multitask architecture leads to a new form of model interpretation because each continuous prediction can be directly explained by the constituent components in the penultimate layer. We demonstrate this new method on a dataset of 50,000 social media comments sourced from YouTube, Twitter, and Reddit and labeled by 11,000 U.S.-based Amazon Mechanical Turk workers to measure a continuous spectrum from hate speech to counterspeech. We evaluate Universal Sentence Encoders, BERT, and RoBERTa as language representation models for the comment text, and compare our predictive accuracy to Google Jigsaw's Perspective API models, showing significant improvement over this standard benchmark.

  • 4 authors
·
Sep 21, 2020

Studying Large Language Model Generalization with Influence Functions

When trying to gain better visibility into a machine learning model in order to understand and mitigate the associated risks, a potentially valuable source of evidence is: which training examples most contribute to a given behavior? Influence functions aim to answer a counterfactual: how would the model's parameters (and hence its outputs) change if a given sequence were added to the training set? While influence functions have produced insights for small models, they are difficult to scale to large language models (LLMs) due to the difficulty of computing an inverse-Hessian-vector product (IHVP). We use the Eigenvalue-corrected Kronecker-Factored Approximate Curvature (EK-FAC) approximation to scale influence functions up to LLMs with up to 52 billion parameters. In our experiments, EK-FAC achieves similar accuracy to traditional influence function estimators despite the IHVP computation being orders of magnitude faster. We investigate two algorithmic techniques to reduce the cost of computing gradients of candidate training sequences: TF-IDF filtering and query batching. We use influence functions to investigate the generalization patterns of LLMs, including the sparsity of the influence patterns, increasing abstraction with scale, math and programming abilities, cross-lingual generalization, and role-playing behavior. Despite many apparently sophisticated forms of generalization, we identify a surprising limitation: influences decay to near-zero when the order of key phrases is flipped. Overall, influence functions give us a powerful new tool for studying the generalization properties of LLMs.

  • 17 authors
·
Aug 7, 2023

Selective Machine Learning of the Average Treatment Effect with an Invalid Instrumental Variable

Instrumental variable methods have been widely used to identify causal effects in the presence of unmeasured confounding. A key identification condition known as the exclusion restriction states that the instrument cannot have a direct effect on the outcome which is not mediated by the exposure in view. In the health and social sciences, such an assumption is often not credible. To address this concern, we consider identification conditions of the population average treatment effect with an invalid instrumental variable which does not satisfy the exclusion restriction, and derive the efficient influence function targeting the identifying functional under a nonparametric observed data model. We propose a novel multiply robust locally efficient estimator of the average treatment effect that is consistent in the union of multiple parametric nuisance models, as well as a multiply debiased machine learning estimator for which the nuisance parameters are estimated using generic machine learning methods, that effectively exploit various forms of linear or nonlinear structured sparsity in the nuisance parameter space. When one cannot be confident that any of these machine learners is consistent at sufficiently fast rates to ensure n-consistency for the average treatment effect, we introduce a new criteria for selective machine learning which leverages the multiple robustness property in order to ensure small bias. The proposed methods are illustrated through extensive simulations and a data analysis evaluating the causal effect of 401(k) participation on savings.

  • 3 authors
·
Jul 27, 2019

Preserving Statistical Validity in Adaptive Data Analysis

A great deal of effort has been devoted to reducing the risk of spurious scientific discoveries, from the use of sophisticated validation techniques, to deep statistical methods for controlling the false discovery rate in multiple hypothesis testing. However, there is a fundamental disconnect between the theoretical results and the practice of data analysis: the theory of statistical inference assumes a fixed collection of hypotheses to be tested, or learning algorithms to be applied, selected non-adaptively before the data are gathered, whereas in practice data is shared and reused with hypotheses and new analyses being generated on the basis of data exploration and the outcomes of previous analyses. In this work we initiate a principled study of how to guarantee the validity of statistical inference in adaptive data analysis. As an instance of this problem, we propose and investigate the question of estimating the expectations of m adaptively chosen functions on an unknown distribution given n random samples. We show that, surprisingly, there is a way to estimate an exponential in n number of expectations accurately even if the functions are chosen adaptively. This gives an exponential improvement over standard empirical estimators that are limited to a linear number of estimates. Our result follows from a general technique that counter-intuitively involves actively perturbing and coordinating the estimates, using techniques developed for privacy preservation. We give additional applications of this technique to our question.

  • 6 authors
·
Nov 10, 2014

Beyond Overall Accuracy: A Psychometric Deep Dive into the Topic-Specific Medical Capabilities of 80 Large Language Models

As Large Language Models (LLMs) are increasingly proposed for high-stakes medical applications, there has emerged a critical need for reliable and accurate evaluation methodologies. Traditional accuracy metrics fail inadequately as they neither capture question characteristics nor offer topic-specific insights. To address this gap, we introduce MedIRT, a rigorous evaluation framework grounded in Item Response Theory (IRT), the gold standard in high-stakes educational testing. Unlike previous research relying on archival data, we prospectively gathered fresh responses from 80 diverse LLMs on a balanced, 1,100-question USMLE-aligned benchmark. Using one unidimensional two-parameter logistic IRT model per topic, we estimate LLM's latent model ability jointly with question difficulty and discrimination, yielding more stable and nuanced performance rankings than accuracy alone. Notably, we identify distinctive ``spiky'' ability profiles, where overall rankings can be misleading due to highly specialized model abilities. While GPT-5 was the top performer in a majority of domains (8 of 11), it was outperformed in Social Science and Communication by Claude-3-opus, demonstrating that even an overall 23rd-ranked model can hold the top spot for specific competencies. Furthermore, we demonstrate IRT's utility in auditing benchmarks by identifying flawed questions. We synthesize these findings into a practical decision-support framework that integrates our multi-factor competency profiles with operational metrics. This work establishes a robust, psychometrically grounded methodology essential for the safe, effective, and trustworthy deployment of LLMs in healthcare.

  • 4 authors
·
Sep 28, 2025

Towards a Deterministic Math Solver for Clinical Language Models

Large language models are unreliable at arithmetic, which is a problem for clinical calculators where a single numerical error changes the recommendation. The standard response is to hardcode each calculator as a validated function, one at a time. We test an alternative: the model does not calculate. Instead, it writes case-specific Python that a restricted local executor runs as a deterministic solver, and the model's task reduces to deciding how to use it. We evaluate this Program-Solve interface on MedCalc-Bench Verified (1,100 cases, 55 calculators) against direct model arithmetic and a hand-written 22-calculator library, using Qwen2.5-7B and Qwen2.5-32B-AWQ, after auditing the benchmark's formulas against current clinical guidelines and flagging 16 of 55 with version, use or coefficient concerns. With formulas and gold variables supplied and both routes reading the whole note, handing off to the solver is not a reliable advantage at 7B (75.31% against 72.02%, a paired +3.29 points with a 95% calculator-cluster interval of [-3.49, 10.38]) but is one at 32B (90.53% against 83.47%, +7.05 [0.47, 14.60], clear of zero). The hand-written library is exact on its 440 supported cases but abstains elsewhere (40.0% overall). Adding an executor thus helps some open-weight models more than others even under matched formula, variable and note access, and is not a substitute for verified formulas or reliable variable extraction either way.