Statistical Methodology
Stable Transport Meta-Analysis for Heterogeneous Cardiovascular Trials: A Nuisance-Anchor Framework with a Sign-Stability Diagnostic
Ibrahim Halil Tanboga
Random-effects meta-analysis summarizes heterogeneous trials by estimating an average effect over the observed evidence base, which may not represent the clinically relevant target population. In cardiovascular medicine, treatment effects vary systematically across era, endpoint definitions, background therapy, and case-mix, making the historical average often misaligned with current decision-making. We propose stable transport meta-analysis (AMT-MA), a nuisance-anchor
estimator that models anchor-aligned variation but does not transport it to the target population. The method combines a weighted-average loss with a scale-normalized softmax regime loss, and incorporates a precision-weighted sign-stability diagnostic with a two-condition abstention rule to avoid reporting a single pooled estimate when stability is not supported. AMT-MA is not intended to minimize RMSE relative to random-effects models, but to redefine the estimand as a stable target-population effect. In a pre-specified ADEMP simulation across six scenarios, AMT-MA (rho = 0.2) showed reduced bias relative to unadjusted pooling and improved coverage in
adversarial settings where classical Wald intervals fail (dominant trial: 0.85 vs 0.01; confounded anchor: 0.86 vs 0.34; anchor shift: 0.91 vs 0.60). WLS meta-regression remained competitive when correctly specified. Under sign-flip heterogeneity, the abstention rule triggered in ~84% of replications, compared with ~28-30% in stable regimes. Applications to post-myocardial infarction streptokinase trials and primary-prevention aspirin trials illustrate how AMT-MA quantifies transport uncertainty and provides a clinically interpretable alternative to averaging heterogeneous effects.
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Machine Learning (Statistics) · Cross-listed from cs.LG
Prior-Fitted Functional Flow: In-Context Generative Models for Pharmacokinetics
César Ojeda, Niklas Hartung, Wilhelm Huisinga et al. (+6 more)
We introduce Prior-Fitted Functional Flows, a generative foundation model for pharmacokinetics that enables zero-shot population synthesis and individual
forecasting without manual parameter tuning. We learn functional vector fields, explicitly conditioned on the sparse, irregular data of an entire study population. This enables the generation of coherent virtual cohorts as well as
forecasting of partially observed patient trajectories with calibrated uncertainty. We construct a new open-access literature corpus to inform our priors, and demonstrate state-of-the-art predictive accuracy on extensive real-world
datasets.
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All authors César Ojeda, Niklas Hartung, Wilhelm Huisinga, Tim Jahn, Purity Kamene Kavwele, Marian Klose, Piyush Kumar, Ramsés J. Sánchez, Darius A. Faroughy
Statistical Methodology · Cross-listed from q-fin.PM
Post-Screening Portfolio Selection
Yoshimasa Uematsu and Shinya Tanaka
We propose post-screening portfolio selection (PS$^2$), a two-step framework for high-dimensional mean–variance investing. First, assets are screened by Lasso-type regression of a constant on excess returns without an intercept. Second, portfolio weights are estimated on the selected set using standard low-dimensional methods. Because strong factors can destroy sparsity in real data, we further introduce PS$^2$ with factors (FPS$^2$), which defactors returns before screening and allows factor investing in the final step. We establish theoretical guarantees, and simulations and an empirical application show competitive performance, especially when sparse screening is appropriate or strong factors are explicitly accommodated.
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Statistics Theory · Cross-listed from cs.LG
Recovery Guarantees for Continual Learning of Dependent Tasks: Memory, Data-Dependent Regularization, and Data-Dependent Weights
Liangzu Peng, Uday Kiran Reddy Tadipatri, Ziqing Xu et al. (+2 more)
Continual learning (CL) is concerned with learning multiple tasks sequentially without forgetting previously learned tasks. Despite substantial empirical advances over recent years, the theoretical development of CL remains in its infancy. At the heart of developing CL theory lies the challenge that the data distribution varies across tasks, and we argue that properly addressing this challenge requires understanding this variation–dependency among tasks. To explicitly model task dependency, we consider nonlinear regression tasks and propose the assumption that these tasks are dependent in such a way that the data of the current task is a nonlinear transformation of previous data. With this model and under natural assumptions, we prove statistical recovery guarantees (more specifically, bounds on estimation errors) for several CL paradigms in practical use, including experience replay with data-independent regularization and data-independent weights that balance the losses of tasks, replay with data-dependent weights, and continual learning with data-dependent regularization (e.g., knowledge
distillation). To the best of our knowledge, our bounds are informative in cases where prior work gives vacuous bounds.
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All authors Liangzu Peng, Uday Kiran Reddy Tadipatri, Ziqing Xu, Eric Eaton, René Vidal
Statistics Theory · Cross-listed from cs.LG
Diverse Dictionary Learning
Yujia Zheng, Zijian Li, Shunxing Fan et al. (+2 more)
Given only observational data $X = g(Z)$, where both the latent variables $Z$ and the generating process $g$ are unknown, recovering $Z$ is ill-posed without additional assumptions. Existing methods often assume linearity or rely on auxiliary supervision and functional constraints. However, such assumptions are rarely verifiable in practice, and most theoretical guarantees break down under even mild violations, leaving uncertainty about how to reliably understand the hidden world. To make identifiability actionable in the real-world scenarios, we take a complementary view: in the general settings where full identifiability is unattainable, what can still be recovered with guarantees, and what biases could be universally adopted? We introduce the problem of diverse dictionary learning to formalize this view. Specifically, we show that intersections, complements, and symmetric differences of latent variables linked to arbitrary observations, along with the latent-to-observed dependency structure, are still identifiable up to appropriate indeterminacies even without strong assumptions. These set-theoretic results can be composed using set
algebra to construct structured and essential views of the hidden world, such as genus-differentia definitions. When sufficient structural diversity is present, they further imply full identifiability of all latent variables. Notably, all identifiability benefits follow from a simple inductive bias during estimation that can be readily integrated into most models. We validate the theory and demonstrate the benefits of the bias on both synthetic and real-world data.
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All authors Yujia Zheng, Zijian Li, Shunxing Fan, Andrew Gordon Wilson, Kun Zhang
Machine Learning (Statistics) · Cross-listed from cs.LG
Contraction and Hourglass Persistence for Learning on Graphs, Simplices, and Cells
Mattie Ji, Indradyumna Roy and Vikas Garg
Persistent homology (PH) encodes global information, such as cycles, and is thus increasingly integrated into graph neural networks (GNNs). PH methods in GNNs typically traverse an increasing sequence of subgraphs. In this work, we first expose limitations of this inclusion procedure. To remedy these shortcomings, we analyze contractions as a principled topological operation, in particular, for graph representation learning. We study the persistence of contraction sequences, which we call Contraction Homology (CH). We establish that forward PH and CH differ in expressivity. We then introduce Hourglass Persistence, a class of topological descriptors that interleave a sequence of inclusions and contractions to boost expressivity, learnability, and stability. We also study related families parametrized by two paradigms. We also discuss how our framework extends to simplicial and cellular networks. We further design efficient
algorithms that are pluggable into end-to-end differentiable GNN pipelines, enabling consistent empirical improvements over many PH methods across standard real-world graph
datasets. Code is available at \href{https://github.com/Aalto-QuML/Hourglass}{this https URL}.
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Statistics Theory · Cross-listed from math.PR
Convergence of Langevin AIS for multimodal distributions
Akshat Agarwal, Gautam Iyer, Aidan Jameson et al. (+2 more)
We study convergence rates of the annealed importance sampling
algorithm (Neal '01) combined with Langevin Monte Carlo when the target is a
multimodal Gibbs measure. The main result shows that for a fixed error threshold, the time complexity is quadratic in the inverse temperature. We identify a simple and useful quantity that controls the sampling error for AIS in a general setting, and then bound this quantity in our setting using spectral estimates. We also study an autonormalized version and obtain bounds for the time complexity in terms of the inverse temperature.
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All authors Akshat Agarwal, Gautam Iyer, Aidan Jameson, Seungjae Son, Wyatt Wimmer
Statistics Theory
Joint Exclusivity
Nawaf Mohammed
We introduce joint exclusivity (JE), a relaxation of mutual exclusivity (ME) for non-negative random vectors that forbids only the simultaneous positivity of all $n$ components. Whereas ME requires the probabilities of positive outcomes to sum to at most one, a JE random vector with prescribed marginals $F_1,\ldots,F_n$ exists if and only if \[ \sum_{i=1}^n \overline{F}_i(0)\le n-1. \] An inclusion–exclusion identity shows that JE laws are determined by their $(n-1)$-dimensional margins and decomposes aggregate stop-loss premiums into those of sub-portfolios. A single wrap-around construction attains the existence bound, minimises the number of claims in convex order and, in frequency–severity models, the aggregate loss, thereby extending the safest-dependence property of ME beyond its admissible range. We also develop canonical and distortion-based constructions with freely chosen face copulas, and an $m$-exclusivity hierarchy between ME and JE with sharp two-sided stop-loss bounds.
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Statistics Theory
Algorithmic Contiguity from Low-Degree Heuristic II: Predicting Detection-Recovery Gaps
Zhangsong Li
The low-degree
polynomial framework has emerged as a powerful tool for providing evidence of statistical-computational gaps in high-dimensional inference. For detection problems, the standard approach bounds the low-degree advantage through an explicit orthonormal basis. However, this method does not extend naturally to estimation tasks, and thus fails to capture the detection-recovery gap phenomenon that arises in many high-dimensional problems. Although several important advances have been made to overcome this limitation \cite{SW22, SW25, CGGV25+}, the existing approaches often rely on delicate, model-specific combinatorial arguments. In this work, we develop a general approach for obtaining conditional computational lower bounds for recovery problems from mild bounds on low-degree testing advantage. Our method combines the notion of algorithmic contiguity in \cite{Li25} with a cross-validation reduction in \cite{DHSS25} that converts successful recovery into a hypothesis test with lopsided success probabilities. In contrast to prior unconditional lower bounds, our argument is conceptually simple, flexible, and largely model-independent. We apply this framework to several canonical inference problems, including planted submatrix, planted dense subgraph,
stochastic block model, multi-frequency angular synchronization, orthogonal group synchronization, and multi-layer
stochastic block model. In the first three settings, our method recovers existing low-degree lower bounds for recovery in \cite{SW22, SW25} via a substantially simpler argument. In the latter three, it gives new evidence for conjectured computational thresholds including the persistence of detection-recovery gaps. Together, these results suggest that mild control of low-degree advantage is often sufficient to explain computational barriers for recovery in high-dimensional statistical models.
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Statistical Methodology
A Null Model for Mapper Subtype Claims
Chad M. Topaz
The Mapper
algorithm from topological data analysis constructs a graph summarizing the shape of a high-dimensional
dataset, and groups of data points identified within this graph are widely interpreted as evidence of distinct subtypes. However, the covariance structure of the data alone can make such groups appear differentiated, even when no subtypes are present. Existing validation approaches do not account for this effect and thus cannot distinguish covariance artifacts from genuine subtypes. We propose a Gaussian null model that generates reference data matching the sample covariance
matrix. We pair it with a test statistic that measures mean-level differentiation between communities. In an idealized setting, we prove that covariance geometry alone causes Mapper communities to differ in their average feature profiles, and we show that a simpler label-permutation baseline cannot detect this effect. Simulations confirm well-controlled Type I error under Gaussian data. We apply the framework to four published Mapper analyses spanning breast cancer gene expression, Congressional voting, NBA player performance, and lower-grade glioma genomics. In every case, once outlier singleton communities are accounted for, the observed differentiation does not exceed what the null produces at the {\alpha} = 0.05 level. This result does not rule out subtypes in these
datasets, but it does indicate that the observed structure is consistent with what covariance geometry alone can produce. Stronger evidence would be needed to support a subtype claim.
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Machine Learning (Statistics)
StrEBM: A Structured Latent Energy-Based Model for Blind Source Separation
Yuan-Hao Wei
This paper proposes StrEBM, a structured latent energy-based model for source-wise structured representation learning. The framework is motivated by a broader goal of promoting identifiable and decoupled latent organization by assigning different latent dimensions their own learnable structural biases, rather than constraining the entire latent representation with a single shared energy. In this sense, blind source separation is adopted here as a concrete and verifiable testbed, through which the
evolution of latent dimensions toward distinct underlying components can be directly examined. In the proposed framework, latent trajectories are optimized directly together with an observation-generation map and source-wise structural parameters. Each latent dimension is associated with its own energy-based formulation, allowing different latent components to gradually evolve toward distinct source-like roles during training. In the present study, this source-wise energy design is instantiated using Gaussian-process-inspired energies with learnable length-scales, but the framework itself is not restricted to Gaussian processes and is intended as a more general structured latent EBM formulation. Experiments on synthetic multichannel signals under linear and nonlinear mixing settings show that the proposed model can recover source components effectively, providing an initial empirical validation of the framework. At the same time, the study reveals important optimization characteristics, including slow late-stage convergence and reduced stability under nonlinear observation mappings. These findings not only clarify the practical behavior of the current GP-based instantiation, but also establish a basis for future investigation of richer source-wise energy families and more robust nonlinear optimization strategies.
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Statistics Applications · Cross-listed from cs.AI
Rectification Difficulty and Optimal Sample Allocation in LLM-Augmented Surveys
Zikun Ye and Hema Yoganarasimhan
Large
Language Models can generate synthetic survey responses at low cost, but their accuracy varies unpredictably across questions. We study the design problem of allocating a fixed budget of human respondents across estimation tasks when cheap LLM predictions are available for every task. Our framework combines three components. First, building on Prediction-Powered Inference, we characterize a question-specific rectification difficulty that governs how quickly the
estimator's variance decreases with human sample size. Second, we derive a closed-form optimal allocation rule that directs more human labels to tasks where the LLM is least reliable. Third, since rectification difficulty depends on unobserved human responses for new surveys, we propose a meta-learning approach, trained on historical data, that predicts it for entirely new tasks without pilot data. The framework extends to general M-estimation, covering regression coefficients and multinomial logit partworths for conjoint analysis. We validate the framework on two
datasets spanning different domains, question types, and LLMs, showing that our approach captures 61-79% of the theoretically attainable efficiency gains, achieving 11.4% and 10.5% MSE reductions without requiring any pilot human data for the target survey.
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Statistical Methodology
Detecting Breast Carcinoma Metastasis on Whole-Slide Images by Partially Subsampled Multiple Instance Learning
Baichen Yu, Xuetong Li, Jing Zhou et al. (+1 more)
Breast cancer is the most prevalent cancer in women worldwide. Histopathology image analysis serves as the gold standard for cancer diagnosis. In this regard, whole-slide imaging (WSI), a revolutionary technology in digital pathology, allows for ultrahigh-resolution tissue analysis. Despite its promise, WSI analysis faces significant computational challenges due to its massive data size and tissue heterogeneity. To address this issue, we present a Gaussian mixture based multiple instance learning (MIL) framework for WSI analysis with partially subsampled instances. Our approach models a WSI as a bag of instances (i.e., randomly cropped sub-images), leveraging a bag-based maximum likelihood
estimator (BMLE) to predict metastases. Furthermore, we introduce a subsampling-based maximum likelihood
estimator (SMLE) to refine predictions by selectively labeling a subset of instances. Extensive evaluations of the breast carcinoma metastasis prediction demonstrate that BMLE surpasses state-of-the-art methods, while the SMLE further improves the prediction accuracy at both bag and instance levels. We find that our method is fairly robust against various plausible model mis-specifications. Theoretical analyses and simulation studies validate the performance and robustness of our methods.
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All authors Baichen Yu, Xuetong Li, Jing Zhou, Hansheng Wang
Statistics Applications
Improving post-operative discharge destination prediction of geriatric patients with generative data augmentation
Pegah Golchian, Pauline Maier, Thomas Kocar et al. (+1 more)
Data scarcity challenges the development and implementation of innovative healthcare solutions. In geriatrics, fall-related injuries are a major cause of hospitalization, functional decline, and mortality in older adults. Optimizing post-operative discharge planning can mitigate these outcomes, but limited data hinders predictive model development. Here, we explored generative machine learning approaches to augment data from the SURGE-Ahead project (Supporting SURgery with Geriatric Co-Management and AI), an initiative addressing geriatric perioperative care. Data from the German geriatric trauma register (AltersTraumaZentrum; ATZ) were incorporated using two strategies: (i) combining SURGE-Ahead and ATZ register data with imputation (ComImp) and (ii) generating synthetic data from SURGE-Ahead alone or combined SURGE-Ahead and the ATZ register
datasets with
Adversarial random forests (ARF). Predictive models, including multinomial logistic regression, random forest, and a prior-fitted
transformer (TabPFN), were trained and evaluated using standard performance metrics: accuracy, area under the receiver operating characteristic curve (ROC AUC), Brier score, and the logistic loss. Random forest and TabPFN performed well (accuracy around 0.84 and AUC around 0.94) and were largely unaffected by augmentation. Logistic regression benefited from augmented data, with predictive performance improving from 0.70 to 0.81 for accuracy and 0.85 to 0.92 for AUC. These results highlight generative data augmentation as a viable approach to enhance simpler predictive models in geriatric care and emphasize the importance of method selection when addressing data scarcity in heterogeneous clinical populations.
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All authors Pegah Golchian, Pauline Maier, Thomas Kocar, Marvin N. Wright
Statistics Theory
Bootstrap consistency for general double/debiased machine learning estimators
Ziming Lin and Fang Han
Double/debiased machine learning (DML) provides a general framework for inference with high-dimensional or otherwise complex nuisance parameters by combining Neyman-orthogonal scores with cross-fitting, thereby circumventing classical Donsker-type conditions in many modern machine-learning settings. Despite its strong empirical performance, bootstrap inference for DML
estimators has received little theoretical justification. This is particularly noteworthy since bootstrap methods are suggested ad used for inference on DML
estimators, even though bootstrap procedures can fail for
estimators that are root-$n$ consistent and asymptotically normal. This paper fills this gap by establishing bootstrap validity for DML
estimators under general exchangeably weighted resampling schemes, with Efron's bootstrap as a special case. Under exactly the same conditions required for the validity of DML itself, we prove that the bootstrap law converges conditionally weakly to the sampling law of the original
estimator.
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Statistics Theory
Learning Mixtures of Nonparametric and Convolutional Measures on Effectively Low-dimensional Affine Spaces
Sunrit Chakraborty and XuanLong Nguyen
In this paper, we develop a finite mixture of convolutional distributions, a statistical model to analyze continuous data distributed approximately on a mixture of low-dimensional affine subspaces. The observations are assumed independent and identically distributed from the mixture of distributions, where each component arises from a convolution of a distribution supported on a low-dimensional subspace with a suitable noise kernel. We discuss theoretical properties of such class of models, including identifiability under very general conditions - in particular, showing that the minimal representation for such mixtures is uniquely identifiable in a semi-parametric setting. We further study the posterior contraction rates for the parameters for a parametrized class of such models where the supports of the component mixing measures are assumed to be convex polytopes under a suitable well-specified
Bayesian regime. This still requires developing novel inverse bounds for problems involving a nested mixture structure, where the mixture kernel is itself another continuous mixture. Our approach for both the identifiability theory and posterior contraction rates is to exploit the
geometric structure of the underlying support of the latent measures. Apart from applications in end-member analysis, spectral unmixing and topic models, this study provides a grounded framework for subspace clustering with the goal of exploring conditions for learning multiple latent low-dimensional structures. We illustrate our findings through careful simulation study, which also includes developing new
algorithms for such class of models
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Machine Learning (Statistics) · Cross-listed from cs.LG
LASER: Low-Rank Activation SVD for Efficient Recursion
Ege Çakar, Ketan Ali Raghu and Lia Zheng
Recursive architectures such as Tiny Recursive Models (TRMs) perform implicit
reasoning through iterative latent computation, yet the
geometric structure of these
reasoning trajectories remains poorly understood. We investigate the activation
manifold of TRMs during recursive unrolling and find that activations occupy an effectively linear, low-dimensional subspace whose principal directions can be tracked dynamically with cheap power iterations. This suggests that weight-sharing concentrates iterative computation along a small number of dominant eigendirections, and we find that this concentration varies sharply across computational sites. We exploit this structure through
LASER (Low-Rank Activation SVD for Efficient Recursion), a dynamic compression framework that maintains an evolving low-rank basis via
matrix-free subspace tracking with a fidelity-triggered reset mechanism, achieving ${\sim}60\%$ activation
memory savings with no statistically significant accuracy degradation. Our analysis raises questions about how recursive architectures allocate representational capacity during implicit
reasoning, and whether this concentration can be exploited to improve the efficiency and stability of latent computation.
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