Papers

Observation refinement changes posterior uncertainty and the likelihood calculation in pseudo-marginal MCMC. We compare their combined effect through finite-run squared-error risk. A sufficient inversion condition relates information gain to accepted event flow and coarse-kernel contraction. A bootstrap construction realizes inversion at every fixed particle count. We then couple cross-event proposals and refresh same-event proposals independently. A swap identity establishes invariance; continuation identities describe subsequent risk. In the same finite model, a rational certificate proves inversion against optimized constant mixtures and repair by selective allocation over an initialization class at a common action-price budget. Reaction-network experiments measure CPU costs. Under finite-pool initialization, selective allocation reduces event mean-squared error by 40.5% against a tuned mixture at 25 post-initialization CPU seconds. Paired transcription observations show how increased particle effort can raise finite-budget error.

We conduct a retrospective analysis of COVID-19 transmission dynamics across U.S. states using a modified population-based Susceptible-Exposed-Infectious-Asymptomatic-Recovered-Deceased (SEIARD) compartmental model. The proposed framework introduces time-varying transmission, reporting, and mortality rates to capture temporal variations in public behavior and policy interventions during the pandemic. In particular, the transmission rate is modeled as a function of population mobility (derived from Google Mobility Reports), with a residual time-decay term capturing the net effect of unobserved factors such as behavioral adaptation and control measures, while reporting is linked to nationwide testing strategies. We employ a Bayesian approach to integrate multiple data sources and quantify uncertainties in model parameters. The model explicitly distinguishes between symptomatic and asymptomatic infectious individuals and links the latent epidemic states to observable quantities, including reported cases and deaths, through a dynamic reporting function. This retrospective modeling framework provides insights into state-level epidemic trajectories and supports data-driven decision-making for optimal allocation of healthcare resources and evaluation of public health interventions during future pandemics. We further apply a clustering analysis to the posterior parameter estimates to identify groups of U.S. states exhibiting similar epidemiological characteristics, revealing substantial regional heterogeneity in transmission intensity, reproduction dynamics, and mortality burden.

This paper develops the statistical foundations of a multivariate general nesting spatio-temporal (MGNST) regression framework for analyzing spatial, temporal, and cross-equation dependence among responses. Four parameter matrices represent spatial lag dependence, spatial error dependence,temporal autoregression, and contemporaneous error covariance. Their off-diagonal elements allow dependence to propagate within and across responses. Matrix restrictions yield eleven specifications encompassing multivariate spatial autoregressive models, multivariate spatial error models, vector autoregressive models with exogenous variables, and independent spatio-temporal regressions as special cases. We establish identifiability conditions using instrumental-variable rank conditions and introduce penalized likelihood estimation and information criteria based on effective degrees of freedom. Monte Carlo experiments examine three data-generating models, three sample sizes, and three levels of spatial dependence. Correct-selection rates under penalized AIC generally increase with sample size and the strength of spatial dependence, while parameter recovery improves as the sample size increases. For socioeconomic data from 198 municipalities in Japan's Kansai region, penalized AIC selects the full MGNST model, whereas penalized BIC selects a response-wise independent spatial error model. Despite selecting models of different complexity, both criteria support temporal persistence and spatial error dependence. The pAIC-selected MGNST model reduces strong spatial autocorrelation in the responses to negligible residual levels, demonstrating its usefulness for identifying and comparing multivariate spatio-temporal dependence structures.

Moment restrictions provide a flexible basis for quasi-Bayesian inference when a full likelihood is unavailable, but the weighting matrix in a quadratic moment criterion determines both the relative importance of the moments and the information scale of posterior updating. We propose curvature-calibrated quasi-Bayesian updating, which uses the inverse of the covariance (or long-run covariance) of the moment conditions evaluated at a self-consistent quasi-posterior center. The resulting fixed-point procedure alternates between covariance estimation and simulation from a fixed-weight quasi-posterior, thereby avoiding parameter-dependent weighting during each simulation run. Under a Bernstein-von Mises condition for the fixed-weight quasi-posterior at the efficient population weight, we show that the calibration map is locally contractive, that its fixed point is consistent at the standard parametric rate, and that the Gaussian approximation continues to hold under the calibrated data-dependent weight, with covariance given by the inverse Godambe information matrix. Under a uniform fourth-moment condition, the scaled quasi-posterior covariance converges to the same matrix, so quasi-posterior and repeated-sampling uncertainty agree to first order. Simulations show improved covariance calibration and interval coverage after a few updates. An application to longitudinal binary-response data illustrates the method with within-subject dependence and overidentified residual moments.

Goal-oriented optimal experimental design (GO-OED) selects experiments according to the expected information gain (EIG) about a quantity of interest (QoI) rather than the full parameter vector. This work develops a variational GO-OED formulation for mixed discrete-continuous QoI laws arising in probabilistic mechanics when thresholding or event-based transformations map a positive-probability set of uncertain inputs to a common value while other inputs produce continuously varying responses. The motivating application is ship roll safety assessment in random waves, where the QoI is the temporal exceedance probability above a prescribed roll-angle threshold. This quantity is zero when no exceedance occurs and varies continuously over positive values otherwise. A purely continuous variational approximation does not dominate a posterior QoI law containing an atom, yielding an infinite Kullback-Leibler divergence and a trivial Barber-Agakov lower bound of $-\infty$. Scoring atom samples using continuous density values instead changes the objective and does not produce a valid lower-bound estimator. We introduce a mixed variational approximation that models the conditional atom probability and continuous component separately, with a normalizing flow used for the latter. An analytical example recovers the correct EIG landscape, while the ship roll application provides stable EIG lower-bound estimates and identifies informative wave conditions for temporal-exceedance-probability inference.

To address the computational and storage challenges often encountered in large-scale survival data analysis, we propose an efficient Poisson subsampling method for the partially linear additive Cox model. This model provides a flexible yet interpretable framework by incorporating linear covariate effects, additive nonparametric components for nonlinear covariates, and a nonparametric baseline hazard function. The proposed method adopts B-spline basis functions to approximate the nonparametric components and employs the decorrelated score technique to construct a Poisson subsampling-based estimation equation, based on which we establish the asymptotic normality of the resulting estimator and derive the optimal subsampling probabilities according to the L-optimality criterion. Furthermore, we design a two-step adaptive algorithm for practical implementation. The proposed approach enables computationally efficient statistical inference for large-scale survival analysis without processing the full dataset. We validate the performance of the proposed method through extensive simulation studies and a real-world application to a lymphoma cancer dataset, demonstrating its efficiency and accuracy in large-scale settings.

Biological research and clinical evidence suggest that treatment response may vary substantially along characteristics, such as comorbidities, genetic variants, environmental, or socio-economic factors. Future precision medicine requires accurate assessment of heterogeneous treatment effects (HTE) to guide optimal clinical decisions at the individual level. We introduce a functional score framework that extends the traditional estimating equations for survival data to nonparametric HTE and generalize the Neyman orthogonality accordingly, thus filling a methodological as well as theoretical gap. Under the Neyman orthogonal functional score framework, we developed the martingale R-learner based on a decomposition of the conditional martingale residuals into residuals of the risk-set propensity score and the marginal martingale, thereby reducing the impact of estimation bias in HTE from nuisance models including (1) marginal survival, and (2) risk-set propensity scores. This enables leveraging advances in machine learning and incorporates flexible estimators for the nuisance functions and attaining the standard optimal nonparametric estimation rate with the oracle property. Numerical experiments demonstrated empirical performance consistent with the theory. We applied the martingale R-learner to estimate the effect of alcohol on dementia using the Honolulu-Asia Aging Study data.

Imputation-based data fusion combines datasets by imputing missing variables in one dataset using information from the other. The validity of imputation-based data fusion relies on accurately preserving both the imputed distributions and the underlying multivariate dependence structure across data sources. However, traditional imputation-based data fusion methods often struggle to preserve the dependence structure, particularly when marginal distributions differ or when complex, nonlinear multivariate dependencies exist. Inadequate preservation of these dependencies can result in distorted joint distributions and biased inference in the fused data. To address this challenge, this study introduces a novel imputation-based data fusion framework that utilises conditional sampling from C-vine and D-vine copulas as the imputation mechanism. This approach flexibly models pairwise and higher-order dependencies while accommodating heterogeneous marginal distributions, thereby generating imputations that more accurately maintain the distribution of the multivariate data. The proposed method is validated through a simulation study using survey data and a real-data application that estimates the negative income distribution in survey data using information from administrative tax records. Results indicate that the proposed method outperforms existing approaches in preserving both the imputed distributions and the dependence structure across datasets.

Diagnostic medical tests and devices provide useful information for evaluating the potential benefits and risks of therapeutic treatments. However, unlike treatments, their impact on health outcomes is generally indirect because measuring diagnostic information typically does not itself affect patient outcomes, which complicates evaluation of their effectiveness. In this work, we develop a causal inference approach for evaluating diagnostic tests by distinguishing explanatory and pragmatic effectiveness. Explanatory effectiveness evaluates whether a diagnostic test result provides treatment-relevant information beyond baseline covariates by explaining additional treatment-effect heterogeneity, which we characterize using a variance-based treatment-effect variable importance measure. Pragmatic effectiveness evaluates whether incorporating this information into personalized treatment decisions improves expected outcomes, a question central to decision-making for patients, clinicians, and other health care stakeholders. We formalize pragmatic effectiveness as a contrast between expected outcomes under optimal personalized treatment rules defined with and without access to the diagnostic test result. We establish identification of the proposed estimand and provide Targeted Maximum Likelihood Estimation (TMLE) and cross-validated TMLE procedures for nonparametric estimation and inference. Simulation studies and a synthetic colorectal cancer application illustrate the proposed estimands and estimation performance. More broadly, this approach provides a causal inference perspective for evaluating AI-enabled devices by distinguishing their dual roles as information-enrichment and personalized decision-optimization tools, clarifying whether AI improves outcomes by expanding information for downstream decisions, improving the decision rule used to act on that information, or through both pathways.

Covariate adjustment improves estimation efficiency in randomized experiments, but standard calibration and augmentation methods, when applied to distribution or survival functions, do not preserve monotonicity—a fundamental property of the estimand. We propose using empirical likelihood with covariate-balancing constraints to construct a covariate-adjusted empirical measure for each treatment arm. Estimators of a broad class of distributional functionals, including cumulative distribution functions, survival functions, quantiles, and restricted mean survival times, are then derived as plug-in functionals of this measure, automatically inheriting proper shape constraints. We establish asymptotic normality with an explicit, guaranteed efficiency gain over unadjusted estimators. The asymptotic distributions are invariant to the randomization scheme, providing a unified inference procedure under simple randomization and all commonly used covariate-adaptive designs satisfying a mild balancing condition. This unified construction, adjusting the empirical measure once and deriving all estimators from it, offers a principled reconciliation of covariate adjustment with shape preservation. Simulations and an application to the SURPASS-4 trial confirm the theoretical gains.

Average dose-response functions are widely used to summarize causal effects of continuous treatments, but most existing methods assume that the observed sample represents the target population. We study a covariate-shift setting in which covariates, treatment, and outcome are observed in a labelled source sample, while only covariates are observed in the target sample. We develop a two-sample local polynomial regression framework based on pseudo-outcomes that use source outcomes to address confounding and target covariates to define the population of interest. We further propose a source-to-target extension of distance covariance optimal weighting (DCOW), designed to remove treatment-covariate dependence in the source sample while aligning the weighted source covariate distribution with the target population. A central theoretical contribution is a weight-level analysis of this optimization-based procedure: we show that the population criterion identifies the oracle source-to-target weights and that approximate empirical minimizers, including exact minimizers as a special case, converge uniformly to these weights under regularity conditions. We also establish consistency and asymptotic normality of the resulting estimator. Simulations show that the proposed method improves target dose-response estimation relative to DCOW, generalized-propensity-score weighting, entropy balancing, and unweighted alternatives. We illustrate the method in a county-level analysis of PM2.5 exposure and subsequent heart-disease mortality using a source-target validation design.

When factor scores replace true latent scores in nonlinear prediction, measurement error attenuates the recoverable variance of any $k$th-order component of the regression function by $\rho^k$ – the $k$th power of the score's coefficient of determination – for any linear score type. This study derives the bound via Hermite polynomial expansion and proposes PV-ANN – plausible values (posterior draws preserving latent variance) combined with artificial neural networks (learning functional form without prespecification). The bound governs recovery of the latent-scale function, not prediction of the outcome from observed indicators, for which factor scores are already sufficient; the two metrics are therefore predicted to dissociate. An 18-condition simulation supports both predictions: in the nonlinear low-reliability conditions PV-ANN closes about four fifths of the function-shape recovery gap between a factor-score learner and one given the true latent values, and the margin widens as reliability falls, while predictive accuracy is not improved, as the theory requires. A Big Five application illustrates the intended exploratory workflow and delineates boundary conditions under weak signal and measurement model misspecification.

Despite the wide variety of existing Buy-`Til-You-Die (BTYD) models, nearly all rely upon the convenient assumption of transactions following a Poisson process. As modern customer bases grow larger and more diverse, a major gap in the marketing literature is BTYD models that can account for heterogeneity in timing patterns across millions of customers. This paper addresses that gap, introducing a family of models that assume transactions follow a Weibull renewal process and developing a highly scalable scheme for parameter estimation based on an amortized variational inference procedure. The proposed model fits to a proprietary dataset of 5 million online retail customers in 8 minutes which would take the current state-of-the-art an estimated 3-4 days. We show both theoretically and empirically that this dramatic improvement in computational performance comes with no appreciable change to either model interpretation or predictive performance. Beyond scalability, gradient-based variational inference also makes it easy to extend the model to covariates, which we illustrate on a public dataset of 4 million political donors during the 2020 US General election cycle. More generally, this paper demonstrates how to blend recent advances in approximate Bayesian inference and the tools of modern machine learning to dramatically improve the efficiency and expressivity of probabilistic models for customer base analysis.

Pairwise randomization can yield substantial efficiency gains in experiments. Yet methodological guidance cautions against pairwise randomization, especially in settings with attrition, partly because common practices for estimation (i.e., pair fixed effects) imply discarding data from incomplete pairs thus exacerbating data loss from attrition. This practice of dropping incomplete pairs reduces statistical power of tests as well as precision of estimates, in paired experiments, compared to designs with less finely stratified treatment assignment. We argue that this concern is misplaced if attrition is independent of treatment status and potential outcomes, and that these issues follow from an inefficient use of the data that remains post-attrition. First, we show how, by using a specific permutation test, it is possible to use all observed units for inference (complete pairs and incomplete pairs where one unit attrits) while still exploiting the pairwise randomization design structure. The test procedure we suggest provides exact size control under the sharp null. Second, we study an optimally weighted estimator that efficiently combines within-pair and across-pair comparisons. Finally, we show that combining these two insights yields a test procedure that dominates the two commonly used inference methods (a paired $t$-test and the two-sample $t$-test) in power, for any level of attrition. Usefully for applied researchers, we show that the efficient procedure can be implemented via a weighted fixed effects regression, straightforward in standard software. In sum, our results provide researchers with practical tools for conducting experiments with pairwise randomization without sacrificing observations or statistical power when facing independent attrition.

Matrix-valued observations arise in multiplex networks, neuroimaging, and other domains where population-level patterns are often low-rank and subjects may express several latent patterns simultaneously. Existing tensor PCA methods provide continuous subject scores but their loading matrices can be difficult to interpret as population prototypes, while low-rank clustering yields interpretable prototypes with hard labels. We introduce a low-rank mixed membership model for matrix-valued data in which the expected value of each subject's matrix is a convex combination of latent low-rank basis matrices. The model yields both interpretable population-level extreme profiles and continuous subject-level memberships. Our multimodal extension shares memberships across modalities with modality-specific basis matrices and can restore identifiability when one modality is insufficient. We establish identifiability under a pure-subject condition, propose a constrained least-squares estimator and scalable algorithm with spectral initialization and low-rank refinement, and derive nonasymptotic error bounds. The estimator achieves a minimax-optimal reconstruction rate up to a logarithmic factor, with separate basis and membership convergence rates under a geometric condition. Simulations corroborate the theoretical rates and show strong performance. In an analysis of Human Connectome Project functional connectivity data, the proposed method identifies interpretable brain connectivity profiles whose estimated memberships are strongly associated with cognitive phenotypes.

Composite likelihood (CL) methods provide a computationally efficient alternative to full likelihood inference for complex multivariate models by replacing the joint likelihood with a product of lower-dimensional marginal or conditional components. Like the MLE, however, the maximum CL estimator (MCLE) is highly sensitive to data contamination. On the other hand, robust divergence-based procedures such as the minimum density power divergence (DPD) estimator require the full joint density and so scale poorly to complex multivariate models. We introduce the composite DPD (CDPD), a genuine statistical divergence built entirely from the low-dimensional component densities defining a CL, combining the computational scalability of CL with the robustness of the DPD. The resulting minimum CDPD estimator (MCDPDE) robustifies the MCLE without requiring integration over the full multivariate sample space. We establish consistency, asymptotic normality, and the influence function of the MCDPDE under regularity conditions on the component models alone, without requiring correct specification of the full joint distribution. We show that it is qualitatively robust for every positive value of its tuning parameter, unlike the MCLE recovered as the limit. Because its components can be chosen at the pairwise or cell level, the framework guards simultaneously against casewise and cellwise contamination. Operating directly on component densities rather than elliptical distance structures, it extends robust inference beyond the elliptical models to which most existing cellwise-robust procedures are confined. We develop computational algorithms implemented in the accompanying R package mvdpd. Simulation studies and real-data applications show that the MCDPDE achieves substantial robustness gains over the MCLE while retaining competitive efficiency under the assumed model.

Inference after variable selection in Cox regression is difficult because simple Wald-type intervals after selection can have poor finite-sample conditional coverage. We study a model-based bootstrap for inference after Cox-Lasso variable selection. The Cox-Lasso is fitted once to the original data to select a set of variables, after which an unpenalized Cox model is fitted using only those variables. Bootstrap samples are generated from a semiparametric plug-in Cox model specified by the coefficient estimate from this unpenalized Cox refit, the Breslow baseline cumulative hazard estimator, and a plug-in censoring distribution. In every bootstrap sample, the selected variable set is kept fixed and only the unpenalized Cox model is refitted. Under oracle-type sparse-model assumptions and standard Cox model regularity conditions, we prove first-order bootstrap validity for this procedure. In the simulation scenarios considered, percentile and studentized bootstrap intervals showed improved conditional coverage relative to the bootstrap-Wald interval in several small- and moderate-sample settings. Their performance was broadly competitive with debiased intervals, although the comparison depended on signal strength, tuning, and selection stability. A SEER breast cancer example illustrates that the procedure can be implemented in a realistic survival analysis and provides interpretable uncertainty quantification for effects reported after variable selection.

Background: Joint models for longitudinal and time-to-event data are widely used in clinical research. However, the choice of functional form linking the biomarker trajectory to event risk is often treated as a technical detail, despite its importance for model assumptions and interpretation. Default specifications may fail to capture clinically relevant features of biomarker trajectories. Methods: We provide a structured overview of functional forms linking longitudinal and survival processes in joint models. We compare association structures including instantaneous effects (current value, slope, and acceleration), cumulative and change-based formulations, shared random effects, and variability-based associations. Using longitudinal white blood cell measurements and overall survival data from the MIRAGE glioblastoma trial, we illustrate how different functional forms capture distinct features of biomarker trajectories and define different biomarker-risk relationships. Results: Instantaneous forms capture the biomarker's current level or short-term dynamics, whereas cumulative and change-based forms reflect longer-term exposure or trends. Variability-based structures quantify instability in the biomarker trajectory as an alternative prognostic signal. Association parameters depend on the functional form, biomarker scale, and time scale, and effect sizes are therefore not directly comparable. In the MIRAGE application, alternative functional forms produced different effect interpretations and, in some cases, different conclusions regarding the biomarker-risk relationship. Conclusions: The choice of functional form is a key modelling decision in joint models and determines the interpretation of the biomarker-risk association. Aligning the functional form with the scientific question is essential for valid interpretation and transparent reporting.

Tabular foundation models (TFMs) achieve strong performance through in-context learning, but context-dependent inference imposes substantial latency and memory costs, hindering large-scale deployment. We propose GEAR (Generative Expansion and Real Anchoring), a modular two-stage framework that distills TFMs into lightweight MLP or tree-based predictors that can be deployed on commodity CPUs. Stage 1 uses synthetic covariates solely as teacher-query locations and trains the student on soft TFM targets, expanding coverage beyond observed rows. Stage 2 re-anchors the student to the target distribution using real labels and out-of-fold teacher predictions, whitch avoids self-labeling leakage. We further derive a risk certificate characterizing the trade-off between generated-query volume and generator fidelity. Experiments on TALENT and TabArena demonstrate the broad applicability of GEAR. Two-stage MLPs outperform supervised MLPs by 1.81–2.00 AUC points on binary tasks and 1.19–1.35 points on multiclass tasks, with additional gains over real-data-only distillation of 1.76–2.19 and 2.09–2.40 points, respectively. On binary tasks, the gains also transfer to LightGBM and XGBoost, and all three student families outperform CatBoost, the strongest non-TFM baseline, in mean AUC. Ablations show gains beyond longer training or alternative warm starts, greater stability from staged than mixed optimization, and generator-dependent diminishing returns as query volume increases. Finally, GEAR reduces median inference time by 57–2866 times and peak prediction memory by 1.9–3.3 times, while retaining higher AUC than matched supervised baselines.

In some fields currently dominated by empirical approaches, such as state of health (SoH) prediction for lithium-ion batteries, phenomenological models motivated by quasi-physical thinking contain parameters to be estimated from experimental data. Often the structure of such models yields fully or partially confounded parameters, which are difficult or even impossible to estimate reliably. To preserve the desired model formulation and simultaneously improve the numerical conditioning for the problem we introduce a ridge regression scheme. An automated method is provided, based on information theoretic measures of model performance, which optimises the ridge regression hyper-parameter at each iteration. The formulae presented require fixed point iteration to solve for the hyper-parameter. Given a suitable starting value, analysis demonstrates convergence is very rapid. The optimal hyper-parameter selection mechanism is incorporated within an efficient regularised iterative generalised least squares mechanism, capable of fitting both heteroscedastic and serially correlated data as required. Simulation confirms the efficacy of the overall method.

Extreme value theory provides a fundamental framework for modeling rare and extreme events; however, threshold selection remains a persistent challenge, particularly in the presence of inliers such as instantaneous or early failures. Such observations commonly arise in applications including reliability studies and environmental data, where clusters of observations near the origin or at the origin can substantially distort classical threshold selection procedures and tail inference. In this paper, we propose a robust modeling framework that accounts for inliers, extremes, and the tail proportion. Parameter estimation is carried out using maximum likelihood. The proposed methodology is compared with classical numerical and graphical diagnostic tools, including the mean excess plot, parameter stability plot, Hill plot, and Pickands plot, as well as existing extreme value mixture models. The theoretical properties of the proposed model are established, and its performance is evaluated through extensive Monte Carlo simulations and real-data applications. The results demonstrate that the proposed methodology provides more accurate threshold estimation and more reliable extreme-value inference in the presence of inliers compared with existing classical approaches. Overall, the proposed methodology provides more accurate threshold estimation and tail inference in the presence of inliers, addressing key limitations of existing methods.

Online changepoint detection is the problem of detecting distributional changes in a data stream in real-time. A large body of methodology exists for the offline (fixed-size) setting, but applying these methods online quickly becomes infeasible since the per-observation computational cost and memory consumption typically grow at least linearly with the sample size. A recently proposed grid-based methodology (Moen, 2026) overcomes this by evaluating an offline test statistic over a sparse geometric grid of split points, with grid points spaced increasingly far apart further in the past. For a wide class of test statistics, this approach keeps update time and memory consumption growing logarithmic in the length of the data stream, while admitting finite-sample guarantees on the detection delay. Building on this methodology, we present gridcp, an open-source Python package that turns offline changepoint tests into efficient online detectors through a single, uniform interface. Users can choose from nine Numba-accelerated built-in tests, spanning changes in the mean, variance, covariance, and regression coefficients, as well as nonparametric tests and generalized likelihood-ratio tests for exponential-family models. Users can also supply their own test, which the package handles identically. For any test, gridcp provides Monte Carlo routines that calibrate the detection threshold to a target false alarm probability or average run length, including data-driven variants when no parametric null model is available. Through simulations and three real-data case studies, we show that calibration is accurate, that runtime scales favorably with both stream length and dimension, and that the complete pipeline, from calibration to deployment, runs efficiently on long real-world streams with only a short detection delay.

Researchers often choose a proxy dataset from many releases, transformations, or seeds. Search can make an invalid release appear adequate, while one adequate release does not establish that its generator is reliable. ProxyGuard controls both errors using prespecified bounded risks and a sealed target set. Named-release mode corrects for multiplicity and certifies specific releases. Direct shared-target mode evaluates independent mechanism draws on a common target, lower-bounds their favorable-score rate, and subtracts a bound on favorable scores contributed by invalid releases. Conditional on the target, release scores are independent, yielding a finite-sample mechanism-reliability guarantee without independent target batches or assumptions on release-level $p$-value dependence. We show that the mean-only penalty is sharp and derive a smooth-score certificate with additive target concentration. In a registered three-requirement study, direct mode raises power from 5.6% to 64.2% at reliability 0.95, while named mode remains stronger under high-signal evidence. Prospective audits span full-pipeline Rice–TVAE, which retrains on every draw, and a non-tabular text mechanism.

Building on a reparameterization for multivariate linear regression that yields a jointly convex penalized likelihood in the reparameterized regression coefficient matrix and the precision matrix, we show that the resulting scaled Gaussian loss is standard self-concordant. This places the joint estimation problem within composite self-concordant optimization and leads to two algorithms: a proximal gradient method and a damped proximal Newton method. In simulations, we evaluate algorithmic robustness, iterations to convergence, and elapsed time. In a protein expression application, compared with the classical-parameterization formulation, the proposed convex formulation attains similar mean squared prediction error and can be substantially faster when the fitted precision matrix is dense.

The emergence of molecular-targeted agents and immune-oncology therapies has fundamentally transformed oncology drug development, necessitating evolution beyond traditional dose-finding approaches designed for cytotoxic agents. While conventional agents exhibit predictable monotonic dose-response relationships, novel anticancer agents often demonstrate plateau-effect patterns where higher doses may compromise therapeutic benefit, requiring identification of optimal biological doses that balance efficacy and tolerability. The FDA's Project Optimus initiative emphasizes comprehensive dose optimization through parallel randomized cohorts and patient backfilling to better understand pharmacological profiles across multiple dose levels. Contemporary drug development increasingly prioritizes combination therapy alongside monotherapy evaluation, yet existing designs typically assume equivalent roles for both agents, diverging from clinical practice where novel agents combine with established treatments having limited dose options. This paper proposes a seamless dose-optimization design that adaptively evaluates both monotherapy and combination therapy based on efficacy and toxicity outcomes through adaptive subtrials with patient backfilling capabilities. The model-assisted framework employs predetermined Bayesian optimal boundaries, eliminating real-time model fitting while accommodating evaluation of both monotherapy and combination therapy and enabling sequential enrollment with strategic backfilling. Simulation studies demonstrate robust performance across diverse dose-response patterns relevant to contemporary oncology. The design addresses critical gaps between methodological assumptions and clinical reality, offering a practical approach that integrates monotherapy and combination therapy evaluation with efficacy-toxicity-based backfilling.

This paper proposes a multi-level Bayesian calibration approach that fuses information from heterogeneous sources and accounts for uncertainties in modeling and measurements for time-dependent multi-component systems. The developed methodology has two elements: quantifying the uncertainty at component and system levels, by fusing all available information, and corrected model prediction. A multi-level Bayesian calibration approach is developed to estimate component-level and system-level parameters using measurement data that are obtained at different time instances for different system components. Such heterogeneous data are consumed in a sequential manner, and an iterative strategy is developed to calibrate the parameters at the two levels. This calibration strategy is implemented for two scenarios: offline and online. The offline calibration uses data that is collected over all the time-steps, whereas online calibration is performed in real-time as new measurements are obtained at each time-step. Analysis models and observation data for the thermo-mechanical behavior of gas turbine engine rotor blades are used to analyze the effectiveness of the proposed approach.

Matching for causal inference can be computationally expensive at scale and can silently change the target population when overlap is limited. We propose Centroid-Referenced Mahalanobis Matching (CRM), which replaces global pairwise search with stratified sampling in two reference coordinates: each unit's Mahalanobis distance from the treated centroid and its Fisher coordinate along the treated-control mean shift. All covariates enter through the treated covariance geometry; CRM is therefore not principal-component preprocessing followed by nearest-neighbor matching. For $n$ units and $p$ pretreatment covariates, its implemented cost is $O(np^2+p^3+n\log n)$, simplifying to $O(np^2+n\log n)$ when $n \ge p$. We derive an error decomposition separating representation, support, discretization, and stochastic components. A pre-matching shortage fraction $\hat{\pi}$ estimates the population support restriction $\pi$, which enters a gap bound under bounded treatment-effect heterogeneity. Final retention is reported separately for capacity-driven exclusions. Under representation sufficiency, smoothness, and adequate cell capacity, CRM has a conservative two-dimensional histogram mean-squared-error bound $O(n_T^{-1/2})$; representation sufficiency is an additional assumption, not a consequence of ignorability given the original covariates. On Criteo, CRM retains at least 99.4% of treated units, has lower MaxSMD than corrected propensity-score matching in 31 of 36 large-scale configurations, and is roughly an order of magnitude faster. Moderate-size simulations favor some pairwise and weighting baselines on balance, locating CRM's contribution in scalability and explicit support diagnostics rather than universal finite-sample dominance.

Ocean eddies are highly dynamic structures marked by frequent splitting and merging events. They exhibit complex spatio-temporal clustering that traditional Poisson models fail to capture. In this paper, a novel spatio-temporal Hawkes process is introduced to model self-exciting eddy fields on the basis of high-frequency ocean flow data. We formulate a triggering kernel that couples the self-excitation intensity with spatial deformation caused by the strain rate magnitude. To characterize the asymptotic behavior of the eddy field, we derive a Volterra integral equation that governs the expected eddy intensity over time and space. We develop an Expectation-Maximization (EM) algorithm that treats the unobserved parent-child relationships as latent branching structures for parameter estimation. We further extend this framework to accommodate a time-varying, non-homogeneous background intensity, modifying both the EM updates and the analytical Volterra solution accordingly. Finally, we propose a two-stage simulation framework utilizing a cluster representation algorithm. The simulated empirical paths of eddy formation are compared together with numerical solution of the Volterra equation for mean rate as validation of the Hawkes model.

Adaptive therapy has emerged as a promising treatment strategy that exploits within-tumour competition to delay disease progression. Implementation, however, typically relies on indirect measurements of tumour burden and must account for potentially substantial patient heterogeneity. In this work, we capture patient-to-patient variability, parameter uncertainty, and imperfect biomarker measurements with a mathematical and statistical model that we calibrate to clinical prostate cancer data using a Bayesian inference framework. We use the resulting virtual cohort to demonstrate that, within the simple but now well-established Lotka-Volterra-based model, adaptive therapy robustly improves time-to-progression for the subset of patients that are predicted to eventually progress by the model. To account for other risk factors associated with larger tumour volumes, we introduce a new metric based on the risk of metastasis that demonstrates how adaptive therapy may be disadvantageous when sustained tumour burden is also considered. Given the ubiquity of uncertainty in oncology, we then describe several future modelling directions that also capture uncertainty in the temporal evolution of the underlying tumour or biomarker dynamics. Finally, we demonstrate how model misspecification and non-identifiability can lead to unreliable predictions, especially if uncertainty is inadequately captured.

Bayesian targets may converge under model refinement even when the exact sensitivities used by gradient-based samplers do not. We study this probability–sensitivity mismatch and its consequences for Metropolized Hamiltonian proposals. A vanishing-amplitude wiggly-energy model first gives the basic analytic obstruction: the potential perturbation tends to zero while its classical derivative is of order $r_\varepsilon/\varepsilon$. We then show that the same scaling arises naturally in a periodic elliptic inverse problem, where homogenization makes the forward map and Gaussian likelihood converge while differentiation with respect to a microscopic scale parameter retains an $O(1)$ oscillatory contribution. This provides a PDE origin for the single-scale wiggly mechanism. The main construction concerns a more demanding nested Weierstrass hierarchy, interpreted as an analytically tractable prototype for repeated corrector contributions across geometrically separated scales. There all previously resolved scales persist, adjacent classical-force increments grow geometrically like $(ab)^N$, and the limiting rough component may fail to possess a classical derivative. In this self-similar setting the matched Jackson quotient is structurally adapted to the refinement through dilation covariance and exact finite closure. Uniform negative-log-likelihood approximation yields explicit total-variation, Hellinger, and bounded quantity-of-interest bounds. Measurable kick–drift–kick maps remain exact after Metropolis correction, local field convergence propagates to fixed-length proposals and kernels, and the first classical HMC half-kick can have no fixed-step refinement limit. Numerical experiments on scale-structured inverse problems test the resulting resolution-stability mechanism across one- and two-dimensional inverse problems.