Diagnosing and managing a patient is a complex, sequential decision making process that requires physicians to obtain information -- such as which tests to perform -- and to act upon it. Recent advances in artificial intelligence (AI) and large language models (LLMs) promise to profoundly impact clinical care. However, current evaluation schemes overrely on static medical question-answering benchmarks, falling short on interactive decision-making that is required in real-life clinical work. Here, we present AgentClinic: a multimodal benchmark to evaluate LLMs in their ability to operate as agents in simulated clinical environments. In our benchmark, the doctor agent must uncover the patient's diagnosis through dialogue and active data collection. We present two open medical agent benchmarks: a multimodal image and dialogue environment, AgentClinic-NEJM, and a dialogue-only environment, AgentClinic-MedQA. We embed cognitive and implicit biases both in patient and doctor agents to emulate realistic interactions between biased agents. We find that introducing bias leads to large reductions in diagnostic accuracy of the doctor agents, as well as reduced compliance, confidence, and follow-up consultation willingness in patient agents. Evaluating a suite of state-of-the-art LLMs, we find that several models that excel in benchmarks like MedQA are performing poorly in AgentClinic-MedQA. We find that the LLM used in the patient agent is an important factor for performance in the AgentClinic benchmark. We show that both having limited interactions as well as too many interaction reduces diagnostic accuracy in doctor agents. The code and data for this work is publicly available at //AgentClinic.github.io.
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We show that the limiting variance of a sequence of estimators for a structured covariance matrix has a general form that appears as the variance of a scaled projection of a random matrix that is of radial type and a similar result is obtained for the corresponding sequence of estimators for the vector of variance components. These results are illustrated by the limiting behavior of estimators for a linear covariance structure in a variety of multivariate statistical models. We also derive a characterization for the influence function of corresponding functionals. Furthermore, we derive the limiting distribution and influence function of scale invariant mappings of such estimators and their corresponding functionals. As a consequence, the asymptotic relative efficiency of different estimators for the shape component of a structured covariance matrix can be compared by means of a single scalar and the gross error sensitivity of the corresponding influence functions can be compared by means of a single index. Similar results are obtained for estimators of the normalized vector of variance components. We apply our results to investigate how the efficiency, gross error sensitivity, and breakdown point of S-estimators for the normalized variance components are affected simultaneously by varying their cutoff value.
While undulatory swimming of elongate limbless robots has been extensively studied in open hydrodynamic environments, less research has been focused on limbless locomotion in complex, cluttered aquatic environments. Motivated by the concept of mechanical intelligence, where controls for obstacle navigation can be offloaded to passive body mechanics in terrestrial limbless locomotion, we hypothesize that principles of mechanical intelligence can be extended to cluttered hydrodynamic regimes. To test this, we developed an untethered limbless robot capable of undulatory swimming on water surfaces, utilizing a bilateral cable-driven mechanism inspired by organismal muscle actuation morphology to achieve programmable anisotropic body compliance. We demonstrated through robophysical experiments that, similar to terrestrial locomotion, an appropriate level of body compliance can facilitate emergent swim through complex hydrodynamic environments under pure open-loop control. Moreover, we found that swimming performance depends on undulation frequency, with effective locomotion achieved only within a specific frequency range. This contrasts with highly damped terrestrial regimes, where inertial effects can often be neglected. Further, to enhance performance and address the challenges posed by nondeterministic obstacle distributions, we incorporated computational intelligence by developing a real-time body compliance tuning controller based on cable tension feedback. This controller improves the robot's robustness and overall speed in heterogeneous hydrodynamic environments.
We demonstrate a comprehensive semiparametric approach to causal mediation analysis, addressing the complexities inherent in settings with longitudinal and continuous treatments, confounders, and mediators. Our methodology utilizes a nonparametric structural equation model and a cross-fitted sequential regression technique based on doubly robust pseudo-outcomes, yielding an efficient, asymptotically normal estimator without relying on restrictive parametric modeling assumptions. We are motivated by a recent scientific controversy regarding the effects of invasive mechanical ventilation (IMV) on the survival of COVID-19 patients, considering acute kidney injury (AKI) as a mediating factor. We highlight the possibility of "inconsistent mediation," in which the direct and indirect effects of the exposure operate in opposite directions. We discuss the significance of mediation analysis for scientific understanding and its potential utility in treatment decisions.
The integrated nested Laplace approximation (INLA) method has become a popular approach for computationally efficient approximate Bayesian computation. In particular, by leveraging sparsity in random effect precision matrices, INLA is commonly used in spatial and spatio-temporal applications. However, the speed of INLA comes at the cost of restricting the user to the family of latent Gaussian models and the likelihoods currently implemented in {INLA}, the main software implementation of the INLA methodology. {inlabru} is a software package that extends the types of models that can be fitted using INLA by allowing the latent predictor to be non-linear in its parameters, moving beyond the additive linear predictor framework to allow more complex functional relationships. For inference it uses an approximate iterative method based on the first-order Taylor expansion of the non-linear predictor, fitting the model using INLA for each linearised model configuration. {inlabru} automates much of the workflow required to fit models using {R-INLA}, simplifying the process for users to specify, fit and predict from models. There is additional support for fitting joint likelihood models by building each likelihood individually. {inlabru} also supports the direct use of spatial data structures, such as those implemented in the {sf} and {terra} packages. In this paper we outline the statistical theory, model structure and basic syntax required for users to understand and develop their own models using {inlabru}. We evaluate the approximate inference method using a Bayesian method checking approach. We provide three examples modelling simulated spatial data that demonstrate the benefits of the additional flexibility provided by {inlabru}.
Evidence to guide healthcare decisions is often limited by a lack of relevant and trustworthy literature as well as difficulty in contextualizing existing research for a specific patient. Large language models (LLMs) could potentially address both challenges by either summarizing published literature or generating new studies based on real-world data (RWD). We evaluated the ability of five LLM-based systems in answering 50 clinical questions and had nine independent physicians review the responses for relevance, reliability, and actionability. As it stands, general-purpose LLMs (ChatGPT-4, Claude 3 Opus, Gemini Pro 1.5) rarely produced answers that were deemed relevant and evidence-based (2% - 10%). In contrast, retrieval augmented generation (RAG)-based and agentic LLM systems produced relevant and evidence-based answers for 24% (OpenEvidence) to 58% (ChatRWD) of questions. Only the agentic ChatRWD was able to answer novel questions compared to other LLMs (65% vs. 0-9%). These results suggest that while general-purpose LLMs should not be used as-is, a purpose-built system for evidence summarization based on RAG and one for generating novel evidence working synergistically would improve availability of pertinent evidence for patient care.
We address the problem of the best uniform approximation of a continuous function on a convex domain. The approximation is by linear combinations of a finite system of functions (not necessarily Chebyshev) under arbitrary linear constraints. By modifying the concept of alternance and of the Remez iterative procedure we present a method, which demonstrates its efficiency in numerical problems. The linear rate of convergence is proved under some favourable assumptions. A special attention is paid to systems of complex exponents, Gaussian functions, lacunar algebraic and trigonometric polynomials. Applications to signal processing, linear ODE, switching dynamical systems, and to Markov-Bernstein type inequalities are considered.
A functional nonlinear regression approach, incorporating time information in the covariates, is proposed for temporal strong correlated manifold map data sequence analysis. Specifically, the functional regression parameters are supported on a connected and compact two--point homogeneous space. The Generalized Least--Squares (GLS) parameter estimator is computed in the linearized model, having error term displaying manifold scale varying Long Range Dependence (LRD). The performance of the theoretical and plug--in nonlinear regression predictors is illustrated by simulations on sphere, in terms of the empirical mean of the computed spherical functional absolute errors. In the case where the second--order structure of the functional error term in the linearized model is unknown, its estimation is performed by minimum contrast in the functional spectral domain. The linear case is illustrated in the Supplementary Material, revealing the effect of the slow decay velocity in time of the trace norms of the covariance operator family of the regression LRD error term. The purely spatial statistical analysis of atmospheric pressure at high cloud bottom, and downward solar radiation flux in Alegria et al. (2021) is extended to the spatiotemporal context, illustrating the numerical results from a generated synthetic data set.
Many economic panel and dynamic models, such as rational behavior and Euler equations, imply that the parameters of interest are identified by conditional moment restrictions. We introduce a novel inference method without any prior information about which conditioning instruments are weak or irrelevant. Building on Bierens (1990), we propose penalized maximum statistics and combine bootstrap inference with model selection. Our method optimizes asymptotic power by solving a data-dependent max-min problem for tuning parameter selection. Extensive Monte Carlo experiments, based on an empirical example, demonstrate the extent to which our inference procedure is superior to those available in the literature.
This contribution introduces a model order reduction approach for an advection-reaction problem with a parametrized reaction function. The underlying discretization uses an ultraweak formulation with an $L^2$-like trial space and an 'optimal' test space as introduced by Demkowicz et al. This ensures the stability of the discretization and in addition allows for a symmetric reformulation of the problem in terms of a dual solution which can also be interpreted as the normal equations of an adjoint least-squares problem. Classic model order reduction techniques can then be applied to the space of dual solutions which also immediately gives a reduced primal space. We show that the necessary computations do not require the reconstruction of any primal solutions and can instead be performed entirely on the space of dual solutions. We prove exponential convergence of the Kolmogorov $N$-width and show that a greedy algorithm produces quasi-optimal approximation spaces for both the primal and the dual solution space. Numerical experiments based on the benchmark problem of a catalytic filter confirm the applicability of the proposed method.
An essential problem in statistics and machine learning is the estimation of expectations involving PDFs with intractable normalizing constants. The self-normalized importance sampling (SNIS) estimator, which normalizes the IS weights, has become the standard approach due to its simplicity. However, the SNIS has been shown to exhibit high variance in challenging estimation problems, e.g, involving rare events or posterior predictive distributions in Bayesian statistics. Further, most of the state-of-the-art adaptive importance sampling (AIS) methods adapt the proposal as if the weights had not been normalized. In this paper, we propose a framework that considers the original task as estimation of a ratio of two integrals. In our new formulation, we obtain samples from a joint proposal distribution in an extended space, with two of its marginals playing the role of proposals used to estimate each integral. Importantly, the framework allows us to induce and control a dependency between both estimators. We propose a construction of the joint proposal that decomposes in two (multivariate) marginals and a coupling. This leads to a two-stage framework suitable to be integrated with existing or new AIS and/or variational inference (VI) algorithms. The marginals are adapted in the first stage, while the coupling can be chosen and adapted in the second stage. We show in several examples the benefits of the proposed methodology, including an application to Bayesian prediction with misspecified models.
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