Deep Learning models have been successfully utilized to extract clinically actionable insights from routinely available histology data. Generally, these models require annotations performed by clinicians, which are scarce and costly to generate. The emergence of self-supervised learning (SSL) methods remove this barrier, allowing for large-scale analyses on non-annotated data. However, recent SSL approaches apply increasingly expansive model architectures and larger datasets, causing the rapid escalation of data volumes, hardware prerequisites, and overall expenses, limiting access to these resources to few institutions. Therefore, we investigated the complexity of contrastive SSL in computational pathology in relation to classification performance with the utilization of consumer-grade hardware. Specifically, we analyzed the effects of adaptations in data volume, architecture, and algorithms on downstream classification tasks, emphasizing their impact on computational resources. We trained breast cancer foundation models on a large public patient cohort and validated them on various downstream classification tasks in a weakly supervised manner on two external public patient cohorts. Our experiments demonstrate that we can improve downstream classification performance whilst reducing SSL training duration by 90%. In summary, we propose a set of adaptations which enable the utilization of SSL in computational pathology in non-resource abundant environments.
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Synthesizing realistic and diverse indoor 3D scene layouts in a controllable fashion opens up applications in simulated navigation and virtual reality. As concise and robust representations of a scene, scene graphs have proven to be well-suited as the semantic control on the generated layout. We present a variant of the conditional variational autoencoder (cVAE) model to synthesize 3D scenes from scene graphs and floor plans. We exploit the properties of self-attention layers to capture high-level relationships between objects in a scene, and use these as the building blocks of our model. Our model, leverages graph transformers to estimate the size, dimension and orientation of the objects in a room while satisfying relationships in the given scene graph. Our experiments shows self-attention layers leads to sparser (7.9x compared to Graphto3D) and more diverse scenes (16%).
Neural-network models have been employed to predict the instantaneous flow close to the wall in a viscoelastic turbulent channel flow. The numerical simulation data at the wall is utilized to predict the instantaneous velocity fluctuations and polymeric-stress fluctuations at three different wall-normal positions. Apart from predicting the velocity fluctuations well in a hibernating flow, the neural-network models are also shown to predict the polymeric shear stress and the trace of the polymeric stresses at a given wall-normal location with reasonably good accuracy. These non-intrusive sensing models can be integrated in an experimental setting to construct the polymeric-stress field in turbulent flows, which otherwise may not be directly quantifiable in experimental measurements.
We provide full theoretical guarantees for the convergence behaviour of diffusion-based generative models under the assumption of strongly log-concave data distributions while our approximating class of functions used for score estimation is made of Lipschitz continuous functions. We demonstrate via a motivating example, sampling from a Gaussian distribution with unknown mean, the powerfulness of our approach. In this case, explicit estimates are provided for the associated optimization problem, i.e. score approximation, while these are combined with the corresponding sampling estimates. As a result, we obtain the best known upper bound estimates in terms of key quantities of interest, such as the dimension and rates of convergence, for the Wasserstein-2 distance between the data distribution (Gaussian with unknown mean) and our sampling algorithm. Beyond the motivating example and in order to allow for the use of a diverse range of stochastic optimizers, we present our results using an $L^2$-accurate score estimation assumption, which crucially is formed under an expectation with respect to the stochastic optimizer and our novel auxiliary process that uses only known information. This approach yields the best known convergence rate for our sampling algorithm.
Test-negative designs are widely used for post-market evaluation of vaccine effectiveness, particularly in cases where randomization is not feasible. Differing from classical test-negative designs where only healthcare-seekers with symptoms are included, recent test-negative designs have involved individuals with various reasons for testing, especially in an outbreak setting. While including these data can increase sample size and hence improve precision, concerns have been raised about whether they introduce bias into the current framework of test-negative designs, thereby demanding a formal statistical examination of this modified design. In this article, using statistical derivations, causal graphs, and numerical simulations, we show that the standard odds ratio estimator may be biased if various reasons for testing are not accounted for. To eliminate this bias, we identify three categories of reasons for testing, including symptoms, disease-unrelated reasons, and case contact tracing, and characterize associated statistical properties and estimands. Based on our characterization, we show how to consistently estimate each estimand via stratification. Furthermore, we describe when these estimands correspond to the same vaccine effectiveness parameter, and, when appropriate, propose a stratified estimator that can incorporate multiple reasons for testing and improve precision. The performance of our proposed method is demonstrated through simulation studies.
Heterogeneous treatment effects are driven by treatment effect modifiers, pre-treatment covariates that modify the effect of a treatment on an outcome. Current approaches for uncovering these variables are limited to low-dimensional data, data with weakly correlated covariates, or data generated according to parametric processes. We resolve these issues by developing a framework for defining model-agnostic treatment effect modifier variable importance parameters applicable to high-dimensional data with arbitrary correlation structure, deriving one-step, estimating equation and targeted maximum likelihood estimators of these parameters, and establishing these estimators' asymptotic properties. This framework is showcased by defining variable importance parameters for data-generating processes with continuous, binary, and time-to-event outcomes with binary treatments, and deriving accompanying multiply-robust and asymptotically linear estimators. Simulation experiments demonstrate that these estimators' asymptotic guarantees are approximately achieved in realistic sample sizes for observational and randomized studies alike. This framework is applied to gene expression data collected for a clinical trial assessing the effect of a monoclonal antibody therapy on disease-free survival in breast cancer patients. Genes predicted to have the greatest potential for treatment effect modification have previously been linked to breast cancer. An open-source R package implementing this methodology, unihtee, is made available on GitHub at //github.com/insightsengineering/unihtee.
Circuit complexity, defined as the minimum circuit size required for implementing a particular Boolean computation, is a foundational concept in computer science. Determining circuit complexity is believed to be a hard computational problem [1]. Recently, in the context of black holes, circuit complexity has been promoted to a physical property, wherein the growth of complexity is reflected in the time evolution of the Einstein-Rosen bridge (``wormhole'') connecting the two sides of an AdS ``eternal'' black hole [2]. Here we explore another link between complexity and thermodynamics for circuits of given functionality, making the physics-inspired approach relevant to real computational problems, for which functionality is the key element of interest. In particular, our thermodynamic framework provides a new perspective on the obfuscation of programs of arbitrary length -- an important problem in cryptography -- as thermalization through recursive mixing of neighboring sections of a circuit, which can be viewed as the mixing of two containers with ``gases of gates''. This recursive process equilibrates the average complexity and leads to the saturation of the circuit entropy, while preserving functionality of the overall circuit. The thermodynamic arguments hinge on ergodicity in the space of circuits which we conjecture is limited to disconnected ergodic sectors due to fragmentation. The notion of fragmentation has important implications for the problem of circuit obfuscation as it implies that there are circuits with same size and functionality that cannot be connected via local moves. Furthermore, we argue that fragmentation is unavoidable unless the complexity classes NP and coNP coincide, a statement that implies the collapse of the polynomial hierarchy of computational complexity theory to its first level.
Behavioral models play an essential role in Model-driven engineering (MDE). Keeping inter-related behavioral models consistent is critical to use them successfully in MDE. However, consistency checking for behavioral models, especially in a heterogeneous scenario, is limited. We propose a methodology to integrate heterogeneous behavioral models to achieve consistency checking in broader scenarios. It is based on aligning the respective behavioral metamodels by defining possible inter-model relations which carry behavioral meaning. Converting the models and their relations to a behavioral formalism enables analysis of global behavioral consistency using model-checking.
Successfully addressing a wide variety of tasks is a core ability of autonomous agents, requiring flexibly adapting the underlying decision-making strategies and, as we argue in this work, also adapting the perception modules. An analogical argument would be the human visual system, which uses top-down signals to focus attention determined by the current task. Similarly, we adapt pre-trained large vision models conditioned on specific downstream tasks in the context of multi-task policy learning. We introduce task-conditioned adapters that do not require finetuning any pre-trained weights, combined with a single policy trained with behavior cloning and capable of addressing multiple tasks. We condition the visual adapters on task embeddings, which can be selected at inference if the task is known, or alternatively inferred from a set of example demonstrations. To this end, we propose a new optimization-based estimator. We evaluate the method on a wide variety of tasks from the CortexBench benchmark and show that, compared to existing work, it can be addressed with a single policy. In particular, we demonstrate that adapting visual features is a key design choice and that the method generalizes to unseen tasks given a few demonstrations.
Any interactive protocol between a pair of parties can be reliably simulated in the presence of noise with a multiplicative overhead on the number of rounds (Schulman 1996). The reciprocal of the best (least) overhead is called the interactive capacity of the noisy channel. In this work, we present lower bounds on the interactive capacity of the binary erasure channel. Our lower bound improves the best known bound due to Ben-Yishai et al. 2021 by roughly a factor of 1.75. The improvement is due to a tighter analysis of the correctness of the simulation protocol using error pattern analysis. More precisely, instead of using the well-known technique of bounding the least number of erasures needed to make the simulation fail, we identify and bound the probability of specific erasure patterns causing simulation failure. We remark that error pattern analysis can be useful in solving other problems involving stochastic noise, such as bounding the interactive capacity of different channels.
One of the main challenges in surrogate modeling is the limited availability of data due to resource constraints associated with computationally expensive simulations. Multi-fidelity methods provide a solution by chaining models in a hierarchy with increasing fidelity, associated with lower error, but increasing cost. In this paper, we compare different multi-fidelity methods employed in constructing Gaussian process surrogates for regression. Non-linear autoregressive methods in the existing literature are primarily confined to two-fidelity models, and we extend these methods to handle more than two levels of fidelity. Additionally, we propose enhancements for an existing method incorporating delay terms by introducing a structured kernel. We demonstrate the performance of these methods across various academic and real-world scenarios. Our findings reveal that multi-fidelity methods generally have a smaller prediction error for the same computational cost as compared to the single-fidelity method, although their effectiveness varies across different scenarios.
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