Multimodality eye disease screening is crucial in ophthalmology as it integrates information from diverse sources to complement their respective performances. However, the existing methods are weak in assessing the reliability of each unimodality, and directly fusing an unreliable modality may cause screening errors. To address this issue, we introduce a novel multimodality evidential fusion pipeline for eye disease screening, EyeMoSt, which provides a measure of confidence for unimodality and elegantly integrates the multimodality information from a multi-distribution fusion perspective. Specifically, our model estimates both local uncertainty for unimodality and global uncertainty for the fusion modality to produce reliable classification results. More importantly, the proposed mixture of Student's $t$ distributions adaptively integrates different modalities to endow the model with heavy-tailed properties, increasing robustness and reliability. Our experimental findings on both public and in-house datasets show that our model is more reliable than current methods. Additionally, EyeMost has the potential ability to serve as a data quality discriminator, enabling reliable decision-making for multimodality eye disease screening.
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Estimating treatment effects over time is relevant in many real-world applications, such as precision medicine, epidemiology, economy, and marketing. Many state-of-the-art methods either assume the observations of all confounders or seek to infer the unobserved ones. We take a different perspective by assuming unobserved risk factors, i.e., adjustment variables that affect only the sequence of outcomes. Under unconfoundedness, we target the Individual Treatment Effect (ITE) estimation with unobserved heterogeneity in the treatment response due to missing risk factors. We address the challenges posed by time-varying effects and unobserved adjustment variables. Led by theoretical results over the validity of the learned adjustment variables and generalization bounds over the treatment effect, we devise Causal DVAE (CDVAE). This model combines a Dynamic Variational Autoencoder (DVAE) framework with a weighting strategy using propensity scores to estimate counterfactual responses. The CDVAE model allows for accurate estimation of ITE and captures the underlying heterogeneity in longitudinal data. Evaluations of our model show superior performance over state-of-the-art models.
Many medical ultrasound video recognition tasks involve identifying key anatomical features regardless of when they appear in the video suggesting that modeling such tasks may not benefit from temporal features. Correspondingly, model architectures that exclude temporal features may have better sample efficiency. We propose a novel multi-head attention architecture that incorporates these hypotheses as inductive priors to achieve better sample efficiency on common ultrasound tasks. We compare the performance of our architecture to an efficient 3D CNN video recognition model in two settings: one where we expect not to require temporal features and one where we do. In the former setting, our model outperforms the 3D CNN - especially when we artificially limit the training data. In the latter, the outcome reverses. These results suggest that expressive time-independent models may be more effective than state-of-the-art video recognition models for some common ultrasound tasks in the low-data regime.
Visual representation learning hold great promise for robotics, but is severely hampered by the scarcity and homogeneity of robotics datasets. Recent works address this problem by pre-training visual representations on large-scale but out-of-domain data (e.g., videos of egocentric interactions) and then transferring them to target robotics tasks. While the field is heavily focused on developing better pre-training algorithms, we find that dataset choice is just as important to this paradigm's success. After all, the representation can only learn the structures or priors present in the pre-training dataset. To this end, we flip the focus on algorithms, and instead conduct a dataset centric analysis of robotic pre-training. Our findings call into question some common wisdom in the field. We observe that traditional vision datasets (like ImageNet, Kinetics and 100 Days of Hands) are surprisingly competitive options for visuo-motor representation learning, and that the pre-training dataset's image distribution matters more than its size. Finally, we show that common simulation benchmarks are not a reliable proxy for real world performance and that simple regularization strategies can dramatically improve real world policy learning. //data4robotics.github.io
An important aspect in the development of small molecules as drugs or agro-chemicals is their systemic availability after intravenous and oral administration.The prediction of the systemic availability from the chemical structure of a poten-tial candidate is highly desirable, as it allows to focus the drug or agrochemicaldevelopment on compounds with a favorable kinetic profile. However, such pre-dictions are challenging as the availability is the result of the complex interplaybetween molecular properties, biology and physiology and training data is rare.In this work we improve the hybrid model developed earlier [34]. We reducethe median fold change error for the total oral exposure from 2.85 to 2.35 andfor intravenous administration from 1.95 to 1.62. This is achieved by trainingon a larger data set, improving the neural network architecture as well as theparametrization of mechanistic model. Further, we extend our approach to predictadditional endpoints and to handle different covariates, like sex and dosage form.In contrast to a pure machine learning model, our model is able to predict newend points on which it has not been trained. We demonstrate this feature by1predicting the exposure over the first 24h, while the model has only been trainedon the total exposure.
MET protein overexpression is a targetable event in non-small cell lung cancer (NSCLC) and is the subject of active drug development. Challenges in identifying patients for these therapies include lack of access to validated testing, such as standardized immunohistochemistry (IHC) assessment, and consumption of valuable tissue for a single gene/protein assay. Development of pre-screening algorithms using routinely available digitized hematoxylin and eosin (H&E)-stained slides to predict MET overexpression could promote testing for those who will benefit most. While assessment of MET expression using IHC is currently not routinely performed in NSCLC, next-generation sequencing is common and in some cases includes RNA expression panel testing. In this work, we leveraged a large database of matched H&E slides and RNA expression data to train a weakly supervised model to predict MET RNA overexpression directly from H&E images. This model was evaluated on an independent holdout test set of 300 over-expressed and 289 normal patients, demonstrating an ROC-AUC of 0.70 (95th percentile interval: 0.66 - 0.74) with stable performance characteristics across different patient clinical variables and robust to synthetic noise on the test set. These results suggest that H&E-based predictive models could be useful to prioritize patients for confirmatory testing of MET protein or MET gene expression status.
Microsatellite instability-high (MSI-H) is a tumor agnostic biomarker for immune checkpoint inhibitor therapy. However, MSI status is not routinely tested in prostate cancer, in part due to low prevalence and assay cost. As such, prediction of MSI status from hematoxylin and eosin (H&E) stained whole-slide images (WSIs) could identify prostate cancer patients most likely to benefit from confirmatory testing and becoming eligible for immunotherapy. Prostate biopsies and surgical resections from de-identified records of consecutive prostate cancer patients referred to our institution were analyzed. Their MSI status was determined by next generation sequencing. Patients before a cutoff date were split into an algorithm development set (n=4015, MSI-H 1.8%) and a paired validation set (n=173, MSI-H 19.7%) that consisted of two serial sections from each sample, one stained and scanned internally and the other at an external site. Patients after the cutoff date formed the temporal validation set (n=1350, MSI-H 2.3%). Attention-based multiple instance learning models were trained to predict MSI-H from H&E WSIs. The MSI-H predictor achieved area under the receiver operating characteristic curve values of 0.78 (95% CI [0.69-0.86]), 0.72 (95% CI [0.63-0.81]), and 0.72 (95% CI [0.62-0.82]) on the internally prepared, externally prepared, and temporal validation sets, respectively. While MSI-H status is significantly correlated with Gleason score, the model remained predictive within each Gleason score subgroup. In summary, we developed and validated an AI-based MSI-H diagnostic model on a large real-world cohort of routine H&E slides, which effectively generalized to externally stained and scanned samples and a temporally independent validation cohort. This algorithm has the potential to direct prostate cancer patients toward immunotherapy and to identify MSI-H cases secondary to Lynch syndrome.
Zoonotic disease transmission between animals and humans is a growing risk and the agricultural context acts as a likely point of transition, with individual heterogeneity acting as an important contributor. Thus, understanding the dynamics of disease spread in the wildlife-livestock interface is crucial for mitigating these risks of transmission. Specifically, the interactions between pigeons and in-door cows at dairy farms can lead to significant disease transmission and economic losses for farmers; putting livestock, adjacent human populations, and other wildlife species at risk. In this paper, we propose a novel spatio-temporal multi-pathogen model with continuous spatial movement. The model expands on the Susceptible-Exposed-Infected-Recovered-Dead (SEIRD) framework and accounts for both within-species and cross-species transmission of pathogens, as well as the exploration-exploitation movement dynamics of pigeons, which play a critical role in the spread of infection agents. In addition to model formulation, we also implement it as an agent-based simulation approach and use empirical field data to investigate different biologically realistic scenarios, evaluating the effect of various parameters on the epidemic spread. Namely, in agreement with theoretical expectations, the model predicts that the heterogeneity of the pigeons' movement dynamics can drastically affect both the magnitude and stability of outbreaks. In addition, joint infection by multiple pathogens can have an interactive effect unobservable in single-pathogen SIR models, reflecting a non-intuitive inhibition of the outbreak. Our findings highlight the impact of heterogeneity in host behavior on their pathogens and allow realistic predictions of outbreak dynamics in the multi-pathogen wildlife-livestock interface with consequences to zoonotic diseases in various systems.
Believable proxies of human behavior can empower interactive applications ranging from immersive environments to rehearsal spaces for interpersonal communication to prototyping tools. In this paper, we introduce generative agents--computational software agents that simulate believable human behavior. Generative agents wake up, cook breakfast, and head to work; artists paint, while authors write; they form opinions, notice each other, and initiate conversations; they remember and reflect on days past as they plan the next day. To enable generative agents, we describe an architecture that extends a large language model to store a complete record of the agent's experiences using natural language, synthesize those memories over time into higher-level reflections, and retrieve them dynamically to plan behavior. We instantiate generative agents to populate an interactive sandbox environment inspired by The Sims, where end users can interact with a small town of twenty five agents using natural language. In an evaluation, these generative agents produce believable individual and emergent social behaviors: for example, starting with only a single user-specified notion that one agent wants to throw a Valentine's Day party, the agents autonomously spread invitations to the party over the next two days, make new acquaintances, ask each other out on dates to the party, and coordinate to show up for the party together at the right time. We demonstrate through ablation that the components of our agent architecture--observation, planning, and reflection--each contribute critically to the believability of agent behavior. By fusing large language models with computational, interactive agents, this work introduces architectural and interaction patterns for enabling believable simulations of human behavior.
Understanding causality helps to structure interventions to achieve specific goals and enables predictions under interventions. With the growing importance of learning causal relationships, causal discovery tasks have transitioned from using traditional methods to infer potential causal structures from observational data to the field of pattern recognition involved in deep learning. The rapid accumulation of massive data promotes the emergence of causal search methods with brilliant scalability. Existing summaries of causal discovery methods mainly focus on traditional methods based on constraints, scores and FCMs, there is a lack of perfect sorting and elaboration for deep learning-based methods, also lacking some considers and exploration of causal discovery methods from the perspective of variable paradigms. Therefore, we divide the possible causal discovery tasks into three types according to the variable paradigm and give the definitions of the three tasks respectively, define and instantiate the relevant datasets for each task and the final causal model constructed at the same time, then reviews the main existing causal discovery methods for different tasks. Finally, we propose some roadmaps from different perspectives for the current research gaps in the field of causal discovery and point out future research directions.
Due to their increasing spread, confidence in neural network predictions became more and more important. However, basic neural networks do not deliver certainty estimates or suffer from over or under confidence. Many researchers have been working on understanding and quantifying uncertainty in a neural network's prediction. As a result, different types and sources of uncertainty have been identified and a variety of approaches to measure and quantify uncertainty in neural networks have been proposed. This work gives a comprehensive overview of uncertainty estimation in neural networks, reviews recent advances in the field, highlights current challenges, and identifies potential research opportunities. It is intended to give anyone interested in uncertainty estimation in neural networks a broad overview and introduction, without presupposing prior knowledge in this field. A comprehensive introduction to the most crucial sources of uncertainty is given and their separation into reducible model uncertainty and not reducible data uncertainty is presented. The modeling of these uncertainties based on deterministic neural networks, Bayesian neural networks, ensemble of neural networks, and test-time data augmentation approaches is introduced and different branches of these fields as well as the latest developments are discussed. For a practical application, we discuss different measures of uncertainty, approaches for the calibration of neural networks and give an overview of existing baselines and implementations. Different examples from the wide spectrum of challenges in different fields give an idea of the needs and challenges regarding uncertainties in practical applications. Additionally, the practical limitations of current methods for mission- and safety-critical real world applications are discussed and an outlook on the next steps towards a broader usage of such methods is given.
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