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We tackle the extension to the vector-valued case of consistency results for Stepwise Uncertainty Reduction sequential experimental design strategies established in [Bect et al., A supermartingale approach to Gaussian process based sequential design of experiments, Bernoulli 25, 2019]. This lead us in the first place to clarify, assuming a compact index set, how the connection between continuous Gaussian processes and Gaussian measures on the Banach space of continuous functions carries over to vector-valued settings. From there, a number of concepts and properties from the aforementioned paper can be readily extended. However, vector-valued settings do complicate things for some results, mainly due to the lack of continuity for the pseudo-inverse mapping that affects the conditional mean and covariance function given finitely many pointwise observations. We apply obtained results to the Integrated Bernoulli Variance and the Expected Measure Variance uncertainty functionals employed in [Fossum et al., Learning excursion sets of vector-valued Gaussian random fields for autonomous ocean sampling, The Annals of Applied Statistics 15, 2021] for the estimation for excursion sets of vector-valued functions.

Wide heterogeneity exists in cancer patients' survival, ranging from a few months to several decades. To accurately predict clinical outcomes, it is vital to build an accurate predictive model that relates patients' molecular profiles with patients' survival. With complex relationships between survival and high-dimensional molecular predictors, it is challenging to conduct non-parametric modeling and irrelevant predictors removing simultaneously. In this paper, we build a kernel Cox proportional hazards semi-parametric model and propose a novel regularized garrotized kernel machine (RegGKM) method to fit the model. We use the kernel machine method to describe the complex relationship between survival and predictors, while automatically removing irrelevant parametric and non-parametric predictors through a LASSO penalty. An efficient high-dimensional algorithm is developed for the proposed method. Comparison with other competing methods in simulation shows that the proposed method always has better predictive accuracy. We apply this method to analyze a multiple myeloma dataset and predict patients' death burden based on their gene expressions. Our results can help classify patients into groups with different death risks, facilitating treatment for better clinical outcomes.

Artificial neural networks are prone to being fooled by carefully perturbed inputs which cause an egregious misclassification. These \textit{adversarial} attacks have been the focus of extensive research. Likewise, there has been an abundance of research in ways to detect and defend against them. We introduce a novel approach of detection and interpretation of adversarial attacks from a graph perspective. For an input image, we compute an associated sparse graph using the layer-wise relevance propagation algorithm \cite{bach15}. Specifically, we only keep edges of the neural network with the highest relevance values. Three quantities are then computed from the graph which are then compared against those computed from the training set. The result of the comparison is a classification of the image as benign or adversarial. To make the comparison, two classification methods are introduced: 1) an explicit formula based on Wasserstein distance applied to the degree of node and 2) a logistic regression. Both classification methods produce strong results which lead us to believe that a graph-based interpretation of adversarial attacks is valuable.

An assurance calculation is a Bayesian alternative to a power calculation. One may be performed to aid the planning of a clinical trial, specifically setting the sample size or to support decisions about whether or not to perform a study. Immuno-oncology (IO) is a rapidly evolving area in the development of anticancer drugs. A common phenomenon that arises from IO trials is one of delayed treatment effects, that is, there is a delay in the separation of the survival curves. To calculate assurance for a trial in which a delayed treatment effect is likely to be present, uncertainty about key parameters needs to be considered. If uncertainty is not considered, then the number of patients recruited may not be enough to ensure we have adequate statistical power to detect a clinically relevant treatment effect. We present a new elicitation technique for when a delayed treatment effect is likely to be present and show how to compute assurance using these elicited prior distributions. We provide an example to illustrate how this could be used in practice. Open-source software is provided for implementing our methods. Our methodology makes the benefits of assurance methods available for the planning of IO trials (and others where a delayed treatment expect is likely to occur).

In the field of semi-supervised medical image segmentation, the shortage of labeled data is the fundamental problem. How to effectively learn image features from unlabeled images to improve segmentation accuracy is the main research direction in this field. Traditional self-training methods can partially solve the problem of insufficient labeled data by generating pseudo labels for iterative training. However, noise generated due to the model's uncertainty during training directly affects the segmentation results. Therefore, we added sample-level and pixel-level uncertainty to stabilize the training process based on the self-training framework. Specifically, we saved several moments of the model during pre-training, and used the difference between their predictions on unlabeled samples as the sample-level uncertainty estimate for that sample. Then, we gradually add unlabeled samples from easy to hard during training. At the same time, we added a decoder with different upsampling methods to the segmentation network and used the difference between the outputs of the two decoders as pixel-level uncertainty. In short, we selectively retrained unlabeled samples and assigned pixel-level uncertainty to pseudo labels to optimize the self-training process. We compared the segmentation results of our model with five semi-supervised approaches on the public 2017 ACDC dataset and 2018 Prostate dataset. Our proposed method achieves better segmentation performance on both datasets under the same settings, demonstrating its effectiveness, robustness, and potential transferability to other medical image segmentation tasks. Keywords: Medical image segmentation, semi-supervised learning, self-training, uncertainty estimation

Large language models based on self-attention mechanisms have achieved astonishing performances not only in natural language itself, but also in a variety of tasks of different nature. However, regarding processing language, our human brain may not operate using the same principle. Then, a debate is established on the connection between brain computation and artificial self-supervision adopted in large language models. One of most influential hypothesis in brain computation is the predictive coding framework, which proposes to minimize the prediction error by local learning. However, the role of predictive coding and the associated credit assignment in language processing remains unknown. Here, we propose a mean-field learning model within the predictive coding framework, assuming that the synaptic weight of each connection follows a spike and slab distribution, and only the distribution, rather than specific weights, is trained. This meta predictive learning is successfully validated on classifying handwritten digits where pixels are input to the network in sequence, and moreover on the toy and real language corpus. Our model reveals that most of the connections become deterministic after learning, while the output connections have a higher level of variability. The performance of the resulting network ensemble changes continuously with data load, further improving with more training data, in analogy with the emergent behavior of large language models. Therefore, our model provides a starting point to investigate the connection among brain computation, next-token prediction and general intelligence.

In clinical trials of longitudinal continuous outcomes, reference based imputation (RBI) has commonly been applied to handle missing outcome data in settings where the estimand incorporates the effects of intercurrent events, e.g. treatment discontinuation. RBI was originally developed in the multiple imputation framework, however recently conditional mean imputation (CMI) combined with the jackknife estimator of the standard error was proposed as a way to obtain deterministic treatment effect estimates and correct frequentist inference. For both multiple and CMI, a mixed model for repeated measures (MMRM) is often used for the imputation model, but this can be computationally intensive to fit to multiple data sets (e.g. the jackknife samples) and lead to convergence issues with complex MMRM models with many parameters. Therefore, a step-wise approach based on sequential linear regression (SLR) of the outcomes at each visit was developed for the imputation model in the multiple imputation framework, but similar developments in the CMI framework are lacking. In this article, we fill this gap in the literature by proposing a SLR approach to implement RBI in the CMI framework, and justify its validity using theoretical results and simulations. We also illustrate our proposal on a real data application.

In light of newly developed standardization methods, we evaluate, via simulation study, how propensity score weighting and standardization -based approaches compare for obtaining estimates of the marginal odds ratio and the marginal hazard ratio. Specifically, we consider how the two approaches compare in two different scenarios: (1) in a single observational study, and (2) in an anchored indirect treatment comparison (ITC) of randomized controlled trials. We present the material in such a way so that the matching-adjusted indirect comparison (MAIC) and the (novel) simulated treatment comparison (STC) methods in the ITC setting may be viewed as analogous to the propensity score weighting and standardization methods in the single observational study setting. Our results suggest that current recommendations for conducting ITCs can be improved and underscore the importance of adjusting for purely prognostic factors.

Electrical circuits are present in a variety of technologies, making their design an important part of computer aided engineering. The growing number of tunable parameters that affect the final design leads to a need for new approaches of quantifying their impact. Machine learning may play a key role in this regard, however current approaches often make suboptimal use of existing knowledge about the system at hand. In terms of circuits, their description via modified nodal analysis is well-understood. This particular formulation leads to systems of differential-algebraic equations (DAEs) which bring with them a number of peculiarities, e.g. hidden constraints that the solution needs to fulfill. We aim to use the recently introduced dissection concept for DAEs that can decouple a given system into ordinary differential equations, only depending on differential variables, and purely algebraic equations that describe the relations between differential and algebraic variables. The idea then is to only learn the differential variables and reconstruct the algebraic ones using the relations from the decoupling. This approach guarantees that the algebraic constraints are fulfilled up to the accuracy of the nonlinear system solver, which represents the main benefit highlighted in this article.

Stress testing refers to the application of adverse financial or macroeconomic scenarios to a portfolio. For this purpose, financial or macroeconomic risk factors are linked with asset returns, typically via a factor model. We expand the range of risk factors by adapting dimension-reduction techniques from unsupervised learning, namely PCA and autoencoders. This results in aggregated risk factors, encompassing a global factor, factors representing broad geographical regions, and factors specific to cyclical and defensive industries. As the adapted PCA and autoencoders provide an interpretation of the latent factors, this methodology is also valuable in other areas where dimension-reduction and explainability are crucial.