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Accelerated life tests (ALTs) play a crucial role in reliability analyses, providing lifetime estimates of highly reliable products. Among ALTs, step-stress design increases the stress level at predefined times, while maintaining a constant stress level between successive changes. This approach accelerates the occurrence of failures, reducing experimental duration and cost. While many studies assume a specific form for the lifetime distribution, in certain applications instead a general form satisfying certain properties should be preferred. Proportional hazard model assumes that applied stresses act multiplicatively on the hazard rate, so the hazards function may be divided into two factors, with one representing the effect of the stress, and the other representing the baseline hazard. In this work we examine two particular forms of baseline hazards, namely, linear and quadratic. Moreover, certain experiments may face practical constraints making continuous monitoring of devices infeasible. Instead, devices under test are inspected at predetermined intervals, leading to interval-censoring data. On the other hand, recent works have shown an appealing trade-off between the efficiency and robustness of divergence-based estimators. This paper introduces the step-stress ALT model under proportional hazards and presents a robust family of minimum density power divergence estimators (MDPDEs) for estimating device reliability and related lifetime characteristics such as mean lifetime and distributional quantiles. The asymptotic distributions of these estimates are derived, providing approximate confidence intervals. Empirical evaluations through Monte Carlo simulations demonstrate their performance in terms of robustness and efficiency. Finally, an illustrative example is provided to demonstrate the usefulness of the model and associated methods developed.

When generating in-silico clinical electrophysiological outputs, such as electrocardiograms (ECGs) and body surface potential maps (BSPMs), mathematical models have relied on single physics, i.e. of the cardiac electrophysiology (EP), neglecting the role of the heart motion. Since the heart is the most powerful source of electrical activity in the human body, its motion dynamically shifts the position of the principal electrical sources in the torso, influencing electrical potential distribution and potentially altering the EP outputs. In this work, we propose a computational model for the simulation of ECGs and BSPMs by coupling a cardiac electromechanical model with a model that simulates the propagation of the EP signal in the torso, thanks to a flexible numerical approach, that simulates the torso domain deformation induced by the myocardial displacement. Our model accounts for the major mechano-electrical feedbacks, along with unidirectional displacement and potential couplings from the heart to the surrounding body. For the numerical discretization, we employ a versatile intergrid transfer operator that allows for the use of different Finite Element spaces to be used in the cardiac and torso domains. Our numerical results are obtained on a realistic 3D biventricular-torso geometry, and cover both cases of sinus rhythm and ventricular tachycardia (VT), solving both the electromechanical-torso model in dynamical domains, and the classical electrophysiology-torso model in static domains. By comparing standard 12-lead ECG and BSPMs, we highlight the non-negligible effects of the myocardial contraction on the EP-outputs, especially in pathological conditions, such as the VT.

Modern randomization methods in clinical trials are invariably adaptive, meaning that the assignment of the next subject to a treatment group uses the accumulated information in the trial. Some of the recent adaptive randomization methods use mathematical programming to construct attractive clinical trials that balance the group features, such as their sizes and covariate distributions of their subjects. We review some of these methods and compare their performance with common covariate-adaptive randomization methods for small clinical trials. We introduce an energy distance measure that compares the discrepancy between the two groups using the joint distribution of the subjects' covariates. This metric is more appealing than evaluating the discrepancy between the groups using their marginal covariate distributions. Using numerical experiments, we demonstrate the advantages of the mathematical programming methods under the new measure. In the supplementary material, we provide R codes to reproduce our study results and facilitate comparisons of different randomization procedures.

The deformed energy method has shown to be a good option for dimensional synthesis of mechanisms. In this paper the introduction of some new features to such approach is proposed. First, constraints fixing dimensions of certain links are introduced in the error function of the synthesis problem. Second, requirements on distances between determinate nodes are included in the error function for the analysis of the deformed position problem. Both the overall synthesis error function and the inner analysis error function are optimized using a Sequential Quadratic Problem (SQP) approach. This also reduces the probability of branch or circuit defects. In the case of the inner function analytical derivatives are used, while in the synthesis optimization approximate derivatives have been introduced. Furthermore, constraints are analyzed under two formulations, the Euclidean distance and an alternative approach that uses the previous raised to the power of two. The latter approach is often used in kinematics, and simplifies the computation of derivatives. Some examples are provided to show the convergence order of the error function and the fulfilment of the constraints in both formulations studied under different topological situations or achieved energy levels.

Objective: Prediction models are popular in medical research and practice. By predicting an outcome of interest for specific patients, these models may help inform difficult treatment decisions, and are often hailed as the poster children for personalized, data-driven healthcare. Many prediction models are deployed for decision support based on their prediction accuracy in validation studies. We investigate whether this is a safe and valid approach. Materials and Methods: We show that using prediction models for decision making can lead to harmful decisions, even when the predictions exhibit good discrimination after deployment. These models are harmful self-fulfilling prophecies: their deployment harms a group of patients but the worse outcome of these patients does not invalidate the predictive power of the model. Results: Our main result is a formal characterization of a set of such prediction models. Next we show that models that are well calibrated before and after deployment are useless for decision making as they made no change in the data distribution. Discussion: Our results point to the need to revise standard practices for validation, deployment and evaluation of prediction models that are used in medical decisions. Conclusion: Outcome prediction models can yield harmful self-fulfilling prophecies when used for decision making, a new perspective on prediction model development, deployment and monitoring is needed.

Bayesian networks are widely utilised in various fields, offering elegant representations of factorisations and causal relationships. We use surjective functions to reduce the dimensionality of the Bayesian networks by combining states and study the preservation of their factorisation structure. We introduce and define corresponding notions, analyse their properties, and provide examples of highly symmetric special cases, enhancing the understanding of the fundamental properties of such reductions for Bayesian networks. We also discuss the connection between this and reductions of homogeneous and non-homogeneous Markov chains.

We present MIPS, a novel method for program synthesis based on automated mechanistic interpretability of neural networks trained to perform the desired task, auto-distilling the learned algorithm into Python code. We test MIPS on a benchmark of 62 algorithmic tasks that can be learned by an RNN and find it highly complementary to GPT-4: MIPS solves 32 of them, including 13 that are not solved by GPT-4 (which also solves 30). MIPS uses an integer autoencoder to convert the RNN into a finite state machine, then applies Boolean or integer symbolic regression to capture the learned algorithm. As opposed to large language models, this program synthesis technique makes no use of (and is therefore not limited by) human training data such as algorithms and code from GitHub. We discuss opportunities and challenges for scaling up this approach to make machine-learned models more interpretable and trustworthy.

Conditioning on variables affected by treatment can induce post-treatment bias when estimating causal effects. Although this suggests that researchers should measure potential moderators before administering the treatment in an experiment, doing so may also bias causal effect estimation if the covariate measurement primes respondents to react differently to the treatment. This paper formally analyzes this trade-off between post-treatment and priming biases in three experimental designs that vary when moderators are measured: pre-treatment, post-treatment, or a randomized choice between the two. We derive nonparametric bounds for interactions between the treatment and the moderator in each design and show how to use substantive assumptions to narrow these bounds. These bounds allow researchers to assess the sensitivity of their empirical findings to either source of bias. We then apply these methods to a survey experiment on electoral messaging.

This work presents a maturity model for assessing catalogues of semantic artefacts, one of the keystones that permit semantic interoperability of systems. We defined the dimensions and related features to include in the maturity model by analysing the current literature and existing catalogues of semantic artefacts provided by experts. In addition, we assessed 26 different catalogues to demonstrate the effectiveness of the maturity model, which includes 12 different dimensions (Metadata, Openness, Quality, Availability, Statistics, PID, Governance, Community, Sustainability, Technology, Transparency, and Assessment) and 43 related features (or sub-criteria) associated with these dimensions. Such a maturity model is one of the first attempts to provide recommendations for governance and processes for preserving and maintaining semantic artefacts and helps assess/address interoperability challenges.

Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.