Searching for Optimal Runtime Assurance via Reachability and Reinforcement Learning

A runtime assurance system (RTA) for a given plant enables the exercise of an untrusted or experimental controller while assuring safety with a backup (or safety) controller. The relevant computational design problem is to create a logic that assures safety by switching to the safety controller as needed, while maximizing some performance criteria, such as the utilization of the untrusted controller. Existing RTA design strategies are well-known to be overly conservative and, in principle, can lead to safety violations. In this paper, we formulate the optimal RTA design problem and present a new approach for solving it. Our approach relies on reward shaping and reinforcement learning. It can guarantee safety and leverage machine learning technologies for scalability. We have implemented this algorithm and present experimental results comparing our approach with state-of-the-art reachability and simulation-based RTA approaches in a number of scenarios using aircraft models in 3D space with complex safety requirements. Our approach can guarantee safety while increasing utilization of the experimental controller over existing approaches

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure

Abstract Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10−3) and candidate genes from knockout mice (P = 5.2 × 10−3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000–185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.</p