Unknown-unknowns are operational scenarios in systems that are not accounted for in the design and test phase. In such scenarios, the operational behavior of the Human-in-loop (HIL) Human-in-Plant (HIP) systems is not guaranteed to meet requirements such as safety and efficacy. We propose a novel framework for analyzing the operational output characteristics of safety-critical HIL-HIP systems that can discover unknown-unknown scenarios and evaluate potential safety hazards. We propose dynamics-induced hybrid recurrent neural networks (DiH-RNN) to mine a physics-guided surrogate model (PGSM) that checks for deviation of the cyber-physical system (CPS) from safety-certified operational characteristics. The PGSM enables early detection of unknown-unknowns based on the physical laws governing the system. We demonstrate the detection of operational changes in an Artificial Pancreas(AP) due to unknown insulin cartridge errors.

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