In the United States, there is still a great disparity in medical care and most profoundly for emergency care, where limited facilities and remote location play a central role. Based on the Wessels Living History Farm report, the doctor to patient ratio in the United States is 30 to 10,000 in large metropolitan areas, only 5 to 10,000 in most rural areas; and the highest death rates are often found in the most rural counties. For emergency patient care, time to definitive treatment is critical. However, deciding the most effective care for an acute patient requires knowledge and experience. Though medical best practice guidelines exist and are in hospital handbooks, they are often lengthy and difficult to apply clinically. The challenges are exaggerated for doctors in rural areas and emergency medical technicians (EMT) during patient transport. This project's solution to transform emergency care at rural hospitals is to use innovative CPS technologies to help hospitals to improve their adherence to medical best practice. The key to assist medical staff with different levels of experience and skills to adhere to medical best practice is to transform required processes described in medical texts to an executable, adaptive, and distributed medical best practice guidance (EMBG) system. Compared to the computerized sepsis best practice protocol, the EMBG system faces a much bigger challenge as it has to adapt the best practice across rural hospitals, ambulances and center hospitals with different levels of staff expertise and equipment capabilities. Using a Global Positioning System analogy, a GPS leads drivers with different route familiarity to their destination through an optimal route based on the drivers' preferences, the EMBG system leads medical personnel to follow the best medical guideline path to provide emergency care and minimize the time to definitive treatment for acute patients. The project makes the following contributions: 1) The codification of complex medical knowledge is an important advancement in knowledge capture and representation; 2) Pathophysiological model driven communication in high speed ambulance advances life critical communication technology; and 3) Reduced complexity software architectures designed for formal verification bridges the gap between formal method research and system engineering.

Part 1: Upper-limb motor impairments arise from a wide range of clinical conditions including amputations, spinal cord injury, or stroke. Addressing lost hand function, therefore, is a major focus of rehabilitation interventions; and research in robotic hands and hand exoskeletons aimed at restoring fine motor control functions gained significant speed recently. Integration of these robots with neural control mechanisms is also an ongoing research direction. We will develop prosthetic and wearable hands controlled via nested control that seamlessly blends neural control based on human brain activity and dynamic control based on sensors on robots. These Hand Augmentation using Nested Decision (HAND) systems will also provide rudimentary tactile feedback to the user. The HAND design framework will contribute to the assistive and augmentative robotics field. The resulting technology will improve the quality of life for individuals with lost limb function. The project will help train engineers skilled in addressing multidisciplinary challenges. Through outreach activities, STEM careers will be promoted at the K-12 level, individuals from underrepresented groups in engineering will be recruited to engage in this research project, which will contribute to the diversity of the STEM workforce. Part 2: The team previously introduced the concept of human-in-the-loop cyber-physical systems (HILCPS). Using the HILCPS hardware-software co-design and automatic synthesis infrastructure, we will develop prosthetic and wearable HAND systems that are robust to uncertainty in human intent inference from physiological signals. One challenge arises from the fact that the human and the cyber system jointly operate on the same physical element. Synthesis of networked real-time applications from algorithm design environments poses a framework challenge. These will be addressed by a tightly coupled optimal nested control strategy that relies on EEG-EMG-context fusion for human intent inference. Custom distributed embedded computational and robotic platforms will be built and iteratively refined. This work will enhance the HILCPS design framework, while simultaneously making novel contributions to body/brain interface technology and assistive/augmentative robot technology. Specifically we will (1) develop a theoretical EEG-EMG-context fusion framework for agile HILCPS application domains; (2) develop theory for and design novel control theoretic solutions to handle uncertainty, blend motion/force planning with high-level human intent and ambient intelligence to robustly execute daily manipulation activities; (3) further develop and refine the HILCPS domain-specific design framework to enable rapid deployment of HILCPS algorithms onto distributed embedded systems, empowering a new class of real-time algorithms that achieve distributed embedded sensing, analysis, and decision making; (4) develop new paradigms to replace, retrain or augment hand function via the prosthetic/wearable HAND by optimizing performance on a subject-by-subject basis.

The objective of this research is to design a semi-automated, efficient, and secure emergency response system to reduce the time it takes emergency vehicles to reach their destinations, while increasing the safety of non-emergency vehicles and emergency vehicles alike. Providing route and maneuver guidance to emergency vehicles and non-emergency vehicles will make emergency travel safer and enable police and other first responders to reach and transport those in need, in less time. This should reduce the number of crashes involving emergency vehicles and associated litigation costs while improving medical outcomes, reducing property damage, and instilling greater public confidence in emergency services. At the same time, non-emergency vehicles will also be offered increased safety and, with the reduction of long delays attributed to emergency vehicles, experience reduced incident-related travel time, which will increase productivity and quality of life for drivers. Incorporating connected vehicles into the emergency response system will also provide synergistic opportunities for non-emergency vehicles, including live updates on accident sites, areas to avoid, and information on emergency routes that can be incorporated into navigation software so drivers can avoid potential delays. While the proposed system will naturally advance the quality of transportation in smart cities, it will also provide a platform for future techniques to build upon. For example, the proposed system could be connected with emergency care facilities to balance the load of emergency patients at hospitals, and act as a catalyst toward the realization of a fully-automated emergency response system. New courses and course modules will be developed to recruit and better prepare a future workforce that is well versed in multi-disciplinary collaborations. Video demos and a testbed will be used to showcase the research to the public. The key research component will be the design of an emergency response system that (1) dynamically determines EV routes, (2) coordinates actions by non-emergency vehicles using connected vehicle technology to efficiently and effectively clear paths for emergency vehicles, (3) is able to adapt to uncertain traffic and network conditions, and (4) is difficult to abuse or compromise. The project will result in (1) algorithms that dynamically select EV routes based on uncertain or limited traffic data, (2) emergency protocols that exploit connected vehicle technology to facilitate emergency vehicles maneuvers, (3) an automation module to assist with decision making and maneuvers, and (4) an infrastructure and vehicle hardening framework that prevents cyber abuse. Experiments will be performed on a testbed and a real test track to validate the proposed research.

Security and privacy concerns in the increasingly interconnected world are receiving much attention from the research community, policymakers, and general public. However, much of the recent and on-going efforts concentrate on security of general-purpose computation and on privacy in communication and social interactions. The advent of cyber-physical systems (e.g., safety-critical IoT), which aim at tight integration between distributed computational intelligence, communication networks, physical world, and human actors, opens new horizons for intelligent systems with advanced capabilities. These systems may reduce number of accidents and increase throughput of transportation networks, improve patient safety, mitigate caregiver errors, enable personalized treatments, and allow older adults to age in their places. At the same time, cyber-physical systems introduce new challenges and concerns about safety, security, and privacy. The proposed project will lead to safer, more secure and privacy preserving CPS. As our lives depend more and more on these systems, specifically in automotive, medical, and Internet-of-Things domains, results obtained in this project will have a direct impact on the society at large. The study of emerging legal and ethical aspects of large-scale CPS deployments will inform future policy decision-making. The educational and outreach aspects of this project will help us build a workforce that is better prepared to address the security and privacy needs of the ever-more connected and technologically oriented society. Cyber-physical systems (CPS) involve tight integration of computational nodes, connected by one or more communication networks, the physical environment of these nodes, and human users of the system, who interact with both the computational part of the system and the physical environment. Attacks on a CPS system may affect all of its components: computational nodes and communication networks are subject to malicious intrusions, and physical environment may be maliciously altered. CPS-specific security challenges arise from two perspectives. On the one hand, conventional information security approaches can be used to prevent intrusions, but attackers can still affect the system via the physical environment. Resource constraints, inherent in many CPS domains, may prevent heavy-duty security approaches from being deployed. This proposal will develop a framework in which the mix of prevention, detection and recovery, and robust techniques work together to improve the security and privacy of CPS. Specific research products will include techniques providing: 1) accountability-based detection and bounded-time recovery from malicious attacks to CPS, complemented by novel preventive techniques based on lightweight cryptography; 2) security-aware control design based on attack resilient state estimator and sensor fusions; 3) privacy of data collected and used by CPS based on differential privacy; and, 4) evidence-based framework for CPS security and privacy assurance, taking into account the operating context of the system and human factors. Case studies will be performed in applications with autonomous features of vehicles, internal and external vehicle networks, medical device interoperability, and smart connected medical home.

Epilepsy is one of the most common neurological disorders, affecting between 0.4% and 1% of the world's population. While seizures can be controlled in approximately two thirds of newly diagnosed patients through the use of one or more antiepileptic drugs (AEDs), the remainder experience seizures even on multiple medications. The primary impacts of the chronic condition of epilepsy on a patient are a lower quality of life, loss of productivity, comorbidities, and increased risk of death. Epilepsy is an intermittent brain disorder, and in localization-related epilepsy, which is the most common form of epilepsy, one or a few discrete brain areas (the seizure focus or seizure foci) are believed to be responsible for seizure initiation. More recent approaches with implantable electrical stimulation seizure control devices hold value as a therapeutic option for the control of seizures. These devices, directly or indirectly, target the seizure focus and seek to control its expression. In this project we will build a multichannel brain implantable device based on emerging cyber physical system (CPS) principles. This brain implantable CPS device will incorporate key design features to make the device dependable, scalable, composable, certifiable, and interoperable. The device will operate over the life of an animal, or a patient, and continuously record brain activity and stimulate the brain when seizure related activity is detected to abort an impending seizure. Episodic brain disorders such as epilepsy have a considerable impact on a patient's productivity and quality of life and may be life-threatening when seizures cannot be controlled with medications. The goal of this project is to create a second generation brain-implantable sensing and stimulating device (BISSD) based on emerging CPS principles and practice. The development of a BISSD as a exemplifies several defining aspects that inform and illustrate core CPS principles. First, to meet the important challenge of regulatory approval a composable, scalable and certifiable framework that supports testing in multiple species is proposed. Second, a BISSD must be wholly integrated with the patient and fully cognizant at every instant of brain state, including dynamic changes in both the normal and abnormal expression of brain physiology and therapeutic intervention. Thus, this project seeks a tight conjunction of the cyber solution that must monitor itself and monitor and stimulate the brain using implanted, adaptable, distributed, and networked electrodes, and the physical system which in this case is the intermittently failing human brain. Third, a BISSD must function for an extensive period of time, up to the life of the patient, because each surgery to place and retrieve a BISSD carries an attendant risk. This requirement necessitates a dependable solution, which this project seeks to reliably achieve through both an understanding of the brain's foreign body response and a unique hierarchical fault-tolerant design. Fourth, an advanced salient approaches to acquire, compress, and analyze sensor signals to achieve real-time monitoring and control of seizures is employed. This project should yield a powerful, scalable CPS framework for robust fault-tolerant implantable medical devices with real-time processing that can grow with advances in sensors, sensing modalities, time-series analysis, real-time computation, control, materials, power and knowledge of underlying biology. The USA has a competitive advantage in the control of seizures in medically refractory epilepsy. In the modern era, epilepsy surgery evolved in the USA in the 1970s and spread from here to other parts of the world. Similarly, the USA enjoys a competitive advantage in BISSDs, and success in this effort will enable the USA to build on and maintain this advantage. In addition to epilepsy, advances made here can be expected to benefit the treatment of other neurological and psychiatric brain disorders.

Part 1: Upper-limb motor impairments arise from a wide range of clinical conditions including amputations, spinal cord injury, or stroke. Addressing lost hand function, therefore, is a major focus of rehabilitation interventions; and research in robotic hands and hand exoskeletons aimed at restoring fine motor control functions gained significant speed recently. Integration of these robots with neural control mechanisms is also an ongoing research direction. We will develop prosthetic and wearable hands controlled via nested control that seamlessly blends neural control based on human brain activity and dynamic control based on sensors on robots. These Hand Augmentation using Nested Decision (HAND) systems will also provide rudimentary tactile feedback to the user. The HAND design framework will contribute to the assistive and augmentative robotics field. The resulting technology will improve the quality of life for individuals with lost limb function. The project will help train engineers skilled in addressing multidisciplinary challenges. Through outreach activities, STEM careers will be promoted at the K-12 level, individuals from underrepresented groups in engineering will be recruited to engage in this research project, which will contribute to the diversity of the STEM workforce. Part 2: The team previously introduced the concept of human-in-the-loop cyber-physical systems (HILCPS). Using the HILCPS hardware-software co-design and automatic synthesis infrastructure, we will develop prosthetic and wearable HAND systems that are robust to uncertainty in human intent inference from physiological signals. One challenge arises from the fact that the human and the cyber system jointly operate on the same physical element. Synthesis of networked real-time applications from algorithm design environments poses a framework challenge. These will be addressed by a tightly coupled optimal nested control strategy that relies on EEG-EMG-context fusion for human intent inference. Custom distributed embedded computational and robotic platforms will be built and iteratively refined. This work will enhance the HILCPS design framework, while simultaneously making novel contributions to body/brain interface technology and assistive/augmentative robot technology. Specifically we will (1) develop a theoretical EEG-EMG-context fusion framework for agile HILCPS application domains; (2) develop theory for and design novel control theoretic solutions to handle uncertainty, blend motion/force planning with high-level human intent and ambient intelligence to robustly execute daily manipulation activities; (3) further develop and refine the HILCPS domain-specific design framework to enable rapid deployment of HILCPS algorithms onto distributed embedded systems, empowering a new class of real-time algorithms that achieve distributed embedded sensing, analysis, and decision making; (4) develop new paradigms to replace, retrain or augment hand function via the prosthetic/wearable HAND by optimizing performance on a subject-by-subject basis.

Laboratory-on-a-chip (LoC) technology is poised to improve global health through development of low-cost, automated point-of-care testing devices. In countries with few healthcare resources, clinics often have drugs to treat an illness, but lack diagnostic tools to identify patients who need them. To enable low-cost diagnostics with minimal laboratory support, this project will investigate domain-specific LoC programming language and compiler design in conjunction with device fabrication technologies (process flows, sensor integration, etc.). The project will culminate by building a working LoC that controls fluid motion through electronic signals supplied by a host PC; a forensic toxicology immunoassay will be programmed in software and executed on the device. This experiment will demonstrate benefits of programmable LoC technology including miniaturization (reduced reagent consumption), automation (reduced costs and uncertainties associated with human interaction), and general-purpose software-programmability (the device can execute a wide variety of biochemical reactions, all specified in software). Information necessary to reproduce the device, along with all software artifacts developed through this research effort, will be publicly disseminated. This will promote widespread usage of software-programmable LoC technology among researchers in the biological sciences, along with public and industrial sectors including healthcare and public health, biotechnology, water supply management, environmental toxicity monitoring, and many others. This project designs and implements a software-programmable cyber-physical laboratory-on-a-chip (LoC) that can execute a wide variety of biological protocols. By integrating sensors during fabrication, the LoC obtains the capability to send feedback in real-time to the PC controller, which can then make intelligent decisions regarding which biological operations to execute next. To bring this innovative and transformative platform to fruition, the project tackles several formidable research challenges: (1) cyber-physical LoC programming models and compiler design; (2) LoC fabrication, including process flows and cyber-physical sensor integration; and (3) LoC applications that rely on cyber-physical sensory feedback and real-time decision-making. By constructing a working prototype LoC, and programming a representative feedback-driven forensic toxicology immunoassay, the project demonstrates that the proposed system can automatically execute biochemical reactions that require a closed feedback loop. Expected broader impacts of the proposed work include reduced cost and increased reliability of clinical diagnostics, engagement with U.S. companies that use LoC technology, training of graduate and undergraduate students, increased engagement and retention efforts targeting women and underrepresented minorities, student-facilitated peer-instruction at UC Riverside, a summer residential program for underrepresented minority high-school students at the University of Tennessee, collaborations with researchers at the Oak Ridge National Laboratory, and creation, presentation, and dissemination of tutorial materials to promote the adoption and use of software-programmable LoCs among the wider scientific community.