PROJECT SUMMARY Although past advances in the field of Anesthesiology have made perioperative medicine remarkably safe for patients by comparison to historical standards, a myriad of important research questions that hold the keys to further progress in the allied fields of Anesthesia, Critical Care, and Pain Medicine remain unanswered. These questions exist in, but are not limited to, the following domains: (1) The mechanisms of action of anesthetic and sedative medications; (2) The systems biology of the perioperative state; (3) The mechanism and prevention of postoperative delirium and cognitive dysfunction; (4) Potential toxicity of anesthetic agents in the developing brain; (5) Maximization of safety related to human factors and communication throughout the perioperative period; (6) Development and testing of care pathways to improve long-term outcomes after surgery; (7) Sepsis and other causes of organ failure in intensive care; (8) Mechanisms and treatment of acute and chronic pain; and (9) Appropriate use of opioids and addiction prevention in the perioperative setting. To address these and other key questions that have the potential to improve public health, it is critically important to develop a core of well-trained and highly motivated physician-scientists within the Anesthesiology specialty who are dedicated to research and academics. The Department of Anesthesiology and Critical Care Medicine (ACCM) at the Johns Hopkins University (JHU) is submitting this renewal application for continued support of Postdoctoral Research Training in Anesthesiology (PRTA). In addition to providing an avenue for the support of Trainees, this program will continue to refine the approach whereby ACCM recruits talented and diverse young scientists engaged in Anesthesiology research and trains them via rigorous career development plans under the guidance of expert Faculty Mentors. Our principal aim is to develop the next generation of physician- scientists by endowing them with the tools and techniques best suited to their research while fostering innovation and the highest standards of scientific rigor. This aim is accomplished through a strong departmental research infrastructure that operates in conjunction with the incredible breadth and depth of the broader JHU scientific enterprise. Appointments are for two years, and key activities are mentored research and the potential for further education in the form of a relevant master's degree. As demonstrated in this application, ACCM has a long and productive history of clinical, translational, and basic research training in Anesthesiology, which the PRTA will continue to build upon and improve. Our previous success is highlighted by the career progression and scientific accomplishments of past Trainees, and our ongoing capacity to fulfill the mission of this Program is apparent in our outstanding pool of current and potential Trainees. We request continued funding for six Trainees per year for the so that...