The purpose of this proposal is to improve public health through renewal of an NIH-supported large-scale network of prehospital and hospital care (called SIREN) created 5 years ago. This network that will continue to oversee the conduct of pragmatic clinical trials addressing emergency medical conditions affecting brain, heart, lung and/or blood as well as life-threatening trauma. The components of this proposal locally include the University of Washington and its Harborview and University Medical Centers (as “Hub”) in concert with King County Emergency Medical Services (KCEMS). This “Hub” will both participate in these clinical trials and provide administrative and academic oversight and leadership over additional community-based facilities in the Pacific Northwest, and an additional academic facility (the University of British Columbia in Vancouver, BC), which will serve as enrolling sites (or “Spokes”) for the conduct of these clinical trials. This proposal does not involve nor seek approval for the conduct of the clinical trials themselves. Rather it strictly creates the network infrastructure for these trials. These trials themselves require independent regulatory approval which will continue to occur through a previously established Central Institutional Review Board (ADVARRA) to which the University of Washington Institutional Review Board has previously ceded oversight upon creation of the SIREN network 5 years ago.