Recombinant Factors for Hemostasis

Trauma deaths are a result of hemorrhage in 37% of civilians and 47% military personnel and are the primary cause of death for individuals under 44 years of age. Current techniques used to treat hemorrhage are inadequate for severe bleeding. Preliminary research indicates that fibrin sealants (FS) alone or in combination with a dressing may be more effective; however, it has not been economically feasible for widespread use because of prohibitive costs related to procuring the proteins. To meet future demands for hemostatic therapies, FS will likely include recombinant human fibrinogen (rFI) and recombinant human Factor XIII (rFXIII). The underlying hypothesis of the research presented in this dissertation is that a liquid fibrin sealant (LFS) composed of recombinant FI, FXIII and FIIa in optimized proportions can assist hemostasis in the presence and absence of a bioresorbable bandage while using considerably fewer biologics than commercial products currently available. This dissertation characterized rFI produced in the milk of transgenic cows, plasma-derived thrombin (pdFIIa) activated by sodium citrate and rFXIIIa expressed in genetically engineered Pichia pastoris with respect to their capacity to serve as components in a LFS. The ratios of these factors were optimized to yield a LFS with a rapid clot formation rate and high viscoelastic strength. This optimized LFS was preliminarily tested ex vivo and in vivo. The clotting kinetics and viscoelastic strength of our optimized LFS was equivalent to those of a commercially available LFS; however, it uses approximately 75% less fibrinogen and thrombin. Our optimal LFS successfully achieved hemostasis in a significant number of the wounds that included extensive tissue and vascular damage. LFS applied without the assistance of a dressing was able to stop bleeding of oozing wounds or those with small vessels; however, a scaffold was needed when wounds contained large vasculature.

Thermal Imagery Applied to Reducing Bird Hazards to Aircraft at Airports

Airports worldwide are at a disadvantage when it comes to being able to spot birds and warn aircrews about the location of flocks either on the ground or close to the airfield. Birds simply cannot be easily seen during the day and are nearly invisible targets for planes at night or during low visibility. Thermal imaging (infrared) devices can be used to allow ground and tower personnel to pinpoint bird locations day or night, thus giving the airport operators the ability to launch countermeasures or simply warn the aircrews. This technology is available now, though it has been predominately isolated to medical and military system modifications. The cost of these devices has dropped significantly in recent years as technology, capability, and availability have continued to increase. Davison Army Airfield (DAAF), which is located about 20 miles south of Ronald Reagan National Airport in Washington, DC, is the transient home to many bird species including an abundance of ducks, seagulls, pigeons, and migrating Canadian geese. Over the past few years, DAAF implemented a variety of measures in an attempt to control the bird hazards on the airfield. Unfortunately, when it came to controlling these birds on or near our runways and aircraft movement areas we were more reactive than proactive. We would do airfield checks several times an hour to detect and deter any birds in these areas. The deterrents used included vehicle/human presence, pyrotechnics, and the periodic use of a trained border collie. At the time, we felt like we were doing all we could to reduce the threat to aircraft and human life. It was not until a near fatal accident in October 1998, when we truly realized how dangerous our operating environment really was to aircraft at or near the airfield. It was at this time, we had a C-12 (twin-engine passenger plane) land on our primary runway at night. The tower cleared the aircraft to land, and upon touchdown to the runway the aircraft collided with a flock of geese. Neither the tower nor the crew of the aircraft saw the geese because they were obscured in the darkness. The end result was 12 dead geese and $374,000 damage to the C-12. Fortunately, there were no human fatalities, but it was painfully clear we needed to improve our method of clearing the runway at night and during low visibility conditions. It was through this realization that we ventured to the U.S. Army Communications and Electronics Command for ideas on ways to deal with our threat. It was through a sub-organization within this command, Night Vision Labs, that we realized the possibilities of modifying thermal imagery and infrared technology to detecting wildlife on airports.