Challenges in presenting high dimensional data to aid in triage in the DARPA virtual soldier project.

One of the goals of the DARPA Virtual Soldier Project is to aid the field medic in the triage of a casualty. In Phase I, we are currently collecting 12 baseline experimental physiological variables and a cardiac gated Computed Tomography (CT) imagery for use in an prototyping a futuristic electronic medical record, the "Holomer". We are using physiological models and Kalman filtering to aid in diagnosis and predict outcomes in relation to cardiac injury. The physiological modeling introduces another few hundred variables. Reducing the complexity of the above into easy-to-read text to aid in the triage by the field medic is the challenge with multiple display solutions. A description of the possible techniques follows.

Contribution of actin cytoskeletal alterations to ATP depletion and calcium-induced proximal tubule cell injury.

The actin cytoskeleton of rabbit proximal tubules was assessed by deoxyribonuclease (DNase) binding, sedimentability of detergent-insoluble actin, laser-scanning confocal microscopy, and ultrastructure during exposure to hypoxia, antimycin, or antimycin plus ionomycin. One-third of total actin was DNase reactive in control cells prior to deliberate depolymerization, and a similar proportion was unsedimentable from detergent lysates during 2.5 h at 100,000 g. Tubules injured by hypoxia or antimycin alone, without glycine, showed Ca(2+)-dependent pathology of the cytoskeleton, consisting of increases in DNase-reactive actin, redistribution of pelletable actin, and loss of microvilli concurrent with lethal membrane damage. In contrast, tubules similarly depleted of ATP and incubated with glycine showed no significant changes of DNase-reactive actin or actin sedimentability for up to 60 min, but, nevertheless, developed substantial loss of basal membrane-associated actin within 15 min and disruption of actin cores and clubbing of microvilli at durations > 30 min. These structural changes that occurred in the presence of glycine were not prevented by limiting Ca2+ availability or pH 6.9. Very rapid and extensive cytoskeletal disruption followed antimycin-plus-ionomycin treatment. In this setting, glycine and pH 6.9 decreased lethal membrane damage but did not ameliorate pathology in the cytoskeleton or microvilli; limiting Ca2+ availability partially protected the cytoskeleton but did not prevent lethal membrane damage. The data suggest that both ATP depletion-dependent but Ca(2+)-independent, as well as Ca(2+)-mediated, processes can disrupt the actin cytoskeleton during acute proximal tubule cell injury; that both types of change occur, despite protection afforded by glycine and reduced pH against lethal membrane damage; and that Ca(2+)-independent processes primarily account for prelethal actin cytoskeletal alterations during simple ATP depletion of proximal tubule cells.

Microencapsulation of chloroquine diphosphate by Eudragit RS100.

Chloroquine diphosphate, a highly water-soluble drug, was encapsulated by using a non-solvent addition coarcevation method. The coating material employed was Eudragit RS100. The liquid manufacturing vehicle was tetrahydrofuran (THF) while the non-solvent liquid was cyclohexane. Polyisobutylene (PIB) was used as an anti-aggregating agent. Particle size as well as shape evaluation was performed. Total drug content, in vitro drug release (from the microcapsules) as well as tasting test experiments were performed. The release studies on the microcapsules revealed an in vitro prolonged release effect while at the same time the bitter taste of the drug appeared to have been considerably masked by this method.