Using the model of resource and time-based triage (MORTT) to guide scarce resource allocation in the aftermath of a nuclear detonation.

Conventional triage algorithms assume unlimited medical resource availability. After a nuclear detonation, medical resources are likely to be particularly limited, suggesting that conventional triage algorithms need to be rethought. To test various hypotheses related to the prioritization of victims in this setting, we developed the model of resource- and time-based triage (MORTT). This model uses information on time to death, probability of survival if treated and if untreated, and time to treat various types of traumatic injuries in an agent-based model in which the time of medical practitioners or materials can be limited. In this embodiment, MORTT focuses solely on triage for surgical procedures in the first 48 hours after a nuclear detonation. MORTT determines the impact on survival based on user-selected prioritization of victims by severity or type of injury. Using MORTT, we found that in poorly resourced settings, prioritizing victims with moderate life-threatening injuries over victims with severe life-threatening injuries saves more lives and reduces demand for intensive care, which is likely to outstrip local and national capacity. Furthermore, more lives would be saved if victims with combined injury (ie, trauma plus radiation >2 Gy) are prioritized after nonirradiated victims with similar trauma.

Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b.

Cbl proteins are ubiquitin protein ligases, which ubiquitinate activated tyrosine kinases and target them for degradation. Both c-Cbl and Cbl-b have an ubiquitin associated (UBA) domain at their C-terminal end. We observed that high molecular weight ubiquitinated proteins constitutively coimmunoprecipitated with transfected and endogenous Cbl-b, but not c-Cbl. The binding site for these ubiquitinated proteins was mapped to the UBA domain of Cbl-b (UBAb). GST-fusion proteins containing the UBAb interacted with ubiquitinated proteins and polyubiquitin chains in vitro, whereas those containing the UBA domain of c-Cbl (UBAc) did not. The UBAb had a much greater affinity for polyubiquitin chains than for monoubiquitin. Analysis of the UBAb and UBAc demonstrate that the affinity for ubiquitin is determined by multiple amino-acid differences between the two domains. Overexpression of the UBAb, but not overexpression of the UBAc, inhibited a variety of ubiquitin-mediated processes such as degradation of ubiquitinated proteins (i.e. EGFR, Mdm-2, and Siah-1). This in vivo result is consistent with the differences in ubiquitin binding observed in vitro between the UBAb and UBAc. This difference in ubiquitin-binding may reflect distinct regulatory functions of c-Cbl and Cbl-b.