Introduction Accuracy and effectiveness analyses of mass casualty triage systems are limited because there are no gold standard definitions for each of the triage categories. Until there is agreement on which patients should be identified by each triage category, it will be impossible to calculate sensitivity and specificity or to compare accuracy between triage systems. Objective To develop a consensus-based, functional gold standard definition for each mass casualty triage category. Methods National experts were recruited through the lead investigators’ contacts and their suggested contacts. Key informant interviews were conducted to develop a list of potential criteria for defining each triage category. Panelists were interviewed in order of their availability until redundancy of themes was achieved. Panelists were blinded to each other’s responses during the interviews. A modified Delphi survey was developed with the potential criteria identified during the interview and delivered to all recruited experts. In the early rounds, panelists could add, remove, or modify criteria. In the final rounds edits were made to the criteria until at least 80% agreement was achieved. Results Thirteen national and local experts were recruited to participate in the project. Six interviews were conducted. Three rounds of voting were performed, with 12 panelists participating in the first round, 12 in the second round, and 13 in the third round. After the first two rounds, the criteria were modified according to respondent suggestions. In the final round, over 90% agreement was achieved for all but one criterion. A single e-mail vote was conducted on edits to the final criterion and consensus was achieved. Conclusion A consensus-based, functional gold standard definition for each mass casualty triage category was been developed. These gold standard definitions can be used to evaluate the accuracy of mass casualty triage systems after an actual incident, during training, or for research.

We found that the 4 most popular mass casualty triage systems preformed similarly in an emergency department-based pediatric population. None of the systems were extremely accurate, and each demonstrated an unacceptable amount of under-triage. Better differentiating between patients categorized as "minimal" and "delayed" may improve the accuracy of mass casualty triage systems.

We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE739–98 localized mostly to the nucleus. The GST-11E7 and GST-11cE739–98 were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc-binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc-binding domain is essential for nuclear localization of 11E7.

We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), 76IRQLQDLLL84, within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch 65VRLVV69 within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the 65VRLVV69 sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex.

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