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Death is no longer an endpoint: a predictive model of murine sepsis
Carolyn Bellinger-Kawahara*1; KP Francis1; D Joh1; A Hubbard2; PR Contag3
(1) 860 Atlantic Avenue, Alameda, CA 94501, USA; (2) Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720; (3) Deparment of Neonatal & Developmental Medicine, Department of Pediatrics, Stanford University, Stanford, CA 94305 *(firstname.lastname@example.org)
We have developed a non-lethal, predictive model of murine sepsis. Using a strain of Pseudomonas aeruginosa constitutively expressing a chromosomally-placed luciferase operon, we have been able to quantitatively monitor the initiation and progress of sepsis in living mice. Mice were infected IP with Ps. aeruginosa and bioluminescent images collected at intervals over a 36 hour period using an ICCD camera system. For sixty hours post-infection, infected mice were also observed hourly and scored for survival. The increase in bioluminescent signal over time could be used to predict survival or death of an individual mouse. Statistical analysis showed that the model was predictive in two aspects. First, the model predicts if a given mouse will survive or die. Second, if the mouse is predicted to die, the model predicts an approximate death hour. Statistical analysis demonstrated that bioluminescent data collected over the first 13 hours post-infection was sufficient for accurate prediction. This non-lethal model can be substituted for many of the assays that currently depend on death as an endpoint, such as LD50, PD50, and ED50 determinations.
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