@article{windoloski_janum_berg_olufsen_2024, title={Characterization of differences in immune responses during bolus and continuous infusion endotoxin challenges using mathematical modelling}, ISSN={["1469-445X"]}, DOI={10.1113/EP091552}, abstractNote={AbstractEndotoxin administration is commonly used to study the inflammatory response, and though traditionally given as a bolus injection, it can be administered as a continuous infusion over multiple hours. Several studies hypothesize that the latter better represents the prolonged and pronounced inflammation observed in conditions like sepsis. Yet very few experimental studies have administered endotoxin using both strategies, leaving significant gaps in determining the underlying mechanisms responsible for their differing immune responses. We used mathematical modelling to analyse cytokine data from two studies administering a 2 ng kg−1 dose of endotoxin, one as a bolus and the other as a continuous infusion over 4 h. Using our model, we simulated the dynamics of mean and subject‐specific cytokine responses as well as the response to long‐term endotoxin administration. Cytokine measurements revealed that the bolus injection led to significantly higher peaks for interleukin (IL)‐8, while IL‐10 reaches higher peaks during continuous administration. Moreover, the peak timing of all measured cytokines occurred later with continuous infusion. We identified three model parameters that significantly differed between the two administration methods. Monocyte activation of IL‐10 was greater during the continuous infusion, while tumour necrosis factor  and IL‐8 recovery rates were faster for the bolus injection. This suggests that a continuous infusion elicits a stronger, longer‐lasting systemic reaction through increased stimulation of monocyte anti‐inflammatory mediator production and decreased recovery of pro‐inflammatory catalysts. Furthermore, the continuous infusion model exhibited prolonged inflammation with recurrent peaks resolving within 2 days during long‐term (20–32 h) endotoxin administration.}, journal={EXPERIMENTAL PHYSIOLOGY}, author={Windoloski, Kristen A. and Janum, Susanne and Berg, Ronan M. G. and Olufsen, Mette S.}, year={2024}, month={Mar} }
 @article{levy_windoloski_ludlam_2021, title={Original Matrix and agent-based modeling of threats to a diamond-backed terrapin population}, volume={340}, ISSN={["1879-3134"]}, DOI={10.1016/j.mbs.2021.108672}, abstractNote={Population models are important tools for evaluating human impacts and potential management approaches on declining species. However, often studies are limited by constraints of the specific modeling approach. In this study we considered the persistence of a diamond-backed terrapin (Malaclemys terrapin) population using two distinct modeling approaches. Two of the models were deterministic matrix models. Analysis of the discrete non-spatial models showed that female adult survival rate had the largest positive impact on population growth while delaying sexual maturity decreased population growth. The matrix models also demonstrated that an increase in crab traps skewed the sex ratio of the population in favor of females. The third model was a stochastic agent-based formulation that evaluated how increases in the number of crab traps and frequency of nest disturbances affected the long-term viability of diamond-backed terrapins. The spatial agent-based model revealed how terrapin mortality was highly sensitive to the proximity of traps to the primary terrapin habitat. Results from this project improve our understanding of threats to diamond-backed terrapins and can be used to guide conservation efforts.}, journal={MATHEMATICAL BIOSCIENCES}, author={Levy, Benjamin and Windoloski, Kristen and Ludlam, John}, year={2021}, month={Oct} }