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Morgan Craig

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2 publications

preprint2026arXiv

Within-host immunology to age-of-infection epidemiology via a virtual cohort

We present a methodology providing a one-directional link from within-host individual heterogeneity to population-level disease transmission dynamics. The methodology works in several steps. A within-host model is investigated numerically to determine pathogen and immunological parameters leading to the largest variation of model responses. These key parameters are used to generate a synthetic population of individuals whose temporal immunological response profiles are recorded. These responses are ranked in terms of the severity of experienced outcomes, from mild infections to death, as a function of time since infection. This is used to parametrise an age-of-infection structured epidemiological model to study the transmission dynamics of the disease at the population level. The approach is illustrated using a within-host model describing SARS-CoV-2 infection and an SIR population-level model.

preprint2015arXiv

A mathematical model of granulopoiesis incorporating the negative feedback dynamics and kinetics of G-CSF/neutrophil binding and internalisation

We develop a physiological model of granulopoiesis which includes explicit modelling of the kinetics of the cytokine granulocyte colony-stimulating factor (G-CSF) incorporating both the freely circulating concentration and the concentration of the cytokine bound to mature neutrophils. G-CSF concentrations are used to directly regulate neutrophil production, with the rate of differentiation of stem cells to neutrophil precursors, the effective proliferation rate in mitosis, the maturation time, and the release rate from the mature marrow reservoir into circulation all dependent on the level of G-CSF in the system. The dependence of the maturation time on the cytokine concentration introduces a state-dependent delay into our differential equation model, and we show how this is derived from an age-structured partial differential equation model of the mitosis and maturation, and also detail the derivation of the rest of our model. The model and its estimated parameters are shown to successfully predict the neutrophil and G-CSF responses to a variety of treatment scenarios, including the combined administration of chemotherapy and exogenous G-CSF. This concomitant treatment was reproduced without any additional fitting to characterise drug-drug interactions.

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