Daniel C. De Souza | Searcharxiv

arXiv2019

Dynamics of a Mathematical Hematopoietic Stem-Cell Population Model

We explore the bifurcations and dynamics of a scalar differential equation with a single constant delay which models the population of human hematopoietic stem cells in the bone marrow. One parameter continuation reveals that with a delay of just a few days, stable periodic dynamics can be generated of all periods from about one week up to one decade! The long period orbits seem to be generated by several mechanisms, one of which is a canard explosion, for which we approximate the dynamics near the slow manifold. Two-parameter continuation reveals parameter regions with even more exotic dynamics including quasi-periodic and phase-locked tori, and chaotic solutions. The panoply of dynamics that we find in the model demonstrates that instability in the stem cell dynamics could be sufficient to generate the rich behaviour seen in dynamic hematological diseases.

math.DS↗

arXiv2018

Response of an oscillatory delay differential equation to a periodic stimulus

Periodic hematological diseases such as cyclical neutropenia or cyclical thrombocytopenia, with their characteristic oscillations of circulating neutrophils or platelets, may pose grave problems for patients. Likewise, periodically administered chemotherapy has the unintended side effect of establishing periodic fluctuations in circulating white cells, red cell precursors and/or platelets. These fluctuations, either spontaneous or induced, often have serious consequences for the patient (e.g. neutropenia, anemia, or thrombocytopenia respectively) which exogenously administered cytokines can partially correct. The question of when and how to administer these drugs is a difficult one for clinicians and not easily answered. In this paper we use a simple model consisting of a delay differential equation with a piecewise linear nonlinearity, that has a periodic solution, to model the effect of a periodic disease or periodic chemotherapy. We then examine the response of this toy model to both single and periodic perturbations, meant to mimic the drug administration, as a function of the drug dose and the duration and frequency of its administration to best determine how to avoid side effects.

math.DS↗