Pamela Burrage

Multiple myeloma (MM) is a plasma cell cancer that occurs in the bone marrow. A leading treatment for MM is the monoclonal antibody Daratumumab, targeting the CD38 receptor, which is highly overexpressed in myeloma cells. In this work we model drug resistance via loss of CD38 expression, which is a proposed mechanism of resistance to Daratumumab treatment. We develop an ODE model that includes drug resistance via two mechanisms: a direct effect in which CD38 expression is lost without cell death in response to Daratumumab, and an indirect effect in which CD38 expression switches on and off in the cancer cells; myeloma cells that do not express CD38 have lower fitness but are shielded from the drug action. The model also incorporates competition with healthy cells, death of healthy cells due to off-target drug effects, and a Michaelis-Menten type immune response. Using optimal control theory, we study the effect of the drug resistance mechanisms and the off-target drug effect on the optimal treatment regime. We identify a general increase in the duration and costs of optimal treatment, as a result of these added mechanisms. Several distinct optimal treatment regimes are identified within the parameter space.

This paper introduces Magnus-based methods for solving stochastic delay-differential equations (SDDEs). We construct Magnus--Euler--Maruyama (MEM) and Magnus--Milstein (MM) schemes by combining stochastic Magnus integrators with Taylor methods for SDDEs. These schemes are applied incrementally between multiples of the delay times. We present proofs of their convergence orders and demonstrate these rates through numerical examples and error graphs. Among the examples, we apply the MEM and MM schemes to both linear and nonlinear problems. We also apply the MEM scheme to a stochastic partial delay-differential equation (SPDDE), comparing its performance with the traditional Euler--Maruyama (EM) method. Under fine spatial discretization, the MEM scheme remains numerically stable while the EM method becomes unstable, yielding a significant computational advantage.

In this paper, we adapt a two-species agent-based cancer model that describes the interaction between cancer cells and healthy cells on a uniform grid to include the interaction with a third species—namely immune cells. We run six different scenarios to explore the competition between cancer and immune cells and the initial concentration of the immune cells on cancer dynamics. We then use coupled equation learning to construct a population-based reaction model for each scenario. We show how they can be unified into a single surrogate population-based reaction model, whose underlying three coupled ordinary differential equations are much easier to analyse than the original agent-based model. As an example, by finding the single steady state of the cancer concentration, we are able to find a linear relationship between this concentration and the initial concentration of the immune cells. This then enables us to estimate suitable values for the competition and initial concentration to reduce the cancer substantially without performing additional complex and expensive simulations from an agent-based stochastic model.

In this paper we consider the numerical solution of fractional differential equations. In particular, we study a step-by-step procedure, defined over a graded mesh, which is based on a truncated expansion of the vector field along the orthonormal Jacobi polynomial basis. Under mild hypotheses, the proposed procedure is capable of getting spectral accuracy. A few numerical examples are reported to confirm the theoretical findings.

Stochastic differential equations (SDEs) are a powerful tool to model fluctuations and uncertainty in complex systems. Although numerical methods have been designed to simulate SDEs effectively, it is still problematic when numerical solutions may be negative, but application problems require positive simulations. To address this issue, we propose balanced implicit Patankar–Euler methods to ensure positive simulations of SDEs. Instead of considering the addition of balanced terms to explicit methods in existing balanced methods, we attempt the deletion of possible negative terms from the explicit methods to maintain positivity of numerical simulations. The designed balanced terms include negative-valued drift terms and potential negative diffusion terms. The proposed method successfully addresses the issue of divisions with very small denominators in our recently designed stochastic Patankar method. Stability analysis shows that the balanced implicit Patankar–Euler method has much better stability properties than our recently designed composite Patankar–Euler method. Four SDE systems are used to examine the effectiveness, accuracy, and convergence properties of balanced implicit Patankar–Euler methods. Numerical results suggest that the proposed balanced implicit Patankar–Euler method is an effective and efficient approach to ensure positive simulations when any appropriate stepsize is used in simulating SDEs of biological regulatory systems.

Stochastic delay-differential equations (SDDEs) are SDEs with dependence on past times. Applications of SDDEs are found in financial modelling, engineering, and Stochastic delay-differential equations (SDDEs) are SDEs with dependence on past times. Applications of SDDEs are found in financial modelling, engineering, and