Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis:A Brief Review

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which lead to chronic pain, poor life quality and, in some cases, mortality. Understanding the biological mechanisms behind the progression of the disease, as well as developing new methods for quantitative predictions of disease progression in the presence/absence of various therapies is important for the success of therapeutic approaches. The aim of this study is to review various quantitative predictive modelling approaches for understanding rheumatoid arthritis. To this end, we start by briefly discussing the biology of this disease and some current treatment approaches, as well as emphasising some of the open problems in the field. Then, we review various mathematical mechanistic models derived to address some of these open problems. We discuss models that investigate the biological mechanisms behind the progression of the disease, as well as pharmacokinetic and pharmacodynamic models for various drug therapies. Furthermore, we highlight models aimed at optimising the costs of the treatments while taking into consideration the evolution of the disease and potential complications.Publisher PDFPeer reviewe

The role of avoidance and learning behaviours on the formation and movement of biological aggregations

Communication forms the basis of any animal aggregation. However, not all organisms communicate the same way. Moreover, different psychological and physiological characteristics of individuals can lead to avoidance behaviours between different individuals. This can have implications on the formation and structure of large biological aggregations. In this article, we use a mathematical model to investigate the effects of avoidance behaviour by a subpopulation, on the spatial dynamics of the whole population. We show that avoidance (exhibited even by a small fraction of the population) can alter the spatio-temporal patterns of the whole groups, leading to new patterns difficult to predict from the case without avoidance. Generally, these patterns show the segregation of the populations into different aggregations (spatially separated) or inside the same aggregation. Moreover, we investigate numerically the situation where individuals can learn to tolerate their neighbours. In this case, we observe an unexpected spatial segregation inside moving aggregations of individuals that tolerate their neighbours and those that avoid their neighbours

Modelling rheumatoid arthritis : a hybrid modelling framework to describe pannus formation in a small joint

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of these aspects, to date there are few such models that can be used to better understand the disease. As a first step in the mechanistic understanding of RA, in this study we introduce a new hybrid mathematical modelling framework that describes pannus formation in a small proximal interphalangeal (PIP) joint. We perform numerical simulations with this new model, to investigate the impact of different levels of immune cells (macrophages and fibroblasts) on the degradation of bone and cartilage. Since many model parameters are unknown and cannot be estimated due to a lack of experiments, we also perform a sensitivity analysis of model outputs to various model parameters (single parameters or combinations of parameters). Finally, we discuss how our model could be applied to investigate current treatments for RA, for example, methotrexate, TNF-inhibitors or tocilizumab, which can impact different model parameters.Publisher PDFPeer reviewe

Bifurcations and chaotic dynamics in a tumour-immune-virus system

Despite mounting evidence that oncolytic viruses can be effective in treating cancer, understanding the details of the interactions between tumour cells, oncolytic viruses and immune cells that could lead to tumour control or tumour escape is still an open problem. Mathematical modelling of cancer oncolytic therapies has been used to investigate the biological mechanisms behind the observed temporal patterns of tumour growth. However, many models exhibit very complex dynamics, which renders them difficult to investigate. In this case, bifurcation diagrams could enable the visualisation of model dynamics by identifying (in the parameter space) the particular transition points between different behaviours. Here, we describe and investigate two simple mathematical models for oncolytic virus cancer therapy, with constant and immunity-dependent carrying capacity. While both models can exhibit complex dynamics, namely fixed points, periodic orbits and chaotic behaviours, only the model with immunity-dependent carrying capacity can exhibit them for biologically realistic situations, i.e., before the tumour grows too large and the experiment is terminated. Moreover, with the help of the bifurcation diagrams we uncover two unexpected behaviours in virus-tumour dynamics: (i) for short virus half-life, the tumour size seems to be too small to be detected, while for long virus half-life the tumour grows to larger sizes that can be detected; (ii) some model parameters have opposite effects on the transient and asymptotic dynamics of the tumour.Publisher PDFPeer reviewe

Non-local kinetic and macroscopic models for self-organised animal aggregations

The last two decades have seen a surge in kinetic and macroscopic models derived to investigate the multi-scale aspects of self-organised biological aggregations. Because the individual-level details incorporated into the kinetic models (e.g., individual speeds and turning rates) make them somewhat difficult to investigate, one is interested in transforming these models into simpler macroscopic models, by using various scaling techniques that are imposed by the biological assumptions of the models. However, not many studies investigate how the dynamics of the initial models are preserved via these scalings. Here, we consider two scaling approaches (parabolic and grazing collision limits) that can be used to reduce a class of non-local 1D and 2D models for biological aggregations to simpler models existent in the literature. Then, we investigate how some of the spatio-temporal patterns exhibited by the original kinetic models are preserved via these scalings. To this end, we focus on the parabolic scaling for non-local 1D models and apply asymptotic preserving numerical methods, which allow us to analyse changes in the patterns as the scaling coefficient ϵ is varied from ϵ=1 (for 1D transport models) to ϵ=0 (for 1D parabolic models). We show that some patterns (describing stationary aggregations) are preserved in the limit ϵ→0, while other patterns (describing moving aggregations) are lost. To understand the loss of these patterns, we construct bifurcation diagrams