Mathematical Medicine and Biology : a Journal of the IMA

Macrophages play a wide range of roles in resolving the inflammatory damage that underlies many medical conditions, and have the ability to adopt different phenotypes in response to different environmental stimuli. Categorising macrophage phenotypes exactly is a difficult task, and there is disparity in the literature around the optimal nomenclature to describe these phenotypes; however, what is clear is that macrophages can exhibit both pro- and anti-inflammatory behaviours dependent upon their phenotype, rendering mathematical models of the inflammatory response potentially sensitive to their description of the macrophage populations that they incorporate...

Altay Prefecture, a typical arid region in northwestern China, has experienced the climate transition from warming-drying to warming-wetting since 1980s and has attracted widespread attention. Nonetheless, it is still unclear how climate change has influenced the distribution of vegetation in this region. In this paper, a reaction-diffusion model of the climate-vegetation system is proposed to study the impact of climate change (precipitation, temperature and carbon dioxide concentration) on vegetation patterns in Altay Prefecture...

Drug resistance is a significant obstacle to effective cancer treatment. To gain insights into how drug resistance develops, we adopted a concept called fitness landscape and employed a phenotype-structured population model by fitting to a set of experimental data on a drug used for ovarian cancer, Olaparib Our modeling approach allowed us to understand how a drug affects the fitness landscape and track the evolution of a population of cancer cells structured with a spectrum of drug resistance. We also incorporated pharmacokinetic (PK) modeling to identify the optimal dosages of the drug that could lead to long-term tumor reduction...

Stochastically perturbed models, where the white noise type stochastic perturbations are proportional to the current system state, the most realistically describe real-life biosystems. However, such models essentially have no equilibrium states apart from one at the origin. This feature makes analysis of such models extremely difficult. Probably, the best result that can be found for such models is finding of accurate estimations of a region in the model phase space that serves as an attractor for model trajectories...

A risk factor model of BMI is an important building block of health simulations aimed at estimating government policy effects with regard to overweight and obesity. We created a model which generates representative population level distributions and which also mimics realistic BMI trajectories at an individual level so that policies aimed at individuals can be simulated. The model is constructed by combining several datasets. First, the population level distribution is extracted from a large, cross-sectional dataset...

We employ the multiphase, moving boundary model of [5] that describes the evolution of a motile, viscous tumour cell phase and an inviscid extracellular liquid phase. This model comprises two partial differential equations that govern the cell volume fraction and the cell velocity, together with a moving boundary condition for the tumour edge, and here we characterise and analyse its travelling-wave and pattern-forming behaviour. Numerical simulations of the model indicate that patterned solutions can be obtained, which correspond to multiple regions of high cell density separated by regions of low cell density...

The emergence of multiple strains of SARS-COV-2 has made it complicated to predict and control the COVID-19 pandemic. Although some vaccines have been effective in reducing the severity of the disease, these vaccines are designed for a speciffic strain of the virus and are usually less effective for other strains. In addition, the waning of vaccine-induced immunity, reinfection of recovered people, and incomplete vaccination are challenging to the vaccination program. In this study, we developed a detailed model to describe the multi-strain transmission dynamics of COVID-19 under vaccination...

Structure-function relationships occur throughout the sciences. Motivated by optimisation of such systems, we develop a framework for estimating the input modes from the singular value decomposition from the action of the forward operator alone. These can then be used to determine the input (structure) changes which induce the largest output (function) changes. The accuracy of the estimate is determined by reference to the method of snapshots. The proposed method is demonstrated on several example problems, and finally used to approximate the optimal airway treatment set for a problem in respiratory physiology...

Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell's viability, cell division, and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics...

Excessive activation of the regulatory cytokine transforming growth factor β (TGF-β) via contraction of airway smooth muscle (ASM) is associated with the development of asthma. In this study, we develop an ordinary differential equation model that describes the change in density of the key airway wall constituents, ASM and extracellular matrix (ECM), and their interplay with subcellular signalling pathways leading to the activation of TGF-β. We identify bistable parameter regimes where there are two positive steady states, corresponding to either reduced or elevated TGF-β concentration, with the latter leading additionally to increased ASM and ECM density...

This paper focuses on tracing the connectivity of white matter fascicles (WMF) in the brain. In particular, a generalized order algorithm based on mixture of non-central Wishart distribution (GMoNCW) model is proposed for this purpose. The proposed algorithm utilizes the generalization of integer order based approach with the mixture of non-central Wishart distribution (MoNCW) model. Pseudo super anomalous behavior of water diffusion inside human brain is the prime motivation of the the present study. We have shown results on multiple synthetic simulations with fibers orientations in two and three directions in each voxel as well as experiments on real data...

The pandemic caused by SARS-CoV-2 is responsible for a terrible health devastation with profoundly harmful consequences for the economic, social and political activities of communities on a global scale. Extraordinary efforts have been made by the world scientific community, who, in solidarity, shared knowledge so that effective vaccines could be produced quickly. However, it is still important to study therapies that can reduce the risk, until group immunity is reached, which, globally, will take a time that is still difficult to predict...

Current understanding of arrhythmia mechanisms and design of anti-arrhythmic drug therapies hinges on the assumption that myocytes from the same region of a single heart have similar, if not identical, action potential waveforms and drug responses. On the contrary, recent experiments reveal significant heterogeneity in uncoupled healthy myocytes both from different hearts as well as from identical regions within a single heart. In this work, a methodology is developed for quantifying the individual electrophysiological properties of large numbers of uncoupled cardiomyocytes under ion channel block in terms of the parameters values of a conceptual fast-slow model of electrical excitability...

In the mathematical epidemiology community, there is an increasing interest in shaping the complex interplay between human behaviour and disease spreading. We give a contribution in this direction by illustrating a method to derive behavioural change epidemic models from a stochastic particle description by the means of kinetic equations. We consider an Susceptible-Infected-Removed-like model where contact rates depend on the behavioural patterns adopted across the population. The selection of the social behaviour happens during the interactions between individuals adopting alternative strategies and it is driven by an imitation game dynamics...

Mal de Debarquement Syndrome (MdDS) is a puzzling central vestibular disorder characterized by a long-lasting perception of oscillatory postural instability that may occur after sea travels or flights. We have postulated that MdDS originates from the post-disembarking persistence of an adaptive internal oscillator consisting of a loop system, involving the right and left vestibular nuclei, and the Purkinje cells of the right and left flocculonodular cerebellar cortex, connected by GABAergic and glutamatergic fibers...

We present an individual-based model for the coevolutionary dynamics between CD8+ cytotoxic T lymphocytes (CTLs) and tumour cells. In this model, every cell is viewed as an individual agent whose phenotypic state is modelled by a discrete variable. For tumour cells this variable represents a parameterisation of the antigen expression profiles, while for CTLs it represents a parameterisation of the target antigens of T-cell receptors (TCRs). We formally derive the deterministic continuum limit of this individual-based model, which comprises a non-local partial differential equation for the phenotype distribution of tumour cells coupled with an integro-differential equation for the phenotype distribution of CTLs...

In this article, we investigate the importance of demography and contact patterns in determining the spread of COVID-19 and to the effectiveness of social distancing policies. We investigate these questions proposing an augmented epidemiological model with an age-structured model, with the population divided into susceptible (S), exposed (E), asymptomatic infectious (A), hospitalized (H), symptomatic infectious (I) and recovered individuals (R), to simulate COVID-19 dissemination. The simulations were carried out using six combinations of four types of isolation policies (work restrictions, isolation of the elderly, community distancing and school closures) and four representative fictitious countries generated over alternative demographic transition stage patterns (aged developed, developed, developing and least developed countries)...

A traditional method of in vitro cell culture involves a monolayer of cells at the base of a petri dish filled with culture medium. While the primary role of the culture medium is to supply nutrients to the cells, drug or other solutes may be added, depending on the purpose of the experiment. Metabolism by cells of oxygen, nutrients and drug is typically governed by Michaelis-Menten (M-M) kinetics. In this paper, a mathematical model of solute transport with M-M kinetics is developed. Upon non-dimensionalization, the reaction/diffusion system is re-characterized in terms of Volterra integral equations, where a parameter $\beta $, the ratio of the initial solute concentration to the M-M constant, proves important: $\beta \ll 1$ is relevant to drug metabolism for the liver, whereas $\beta \gg 1$ is more appropriate in the case of oxygen metabolism...

Hepatitis is the term used to describe inflammation in the liver. It is associated with a high rate of mortality, but the underlying disease mechanisms are not completely understood and treatment options are limited. We present a mathematical model of hepatitis that captures the complex interactions between hepatocytes (liver cells), hepatic stellate cells (cells in the liver that produce hepatitis-associated fibrosis) and the immune components that mediate inflammation. The model is in the form of a system of ordinary differential equations...

This paper describes computer models of three interventions used for treating refractory pulmonary hypertension (RPH). These procedures create either an atrial septal defect, a ventricular septal defect or, in the case of a Potts shunt, a patent ductus arteriosus. The aim in all three cases is to generate a right-to-left shunt, allowing for either pressure or volume unloading of the right side of the heart in the setting of right ventricular failure, while maintaining cardiac output. These shunts are created, however, at the expense of introducing de-oxygenated blood into the systemic circulation, thereby lowering the systemic arterial oxygen saturation...