Memory effects in disease modelling through kernel estimates with oscillatory time history.

We design a linear chain trick algorithm for dynamical systems for which we have oscillatory time histories in the distributed time delay. We make use of this algorithmic framework to analyse memory effects in disease evolution in a population. The modelling is based on a susceptible-infected-recovered SIR-model and on a susceptible-exposed-infected-recovered SEIR-model through a kernel that dampens the activity based on the recent history of infectious individuals. This corresponds to adaptive behavior in the population or through governmental non-pharmaceutical interventions. We use the linear chain trick to show that such a model may be written in a Markovian way, and we analyze the stability of the system. We find that the adaptive behavior gives rise to either a stable equilibrium point or a stable limit cycle for a close to constant number of susceptibles, i.e. locally in time. We also show that the attack rate for this model is lower than it would be without the dampening, although the adaptive behavior disappears as time goes to infinity and the number of infected goes to zero.

A Kinetic Finite Volume Discretization of the Multidimensional PIDE Model for Gene Regulatory Networks.

In this paper, a finite volume discretization scheme for partial integro-differential equations (PIDEs) describing the temporal evolution of protein distribution in gene regulatory networks is proposed. It is shown that the obtained set of ODEs can be formally represented as a compartmental kinetic system with a strongly connected reaction graph. This allows the application of the theory of nonnegative and compartmental systems for the qualitative analysis of the approximating dynamics. In this framework, it is straightforward to show the existence, uniqueness and stability of equilibria. Moreover, the computation of the stationary probability distribution can be traced back to the solution of linear equations. The discretization scheme is presented for one and multiple dimensional models separately. Illustrative computational examples show the precision of the approach, and good agreement with previous results in the literature.

Pattern Formation in Mesic Savannas.

We analyze a spatially extended version of a well-known model of forest-savanna dynamics, which presents as a system of nonlinear partial integro-differential equations, and study necessary conditions for pattern-forming bifurcations. Homogeneous solutions dominate the dynamics of the standard forest-savanna model, regardless of the length scales of the various spatial processes considered. However, several different pattern-forming scenarios are possible upon including spatial resource limitation, such as competition for water, soil nutrients, or herbivory effects. Using numerical simulations and continuation, we study the nature of the resulting patterns as a function of system parameters and length scales, uncovering subcritical pattern-forming bifurcations and observing significant regions of multistability for realistic parameter regimes. Finally, we discuss our results in the context of extant savanna-forest modeling efforts and highlight ongoing challenges in building a unifying mathematical model for savannas across different rainfall levels.

Haar wavelets method for solving class of coupled systems of linear fractional Fredholm integro-differential equations.

In this paper, firstly, the " Haar wavelet method " is used to give approximate solutions for coupled systems of linear fractional Fredholm integro-differential equations. Moreover, we consider the fractional derivative to be described in the Caputo sense. The general idea of this technique is simply based on reducing this kinds of coupled systems into systems of algebraic equations which are easily to deal with and solve. Also, Laplace transform operator is included to develop a sophisticated approach which we called " Laplace Haar wavelet method " as an adjustment to " Haar wavelet method " to reduce the error and computational time. We provide illustrative examples to confirm validity, efficiency, accuracy, and applicability of the proposed methods.

An age-of-infection model with both symptomatic and asymptomatic infections.

We formulate a general age-of-infection epidemic model with two pathways: the symptomatic infections and the asymptomatic infections. We then calculate the basic reproduction number [Formula: see text] and establish the final size relation. It is shown that the ratio of accumulated counts of symptomatic patients and asymptomatic patients is determined by the symptomatic ratio f which is defined as the probability of eventually becoming symptomatic after being infected. We also formulate and study a general age-of-infection model with disease deaths and with two infection pathways. The final size relation is investigated, and the upper and lower bounds for final epidemic size are given. Several numerical simulations are performed to verify the analytical results.

Cross immunity protection and antibody-dependent enhancement in a distributed delay dynamic model.

Dengue fever is endemic in tropical and subtropical countries, and certain important features of the spread of dengue fever continue to pose challenges for mathematical modelling. Here we propose a system of integro-differential equations (IDE) to study the disease transmission dynamics that involve multi-serotypes and cross immunity. Our main objective is to incorporate and analyze the effect of a general time delay term describing acquired cross immunity protection and the effect of antibody-dependent enhancement (ADE), both characteristics of Dengue fever. We perform qualitative analysis of the model and obtain results to show the stability of the epidemiologically important steady solutions that are completely determined by the basic reproduction number and the invasion reproduction number. We establish the global dynamics by constructing a suitable Lyapunov functional. We also conduct some numerical experiments to illustrate bifurcation structures, indicating the occurrence of periodic oscillations for a specific range of values of a key parameter representing ADE.

An epi-evolutionary model for predicting the adaptation of spore-producing pathogens to quantitative resistance in heterogeneous environments.

We have modeled the evolutionary epidemiology of spore-producing plant pathogens in heterogeneous environments sown with several cultivars carrying quantitative resistances. The model explicitly tracks the infection-age structure and genetic composition of the pathogen population. Each strain is characterized by pathogenicity traits determining its infection efficiency and a time-varying sporulation curve taking into account lesion aging. We first derived a general expression of the basic reproduction number R 0 for fungal pathogens in heterogeneous environments. We show that the evolutionary attractors of the model coincide with local maxima of R 0 only if the infection efficiency is the same on all host types. We then studied the contribution of three basic resistance characteristics (the pathogenicity trait targeted, resistance effectiveness, and adaptation cost), in interaction with the deployment strategy (proportion of fields sown with a resistant cultivar), to (i) pathogen diversification at equilibrium and (ii) the shaping of transient dynamics from evolutionary and epidemiological perspectives. We show that quantitative resistance affecting only the sporulation curve will always lead to a monomorphic population, whereas dimorphism (i.e., pathogen diversification) can occur if resistance alters infection efficiency, notably with high adaptation costs and proportions of the resistant cultivar. Accordingly, the choice of the quantitative resistance genes operated by plant breeders is a driver of pathogen diversification. From an evolutionary perspective, the time to emergence of the evolutionary attractor best adapted to the resistant cultivar tends to be shorter when resistance affects infection efficiency than when it affects sporulation. Conversely, from an epidemiological perspective, epidemiological control is always greater when the resistance affects infection efficiency. This highlights the difficulty of defining deployment strategies for quantitative resistance simultaneously maximizing epidemiological and evolutionary outcomes.

Local asymptotic stability of a system of integro-differential equations describing clonal evolution of a self-renewing cell population under mutation.

In this paper we consider a system of non-linear integro-differential equations (IDEs) describing evolution of a clonally heterogeneous population of malignant white blood cells (leukemic cells) undergoing mutation and clonal selection. We prove existence and uniqueness of non-trivial steady states and study their asymptotic stability. The results are compared to those of the system without mutation. Existence of equilibria is proved by formulating the steady state problem as an eigenvalue problem and applying a version of the Krein-Rutmann theorem for Banach lattices. The stability at equilibrium is analysed using linearisation and the Weinstein-Aronszajn determinant which allows to conclude local asymptotic stability.

Operational matrices based on the shifted fifth-kind Chebyshev polynomials for solving nonlinear variable order integro-differential equations.

In this research, we study a general class of variable order integro-differential equations (VO-IDEs). We propose a numerical scheme based on the shifted fifth-kind Chebyshev polynomials (SFKCPs). First, in this scheme, we expand the unknown function and its derivatives in terms of the SFKCPs. To carry out the proposed scheme, we calculate the operational matrices depending on the SFKCPs to find an approximate solution of the original problem. These matrices, together with the collocation points, are used to transform the original problem to form a system of linear or nonlinear algebraic equations. We discuss the convergence of the method and then give an estimation of the error. We end by solving numerical tests, which show the high accuracy of our results.

A Mathematical Study of the Influence of Hypoxia and Acidity on the Evolutionary Dynamics of Cancer.

Hypoxia and acidity act as environmental stressors promoting selection for cancer cells with a more aggressive phenotype. As a result, a deeper theoretical understanding of the spatio-temporal processes that drive the adaptation of tumour cells to hypoxic and acidic microenvironments may open up new avenues of research in oncology and cancer treatment. We present a mathematical model to study the influence of hypoxia and acidity on the evolutionary dynamics of cancer cells in vascularised tumours. The model is formulated as a system of partial integro-differential equations that describe the phenotypic evolution of cancer cells in response to dynamic variations in the spatial distribution of three abiotic factors that are key players in tumour metabolism: oxygen, glucose and lactate. The results of numerical simulations of a calibrated version of the model based on real data recapitulate the eco-evolutionary spatial dynamics of tumour cells and their adaptation to hypoxic and acidic microenvironments. Moreover, such results demonstrate how nonlinear interactions between tumour cells and abiotic factors can lead to the formation of environmental gradients which select for cells with phenotypic characteristics that vary with distance from intra-tumour blood vessels, thus promoting the emergence of intra-tumour phenotypic heterogeneity. Finally, our theoretical findings reconcile the conclusions of earlier studies by showing that the order in which resistance to hypoxia and resistance to acidity arise in tumours depend on the ways in which oxygen and lactate act as environmental stressors in the evolutionary dynamics of cancer cells.

Diauxic Growth at the Mesoscopic Scale.

In the present paper, we study a diauxic growth that can be generated by a class of model at the mesoscopic scale. Although the diauxic growth can be related to the macroscopic scale, similarly to the logistic scale, one may ask whether models on mesoscopic or microscopic scales may lead to such a behavior. The present paper is the first step towards the developing of the mesoscopic models that lead to a diauxic growth at the macroscopic scale. We propose various nonlinear mesoscopic models conservative or not that lead directly to some diauxic growths.

Nonlocal and local models for taxis in cell migration: a rigorous limit procedure.

A rigorous limit procedure is presented which links nonlocal models involving adhesion or nonlocal chemotaxis to their local counterparts featuring haptotaxis and classical chemotaxis, respectively. It relies on a novel reformulation of the involved nonlocalities in terms of integral operators applied directly to the gradients of signal-dependent quantities. The proposed approach handles both model types in a unified way and extends the previous mathematical framework to settings that allow for general solution-dependent coefficient functions. The previous forms of nonlocal operators are compared with the new ones introduced in this paper and the advantages of the latter are highlighted by concrete examples. Numerical simulations in 1D provide an illustration of some of the theoretical findings.

Mathematical models for cell migration: a non-local perspective.

We provide a review of recent advancements in non-local continuous models for migration, mainly from the perspective of its involvement in embryonal development and cancer invasion. Particular emphasis is placed on spatial non-locality occurring in advection terms, used to characterize a cell's motility bias according to its interactions with other cellular and acellular components in its vicinity (e.g. cell-cell and cell-tissue adhesions, non-local chemotaxis), but we also briefly address spatially non-local source terms. Following a short introduction and description of applications, we give a systematic classification of available PDE models with respect to the type of featured non-localities and review some of the mathematical challenges arising from such models, with a focus on analytical aspects. This article is part of the theme issue 'Multi-scale analysis and modelling of collective migration in biological systems'.

Implicit Riesz wavelets based-method for solving singular fractional integro-differential equations with applications to hematopoietic stem cell modeling.

Riesz wavelets in L 2 ( R ) have been proven as a useful tool in the context of both pure and numerical analysis in many applications, due to their well prevailing and recognized theory and its natural properties such as sparsity and stability which lead to a well-conditioned scheme. In this paper, an effective and accurate technique based on Riesz wavelets is presented for solving weakly singular type of fractional order integro-differential equations with applications to solve system of fractional order model that describe the dynamics of uninfected, infected and free virus carried out by cytotoxic T lymphocytes (CTL). The Riesz wavelet in this work is constructed via the smoothed pseudo-splines refinable functions. The advantage of using such wavelets, in the context of fractional and integro-differential equations, lies on the simple structure of the reduced systems and in the powerfulness of obtaining approximated solutions for such equations that have weakly singular kernels. The proposed method shows a good performance and high accuracy orders.

A Collocation Method for Numerical Solution of Nonlinear Delay Integro-Differential Equations for Wireless Sensor Network and Internet of Things.

Wireless sensor network and industrial internet of things have been a growing area of research which is exploited in various fields such as smart home, smart industries, smart transportation, and so on. There is a need of a mechanism which can easily tackle the problems of nonlinear delay integro-differential equations for large-scale applications of Internet of Things. In this paper, Haar wavelet collocation technique is developed for the solution of nonlinear delay integro-differential equations for wireless sensor network and industrial Internet of Things. The method is applied to nonlinear delay Volterra, delay Fredholm and delay Volterra-Fredholm integro-differential equations which are based on the use of Haar wavelets. Some examples are given to show the computational efficiency of the proposed technique. The approximate solutions are compared with the exact solution. The maximum absolute and mean square roots errors for distant number of collocation points are also calculated. The results show that Haar method is efficient for solving these equations for industrial Internet of Things. The results are compared with existing methods from the literature. The results exhibit that the method is simple, precise and efficient.

A stochastic model for cancer metastasis: branching stochastic process with settlement.

We introduce a new stochastic model for metastatic growth, which takes the form of a branching stochastic process with settlement. The moving particles are interpreted as clusters of cancer cells, while stationary particles correspond to micro-tumours and metastases. The analysis of expected particle location, their locational variance, the furthest particle distribution and the extinction probability leads to a common type of differential equation, namely, a non-local integro-differential equation with distributed delay. We prove global existence and uniqueness results for this type of equation. The solutions' asymptotic behaviour for long time is characterized by an explicit index, a metastatic reproduction number $R_0$: metastases spread for $R_{0}>1$ and become extinct for $R_{0}<1$. Using metastatic data from mouse experiments, we show the suitability of our framework to model metastatic cancer.

A structured population model of clonal selection in acute leukemias with multiple maturation stages.

Recent progress in genetic techniques has shed light on the complex co-evolution of malignant cell clones in leukemias. However, several aspects of clonal selection still remain unclear. In this paper, we present a multi-compartmental continuously structured population model of selection dynamics in acute leukemias, which consists of a system of coupled integro-differential equations. Our model can be analysed in a more efficient way than classical models formulated in terms of ordinary differential equations. Exploiting the analytical tractability of this model, we investigate how clonal selection is shaped by the self-renewal fraction and the proliferation rate of leukemic cells at different maturation stages. We integrate analytical results with numerical solutions of a calibrated version of the model based on real patient data. In summary, our mathematical results formalise the biological notion that clonal selection is driven by the self-renewal fraction of leukemic stem cells and the clones that possess the highest value of this parameter are ultimately selected. Moreover, we demonstrate that the self-renewal fraction and the proliferation rate of non-stem cells do not have a substantial impact on clonal selection. Taken together, our results indicate that interclonal variability in the self-renewal fraction of leukemic stem cells provides the necessary substrate for clonal selection to act upon.

Global stability with selection in integro-differential Lotka-Volterra systems modelling trait-structured populations.

We analyse the asymptotic behaviour of integro-differential equations modelling N populations in interaction, all structured by different traits. Interactions are modelled by non-local terms involving linear combinations of the total number of individuals in each population. These models have already been shown to be suitable for the modelling of drug resistance in cancer, and they generalize the usual Lotka-Volterra ordinary differential equations. Our aim is to give conditions under which there is persistence of all species. Through the analysis of a Lyapunov function, our first main result gives a simple and general condition on the matrix of interactions, together with a convergence rate. The second main result establishes another type of condition in the specific case of mutualistic interactions. When either of these conditions is met, we describe which traits are asymptotically selected.

Analysis of stability for stochastic delay integro-differential equations.

In this paper, we concern stability of numerical methods applied to stochastic delay integro-differential equations. For linear stochastic delay integro-differential equations, it is shown that the mean-square stability is derived by the split-step backward Euler method without any restriction on step-size, while the Euler-Maruyama method could reproduce the mean-square stability under a step-size constraint. We also confirm the mean-square stability of the split-step backward Euler method for nonlinear stochastic delay integro-differential equations. The numerical experiments further verify the theoretical results.

An Alternative Formulation for a Distributed Delayed Logistic Equation.

We study an alternative single species logistic distributed delay differential equation (DDE) with decay-consistent delay in growth. Population oscillation is rarely observed in nature, in contrast to the outcomes of the classical logistic DDE. In the alternative discrete delay model proposed by Arino et al. (J Theor Biol 241(1):109-119, 2006), oscillatory behavior is excluded. This study adapts their idea of the decay-consistent delay and generalizes their model. We establish a threshold for survival and extinction: In the former case, it is confirmed using Lyapunov functionals that the population approaches the delay modified carrying capacity; in the later case the extinction is proved by the fluctuation lemma. We further use adaptive dynamics to conclude that the evolutionary trend is to make the mean delay in growth as short as possible. This confirms Hutchinson's conjecture (Hutchinson in Ann N Y Acad Sci 50(4):221-246, 1948) and fits biological evidence.