Kinetic theory of age-structured stochastic birth-death processes

Classical age-structured mass-action models such as the McKendrick-von Foerster equation have been extensively studied but are unable to describe stochastic fluctuations or population-size-dependent birth and death rates. Stochastic theories that treat semi-Markov age-dependent processes using, e.g., the Bellman-Harris equation do not resolve a population's age structure and are unable to quantify population-size dependencies. Conversely, current theories that include size-dependent population dynamics (e.g., mathematical models that include carrying capacity such as the logistic equation) cannot be easily extended to take into account age-dependent birth and death rates. In this paper, we present a systematic derivation of a new, fully stochastic kinetic theory for interacting age-structured populations. By defining multiparticle probability density functions, we derive a hierarchy of kinetic equations for the stochastic evolution of an aging population undergoing birth and death. We show that the fully stochastic age-dependent birth-death process precludes factorization of the corresponding probability densities, which then must be solved by using a Bogoliubov-–Born–-Green–-Kirkwood-–Yvon-like hierarchy. Explicit solutions are derived in three limits: no birth, no death, and steady state. These are then compared with their corresponding mean-field results. Our results generalize both deterministic models and existing master equation approaches by providing an intuitive and efficient way to simultaneously model age- and population-dependent stochastic dynamics applicable to the study of demography, stem cell dynamics, and disease evolution

Stochastic multi-scale models of competition within heterogeneous cellular populations: simulation methods and mean-field analysis

We propose a modelling framework to analyse the stochastic behaviour of heterogeneous, multi-scale cellular populations. We illustrate our methodology with a particular example in which we study a population with an oxygen-regulated proliferation rate. Our formulation is based on an age-dependent stochastic process. Cells within the population are characterised by their age. The age-dependent (oxygen-regulated) birth rate is given by a stochastic model of oxygen-dependent cell cycle progression. We then formulate an age-dependent birth-and-death process, which dictates the time evolution of the cell population. The population is under a feedback loop which controls its steady state size: cells consume oxygen which in turns fuels cell proliferation. We show that our stochastic model of cell cycle progression allows for heterogeneity within the cell population induced by stochastic effects. Such heterogeneous behaviour is reflected in variations in the proliferation rate. Within this set-up, we have established three main results. First, we have shown that the age to the G1/S transition, which essentially determines the birth rate, exhibits a remarkably simple scaling behaviour. This allows for a huge simplification of our numerical methodology. A further result is the observation that heterogeneous populations undergo an internal process of quasi-neutral competition. Finally, we investigated the effects of cell-cycle-phase dependent therapies (such as radiation therapy) on heterogeneous populations. In particular, we have studied the case in which the population contains a quiescent sub-population. Our mean-field analysis and numerical simulations confirm that, if the survival fraction of the therapy is too high, rescue of the quiescent population occurs. This gives rise to emergence of resistance to therapy since the rescued population is less sensitive to therapy

Survival of small populations under demographic stochasticity

We estimate the mean time to extinction of small populations in an environment with constant carrying capacity but under stochastic demography. In particular, we investigate the interaction of stochastic variation in fecundity and sex ratio under several different schemes of density dependent population growth regimes. The methods used include Markov chain theory, Monte Carlo simulations, and numerical simulations based on Markov chain theory. We find a strongly enhanced extinction risk if stochasticity in sex ratio and fluctuating population size act simultaneously as compared to the case where each mechanism acts alone. The distribution of extinction times deviates slightly from a geometric one, in particular for short extinction times. We also find that whether maximization of intrinsic growth rate decreases the risk of extinction or not depends strongly on the population regulation mechanism. If the population growth regime reduces populations above the carrying capacity to a size below the carrying capacity for large r (overshooting) then the extinction risk increases if the growth rate deviates from an optimal r-value

Stochastic and deterministic models for age-structured populations with genetically variable traits

Understanding how stochastic and non-linear deterministic processes interact is a major challenge in population dynamics theory. After a short review, we introduce a stochastic individual-centered particle model to describe the evolution in continuous time of a population with (continuous) age and trait structures. The individuals reproduce asexually, age, interact and die. The 'trait' is an individual heritable property (d-dimensional vector) that may influence birth and death rates and interactions between individuals, and vary by mutation. In a large population limit, the random process converges to the solution of a Gurtin-McCamy type PDE. We show that the random model has a long time behavior that differs from its deterministic limit. However, the results on the limiting PDE and large deviation techniques \textit{\`a la} Freidlin-Wentzell provide estimates of the extinction time and a better understanding of the long time behavior of the stochastic process. This has applications to the theory of adaptive dynamics used in evolutionary biology. We present simulations for two biological problems involving life-history trait evolution when body size is plastic and individual growth is taken into account.Comment: This work is a proceeding of the CANUM 2008 conferenc

Ordering dynamics in the voter model with aging

The voter model with memory-dependent dynamics is theoretically and numerically studied at the mean-field level. The `internal age', or time an individual spends holding the same state, is added to the set of binary states of the population, such that the probability of changing state (or activation probability $p_i$) depends on this age. A closed set of integro-differential equations describing the time evolution of the fraction of individuals with a given state and age is derived, and from it analytical results are obtained characterizing the behavior of the system close to the absorbing states. In general, different age-dependent activation probabilities have different effects on the dynamics. When the activation probability $p_i$ is an increasing function of the age $i$, the system reaches a steady state with coexistence of opinions. In the case of aging, with $p_i$ being a decreasing function, either the system reaches consensus or it gets trapped in a frozen state, depending on the value of $p_\infty$ (zero or not) and the velocity of $p_i$ approaching $p_\infty$. Moreover, when the system reaches consensus, the time ordering of the system can be exponential ($p_\infty>0$) or power-law like ($p_\infty=0$). Exact conditions for having one or another behavior, together with the equations and explicit expressions for the exponents, are provided

Theoretical connections between mathematical neuronal models corresponding to different expressions of noise

Identifying the right tools to express the stochastic aspects of neural activity has proven to be one of the biggest challenges in computational neuroscience. Even if there is no definitive answer to this issue, the most common procedure to express this randomness is the use of stochastic models. In accordance with the origin of variability, the sources of randomness are classified as intrinsic or extrinsic and give rise to distinct mathematical frameworks to track down the dynamics of the cell. While the external variability is generally treated by the use of a Wiener process in models such as the Integrate-and-Fire model, the internal variability is mostly expressed via a random firing process. In this paper, we investigate how those distinct expressions of variability can be related. To do so, we examine the probability density functions to the corresponding stochastic models and investigate in what way they can be mapped one to another via integral transforms. Our theoretical findings offer a new insight view into the particular categories of variability and it confirms that, despite their contrasting nature, the mathematical formalization of internal and external variability are strikingly similar

Toward an integrated workforce planning framework using structured equations

Strategic Workforce Planning is a company process providing best in class, economically sound, workforce management policies and goals. Despite the abundance of literature on the subject, this is a notorious challenge in terms of implementation. Reasons span from the youth of the field itself to broader data integration concerns that arise from gathering information from financial, human resource and business excellence systems. This paper aims at setting the first stones to a simple yet robust quantitative framework for Strategic Workforce Planning exercises. First a method based on structured equations is detailed. It is then used to answer two main workforce related questions: how to optimally hire to keep labor costs flat? How to build an experience constrained workforce at a minimal cost