We study model embeddability, which is a variation of the famous embedding problem in probability theory, when apart from the requirement that the Markov matrix is the matrix exponential of a rate matrix, we additionally ask that the rate matrix follows the model structure. We provide a characterisation of model embeddable Markov matrices corresponding to symmetric group-based phylogenetic models. In particular, we provide necessary and sufficient conditions in terms of the eigenvalues of symmetric group-based matrices. To showcase our main result on model embeddability, we provide an application to hachimoji models, which are eight-state models for synthetic DNA. Moreover, our main result on model embeddability enables us to compute the volume of the set of model embeddable Markov matrices relative to the volume of other relevant sets of Markov matrices within the model.

Phylogenetic networks can represent evolutionary events that cannot be described by phylogenetic trees. These networks are able to incorporate reticulate evolutionary events such as hybridization, introgression, and lateral gene transfer. Recently, network-based Markov models of DNA sequence evolution have been introduced along with model-based methods for reconstructing phylogenetic networks. For these methods to be consistent, the network parameter needs to be identifiable from data generated under the model. Here, we show that the semi-directed network parameter of a triangle-free, level-1 network model with any fixed number of reticulation vertices is generically identifiable under the Jukes-Cantor, Kimura 2-parameter, or Kimura 3-parameter constraints.

This paper is motivated by a question related to the control of amplitude and frequency of breathing. We present a simplified mathematical model, consisting of two piecewise linear ordinary differential equations, that could represent gas exchange in the lungs. We then define and solve an optimal control problem with unknown durations of inhalation and exhalation, subject to several constraints. The durations are divided such that one of the state variables is strictly increasing during the first phase and decreasing during the second phase. The optimal control problem can be solved analytically. One analytical solution is found when the forcing is a given sinusoidal function with unknown period and amplitude. Other analytical solutions are found when the forcing function, the period and the duration of the first phase are unknown but the amplitude is given. Our results show that different cost functions can produce different optimal forcing functions. We also show that the shape of these functions does not affect the average levels of oxygen in the lungs-the average level of oxygen is only dependent on the amplitude and period of breathing in the model we present.

Nonpharmaceutical interventions (NPI) such as banning public events or instituting lockdowns have been widely applied around the world to control the current COVID-19 pandemic. Typically, this type of intervention is imposed when an epidemiological indicator in a given population exceeds a certain threshold. Then, the nonpharmaceutical intervention is lifted when the levels of the indicator used have decreased sufficiently. What is the best indicator to use? In this paper, we propose a mathematical framework to try to answer this question. More specifically, the proposed framework permits to assess and compare different event-triggered controls based on epidemiological indicators. Our methodology consists of considering some outcomes that are consequences of the nonpharmaceutical interventions that a decision maker aims to make as low as possible. The peak demand for intensive care units (ICU) and the total number of days in lockdown are examples of such outcomes. If an epidemiological indicator is used to trigger the interventions, there is naturally a trade-off between the outcomes that can be seen as a curve parameterized by the trigger threshold to be used. The computation of these curves for a group of indicators then allows the selection of the best indicator the curve of which dominates the curves of the other indicators. This methodology is illustrated with indicators in the context of COVID-19 using deterministic compartmental models in discrete-time, although the framework can be adapted for a larger class of models.

A nonlocal and delayed cholera model with two transmission mechanisms in a spatially heterogeneous environment is derived. We introduce two basic reproduction numbers, one is for the bacterium in the environment and the other is for the cholera disease in the host population. If the basic reproduction number for the cholera bacterium in the environment is strictly less than one and the basic reproduction number of infection is no more than one, we prove globally asymptotically stability of the infection-free steady state. Otherwise, the infection will persist and there exists at least one endemic steady state. For the special homogeneous case, the endemic steady state is actually unique and globally asymptotically stable. Under some conditions, the basic reproduction number of infection is strictly decreasing with respect to the diffusion coefficients of cholera bacteria and infectious hosts. When these conditions are violated, numerical simulation suggests that spatial diffusion may not only spread the infection from high-risk region to low-risk region, but also increase the infection level in high-risk region.

Tree shape statistics provide valuable quantitative insights into evolutionary mechanisms underpinning phylogenetic trees, a commonly used graph representation of evolutionary relationships among taxonomic units ranging from viruses to species. We study two subtree counting statistics, the number of cherries and the number of pitchforks, for random phylogenetic trees generated by two widely used null tree models: the proportional to distinguishable arrangements (PDA) and the Yule-Harding-Kingman (YHK) models. By developing limit theorems for a version of extended Pólya urn models in which negative entries are permitted for their replacement matrices, we deduce the strong laws of large numbers and the central limit theorems for the joint distributions of these two counting statistics for the PDA and the YHK models. Our results indicate that the limiting behaviour of these two statistics, when appropriately scaled using the number of leaves in the underlying trees, is independent of the initial tree used in the tree generating process.

Many species are annual breeders who, between reproductive events, consume resources and may die. Their resource often reproduces continuously or has short, overlapping generations. An accurate model for such life cycles needs to represent both, the discrete- and the continuous-time processes in the community. The dynamics of a single discrete breeder and its resource can differ significantly from that of a fully continuous consumer-resource community (e.g., Lotka-Volterra) and that of a fully discrete one (e.g., Nicholson-Bailey). We study the dynamics of multiple discrete breeders on a single resource and identify a number of coexistence mechanisms and complex dynamics. The resource grows logistically, resource consumption is linear and consumer reproduction can be linear or nonlinear. We derive explicit conditions for the positive equilibrium state to exist and for mutual invasion to occur at that equilibrium. Stable equilibrium coexistence of more than one consumer is possible only when reproduction is nonlinear. Higher resource growth rate generally allows more consumers to stably coexist. Our explicit formulas allow us to generate communities of many coexisting consumers. Total biomass in the system seems to increase with the number of coexisting consumers. Complex patterns of coexistence arise, including bistability of equilibrium and non-equilibrium coexistence. The mixed continuous-discrete modeling approach can easily be adapted to study how certain aspects of global change affect discrete breeder communities.

We study a fast-slow version of an SIRS epidemiological model on homogeneous graphs, obtained through the application of the moment closure method. We use GSPT to study the model, taking into account that the infection period is much shorter than the average duration of immunity. We show that the dynamics occurs through a sequence of fast and slow flows, that can be described through 2-dimensional maps that, under some assumptions, can be approximated as 1-dimensional maps. Using this method, together with numerical bifurcation tools, we show that the model can give rise to periodic solutions, differently from the corresponding model based on homogeneous mixing.

Bone is constantly being renewed: in the adult skeleton, bone resorption and formation are in a tightly coupled balance, allowing for a constant bone density to be maintained. Yet this micro-environment provides the necessary conditions for the growth and proliferation of tumor cells, and thus bone is a common site for the development of metastases, mainly from primary breast and prostate cancer. Mathematical and computational models with differential equations can replicate this bone remodeling process. These models have been extended to include the effects of disruptive tumor pathologies in the bone dynamics, as metastases contribute to the decoupling between bone resorption and formation and to the self-perpetuating tumor growth cycle. Such models may also contemplate the counteraction effects of currently used therapies, and, in the case of treatments with drugs, their pharmocokinetics and pharmacodynamics. We present a thorough overview of biochemical models for bone remodeling, in the presence of a tumour together with anti-cancer and anti-resorptive therapy, formulated as systems of first-order differential equations, or simplified using variable order derivatives. The latter models, of which some are new to this paper, result in equations with fewer parameters, and allow accounting for anomalous diffusion processes. In this way, more compact and parsimonious models, that promptly highlight tumorous bone interactions, are achieved, providing an effective framework to counteract the loss of bone integrity on the affected areas.

Mathematical models are formal and simplified representations of the knowledge related to a phenomenon. In classical epidemic models, a major simplification consists in assuming that the infectious period is exponentially distributed, then implying that the chance of recovery is independent on the time since infection. Here, we first attempt to investigate the consequences of relaxing this assumption on the performances of time-variant disease control strategies by using optimal control theory. In the framework of a basic susceptible-infected-removed (SIR) model, an Erlang distribution of the infectious period is considered and optimal isolation strategies are searched for. The objective functional to be minimized takes into account the cost of the isolation efforts per time unit and the sanitary costs due to the incidence of the epidemic outbreak. Applying the Pontryagin's minimum principle, we prove that the optimal control problem admits only bang-bang solutions with at most two switches. In particular, the optimal strategy could be postponing the starting intervention time with respect to the beginning of the outbreak. Finally, by means of numerical simulations, we show how the shape of the optimal solutions is affected by the different distributions of the infectious period, by the relative weight of the two cost components, and by the initial conditions.

Specimens are collected from N different sources. Each specimen has probability p of being contaminated (in the case of a disease, e.g., p is the prevalence rate), independently of the other specimens. Suppose we can apply group testing, namely take small portions from several specimens, mix them together, and test the mixture for contamination, so that if the test turns positive, then at least one of the samples in the mixture is contaminated. In this paper we give a detailed probabilistic analysis of a binary search scheme, we propose, for determining all contaminated specimens. More precisely, we study the number T(N) of tests required in order to find all the contaminated specimens, if this search scheme is applied. We derive recursive and, in some cases, explicit formulas for the expectation, the variance, and the characteristic function of T(N). Also, we determine the asymptotic behavior of the moments of T(N) as [Formula: see text] and from that we obtain the limiting distribution of T(N) (appropriately normalized), which turns out to be normal.

Two stochastic models are proposed to describe the evolution of the COVID-19 pandemic. In the first model the population is partitioned into four compartments: susceptible S, infected I, removed R and dead people D. In order to have a cross validation, a deterministic version of such a model is also devised which is represented by a system of ordinary differential equations with delays. In the second stochastic model two further compartments are added: the class A of asymptomatic individuals and the class L of isolated infected people. Effects such as social distancing measures are easily included and the consequences are analyzed. Numerical solutions are obtained with Monte Carlo simulations. Quantitative predictions are provided which can be useful for the evaluation of political measures, e.g. the obtained results suggest that strategies based on herd immunity are too risky. Finally, the models are calibrated on data referring to the second wave of infection in Italy.