Having control over species abundances and community resilience is of great interest for experimental, agricultural, industrial and conservation purposes. Here, we theoretically explore the possibility of manipulating ecological communities by modifying pairwise interactions. Specifically, we establish which interaction values should be modified, and by how much, in order to alter the composition or resilience of a community towards a favorable direction. While doing so, we also take into account the experimental difficulties in making such modifications by including in our optimization process, a cost parameter, which penalizes large modifications. In addition to prescribing what changes should be made to interspecies interactions given some modification cost, our approach also serves to establish the limits of community control, i.e. how well can one approach an ecological goal at best, even when not constrained by cost.

In this paper we introduce random proliferation models on graphs. We consider two types of particles: type-1/mutant/invader/red particles proliferates on a population of type-2/wild-type/resident/blue particles. Unlike the well-known Moran model on graphs -as introduced in Lieberman et al. (2005)-, type-1 particles can occupy in a single iteration several neighbouring sites previously occupied by type-2 particles. Two variants are considered, depending on the random distribution involving the proliferation mechanism: Bernoulli and binomial proliferation. By comparison with fixation probability of type-1 particles in the Moran process, critical parameters are introduced. Properties of proliferation are studied and some particular cases are analytically solved. Finally, by updating the parameters that drive the processes through a density-dependent mechanism, it is possible to capture additional relevant features as fluctuating waves of type-1 particles over long periods of time. In fact, the models can be adapted to tackle more general, complex and realistic situations.

An accurate estimate of the number of infected individuals in any disease is crucial. Current estimates are mainly based on the fraction of positive samples or the total number of positive samples. However, both methods are biased and sensitive to the sampling depth. We here propose an alternative method to use the attributes of each sample to estimate the change in the total number of positive patients in the total population. We present a Bayesian estimator assuming a combination of condition and time-dependent probability of being positive, and mixed implicit-explicit solution for the probability of a person with conditions i at time t of being positive. We use this estimate to predict the total probability of being positive at a given day t. We show that these estimate results are smooth and not sensitive to the properties of the samples. Moreover, these results are a better predictor of future mortality.

Chromatin remodeling is an essential form of gene regulation that is involved in a variety of biological processes. We develop a theoretical model that takes advantage of percolation effects at the level of nucleosome interactions, which allows for ultrasensitive chromatin expansion. This model is non-cooperative and readily provides spatial bounds to the expansion region, preventing uncontrolled remodeling events. We explore different chromatin architectures and the ultrasensitivity of the chromatin density as a function of transcription factor concentration. We also compare our model with experimental data involving an inhibitor of nucleosome acetylation. These results suggest a novel mechanism for spatially-bounded chromatin remodeling and they provide means for quantitative comparisons between proposed models of chromatin architecture.

The rate of drug delivery to cells and the subsequent rate of drug metabolism are dependent on the cell membrane permeability to the drug. In some cases, tissue may be composed of different types of cells that exhibit order of magnitude differences in their membrane permeabilities. This paper presents a brief review of the components of the tissue scale three-compartment pharmacokinetic model of drug delivery to single-cell-type populations. The existing model is extended to consider tissue composed of two different cell types. A case study is presented of infusion mediated delivery of doxorubicin to a tumor that is composed of a drug reactive cell type and of a drug resistive cell type. The membrane permeabilities of the two cell types differ by an order of magnitude. A parametric investigation of the population composition is conducted and it is shown that the drug metabolism of the low permeability cells are negatively influenced by the fraction of the tissue composed of the permeable drug reactive cells. This is because when the population is composed mostly of drug permeable cells, the extracellular space is rapidly depleted of the drug. This has two compounding effects: (i) locally there is simply less drug available to the neighboring drug resistant cells, and (ii) the depletion of the drug from the extracellular space near the vessel-tissue interface leaves less drug to be transported to both cell types farther away from the vessel.

Using spatialised population measurements and related geographic habitat data, it is feasible nowadays to derive parsimonious spatially explicit population models and to carry on their parameter estimation. To achieve such goal, reaction-diffusion models are common in conservation biology and agricultural plant health where they are used, for example, for landscape planning or epidemiological surveillance. Unfortunately, if the mathematical methods and computational power are readily available, biological measurements are not. Despite the high throughput of some habitat related remote sensors, the experimental cost of biological measurements are one of the worst bottleneck against a widespread usage of reaction-diffusion models. Hence we will recall some classical methods for optimal experimental design that we deem useful to spatial ecologist. Using two case studies, one in landscape ecology and one in conservation biology, we will show how to construct a priori experimental design minimizing variance of parameter estimates, enabling optimal experimental setup under constraints.

Metapopulation models have been a powerful tool for both theorizing and simulating epidemic dynamics. In a metapopulation model, one considers a network composed of subpopulations and their pairwise connections, and individuals are assumed to migrate from one subpopulation to another obeying a given mobility rule. While how different mobility rules affect epidemic dynamics in metapopulation models has been studied, there have been relatively few efforts on comparison of the effects of simple (i.e., unbiased) random walks and more complex mobility rules. Here we study a susceptible-infectious-susceptible (SIS) dynamics in a metapopulation model in which individuals obey a parametric second-order random-walk mobility rule called the node2vec. We map the second-order mobility rule of the node2vec to a first-order random walk in a network whose each node is a directed edge connecting a pair of subpopulations and then derive the epidemic threshold. For various networks, we find that the epidemic threshold is large (therefore, epidemic spreading tends to be suppressed) when the individuals infrequently backtrack or infrequently visit the common neighbors of the currently visited and the last visited subpopulations than when the individuals obey the simple random walk. The amount of change in the epidemic threshold induced by the node2vec mobility is in general not as large as, but is sometimes comparable with, the one induced by the change in the diffusion rate for individuals.

Household-structured infectious disease models consider the increased transmission potential between individuals of the same household when compared with two individuals in different households. Accounting for these heterogeneities in transmission enables control measures to be more effectively planned. Ideally, pre-control data may be used to fit such a household-structured model at an endemic steady state, before making dynamic forward-predictions under different proposed strategies. However, this requires the accurate calculation of the steady states for the full dynamic model. We observe that steady state SIS dynamics with household structure cannot necessarily be described by the master equation for a single household, instead requiring consideration of the full system. However, solving the full system of equations becomes increasingly computationally intensive, particularly for higher-dimensional models. We compare two approximations to the full system: the single household master equation; and a proposed alternative method, using the Fokker-Planck equation. Moment closure is another commonly used method, but for more complicated systems, the equations quickly become unwieldy and very difficult to derive. In comparison, using the master equation for a single household is easily implementable, however it can be quite inaccurate. In this paper we compare these methods in terms of accuracy and ease of implementation. We find that there are regions of parameter space in which each method outperforms the other, and that these regions of parameter space can be characterised by the infection prevalence, or by the correlation between household states.

Retinitis pigmentosa (RP) is the term used to denote a group of inherited retinal-degenerative conditions that cause progressive sight loss. Individuals with this condition lose their light-sensitive photoreceptor cells, known as rods and cones, over a period of years to decades; degeneration starting in the retinal periphery, and spreading peripherally and centrally over time. RP is a rod-cone dystrophy, meaning that rod health and function are affected earlier and more severely than that of cones. Rods degenerate due to an underlying mutation, whereas the reasons for cone degeneration are unknown. A number of mechanisms have been proposed to explain secondary cone loss and the spatio-temporal patterns of retinal degeneration in RP. One of the most promising is the trophic factor hypothesis, which suggests that rods produce a factor necessary for cone survival, such that, when rods degenerate, cone degeneration follows. In this paper we formulate and analyse mathematical models of human RP under the trophic factor hypothesis. These models are constructed as systems of reaction-diffusion partial differential equations in one spatial dimension, and are solved and analysed using a combination of numerical and analytical methods. We predict the conditions under which cones will degenerate following the loss of a patch of rods from the retina, the critical trophic factor treatment rate required to prevent cone degeneration following rod loss and the spatio-temporal patterns of cone loss that would result if the trophic factor mechanism alone were responsible for retinal degeneration.

We introduce a compartmental epidemic model to describe the spread of COVID-19 within a population, assuming that a vaccine is available, but vaccination is not mandatory. The model takes into account vaccine hesitancy and the refusal of vaccination by individuals, which take their decision on vaccination based on both the present and past information about the spread of the disease. Theoretical analysis and simulations show that voluntary vaccination can certainly reduce the impact of the disease but is unable to eliminate it. We also demonstrate how the information-related parameters affect the dynamics of the disease. In particular, vaccine hesitancy and refusal are better contained in case of widespread information coverage and short-term memory. Finally, the possible impact of seasonality on the spread of the disease is investigated.

Consciousness has been hypothesized to operate as a global workspace, which accesses and integrates multimodal information in a unified manner, supports expectation violation monitoring and reduction, and the motivation, programming and control of action. One important yet open issue concerns how the subjective perspective at the core of consciousness, and subjective properties of manifestation of the environment in such perspective as an embodied experience, play a role in such process. We operationalised the concept of subjective perspective using the principles of the Projective Consciousness Model (PCM), based on the projective geometrical concept of Field of Consciousness. We show how these principles can account for documented relationships between appraisal and distance as an inverse distance law, yield a generative model of affective and epistemic drives based on purely subjective parameters, such as the apparent size of objects, and can be generalised to implement Theory of Mind, in a manner that is consistent with simulation theory. We used simulations of artificial agents, based on psychological rationale, to demonstrate how different model parameters could generate a variety of emergent adaptive and maladaptive behaviours that are relevant to developmental and clinical psychology: the ability to be resilient in the face of obstacles through imaginary projections, the emergence of social approach and joint attention behaviours, the ability to take advantage of false beliefs attributed to others, the emergence of avoidance behaviours as observed in social anxiety disorders, the presence of restricted interests as observed in autism spectrum disorders. The simulation of agents was applied to a specific robotic context, and agents' behaviours were demonstrated by controlling the corresponding robots. Our results contribute to advance the scientific understanding of the causal relationships between core aspects of the phenomenology of consciousness and its functions in human cybernetics.

Many studies examine how the landscape affects memory-informed movement patterns, but very few examine how memory-informed foragers influence the landscape. This reverse relationship is an important factor in preventing the continued decline of many ecosystem services. We investigate this question in the context of crop pollination services by wild bees, a critical ecosystem service that is in steep decline. Many studies suggest that adding wild flower patches near crops can result in higher crop pollination services, but specific advice pertaining to the optimal location and density of these wild flower patches is lacking, as well as any estimate of the expected change in crop pollination services. In this work, we seek to understand what is the optimal placement of a flower patch relative to a single crop field, during crop bloom and considering spatial factors alone. We develop an individual based model of memory-based foraging by bumble bees to simulate bee movement from a single nest while the crop is in bloom, and measure the resulting crop pollination services. We consider a single crop field enhanced with a wild flower patch in a variable location, and measure crop flower visitation over the course of a single day. We analyze the pollination intensity and spatial distribution of flower visits to determine optimal wild flower patch placement for an isolated crop field. We find that the spatial arrangement of crop and wild flower patch have a significant effect on the number of crop flower visits, and that these effects arise from the memory-informed foraging pattern. The most effective planting locations are either in the centre of the crop field or on the far side of the crop field, away from the single bumble bee nest.

In modelling pathogen evolution during epidemics, it is important to understand the interactions between within-host infection dynamics and between-host pathogen transmission. Multiscale models often assume an immune response that is highly responsive to pathogen dynamics. Empirical evidence, however, suggests that the immune response in acute infections is triggered and programmatic. This leads to somewhat more predictable infection trajectories where transition times and, consequently, the infectious window are non-exponentially distributed. Here, we develop a within-host model where the immune response is triggered by pathogen growth but otherwise develops independently, and use this to obtain analytic expressions for the infectious period and peak pathogen load. This allows us to model the basic reproductive number in terms of explicit functional relationships among within-host traits including the growth rate of the pathogen. We find that the dependence of pathogen load and the infectious window on within-host parameters constrains the evolution of the pathogen growth rate. At low growth rate, selection favours a higher pathogen load and therefore increasing pathogen growth rate. At high growth rates, selection for a longer infectious window trades off against selection against the effects of virulence. At intermediate growth rates the basic reproductive number is relatively insensitive to changes in the growth rate. The resulting "flat" region of the pathogen fitness landscape is due to the stability of the programmatic immune response in clearing the infection.

The recent advances in cancer immunotherapy boosted the development of tumor-immune system models, with the aim to indicate more efficient treatments. Physical understanding is however difficult to be acquired, due to the complexity and the multi-scale dynamics of these models. In this work, the dynamics of a fundamental model formulating the interactions of tumor cells with natural killer cells, CD8+ T cells and circulating lymphocytes is examined. It is first shown that the long-term evolution of the system towards high-tumor or tumor-free equilibria is determined by the dynamics of an initial explosive stage of tumor progression. Focusing on this stage, the algorithmic Computational Singular Perturbation methodology is employed to identify the underlying mechanisms confining the system's evolution and the governing slow dynamics along them. These insights are preserved along different tumor-immune system and patient-dependent realizations. On top of these identifications, a novel reduced model is algorithmically constructed, which accurately predicts the dynamics of the system during the explosive stage and includes half of the parameters of the detailed model. The present analysis demonstrates the potential of algorithmic asymptotic analysis for acquiring physical understanding and for simplifying the complexity of cancer immunology models. Along with the current techniques on the field, this analysis can provide guidelines for more effective treatment development.

Division of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene effects on fecundity and activity are influenced by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.

We propose a mathematical model to investigate the antibody-dependent enhancement (ADE) phenomenon during secondary dengue infection. The model consists of an ODE system that describes the interaction of the dengue virus with macrophages and memory B and T cell role during the infection. The qualitative model analysis is done in terms of memory B and T cell cloning parameters and the basic reproduction number R0. In the absence of memory B and T cell cloning, if R0<1 the dengue virus population extinguishes, while for R0>1, it tends asymptotically to a positive equilibrium. However, when we consider the memory B cell cloning, it is possible to occur dengue infection even when R0<1. Memory T cells have an essential role in eliminating the possibility of ADE occurrence when R0<1.

Comment on J Theor Biol. 2020 Feb 7;486:110102.

Mycobacterium avium complex (MAC), is known for colonizing and infecting humans following inhalation of the bacteria. MAC pulmonary disease is notoriously difficult to treat and prone to recurrence. Both the incidence and prevalence MAC pulmonary disease have been increasing globally. MAC is well known to form biofilms in the environment. In vitro, these biofilms have been shown to aid MAC in epithelial cell invasion, protect MAC from phagocytosis, and cause premature apoptosis in macrophages. In vivo, the system of interactions between MAC, biofilms and host macrophages is complex, difficult to replicate in vitro and in animal models, has not been fully characterized. Here we present a three-dimensional agent-based model of a lung airway to help understand how these interactions evolve in the first 14 days post-bacterial inhalation. We parameterized the model using published data and performed uncertainty analysis to characterize outcomes and parameters' effects on those outcomes. Model results show diverse outcomes, including wide ranges of macrophage recruitment levels, and bacterial loads and phenotype distribution. Though most bacteria are phagocytosed by macrophages and remain intracellular, there are also many simulations in which extracellular bacteria continue to drive the colonization and infection. Initial parameters dictating host immune levels, bacterial loads introduced to the airway, and biofilm conditions have significant and lasting impacts on the course of these results. Additionally, though macrophage recruitment is key for suppressing bacterial loads, there is evidence of significant excess recruitment that fail to impact bacterial numbers. These results highlight a need and identify a path for further exploration into the inhalation events in MAC infection. Early infection dynamics could have lasting impacts on the development of nodular bronchiectatic or fibrocavitary disease as well as inform possible preventative and treatment intervention targeting biofilm-macrophage interactions.

The formation of new vascular networks is essential for tissue development and regeneration, in addition to playing a key role in pathological settings such as ischemia and tumour development. Experimental findings in the past two decades have led to the identification of a new mechanism of neovascularisation, known as cluster-based vasculogenesis, during which endothelial progenitor cells (EPCs) mobilised from the bone marrow are capable of bridging distant vascular beds in a variety of hypoxic settings in vivo. This process is characterised by the formation of EPC clusters during its early stages and, while much progress has been made in identifying various mechanisms underlying cluster formation, we are still far from a comprehensive description of such spatio-temporal dynamics. In order to achieve this, we propose a novel mathematical model of the early stages of cluster-based vasculogenesis, comprising of a system of nonlocal partial differential equations including key mechanisms such as endogenous chemotaxis, matrix degradation, cell proliferation and cell-to-cell adhesion. We conduct a linear stability analysis on the system and solve the equations numerically. We then conduct a parametric analysis of the numerical solutions of the one-dimensional problem to investigate the role of underlying dynamics on the speed of cluster formation and the size of clusters, measured via appropriate metrics for the cluster width and compactness. We verify the key results of the parametric analysis with simulations of the two-dimensional problem. Our results, which qualitatively compare with data from in vitro experiments, elucidate the complementary role played by endogenous chemotaxis and matrix degradation in the formation of clusters, suggesting chemotaxis is responsible for the cluster topology while matrix degradation is responsible for the speed of cluster formation. Our results also indicate that the nonlocal cell-to-cell adhesion term in our model, even though it initially causes cells to aggregate, is not sufficient to ensure clusters are stable over long time periods. Consequently, new modelling strategies for cell-to-cell adhesion are required to stabilise in silico clusters. We end the paper with a thorough discussion of promising, fruitful future modelling and experimental research perspectives.

A physiologically based three-dimensional (3D) hemodynamic model is developed to predict the experimentally observed blood oxygen level dependent (BOLD) responses versus the cortical depth induced by visual stimuli. Prior 2D approximations are relaxed in order to analyze 3D blood flow dynamics as a function of cortical depth. Comparison of the predictions with experimental data for evoked stimuli demonstrates that the full 3D model performs at least as well as previous approaches while remaining parsimonious. In particular, the 3D model requires significantly fewer assumptions and model parameters than previous models such that there is no longer need to define depth-specific parameter values for spatial spreading, peak amplitude, and hemodynamic velocity.

A major question in cultural-evolution studies is the phenotype of individual learners. Evidence suggests that social dominance is one influential factor, where socially subordinate individuals are more apt to learning of trial-and-error type than the dominants. Despite the accumulating evidence, the evolutionary dynamics leading to such outcomes remains largely elusive, partly because of the cost of individual learning. Here, we provide an evolutionary game framework to study the influence of social dominance on individual's learning decisions. We show that subordinates are indeed more apt to individual learning, because they gain a lot when individual learning is successful but lose little when it fails. We also predict that an evolutionary limit-cycle, in which dominants' and subordinates' behavior change over evolutionary time, may occur in such a case. We additionally showed that group-wide knowledge-gain is poor in egalitarian groups compared to moderately despotic ones. Our model sheds light onto the consequence of tactics played between dominants and subordinates for the evolution of individual learning.

Sigmoid growth models, such as the logistic, Gompertz and Richards' models, are widely used to study population dynamics ranging from microscopic populations of cancer cells, to continental-scale human populations. Fundamental questions about model selection and parameter estimation are critical if these models are to be used to make practical inferences. However, the question of parameter identifiability - whether a data set contains sufficient information to give unique or sufficiently precise parameter estimates - is often overlooked. We use a profile-likelihood approach to explore practical parameter identifiability using data describing the re-growth of hard coral. With this approach, we explore the relationship between parameter identifiability and model misspecification, finding that the logistic growth model does not suffer identifiability issues for the type of data we consider whereas the Gompertz and Richards' models encounter practical non-identifiability issues. This analysis of parameter identifiability and model selection is important because different growth models are in biological modelling without necessarily considering whether parameters are identifiable. Standard practices that do not consider parameter identifiability can lead to unreliable or imprecise parameter estimates and potentially misleading mechanistic interpretations. For example, using the Gompertz model, the estimate of the time scale of coral re-growth is 625 days when we estimate the initial density from the data, whereas it is 1429 days using a more standard approach where variability in the initial density is ignored. While tools developed here focus on three standard sigmoid growth models only, our theoretical developments are applicable to any sigmoid growth model and any appropriate data set. MATLAB implementations of all software are available on GitHub.

Chromatin regulation is a key pathway cells use to regulate gene expression in response to temporal stimuli, and is becoming widely used as a platform for synthetic biology applications. Here, we build a mathematical framework for analyzing the response of genetic circuits containing chromatin regulators to temporal signals in mammalian cell populations. Chromatin regulators can silence genes in an all-or-none fashion at the single-cell level, with individual cells stochastically transitioning between active, reversibly silent, and irreversibly silent gene states at constant rates over time. We integrate this mode of regulation with classical gene regulatory motifs, such as autoregulatory and incoherent feedforward loops, to determine the types of responses achievable with duration-dependent signaling. We demonstrate that repressive regulators without long-term epigenetic memory can filter out high frequency noise, and as part of an autoregulatory loop can precisely tune the fraction of cells in a population that expresses a gene of interest. Additionally, we find that repressive regulators with epigenetic memory can sum up and encode the total duration of their recruitment in the fraction of cells irreversibly silenced and, when included in a feed forward loop, enable perfect adaptation. Last, we use an information theoretic approach to show that all-or-none stochastic silencing can be used by populations to transmit information reliably and with high fidelity even in very simple genetic circuits. Altogether, we show that chromatin-mediated gene control enables a repertoire of complex cell population responses to temporal signals and can transmit higher information levels than previously measured in gene regulation.

We here propose a one-dimensional spatially explicit phenotype-structured model to analyze selected aspects of avascular tumor progression. In particular, our approach distinguishes viable and necrotic cell fractions. The metabolically active part of the disease is, in turn, differentiated according to a continuous trait, that identifies cell variants with different degrees of motility and proliferation potential. A parabolic partial differential equation (PDE) then governs the spatio-temporal evolution of the phenotypic distribution of active cells within the host tissue. In this respect, active tumor agents are allowed to duplicate, move upon haptotactic and pressure stimuli, and eventually undergo necrosis. The mutual influence between the emerging malignancy and its environment (in terms of molecular landscape) is implemented by coupling the evolution law of the viable tumor mass with a parabolic PDE for oxygen kinetics and a differential equation that accounts for local consumption of extracellular matrix (ECM) elements. The resulting numerical realizations reproduce tumor growth and invasion in a number scenarios that differ for cell properties (i.e., individual migratory behavior, duplication, and mutation potential) and environmental conditions (i.e., level of tissue oxygenation and homogeneity in the initial matrix profile). In particular, our simulations show that, in all cases, more mobile cell variants occupy the front edge of the tumor, whereas more proliferative clones are selected at more internal regions. A necrotic core constantly occupies the bulk of the mass due to nutrient deprivation. This work may eventually suggest some biomedical strategies to partially reduce tumor aggressiveness, i.e., to enhance necrosis of malignant tissue and to promote the presence of more proliferative cell phenotypes over more invasive ones.

The annual death statistics due to vector-borne diseases transmitted by Aedes mosquitoes cause a still growing concern for the public health in the affected regions. An improved understanding of how climatic and population changes impact the spread of Aedes aegypti will help estimate the future populations exposure and vulnerability, and is essential to the improvement of public health preparedness. We apply an empirically well-investigated process-based mathematical model based on the life cycle of the mosquito to assess how climate scenarios (Representative Concentration Pathways (RCP)) and population scenarios (Shared Socioeconomic Pathways (SSP)) will affect the growth and potential distribution of this mosquito in China. Our results show that the risk area is predicted to expand considerably, increasing up to 21.46% and 24.75% of China's land area in 2050 and 2070, respectively, and the new added area lies mainly in the east and center of China. The population in the risk area grows substantially up to 2050 and then drops down steadily. However, these predicted changes vary noticeably among different combinations between RCPs and SSPs with the RCP2.6*SSP4 yielding the most favorable scenario in 2070, representing approximately 14.11% of China's land area and 113 cities at risk, which is slightly lower compared to 2019. Our results further reveal that there is a significant trade-off between climatic and human population impacts on the spreading of Aedes aegypti, possibly leading to an overestimation (underestimation) in sparsely (densely) populated areas if the populations impact on the mosquito's life history is unaccounted for. These results suggest that both climate and population changes are crucial factors in the formation of the populations exposure to Aedes-borne virus transmission in China, however, a reduced population growth rate may slow down the spread of this mosquito by effectively counteracting the climate warming impacts.

During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) including school closures, workplace closures and social distancing policies have been employed worldwide to reduce transmission and prevent local outbreaks. However, transmission and the effectiveness of NPIs depend strongly on age-related factors including heterogeneities in contact patterns and pathophysiology. Here, using SARS-CoV-2 as a case study, we develop a branching process model for assessing the risk that an infectious case arriving in a new location will initiate a local outbreak, accounting for the age distribution of the host population. We show that the risk of a local outbreak depends on the age of the index case, and we explore the effects of NPIs targeting individuals of different ages. Social distancing policies that reduce contacts outside of schools and workplaces and target individuals of all ages are predicted to reduce local outbreak risks substantially, whereas school closures have a more limited impact. In the scenarios considered here, when different NPIs are used in combination the risk of local outbreaks can be eliminated. We also show that heightened surveillance of infectious individuals reduces the level of NPIs required to prevent local outbreaks, particularly if enhanced surveillance of symptomatic cases is combined with efforts to find and isolate nonsymptomatic infected individuals. Our results reflect real-world experience of the COVID-19 pandemic, during which combinations of intense NPIs have reduced transmission and the risk of local outbreaks. The general modelling framework that we present can be used to estimate local outbreak risks during future epidemics of a range of pathogens, accounting fully for age-related factors.