Tumor microenvironment as a metapopulation model: The effects of angiogenesis, emigration and treatment modalities.

Tumors consist of heterogeneous cell subpopulations that may develop differing phenotypes, such as increased cell growth, metastatic potential and treatment sensitivity or resistance. To study the dynamics of cancer development at a single-cell level, we model the tumor microenvironment as a metapopulation, in which habitat patches correspond to possible sites for cell subpopulations. Cancer cells may emigrate into dispersal pool (e.g. circulation system) and spread to new sites (i.e. metastatic disease). In the patches, cells divide and new variants may arise, possibly leading into an invasion provided the aberration promotes the cell growth. To study such adaptive landscape of cancer ecosystem, we consider various evolutionary strategies (phenotypes), such as emigration and angiogenesis, which are important determinants during early stages of tumor development. We use the metapopulation fitness of new variants to investigate how these strategies evolve through natural selection and disease progression. We further study various treatment effects and investigate how different therapy regimens affect the evolution of the cell populations. These aspects are relevant, for example, when examining the dynamic process of a benign tumor becoming cancerous, and what is the best treatment strategy during the early stages of cancer development. It is shown that positive angiogenesis promotes cancer cell growth in the absence of anti-angiogenic treatment, and that the anti-angiogenic treatment reduces the need of cytotoxic treatment when used in a combination. Interestingly, the model predicts that treatment resistance might become a favorable quality to cancer cells when the anti-angiogenic treatment is intensive enough. Thus, the optimal treatment dosage should remain below a patient-specific level to avoid treatment resistance.

Evaluating strategies for spatial allocation of vaccines based on risk and centrality.

When vaccinating a large population in response to an invading pathogen, it is often necessary to prioritize some individuals to be vaccinated first. One way to do this is to choose individuals to vaccinate based on their location. Methods for this prioritization include strategies that target those regions most at risk of importing the pathogen, and strategies that target regions with high centrality on the travel network. We use a simple infectious disease epidemic model to compare a risk-targeting strategy to two different centrality-targeting strategies based on betweenness centrality and random walk percolation centrality, respectively. We find that the relative effectiveness of these strategies in reducing the total number of infections varies with the basic reproduction number of the pathogen, travel rates, structure of the travel network and vaccine availability. We conclude that when a pathogen has high spreading capacity, or when vaccine availability is limited, centrality-targeting strategies should be considered as an alternative to the more commonly used risk-targeting strategies.

Metapopulation modelling of long-term urban habitat-loss scenarios.

CONTEXT: Increasing human populations in urban areas pose a threat to species' persistence through habitat loss and fragmentation. It is therefore essential that we develop methods to investigate critical habitat loss thresholds and least detrimental landscape configurations. OBJECTIVES: We develop a framework to assess how the pattern of habitat loss impacts the ecological and social characteristics of a landscape and how this varies depending on the species and criteria by which it is judged. METHODS: We use a scenario-based approach to test six propositions in which habitat is lost preferentially based on patch characteristics. We use eight bird and two amphibian species as indicator species. To compare scenarios, we present a method combining the output from a metapopulation model with measures of social impacts of land-cover change in a multiple criteria decision analysis. We also determine whether a habitat loss threshold exists, below which small loss of habitat can lead to large loss of species' occupancy. RESULTS: We found that, of the scenarios presented, preferentially losing common habitats and smaller patches was least detrimental for both ecological and social factors. Threshold effects were found for all but the generalist bird species. CONCLUSIONS: We have outlined a workflow which allows for transparent, repeatable comparison between landscapes. This workflow can be used to compare urban landscape plans, or to develop general understanding of the impacts of different forms of habitat loss. Reassuringly, the recommendations based on the scenarios presented are in keeping with received conservation wisdom: to prioritise larger and/or rarer patches.

Returns from matching management resolution to ecological variation in a coral reef fishery.

When managing heterogeneous socioecological systems, decision-makers must choose a spatial resolution at which to define management policies. Complex spatial policies allow managers to better reflect underlying ecological and economic heterogeneity, but incur higher compliance and enforcement costs. To choose the most appropriate management resolution, we need to characterize the relationship between management resolution and performance. We parameterize a model of the commercial coral trout fishery in the Great Barrier Reef, Australia, which is currently managed by a single, spatially homogeneous management policy. We use this model to estimate how the spatial resolution of management policies affect the amount of revenue generated, and assess whether a more spatially complex policy can be justified. Our results suggest that economic variation is likely to be a more important source of heterogeneity than ecological differences, and that the majority of this variation can be captured by a relatively simple spatial management policy. Moreover, while an increase in policy resolution can improve performance, the location of policy changes also needs to align with ecological and socioeconomic variation. Interestingly, the highly complex process of larval dispersal, which plays a critical ecological role in coral reef ecosystem dynamics, may not demand equally complex management policies.