The influenza pandemic preparedness planning tool InfluSim

BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Robust Biomarkers: Methodologically Tracking Causal Processes in Alzheimer’s Measurement

In biomedical measurement, biomarkers are used to achieve reliable prediction of, and useful causal information about patient outcomes while minimizing complexity of measurement, resources, and invasiveness. A biomarker is an assayable metric that discloses the status of a biological process of interest, be it normative, pathophysiological, or in response to intervention. The greatest utility from biomarkers comes from their ability to help clinicians (and researchers) make and evaluate clinical decisions. In this paper we discuss a specific methodological use of clinical biomarkers in pharmacological measurement: Some biomarkers, called ‘surrogate markers’, are used to substitute for a clinically meaningful endpoint corresponding to events and their penultimate risk factors. We confront the reliability of clinical biomarkers that are used to gather information about clinically meaningful endpoints. Our aim is to present a systematic methodology for assessing the reliability of multiple surrogate markers (and biomarkers in general). To do this we draw upon the robustness analysis literature in the philosophy of science and the empirical use of clinical biomarkers. After introducing robustness analysis we present two problems with biomarkers in relation to reliability. Next, we propose an intervention-based robustness methodology for organizing the reliability of biomarkers in general. We propose three relevant conditions for a robust methodology for biomarkers: (R1) Intervention-based demonstration of partial independence of modes: In biomarkers partial independence can be demonstrated through exogenous interventions that modify a process some number of “steps” removed from each of the markers. (R2) Comparison of diverging and converging results across biomarkers: By systematically comparing partially-independent biomarkers we can track under what conditions markers fail to converge in results, and under which conditions they successfully converge. (R3) Information within the context of theory: Through a systematic cross-comparison of the markers we can make causal conclusions as well as eliminate competing theories. We apply our robust methodology to currently developing Alzheimer’s research to show its usefulness for making causal conclusions

Coping with Temperature at the Warm Edge – Patterns of Thermal Adaptation in the Microbial Eukaryote Paramecium caudatum

Ectothermic organisms are thought to be severely affected by global warming since their physiological performance is directly dependent on temperature. Latitudinal and temporal variations in mean temperatures force ectotherms to adapt to these complex environmental conditions. Studies investigating current patterns of thermal adaptation among populations of different latitudes allow a prediction of the potential impact of prospective increases in environmental temperatures on their fitness.In this study, temperature reaction norms were ascertained among 18 genetically defined, natural clones of the microbial eukaryote Paramecium caudatum. These different clones have been isolated from 12 freshwater habitats along a latitudinal transect in Europe and from 3 tropical habitats (Indonesia). The sensitivity to increasing temperatures was estimated through the analysis of clone specific thermal tolerances and by relating those to current and predicted temperature data of their natural habitats. All investigated European clones seem to be thermal generalists with a broad thermal tolerance and similar optimum temperatures. The weak or missing co-variation of thermal tolerance with latitude does not imply local adaptation to thermal gradients; it rather suggests adaptive phenotypic plasticity among the whole European subpopulation. The tested Indonesian clones appear to be locally adapted to the less variable, tropical temperature regime and show higher tolerance limits, but lower tolerance breadths.Due to the lack of local temperature adaptation within the European subpopulation, P. caudatum genotypes at the most southern edge of their geographic range seem to suffer from the predicted increase in magnitude and frequency of summer heat waves caused by climate change

Early Developmental Responses to Seedling Environment Modulate Later Plasticity to Light Spectral Quality

Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation) and simulated foliage shade (which affects phytochrome-mediated shade avoidance). Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red∶far red (R∶FR). Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments

Persistence Increases with Diversity and Connectance in Trophic Metacommunities

We are interested in understanding if metacommunity dynamics contribute to the persistence of complex spatial food webs subject to colonization-extinction dynamics. We study persistence as a measure of stability of communities within discrete patches, and ask how do species diversity, connectance, and topology influence it in spatially structured food webs.We answer this question first by identifying two general mechanisms linking topology of simple food web modules and persistence at the regional scale. We then assess the robustness of these mechanisms to more complex food webs with simulations based on randomly created and empirical webs found in the literature. We find that linkage proximity to primary producers and food web diversity generate a positive relationship between complexity and persistence in spatial food webs. The comparison between empirical and randomly created food webs reveal that the most important element for food web persistence under spatial colonization-extinction dynamics is the degree distribution: the number of prey species per consumer is more important than their identity.With a simple set of rules governing patch colonization and extinction, we have predicted that diversity and connectance promote persistence at the regional scale. The strength of our approach is that it reconciles the effect of complexity on stability at the local and the regional scale. Even if complex food webs are locally prone to extinction, we have shown their complexity could also promote their persistence through regional dynamics. The framework we presented here offers a novel and simple approach to understand the complexity of spatial food webs

External representations and scientific understanding

This paper provides an inferentialist account of model-based understanding by combining a counterfactual account of explanation and an inferentialist account of representation with a view of modeling as extended cognition. This account makes it understandable how the manipulation of surrogate systems like models can provide genuinely new empirical understanding about the world. Similarly, the account pro- vides an answer to the question how models, that always incorporate assumptions that are literally untrue of the model target, can still provide factive explanations. Finally, the paper shows how the contrastive counterfactual theory of explanation can provide tools for assessing the explanatory power of models.Peer reviewe

Adaptation, compromise, and constraint: the development, morphometrics, and behavioral basis of a fighter-flier polymorphism in male Hoplothrips karnyi (Insecta: Thysanoptera)

Males of the colonial, wing-polymorphic thrips Hoplothrips karnyi (Hood) fight each other with their forelegs in defense of communal female oviposition areas. In this study, males were reared individually under varying conditions of food deprivation to investigate the developmental cues used in morph determination and the relationships between wing morph, developmental time in each instar, propupal weight, and five adult morphological characters associated with fighting ability and dispersal ability. Males deprived of food for five days midway through the second (final) larval instar had smaller propupal weights and were more likely to develop wings than males deprived of food in the first instar or control males. However, the mean propupal weight of all males that developed wings was not significantly less than that of wingless males. Wing morph of female parents had no measurable effect on this character in the offspring. Wingless males possess relatively larger fore-femora and prothoraces than do winged males, but winged males possess relatively larger pterothoraces (Fig. 1). Behavioral observations of wingless and winged males of similar weight as propupae showed that wingless males won fights and became dominant in oviposition areas. Thus, a trade-off exists between characters associated with male fighting and dispersal ability. The cost of wings, in terms of fore-femora size and prothorax size, increased with propupal weight. Wingless males that developed in the experimental treatment that produced a high proportion of winged males were relatively small in size, and were intermediate in body shape with respect to winged males and other wingless males (Fig. 2). This shape intermediacy indicates that there may be developmental constraints on alternative tactics of resource allocation. Total developmental time varied between wing morphs, but was not correlated with propupal weight or adult morphological characters of winged or wingless males. For wingless males that developed in the treatment that produced a high proportion of winged males, adult morphological characters were negatively correlated with the duration of the second instar. This correlation suggests that the development of small wingless males involves a compromise between the benefits of large adult size and the costs of prolonging the second instar to increase the probability of becoming larger.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46886/1/265_2004_Article_BF00299892.pd