Journal of theoretical biology
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It is one of the fundamental problems in biology and social sciences how to maintain high levels of cooperation among selfish individuals. Theorists present an effective mechanism promoting cooperation by allowing for voluntary participation in public goods games. ⋯ Our research shows that the payoffs of the loners have a significant effect in anonymous voluntary public goods games by this introduction and that the dynamics will drive the system to a fixed point, which is different from the Nash equilibrium. In addition, we also qualitatively explain the existing experimental results.
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Computational models are employed as tools to investigate possible mechanoregulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet established. The objective of this study was to determine the most important cellular characteristics of a mechanoregulatory model describing both cell phenotype-specific and mechanobiological processes that are active during bone healing using a statistical approach. ⋯ Some fibrous connective tissue- and cartilage formation was beneficial to bone healing, but too much of either tissue delayed bone formation. The identified significant parameters and processes are further confirmed by in vivo animal experiments in the literature. This study illustrates the potential of design of experiments methods for evaluating computational mechanobiological model parameters and suggests that further experiments should preferably focus at establishing values of parameters related to cartilage formation and degradation.
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Intracarotid cold saline infusion (ICSI) is potentially much faster than whole-body cooling and more effective than cooling caps in inducing therapeutic brain cooling. One drawback of ICSI is hemodilution and volume loading. We hypothesized that cooling caps could enhance brain cooling with ICSI and minimize hemodilution and volume loading. ⋯ The combination model had lower ICSI flow rates than the ICSI model resulting in a 55% reduction of infusion volume over a 6h period and higher hematocrit values compared to the ICSI model. Moreover, in the combination model, the ICSI flow rate decreased to zero after 4h, and hypothermia was subsequently maintained solely by the cooling cap. This is the first study supporting a role of cooling caps in therapeutic hypothermia in adults.
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Phenomenological computational models of tissue regeneration and bone healing have been only partially successful in predicting experimental observations. This may be a result of simplistic modeling of cellular activity. Furthermore, phenomenological models are limited when considering the effects of combined physical and biological interventions. ⋯ The additional value of the presented model and the importance of including cell-phenotype specific activities when modeling tissue differentiation and bone healing, were demonstrated by comparing the predictions with phenomenological models. The model's capacity was established by showing that it can correctly predict several aspects of bone healing, including cell and tissue distributions during normal fracture healing. Furthermore, it was able to predict experimentally established alterations due to excessive mechanical stimulation, periosteal stripping and impaired effects of cartilage remodeling.
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The process of fracture healing involves the action and interaction of many cells, regulated by biochemical and mechanical signals. Vital to a successful healing process is the restoration of a good vascular network. In this paper, a continuous mathematical model is presented that describes the different fracture healing stages and their response to biochemical stimuli only (a bioregulatory model); mechanoregulatory effects are excluded here. ⋯ Numerical simulations of compromised healing situations showed that the establishment of a vascular network in response to angiogenic growth factors is a key factor in the healing process. Furthermore, a correct description of cell migration is also shown to be essential to the prediction of realistic spatiotemporal tissue distribution patterns in the fracture callus. The mathematical framework presented in this paper can be an important tool in furthering the understanding of the mechanisms causing compromised healing and can be applied in the design of future fracture healing experiments.