23 research outputs found

    Traveling waves in a coarse-grained model of volume-filling cell invasion: Simulations and comparisons

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    Many reaction–diffusion models produce traveling wave solutions that can be interpreted as waves of invasion in biological scenarios such as wound healing or tumor growth. These partial differential equation models have since been adapted to describe the interactions between cells and extracellular matrix (ECM), using a variety of different underlying assumptions. In this work, we derive a system of reaction–diffusion equations, with cross-species density-dependent diffusion, by coarse-graining an agent-based, volume-filling model of cell invasion into ECM. We study the resulting traveling wave solutions both numerically and analytically across various parameter regimes. Subsequently, we perform a systematic comparison between the behaviors observed in this model and those predicted by simpler models in the literature that do not take into account volume-filling effects in the same way. Our study justifies the use of some of these simpler, more analytically tractable models in reproducing the qualitative properties of the solutions in some parameter regimes, but it also reveals some interesting properties arising from the introduction of cell and ECM volume-filling effects, where standard model simplifications might not be appropriate

    The Foot Orthoses versus Hip eXercises (FOHX) trial for patellofemoral pain:a protocol for a randomized clinical trial to determine if foot mobility is associated with better outcomes from foot orthoses

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    Background: Patellofemoral pain (PFP) is a prevalent, often recalcitrant and multifactorial knee pain condition. One method to optimize treatment outcome is to tailor treatments to the patient's presenting characteristics. Foot orthoses and hip exercises are two such treatments for PFP with proven efficacy yet target different ends of the lower limb with different proposed mechanisms of effect. These treatments have not been compared head-to-head, so there is a dearth of evidence for which to use clinically. Only foot orthoses have been explored for identifying patient characteristics that might predict a beneficial effect with either of these two treatments. Preliminary evidence suggests patients will do well with foot orthoses if they have a midfoot width in weight bearing that is≥11mm more than in non-weight bearing, but this has yet to be verified in a study that includes a comparator treatment and an adequate sample size. This trial will determine if: (i) hip exercises are more efficacious than foot orthoses, and (ii) greater midfoot width mobility will be associated with success with foot orthoses, when compared to hip exercises. Methods: Two hundred and twenty participants, aged 18-40 years, with a clinical diagnosis of PFP will be randomly allocated with a 1:1 ratio to receive foot orthoses or progressive resisted hip exercises, and stratified into two subgroups based on their presenting midfoot width mobility (high mobility defined as ≥11mm). The primary outcome will be a 7-point Likert scale for global rating of change. All analyses will be conducted on an intention-to-treat basis using regression models. Discussion: This trial is designed to compare the efficacy of foot orthoses versus hip exercise, as well as to determine if high midfoot width mobility is associated with better outcomes with foot orthoses when compared to hip exercises. Results of this trial will assist clinicians in optimising the management of those with PFP by testing whether a simple measure of midfoot width mobility can help to determine which patients are most likely to benefit from foot orthoses. Trial registration: This trial is registered on the Australian New Zealand Clinical Trials Register (ACTRN12614000260628

    Modeling the extracellular matrix in cell migration and morphogenesis:a guide for the curious biologist

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    The extracellular matrix (ECM) is a highly complex structure through which biochemical and mechanical signals are transmitted. In processes of cell migration, the ECM also acts as a scaffold, providing structural support to cells as well as points of potential attachment. Although the ECM is a well-studied structure, its role in many biological processes remains difficult to investigate comprehensively due to its complexity and structural variation within an organism. In tandem with experiments, mathematical models are helpful in refining and testing hypotheses, generating predictions, and exploring conditions outside the scope of experiments. Such models can be combined and calibrated with in vivo and in vitro data to identify critical cell-ECM interactions that drive developmental and homeostatic processes, or the progression of diseases. In this review, we focus on mathematical and computational models of the ECM in processes such as cell migration including cancer metastasis, and in tissue structure and morphogenesis. By highlighting the predictive power of these models, we aim to help bridge the gap between experimental and computational approaches to studying the ECM and to provide guidance on selecting an appropriate model framework to complement corresponding experimental studies

    Development of a global measure of job embeddedness and integration into a traditional model of voluntary turnover

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    Recent research on job embeddedness has found that both on- and off-the-job forces can act to bind people to their jobs. The present study extended this line of research by examining how job embeddedness may be integrated into a traditional model of voluntary turnover. This study also developed and tested a global, reflective measure of job embeddedness that overcomes important limitations and serves as a companion to the original composite measure. Results of this longitudinal study found that job embeddedness predicted voluntary turnover beyond job attitudes and core variables from traditional models of turnover. Results also found that job embeddedness interacted with job satisfaction to predict voluntary turnover, suggesting that the job embeddedness construct extends beyond the unfolding model of turnover (T. R. Mitchell & T. W. Lee, 2001) it originated from
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