34 research outputs found

    Correlates of Discordance between Perceived and Objective Distances to Local Fruit and Vegetable Retailers

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    Background: Perceptions of neighbourhood attributes such as proximity of food retailers that are discordant with objective measures of the same are associated with poor health behaviours and weight gain. Factors associated with discordant perceptions are likely relevant to planning more effective interventions to improve health. Purpose: Analysis of cross-sectional relationships between individual and neighbourhood factors and overestimations of walking distances to local fruit/vegetable retailers (FVR). Methods: Perceived walking times, converted to distances, between participant residences and FVR were compared with objectively-assessed road network distances calculated with a Geographic Information System for n = 1305 adults residing in Adelaide, South Australia. Differences between perceived and objective distances were expressed as ‘overestimated’ distances and were analysed relative to perceptions consistent with objective distances. Cross-sectional associations were evaluated between individual socio-demographic, health, and area-level characteristics and overestimated distances to FVR using multilevel logistic regression. Results: Agreement between objective and perceived distances between participants’ residence and the nearest FVR was only fair (weighted kappa = 0.22). Overestimated distances to FVR were positively associated with mental well-being, and were negatively associated with household income, physical functioning, sense of community, and objective distances to greengrocers. Conclusions: Individual characteristics and features of neighbourhoods were related to overestimated distances to FVR. Sense of connectivity and shared identity may shape more accurate understandings of local resource access, and offer a focal point for tailored public health initiatives that bring people together to achieve improved health behaviour

    Patient-Specific Metrics of Invasiveness Reveal Significant Prognostic Benefit of Resection in a Predictable Subset of Gliomas

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    Object Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas. Methods In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness. Results We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors). Conclusions These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection

    Evaluating the Effect of Tissue Anisotropy on Brain Tumor Growth using a Mechanically-coupled Reaction-Diffusion Model

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    Glioblastoma (GBM), the most frequent malignant brain tumor in adults, is char- acterized by rapid growth and healthy tissue invasion. Long-term prognosis for GBM remains poor with median overall survival between 1 y to 2 y [15]. GBM presents with different growth phenotypes, ranging from invasive tumors without notable mass-effect to strongly displacing lesions. Biomechanical forces, such as those resulting from displacive tumor growth, shape the tumor environment and contribute to tumor progression [9]. We present an extended version of a mechanically–coupled reaction-diffusion model of brain tu- mor growth [1] that simulates tumor evolution over time and across different brain regions using literature-based parameter estimates for tumor cell proliferation, as well as isotropic motility, and mechanical tissue properties. This model yielded realistic estimates of the mechanical impact of a growing tumor on intra-cranial pressure. However, comparison to imaging data showed that asymmetric shapes could not be reproduced by isotropic growth assumptions. We modified this model to account for structural tissue anisotropy which is known to affect the directionality of tumor cell migration and may influence the mechanical behavior of brain tissue. Tumors were seeded at multiple locations in a human MR-DTI brain atlas and their spatio-temporal evolution was simulated using the Finite-Element Method. We evaluated the impact of tissue anisotropy on the model’s ability to reproduce the aspherical shapes of real pathologies by comparing predicted lesions to publicly available GBM imaging data. We found the impact on tumor shape to be strongly location dependent and highest for tumors located in brain regions that are characterized by a single dominant white matter direction, such as the corpus callosum. However, despite strongly anisotropic growth assumptions, all simulated tumors remained more spherical than real lesions at the corresponding location and similar volume. This finding is in agreement with previous studies [17, 6] suggesting that anisotropic cell migration along white matter fiber tracks is not a major determinant of tumor shape in the setting of reaction-diffusion based tumor growth models and for most locations across the brain

    The early years: Prevention rather than intervention

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    In this symposium, a panel will focus on some key issues relating to the promotion of physical activity in early childhood settings. The session will conclude with a discussion involving all presenters. Participants have the chance to ask questions, raise further issues, and to discuss the implications for services and communities. How active is enough? Dr Beth Hands will discuss the implications of the current UK, USA, and draft Australian Guidelines for Physical Activity for young children. What do they mean and how can they be implemented? Measuring success - How do we know which initiatives work? Dr Judy Miller will discuss some key issues related to physical activity and motor development research with young children. ... We expect the symposium to be controversial and we will allow time for dialogue and debate

    Are perceived and objective distances to fresh food and physical activity resources associated with cardiometabolic risk?

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    Perceived and objective measures of neighbourhood features have shown limited correspondence. Few studies have examined whether discordance between objective measures and individual perceptions of neighbourhood environments relates to individual health. Individuals with mismatched perceptions may benefit from initiatives to improve understandings of resource availability. This study utilised data from n = 1491 adult participants in a biomedical cohort to evaluate cross-sectional associations between measures of access (perceived, objective, and perceived-objective mismatch) to fruit and vegetable retailers (FVR) and public open space (POS), and clinically-measured metabolic syndrome and its component risk factors: central obesity, dyslipidaemia, hypertension and pre-diabetes/diabetes. Access measures included perceived distances from home to the nearest FVR and POS, corresponding objectively-assessed road network distances, and the discordance between perceived and objective distances (overestimated (i.e., mismatched) distances versus matched perceived-objective distances). Individual and neighbourhood measures were spatially joined using a geographic information system. Associations were evaluated using multilevel logistic regression, accounting for individual and area-level covariates. Hypertension was positively associated with perceived distances to FVR (odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.02, 1.28) and POS (OR = 1.19, 95% CI = 1.05, 1.34), after accounting for covariates and objective distances. Hypertension was positively associated with overestimating distances to FVR (OR = 1.36, 95% CI = 1.02, 1.80). Overestimating distances to POS was positively associated with both hypertension (OR = 1.42, 95% CI = 1.11, 1.83) and dyslipidaemia (OR = 1.25, 95% CI = 1.00, 1.57). Results provide new evidence for specific associations between perceived and overestimated distances from home to nearby resources and cardiometabolic risk factors

    Mammalian tolloid proteinases: role in growth factor signalling

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    Tolloid proteinases are essential for tissue patterning and extracellular matrix assembly. The members of the family differ in their substrate specificity and activity, despite sharing similar domain organization. The mechanisms underlying substrate specificity and activity are complex, with variation between family members, and depend on both multimerization and substrate interaction. In addition, enhancers, such as Twisted gastrulation (Tsg), promote cleavage of tolloid substrate, chordin, to regulate growth factor signalling. Although Tsg and mammalian tolloid (mTLD) are involved in chordin cleavage, no interaction has been detected between them, suggesting Tsg induces a change in chordin to increase susceptibility to cleavage. All members of the tolloid family bind the N terminus of latent TGFβ‐binding protein‐1, providing support for their role in TGFβ signalling

    The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.

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    Chordin-mediated regulation of bone morphogenetic protein (BMP) family growth factors is essential in early embryogenesis and adult homoeostasis. Chordin binds to BMPs through cysteine-rich von Willebrand factor type C (vWC) homology domains and blocks them from interacting with their cell surface receptors. These domains also self-associate and enable chordin to target related proteins to fine-tune BMP regulation. The chordin-BMP inhibitory complex is strengthened by the secreted glycoprotein twisted gastrulation (Tsg); however, inhibition is relieved by cleavage of chordin at two specific sites by tolloid family metalloproteases. As Tsg enhances this cleavage process, it serves a dual role as both promoter and inhibitor of BMP signalling. Recent developments in chordin research suggest that rather than simply being by-products, the cleavage fragments of chordin continue to play a role in BMP regulation. In particular, chordin cleavage at the C-terminus potentiates its anti-BMP activity in a type-specific manner
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