4,488 research outputs found

    Impact of social complexity on outcomes in cystic fibrosis after transfer to adult care

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    Objective This study evaluates the roles of medical and social complexity in health care use outcomes in cystic fibrosis (CF) after transfer from pediatric to adult care. Methods Retrospective cohort design included patients with CF who were transitioned into adult care at Indiana University from 2005 to 2015. Predictor variables included demographic and comorbidity data, age at transition, treatment complexity score (TCS), and an objective scoring measure of their social complexity (Bob's Level of Social Support, BLSS). Outcome variables included outpatient visit rates and hospitalization rates. Pearson's correlations and linear regression were used to analyze the data. Results The median age of the patients (N = 133) at the time of transition was 20 (IQR 19‐23) years. The mean FEV1 % predicted at transition was 69 ± 24%. TCS correlated with outpatient visit rates (r = 0.3, P = 0.003), as well as hospitalization rates (r = 0.4, P < 0.001); while the BLSS only correlated with hospitalization rates (r = 0.7, P < 0.001). After adjusting for covariates, the strongest predictors of post‐transfer hospitalizations are BLSS (P < 0.0001) and pre‐transfer hospitalization rate (P < 0.0001). Conclusion Greater treatment complexity is associated with greater healthcare utilization overall, while greater social complexity is associated with increased hospitalizations (but not outpatient visits). Screening young adults for social complexity may identify high‐risk subpopulations and allow for patient centered interventions to support them and prevent avoidable health care use

    Membrane glucocorticoid receptors are localised in the extracellular matrix and signal through the MAPK pathway in mammalian skeletal muscle fibres

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    A number of studies have previously proposed the existence of glucocorticoid receptors on the plasma membrane of many cell types including skeletal muscle fibres. However, their exact localisation and the cellular signalling pathway(s) they utilise to communicate with the rest of the cell are still poorly understood. In this study, we investigated the localisation and the mechanism(s) underlying the non-genomic physiological functions of these receptors in mouse skeletal muscle cells. The results show that the receptors were localised in the cytoplasm in myoblasts, in the nucleus in myotubes and in the extracellular matrix, in satellite cells and in the proximity of mitochondria in adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent manner. Treating small skeletal muscle fibre bundles with the synthetic glucocorticoid, beclomethasone dipropionate, increased the phosphorylation (=activation) of extracellular-signal regulated kinase 1&2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. This occurred within 5min and depended on the fibre-type and the duration of the treatment. It was also abolished by the glucocorticoid receptor inhibitor, mifepristone, and a monoclonal antibody against the receptor. From these results we conclude that the non-genomic/non-canonical physiological functions of glucocorticoids, in adult skeletal muscle fibres are mediated by a glucocorticoid receptor localised in the extracellular matrix, in satellite cells and close to mitochondria and involve activation of the MAPK pathway

    Water conservation and demand management: Policy implications at the local level

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    Magister Artium (Development Studies) - MA(DVS)South Africa is currently experiencing the global phenomenon of water shortage. Current water requirements for domestic use, industries and agriculture far exceed local supplies in many parts of the country. It is for this reason that the South African government has to formulate a variety of policies that govern and regulate the use of water

    Dependence of ablative ability of high-intensity focused ultrasound cavitation-based histotripsy on mechanical properties of agar

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    Cavitation-based histotripsy uses high-intensity focused ultrasound at low duty factor to create bubble clouds inside tissue to liquefy a region, and provides better fidelity to planned lesion coordinates and the ability to perform real-time monitoring. The goal of this study was to identify the most important mechanical properties for predicting lesion dimensions, among these three: Young\u27s modulus, bending strength, and fracture toughness. Lesions were generated inside tissue-mimicking agar, and correlations were examined between the mechanical properties and the lesion dimensions, quantified by lesion volume and by the width and length of the equivalent bubble cluster. Histotripsy was applied to agar samples with varied properties. A cuboid of 4.5mm width (lateral to focal plane) and 6mm depth (along beam axis) was scanned in a raster pattern with respective step sizes of 0.75 and 3mm. The exposure at each treatment location was either 15, 30, or 60s. Results showed that only Young\u27s modulus influenced histotripsy\u27s ablative ability and was significantly correlated with lesion volume and bubble cluster dimensions. The other two properties had negligible effects on lesion formation. Also, exposure time differentially affected the width and depth of the bubble cluster volume

    In Silico Generation of Alternative Hypotheses Using Causal Mapping (CMAP)

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    Previously, we introduced causal mapping (CMAP) as an easy to use systems biology tool for studying the behavior of biological processes that occur at the cellular and molecular level. CMAP is a coarse-grained graphical modeling approach in which the system of interest is modeled as an interaction map between functional elements of the system, in a manner similar to portrayals of signaling pathways commonly used by molecular cell biologists. CMAP describes details of the interactions while maintaining the simplicity of other qualitative methods (e.g., Boolean networks)

    In situ estimation of subsurface hydro-geomechanical properties using the groundwater response to semi-diurnal Earth and atmospheric tides

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    Subsurface hydro-geomechanical properties crucially underpin the management of Earth\u27s resources, yet they are predominantly measured on core samples in the laboratory while little is known about the representativeness of in situ conditions. The impact of Earth and atmospheric tides on borehole water levels is ubiquitous and can be used to characterise the subsurface. We illustrate that disentangling the groundwater response to Earth (M₂) and atmospheric tidal (S₂) forces in conjunction with established hydraulic and linear poroelastic theories leads to a complete determination of the whole hydro-geomechanical parameter space for unconsolidated systems. Further, the characterisation of consolidated systems is possible when using literature estimates of the grain compressibility. While previous field investigations have assumed a Poisson\u27s ratio from literature values, our new approach allows for its estimation under in situ field conditions. We apply this method to water level and barometric pressure records from four field sites with contrasting hydrogeology. Estimated hydro-geomechanical properties (e.g. specific storage; hydraulic conductivity; porosity; shear, Young\u27s, and bulk moduli; Skempton\u27s and Biot–Willis coefficients; and undrained or drained Poisson\u27s ratios) are comparable to values reported in the literature, except for consistently negative drained Poisson\u27s ratios, which is surprising. Our results reveal an anisotropic response to strain, which is expected for heterogeneous (layered) lithological profiles. Closer analysis reveals that negative Poisson\u27s ratios can be explained by in situ conditions differing to those from typical laboratory core tests and the small strains generated by Earth and atmospheric tides. Our new approach can be used to passively, and therefore cost-effectively, estimate subsurface hydro-geomechanical properties representative of in situ conditions and it improves our understanding of the relationship between geological heterogeneity and geomechanical behaviour
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