171 research outputs found

    Geomorphological effectiveness of floods to rework gravel bars:insight from hyperscale topography and hydraulic modelling

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    Bars are key morphological units in river systems, fashioning the sediment regime and bedload transport processes within a reach. Reworking of these features underpins channel adjustment at larger scales, thereby acting as a key determinant of channel stability. Despite their importance to channel evolution, few investigations have acquired spatially continuous data on bar morphology and sediment‐size to investigate bar reworking. To this end, four bars along a 10 km reach of a wandering gravel‐bed river were surveyed with Terrestrial Laser Scanning (TLS), capturing downstream changes in slope, bed material size and channel planform. Detrended standard deviations (σz) were extracted from TLS point clouds and correlated to underlying physically measured median grain‐size (D50), across a greater range of σz values than have hitherto been reported. The resulting linear regression model was used to create a 1 m resolution median grain‐size map. A fusion of airborne LiDAR and optical‐empirical bathymetric mapping was used to develop reach‐scale Digital Elevation Models (DEMs) for rapid two‐dimensional hydraulic modelling using JFlow® software. The ratio of dimensionless shear stress over critical shear stress was calculated for each raster cell to calculate the effectiveness of a range of flood events (2.33‐100 year recurrence intervals) to entrain sediment and rework bar units. Results show that multiple bar forming discharges exist, whereby frequent flood flows rework tail and back‐channel areas, whilst much larger, less frequent floods are required to mobilise the coarser sediment fraction on bar heads. Valley confinement is shown to exert a primary influence on patterns of bar reworking. Historical aerial photography, hyperscale DEMs and hydraulic modelling are used to explain channel adjustment at the reach scale. The proportion of the bar comprised of more frequently entrained units (tail, back channel, supra‐platform) relative to more static units (bar head) exerts a direct influence upon geomorphic sensitivity

    International Consortium for Health Outcomes Measurement (ICHOM): Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients

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    Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group's objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide

    A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

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    AbstractVirotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer

    Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease

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    In chronic inflammatory conditions increased endogenous release of specific cytokines (TNFα, IL-1, IL-6, IFNγ and others) is presumed. It has been shown that those of monocyte lineage play a key role in cytokine expression and synthesis. This may be associated with changes in iron metabolism and impaired erythropoiesis and may lead to development of anaemia in patients with rheumatoid arthritis. Firstly, increased synthesis of acute phase proteins, like ferritin, during chronic inflammation is proposed as the way by which the toxic effect of iron and thereby the synthesis of free oxy-radicals causing the damage on the affected joints, may be reduced. This is associated with a shift of iron towards the mononuclear phagocyte system which may participate in the development of anaemia of chronic disease. Secondly, an inhibitory action of inflammatory cytokines (TNFα, IL-1), on proliferation and differentiation of erythroid progenitors as well as on synthesis of erythropoietin has been shown, thereby also contributing to anaemia. Finally, chronic inflammation causes multiple, complex disturbances in the delicate physiologic equilibrium of interaction between cytokines and cells (erythroid progenitors, cells of mononuclear phagocyte system and erythropoietin producing cells) leading to development of anaemia of chronic disease (Fig. 1)
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