778 research outputs found

    Evaluation of the implementation of curriculum materials for civics in the Netherlands

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    Discusses a study evaluating the implementation of curriculum materials for civics in the Netherlands. Pedagogical principles aimed at increasing students' social commitment; Central research question; Exploration of broad context for implementation; Actual use of teaching packages by teachers

    The vulnerable microcirculation in the critically ill pediatric patient

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    In neonates, cardiovascular system development does not stop after the transition from intra-uterine to extra-uterine life and is not limited to the macrocirculation. The microcirculation (MC), which is essential for oxygen, nutrient, and drug delivery to tissues and cells, also develops. Developmental changes in the microcirculatory structure continue to occur during the initial weeks of life in healthy neonates. The physiologic hallmarks of neonates and developing children make them particularly vulnerable during critical illness; however, the cardiovascular monitoring possibilities are limited compared with critically ill adult patients. Therefore, the development of non-invasive methods for monitoring the MC is necessary in pediatric critical care for early identification of impending deterioration and to enable the initiation and titration of therapy to ensure cell survival. To date, the MC may be non-invasively monitored at the bedside using hand-held videomicroscopy, which provides useful information regarding the microcirculation. There is an increasing number of studies on the MC in neonates and pediatric patients; however, additional steps are necessary to transition MC monitoring from bench to bedside. The recently introduced concept of hemodynamic coherence describes the relationship between changes in the MC and macrocirculation. The loss of hemodynamic coherence may result in a depressed MC despite an improvement in the macrocirculation, which represents a condition associated with adverse outcomes. In the pediatric intensive care unit, the concept of hemodynamic coherence may function as a framework to develop microcirculatory measurements towards implementation in daily clinical practice

    Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria

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    Contains fulltext : 69450.pdf ( ) (Open Access)BACKGROUND: Neurons require an elaborate system of intracellular transport to distribute cargo throughout axonal and dendritic projections. Active anterograde and retrograde transport of mitochondria serves in local energy distribution, but at the same time also requires input of ATP. Here we studied whether brain-type creatine kinase (CK-B), a key enzyme for high-energy phosphoryl transfer between ATP and CrP in brain, has an intermediary role in the reciprocal coordination between mitochondrial motility and energy distribution. Therefore, we analysed the impact of brain-type creatine kinase (CK-B) deficiency on transport activity and velocity of mitochondria in primary murine neurons and made a comparison to the fate of amyloid precursor protein (APP) cargo in these cells, using live cell imaging. RESULTS: Comparison of average and maximum transport velocities and global transport activity showed that CK-B deficiency had no effect on speed of movement of mitochondria or APP cargo, but that the fraction of motile mitochondria was significantly increased by 36% in neurons derived from CK-B knockout mice. The percentage of motile APP vesicles was not altered. CONCLUSION: CK-B activity does not directly couple to motor protein activity but cells without the enzyme increase the number of motile mitochondria, possibly as an adaptational strategy aimed to enhance mitochondrial distribution versatility in order to compensate for loss of efficiency in the cellular network for ATP distribution

    Using a composite flow law to model deformation in the NEEM deep ice core, Greenland — Part 2: The role of grain size and premelting on ice deformation at high homologous temperature

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    The ice microstructure in the lower part of the North Greenland Eemian Ice Drilling (NEEM) ice core consists of relatively fine-grained ice with a single maximum crystallographic preferred orientation (CPO) alternated by much coarser-grained ice with a partial (great circle) girdle or multi-maxima CPO. In this study, the grain-size-sensitive (GSS) composite flow law of Goldsby and Kohlstedt (2001) was used to study the effects of grain size and premelting (liquid-like layer along the grain boundaries) on strain rate in the lower part of the NEEM ice core. The results show that the strain rates predicted in the fine-grained layers are about an order of magnitude higher than in the much coarser-grained layers. The dominant deformation mechanisms, based on the flow relation of Goldsby and Kohlstedt (2001), between the layers is also different, with basal slip rate limited by grain boundary sliding (GBS-limited creep) being the dominant deformation mechanism in the finer-grained layers, while GBS-limited creep and dislocation creep (basal slip rate limited by non-basal slip) contribute both roughly equally to bulk strain in the coarse-grained layers. Due to the large difference in microstructure between finer-grained ice and the coarse-grained ice at premelting temperatures (T>262 K), it is expected that the fine-grained layers deform at high strain rates, while the coarse-grained layers are relatively stagnant. The difference in microstructure, and consequently in viscosity, between impurity-rich and low-impurity ice can have important consequences for ice dynamics close to the bedrock

    Accuracy and the influence of marrow fat on quantitative CT and dual-energy X-ray absorptiometry measurements of the femoral neck in vitro

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    Abstract Bone mineral measurements with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) were compared with chemical analysis (ChA) to determine (1) the accuracy and (2) the influence of bone marrow fat. Total bone mass of 19 human femoral necks in vitro was determined with QCT and DXA before and after defatting. ChA consisted of defatting and decalcification of the femoral neck samples for determination of bone mineral mass (BmM) and amount of fat. The mean BmM was 4.49 g. Mean fat percentage was 37.2% (23.3%–48.5%). QCT, DXA and ChA before and after defatting were all highly correlated (r>0.96,p<0.0001). Before defatting the QCT values were on average 0.35 g less than BmM and the DXA values were on average 0.65 g less than BmM. After defatting, all bone mass values increased; QCT values were on average 0.30 g more than BmM and DXA values were 0.29 g less than BmM. It is concluded that bone mineral measurements of the femoral neck with QCT and DXA are highly correlated with the chemically determined bone mineral mass and that both techniques are influenced by the femoral fat content

    Brand and generic use of inhalation medication and frequency of switching in children and adults : a population-based cohort study

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    BACKGROUND: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. AIM: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. METHODS: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). CONCLUSION: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted
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