5,547 research outputs found

    Growth, Body Composition, and Lung Function in Prepubertal Children with Cystic Fibrosis Diagnosed by Newborn Screening

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    Background: Children with cystic fibrosis (CF) are at risk of altered body composition (BC). Newborn screening (NBS) may lead to improved BC outcomes. We investigated BC and its relationship with lung function in prepubertal children diagnosed with CF by NBS. Secondary aims explored predictors of fat‐free mass (FFM) and lung function. / Methods: Thirty‐seven screened (non‐meconium ileus) children with CF (20 boys) born 2007–2012 had a dual‐energy x‐ray absorptiometry scan at 5–8 years to determine whole‐body (WB) and appendicular BC. Anthropometry was performed and routine spirometry recorded. Results were converted to z‐scores, height‐adjusted (fat mass index [FMI] and FFM index [FFMI]) and compared with population mean values. Predictors of forced expiratory volume in 1 second (FEV1) were assessed using linear regression. / Results: Height, body mass index (BMI), and FEV1 were within normal limits, however, weight and BC were significantly low compared with reference data (weight, P = .03; WB FMI, P = .001; WB FFMI, P = .009). Gender differences were detected, with lower appendicular BC in boys and lower weight, BMI, and BC in girls. The association between FEV1 and WB FFMI (r = 0.38; P = .02) was stronger than with BMI (r = 0.29; P = .08). WB FFMI was the only significant predictor of FEV1 in a multivariable model (95% CI, 0.11–0.99; P = .016). / Conclusion: In this NBS CF population, gender differences in growth and BC were apparent despite preserved lung function. These results support BC assessment in prepubertal children, particularly girls, with an opportunity to direct interventions to optimize FFM

    Torsional behaviour of rectangular hollow sections.

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    The results of a series of full-scale torsion tests on rectangular hollow sections (RHS) are presented and discussed. The observed torque–twist behaviour is compared to that predicted by an extended version of Marshall’s simplified thick wall torsion theory and finite element (FE) analysis, and significant differences are highlighted and examined. The behaviour predicted by the FE models is shown to be identical to that predicted by Marshall’s thick wall theory, which forms the basis of the British and European design procedures. However, even though the experimental measurements agree with the FE and theoretical predictions in the elastic range, the measurements of torsional capacity are significantly lower than those calculated, and this has important implications for design that may be wider than just torsion of RHS. A number of potential causes for this behaviour are examined, but it is yet to be fully explained. Evidence of similar behaviour in previous large-scale testing is highlighted and discussed

    The role of extracellular vesicles in biomineralisation:current perspective and application in regenerative medicine

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    Extracellular vesicles comprise a heterogenous population of exosomes and microvesicles that have critical roles in intercellular signalling and tissue development. These complex particles have been implicated as mediators of the therapeutic effects of stem cells via the transfer of an assorted cargo of proteins and nucleic acids, which can modulate inflammation and enhance endogenous regeneration in a range of tissues. In addition, extracellular vesicles have the capacity to be loaded with therapeutic molecules for targeted delivery of pharmaceuticals. The versatility, biostability and biocompatibility of extracellular vesicles make them appealing for regenerative medicine and may endow considerable advantages over single molecule approaches. Furthermore, since production can be optimised and assessed ex vivo, extracellular vesicles present a decreased risk of neoplastic transformation when compared with cell-based methods. To date, the contribution of vesicles to tissue development has perhaps been most comprehensively defined within hard tissues, such as endochondral bone, where they were first identified in 1969 and henceforth referred to as matrix vesicles. Within developing bone, vesicles function as vehicles for the delivery of pro-osteogenic factors and initiate early nucleational events necessary for matrix mineralisation. However, advancement in our understanding of the biogenesis and characterisation of matrix vesicles has occurred largely in parallel to associated developments in wider extracellular vesicle biology. As such, there is a requirement to align current understanding of matrix vesicle–mediated mineralisation within the context of an evolving literature surrounding exosomes and microvesicles. In this review, we present an overview of current progress and opinion surrounding the application of vesicles in regenerative medicine with a primary focus on their potential as an acellular approach for enhancing hard tissue regeneration. This is balanced with an assessment of areas where further development is required to maximise their application for regenerative medicine

    Estimation of the effect of SLCO1B1 polymorphisms on lopinavir plasma concentration in HIV-Infected Adults

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    Background—The organic anion transporting polypeptides (OATP)/SLCO family represents an important class of hepatic drug uptake transporters that mediate the sodium independent transport of a diverse range of amphipathic organic compounds, including the protease inhibitors. The SLCO1B1 521T>C (rs4149056) single nucleotide polymorphism (SNP) has been consistently associated with reduced transport activity in vivo, and we previously showed an association of this polymorphism with lopinavir plasma concentrations. The aim of this study was to develop a population pharmacokinetic (PK) model to quantify the impact of 521T>C. Methods—A population PK analysis was performed with 594 plasma samples from 375 patients receiving lopinavir/ritonavir. Non-linear mixed effects modelling was applied to explore the effects of SLCO1B1 521T>C and patient demographics. Simulations of the lopinavir concentration profile were performed with different dosing regimens considering the different alleles. Results—A one-compartment model with first-order absorption best described the data. Population clearance was 5.67 L/h with inter-patient variability of 37%. Body weight was the only demographic factor influencing clearance, which increased 0.5 L/h for every 10 kg increase. Homozygosity for the C allele was associated with a 37% lower clearance, and 14% for heterozygosity, which were statistically significant. Conclusion—These data show an association between SLCO1B1 521T>C and lopinavir clearance. The association is likely to be mediated through reduced uptake by hepatocytes leading to higher plasma concentrations of lopinavir. Further studies are now required to confirm the association and to assess the influence of other polymorphisms in the SLCO family on lopinavir PK

    The Fundamental Plane of Radio Galaxies

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    We collected photometrical and dynamical data for 73 low red-shift (z<0.2) Radio Galaxies (LzRG) in order to study their Fundamental Plane (FP). For 22 sources we also present new velocity dispersion data, that complement the photometric data given in our previous study of LzRG (Govoni et al. 2000a). It is found that the FP of LzRG is similar to the one defined by non-active elliptical galaxies, with LzRG representing the brightest end of the population of early type galaxies. Since the FP mainly reflects the virial equilibrium condition, our result implies that the global properties of early--type galaxies (defining the FP) are not influenced by the presence of gas accretion in the central black hole. This is fully in agreement with the recent results in black hole demography, showing that virtually all luminous spheroidal galaxies host a massive black hole and therefore may potentially become active. We confirm and extend to giant ellipticals the systematic increase of the mass-to-light ratio with galaxy luminosity.Comment: 8 pages, 3 figures, accepted for publication in A&

    Coordinated Cluster/Double Star Observations of Dayside Reconnection Signatures

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    The recent launch of the equatorial spacecraft of the Double Star mission, TC-1, has provided an unprecedented opportunity to monitor the southern hemisphere dayside magnetopause boundary layer in conjunction with northern hemisphere observations by the quartet of Cluster spacecraft. We present first results of one such situation where, on 6 April 2004, both Cluster and the Double Star TC-1 spacecraft were on outbound transits through the dawnside magnetosphere. The observations are consistent with ongoing reconnection on the dayside magnetopause, resulting in a series of flux transfer events (FTEs) seen both at Cluster and TC-1, which appear to lie north and south of the reconnection line, respectively. In fact, the observed polarity and motion of each FTE signature advocates the existence of an active reconnection region consistently located between the positions of Cluster and TC-1, with Cluster observing northward moving FTEs with +/− polarity, whereas TC-1 sees −/+ polarity FTEs. This assertion is further supported by the application of a model designed to track flux tube motion for the prevailing interplanetary conditions. The results from this model show, in addition, that the low-latitude FTE dynamics are sensitive to changes in convected upstream conditions. In particular, changing the interplanetary magnetic field (IMF) clock angle in the model suggests that TC-1 should miss the resulting FTEs more often than Cluster and this is borne out by the observations

    Real-time Classification of Vehicle Types within Infra-red Imagery

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    Real-time classification of vehicles into sub-category types poses a significant challenge within infra-red imagery due to the high levels of intra-class variation in thermal vehicle signatures caused by aspects of design, current operating duration and ambient thermal conditions. Despite these challenges, infra-red sensing offers significant generalized target object detection advantages in terms of all-weather operation and invariance to visual camouflage techniques. This work investigates the accuracy of a number of real-time object classification approaches for this task within the wider context of an existing initial object detection and tracking framework. Specifically we evaluate the use of traditional feature-driven bag of visual words and histogram of oriented gradient classification approaches against modern convolutional neural network architectures. Furthermore, we use classical photogrammetry, within the context of current target detection and classification techniques, as a means of approximating 3D target position within the scene based on this vehicle type classification. Based on photogrammetric estimation of target position, we then illustrate the use of regular Kalman filter based tracking operating on actual 3D vehicle trajectories. Results are presented using a conventional thermal-band infra-red (IR) sensor arrangement where targets are tracked over a range of evaluation scenarios
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