242 research outputs found

    Poro-mechanical analysis of a biomimetic scaffold for osteochondral defects

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    Osteochondral defects are focal areas of damage involving articular cartilage and sub-chondral bone. Tissue engineering scaffolds are used to improve the organism regeneration ability for this kind of injury, serving as biocompatible structures for cell viability and differentiation. Since biomechanical cues such as substrate stiffness, loading conditions and fluid permeation are fundamental for successful tissue repair, understanding how these features vary in the scaffold is of primary importance. Here we present a mathematical model based on porous media mechanics for the analysis of a tissue engineering scaffold. We consider a three-layered scaffold mimicking a complete osteochondral tissue and vary the mechanical properties of the intermediate layer over a physiological range. Our results show that the interstitial fluid pressure and the vertical component of the solid effective stress depend significantly on the stiffness and permeability of the intermediate layer under mechanical loading. By properly tuning these material properties, regimes of slow or fast temporal variations of mechanical stress can be obtained in the scaffold layer of interest

    Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

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    Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

    Exclusive Photoproduction of the Cascade (Xi) Hyperons

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    We report on the first measurement of exclusive Xi-(1321) hyperon photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The final state is identified by the missing mass in p(gamma,K+ K+)X measured with the CLAS detector at Jefferson Laboratory. We have detected a significant number of the ground-state Xi-(1321)1/2+, and have estimated the total cross section for its production. We have also observed the first excited state Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss the possibilities of a search for the recently proposed Xi5-- and Xi5+ pentaquarks.Comment: submitted to Phys. Rev.

    Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis

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    <p>Abstract</p> <p>Background</p> <p>Cerebrotendinous xanthomatosis (CTX) is a rare lipid-storage disease. Neuromuscular abnormality and autonomic system (ANS) dysfuction in CTX are rarely examined in large-scale studies in the literature. We studied the peripheral nervous system, myopathology, and autonomic system of four CTX patients and performed a literature review of the reported CTX patients with peripheral neuropathy.</p> <p>Methods</p> <p>Four biochemically and genetically confirmed CTX patients, belonging to two families, were included for study and all received nerve conduction study (NCS), muscle biopsy for histopathologic and ultrastructural study, skin biopsy for intraepidermal nerve fiber (INEF) density measurement, autonomic testings including sympathetic skin response, R-R interval variation and head-up tilt test using an automated tilt table to record the changes of blood pressure and heart rate in different postures. The Q-Sweat test was also applied for the detection of sweat amount and onset time of response. The clinical characteristics, study methods and results of 13 studies of peripheral neuropathy in CTX patients in the literature were also recorded for analysis.</p> <p>Results</p> <p>The results of NCS study showed axonal sensory-motor polyneuropathy in three CTX cases and mixed axonal and demyelinating sensor-motor polyneuropathy in one. The myopathological and histopathologic studies revealed mild denervation characteristics, but the ultrastructural study revealed changes of mitochondria and the membranous system, and increased amounts of glycogen, lipofuscin and lipid deposition. The ANS study revealed different degrees of abnormalities in the applied tests and the INEF density measurement showed small fiber neuropathy in three of the four CTX patients. The literature review of peripheral neuropathy in CTX revealed different types of peripheral neuropathy, of which axonal peripheral neuropathy was the most common.</p> <p>Conclusions</p> <p>Peripheral neuropathy, especially the subtype of axonal sensori-motor neuropathy, is common in patients with CTX. Evidence of lipid metabolic derangement in CTX can be reflected in ultrastructural studies of muscles. With an adequate multi-parametric evaluation, a high incidence of ANS abnormalities can be seen in this rare lipid-storage disease, and a high incidence of small fiber involvement is also reflected in the IENF density measurement of skin biopsies.</p

    A Synaptic Mechanism for Temporal Filtering of Visual Signals

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    The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties

    Consumer perceptions of beef healthiness: results from a qualitative study in four European countries

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    <p>Abstract</p> <p>Background</p> <p>Consumer perception of the healthiness of beef is an important determinant of beef consumption. However, little is known about how consumers perceive the healthiness of beef. The aim of this study is to shed light on the associations between beef and health.</p> <p>Methods</p> <p>Eight focus group discussions were conducted in four European countries (France, UK, Germany, Spain), each consisting of seven to nine participants. A content analysis was performed on the transcripts of these discussions.</p> <p>Results</p> <p>Although beef was generally perceived as healthful, focus group participants expected positive as well as negative effects of beef consumption on their health. Labelled, branded, fresh and lean beef were perceived as signalling healthful beef, in contrast with further processed and packaged beef. Consumers felt that their individual choices could make a difference with respect to the healthiness of beef consumed. Focus group participants were not in favour of improving beef healthiness during processing, but rather focussed on appropriate consumption behaviour and preparation methods.</p> <p>Conclusions</p> <p>The individual responsibility for health implies that consumers should be able to make correct judgements about how healthful their food is. However, the results of this study indicate that an accurate assessment of beef healthiness is not always straightforward. The presented results on consumer perceptions of beef healthiness provide insights into consumer decision making processes, which are important for the innovation and product differentiation in the European beef sector, as well as for public health policy decisions related to meat consumption in general and beef consumption in particular.</p

    Gravitational sliding of the Mt. Etna massif along a sloping basement

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    Geological field evidence and laboratory modelling indicate that volcanoes constructed on slopes slide downhill. If this happens on an active volcano, then the movement will distort deformation data and thus potentially compromise interpretation. Our recent GPS measurements demonstrate that the entire edifice of Mt. Etna is sliding to the ESE, the overall direction of slope of its complex, rough sedimentary basement. We report methods of discriminating the sliding vector from other deformation processes and of measuring its velocity, which averaged 14 mm year−1 during four intervals between 2001 and 2012. Though sliding of one sector of a volcano due to flank instability is widespread and well-known, this is the first time basement sliding of an entire active volcano has been directly observed. This is important because the geological record shows that such sliding volcanoes are prone to devastating sector collapse on the downslope side, and whole volcano migration should be taken into account when assessing future collapse hazard. It is also important in eruption forecasting, as the sliding vector needs to be allowed for when interpreting deformation events that take place above the sliding basement within the superstructure of the active volcano, as might occur with dyke intrusion or inflation/deflation episodes
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