Mucopolysaccharidosis VI

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B leading to the accumulation of dermatan sulfate. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (generally >100 μg/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 μg/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS VI, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. Diagnosis generally requires evidence of clinical phenotype, arylsulfatase B enzyme activity <10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS I, II IVA, VII), sialidosis and mucolipidosis. Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme®), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided

Visually guided self supervised learning of speech representations

Self supervised representation learning has recently attracted a lot of research interest for both the audio and visual modalities. However, most works typically focus on a particular modality or feature alone and there has been very limited work that studies the interaction between the two modalities for learning self supervised representations. We propose a framework for learning audio representations guided by the visual modality in the context of audiovisual speech. We employ a generative audio-to-video training scheme in which we animate a still image corresponding to a given audio clip and optimize the generated video to be as close as possible to the real video of the speech segment. Through this process, the audio encoder network learns useful speech representations that we evaluate on emotion recognition and speech recognition. We achieve state of the art results for emotion recognition and competitive results for speech recognition. This demonstrates the potential of visual supervision for learning audio representations as a novel way for self-supervised learning which has not been explored in the past. The proposed unsupervised audio features can leverage a virtually unlimited amount of training data of unlabelled audiovisual speech and have a large number of potentially promising applications

Intradurale Katheter-Lyse in einer Patientin mit einem langstreckigen traumatischen subduralen spinalen Hämatom

Burrell showman's steam traction engine No.3561 (built 1915) - registration 'HR3964' 'Earl Kitchener' - in the livery of 'R. Edwards and Sons Limited - photographed at Tewkesbury Steam Rally, 1970

Cyclic response of RC beam-column joints strengthened with transverse steel bars and with C-FRP diagonal ties

The use of additional bars, internally placed through drill holes, in external beam-column connections subjected to cyclic loading, as shear reinforcement is experimentally investigated.The presented experimental work includes tests of full-scale specimens with different reinforcement arrangements in the joint area, they are as follows: (a) the JB0V control specimen with two (extra) vertical side bars without shear reinforcement in the joint area and, (b) the JB0R joint, same as in the case of the control specimen, without the extra vertical bars, but with four additional steel bars that were placed in holes, which were drilled through the concrete of the joint body for this purpose, (c) the JB0VFX joint, the damaged control specimen repaired and strengthened with C-FRP diagonal ties (rope connections) through the joint area. The effectiveness of these additional bars and ropes as a shear reinforcement on the overall seismic performance of the tested joint is examined.A comparison between the test results of the examined specimens indicated that the applied retrofitting technique is appropriate for the enhancement of the overall hysteretic performance of the beam-column joints in terms of load carrying capacity, stiffness and hysteretic energy dissipation