The effects of different test methods on the just noticeable difference of clarity index for music.

The just noticeable differences (JNDs) of room acoustics metrics are necessary for research and design of performing arts venues. The goal of this work was to evaluate the effects of different testing methods on the measured JND of clarity index for music (C80). An initial study was conducted to verify the findings of other published works that the C80 JND is approximately 1 dB, as currently listed in ISO 3382:2009 (International Organization for Standardization, Switzerland, 2009), however, the results suggested a higher value. In the second study, the effects of using two variations of the method of constant stimuli were examined, where one variation required the subjects to evaluate the pair of signals by listening to each of them in their entirety, while the second approach allowed the participants to switch back and forth in real-time. More consistent results were obtained with the latter variation and the results indicated a C80 JND greater than 1 dB. In the final study, an extensive training period using the first variation was required, based on the second study, and the data were collected using the second variation. The analysis revealed that for the conditions used in this study (concert hall and chamber music hall) that the C80 JND is approximately 3 dB.

Management of maxillofacial injuries with severe oronasal hemorrhage: a multicenter perspective.

BACKGROUND: Airway establishment and hemorrhage control may be difficult to achieve in patients with massive oronasal bleeding from maxillofacial injuries. This study was formulated to develop effective algorithms for managing these challenging injuries. METHODS: Trauma registries from nine trauma centers were queried over a 7-year period for injuries with abbreviated injury scale face >/= 3 and transfusion of >/=3 units of blood within 24 hours. Patients in whom no significant bleeding was attributed to maxillofacial trauma were excluded. Patient demographics, injury severity measures, airway management, hemostatic procedures, and outcome were analyzed. RESULTS: Ninety patients were identified. Median injury severity scores for 60 blunt trauma patients was 34 versus 17 for 30 patients with penetrating wounds (p < 0.05). Initial airway management was by endotracheal intubation in 72 (80%) patients. Emergent cricothyrotomy and tracheostomy were necessary in 7 (8%) and 5 (6%) patients, respectively. Seventeen (57%) patients with penetrating wounds were taken directly to the operating room for airway control and initial efforts at hemostasis versus 12 (20%) patients with blunt trauma (p < 0.05). Anterior or posterior or both packing alone controlled bleeding in only 29% of patients in whom it was used. Transarterial embolization (TAE) was used in 12 (40%) patients with penetrating injuries and 20 (33%) patients with blunt trauma. TAE was successful for definitive control of hemorrhage in 87.5% of patients. Overall mortality rate was 24.4%, with 6 (7%) deaths directly attributable to maxillofacial injuries. CONCLUSIONS: Initial airway control was achieved by endotracheal intubation in most patients. Patients with penetrating wounds were more frequently taken directly to the operating room for airway management and initial efforts at hemostasis. Patients with blunt trauma were much more likely to have associated injuries which affected treatment priorities. TAE was highly successful in controlling hemorrhage.

Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease.

Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic buildup in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target--the lysosomes. A fluid-phase endocytic marker was similarly mistargeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process and point toward new avenues for the development of pharmacological intervention.

Autophagy and lysosomes in Pompe disease.

In Pompe disease, a deficiency of lysosomal acid alpha-glucosidase, intralysosomal glycogen accumulates in multiple tissues, with skeletal and cardiac muscle most severely affected.(1) Complete enzyme deficiency results in rapidly progressive infantile cardiomyopathy and skeletal muscle myopathy that is fatal within the first two years of life. Patients with partial enzyme deficiency suffer from skeletal muscle myopathy and experience shortened lifespan due to respiratory failure. The major advance has been the development of enzyme replacement therapy, which recently became available for Pompe patients. However, the effective clearance of skeletal muscle glycogen, as shown by both clinical and preclinical studies, has proven more difficult than anticipated.(2-4) Our recent work published in Annals of Neurology(5) was designed to cast light on the problem, and was an attempt to look beyond the lysosomes by analyzing the downstream events affected by the accumulation of undigested substrate in lysosomes. We have found that the cellular pathology in Pompe disease spreads to affect both endocytic (the route of the therapeutic enzyme) and autophagic (the route of glycogen) pathways, leading to excessive autophagic buildup in therapy-resistant skeletal muscle fibers of the knockout mice.