683 research outputs found

    Production Perspectives of Heavy Metal Record Producers

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    The study of the recorded artefact from a musicological perspective continues to unfold through contemporary research. Whilst an understanding of the scientific elements of recorded sound is well documented, the exploration of the production and the artistic nature of this endeavour is still developing. This article explores phenomenological aspects of producing heavy metal music from the perspective of seven renowned producers working within the genre. Through a series of interviews and subsequent in-depth analysis, particular sonic qualities are identified as key within the production of this work: Impact; energy; precision; and extremity. A conceptual framework is then put forward for understanding the production methodology of recorded heavy metal music, and how developing technology has influenced the production of the genre

    Development and preliminary evaluation of the VPS ReplaySuite: a virtual double-headed microscope for pathology

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    BACKGROUND: Advances in computing and telecommunications have resulted in the availability of a range of online tools for use in pathology training and quality assurance. The majority focus on either enabling pathologists to examine and diagnose cases, or providing image archives that serve as reference material. Limited emphasis has been placed on analysing the diagnostic process used by pathologists to reach a diagnosis and using this as a resource for improving diagnostic performance. METHODS: The ReplaySuite is an online pathology software tool that presents archived virtual slide examinations to pathologists in an accessible video-like format, similar to observing examinations with a double-headed microscope. Delivered through a customised web browser, it utilises PHP (Hypertext PreProcessor) to interact with a remote database and retrieve data describing virtual slide examinations, performed using the Virtual Pathology Slide (VPS). To demonstrate the technology and conduct a preliminary evaluation of pathologists opinions on its potential application in pathology training and quality assurance, 70 pathologists were invited to use the application to review their own and other pathologists examinations of 10 needle-core breast biopsies and complete an electronic survey. 9 pathologists participated, and all subsequently completed an exit survey. RESULTS: Of those who replayed an examination by another pathologist, 83.3% (5/6) agreed that replays provided an insight into the examining pathologists diagnosis and 33.3% (2/6) reconsidered their own diagnosis for at least one case. Of those who reconsidered their original diagnosis, all re-classified either concordant with group consensus or original glass slide diagnosis. 77.7% (7/9) of all participants, and all 3 participants who replayed more than 10 examinations stated the ReplaySuite to be of some or great benefit in pathology training and quality assurance. CONCLUSION: Participants conclude the ReplaySuite to be of some or of great potential benefit to pathology training and quality assurance and consider the ReplaySuite to be beneficial in evaluating the diagnostic trace of an examination. The ReplaySuite removes temporal and spatial issues that surround the use of double-headed microscopes by allowing examinations to be reviewed at different times and in different locations to the original examination. While the evaluation set was limited and potentially subject to bias, the response of participants was favourable. Further work is planned to determine whether use of the ReplaySuite can result in improved diagnostic ability

    New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

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    The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

    Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

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    Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion

    Hearing aid effectiveness after aural rehabilitation - individual versus group (HEARING) trial: RCT design and baseline characteristics

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    <p>Abstract</p> <p>Background</p> <p>Hearing impairment is the most common body system disability in veterans. In 2008, nearly 520,000 veterans had a disability for hearing loss through the Department of Veterans Affairs (VA). Changes in eligibility for hearing aid services, along with the aging population, contributed to a greater than 300% increase in the number of hearing aids dispensed from 1996 to 2006. In 2006, the VA committed to having no wait times for patient visits while providing quality clinically-appropriate care. One approach to achieving this goal is the use of group visits as an alternative to individual visits. We sought to determine: 1) if group hearing aid fitting and follow-up visits were at least as effective as individual visits, and 2) whether group visits lead to cost savings through the six month period after the hearing aid fitting. We describe the rationale, design, and characteristics of the baseline cohort of the first randomized clinical trial to study the impact of group versus individual hearing aid fitting and follow-up visits.</p> <p>Methods</p> <p>Participants were recruited from the VA Puget Sound Health Care System Audiology Clinic. Eligible patients had no previous hearing aid use and monaural or binaural air-conduction hearing aids were ordered at the evaluation visit. Participants were randomized to receive the hearing aid fitting and the hearing aid follow-up in an individual or group visit. The primary outcomes were hearing-related function, measured with the first module of the Effectiveness of Aural Rehabilitation (Inner EAR), and hearing aid adherence. We tracked the total cost of planned and unplanned audiology visits over the 6-month interval after the hearing aid fitting.</p> <p>Discussion</p> <p>A cohort of 659 participants was randomized to receive group or individual hearing aid fitting and follow-up visits. Baseline demographic and self-reported health status and hearing-related measures were evenly distributed across the treatment arms.</p> <p>Outcomes after the 6-month follow-up period are needed to determine if group visits were as least as good as those for individual visits and will be reported in subsequent publication.</p> <p>Trial Registration</p> <p>NCT00260663</p

    Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

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    Oral capecitabine (Xeloda&lt;sup&gt;&#174;&lt;/sup&gt;) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by &gt;75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

    A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0

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    <p>Abstract</p> <p>Background</p> <p>Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver.</p> <p>Case Presentation</p> <p>Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the <it>GYS2 </it>gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c.736 C>T; R243X) and a novel frameshift mutation (966_967delGA/insC) which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion.</p> <p>Conclusion</p> <p>The current results expand the spectrum of known mutations in <it>GYS2 </it>and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions.</p

    Enterococcal colonization of infants in a neonatal intensive care unit: associated predictors, risk factors and seasonal patterns

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    <p>Abstract</p> <p>Background</p> <p>During and shortly after birth, newborn infants are colonized with enterococci. This study analyzes predictors for early enterococcal colonization of infants in a neonatal intensive care unit and describes risk factors associated with multidrugresistant enterococci colonization and its seasonal patterns.</p> <p>Methods</p> <p>Over a 12-month period, we performed a prospective epidemiological study in 274 infants admitted to a neonatal intensive care unit. On the first day of life, we compared infants with enterococcal isolates detected in meconium or body cultures to those without. We then tested the association of enterococcal colonization with peripartal predictors/risk factors by using bivariate and multivariate statistical methods.</p> <p>Results</p> <p>Twenty-three percent of the infants were colonized with enterococci. The three most common enterococcal species were <it>E. faecium </it>(48% of isolates), <it>E. casseliflavus </it>(25%) and <it>E. faecalis </it>(13%). Fifty-seven percent of the enterococci found were resistant to three of five antibiotic classes, but no vancomycin-resistant isolates were observed. During winter/spring months, the number of enterococci and multidrug-resistant enterococci were higher than in summer/fall months (p = 0.002 and p < 0.0001, respectively). With respect to enterococcal colonization on the first day of life, predictors were prematurity (p = 0.043) and low birth weight (p = 0.011). With respect to colonization with multidrug-resistant enterococci, risk factors were prematurity (p = 0.0006), low birth weight (p < 0.0001) and prepartal antibiotic treatment (p = 0.019). Using logistic regression, we determined that gestational age was the only parameter significantly correlated with multidrug-resistant enterococci colonization. No infection with enterococci or multidrugresistant enterococci in the infants was detected. The outcome of infants with and without enterococcal colonization was the same with respect to death, necrotizing enterocolitis, intracerebral hemorrhage and bronchopulmonary dysplasia.</p> <p>Conclusion</p> <p>In neonatal intensive care units, an infant's susceptibility to early colonization with enterococci in general, and his or her risk for colonization with multidrug-resistant enterococci in particular, is increased in preterm newborns, especially during the winter/spring months. The prepartal use of antibiotics with no known activity against enterococci appears to increase the risk for colonization with multidrug-resistant enterococci.</p

    Understanding the links between hearing impairment and dementia : development and validation of the social and emotional impact of hearing impairment (SEI-HI) questionnaire

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    Background The links between hearing impairment (HI) and dementia have been well documented, but factors mediating this relationship remain unknown. Major consequences of HI are social and emotional dysfunction, and as the risk of dementia increases linearly with the severity of HI, it is plausible that socio-emotional difficulties may play a role in this association. Objective The aim of this study was to develop and validate a tool to analyse levels of hearing-related disability, to investigate ultimately whether subjective disability contributes to risk of cognitive impairment compared with hearing thresholds alone. Methods Development and validation of the questionnaire, the Social and Emotional Impact of Hearing Impairment (SEI-HI), was conducted in four phases: (1) content; (2) scoring and outcomes; (3) validation; (4) feasibility in a sample of people with cognitive impairment. Results Considerable evidence was found for the internal and external reliability of the tool with high construct validity, concurrent validity and test-retest values of the SEI-HI questionnaire. A feasibility check on 31 patients with mild cognitive impairment or dementia showed the SEI-HI questionnaire was easy to administer and well-received. Conclusion The SEI-HI questionnaire is a relevant instrument to assess hearing-related disability which can be used in people with cognitive decline to assess further impact on risk of developing dementia
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