2,930 research outputs found

    3D mid-air audio-haptic navigation for digital signage

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    In this workshop we discuss the application of using mid-air haptics to provide directions for navigation to users in large indoor spaces. We propose a feed-forward approach from objects and locations that enable a physical way of thinking, communication and general accessibility

    Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

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    © 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

    One-stage laparoscopic-assisted resection of gastrojejunocolic fistula after gastrojejunostomy for duodenal ulcer: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Gastrojejunocolic fistula is a rare condition after gastrojejunostomy. It was thought to be a late complication related to stomal ulcers as a result of inadequate gastrectomy or incomplete vagotomy. We report a case of gastrojejunocolic fistula after gastrojejunostomy for peptic ulcer treated with one-stage laparoscopic resection.</p> <p>Case presentation</p> <p>A 41-year-old Japanese man complained of diarrhea for 10 months, as well as severe weight loss and weakness. After admission, we immediately started intravenous hyperalimentation. On performing colonoscopy and barium swallow, gastrojejunocolic fistula was observed close to the gastrojejunostomy site leading to the transverse colon. After our patient's nutritional status had improved, one-stage surgical intervention was performed laparoscopically. After the operation, our patient recovered uneventfully and his body weight increased by 5 kg within three months.</p> <p>Conclusions</p> <p>Modern management of gastrojejunocolic fistula is a one-stage resection because of the possibility of early recovery from malnutrition using parenteral nutritional methods. Today, laparoscopic one-stage en bloc resection may be feasible for patients with gastrojejunocolic fistula due to the development of laparoscopic instruments and procedures. We describe the first case of gastrojejunocolic fistula treated laparoscopically by one-stage resection and review the literature.</p

    High glucose up-regulates ENaC and SGK1 expression in HCD-cells

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    Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised. Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry. Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level. Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy

    An exploratory study looking at the relationship marketing techniques used in the music festival industry

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    There are current issues and trends in the music festival market, which may affect the success of an event, and market saturation is at the forefront of these issues. Previous literature, maintaining the need for a marketing approach to festivals, identifi es the need for maintaining strong stakeholder relationships in order to succeed in a business environment; attention has been focused to the theory of relationship marketing (RM) because of the recognition that this practice is complementary to the marketing of festivals. The very nature of the music festival as an annual, usually, 4-day event means that effective marketing is needed to keep connections with the consumer throughout the year. This article focuses on the RM techniques utilised within the music festival industry from the viewpoint of the festival organiser in an attempt to establish how festival organisations value and monitor organisational relationships. This article explores the extent to which these relationships are valued and managed; furthermore, the variations between these intricate relationships are considered by focusing on those held with the organisation ’ s consumers and sponsors, the results of which have provided the ability to establish the importance and relevance of RM to the industry and further identify the marketing communication methods employed to establish and maintain such relationships. In-depth, convergent interviews have been conducted with a segment of music festival organisers from a range of events. The results have been integrated with the study of current literature to best exemplify these issues. It has been established that RM has a strong role in today ’ s commercial and independent music festival industry; technological advances are enabling the organiser to support online relationships further and increase consumer loyalty. There is a need to expand the research further because of the complexity of organisational relationships and the varying categories of festivals

    Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

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    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

    Enhanced warming over the global subtropical western boundary currents

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    Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Climate Change 2 (2012): 161-166, doi:10.1038/nclimate1353.Subtropical western boundary currents are warm, fast flowing currents that form on the western side of ocean basins. They carry warm tropical water to the mid-latitudes and vent large amounts of heat and moisture to the atmosphere along their paths, affecting atmospheric jet streams and mid-latitude storms, as well as ocean carbon uptake. The possibility that these highly energetic and nonlinear currents might change under greenhouse gas forcing has raised significant concerns, but detecting such changes is challenging owing to limited observations. Here, using reconstructed sea surface temperature datasets and newly developed century-long ocean and atmosphere reanalysis products, we find that the post-1900 surface ocean warming rate over the path of these currents is two to three times faster than the global mean surface ocean warming rate. The accelerated warming is associated with a synchronous poleward shift and/or intensification of global subtropical western boundary currents in conjunction with a systematic change in winds over both hemispheres. This enhanced warming may reduce ocean's ability to absorb anthropogenic carbon dioxide over these regions. However, uncertainties in detection and attribution of these warming trends remain, pointing to a need for a long-term monitoring network of the global western boundary currents and their extensions.This work is supported by China National Key Basic Research Project (2007CB411800) and National Natural Science Foundation Projects (40788002, 40921004). WC is supported by the Australian Climate Change Science program and the Southeast Australia Climate Initiative. HN is supported in part by the Japanese Ministry of Education, Culture, Sports, Science and Technology through Grant-in-Aid for Scientific Research on Innovative Areas #2205 and by the Japanese Ministry of Environment through Global Environment Research Fund (S-5). MJM is supported by NOAA’s Climate Program Office.2012-07-2

    The MacGyver effect: alive and well in health services research?

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    <p>Abstract</p> <p>Background</p> <p>In a manner similar to the television action hero MacGyver, health services researchers need to respond to the pressure of unpredictable demands and constrained time frames. The results are often both innovative and functional, with the creation of outputs that could not have been anticipated in the initial planning and design of the research.</p> <p>Discussion</p> <p>In the conduct of health services research many challenges to robust research processes are generated as a result of the interface between academic research, health policy and implementation agendas. Within a complex and rapidly evolving environment the task of the health services researcher is, therefore, to juggle sometimes contradictory pressures to produce valid results.</p> <p>Summary</p> <p>This paper identifies the MacGyver-type dilemmas which arise in health services research, wherein innovation may be called for, to maintain the intended scientific method and rigour. These 'MacGyver drivers' are framed as opposing issues from the perspective of both academic and public policy communities. The ideas expressed in this paper are illustrated by four examples from research projects positioned at the interface between public policy strategy and academia.</p

    Predicting protein functions by relaxation labelling protein interaction network

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    <p>Abstract</p> <p>Background</p> <p>One of key issues in the post-genomic era is to assign functions to uncharacterized proteins. Since proteins seldom act alone; rather, they must interact with other biomolecular units to execute their functions. Thus, the functions of unknown proteins may be discovered through studying their interactions with proteins having known functions. Although many approaches have been developed for this purpose, one of main limitations in most of these methods is that the dependence among functional terms has not been taken into account.</p> <p>Results</p> <p>We developed a new network-based protein function prediction method which combines the likelihood scores of local classifiers with a relaxation labelling technique. The framework can incorporate the inter-relationship among functional labels into the function prediction procedure and allow us to efficiently discover relevant non-local dependence. We evaluated the performance of the new method with one other representative network-based function prediction method using E. coli protein functional association networks.</p> <p>Conclusion</p> <p>Our results showed that the new method has better prediction performance than the previous method. The better predictive power of our method gives new insights about the importance of the dependence between functional terms in protein functional prediction.</p

    Dysphagia as a manifestation of esophageal tuberculosis: a report of two cases

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    <p>Abstract</p> <p>Introduction</p> <p>Esophageal involvement by <it>Mycobacterium tuberculosis </it>is rare and the diagnosis is frequently made by means of an esophageal biopsy during the evaluation of dysphagia. There are few cases reported in the literature.</p> <p>Case presentation</p> <p>We present two cases of esophageal tuberculosis in 85- and 65-year-old male Caucasian patients with initial complaints of dysphagia and epigastric pain. Upper gastrointestinal endoscopy resulted in the diagnosis of esophageal tuberculosis following the biopsy of lesions of irregular mucosa in one case and a sessile polyp in the other. Pulmonary tuberculosis was detected in one patient. In one patient esophageal stricture developed as a complication. Antituberculous therapy was curative in both patients.</p> <p>Conclusion</p> <p>Although rare, esophageal tuberculosis has to be kept in mind in the differential diagnosis of dysphagia. Pulmonary involvement has important implications for contact screening.</p
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