370 research outputs found

    Growth, decline and locational change in the English silk industry of the nineteenth century: a study in historical geography

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    The English silk industry, by its extreme fluctuations in profitability and its widespread distribution makes an interesting geographical case study of some of the forces which affected the location of industry during the Industrial Revolution. This thesis sets out to analyse the industry's changing location in times of expansion and contraction, particularly in its mechanised branches, during the nineteenth century. The broad locational pattern of the silk industry was established during the eighteenth century when a considerable increase in the size of the industry was accompanied by spatial expansion: the old concentrations of manufacturing in London declined in importance and new centres, particularly in the Pennine province, but also in parts of southern England assumed greater significance. The first four chapters examine the factors, for example power supplies and competition for labour, which influenced its location. Because of its uncertain profitability, there were few districts in which silk could dominate the local labour force and so secure a measure of protection from stronger industries. Its labour force was thus liable to be eroded during the industry's frequent recessions and was only rebuilt with difficulty in subsequent booms. The supply of labour is therefore seen as a major factor affecting the changing location of silk manufacture, though competition for other resources, such as power and factory space were also significant, particularly in the Pennine province. The broad pattern of the industry's distribution had been established by the mid-nineteenth century and from this time there is a wealth of statistical information available for the size and distribution of the industry in the Factory Inspectors' Returns and the Census. Chapter 5 uses these sources to give a systematic account of the distribution and structure of the industry in about 1850. Despite its widespread distribution it is evident that there existed compact localities in which silk manufacturing was concentrated and that here the domestic, as well as the factory workers were found. Moreover, there were four districts, London, Lancashine the South West Pennines and Coventry which were the dominant centres of the trade and together accounted for most of the industry's employment. From an analysis of the technical data contained in the Factory Inspectors' Returns it is possible to distinguish some regional contrasts in the technical advancement and organisation of the industry. Chapter 6 concludes that in general silk manufacturing in the south was labour intensive and technically backward while in the Pennines contact and competition with the other textile trades made for a more advanced industry. Chapters 7 and 8 analyse the reaction in the various regions to one of the most extreme fluctuations in fortune that the industry experienced, in terms both of changing techniques and organisation and of the size and distribution of the labour force. Differences between the throwing and weaving branches in their response to boom and slump were apparent and the greater strength of the Pennine industry was again demonstrated. Finally Chapter 9 examines the long term decline of the industry after the Free Trade Treaty of 1860. Competition exposed the weaknesses of the industry and at a national level contraction was inevitable. But some of the regional specialisms had the ability to persist despite the general malaise, and it was not until the twentieth century that silk manufacturing was located almost entirely in one region, the South West Pennines

    Clustering approaches to improve the performance of low cost air pollution sensors

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    Low cost air pollution sensors have substantial potential for atmospheric research and for the applied control of pollution in the urban environment, including more localized warnings to the public. The current generation of single-chemical gas sensors experience degrees of interference from other co-pollutants and have sensitivity to environmental factors such as temperature, wind speed and supply voltage. There are uncertainties introduced also because of sensor-to-sensor response variability, although this is less well reported. The sensitivity of Metal Oxide Sensors (MOS) to volatile organic compounds (VOCs) changed with relative humidity (RH) by up to a factor of five over the range 19-90%RH and with an uncertainty in the correction of a factor two at any given RH. The short-term (second to minute) stabilities of MOS and electrochemical CO sensor responses were reasonable. During more extended use inter-sensor quantitative comparability was degraded due to unpredictable variability in individual sensor responses (to either measurand or interference or both) drifting over timescales of several hours to days. For timescales longer than a week identical sensors showed slow, often downwards, drifts in their responses which diverged across six CO sensors by up to 30% after two weeks. The measurement derived from the median sensor within clusters of 6, 8 and up to 21 sensors was evaluated against individual sensor performance and external reference values. The clustered approach maintained the cost competitiveness of a sensor device, but the median concentration from the ensemble of sensor signals largely eliminated the randomised hour-to-day response drift seen in individual sensors and excluded the effects of small numbers of poorly performing sensors that drifted significantly over longer time periods. The results demonstrate that for individual sensors to be optimally comparable to one another, and to reference instruments, they would likely require frequent calibration. The use of a cluster median value eliminates unpredictable medium term response changes, and other longer term outlier behaviours, extending the likely period needed between calibration and making a linear interpolation between calibrations more appropriate. Through the use of sensor clusters rather than individual sensors existing low cost technologies could deliver significantly improved quality of observations

    The Process of Organ Donation from Non-Living Donors: A Case-Based Journey from Potential Donor Identification to Organ Procurement

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    Each year, thousands of people worldwide succumb to end-organ failure while awaiting life-saving transplantation procedures. The shortage of organs continues with no signs of easing in the foreseeable future. The availability of organs from living donors continues to be constrained. At the same time, the cumulative knowledge of organ preservation is advancing steadily resulting in an enhanced ability to utilize a growing number of previously unsuitable tissue and organ gifts. Our ability to procure and preserve more organs is accompanied by the increasing use of so-called “expanded criteria” donors, or those whose organs may not have been suitable without modern advances in organ preservation science. Within the overall context of organ donation from non-living donors, the importance of physiologic and end-organ optimization cannot be understated. This chapter discusses our current state of understanding of optimized organ procurement approaches derived from practical experiences and “lessons learned” at a high-performing, community-based tertiary referral hospital

    Infraglenoidal scapular notching in reverse total shoulder replacement: a prospective series of 60 cases and systematic review of the literature

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    <p>Abstract</p> <p>Background</p> <p>The impact of infraglenoidal scapular notching in reversed total shoulder arthroplasty (RTSA) is still controversially discussed. Our goal was to evaluate its potential influence on subjective shoulder stability and clinical outcome. We hypothesized that subjective instability and clinical outcome after implantation of RTSA correlates with objective scapular notching.</p> <p>Methods</p> <p>Sixty shoulders were assessed preoperatively and at minimum 2-year follow-up for active range of motion and by use of the Oxford instability score, Rowe score for instability, Constant score for pain, Constant shoulder score, DASH score. All shoulders were evaluated on anterior-posterior and axillary lateral radiographic views. These X-ray scans were classified twice by two orthopaedic surgeons with respect to infraglenoidal scapular notching according to the classification of Nerot. Notching was tested for correlation with clinical outcome scores to the evaluated notching.</p> <p>Results</p> <p>We found no significant correlation between infraglenoidal scapular notching and clinical outcomes after a mid-term follow-up from 24 to 60 months, but at the final follow-up of 60 months and more, we did see statistically significant, positive correlations between infraglenoidal scapular notching and the Constant pain score as well as active range of motion. At mean follow-up of 42 months (range from 24 to 96 months) we found no significant correlation between subjective instability and infraglenoidal scapular notching.</p> <p>Conclusions</p> <p>We conclude that patients' subjective impression on their shoulders' stability is not correlating with radiological signs of infraglenoidal scapular notching. Nevertheless clinical parameters are affected by infraglenoidal scapular notching, at least in the long term</p

    Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma

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    Background: The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods: Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results: Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions: Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01088815

    PReVENT - protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial

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    Background It is uncertain whether lung-protective mechanical ventilation using low tidal volumes should be used in all critically ill patients, irrespective of the presence of the acute respiratory distress syndrome (ARDS). A low tidal volume strategy includes use of higher respiratory rates, which could be associated with increased sedation needs, a higher incidence of delirium, and an increased risk of patient-ventilator asynchrony and ICU-acquired weakness. Another alleged side-effect of low tidal volume ventilation is the risk of atelectasis. All of these could offset the beneficial effects of low tidal volume ventilation as found in patients with ARDS. Methods/Design PReVENT is a national multicenter randomized controlled trial in invasively ventilated ICU patients without ARDS with an anticipated duration of ventilation of longer than 24 hours in 5 ICUs in The Netherlands. Consecutive patients are randomly assigned to a low tidal volume strategy using tidal volumes from 4 to 6 ml/kg predicted body weight (PBW) or a high tidal volume ventilation strategy using tidal volumes from 8 to 10 ml/kg PBW. The primary endpoint is the number of ventilator-free days and alive at day 28. Secondary endpoints include ICU and hospital length of stay (LOS), ICU and hospital mortality, the incidence of pulmonary complications, including ARDS, pneumonia, atelectasis, and pneumothorax, the cumulative use and duration of sedatives and neuromuscular blocking agents, incidence of ICU delirium, and the need for decreasing of instrumental dead space. Discussion PReVENT is the first randomized controlled trial comparing a low tidal volume strategy with a high tidal volume strategy, in patients without ARDS at onset of ventilation, that recruits a sufficient number of patients to test the hypothesis that a low tidal volume strategy benefits patients without ARDS with regard to a clinically relevant endpoin

    PROGNOSTIC IMPLICATION OF THE MITRAL VALVE TENTING GEOMETRY IN PATIENTS WITH DILATED CARDIOMYOPATHY: TRANSTHORACIC REAL-TIME 3D ECHOCARDIOGRAPHIC STUDY

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    BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
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