2,419 research outputs found

    The Impact of an Independent Sector Treatment Centre on Basic Surgical Training

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    The reorganisation of postgraduate medical training in the UK as a result of Calman reforms, the New Deal and the implementation of the European workingTime regulations (EwTr) has led to a substantial reduction in working hours and a fall in operative experience for surgical trainees. The move of large volumes of minor and intermediate NHS surgical caseload into independently run hospitals and specialist centres (of which the Southampton NHS Treatment Centre, an independent sector treatment centre (ISTC) is a well-established example) has also radically altered the basic surgical training environment. The Southampton ISTC is run on contract by Care UK and is medically staffed by a mix of full-time Care UK employees from the UK and abroad as well as by visiting consultants from University Hospital Southampton NHS foundationTrust (UHSFT

    F21RS SGCR No. 19 (Lauren Shaw, Student Media Board)

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    A Concurrent Resolution To appoint Lauren Shaw as an SG representative on the student media boar

    Insulin resistance, obesity and the metabolic syndrome. Is there a therapeutic role for endothelin-1 antagonists?

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    There is increasing evidence to suggest that chronic activation of the endothelin-1 system can lead to heterologous desensitization of the glucose-regulatory and mitogenic actions of insulin with subsequent development of glucose intolerance, hyperinsulinemia, impaired endothelial function and exacerbation of cardiovascular disease. Effects are mediated through a variety of mechanisms that include attenuation of key insulin signalling pathways and decreased tyrosine phosphorylation of insulin receptor substrates IRS-1, SHC and G alpha q/11. Other actions involve hemodynamic changes leading to reduced delivery of insulin and glucose to peripheral tissues as well as enhanced hepatic glycogenolysis, decreased glucose-transporter translocation and modulation of various adipokines that regulate insulin action. Overall the data suggest that ET-1 antagonists may provide an effective means of improving cardiac dysfunction and favourably influencing glucose tolerance in obese humans and patients with early insulin sensitivity where there is clear evidence for activation of the ET-1 system. Although most effects of ET-1 that modulate mechanisms leading to glucose intolerance appear to involve the ETA receptor subtype recent data indicates that combined ETA/ETB receptor antagonists may function as effectively as selective ETA blockers. Prospective trials are needed to assess whether ET-1 antagonists, either alone or in combination, are superior to other more conventional therapies such as insulin sensitizers and to evaluate effects of combined treatments on the development of insulin resistance and the progression of diabetes. Early screening of patients at risk for evidence of ET-1 activation would help to identify subjects who may benefit most from such treatment

    Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?

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    Alcoholic hepatitis is characterised histologically by an intense inflammatory cell infiltrate made up predominantly of neutrophils but including other cell types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion, which is mediated via receptors on the leukocyte surface including leukocyte function associated antigen-1 (LFA-1) which binds to the ligand intercellular adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and LFA-1 expression in liver biopsy specimens from patients with alcoholic liver disease was examined to ascertain whether this pathway of leukocyte adhesion is involved in the tissue damage of alcoholic hepatitis. Specimens were stained for ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on liver components were examined. ICAM-1 expression on hepatocytes was significantly greater in alcoholic hepatitis compared with fatty liver (p less than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005) and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1 expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1 pathway may therefore be involved in leukocyte mediated tissue damage during alcoholic hepatitis

    Experimental investigation of the temperature effect on the structural response of SG-laminated reinforced glass beams

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    To generate high-level redundancy for structural glass beams, a novel concept of laminating a metal reinforcement to a structural glass beam has been developed at Delft University of Technology (TU Delft). This concept makes use of the relatively stiff polymer interlayer material SentryGlas (SG) to bond the metal to the glass. However, due to the visco-elastic properties of the SG, its stiffness varies at different temperature levels. To what extent this temperature dependency has an effect on the structural response of the beam composite has been experimentally investigated in cooperation with Ghent University (UGent) and is the subject of current publication. Two separate series of pull-out tests, to investigate the bond strength, and beam tests, to investigate the post-breakage response, have been conducted at -20, 23 and 60 degrees C. The pull-out tests revealed a high temperature dependency of the bond strength of SG. This temperature dependency also had an effect on the structural response of the beams. However, regardless of temperature level all beams showed high-level plastic response and high redundancy. It is therefore concluded that temperature levels of -20 to 60 degrees C do not endanger the structural safety of SG-laminated reinforced glass beams.RESSLA

    Blocking TLR-TICAM-1 pathway by RSV sG

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    Monocyte-derived dendritic cells (mDCs) recognize viral RNA extrinsically by TLR3 on the membrane and intrinsically RIG-I/MDA5 in the cytoplasm to induce type I interferons (IFNs) and mDC maturation. When mDCs were treated with live or UV-irradiated respiratory syncytial virus (RSV), early (~4 h) induction of IFN-β detected in other virus infections was barely observed. Live RSV subsequently replicated to activate the cytoplasmic IFN-inducing pathway leading to robust type I IFN induction. We found that RSV initial attachment to cells blocked polyI:C-mediated IFN-β induction, and this early IFN-β-modulating event was abrogated by Abs against envelope proteins of RSV, demonstrating the presence of a IFN-regulatory mode by early RSV attachment to host cells. By IFN-stimulated response element (ISRE) reporter analysis in HEK293 cells, polyI:C- or LPS-mediated ISRE activation was dose-dependently inhibited by live and inactive RSV to a similar extent. Of the RSV envelope proteins, simultaneously-expressed or exogenously-added RSV G or soluble G (sG) proteins inhibited TLR3/4-mediated ISRE activation in HEK293 cells. sG proteins expressed in cells did not affect the RIG-I/MDA5 pathway but inhibited the TLR adaptor TRIF/TICAM-1 pathway for ISRE activation. Finally, extrinsically-added sG protein suppressed the production of IFN-β in mDCs. Although the molecular mechanism of this extrinsic functional mode of the RSV G protein remains undetermined, G proteins may neutralize the F protein function that promotes IFN-mediated mDC modulation via TLR4 and may cause insufficient raising cell-mediated immunity against RSV

    KNOTTING AND SUPERCOILING IN CIRCULAR DNA - A MODEL INCORPORATING THE EFFECT OF ADDED SALT

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    We consider a model of a circular polyelectrolyte, such as DNA, in which the molecule is represented by a polygon in the three-dimensional simple cubic lattice. A short-range attractive force between nonbonded monomers is included (to account for solvent quality) together with a screened Coulomb potential (to account for the effect of added salt). We compute the probability that the ring is knotted as a function of the number of monomers in the ring, and of the ionic strength of the solution. The results show the same general behavior as recent experimental results by Shaw and Wang [Science 260, 533 (1993)] and by Rybenkov, Cozzarelli, and Vologodskii [Proc. Natl. Acad. Sci. U.S.A. 90, 5307 (1993)] on the knot probability in circular DNA as a function of added salt. In addition, we compute the writhe of the polygon and show that this also increases as the ionic strength increases. The writhe computations model the conformational behavior of nicked circular duplex DNA molecules in salt solution

    Final follow-up of the Multicentre Aneurysm Screening Study (MASS) randomized trial of abdominal aortic aneurysm screening

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    Background: The long-term effects of abdominal aortic aneurysm (AAA) screening were investigated in extended follow-up from the UK Multicentre Aneurysm Screening Study (MASS) randomized trial. Methods: A population-based sample ofmen aged 65–74 years were randomized individually to invitation to ultrasound screening (invited group) or to a control group not offered screening. Patients with an AAA (3·0 cm or larger) detected at screening underwent surveillance and were offered surgery after predefined criteria had been met. Cause-specific mortality data were analysed using Cox regression. Results: Some 67 770 men were enrolled in the study. Over 13 years, there were 224 AAA-related deaths in the invited group and 381 in the control group, a 42 (95 per cent confidence interval 31 to 51) per cent reduction. There was no evidence of effect on other causes of death, but there was an overall reduction in all-cause mortality of 3 (1 to 5) per cent. The degree of benefit seen in earlier years of follow-up was slightly diminished by the occurrence of AAA ruptures in those with an aorta originally screened normal. About half of these ruptures had a baseline aortic diameter in the range 2·5–2·9 cm. It was estimated that 216 men need to be invited to screening to save one death over the next 13 years. Conclusion: Screening resulted in a reduction in all-cause mortality, and the benefit in AAA-related mortality continued to accumulate throughout follow-up. Registration number: ISRCTN37381646 (http://www.controlled-trials.com)

    Preliminary survey of araceae of Sg. Rawog conservation Area, Segaliud Lokan forest researve (FMU 19B)

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    Considering that Sg. Rawog Conservation Area has been logged, it was thus with considerable surprise that the author encountered Rhaphidophora fluminea Ridl. along the river bank of Sg. Rawog since its first collection in 1897 from Bonggaya. Homalomena gempal Kartini, P.C Boyce and W.S Yeng was found growing on the sandstone of the river bank. Two interesting species of Schismatoglottis belong to the Trifiscata Complex were found not far from river bank of Trail 11. Alocasia princeps W. Bull and A. sarawakensis M. Hotta were found inside the forest at all trails except in the heath forest (Trail C49). Aroids climbers, namely Amydrium medium (Zoll. & Moritzi) Nicolson, Pothos sp., Rhaphidophora lativeginata M. Hotta, Scindapsus pictus Hassk. and Scindapsus sp. were found scattered in the inner area of the forest. In conclusion, the area around the river bank of Sg. Rawog represented aroid species found in pristine forest

    Temporal and spatial variability in speakers with Parkinson's Disease and Friedreich's Ataxia

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    Speech variability in groups of speakers with Parkinson's disease (PD) and with Friedreich's ataxia was compared with healthy controls. Speakers repeated the same phrase 20 times at one of two rates (fast or habitual). A non-linear analysis of variability was performed which used some of the principles behind the spatio-temporal index (STI). The STI usually employs variation in lip displacement over repetitions of the same utterance and a linear analysis of such signals is conducted to represent the combined variation in spatial and temporal control. When working with patients, audio measures (here we used speech energy) are preferred over kinematics ones as they are minimally disruptive to speech. Non-linear methods allow spatial variability to be estimated separately from temporal variability. The results are tentatively interpreted as showing that PD speakers were distinguished from healthy control speakers in spatial variability and ataxic speakers were distinguished from controls in temporal variability. These findings are consistent with the speech symptoms reported for these disorders. We conclude that the non-linear analysis using the speech energy measure is worth investigating further as it is potentially revealing of the differences underlying these two pathologies
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