1,415 research outputs found

    Anaesthetic management of endoscopic resection of juvenile nasopharyngeal angiofibroma: our experience and a review of the literature

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    Background: Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign, vascular tumour in adolescent males with potential life-threatening complications. Advances in endoscopic surgery, invasive monitoring and hypotensive anaesthesia have made JNAs amenable to endoscopic surgical resection. We present the anaesthetic management of endoscopic resection of 14 JNAs, together with a review.Method: The medical records of patients who underwent endoscopic excision of JNAs within the last seven years were reviewed retrospectively. Information was collected and analysed with regard to demographics, preoperative evaluation, intraoperative management, complications and postoperative course. Fourteen patients were included in the study. If the surgery needed to be converted to open surgery, the patients were excluded from the study.Results: The age of the patients ranged from 10-18 years. Two patients had preoperative embolisation of the feeding vessel. Standard anaesthesia induction technique, together with invasive monitoring, was used. Controlled hypotension (mean arterial pressure of 60 ± 5 mmHg) was achieved with the help of inhalational anaesthetics, vasodilators and beta blockers. Mean duration of surgery was 197.14 ± 77 minutes, and median blood loss was 500 ml (100- 4 300 ml). Seven patients were extubated in the operating room. The other seven patients remained intubated for 24 hours owing to extensive surgery with a risk of postoperative bleeding, and were monitored either in the postoperative care unit (five patients) or the intensive care unit (two patients). There was no significant morbidity or mortality in any of the patients.Conclusion: JNAs remain a challenge for anaesthesiologists because of excessive intraoperative bleeding. Anaesthetists should be aware of recent techniques to reduce tumour vascularity, such as embolisation of the feeding vessel and controlled hypotension. Invasive monitoring, together with multimodal blood conservation strategies, decreases blood loss and provides a clear field of vision for endoscopic surgery.Keywords: anaesthetic management, JNA, endoscopic resection, controlled hypotensio

    E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia

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    Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1). Here, we show that S.aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S.aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S.aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme. © 2014 The Authors

    Global Symmetries and D-Terms in Supersymmetric Field Theories

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    We study the role of D-terms in supersymmetry (SUSY) breaking. By carefully analyzing the SUSY multiplets containing various conserved currents in theories with global symmetries, we obtain a number of constraints on the renormalization group flow in supersymmetric field theories. Under broad assumptions, these results imply that there are no SUSY-breaking vacua, not even metastable ones, with parametrically large D-terms. This explains the absence of such D-terms in models of dynamical SUSY-breaking. There is, however, a rich class of calculable models which generate comparable D-terms and F-terms through a variety of non-perturbative effects; these D-terms can be non-abelian. We give several explicit examples of such models, one of which is a new calculable limit of the 3-2 model.Comment: 34 pages, 2 figures; reference added, minor change

    Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

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    Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man

    Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey

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    Abstract Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a postgraduate education. Conclusions This study provides insight on the ability of a fortification policy to benefit the groups at highest risk of poor folate intakes in a population. However, bread consumption among the target group of childbearing women appears to have declined since the data used in previous dietary modeling were collected. Thus, it seems prudent to re-model dietary folic acid intakes based on more recent national survey data prior to the implementation of a mandatory folic acid fortification policy.</p

    The Effect of Thermal Reduction on the Photoluminescence and Electronic Structures of Graphene Oxides

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    [[abstract]]Electronic structures of graphene oxide (GO) and hydro-thermally reduced graphene oxides (rGOs)processed at low temperatures (120–1806C) were studied using X-ray absorption near-edge structure XANES), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS). C K-edge XANES spectra of rGOs reveal that thermal reduction restores C 5 C sp2 bonds and removes some of the oxygen and hydroxyl groups of GO, which initiates the evolution of carbonaceous species. The combination of C K-edge XANES and Ka XES spectra shows that the overlapping p and p* orbitals in rGOs and GO are similar to that of highly ordered pyrolytic graphite (HOPG), which has no band-gap. C Ka RIXS spectra provide evidence that thermal reduction changes the density of states (DOSs) that is generated in the p-region and/or in the gap between the p and p* levels of the GO and rGOs. Two-dimensional C Ka RIXS mapping of the heavy reduction of rGOs further confirms that the residual oxygen and/or oxygen-containing functional groups modify the p and s features, which are dispersed by the photon excitation energy. The dispersion behavior near the K point is approximately linear and differs from the parabolic-like dispersion observed in HOPG.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]GB

    Efficiency of European public higher education institutions: a two-stage multicountry approach

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    The purpose of this study is to examine efficiency and its determinants in a set of higher education institutions (HEIs) from several European countries by means of non-parametric frontier techniques. Our analysis is based on a sample of 259 public HEIs from 7 European countries across the time period of 2001–2005. We conduct a two-stage DEA analysis (Simar and Wilson in J Economet 136:31–64, 2007), first evaluating DEA scores and then regressing them on potential covariates with the use of a bootstrapped truncated regression. Results indicate a considerable variability of efficiency scores within and between countries. Unit size (economies of scale), number and composition of faculties, sources of funding and gender staff composition are found to be among the crucial determinants of these units’ performance. Specifically, we found evidence that a higher share of funds from external sources and a higher number of women among academic staff improve the efficiency of the institution

    CSMET: Comparative Genomic Motif Detection via Multi-Resolution Phylogenetic Shadowing

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    Functional turnover of transcription factor binding sites (TFBSs), such as whole-motif loss or gain, are common events during genome evolution. Conventional probabilistic phylogenetic shadowing methods model the evolution of genomes only at nucleotide level, and lack the ability to capture the evolutionary dynamics of functional turnover of aligned sequence entities. As a result, comparative genomic search of non-conserved motifs across evolutionarily related taxa remains a difficult challenge, especially in higher eukaryotes, where the cis-regulatory regions containing motifs can be long and divergent; existing methods rely heavily on specialized pattern-driven heuristic search or sampling algorithms, which can be difficult to generalize and hard to interpret based on phylogenetic principles. We propose a new method: Conditional Shadowing via Multi-resolution Evolutionary Trees, or CSMET, which uses a context-dependent probabilistic graphical model that allows aligned sites from different taxa in a multiple alignment to be modeled by either a background or an appropriate motif phylogeny conditioning on the functional specifications of each taxon. The functional specifications themselves are the output of a phylogeny which models the evolution not of individual nucleotides, but of the overall functionality (e.g., functional retention or loss) of the aligned sequence segments over lineages. Combining this method with a hidden Markov model that autocorrelates evolutionary rates on successive sites in the genome, CSMET offers a principled way to take into consideration lineage-specific evolution of TFBSs during motif detection, and a readily computable analytical form of the posterior distribution of motifs under TFBS turnover. On both simulated and real Drosophila cis-regulatory modules, CSMET outperforms other state-of-the-art comparative genomic motif finders

    Top scoring pairs for feature selection in machine learning and applications to cancer outcome prediction

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    &lt;b&gt;Background&lt;/b&gt; The widely used k top scoring pair (k-TSP) algorithm is a simple yet powerful parameter-free classifier. It owes its success in many cancer microarray datasets to an effective feature selection algorithm that is based on relative expression ordering of gene pairs. However, its general robustness does not extend to some difficult datasets, such as those involving cancer outcome prediction, which may be due to the relatively simple voting scheme used by the classifier. We believe that the performance can be enhanced by separating its effective feature selection component and combining it with a powerful classifier such as the support vector machine (SVM). More generally the top scoring pairs generated by the k-TSP ranking algorithm can be used as a dimensionally reduced subspace for other machine learning classifiers.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; We developed an approach integrating the k-TSP ranking algorithm (TSP) with other machine learning methods, allowing combination of the computationally efficient, multivariate feature ranking of k-TSP with multivariate classifiers such as SVM. We evaluated this hybrid scheme (k-TSP+SVM) in a range of simulated datasets with known data structures. As compared with other feature selection methods, such as a univariate method similar to Fisher's discriminant criterion (Fisher), or a recursive feature elimination embedded in SVM (RFE), TSP is increasingly more effective than the other two methods as the informative genes become progressively more correlated, which is demonstrated both in terms of the classification performance and the ability to recover true informative genes. We also applied this hybrid scheme to four cancer prognosis datasets, in which k-TSP+SVM outperforms k-TSP classifier in all datasets, and achieves either comparable or superior performance to that using SVM alone. In concurrence with what is observed in simulation, TSP appears to be a better feature selector than Fisher and RFE in some of the cancer datasets.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; The k-TSP ranking algorithm can be used as a computationally efficient, multivariate filter method for feature selection in machine learning. SVM in combination with k-TSP ranking algorithm outperforms k-TSP and SVM alone in simulated datasets and in some cancer prognosis datasets. Simulation studies suggest that as a feature selector, it is better tuned to certain data characteristics, i.e. correlations among informative genes, which is potentially interesting as an alternative feature ranking method in pathway analysis
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