30,127 research outputs found

    Symbolic computation for evaluation of measurement uncertainty

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    In recent years, with the rapid development of symbolic computation, the integration of symbolic and numeric methods is increasingly applied in various applications. This paper proposed the use of symbolic computation for the evaluation of measurement uncertainty. The general method and procedure are discussed, and its great potential and powerful features for measurement uncertainty evaluation has been demonstrated through examples

    Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement.

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    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive metabolic disorder caused by a deficiency of thymidine phosphorylase (TP, EC2.4.2.4) due to mutations in the nuclear gene TYMP. TP deficiency leads to plasma and tissue accumulations of thymidine and deoxyuridine which generate imbalances within the mitochondrial nucleotide pools, ultimately leading to mitochondrial dysfunction.1 MNGIE is characterized clinically by leukoencephalopathy, external ophthalmoplegia, peripheral polyneuropathy, cachexia, and enteric neuromyopathy manifesting as gastrointestinal dysmotility. The condition is relentlessly progressive, with patients usually dying from a combination of nutritional and neuromuscular failure at an average age of 37 years.2 Allogeneic hematopoietic stem cell transplantation (AHSCT) offers a permanent cure. Clinical and biochemical improvements following AHSCT have been reported but it carries a high mortality risk and is limited by matched donor availability.3 A consensus proposal for standardizing AHSCT recommends treatment of patients without irreversible end-stage disease and with an optimally matched donor; a majority of patients are ineligible and thus there is a critical requirement for an alternative treatment

    Renormalization Constants of Quark Operators for the Non-Perturbatively Improved Wilson Action

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    We present the results of an extensive lattice calculation of the renormalization constants of bilinear and four-quark operators for the non-perturbatively O(a)-improved Wilson action. The results are obtained in the quenched approximation at four values of the lattice coupling by using the non-perturbative RI/MOM renormalization method. Several sources of systematic uncertainties, including discretization errors and final volume effects, are examined. The contribution of the Goldstone pole, which in some cases may affect the extrapolation of the renormalization constants to the chiral limit, is non-perturbatively subtracted. The scale independent renormalization constants of bilinear quark operators have been also computed by using the lattice chiral Ward identities approach and compared with those obtained with the RI-MOM method. For those renormalization constants the non-perturbative estimates of which have been already presented in the literature we find an agreement which is typically at the level of 1%.Comment: 36 pages, 13 figures. Minor changes in the text and in one figure. Accepted for publication on JHE

    Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

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    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

    Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.

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    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.This work was supported by the Vanderbilt Meharry Center for AIDS Research (NIH grant number P30 AI54999); the NIH Fogarty International Center, Office of the Director, National Institutes of Health, National Heart, Blood, and Lung Institute, and National Institute of Mental Health, through the Vanderbilt-Emory-Cornell-Duke Consortium for Global Health Fellows (grant number R25 TW009337); the National Center for Advancing Translational Sciences (CTSA award number UL1TR000445) and the European and Developing Countries Clinical Trials Partnership (grant IP.2009.33011.004)

    Firm life cycle and advisory directors

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    This article investigates whether the presence of advisory directors and monitoring directors varies across firm life cycle stages. We follow a parsimonious life cycle proxy based on the predicted behaviour of operating, investing and financing cash flows across the different life cycle stages that result from firm performance and the allocation of resources. Using an Australian sample, this study shows that compared to mature-stage firms, firms in the introduction, shake-out and decline stages have more advisory directors. With respect to the demand for monitoring directors, we find that compared to mature-stage firms, firms in the introduction, shake-out and decline stages have fewer monitoring directors on the board. We contribute to the literature on boards of directors by documenting that firms choose an optimal board structure based on their economic characteristics

    Healthcare professionals’ perceptions of alcoholintoxicated trauma patients: Implications for healthcare delivery at South Rand Hospital Emergency Department

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    Objectives: The objectives of this study were to explore healthcare professionals’ (HCPs) perceptions about patients who had been assaulted, who consult under the influence of alcohol, and to make them aware of their attitudes towards these patients, with a view to improving their care.Design: An explorative, descriptive study with 15 HCPs purposively  selected across professional categories, qualifications, work experience, gender and age. These HCPs participated in four focus group interviews on intoxicated patients who had been assaulted. The interviews were audio-taped and supplemented with field and observational notes. Themes were identified using the cut-and-paste method and grouped into categories. Findings were subjected to mental triangulation, peer review and member check, and were compared with those in the literature.Settings and subjects: HCPs who treat assault patients within the emergency department (ED) of South Rand Hospital, Rosettenville, comprised the study population. They expressed their perceptions and inner feeling about patients under the influence of alcohol who had been assaulted. Interviews were carried out in the boardroom of the hospital.Outcome measures: HCPs’ awareness of their attitudes towards assaulted patients under the influence of alcohol Results: Frustration, anger, a desire to punish intoxicated patients and concern about wastage of hospital resources were some of the stressors experienced by HCPs. Exposure to health hazards and a poor security system were concerns that arose following intimidation, aggression and verbal abuse from alcohol-intoxicated patients who had been assaulted.Conclusion: HCPs experience negative emotions and develop negative attitudes in response to alcohol-intoxicated patients who have been assaulted

    Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells

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    BACKGROUND: Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. METHODS: Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone (10(−8)–10(−6) M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×10(−6) M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. RESULTS: Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. CONCLUSIONS: Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways

    DeWitt-Virasoro construction

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    We study a particular approach for analyzing worldsheet conformal invariance for bosonic string propagating in a curved background using hamiltonian formalism. We work in the Schrodinger picture of a single particle description of the problem where the particle moves in an infinite-dimensional space. Background independence is maintained in this approach by adopting DeWitt's (Phys.Rev.85:653-661,1952) coordinate independent formulation of quantum mechanics. This enables us to construct certain background independent notion of Virasoro generators, called DeWitt-Virasoro (DWV) generators, and invariant matrix elements of an arbitrary operator constructed out of them in spin-zero representation. We show that the DWV algebra is given by the Witt algebra with additional anomalous terms that vanish for Ricci-flat backgrounds. The actual quantum Virasoro generators should be obtained by first introducing the vacuum state and then normal ordering the DWV generators with respect to that. We demonstrate the procedure in the simple cases of flat and pp-wave backgrounds. This is a shorter version of arXiv:0912.3987 [hep-th] with many technical derivations omitted.Comment: 18 pages, shorter version of arXiv:0912.3987 [hep-th] accepted for publication in Pramana - Journal of Physic
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