620 research outputs found

    Representation and Governance in International Organizations

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    What does representation mean when applied to international organizations? While many scholars working on normative questions related to global governance often make use of the concept of representation, few have addressed specifics of applying the concept to the rules and practices by which IOs operate. This article examines representation as a fundamental, albeit often neglected, norm of governance which, if perceived to be deficient or unfair, can interfere with other components of governance, as well as with performance of an organization’s core tasks by undermining legitimacy. We argue that the concept of representation has been neglected in the ongoing debates about good governance and democratic deficits within IOs. We aim to correct this by drawing on insights from normative political theory considerations of representation. The article then applies theoretical aspects of representation to the governance of the International Monetary Fund. We determine that subjecting IOs to this kind of conceptual scrutiny highlights important deficiencies in representational practices in global politics. Finally, our conclusion argues scholars of global governance need to address the normative and empirical implications of conceptualizing representation at the supranational level

    Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study.

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    ObjectiveWe examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.Research design and methodsBetween 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.ResultsObserved apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.ConclusionsEasily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults

    On free evolution of self gravitating, spherically symmetric waves

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    We perform a numerical free evolution of a selfgravitating, spherically symmetric scalar field satisfying the wave equation. The evolution equations can be written in a very simple form and are symmetric hyperbolic in Eddington-Finkelstein coordinates. The simplicity of the system allow to display and deal with the typical gauge instability present in these coordinates. The numerical evolution is performed with a standard method of lines fourth order in space and time. The time algorithm is Runge-Kutta while the space discrete derivative is symmetric (non-dissipative). The constraints are preserved under evolution (within numerical errors) and we are able to reproduce several known results.Comment: 15 pages, 15 figure

    Embedded Fiber Optic Probes to Measure Detonation Velocities Using the PDV

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    Author Institution: Lawrence Livermore National LaboratoryAuthor Institution: Los Alamos National LaboratorySlides presented at the 5th Annual Photonic Doppler Velocimetry (PDV) Users Conference held at The Ohio State University, Columbus, Ohio, September 8-9, 2010

    Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD

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    B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-κB (NF-κB), BAFF-, and B cell receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing signaling from the cell surface to the nucleus. We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8 mice), which is a deubiquitinating enzyme that is integral to NF-κB signaling. This shorter CYLD protein lacks the TRAF2 and NEMO binding sites present in full-length CYLD. A dramatic expansion of mature B lymphocyte populations in all peripheral lymphoid organs occurs in this strain. The B lymphocytes themselves exhibit prolonged survival and manifest a variety of signaling disarrangements that do not occur in mice with a complete deletion of CYLD. Although both the full-length and the mutant CYLD are able to interact with Bcl-3, a predominant nuclear accumulation of Bcl-3 occurs in the CYLD mutant B cells. More dramatic, however, is the accumulation of the NF-κB proteins p100 and RelB in CYLDex7/8 B cells, which, presumably in combination with nuclear Bcl-3, results in increased levels of Bcl-2 expression. These findings suggest that CYLD can both positively and negatively regulate signal transduction and homeostasis of B cells in vivo, depending on the expression of CYLD splice variants

    The impact of the ‘hub and spoke’ model of care for lung cancer and equitable access to surgery

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    Objectives: To determine the influence of where a patient is first seen (either surgical or non-surgical centre) and patient features on having surgery for non-small cell lung cancer (NSCLC). Design: Cross-sectional study from individual patients, between 1January 2008 and 31March 2012. Setting: Linked National Lung Cancer Audit and Hospital Episode Statistics datasets. Participants: 95 818 English patients with a diagnosis of NSCLC, of whom 12 759 (13%) underwent surgical resection. Main outcome measure: Odds of having surgery based on the empirical catchment population of the 30 thoracic surgical centres in England and whether the patient is first seen in a surgical centre or a non-surgical centre. Results: Patients were more likely to be operated on if they were first seen at a surgical centre (OR 1.37; 95% CI 1.29 to 1.45). This was most marked for surgical centres with the largest catchment populations. In these surgical centres with large catchment populations, the resection rate for local patients was 18% and for patients first seen in a non-surgical centre within catchment was 12%. Conclusions: Surgical centres that serve the largest catchment populations have high resection rates for patients first seen in their own centre but, in contrast, low resection rates for patients first seen at the surrounding centres they serve. Our findings demonstrate the importance of going further than relating resection rates to hospital volume or surgeon number, and show that there is a pressing need to design lung cancer services which enable all patients, including those first seen at non-surgical centres, to have equal access to lung cancer surgery

    The clonal evolution of metastatic colorectal cancer

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    Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed both monoclonal and polyclonal seeding models. In four cases, metastasis-seeding clones were not identified in any primary region, consistent with a metastasis-seeding-metastasis model. PDXs underrepresented the subclonal heterogeneity of parental tumors. These suggest that single sample tumor sequencing and current PDX models may be insufficient to guide precision medicine
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