156 research outputs found

    Welfare and Revenue Guarantees for Competitive Bundling Equilibrium

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    We study equilibria of markets with mm heterogeneous indivisible goods and nn consumers with combinatorial preferences. It is well known that a competitive equilibrium is not guaranteed to exist when valuations are not gross substitutes. Given the widespread use of bundling in real-life markets, we study its role as a stabilizing and coordinating device by considering the notion of \emph{competitive bundling equilibrium}: a competitive equilibrium over the market induced by partitioning the goods for sale into fixed bundles. Compared to other equilibrium concepts involving bundles, this notion has the advantage of simulatneous succinctness (O(m)O(m) prices) and market clearance. Our first set of results concern welfare guarantees. We show that in markets where consumers care only about the number of goods they receive (known as multi-unit or homogeneous markets), even in the presence of complementarities, there always exists a competitive bundling equilibrium that guarantees a logarithmic fraction of the optimal welfare, and this guarantee is tight. We also establish non-trivial welfare guarantees for general markets, two-consumer markets, and markets where the consumer valuations are additive up to a fixed budget (budget-additive). Our second set of results concern revenue guarantees. Motivated by the fact that the revenue extracted in a standard competitive equilibrium may be zero (even with simple unit-demand consumers), we show that for natural subclasses of gross substitutes valuations, there always exists a competitive bundling equilibrium that extracts a logarithmic fraction of the optimal welfare, and this guarantee is tight. The notion of competitive bundling equilibrium can thus be useful even in markets which possess a standard competitive equilibrium

    Glutamine Synthetase 1 Increases Autophagy Lysosomal Degradation of Mutant Huntingtin Aggregates in Neurons, Ameliorating Motility in a Drosophila Model for Huntington's Disease

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    Glutamine Synthetase 1 (GS1) is a key enzyme that catalyzes the ATP-dependent synthesis of l-glutamine from l-glutamate and is also member of the Glutamate Glutamine Cycle, a complex physiological process between glia and neurons that controls glutamate homeostasis and is often found compromised in neurodegenerative diseases including Huntington's disease (HD). Here we report that the expression of GS1 in neurons ameliorates the motility defects induced by the expression of the mutant Htt, using a Drosophila model for HD. This phenotype is associated with the ability of GS1 to favor the autophagy that we associate with the presence of reduced Htt toxic protein aggregates in neurons expressing mutant Htt. Expression of GS1 prevents the TOR activation and phosphorylation of S6K, a mechanism that we associate with the reduced levels of essential amino acids, particularly of arginine and asparagine important for TOR activation. This study reveals a novel function for GS1 to ameliorate neuronal survival by changing amino acids' levels that induce a "starvation-like" condition responsible to induce autophagy. The identification of novel targets that inhibit TOR in neurons is of particular interest for the beneficial role that autophagy has in preserving physiological neuronal health and in the mechanisms that eliminate the formation of toxic aggregates in proteinopathies

    Impact of 123 I-MIBG scintigraphy on clinical decision making in pheochromocytoma and paraganglioma

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    CONTEXT Cross sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is regarded as a first-choice modality for tumor localization in patients with pheochromocytoma and paraganglioma (PPGL). 123I-labeled metaiodobenzylguanidine (123I-MIBG) is widely used for functional imaging but the added diagnostic value is controversial. OBJECTIVE To establish the virtual impact of adding 123I-MIBG scintigraphy to CT or MRI on diagnosis and treatment of PPGL. DESIGN International multicenter retrospective study. INTERVENTION None. PATIENTS 236 unilateral adrenal, 18 bilateral adrenal, 48 unifocal extra-adrenal, 12 multifocal and 26 metastatic PPGL. MAIN OUTCOME MEASURES Patients underwent both anatomical imaging (CT and/or MRI) and 123I-MIBG scintigraphy. Local imaging reports were analyzed centrally by two independent observers who were blinded to the diagnosis. Imaging-based diagnoses determined by CT/MRI only, 123I-MIBG only, and CT/MRI combined with 123I-MIBG scintigraphy were compared with the correct diagnoses. RESULTS The rates of correct imaging-based diagnoses determined by CT/MRI only versus CT/MRI plus 123I-MIBG scintigraphy were similar: 89.4 versus 88.8%, respectively, (P=0.50). Adding 123I-MIBG scintigraphy to CT/MRI resulted in a correct change in the imaging-based diagnosis and ensuing virtual treatment in four cases (1.2%: two metastatic instead of non-metastatic, one multifocal instead of single, one unilateral instead of bilateral adrenal) at the cost of an incorrect change in seven cases (2.1%: four metastatic instead of non-metastatic, two multifocal instead of unifocal and one bilateral instead of unilateral adrenal). CONCLUSIONS For the initial localization of PPGL, the addition of 123I-MIBG scintigraphy to CT/MRI rarely improves the diagnostic accuracy at the cost of incorrect interpretation in others, even when 123I-MIBG scintigraphy is restricted to patients who are at risk for metastatic disease. In this setting, the impact of 123I-MIBG scintigraphy on clinical decision-making appears very limited

    Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy

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    Few data are available regarding vertebral fracture risk in patients treated with corticosteroids including patients with interstitial lung disease (ILD). The aim of the present study was to identify risk factors for symptomatic vertebral fracture analyzed in patients with newly diagnosed autoimmune diseases. This was an observational cohort study conducted in the National Hospital Organization-EBM study group from 2006 to 2008. The study subjects were autoimmune disease patients who were newly treated with glucocorticoids (GCs). The primary endpoint was the first occurrence of vertebral fracture diagnosed by x-rays. Cox proportional-hazards regression was used to determine independent risk factors for vertebral fracture with covariates including sex, age, comorbidity, laboratory data, use of immunosuppressants, and dose of GCs. Survival was analyzed according to the Kaplan-Meier method and assessed by the log-rank test. Among 604 patients of mean age 59.5 years and mean GC dose 50.4mg/d (first 1 months), 19 patient (3.1%) had at least 1 symptomatic vertebral fracture during 1.9 years of follow-up period. Cox regression model demonstrated that the relative risk for symptomatic vertebral fracture was independently higher in patient with ILD (hazard ratio [HR]=2.86, 95% confidence interval [CI]=1.10-7.42, P=0.031) and in every 10-year increment of the age of disease onset (HR=1.57, 95% CI=1.09-2.26, P=0.015). Kaplan-Meier analyses demonstrated that the incidence of vertebral fractures in patients with ILD was significantly higher in comparison with those without ILD. Our results indicate a higher risk of vertebral facture in patients with ILD and elderly patients during the initial GC treatment against autoimmune diseases. There is a need for further, even longer-term, prospective studies subjected patients with autoimmune disease, including ILD, under GC treatment

    Observation of Top Quark Production in Proton-Nucleus Collisions

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    Precautionary Effect and Variations of the Value of Information

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    SOSORT consensus paper: school screening for scoliosis. Where are we today?

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    This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure
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