1,513 research outputs found

    Interpreting the ERM Crisis: Country-Specific and Systemic Issues

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    Most interpretations of the Exchange Rate Mechanism crisis in 1992-93 ignore the key role played by structural policy spillovers among European countries, and overlook the effects of coordination (or lack thereof) of monetary and exchange rate policies among the countries making up the periphery of the system. This paper provides a simple analytical framework, able to encompass the recent literature on currency crises, while developing it by bringing out the decisive role of the strategic interactions among national policy makers in a multi-country monetary and exchange rate game. In contrast to an approach that focuses exclusively on country-specific issues, a systemic view is ultimately able to unravel more coherently, and more convincingly, the "puzzles" of the ERM crisis.

    Modeling the Halpha line emission around classical T Tauri stars using magnetospheric accretion and disk wind models

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    Spectral observations of classical T Tauri stars show a wide range of line profiles, many of which reveal signs of matter inflow and outflow. Halpha is the most commonly observed line profile due to its intensity, and it is highly dependent on the characteristics of the surrounding environment of these stars. Our aim is to analyze how the Halpha line profile is affected by the various parameters of our model which contains both the magnetospheric and disk wind contributions to the Halpha flux. We used a dipolar axisymmetric stellar magnetic field to model the stellar magnetosphere and a modified Blandford & Payne model was used in our disk wind region. A three-level atom with continuum was used to calculate the required Hydrogen level populations. We use the Sobolev approximation and a ray-by-ray method to calculate the integrated line profile. Through an extensive study of the model parameter space, we have investigated the contribution of many of the model parameters on the calculated line profiles. Our results show that the Halpha line is strongly dependent on the densities and temperatures inside the magnetosphere and the disk wind region. The bulk of the flux comes, most of the time, from the magnetospheric component for standard classical T Tauri stars parameters, but the disk wind contribution becomes more important as the mass accretion rate, the temperatures and densities inside the disk wind increase. We have also found that most of the disk wind contribution to the Halpha line is emitted at the innermost region of the disk wind. Models that take into consideration both inflow and outflow of matter are a necessity to fully understand and describe classical T Tauri stars.Comment: 15 pages, 9 figures, accepted for publication in Astronomy & Astrophysics. Revised version with English correction

    Effective connectivity reveals strategy differences in an expert calculator

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    Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

    The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

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    CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

    Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries

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    IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS:The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES:Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS

    Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

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    We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

    Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study

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    Abstract RATIONALE: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. OBJECTIVES: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. METHODS: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. MEASUREMENTS AND MAIN RESULTS: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159-1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. CONCLUSIONS: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073)

    Crystal structures and binding dynamics of Odorant-Binding Protein 3 from two aphid species Megoura viciae and Nasonovia ribisnigri

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    Aphids use chemical cues to locate hosts and find mates. The vetch aphid Megoura viciae feeds exclusively on the Fabaceae, whereas the currant-lettuce aphid Nasonovia ribisnigri alternates hosts between the Grossulariaceae and Asteraceae. Both species use alarm pheromones to warn of dangers. For N. ribisnigri this pheromone is a single component (E)-β-farnesene but M. viciae uses a mixture of (E)-β-farnesene, (-)-α- pinene, β-pinene, and limonene. Odorant-binding proteins (OBP) are believed to capture and transport such semiochemicals to their receptors. Here, we report the first aphid OBP crystal structures and examine their molecular interactions with the alarm pheromone components. Our study reveals some unique structural features: 1) the lack of internal ligand binding site; 2) a striking groove in the surface of the proteins as a putative binding site; 3) the N-terminus rather than the C-terminus occupies the site closing off the conventional OBP pocket. The results from fluorescent binding assays, molecular docking and dynamics demonstrate that OBP3 from M. viciae can bind to all four alarm pheromone components and the differential ligand binding between these very similar OBP3s from the two aphid species is determined mainly by the direct π-π interactions between ligands and the aromatic residues of OBP3s in the binding pocket

    Average flow constraints and stabilizability in uncertain production-distribution systems

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    We consider a multi-inventory system with controlled flows and uncertain demands (disturbances) bounded within assigned compact sets. The system is modelled as a first-order one integrating the discrepancy between controlled flows and demands at different sites/nodes. Thus, the buffer levels at the nodes represent the system state. Given a long-term average demand, we are interested in a control strategy that satisfies just one of two requirements: (i) meeting any possible demand at each time (worst case stability) or (ii) achieving a predefined flow in the average (average flow constraints). Necessary and sufficient conditions for the achievement of both goals have been proposed by the authors. In this paper, we face the case in which these conditions are not satisfied. We show that, if we ignore the requirement on worst case stability, we can find a control strategy driving the expected value of the state to zero. On the contrary, if we ignore the average flow constraints, we can find a control strategy that satisfies worst case stability while optimizing any linear cost on the average control. In the latter case, we provide a tight bound for the cost

    Rice Responses to Water Limiting Conditions: Improving Stress Management by Exploiting Genetics and Physiological Processes

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    Water-limiting conditions can severely affect rice yield. Therefore, increasing plant tolerance to water stress is a priority for many rice breeding programs. However, improving rice tolerance to this abiotic stress comes with several complications related to the seeding practices, the adopted water management system and the growth stage where water stress occurs. For this reason, it is challenging to outline single ideotypes showing traits suitable for overcoming drought at different times during the life cycle of rice in diverse cropping ecosystems. The current knowledge of genomics and biochemicals can contribute to drawing rice ideotypes flexible towards diverse water availability conditions. Traits identified in accessions of the wild ancestor of cultivated rice, as well as other wild rice species, in Oryza glaberrima and weedy rice were demonstrated to confer enhanced tolerance to water stress, while screenings of cultivated rice germplasms identified several genes/loci improving water stress resistance. New frontiers are represented by the dissection of the epigenetic control of stress tolerance and the implementation of the contribution of favorable microbiota. Innovative breeding technologies, whose feasibility is related to advancements in genomic analyses, are contributing to enhancing the knowledge-based development of water stress-tolerant rice varieties
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