2,140 research outputs found

    Trigger, an active release experiment that stimulated auroral particle precipitation and wave emissions

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    The experiment design, including a description of the diagnostic and chemical release payload, and the general results are given for an auroral process simulation experiment. A drastic increase of the field aligned charged particle flux was observed over the approximate energy range 10 eV to more than 300 keV, starting about 150 ms after the release and lasting about one second. The is evidence of a second particle burst, starting one second after the release and lasting for tens of seconds, and evidence for a periodic train of particle bursts occurring with a 7.7 second period from 40 to 130 seconds after the release. A transient electric field pulse of 200 mv/m appeared just before the particle flux increase started. Electrostatic wave emissions around 2 kHz, as well as a delayed perturbation of the E-region below the plasma cloud were also observed. Some of the particle observations are interpreted in terms of field aligned electrostatic acceleration a few hundred kilometers above the injected plasma cloud. It is suggested that the acceleration electric field was created by an instability driven by field aligned currents originating in the plasma cloud

    Development and validation of a method to estimate COPD severity in multiple datasets: a retrospective study

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    Introduction Outcomes in chronic obstructive pulmonary disease (COPD) such as symptoms, hospitalisations and mortality rise with increasing disease severity. However, the heterogeneity of electronic medical records presents a significant challenge in measuring severity across geographies. We aimed to develop and validate a method to approximate COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 classification scheme, which categorises patients based on forced expiratory volume in 1 s, hospitalisations and the modified Medical Research Council dyspnoea scale or COPD Assessment Test. Methods This analysis was part of a comprehensive retrospective study, including patients sourced from the IQVIA Medical Research Data [IMRD; incorporating data from The Health Improvement Network (THIN), a Cegedim database] and the Clinical Practice Research Datalink (CPRD) in the UK, the Disease Analyzer in Germany and the Longitudinal Patient Data in Italy, France and Australia. Patients in the CPRD with the complete set of information required to calculate GOLD 2011 groups were used to develop the method. Ordinal logistic models at COPD diagnosis and at index (first episode of triple therapy) were then used to validate the method to estimate COPD severity, and this was applied to the full study population to estimate GOLD 2011 categories. Results Overall, 4579 and 12,539 patients were included in the model at COPD diagnosis and at index, respectively. Models correctly classified 74.4% and 75.9% of patients into severe and non-severe categories at COPD diagnosis and at index, respectively. Age, gender, time between diagnosis and start of triple therapy, healthcare resource use, comorbid conditions and prescriptions were included as covariates. Conclusion This study developed and validated a method to approximate disease severity based on GOLD 2011 categories that can potentially be used in patients without all the key parameters needed for this calculation

    Pure-radiation gravitational fields with a simple twist and a Killing vector

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    Pure-radiation solutions are found, exploiting the analogy with the Euler- Darboux equation for aligned colliding plane waves and the Euler-Tricomi equation in hydrodynamics of two-dimensional flow. They do not depend on one of the spacelike coordinates and comprise the Hauser solution as a special subcase.Comment: revtex, 9 page

    Prescribing pathways to triple therapy: a multi-country, retrospective observational study of adult patients with chronic obstructive pulmonary disease

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    Introduction Maintenance treatment strategies in COPD recommend inhaled corticosteroid (ICS) + long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist (LABA) triple therapy after initial dual therapy. Little is known about how treatment pathways to triple therapy vary across countries in clinical practice. Methods This multi-country, retrospective cohort study (conducted 1 January 2005–1 May 2016) included patients with a COPD diagnosis, and (UK only) evidence of smoking history, or (France, Italy, Germany, and Australia) an indicator confirming COPD diagnosis, a first instance of triple therapy recorded during the study period and ≥ 12 months of data prior to this date. Treatment pathways to triple therapy were analyzed in patients whose first instance of triple therapy was on or after the initial COPD diagnosis. The proportion of patients who initiated triple therapy prior to initial COPD diagnosis was also estimated. Meta-analyses of the main results were performed. Results In 130,729 patients across all countries, mean age (standard deviation) ranged from 63.4 (10.4) years (Germany) to 69.8 (9.9) years (Italy), and median time (interquartile range) from initial COPD diagnosis to first prescription of triple therapy ranged from 16.9 (5.7–36.2) months (Australia) to 42.5 (13.9–87.4) months (UK). ICS + LABA was the most common treatment pathway prior to triple therapy in the UK, Germany, and Italy (27.3%–31.6%); no previous maintenance therapy prior to triple therapy was the most common pathway in France and Australia (32.5% and 37.9%, respectively). Meta-analyses provided a pooled estimate of 20.4% (95% confidence interval: 13.8%–29.1%) for the proportion of patients initiating triple therapy at or before initial COPD diagnosis. Conclusions In this retrospective cohort study, treatment pathways to triple therapy were diverse within and between countries. The differing impact of treatments may affect quality of life and disease control in patients with COPD. Further analyses should investigate factors influencing pathways to triple therapy

    A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers

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    Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population

    Paradoxical roles of antioxidant enzymes:Basic mechanisms and health implications

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    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate “paradoxical” outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of “antioxidant” nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that “paradoxical” roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways

    Mapping of periodically poled crystals via spontaneous parametric down-conversion

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    A new method for characterization of periodically poled crystals is developed based on spontaneous parametric down-conversion. The method is demonstrated on crystals of Y:LiNbO3, Mg:Y:LiNbO3 with non-uniform periodically poled structures, obtained directly under Czochralski growth procedure and designed for application of OPO in the mid infrared range. Infrared dispersion of refractive index, effective working periods and wavelengths of OPO were determined by special treatment of frequency-angular spectra of spontaneous parametric down-conversion in the visible range. Two-dimensional mapping via spontaneous parametric down-conversion is proposed for characterizing spatial distribution of bulk quasi-phase matching efficiency across the input window of a periodically poled sample.Comment: 19 pages, 6 figure

    Realising consilience: How better communication between archaeologists, historians and natural scientists can transform the study of past climate change in the Mediterranean

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    This paper reviews the methodological and practical issues relevant to the ways in which natural scientists, historians and archaeologists may collaborate in the study of past climatic changes in the Mediterranean basin. We begin by discussing the methodologies of these three disciplines in the context of the consilience debate, that is, attempts to unify different research methodologies that address similar problems. We demonstrate that there are a number of similarities in the fundamental methodology between history, archaeology, and the natural sciences that deal with the past ("palaeoenvironmental sciences"), due to their common interest in studying societal and environmental phenomena that no longer exist. The three research traditions, for instance, employ specific narrative structures as a means of communicating research results. We thus present and compare the narratives characteristic of each discipline; in order to engage in fruitful interdisciplinary exchange, we must first understand how each deals with the societal impacts of climatic change. In the second part of the paper, we focus our discussion on the four major practical issues that hinder communication between the three disciplines. These include terminological misunderstandings, problems relevant to project design, divergences in publication cultures, and differing views on the impact of research. Among other recommendations, we suggest that scholars from the three disciplines should aim to create a joint publication culture, which should also appeal to a wider public, both inside and outside of academia
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