Assessing the clinical value of fast onset and sustained duration of action of long-acting bronchodilators for COPD

Date of Aceptance: 12/02/2015 Acknowledgments The authors were assisted in the preparation of the manuscript by Sarah Filcek, a professional medical writer at CircleScience (Tytherington, UK), part of KnowledgePoint360, an Ashfield Company. This assistance was funded by Novartis Pharmaceuticals. Copyright © 2015. Published by Elsevier Ltd.Peer reviewedPublisher PD

Electron-Neutrino Bremsstrahlung in Electro-Weak Theory

The electron-neutrino bremsstrahlung process has been considered in the framework of electro-weak theory. The scattering cross section has been calculated in the center of mass frame and approximated to extreme relativistic as well as non-relativistic case. The rate of energy-loss via this type of bremsstrahlung process has been obtained both in non-degenerate and degenerate region. The effect of this electron-neutrino bremsstrahlung process in different ranges of temperature and density characterizing the late stages of stellar evolution has been discussed. It is found from our study that this bremsstrahlung process is highly important in the non-degenerate region, although it might have some significant effect in the extreme relativistic degenerate region.Comment: 18 pages including 4 figures and 1 table; Published in J. Phys

Long-acting bronchodilators in COPD: where are we now and where are we going?

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Bremsstrahlung neutrinos from electron-electron scattering in a relativistic degenerate electron plasma

We present a calculation of neutrino pair bremsstrahlung due to electron-electron scattering in a relativistic degenerate plasma of electrons. Proper treatment of the in-medium photon propagator, i.e., inclusion of Debye screening of the longitudinal part and Landau damping of the transverse part, leads to a neutrino emissivity which is several orders of magnitude larger than when Debye screening is imposed for the tranverse part. Our results show that this in-medium process can compete with other sources of neutrino radiation and can, in some cases, even be the dominant neutrino emission mechanism. We also discuss the natural extension to quark-quark bremsstrahlung in gapped and ungapped quark matter.Comment: 15 pages, 7 figure

Supporting inheritance hierarchy changes in model-based regression test selection

Models can be used to ease and manage the development, evolution, and runtime adaptation of a software system. When models are adapted, the resulting models must be rigorously tested. Apart from adding new test cases, it is also important to perform regression testing to ensure that the evolution or adaptation did not break existing functionality. Since regression testing is performed with limited resources and under time constraints, regression test selection (RTS) techniques are needed to reduce the cost of regression testing. Applying model-level RTS for model-based evolution and adaptation is more convenient than using code-level RTS because the test selection process happens at the same level of abstraction as that of evolution and adaptation. In earlier work, we proposed a model-based RTS approach called MaRTS to be used with a fine-grained model-based adaptation framework that targets applications implemented in Java. MaRTS uses UML models consisting of class and activity diagrams. It classifies test cases as obsolete, reusable, or retestable based on changes made to UML class and activity diagrams of the system being adapted. However, MaRTS did not take into account the changes made to the inheritance hierarchy in the class diagram and the impact of these changes on the selection of test cases. This paper extends MaRTS to support such changes, and demonstrates that the extended approach performs as well as or better than code-based RTS approaches in safely selecting regression test cases. While MaRTS can generally be used during any model-driven development or model-based evolution activity, we have developed it in the context of runtime adaptation. We evaluated the extended MaRTS on a set of applications, and compared the results with code-based RTS approaches that also support changes to the inheritance hierarchy. The results showed that the extended MaRTS selected all the test cases relevant to the inheritance hierarchy changes, and that the fault detection ability of the selected test cases was never lower than that of the baseline test cases. The extended MaRTS achieved comparable results to a graph-walk code-based RTS approach (DejaVu), and showed a higher reduction in the number of selected test cases when compared with a static analysis code-based RTS approach (ChEOPSJ)

A modelling language for the effective design of Java annotations

This is the author's version of the work. It is posted here for your personal use. Not for redistribution. The definitive Version of Record was published in SAC '15 Proceedings of the 30th Annual ACM Symposium on Applied Computing, http://dx.doi.org/10.1145/2695664.2695717.This paper describes a new modelling language for the ef- fective design of Java annotations. Since their inclusion in the 5th edition of Java, annotations have grown from a use- ful tool for the addition of meta-data to play a central role in many popular software projects. Usually they are con- ceived as sets with dependency and integrity constraints within them; however, the native support provided by Java for expressing this design is very limited. To overcome its de ciencies and make explicit the rich conceptual model which lies behind a set of annotations, we propose a domain-speci c modelling language. The proposal has been implemented as an Eclipse plug- in, including an editor and an integrated code generator that synthesises annotation processors. The language has been tested using a real set of annotations from the Java Per- sistence API (JPA). It has proven to cover a greater scope with respect to other related work in di erent shared areas of application.This work was supported by the Spanish Ministry of Economy and Competitivity with project Go-Lite (TIN2011-24139) and the Community of Madrid with project SICOMORO (S2013/ICE-3006)

Current opinion: Pharmacological approaches in asthma and COPD

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Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review

Coronavirus disease 2019 (COVID-19) is highly infectious. It has been highlighted that if not expertly and individually managed with consideration of the vasocentric features, a COVID-19 patient with an acute respiratory distress syndrome (CARDS) may eventually develop multiorgan failure. Unfortunately, there is still no definite drug for CARDS that is capable of reducing either short-term or long-term mortality and no specific treatments for COVID-19 exist right now. In this narrative review, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science, and Google Scholar and ClinicalTrials.gov, we have examined the emerging evidence on the possible treatment of CARDS. Although numerous pharmacologic therapies to improve clinical outcomes in CARDS have been studied also in clinical trials, none have shown efficacy and there is great uncertainty about their effectiveness. There is still no recommendation for the therapeutic use of any specific agent to treat CARDS because no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale trials. However, there exist a number of drugs that may be useful at least in some patients. The real challenge now is to link the right patient to the right treatment

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient