Mechanistic insights in the antibiotic tolerance of Pseudomonas aeruginosa biofilms

Pseudomonas aeruginosa is a pathogen of high clinical relevance, responsible for many deadly infections and showing high resistance to current antimicrobial agents. In the human body, P. aeruginosa grows as a microbial community embedded in a matrix of extracellular polymeric substances, called biofilm, which promotes the survival of bacteria upon antibiotic exposure and environmental stresses. The goal of this thesis is to identify genetic determinants responsible for P. aeruginosa biofilm tolerance to antibiotics that may serve to identify new targets for drug development and innovative therapeutic strategies. To do so, we selected biofilm relevant genes based on previous transcriptomic studies and characterized their involvement in biofilm tolerance to antibiotics using the public P. aeruginosa MPAO1 transposon insertion library. We showed that the inactivation of the Pf phage gene, PA0720, or the flagellin gene, fliC, led to the complete removal of biofilms with 4-fold lower gentamicin concentration. We demonstrated that the downregulation of certain genes (e.g., coxC, pprB, PA3785) correlates with enhanced gentamicin tolerance in P. aeruginosa. Finally, we highlighted that the repression of the flagellum gene, flgE, in cystic fibrosis infections is an active mechanism of adaptation employed by P. aeruginosa to alter its biofilm structure and promote antibiotic tolerance. In conclusion, this thesis gives insight in what should be considered when investigating P. aeruginosa clinical strains and reveals new targets for drug development and new markers to predict antibiotic resistance

Development and implementation of a virtual laboratory for fundamentals on power systems

Abstract In almost any engineering department, a laboratory is an integral part of the educational process. The laboratory is a key component in the field of engineering in general, and electrical power engineering in particular. The virtual laboratory (VL) is a simulated experiment run by students on a computer station program; it can transform the conventional laboratory experiments into an interactive virtual environment, allowing simple and complex phenomena to be investigated by students just by changing the parameters and conditions of the experiments. This paper describes the development and the implementation of a VL, named VLABPOWER, for fundamentals on power systems. Mainly, electrical power engineering students will using to increase their understanding and to bridge the gap that exists between the theoretical part in the class and the practical at the traditional (real) laboratory and to better prepare before going to the traditional laboratory. The purpose of this work is to develop and implement a VL in order to enable students to have a better understanding of the experiments done in the traditional laboratory and to familiarize themselves with the different components used for those experiments. It presents a virtual interactive experiment environment that simulates the physical conditions on the transmission line. Moreover, it discusses and explains different types of short circuit faults such as symmetrical and unsymmetrical faults, modeling of different type of lines, and load condition analysis

Jules Romains' Vision of a United Europe in Interwar France: Legacy and Ambiguities

The interwar period in Europe was characterised by a multi-faceted movement in favour of European integration. After the slaughter of the First World War, many intellectuals, writers, industrialists and politicians brought the idea of European unity to the fore and engaged in various actions, from setting up organisations to lobbying governments, to promote the unification of Europe. Much research has been carried out on the leading figures of these pro-European activities but amongst the wealth of this period other actors have tended to be forgotten. Such is the case with the French writer Jules Romains, who not only coined “Europeanism”, the word that would define the whole movement in favour of Europe, but who also actively participated in promoting a united Europe. This article seeks to introduce and discuss Romains’ ideas on Europe. It will demonstrate that his vision was very coherent within the framework of his Unanimist philosophy but was undermined by serious ambiguities. It will also demonstrate that his ideas are of great interest for what they reveal about the interwar period in France and Europe, what they bring to the genealogy of the European project, as set up after the Second World War, and for the ambiguities at the core of his concept of Europe, which are still very much at the heart of many of today’s debates about the European Union

ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary

These guidelines address the diagnosis and management of atherosclerotic, aneurysmal, and thromboembolic peripheral arterial diseases (PADs). The clinical manifestations of PAD are a major cause of acute and chronic illness, are associated with decrements in functional capacity and quality of life, cause limb amputation, and increase the risk of death. Whereas the term “peripheral arterial disease” encompasses a large series of disorders that affect arterial beds exclusive of the coronary arteries, this writing committee chose to limit the scope of the work of this document to include the disorders of the abdominal aorta, renal and mesenteric arteries, and lower extremity arteries. The purposes of the full guidelines are to (a) aid in the recognition, diagnosis, and treatment of PAD of the aorta and lower extremities, addressing its prevalence, impact on quality of life, cardiovascular ischemic risk, and risk of critical limb ischemia (CLI); (b) aid in the recognition, diagnosis, and treatment of renal and visceral arterial diseases; and (c) improve the detection and treatment of abdominal and branch artery aneurysms. Clinical management guidelines for other arterial beds (e.g., the thoracic aorta, carotid and vertebral arteries, and upper-extremity arteries) have been excluded from the current guidelines to focus on the infradiaphragmatic arterial system and in recognition of the robust evidence base that exists for the aortic, visceral, and lower extremity arteries

ABINIT: Overview and focus on selected capabilities

Paper published as part of the special topic on Electronic Structure SoftwareABINIT is probably the first electronic-structure package to have been released under an open-source license about 20 years ago. It implements density functional theory, density-functional perturbation theory (DFPT), many-body perturbation theory (GW approximation and Bethe–Salpeter equation), and more specific or advanced formalisms, such as dynamical mean-field theory (DMFT) and the “temperaturedependent effective potential” approach for anharmonic effects. Relying on planewaves for the representation of wavefunctions, density, and other space-dependent quantities, with pseudopotentials or projector-augmented waves (PAWs), it is well suited for the study of periodic materials, although nanostructures and molecules can be treated with the supercell technique. The present article starts with a brief description of the project, a summary of the theories upon which ABINIT relies, and a list of the associated capabilities. It then focuses on selected capabilities that might not be present in the majority of electronic structure packages either among planewave codes or, in general, treatment of strongly correlated materials using DMFT; materials under finite electric fields; properties at nuclei (electric field gradient, Mössbauer shifts, and orbital magnetization); positron annihilation; Raman intensities and electro-optic effect; and DFPT calculations of response to strain perturbation (elastic constants and piezoelectricity), spatial dispersion (flexoelectricity), electronic mobility, temperature dependence of the gap, and spin-magnetic-field perturbation. The ABINIT DFPT implementation is very general, including systems with van der Waals interaction or with noncollinear magnetism. Community projects are also described: generation of pseudopotential and PAW datasets, high-throughput calculations (databases of phonon band structure, second-harmonic generation, and GW computations of bandgaps), and the library LIBPAW. ABINIT has strong links with many other software projects that are briefly mentioned.This work (A.H.R.) was supported by the DMREF-NSF Grant No. 1434897, National Science Foundation OAC-1740111, and U.S. Department of Energy DE-SC0016176 and DE-SC0019491 projects. N.A.P. and M.J.V. gratefully acknowledge funding from the Belgian Fonds National de la Recherche Scientifique (FNRS) under Grant No. PDR T.1077.15-1/7. M.J.V. also acknowledges a sabbatical “OUT” grant at ICN2 Barcelona as well as ULiège and the Communauté Française de Belgique (Grant No. ARC AIMED G.A. 15/19-09). X.G. and M.J.V. acknowledge funding from the FNRS under Grant No. T.0103.19-ALPS. X.G. and G.-M. R. acknowledge support from the Communauté française de Belgique through the SURFASCOPE Project (No. ARC 19/24-057). X.G. acknowledges the hospitality of the CEA DAM-DIF during the year 2017. G.H. acknowledges support from the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division under Contract No. DE-AC02-05-CH11231 (Materials Project Program No. KC23MP). The Belgian authors acknowledge computational resources from supercomputing facilities of the University of Liège, the Consortium des Equipements de Calcul Intensif (Grant No. FRS-FNRS G.A. 2.5020.11), and Zenobe/CENAERO funded by the Walloon Region under Grant No. G.A. 1117545. M.C. and O.G. acknowledge support from the Fonds de Recherche du Québec Nature et Technologie (FRQ-NT), Canada, and the Natural Sciences and Engineering Research Council of Canada (NSERC) under Grant No. RGPIN-2016-06666. The implementation of the libpaw library (M.T., T.R., and D.C.) was supported by the ANR NEWCASTLE project (Grant No. ANR-2010-COSI-005-01) of the French National Research Agency. M.R. and M.S. acknowledge funding from Ministerio de Economia, Industria y Competitividad (MINECO-Spain) (Grants Nos. MAT2016-77100-C2-2-P and SEV-2015-0496) and Generalitat de Catalunya (Grant No. 2017 SGR1506). This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation program (Grant Agreement No. 724529). P.G. acknowledges support from FNRS Belgium through PDR (Grant No. HiT4FiT), ULiège and the Communauté française de Belgique through the ARC project AIMED, the EU and FNRS through M.ERA.NET project SIOX, and the European Funds for Regional Developments (FEDER) and the Walloon Region in the framework of the operational program “Wallonie-2020.EU” through the project Multifunctional thin films/LoCoTED. The Flatiron Institute is a division of the Simons Foundation. A large part of the data presented in this paper is available directly from the Abinit Web page www.abinit.org. Any other data not appearing in this web page can be provided by the corresponding author upon reasonable request.Peer reviewe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)