Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Création d’une frange pionnière sur les rives du canal de Panama

1. Introduction La récente mise en vigueur des Traités sur le Canal de Panama, le 1 er Octobre 1979, règle un grave désaccord international qui menaçait la sécurité du transport maritime et attire l’attention sur un problème qui peut mettre en péril le fonctionnement efficace de la voie interocéanique. Il s’agit du rapide développement de franges pionnières rurales et urbaines qui perturbent sérieusement les régimes hydrologiques du centre de l’isthme de Panama. Le Canal de Panama qui, du poi..

Hardware-in-the-Loop Scheme of Linear Controllers Tuned through Genetic Algorithms for BLDC Motor Used in Electric Scooter under Variable Operation Conditions

Outrunner brushless DC motors (BLDC) are a type of permanent magnet synchronous motor (PMSM) widely used in electric micro-mobility vehicles, such as scooters, electric bicycles, wheelchairs, and segways, among others. Those vehicles have many operational constraints because they are driven directly by the user with light protective wearing. Therefore, to improve control strategies to make the drive safer, it is essential to model the traction system over a wide range of operating conditions in a street environment. In this work, we developed an electro-mechanical model based on the Hardware-in-the-Loop (HIL) structure for a two-wheeler electric scooter, using the BLDC motor to explore its response and to test linear controllers for speed and torque management under variable operating conditions. The proposed model includes motor parameters, power electronics component characteristics, mechanical structure, and external operating conditions. Meanwhile the linear controllers will be adjusted or tuned though a heuristic approach based on Genetic Algorithms (GAs) to optimize the system’s response. The HIL scheme will be able to simulate a wide range of conditions such as user weight, slopes, wind speed changes, and combined conditions. The designed model can be used to improve the design of the controller and estimate mechanical and electrical loads. Finally, the results of the controller tests show how the proposed cascade scheme, tuned through the GA, improves the system behavior and reduces the mean square error with respect to a classical tuning approach between 20% and 60%

Les phénomènes de frontière dans les pays tropicaux

Les frontières pionnières sont un thème central dans les recherches du célèbre géographe français Pierre Monbeig. À l’occasion du colloque Les Phénomènes de « frontière » dans les pays tropicaux, tenu du 12 au 15 décembre 1979, plus de quarante intervenants ou auteurs de communication – dont notamment Claude Bataillon – ont rendu hommage à ce spécialiste de l’Amérique du Sud. Cette rencontre est le résultat de recherches menées au cours des années 1970, dont résultent les sujets comme le développement des frontières pionnières, ou encore les politiques d’État liées aux opérations industrielles. L’un des problèmes majeurs soulevé ici est la destruction de l’environnement, due à la constante expansion de l’agriculture qui menace les écosystèmes d’Amérique latine. Les évolutions technologiques sont ici vues comme mettant en péril le monde du travail, qui a alors moins besoin de main-d’œuvre qu’auparavant pour une plus grande production. Les membres de ce colloque prouvent que le sujet des phénomènes de frontières est encore d’actualité, et démontrent que les fronts pionniers sont dans une recherche constante de ressources non utilisées, cherchant sans cesse à se développer au dépend de certains écosystèmes. Il n’est pas inutile de rappeler que l’Amazonie est l’une des dernières régions encore sauvage, mais elle disparaît peu à peu sous l’avancée inexorable des frontières pionnières

Carbon steel corrosion: a review of key surface properties and characterization methods

Corrosion is a subject of interest to interdisciplinary research communities, combining fields of materials science, chemistry, physics, metallurgy and chemical engineering. In order to understand mechanisms of corrosion and the function of corrosion inhibitors, the reactions at the interfaces between the corrosive electrolyte and a steel surface, particularly at the initial stages of the corrosion process, need to be described. Naturally, these reactions are strongly affected by the nature and properties of the steel surfaces. It is however seen that the majority of recent corrosion and corrosion-inhibition investigations are limited to electrochemical testing, with ex situ analysis of the treated steels (post-exposure analysis). The characterization of materials and their surface properties, such as texture and morphology, are not being considered in most studies. Similarly, in situ investigations of the initial stages of the corrosion reactions using advanced surface characterization techniques are scarce. In this review, attention is brought to the importance of surface features of carbon steels, such as texture and surface energy, along with defects dislocation related to mechanical processing of carbon steels. This work is extended to a critical review of surface analytical techniques used for characterization of carbon steels in corrosive media with particular focus on examining steel surfaces treated with corrosion inhibitors. Further, emerging surface analysis techniques and their applicability to analyse carbon steels in corrosive media are discussed. The importance of surface properties is commonly addressed by surface scientists as well as researchers in other chemistry fields such as nanotechnology, fuel cells, and catalysis. This article is expected to appeal to a broad scientific community, including but not limited to corrosion scientists, material chemists, analytical chemists, metal physicists, corrosion and materials engineers