Population Genetic Structure of Listeria monocytogenes Strains as Determined by Pulsed-Field Gel Electrophoresis and Multilocus Sequence Typing

Listeria monocytogenes is a ubiquitous bacterium that may cause the foodborne illness listeriosis. Only a small amount of data about the population genetic structure of strains isolated from food is available. This study aimed to provide an accurate view of the L. monocytogenes food strain population in France. From 1999 to 2014, 1,894 L. monocytogenes strains were isolated from food at the French National Reference Laboratory for L. monocytogenes and classified according to the five risk food matrices defined by the European Food Safety Authority (EFSA). A total of 396 strains were selected on the basis of different pulsed-field gel electrophoresis (PFGE) clusters, serotypes, and strain origins and typed by multilocus sequence typing (MLST), and the MLST results were supplemented with MLST data available from Institut Pasteur, representing human and additional food strains from France. The distribution of sequence types (STs) was compared between food and clinical strains on a panel of 675 strains. High congruence between PFGE and MLST was found. Out of 73 PFGE clusters, the two most prevalent corresponded to ST9 and ST121. Using original statistical analysis, we demonstrated that (i) there was not a clear association between ST9 and ST121 and the food matrices, (ii) serotype IIc, ST8, and ST4 were associated with meat products, and (iii) ST13 was associated with dairy products. Of the two major STs, ST121 was the ST that included the fewest clinical strains, which might indicate lower virulence. This observation may be directly relevant for refining risk analysis models for the better management of food safety. IMPORTANCE This study showed a very useful backward compatibility between PFGE and MLST for surveillance. The results enabled better understanding of the population structure of L. monocytogenes strains isolated from food and management of the health risks associated with L. monocytogenes food strains. Moreover, this work provided an accurate view of L. monocytogenes strain populations associated with specific food matrices. We clearly showed that some STs were associated with food matrices, such as meat, meat products, and dairy products. We opened the way to source attribution modeling in order to quantify the relative importance of the main food matrices

SAXO+ upgrade : second stage AO system end-to-end numerical simulations

SAXO+ is a proposed upgrade to SAXO, the AO system of the SPHERE instrument on the ESO Very Large Telescope. It will improve the capabilities of the instrument for the detection and characterization of young giant planets. It includes a second stage adaptive optics system composed of a dedicated near-infrared wavefront sensor and a deformable mirror. This second stage will remove the residual wavefront errors left by the current primary AO loop (SAXO). This paper focuses on the numerical simulations of the second stage (SAXO+) and concludes on the impact of the main AO parameters used to build the design strategy. Using an end-to-end AO simulation tool (COMPASS), we investigate the impact of several parameters on the performance of the AO system. We measure the performance in minimizing the star residuals in the coronagraphic image. The parameters that we study are : the second stage frequency, the photon flux on each WFS, the first stage gain and the DM number of actuators of the second stage. We show that the performance is improved by a factor 10 with respect to the current AO system (SAXO). The optimal second stage frequency is between 1 and 2 kHz under good observing conditions. In a red star case, the best SAXO+ performance is achieved with a low first stage gain of 0.05, which reduces the first stage rejection.Comment: 10 pages, 8 figures. Submitted to AO4ELT7 conference proceeding

DYRK1A, a Novel Determinant of the Methionine-Homocysteine Cycle in Different Mouse Models Overexpressing this Down-Syndrome-Associated Kinase

BACKGROUND:Hyperhomocysteinemia, characterized by increased plasma homocysteine level, is associated with an increased risk of atherosclerosis. On the contrary, patients with Down syndrome appear to be protected from the development of atherosclerosis. We previously found a deleterious effect of hyperhomocysteinemia on expression of DYRK1A, a Down-syndrome-associated kinase. As increased expression of DYRK1A and low plasma homocysteine level have been associated with Down syndrome, we aimed to analyze the effect of its over-expression on homocysteine metabolism in mice. METHODOLOGY/PRINCIPAL FINDINGS:Effects of DYRK1A over-expression were examined by biochemical analysis of methionine metabolites, real-time quantitative reverse-transcription polymerase chain reaction, and enzyme activities. We found that over-expression of Dyrk1a increased the hepatic NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase activities, concomitant with decreased level of plasma homocysteine in three mice models overexpressing Dyrk1a. Moreover, these effects were abolished by treatment with harmine, the most potent and specific inhibitor of Dyrk1a. The increased NAD(P)H:quinone oxidoreductase and S-adenosylhomocysteine hydrolase activities were also found in lymphoblastoid cell lines from patients with Down syndrome. CONCLUSIONS/SIGNIFICANCE:Our results might give clues to understand the protective effect of Down syndrome against vascular defect through a decrease of homocysteine level by DYRK1A over-expression. They reveal a link between the Dyrk1a signaling pathway and the homocysteine cycle

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/)

Pilule et préservatif, substitution ou association? Une analyse des biographies contraceptives des jeunes femmes en France de 1978 à 2000

La pratique contraceptive des jeunes (15-29 ans) a connu deux évolutions importantes au cours des dernières décennies en France. Tout d'abord, et dès la fin des années 1960, l'utilisation de la pilule s'est généralisée dans cette classe d'âges. Sa diffusion n'était cependant pas terminée lorsque surgit l'épidémie du sida, à la fin des années 1980. À la suite des campagnes de prévention du VIH, les jeunes ont massivement adopté le préservatif comme première méthode contraceptive, avec deux conséquences : une extension de la couverture contraceptive (à la fin des années 1990, presque tous les premiers rapports étaient protégés), et un report de l'âge à la première utilisation de la pilule. Dans ce contexte, on peut penser que l'introduction du préservatif a pu détourner une partie des jeunes de la pilule. En utilisant à la fois les données transversales des quatre dernières enquêtes nationales sur la contraception (Ined-Inserm), et les biographies contraceptives complètes collectées dans la dernière d'entre elles (Cocon), nous montrons que la proportion d'utilisatrices de la pilule n'a diminué - au milieu des années 1980 - qu'au premier rapport, et que l'utilisation beaucoup plus fréquente du préservatif au moment de ce rapport a finalement conduit les jeunes à utiliser ensuite rapidement la pilule

The Pill and the Condom, Substitution or Association? An Analysis of the Contraceptive Histories of Young Women in France, 1978-2000

La pratique contraceptive des jeunes (15-29 ans) a connu deux évolutions importantes au cours des dernières décennies en France. Tout d'abord, et dès la fin des années 1960, l'utilisation de la pilule s'est généralisée dans cette classe d'âges. Sa diffusion n'était cependant pas terminée lorsque surgit l'épidémie du sida, à la fin des années 1980. À la suite des campagnes de prévention du VIH, les jeunes ont massivement adopté le préservatif comme première méthode contraceptive, avec deux conséquences : une extension de la couverture contraceptive (à la fin des années 1990, presque tous les premiers rapports étaient protégés), et un report de l'âge à la première utilisation de la pilule. Dans ce contexte, on peut penser que l'introduction du préservatif a pu détourner une partie des jeunes de la pilule. En utilisant à la fois les données transversales des quatre dernières enquêtes nationales sur la contraception (Ined-Inserm), et les biographies contraceptives complètes collectées dans la dernière d'entre elles (Cocon), nous montrons que la proportion d'utilisatrices de la pilule n'a diminué - au milieu des années 1980 - qu'au premier rapport, et que l'utilisation beaucoup plus fréquente du préservatif au moment de ce rapport a finalement conduit les jeunes à utiliser ensuite rapidement la pilule

Global sensitivity analysis for models described by continuous time Markov chains with application to epidemic models

Workshop held online.National audienc