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/)

Something wicked this way comes: How well did UK newspapers support the public debate of Avian Influenza as a wicked problem?

The news media in general, and newspapers in particular, are supposed to provide a forum for public debate. These expectations of news media take on a heightened relevance in the case of wicked problems precisely because of the irreducible complexity, the inherent tensions, and the multiplicity of stakeholders and conflicting interests involved in such issues. Both their material complexity and lack of consensus make wicked problems difficult to address. This study uses British newspaper coverage of the H5N1 avian influenza outbreak (2003–2008) to determine if under near ideal conditions, newspaper coverage in the UK is compatible with the expectation that newspapers provide a forum that supports constructive societal debate of a complex, wicked problem. We chose to work with avian influenza because it was extensively covered, evidence rich, and not captive to clear partisan constructions. Our frame analysis examined 254 relevant newspaper articles published in seven national circulation outlets between 2003 and 2008. Newspaper coverage did reflect multiple problem definitions and causal interpretations of avian influenza, which is consistent with the expectation that the media inform and open up public debate. Coverage did not, however, link avian flu to other related issues, engage in systemic contestation or problematise structure. Finally, we found that, despite heterogeneous problem definitions, there was near consensus on a single technical solution. This coverage does not appear to support the open, constructive and informed public debate whose promise justifies the privileges given to news media

The chick diffusion: how newspapers fail to meet normative expectations regarding their democratic role in public debate

Media scholarship has commonly regarded newspapers as an essential element of strong democratic societies: a forum that structures public debate, providing engaged citizens with coherent frameworks to identify, interpret and tackle complex issues. Despite general agreement on the merits of this goal, there is little empirical evidence suggesting it approximates the democratic role historically played by newspapers. We examined three decades of newspaper coverage of chicken meat production in the UK to find evidence relevant to the normative expectations of the democratic role of newspapers as forum for public debate, by means of a two-stage framing analysis of 766 relevant articles from seven outlets. We found mutually disconnected episodic coverage of specific issues whose aggregate effect is consistent with the diffusion rather than the structuring of public debate. Newspapers here afforded polemic rather than the systemic contestation expected. The polemic contestation we found, with diffusion of public debate as an emergent political effect, troubles the assumptions subsequent to which it is possible to argue for the democratic role of newspapers

Chickens, Inc.: Was UK Newspapers’ Framing of the Chicken Meat Production Industry Compatible with Holding Corporate Power to Account?

Journalism is presented as fundamental to democratic accountability in that news media are both able and expected to hold power to account. Such normative expectations, which justify the protections given journalists and news media, are most frequently studied with regards to state power as the natural object of press scrutiny. This article reports on a successful effort to conduct a replicable analysis of a paradigmatic case of corporate power, the UK chicken meat production industry, that asked whether and how newspapers hold corporate power to account. The analytic framework that we developed to support our two-stage framing analysis decomposed accountability into problematization, causal interpretation and attributions of responsibility, thus allowing us to systematically describe how newspapers shape the public debates in a large heterogeneous dataset. We examined a census of relevant articles from seven UK outlets published between 1985 and 2016 (N = 766). While we were pleased to find that our method, if labor intensive, was fully workable, we were concerned to find that media practice was not compatible with holding corporate power to account. These findings raise serious concerns at the levels of this case, for media practice and for media scholarship

The Chick Diffusion: How Newspapers Fail to Meet Normative Expectations Regarding Their Democratic Role in Public Debate

Media scholarship has commonly regarded newspapers as an essential element of strong democratic societies: a forum that structures public debate, providing engaged citizens with coherent frameworks to identify, interpret and tackle complex issues. Despite general agreement on the merits of this goal, there is little empirical evidence suggesting it approximates the democratic role historically played by newspapers. We examined three decades of newspaper coverage of chicken meat production in the UK to find evidence relevant to the normative expectations of the democratic role of newspapers as forum for public debate, by means of a two-stage framing analysis of 766 relevant articles from seven outlets. We found mutually disconnected episodic coverage of specific issues whose aggregate effect is consistent with the diffusion rather than the structuring of public debate. Newspapers here afforded polemic rather than the systemic contestation expected. The polemic contestation we found, with diffusion of public debate as an emergent political effect, troubles the assumptions subsequent to which it is possible to argue for the democratic role of newspapers

From local to regional 3D litho-structural modelling: a methodology towards multi-scale landslide susceptibility and hazard assessment

info:eu-repo/semantics/publishe

Diastereoselective Synthesis of Nonplanar 3-Amino-1,2,4-oxadiazine Scaffold: Structure Revision of Alchornedine

International audienceHerein, we report the diastereoselective synthesis of a 3-amino-1,2,4-oxadiazine (AOXD) scaffold. The presence of a N–O bond in the ring prevents the planar geometry of the aromatic system and induces a strong decrease in the basicity of the guanidine moiety. While DIBAL-H appeared to be the most efficient reducing agent because it exhibited high diastereoselectivity, we observed various behaviors of the Mitsunobu reaction on the resulting β-aminoalcohol, leading to either inversion or retention of the configuration depending on the steric hindrance in the vicinity of the hydroxy group. The physicochemical properties (pKa and log D) and hepatic stability of several AOXD derivatives were experimentally determined and found that the AOXD scaffold possesses promising properties for drug development. Moreover, we synthesized alchornedine, the only natural product with the AOXD scaffold. Based on a comparison of the analytical data, we found that the reported structure of alchornedine was incorrect and hypothesized a new one

Generation of Immunodeficient Rats With Rag1 and Il2rg Gene Deletions and Human Tissue Grafting Models

International audienc

Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study

International audienceBackground: Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population.Results: Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%). A targeted therapy could be proposed to 22 patients (64%), either through a clinical trial (n=15) and/or using already registered drugs (n=21). Ten patients (29%) eventually received targeted treatment, 2 of them deriving clinical benefit. Of 22 patients subjected to mouse implantation, 10 had successful xenografting (45%), mostly in triple-negative aBC.Methods: aBC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study (ClinicalTrials.gov, NCT01521676). Genomic profiling was established by whole-genome array comparative genomic hybridization (aCGH) and targeted next-generation sequencing (NGS) of 365 candidate cancer genes. For a subset of patients, a sample of fresh tumor was orthotopically implanted in humanized cleared fat pads of NSG mice for establishing PDX.Conclusions: Precision medicine can be implemented in a single center in the context of clinical practice and may allow genomic-driven treatment in approximately 30% of aBC patients. PDX may be obtained in a significant fraction of cases

A 220GOPS 96-Core Processor with 6 Chiplets 3D-Stacked on an Active Interposer Offering 0.6ns/mm Latency, 3Tb/s/mm 2 Inter-Chiplet Interconnects and 156mW/mm 2 @ 82%-Peak-Efficiency DC-DC Converters

International audienceIn the context of high performance computing, the integration of more computing capabilities with generic cores or dedicated accelerators for AI application is raising more and more challenges. Due to the increasing costs of advanced nodes and the difficulties of shrinking analog and circuit IOs, alternative architecture solutions to single die are becoming mainstream. Chiplet-based systems using 3D technologies enable modular and scalable architecture and technology partitioning. Nevertheless, there are still limitations due to chiplet integration on passive interposers – silicon or organic. In this paper we present the first CMOS active interposer, integrating i) power management without any external components, ii) distributed interconnects enabling any chiplet-to-chiplet communication, iii) system infrastructure, Design-for-Test, and circuit IOs. The INTACT circuit prototype integrates 6 chiplets in FDSOI 28nm technology, which are 3D-stacked onto this active interposer in 65nm process, offering a total of 96 computing cores. Full scalability of the computing system is achieved using an innovative scalable cache coherent memory hierarchy, enabled by distributed Network-on-Chips, with 3Tbit/s/mm2 high bandwidth 3D-plug interfaces using 20μm pitch micro-bumps, 0.6ns/mm low latency asynchronous interconnects, while the 6 chiplets are locally power-supplied with 156mW/mm2@ 82%-peak-efficiency DC-DC converters through the active interposer. Thermal dissipation is studied showing the feasibility of such approach