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/)

UV and X-ray structural studies of a 101-residue long Tat protein from a HIV-1 primary isolate and of its mutated, detoxified, vaccine candidate.

International audienceThe 101-residue long Tat protein of primary isolate 133 of the human immunodeficiency virus type 1 (HIV-1), wt-Tat(133) displays a high transactivation activity in vitro, whereas the mutant thereof, STLA-Tat(133), a vaccine candidate for HIV-1, has none. These two proteins were chemically synthesized and their biological activity was validated. Their structural properties were characterized using circular dichroism (CD), fluorescence emission, gel filtration, dynamic light scattering, and small angle X-ray scattering (SAXS) techniques. SAXS studies revealed that both proteins were extended and belong to the family of intrinsically unstructured proteins. CD measurements showed that wt-Tat(133) or STLA-Tat(133) underwent limited structural rearrangements when complexed with specific fragments of antibodies. Crystallization trials have been performed on the two forms, assuming that the Tat(133) proteins might have a better propensity to fold in supersaturated conditions, and small crystals have been obtained. These results suggest that biologically active Tat protein is natively unfolded and requires only a limited gain of structure for its function

Population and Affective Perception: Biopolitics and Anticipatory Action in US Counterinsurgency Doctrine

This paper analyses the biopolitical logics of current US counterinsurgency doctrine in the context of the multiple forms of biopower that make up the “war on terror”. It argues that counterinsurgency doctrine aims to prevent spectral networked insurgencies by intervening on the “environment” of insurgent formation—the relations between three different enactments of “population” (species being, logistical life and ways of life) and a fourth—affectively imbued perception. Counterinsurgency is best characterised, then, as an “environmentality” (Foucault M 2008 The Birth of Biopolitics: Lectures at the Collége De France, 1978–1979. Translated by G Burchell. London: Palgrave Macmillan) that redeploys elements from other forms of biopolitics alongside an emphasis on network topologies, future-orientated action and affective perception

The two faces of security in hybrid political orders: a framework for analysis and research

This paper reframes the security and development debate through fresh theoretical lenses, which view security as highly contested both in the realm of politics and in the realm of ideas. For some analysts security concerns political power, including the use of organised force to establish and maintain social orders and to protect them from external and internal threats. For others it is about how individuals and communities are protected (or protect themselves) from violence, abuse of power and other existential risks. We integrate both approaches whilst placing our focus on the deep tensions between them. Combining them is especially apposite in the hybrid political orders of conflict-torn regions in the developing world – where the state and its monopoly of violence are contested and diverse state and non-state security actors coexist, collaborate or compete