Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Climate Change Leadership in the eyes of Business

In 2015, the COP21 creates a new hybrid mode of multilateral governance, which aims to make the action of non-states actors a bridge between the political commitments and the government’s actions. The business world is one of these actors with ambitious new roles to implement the Paris Agreements and its NDCs. Yet it seems that nobody has yet questioned whether companies can also act as leaders at their level or at least help their country/organisation to take the lead. To understand how business perceived their roles in the governance landscape post Paris-Agreement, several questions were asked to see what kind of leadership themselves were looking for. Who are the designated leaders for business when it comes to climate leadership? How have them evolved ? Why are they recognized as such? And what is the role of business in delivering Parties' NDCs in the post Paris-Agreement area? Thanks to a unique data collection of questionnaires distributed on COP22 to 25, it appeared that European leadership is not only the most consistent but also the most recognised, although the other EU partners in the BIG3 are far from demeriting. As the issue is particularly political, it was found that the recognition of leadership is not only due to certain leaders but also to many laws, which create and restrict many opportunities for business. The history and culture of the countries concerned also provided many answers. Finally, it seemed unanimous that a cooperative work between governments and business would allow a better and faster reach of both NDCs and SDGs

Climate Change Leadership in the eyes of Business

In 2015, the COP21 creates a new hybrid mode of multilateral governance, which aims to make the action of non-states actors a bridge between the political commitments and the government’s actions. The business world is one of these actors with ambitious new roles to implement the Paris Agreements and its NDCs. Yet it seems that nobody has yet questioned whether companies can also act as leaders at their level or at least help their country/organisation to take the lead. To understand how business perceived their roles in the governance landscape post Paris-Agreement, several questions were asked to see what kind of leadership themselves were looking for. Who are the designated leaders for business when it comes to climate leadership? How have them evolved ? Why are they recognized as such? And what is the role of business in delivering Parties' NDCs in the post Paris-Agreement area? Thanks to a unique data collection of questionnaires distributed on COP22 to 25, it appeared that European leadership is not only the most consistent but also the most recognised, although the other EU partners in the BIG3 are far from demeriting. As the issue is particularly political, it was found that the recognition of leadership is not only due to certain leaders but also to many laws, which create and restrict many opportunities for business. The history and culture of the countries concerned also provided many answers. Finally, it seemed unanimous that a cooperative work between governments and business would allow a better and faster reach of both NDCs and SDGs

Climate Change Leadership in the eyes of Business

In 2015, the COP21 creates a new hybrid mode of multilateral governance, which aims to make the action of non-states actors a bridge between the political commitments and the government’s actions. The business world is one of these actors with ambitious new roles to implement the Paris Agreements and its NDCs. Yet it seems that nobody has yet questioned whether companies can also act as leaders at their level or at least help their country/organisation to take the lead. To understand how business perceived their roles in the governance landscape post Paris-Agreement, several questions were asked to see what kind of leadership themselves were looking for. Who are the designated leaders for business when it comes to climate leadership? How have them evolved ? Why are they recognized as such? And what is the role of business in delivering Parties' NDCs in the post Paris-Agreement area? Thanks to a unique data collection of questionnaires distributed on COP22 to 25, it appeared that European leadership is not only the most consistent but also the most recognised, although the other EU partners in the BIG3 are far from demeriting. As the issue is particularly political, it was found that the recognition of leadership is not only due to certain leaders but also to many laws, which create and restrict many opportunities for business. The history and culture of the countries concerned also provided many answers. Finally, it seemed unanimous that a cooperative work between governments and business would allow a better and faster reach of both NDCs and SDGs

Climate Change Leadership in the eyes of Business

In 2015, the COP21 creates a new hybrid mode of multilateral governance, which aims to make the action of non-states actors a bridge between the political commitments and the government’s actions. The business world is one of these actors with ambitious new roles to implement the Paris Agreements and its NDCs. Yet it seems that nobody has yet questioned whether companies can also act as leaders at their level or at least help their country/organisation to take the lead. To understand how business perceived their roles in the governance landscape post Paris-Agreement, several questions were asked to see what kind of leadership themselves were looking for. Who are the designated leaders for business when it comes to climate leadership? How have them evolved ? Why are they recognized as such? And what is the role of business in delivering Parties' NDCs in the post Paris-Agreement area? Thanks to a unique data collection of questionnaires distributed on COP22 to 25, it appeared that European leadership is not only the most consistent but also the most recognised, although the other EU partners in the BIG3 are far from demeriting. As the issue is particularly political, it was found that the recognition of leadership is not only due to certain leaders but also to many laws, which create and restrict many opportunities for business. The history and culture of the countries concerned also provided many answers. Finally, it seemed unanimous that a cooperative work between governments and business would allow a better and faster reach of both NDCs and SDGs

Climate Change Leadership in the eyes of Business

In 2015, the COP21 creates a new hybrid mode of multilateral governance, which aims to make the action of non-states actors a bridge between the political commitments and the government’s actions. The business world is one of these actors with ambitious new roles to implement the Paris Agreements and its NDCs. Yet it seems that nobody has yet questioned whether companies can also act as leaders at their level or at least help their country/organisation to take the lead. To understand how business perceived their roles in the governance landscape post Paris-Agreement, several questions were asked to see what kind of leadership themselves were looking for. Who are the designated leaders for business when it comes to climate leadership? How have them evolved ? Why are they recognized as such? And what is the role of business in delivering Parties' NDCs in the post Paris-Agreement area? Thanks to a unique data collection of questionnaires distributed on COP22 to 25, it appeared that European leadership is not only the most consistent but also the most recognised, although the other EU partners in the BIG3 are far from demeriting. As the issue is particularly political, it was found that the recognition of leadership is not only due to certain leaders but also to many laws, which create and restrict many opportunities for business. The history and culture of the countries concerned also provided many answers. Finally, it seemed unanimous that a cooperative work between governments and business would allow a better and faster reach of both NDCs and SDGs

Philippe Vilain, à la recherche de l’amour perdu…

Le narrateur des romans de Philippe Vilain est toujours soit un perdant passif de l’amour, dépossédé de l’être qu’il a aimé, soit un perdeur actif : il ruine la relation amoureuse qui s’est construite. Mais que perd-il ? Ne perd-il que l’objet de son amour ? Se perd-il lui même ? S’agit-il de perdre un amour pour mieux retrouver l’amour ? pour mieux se retrouver soi ? Ou s’agit-il de retrouver autre chose et quoi ? Vers quelle vérité conduit cette recherche, cette quête, infiniment recommencée, cette tentative d’épuisement de ce topos. Les amours perdues, comme le temps perdu, quand elles sont retrouvées dans la mise en récit littéraire, redonnent, finalement, à l’amour, tout son absolu, toute sa puissance et toute sa grandeur : l’amour perdu et retrouvé, c’est le fondement de la création et de la Littérature selon Philippe Vilain.The narrator of Philippe Vilain's novels is always either a passive loser of love, dispossessed of the being he loved, or an active loser: he ruins the romantic relationship that has been built. But what does he lose? Does he only lose the object of his love? Is he losing himself? Is it about losing a love to better find love again? to better find oneself? Or is it about finding something else and what? Towards what truth does this research lead, this quest, infinitely repeated, this attempt to exhaust this topos. Lost loves, like lost time, when they are rediscovered in the literary narrative, ultimately restore love to all its absoluteness, all its power and all its grandeur: love lost and found again is the foundation of Creation and Literature according to Philippe Vilain

Utilisation de la cycloserine dans les tuberculoses multiresistantes

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A step by step guide to using Visual Field Analysis v1

In this protocol, we provide a step by step guide to using Visual Field Analysis (VFA) successfully. VFA is a python program based on DeepLabCut toolbox (Nath et al., 2019). Using our program, it is possible to score reliably the eye use, activity, and time spent in different zones of different animal species and experimental paradigms for more reproducible research. </p