A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Observational study of the effect of heparin-containing flush solutions on the incidence of arterial catheter occlusion

The National Patient Safety Agency (NPSA) highlighted potential dangers associated with arterial lines in 2008, recommending the use of saline-only flush solutions. The incidence of catheter thrombosis appeared to increase following the implementation of this guidance in some units. The objective of the current study was to observe local practice regarding the use of heparin in arterial catheter flush solutions, and subsequent arterial catheter occlusion rates. This was an observational study in which data were collected prospectively from 445 catheter insertions in unselected intensive care patients in eight member hospitals of the Association of North Western Intensive Care Units (ANWICU). Catheters flushed with heparinised solutions had a significantly increased median lifespan of 102 hours versus 72 hours for saline-flushed catheters (p&lt;0.01). The likelihood of line blockage was significantly decreased in the heparin group (7.9%) compared with the saline group (41.2%, p&lt;0.0001). Our results suggest that routine use of heparinised flush solutions is associated with increased catheter lifespan and reduced catheter thrombosis. We believe that there is justification for an adequately powered, randomised controlled trial. Current NPSA guidance may need to be reviewed. </jats:p

ECCO 2 R therapy in the ICU: consensus of a European round table meeting

BACKGROUND With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO$_{2}$ removal (ECCO$_{2}$R). However, current evidence in these indications is limited. A European ECCO$_{2}$R Expert Round Table Meeting was convened to further explore the potential for this treatment approach. METHODS A modified Delphi-based method was used to collate European experts' views to better understand how ECCO$_{2}$R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus. RESULTS Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO$_{2}$R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO$_{2}$R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO$_{2}$R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO$_{2}$ levels. Driving pressure (≥ 14 cmH$_{2}$O) followed by plateau pressure (P$_{plat}$; ≥ 25 cmH$_{2}$O) was considered the most important criteria for ECCO$_{2}$R initiation. Key treatment targets for patients with ARDS undergoing ECCO$_{2}$R included pH (> 7.30), respiratory rate ( 7.30-7.35), respiratory rate (< 20-25 breaths/min), decrease of PaCO$_{2}$ (by 10-20%), weaning from NIV, decrease in HCO$_{3}$$^{-}$ and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group. CONCLUSIONS Insights from this group of experienced physicians suggest that ECCO$_{2}$R therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration ClinicalTrials.gov Identifier: NCT02654327

Measurement of the Mass of the Z-Boson and the Energy Calibration of Lep

Contains fulltext : 26847___.PDF (publisher's version ) (Open Access

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

Electroweak parameters of the Z0^0 resonance and the standard model

Media temporalities of the elderly : evolutions in stability This article shows the context of analysis and the first results of a research on media temporalities of the elderly. Several works have finely analysed the diversity of the media practices and studied meanings of media uses. I wish to continue these analyses by insisting on the evolutionary and dynamic aspect of the practices and temporalities of users having expanded, enhanced, so called "interactive" radio and especially television programming. A priori, the elderly, upon retirement, have a "full-time free time". Their media practices seem strongly influenced by their first experiments ; the appropriation of the various peripheral accessories which gradually came with the media, to the latest digital ones, seems to reinforce their habits of watching television. Their representations and relations with times and media are very far away from the image of television like omnipresent media or "devourer of time". Rather, their media practices are to be understood like a temporality of the occupation, according to the expression of Gerard Derèze, characterized by interest and utility. A particular glance at the users who do not carry out a systematic selection of the programs, accepting the unforeseen, highlights an approach of media and time that allow "useful encounter" which I would qualify in a first stage by : "chance and encounter" and "random and the following". The few points presented here make me assume that the global relation of the autonomous elderly persons to the media can evolve when confronted to their new temporal framework and the new program offer, whereas their representations and use of the media remain quite stable

Electroweak parameters of the Z0^0 resonance and the standard model

Media temporalities of the elderly : evolutions in stability This article shows the context of analysis and the first results of a research on media temporalities of the elderly. Several works have finely analysed the diversity of the media practices and studied meanings of media uses. I wish to continue these analyses by insisting on the evolutionary and dynamic aspect of the practices and temporalities of users having expanded, enhanced, so called "interactive" radio and especially television programming. A priori, the elderly, upon retirement, have a "full-time free time". Their media practices seem strongly influenced by their first experiments ; the appropriation of the various peripheral accessories which gradually came with the media, to the latest digital ones, seems to reinforce their habits of watching television. Their representations and relations with times and media are very far away from the image of television like omnipresent media or "devourer of time". Rather, their media practices are to be understood like a temporality of the occupation, according to the expression of Gerard Derèze, characterized by interest and utility. A particular glance at the users who do not carry out a systematic selection of the programs, accepting the unforeseen, highlights an approach of media and time that allow "useful encounter" which I would qualify in a first stage by : "chance and encounter" and "random and the following". The few points presented here make me assume that the global relation of the autonomous elderly persons to the media can evolve when confronted to their new temporal framework and the new program offer, whereas their representations and use of the media remain quite stable