10 research outputs found
Complete genome sequence of Archaeoglobus profundus type strain (AV18T)
Archaeoglobus profundus (Burggraf et al. 1990) is a hyperthermophilic archaeon in the euryarchaeal class Archaeoglobi, which is currently represented by the single family Archaeoglobaceae, containing six validly named species and two strains ascribed to the genus 'Geoglobus' which is taxonomically challenged as the corresponding type species has no validly published name. All members were isolated from marine hydrothermal habitats and are obligate anaerobes. Here we describe the features of the organism, together with the complete genome sequence and annotation. This is the second completed genome sequence of a member of the class Archaeoglobi. The 1,563,423 bp genome with its 1,858 protein-coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project
Complete genome sequence of Methanothermus fervidus type strain (V24ST)
Methanothermus fervidus Stetter 1982 is the type strain of the genus Methanothermus. This hyperthermophilic genus is of a thought to be endemic in Icelandic hot springs. M. fervidus was not only the first characterized organism with a maximal growth temperature (97°C) close to the boiling point of water, but also the first archaeon in which a detailed functional analysis of its histone protein was reported and the first one in which the function of 2,3-cyclodiphosphoglycerate in thermoadaptation was characterized. Strain V24ST is of interest because of its very low substrate ranges, it grows only on H2 + CO2. This is the first completed genome sequence of the family Methanothermaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 1,243,342 bp long genome with its 1,311 protein-coding and 50 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
Renovating the Republic: Unified Germany confronts its history – both deep and recent – as it defines itself for the 21st century
Germany and America go way back. German soldiers fought in the American Revolutionary War, and German settlers already had begun finding their way to America before the colonies became a nation. By the 1850s, many Germans had settled in the Midwest, and they followed the frontier west to the Great Plains. Germans were the largest group of immigrants arriving in Nebraska between 1854 and 1894, and by 1900, almost 20 percent of the state was first- and second-generation Germans. For the past year, a group of University of Nebraska-Lincoln journalism students has closely examined this foreign country that, perhaps more than any other, helped shape the Cornhusker State. In January, 13 students spent 10 days in Berlin, interviewing Germans in government offices and nightclubs, at universities and mosques. To a large extent, what they found was a tale of two 9/11’s. Without question, Germany’s long and complicated relationship with the United States – as a source of substantial immigration, as an enemy in two world wars and as a key ally in a protracted East-West Cold War – was changed by the events of Sept. 11, 2001. Germany, less inclined to rely on military power to solve international crises, supported U.S. moves in Afghanistan but not in Iraq, straining relations with the U.S. Since then, Germany’s own security has been tested by global terrorism. But there was an earlier, even more profound 9/11 for Germany. On Nov. 9, 1989 – which, when written European-style, with the day before the month, becomes 9.11.1989 – Germans began tearing down the Berlin Wall. When the dust settled, the Soviet Union was gone, and Germany – split into East and West for 40 years – was reunited. These two dates – British writer Timothy Garton Ash argues that one marks the end of the 20th century and the other the beginning of the 21st – color nearly everything happening today in Germany. Our students’ work was aided immensely by Germany’s Goethe-Institut, especially our Berlin tour guides Gerrit Book and Anna Held, and by the German Foreign Office, which assisted with travel expenses. We would also like to thank Viola Drath for her help and inspiration, and Wolfgang Drautz, consul general, and Winfried Völkering, vice consul, in the German Consulate General in Chicago. Contents Opening Essay: The Road to Rebirth Culture: Endless Possibilities Economy: Struggle for Success Health Care: Splintered Coverage Social Market: Cornerstone of a Democracy Currency: All About Change Military: Beyond Their Borders Checkpoint Charlie: From Tanks to Tourism Terrorism: A New Sense of Urgency Religion: Living Side by Side Government and Religion: Assessing Religion Memorials: Monumental Debate Immigration: No Place to Call Home Citizenship: Seeking Acceptance Education: Failing Grade Kennedy School: Bridging the Divide Universities: Change in Focus Women: Redefining Their Roles European Union: Coming Together A non-optimized version of the PDF file (170 MB) is attached below as an “Additional file.
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Complete genome sequence of Archaeoglobus profundus type strain (AV18).
Archaeoglobus profundus (Burggraf et al. 1990) is a hyperthermophilic archaeon in the euryarchaeal class Archaeoglobi, which is currently represented by the single family Archaeoglobaceae, containing six validly named species and two strains ascribed to the genus 'Geoglobus' which is taxonomically challenged as the corresponding type species has no validly published name. All members were isolated from marine hydrothermal habitats and are obligate anaerobes. Here we describe the features of the organism, together with the complete genome sequence and annotation. This is the second completed genome sequence of a member of the class Archaeoglobi. The 1,563,423 bp genome with its 1,858 protein-coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project
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Complete genome sequence of Methanothermus fervidus type strain (V24S).
Methanothermus fervidus Stetter 1982 is the type strain of the genus Methanothermus. This hyperthermophilic genus is of a thought to be endemic in Icelandic hot springs. M. fervidus was not only the first characterized organism with a maximal growth temperature (97°C) close to the boiling point of water, but also the first archaeon in which a detailed functional analysis of its histone protein was reported and the first one in which the function of 2,3-cyclodiphosphoglycerate in thermoadaptation was characterized. Strain V24S(T) is of interest because of its very low substrate ranges, it grows only on H(2) + CO(2). This is the first completed genome sequence of the family Methanothermaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 1,243,342 bp long genome with its 1,311 protein-coding and 50 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project
Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19
International audienc
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Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.
In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.
Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.
Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.
US National Institutes of Health and Operation Warp Spee
Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF
BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes