| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 5. |
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| 7. |
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| 8. |
- Medema, M. H., et al.
(författare)
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Minimum Information about a Biosynthetic Gene cluster
- 2015
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 11:9, s. 625-631
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Forskningsöversikt (refereegranskat)abstract
- A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
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| 9. |
- Abgrall, N., et al.
(författare)
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The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
- 2017
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Ingår i: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
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Konferensbidrag (refereegranskat)abstract
- The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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| 10. |
- van de Munckhof, A., et al.
(författare)
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Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase
- 2022
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
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| 11. |
- Bode, G.H., et al.
(författare)
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Detection of peptide-based nanoparticles in blood plasma by ELISA
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 10:5, s. Art. no. e0126136-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of the current study was to develop a method to detect peptide-linked nanoparticles in blood plasma. Materials & Methods: A convenient enzyme linked immunosorbent assay (ELISA) was developed for the detection of peptides functionalized with biotin and fluorescein groups. As a proof of principle, polymerized pentafluorophenyl methacrylate nanoparticles linked to biotin-carboxyfluorescein labeled peptides were intravenously injected in Wistar rats. Serial blood plasma samples were analyzed by ELISA and by liquid chromatography mass spectrometry (LC/MS) technology. Results: The ELISA based method for the detection of FITC labeled peptides had a detection limit of 1 ng/mL. We were able to accurately measure peptides bound to pentafluorophenyl meth-acrylate nanoparticles in blood plasma of rats, and similar results were obtained by LC/MS. Conclusions: We detected FITC-labeled peptides on pentafluorophenyl methacrylate nanoparticles after injection in vivo. This method can be extended to detect nanoparticles with different chemical compositions.
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| 12. |
- Ohman, E. Magnus, et al.
(författare)
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Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1) : a double-blind, multicentre, randomised trial
- 2017
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10081, s. 1799-1808
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Tidskriftsartikel (refereegranskat)abstract
- Background Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2.5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months.Methods In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1: 1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2.5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395.Findings Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1.09 [95% CI 0.80-1.50]; p=0.5840).Interpretation A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach.
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| 13. |
- Povsic, Thomas J., et al.
(författare)
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P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes
- 2019
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Ingår i: JAMA cardiology. - : AMER MEDICAL ASSOC. - 2380-6583 .- 2380-6591. ; 4:7, s. 680-684
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Tidskriftsartikel (refereegranskat)abstract
- Importance Physician behavior in response to knowledge of a patient’s CYP2C19 clopidogrel metabolizer status is unknown.Objective To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial.Design, Setting, and Participants The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019.Interventions Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization.Main Outcomes and Measures Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected.Results Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated.Conclusions and Relevance Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach.
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| 14. |
- Scirica, B. M., et al.
(författare)
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Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial
- 2010
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Ingår i: European Heart Journal. - 0195-668X. ; 31:16, s. 1993-2005
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Tidskriftsartikel (refereegranskat)abstract
- Aims Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin-angiotensin-aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo. Methods and results AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function
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| 15. |
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| 16. |
- Chomiuk, L., et al.
(författare)
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Binary orbits as the driver of gamma-ray emission and mass ejection in classical novae
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 514:7522, s. 339-
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Tidskriftsartikel (refereegranskat)abstract
- Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems(1). Novae typically expel about 10(-4) solar masses of material at velocities exceeding 1,000 kilometres per second. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of thermonuclear energy(2), prolonged optically thick winds(3) or binary interaction with the nova envelope(4). Classical novae are now routinely detected at gigaelectronvolt gamma-ray wavelengths(5), suggesting that relativistic particles are accelerated by strong shocks in the ejecta. Here we report high-resolution radio imaging of the gamma-ray-emitting nova V959 Mon. We find that its ejecta were shaped by the motion of the binary system: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion(6,7). At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae(8), explaining why many novae are gamma-ray emitters(5).
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| 17. |
- d'Alessandro, Elisa, et al.
(författare)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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Tidskriftsartikel (refereegranskat)abstract
- Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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| 18. |
- Kälsch, Hagen, et al.
(författare)
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Are air pollution and traffic noise independently associated with atherosclerosis : the Heinz Nixdorf Recall Study
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:13, s. 853-60
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Living close to high traffic has been linked to subclinical atherosclerosis, however it is not clear, whether fine particulate matter (PM) air pollution or noise, two important traffic-related exposures, are responsible for the association. We investigate the independent associations of long-term exposure to fine PM and road traffic noise with thoracic aortic calcification (TAC), a reliable measure of subclinical atherosclerosis.METHODS AND RESULTS: We used baseline data (2000-2003) from the German Heinz Nixdorf Recall Study, a population-based cohort of 4814 randomly selected participants. We assessed residential long-term exposure to PM with a chemistry transport model, and to road traffic noise using façade levels from noise models as weighted 24 h mean noise (Lden) and night-time noise (Lnight). Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. We used multiple linear regression to estimate associations of environmental exposures with ln(TAC+1), adjusting for each other, individual, and neighbourhood characteristics. In 4238 participants (mean age 60 years, 49.9% male), PM2.5 (aerodynamic diameter ≤2.5 µm) and Lnight are both associated with an increasing TAC-burden of 18.1% (95% CI: 6.6; 30.9%) per 2.4 µg/m(3) PM2.5 and 3.9% (95% CI 0.0; 8.0%) per 5dB(A) Lnight, respectively, in the full model and after mutual adjustment. We did not observe effect measure modification of the PM2.5 association by Lnight or vice versa.CONCLUSION: Long-term exposure to fine PM and night-time traffic noise are both independently associated with subclinical atherosclerosis and may both contribute to the association of traffic proximity with atherosclerosis.
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| 19. |
- Luo, Y. -W, et al.
(författare)
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Database of diazotrophs in global ocean : abundance, biomass and nitrogen fixation rates
- 2012
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 4:1, s. 47-73
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Tidskriftsartikel (refereegranskat)abstract
- Marine N-2 fixing microorganisms, termed di-azotrophs, are a key functional group in marine pelagic ecosystems. The biological fixation of dinitrogen ( N-2) to bioavailable nitrogen provides an important new source of nitrogen for pelagic marine ecosystems and influences primary productivity and organic matter export to the deep ocean. As one of a series of efforts to collect biomass and rates specific to different phytoplankton functional groups, we have constructed a database on diazotrophic organisms in the global pelagic upper ocean by compiling about 12 000 direct field measurements of cyanobacterial diazotroph abundances (based on microscopic cell counts or qPCR assays targeting the nifH genes) and N-2 fixation rates. Biomass conversion factors are estimated based on cell sizes to convert abundance data to diazotrophic biomass. The database is limited spatially, lacking large regions of the ocean especially in the Indian Ocean. The data are approximately log-normal distributed, and large variances exist in most sub-databases with non-zero values differing 5 to 8 orders of magnitude. Reporting the geometric mean and the range of one geometric standard error below and above the geometric mean, the pelagic N-2 fixation rate in the global ocean is estimated to be 62 (52-73) Tg Nyr(-1) and the pelagic diazotrophic biomass in the global ocean is estimated to be 2.1 (1.4-3.1) Tg C from cell counts and to 89 (43-150) Tg C from nifH- based abundances. Reporting the arithmetic mean and one standard error instead, these three global estimates are 140 +/- 9.2 Tg Nyr(-1), 18 +/- 1.8 Tg C and 590 +/- 70 Tg C, respectively. Uncertainties related to biomass conversion factors can change the estimate of geometric mean pelagic diazotrophic biomass in the global ocean by about +/- 70 %. It was recently established that the most commonly applied method used to measure N-2 fixation has underestimated the true rates. As a result, one can expect that future rate measurements will shift the mean N-2 fixation rate upward and may result in significantly higher estimates for the global N-2 fixation. The evolving database can nevertheless be used to study spatial and temporal distributions and variations of marine N-2 fixation, to validate geochemical estimates and to parameterize and validate biogeochemical models, keeping in mind that future rate measurements may rise in the future.
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| 20. |
- Lynch, David K., et al.
(författare)
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NOVA V2362 CYGNI (NOVA CYGNI 2006): SPITZER, SWIFT, AND GROUND-BASED SPECTRAL EVOLUTION
- 2008
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Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 136:number 5, 2008 November, s. 1815-1827
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Tidskriftsartikel (refereegranskat)abstract
- Nova V2362 Cygni has undergone a number of very unusual changes. Ground-based spectroscopy initially revealed a normal sequence of events: the object faded and its near-infrared emission lines gradually shifted to higher excitation conditions until about day 100 when the optical fading reversed and the object slowly brightened. This was accompanied by a rise in the Swift X-ray telescope flux and a sudden shift in excitation of the visible and IR spectrum back to low levels. The new lower excitation spectrum revealed broad line widths and many P-Cygni profiles, all indicative of the ejection of a second shell. Eventually, dust formed, the X-ray brightness—apparently unaffected by dust formation—peaked and then declined, and the object faded at all wavelengths. The Spitzer dust spectra revealed a number of solid-state emission features that, at this time, are not identified.
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| 21. |
- Makelele, I. A., et al.
(författare)
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Conservative N cycling despite high atmospheric deposition in early successional African tropical lowland forests
- 2022
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 477, s. 743-758
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Tidskriftsartikel (refereegranskat)abstract
- Background Across the tropics, the share of secondary versus primary forests is strongly increasing. The high rate of biomass accumulation during this secondary succession relies on the availability of essential nutrients, such as nitrogen (N). Nitrogen primarily limits many young secondary forests in the tropics. However, recent studies have shown that forests of the Congo basin are subject to high inputs of atmospheric N deposition, potentially alleviating this N limitation in early succession. Methods To address this hypothesis, we assessed the N status along a successional gradient of secondary forests in the Congo basin. In a set-up of 18 plots implemented along six successional stages, we quantified year-round N deposition, N leaching, N2O emission and the N flux of litterfall and fine root assimilation. Additionally, we determined the N content and C:N stoichiometry for canopy leaves, fine roots, and litter, as well as delta N-15 of canopy leaves. Results We confirmed that these forests receive high amounts of atmospheric N deposition, with an increasing deposition as forest succession proceeds. Additionally, we noted lower C:N ratios, and higher N leaching losses, N2O emission, and foliar delta N-15 in older secondary forest (60 years). In contrast, higher foliar, litter and root C:N ratios, and lower foliar delta N-15, N leaching, and N2O emission in young (< 20 years) secondary forest were observed. Conclusions Altogether, we show that despite high N deposition, this early forest succession still shows conservative N cycling characteristics, which are likely indicating N limitation early on in secondary forest succession. As secondary succession advances, the N cycle gradually becomes more open.
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| 22. |
- Udell, J. A., et al.
(författare)
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Inhibition of the Renin-Angiotensin System Reduces the Rise in Serum Aldosterone in Acute Coronary Syndrome Patients with Preserved Left Ventricular Function: Observations from the AVANT GARDE-TIMI 43 Trial
- 2013
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:6, s. 959-967
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute coronary syndrome (ACS) activates neurohormonal pathways, including elevations in circulating aldosterone, with deleterious cardiovascular effects. We aimed to determine if early, more complete renin-angiotensin-aldosterone system inhibition (RAASI) in post-ACS patients without ventricular dysfunction or heart failure would result in a graded reduction in aldosterone concentrations.METHODS: We performed serial measurement of serum aldosterone within the Aliskiren and Valsartan to Reduce NT-proBNP via Renin-Angiotensin-Aldosterone-System Blockade (AVANT GARDE)/Thrombolysis in Myocardial Infarction (TIMI) 43 trial, a randomized double-blind, placebo controlled trial of RAASI by valsartan, aliskiren, or both in post-ACS patients with preserved ventricular function but increased natriuretic peptides. Aldosterone was measured at randomization and week 8.RESULTS: Median aldosterone concentrations were comparable across treatment arms at baseline (9.26 ng/dL; interquartile range 7.11-12.76; n = 1073). In the placebo group, there was a significant increase in aldosterone over 8 weeks (19.7% rise, 2.20 (0.36) ng/dL, P < 0.0001) that was significantly reduced across active RAASI therapies (1.36 (0.40) ng/dL with aliskiren; 1.02 (0.37) ng/dL with valsartan; and 0.85 (0.37) ng/dL with combination therapy, P trend = 0.008). Compared to placebo, RAASI monotherapy resulted in a pooled relative absolute aldosterone change of -1.01 (0.45) ng/dL (P = 0.026 vs placebo), and combination therapy resulted in a relative absolute aldosterone change of -1.35 (0.52) ng/dL (P = 0.01 vs placebo). No significant difference in aldosterone concentrations was achieved between dual vs single RAASI (P = 0.47).CONCLUSIONS: In ACS patients with preserved ventricular function but increased natriuretic peptides, serum aldosterone rises over time and is blunted by more complete RAASI. The clinical implications and role for RAASI in this population warrant further investigation.
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| 23. |
- Zangi, HA, et al.
(författare)
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EULAR recommendations for patient education for people with inflammatory arthritis
- 2015
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:6, s. 954-962
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Tidskriftsartikel (refereegranskat)abstract
- The task force aimed to: (1) develop evidence-based recommendations for patient education (PE) for people with inflammatory arthritis, (2) identify the need for further research on PE and (3) determine health professionals’ educational needs in order to provide evidence-based PE.MethodsA multidisciplinary task force, representing 10 European countries, formulated a definition for PE and 10 research questions that guided a systematic literature review (SLR). The results from the SLR were discussed and used as a basis for developing the recommendations, a research agenda and an educational agenda. The recommendations were categorised according to level and strength of evidence graded from A (highest) to D (lowest). Task force members rated their agreement with each recommendation from 0 (total disagreement) to 10 (total agreement).ResultsBased on the SLR and expert opinions, eight recommendations were developed, four with strength A evidence. The recommendations addressed when and by whom PE should be offered, modes and methods of delivery, theoretical framework, outcomes and evaluation. A high level of agreement was achieved for all recommendations (mean range 9.4–9.8). The task force proposed a research agenda and an educational agenda.ConclusionsThe eight evidence-based and expert opinion-based recommendations for PE for people with inflammatory arthritis are intended to provide a core framework for the delivery of PE and training for health professionals in delivering PE across Europe.
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| 24. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 25. |
- Al-Abbadi, Mousa A., et al.
(författare)
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A Proposal for the Performance, Classification, and Reporting of Lymph Node Fine-Needle Aspiration Cytopathology : The Sydney System
- 2020
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Ingår i: Acta Cytologica. - : S. Karger AG. - 0001-5547 .- 1938-2650. ; 64:4, s. 306-322
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The evaluation of lymph nodes (LN) by fine-needle aspiration cytology (FNAC) is routinely used in many institutions but it is not uniformly accepted mainly because of the lack of guidelines and a cytopathological diagnostic classification. A committee of cytopathologists has developed a system of performance, classification, and reporting for LN-FNAC. METHODS: The committee members prepared a document that has circulated among them five times; the final text has been approved by all the participants. It is based on a review of the international literature and on the expertise of the members. The system integrates clinical and imaging data with cytopathological features and ancillary techniques. The project has received the endorsement and patronage of the International Academy of Cytology and the European Federation of the Cytology Societies. RESULTS: Clinical, imaging, and serological data of lymphadenopathies, indications for LN-FNAC, technical procedures, and ancillary techniques are evaluated with specific recommendations. The reporting system includes two diagnostic levels. The first should provide basic diagnostic information and includes five categories: inadequate/insufficient, benign, atypical lymphoid cells of undetermined/uncertain significance, suspicious, and malignant. For each category, specific recommendations are provided. The second diagnostic level, when achievable, should produce the identification of specific benign or malignant entities and additional information by utilizing ancillary testing. CONCLUSION: The authors believe that the introduction of this system for performing and reporting LN-FNAC may improve the quality of the procedure, the report, and the communication between cytopathologists and the clinicians. This system may lead to a greater acceptance and utilization of LN-FNAC and to a better interdisciplinary understanding of the results of this procedure.
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| 26. |
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| 27. |
- Andresen, Louise C., 1974, et al.
(författare)
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Amino acid and N mineralization dynamics in heathland soil after long-term warming and repetitive drought
- 2015
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Ingår i: Soil. - : Copernicus GmbH. - 2199-3971 .- 2199-398X. ; 1:1, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- Monomeric organic nitrogen (N) compounds such as free amino acids (FAAs) are an important resource for both plants and soil microorganisms and a source of ammonium (NH4+) via microbial FAA mineralization. We compared gross FAA dynamics with gross N mineralization in a Dutch heathland soil using a 15N tracing technique. A special focus was made on the effects of climate change factors warming and drought, followed by rewetting. Our aims were to (1) compare FAA mineralization (NH4+ production from FAAs) with gross N mineralization, (2) assess gross FAA production rate (depolymerization) and turnover time relative to gross N mineralization rate, and (3) assess the effects of a 14 years of warming and drought treatment on these rates. The turnover of FAA in the soil was ca. 3 h, which is almost 2 orders of magnitude faster than that of NH4+ (i.e. ca. 4 days). This suggests that FAA is an extensively used resource by soil microorganisms. In control soil (i.e. no climatic treatment), the gross N mineralization rate (10 ± 2.9 μg N g−1 day−1) was 8 times smaller than the total gross FAA production rate of five AAs (alanine, valine, leucine, isoleucine, proline: 127.4 to 25.0 μg N g−1 day−1). Gross FAA mineralization (3.4 ± 0.2 μg N g−1 day−1) contributed 34% to the gross N mineralization rate and is therefore an important component of N mineralization. In the drought treatment, a 6–29% reduction in annual precipitation caused a decrease of gross FAA production by 65% and of gross FAA mineralization by 41% compared to control. On the other hand, gross N mineralization was unaffected by drought, indicating an increased mineralization of other soil organic nitrogen (SON) components. A 0.5–1.5 °C warming did not significantly affect N transformations, even though gross FAA production declined. Overall our results suggest that in heathland soil exposed to droughts a different type of SON pool is mineralized. Furthermore, compared to agricultural soils, FAA mineralization was relatively less important in the investigated heathland. This indicates more complex mineralization dynamics in semi-natural ecosystems.
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| 28. |
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| 29. |
- Andresen, Louise C., 1974, et al.
(författare)
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Depolymerization and mineralization – investigating N availability by a novel 15N tracing model
- 2016
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Ingår i: SOIL. - : Copernicus GmbH. - 2199-398X. ; 2:3, s. 433-442
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Depolymerization of soil organic matter such as proteins and peptides into monomers (e.g. amino acids) is currently thought to be the rate limiting step for N availability in terrestrial N cycles. The mineralization of free amino acids (FAA), liberated by depolymerization of peptides, is an important fraction of the total N mineralization. Accurate assessment 10 of peptide depolymerization and FAA mineralization rates is important in order to gain a better understanding of the N cycle dynamics. Due to the short time span, soil disturbance and unnatural high FAA content during the first few hours after the labelling with the traditional 15N pool dilution experiments, analytical models might overestimate peptide depolymerization rate. In this paper, we present an extended numerical 15N tracing model Ntrace which incorporates the FAA pool and related N processes in order to 1) provide a more robust and coherent estimation of production and mineralization rates of FAAs; 2) 15 and 2) suggest an amino acid N use efficiency (NUEFAA) for soil microbes, which is a more realistic estimation of soil microbial NUE compared to the NUE estimated by analytical methods. We compare analytical and numerical approaches for two forest soils; suggest improvements of the experimental work for future studies; and conclude that: i) FAA mineralization might be as equally an important rate limiting step for gross N mineralization as peptide depolymerization rate is, because about half of all depolymerized peptide N is consecutively being mineralized; and that ii) FAA mineralization and FAA 20 immobilization rates should be used for assessing NUEFAA.
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| 30. |
- Andresen, Louise C., 1974, et al.
(författare)
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Free amino acids in the rhizosphere
- 2014
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Ingår i: 19th European Nitrogen Cycle Meeting. September 10-12th 2014, Gent, Belgium.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 31. |
- Andresen, Louise C., 1974, et al.
(författare)
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Nitrogen dynamics after two years of elevated CO2 in phosphorus limited Eucalyptus woodland
- 2020
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 150, s. 297-312
-
Tidskriftsartikel (refereegranskat)abstract
- It is uncertain how the predicted further rise of atmospheric carbon dioxide (CO2) concentration will affect plant nutrient availability in the future through indirect effects on the gross rates of nitrogen (N) mineralization (production of ammonium) and depolymerization (production of free amino acids) in soil. The response of soil nutrient availability to increasing atmospheric CO2 is particularly important for nutrient poor ecosystems. Within a FACE (Free-Air Carbon dioxide Enrichment) experiment in a native, nutrient poor Eucalyptus woodland (EucFACE) with low soil organic matter (≤ 3%), our results suggested there was no shortage of N. Despite this, microbial N use efficiency was high (c. 90%). The free amino acid (FAA) pool had a fast turnover time (4 h) compared to that of ammonium (NH4+) which was 11 h. Both NH4-N and FAA-N were important N pools; however, protein depolymerization rate was three times faster than gross N mineralization rates, indicating that organic N is directly important in the internal ecosystem N cycle. Hence, the depolymerization was the major provider of plant available N, while the gross N mineralization rate was the constraining factor for inorganic N. After two years of elevated CO2, no major effects on the pools and rates of the soil N cycle were found in spring (November) or at the end of summer (March). The limited response of N pools or N transformation rates to elevated CO2 suggest that N availability was not the limiting factor behind the lack of plant growth response to elevated CO2, previously observed at the site.
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| 32. |
- Andresen, Louise C., 1974, et al.
(författare)
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Patterns of free amino acids in tundra soils reflect mycorrhizal type, shrubification, and warming
- 2022
-
Ingår i: Mycorrhiza. - : Springer Science and Business Media LLC. - 0940-6360 .- 1432-1890. ; 32:3-4, s. 305-313
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Tidskriftsartikel (refereegranskat)abstract
- The soil nitrogen (N) cycle in cold terrestrial ecosystems is slow and organically bound N is an important source of N for plants in these ecosystems. Many plant species can take up free amino acids from these infertile soils, either directly or indirectly via their mycorrhizal fungi. We hypothesized that plant community changes and local plant community differences will alter the soil free amino acid pool and composition; and that long-term warming could enhance this effect. To test this, we studied the composition of extractable free amino acids at five separate heath, meadow, and bog locations in subarctic and alpine Scandinavia, with long-term (13 to 24 years) warming manipulations. The plant communities all included a mixture of ecto-, ericoid-, and arbuscular mycorrhizal plant species. Vegetation dominated by grasses and forbs with arbuscular and non-mycorrhizal associations showed highest soil free amino acid content, distinguishing them from the sites dominated by shrubs with ecto- and ericoid-mycorrhizal associations. Warming increased shrub and decreased moss cover at two sites, and by using redundancy analysis, we found that altered soil free amino acid composition was related to this plant cover change. From this, we conclude that the mycorrhizal type is important in controlling soil N cycling and that expansion of shrubs with ectomycorrhiza (and to some extent ericoid mycorrhiza) can help retain N within the ecosystems by tightening the N cycle.
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| 33. |
- Andresen, Louise C., 1974, et al.
(författare)
-
Simultaneous quantification of depolymerization and mineralization rates by a novel 15N tracing model
- 2016
-
Ingår i: SOIL. - : Copernicus GmbH. - 2199-398X. ; 2, s. 433-442
-
Tidskriftsartikel (refereegranskat)abstract
- The depolymerization of soil organic matter, such as proteins and (oligo-)peptides, into monomers (e.g. amino acids) is currently considered to be the rate-limiting step for nitrogen (N) availability in terrestrial ecosystems. The mineralization of free amino acids (FAAs), liberated by the depolymerization of peptides, is an important fraction of the total mineralization of organic N. Hence, the accurate assessment of peptide depoly- merization and FAA mineralization rates is important in order to gain a better process-based understanding of the soil N cycle. In this paper, we present an extended numerical 15 N tracing model Ntrace , which incorporates the FAA pool and related N processes in order to provide a more robust and simultaneous quantification of de- polymerization and gross mineralization rates of FAAs and soil organic N. We discuss analytical and numerical approaches for two forest soils, suggest improvements of the experimental work for future studies, and conclude that (i) when about half of all depolymerized peptide N is directly mineralized, FAA mineralization can be as important a rate-limiting step for total gross N mineralization as peptide depolymerization rate; (ii) gross FAA mineralization and FAA immobilization rates can be used to develop FAA use efficiency (NUEFAA), which can reveal microbial N or carbon (C) limitation.
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| 34. |
- Bruns, S. B., et al.
(författare)
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Reporting errors and biases in published empirical findings: Evidence from innovation research
- 2019
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Ingår i: Research Policy. - : Elsevier BV. - 0048-7333. ; 48:9
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Tidskriftsartikel (refereegranskat)abstract
- Errors and biases in published results compromise the reliability of empirical research, posing threats to the cumulative research process and to evidence-based decision making. We provide evidence on reporting errors and biases in innovation research. We find that 45% of the articles in our sample contain at least one result for which the provided statistical information is not consistent with reported significance levels. In 25% of the articles, at least one strong reporting error is diagnosed where a statistically non-significant finding becomes significant or vice versa using the common significance threshold of 0.1. The error rate at the test level is very small with 4.0% exhibiting any error and 1.4% showing strong errors. We also find systematically more marginally significant findings compared to marginally non-significant findings at the 0.05 and 0.1 thresholds of statistical significance. These discontinuities indicate the presence of reporting biases. Explorative analysis suggests that discontinuities are related to authors’ affiliations and to a lesser extent the article's rank in the issue and the style of reporting. © 2019 Elsevier B.V.
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| 35. |
- Bräuer, Alois, et al.
(författare)
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Structural snapshots of the minimal PKS system responsible for octaketide biosynthesis
- 2020
-
Ingår i: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 12:8
-
Tidskriftsartikel (refereegranskat)abstract
- The invariable core of a type II polyketide synthase has been characterized using X-ray crystallography, simulations, mutagenesis experiments and functional assays. The characterization of the ternary acyl carrier protein complexes provides a mechanistic understanding of the reactivity and could inform future engineering of this complex biosynthetic machinery. Type II polyketide synthases (PKSs) are multi-enzyme complexes that produce secondary metabolites of medical relevance. Chemical backbones of such polyketides are produced by minimal PKS systems that consist of a malonyl transacylase, an acyl carrier protein and an alpha/beta heterodimeric ketosynthase. Here, we present X-ray structures of all ternary complexes that constitute the minimal PKS system for anthraquinone biosynthesis inPhotorhabdus luminescens. In addition, we characterize this invariable core using molecular simulations, mutagenesis experiments and functional assays. We show that malonylation of the acyl carrier protein is accompanied by major structural rearrangements in the transacylase. Principles of an ongoing chain elongation are derived from the ternary complex with a hexaketide covalently linking the heterodimeric ketosynthase with the acyl carrier protein. Our results for the minimal PKS system provide mechanistic understanding of PKSs and a fundamental basis for engineering PKS pathways for future applications.
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| 36. |
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| 37. |
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| 38. |
- Haupt, Riccardo, et al.
(författare)
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The ‘Survivorship Passport’ for childhood cancer survivors
- 2018
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 102, s. 69-81
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. Method: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors’ organisations within the European Union–funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. Results: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. Conclusions: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS.
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| 39. |
- Islam, Fhokrul, et al.
(författare)
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Systematics of electronic and magnetic properties in the transition metal doped Sb2Te3 quantum anomalous Hall platform
- 2018
-
Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 97:15
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Tidskriftsartikel (refereegranskat)abstract
- The quantum anomalous Hall effect (QAHE) has recently been reported to emerge in magnetically doped topological insulators. Although its general phenomenology is well established, the microscopic origin is far from being properly understood and controlled. Here, we report on a detailed and systematic investigation of transition metal (TM) doped Sb2Te3. By combining density functional theory calculations with complementary experimental techniques, i.e., scanning tunneling microscopy, resonant photoemission, and x-raymagnetic circular dichroism, we provide a complete spectroscopic characterization of both electronic and magnetic properties. Our results reveal that the TM dopants not only affect the magnetic state of the host material, but also significantly alter the electronic structure by generating impurity-derived energy bands. Our findings demonstrate the existence of a delicate interplay between electronic and magnetic properties in TM doped topological insulators. In particular, we find that the fate of the topological surface states critically depends on the specific character of the TM impurity: while V-and Fe-doped Sb2Te3 display resonant impurity states in the vicinity of the Dirac point, Cr and Mn impurities leave the energy gap unaffected. The single-ion magnetic anisotropy energy and easy axis, which control the magnetic gap opening and its stability, are also found to be strongly TM impurity dependent and can vary from in plane to out of plane depending on the impurity and its distance from the surface. Overall, our results provide general guidelines for the realization of a robust QAHE in TM doped Sb2Te3 in the ferromagnetic state.
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| 40. |
- Linnell, Stephanie F., et al.
(författare)
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Enhanced oxygen redox reversibility and capacity retention of titanium-substituted Na-4/7[1/7Ti1/7Mn5/7]O-2 in sodium-ion batteries
- 2022
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 10:18, s. 9941-9953
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Tidskriftsartikel (refereegranskat)abstract
- Anion redox reactions offer a means of enhancing the capacity of layered sodium transition metal oxide positive electrode materials. However, oxygen redox reactions typically show limited reversibility and irreversible structural changes upon cycling, resulting in rapid capacity loss. Here, the Ti-substituted Na-4/7[1/7Ti1/7Mn5/7]O-2 (where represents a transition metal vacancy) is presented as a positive electrode material for sodium-ion batteries. Na-4/7[1/7Ti1/7Mn5/7]O-2 delivers a reversible capacity of 167 mA h g(-1) after 25 cycles at 10 mA g(-1) within the voltage range of 1.6-4.4 V and presents enhanced stability compared with Na-4/7[Mn-1/7(6/7)]O-2 over the voltage range 3.0-4.4 V. The structural and electronic structural changes of this Ti4+ substituted phase are investigated by powder X-ray diffraction, X-ray absorption spectroscopy, electron paramagnetic resonance and Raman spectroscopy, supported by density functional theory calculations. These results show that the Na-4/7[Mn-1/7(6/7)]O-2 structure is maintained between 3.0 and 4.4 V, and the presence of TiO6 octahedra in Na-4/7[1/7Ti1/7Mn5/7]O-2 relieves structural distortions from Jahn-Teller distorted Mn3+O6 between 1.6 and 4.4 V. Furthermore, Ti4+ substitution stabilises the adjacent O 2p orbitals and raises the ionicity of the Mn-O bonds, increasing the operating potential of Na-4/7[1/7Ti1/7Mn5/7]O-2. Thereby providing evidence that the improved electrochemical performance of Na-4/7[1/7Ti1/7Mn5/7]O-2 can be attributed to Ti4+ substitution. This work provides insight and strategies for improving the structural stability and electrochemical performance of sodium layered oxides.
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| 41. |
- Mathieu, C, et al.
(författare)
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Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial
- 2016
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 39:10, s. 1702-1710
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether liraglutide added to treat-to-target insulin improves glycemic control and reduces insulin requirements and body weight in subjects with type 1 diabetes.RESEARCH DESIGN AND METHODSA 52-week, double-blind, treat-to-target trial involving 1,398 adults randomized 3:1 to receive once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or placebo added to insulin.RESULTSHbA1c level was reduced 0.34–0.54% (3.7–5.9 mmol/mol) from a mean baseline of 8.2% (66 mmol/mol), and significantly more for liraglutide 1.8 and 1.2 mg compared with placebo (estimated treatment differences [ETDs]: 1.8 mg liraglutide −0.20% [95% CI −0.32; −0.07]; 1.2 mg liraglutide −0.15% [95% CI −0.27; −0.03]; 0.6 mg liraglutide −0.09% [95% CI −0.21; 0.03]). Insulin doses were reduced by the addition of liraglutide 1.8 and 1.2 mg versus placebo (estimated treatment ratios: 1.8 mg liraglutide 0.92 [95% CI 0.88; 0.96]; 1.2 mg liraglutide 0.95 [95% CI 0.91; 0.99]; 0.6 mg liraglutide 1.00 [95% CI 0.96; 1.04]). Mean body weight was significantly reduced in all liraglutide groups compared with placebo ETDs (1.8 mg liraglutide −4.9 kg [95% CI −5.7; −4.2]; 1.2 mg liraglutide −3.6 kg [95% CI −4.3; −2.8]; 0.6 mg liraglutide −2.2 kg [95% CI −2.9; −1.5]). The rate of symptomatic hypoglycemia increased in all liraglutide groups (estimated rate ratios: 1.8 mg liraglutide 1.31 [95% CI 1.07; 1.59]; 1.2 mg liraglutide 1.27 [95% CI 1.03; 1.55]; 0.6 mg liraglutide 1.17 [95% CI 0.97; 1.43]), and hyperglycemia with ketosis increased significantly for liraglutide 1.8 mg only (event rate ratio 2.22 [95% CI 1.13; 4.34]).CONCLUSIONSLiraglutide added to insulin therapy reduced HbA1c levels, total insulin dose, and body weight in a population that was generally representative of subjects with type 1 diabetes, accompanied by increased rates of symptomatic hypoglycemia and hyperglycemia with ketosis, thereby limiting clinical use in this group.
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| 42. |
- Murray, Alison E., et al.
(författare)
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Roadmap for naming uncultivated Archaea and Bacteria
- 2020
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
-
Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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| 43. |
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| 44. |
- Qian, C., et al.
(författare)
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Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind placebo controlled multicenter study
- 2021
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Ingår i: Clinical Neurology and Neurosurgery. - : Elsevier BV. - 0303-8467. ; 202
-
Tidskriftsartikel (refereegranskat)abstract
- Backround: Venous thromboembolism (VTE) after primary intracerebral hemorrhage (ICH) worsens patient prognosis. Administering low-molecular weight heparins (LMWH) to prevent VTE early (24 h) may increase the risk of hematoma enlargement, whereas administering late (72 h) after onset may decrease its effect on VTE prevention. The authors investigated when it is safe and effective to start LMWH in ICH patients. Methods: In the setting of double blinded, placebo controlled randomization, patients >18 years of age with paretic lower extremity, and admitted to the emergency room within 12 h of the onset of ICH, were randomized into two groups. Patients in the enoxaparin group received 20 mg twice a day 24 h (early) after the onset of ICH and in the placebo group 72 h (late) after onset respectively. Both groups immediately received intermittent pneumatic compression stockings at the ER. Patients were prospectively and routinely screened for VTE and hemorrhagic complications 1 day after entering the study and again before discharge. Results: 139 patients were included for randomization in this study. Only 3 patients developed VTE, 2 in the early enoxaparin group and one in the late enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901), risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not differ significantly between the groups. Conclusion: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after the hemorrhage. Risk of hemorrhage enlargement is not associated with early LMWH treatment. Administering LMWH late did not increase VTEs.
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| 45. |
- Riddell, Michael C, et al.
(författare)
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Exercise management in type 1 diabetes: a consensus statement.
- 2017
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:5, s. 377-390
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a challenging condition to manage for various physiological and behavioural reasons. Regular exercise is important, but management of different forms of physical activity is particularly difficult for both the individual with type 1 diabetes and the health-care provider. People with type 1 diabetes tend to be at least as inactive as the general population, with a large percentage of individuals not maintaining a healthy body mass nor achieving the minimum amount of moderate to vigorous aerobic activity per week. Regular exercise can improve health and wellbeing, and can help individuals to achieve their target lipid profile, body composition, and fitness and glycaemic goals. However, several additional barriers to exercise can exist for a person with diabetes, including fear of hypoglycaemia, loss of glycaemic control, and inadequate knowledge around exercise management. This Review provides an up-to-date consensus on exercise management for individuals with type 1 diabetes who exercise regularly, including glucose targets for safe and effective exercise, and nutritional and insulin dose adjustments to protect against exercise-related glucose excursions.
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| 46. |
- Scutelnic, Adrian, et al.
(författare)
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Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
- 2022
-
Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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| 47. |
- Sherry, Nicole, et al.
(författare)
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Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial
- 2011
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 378:9790, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Background Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve beta-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab. less thanbrgreater than less thanbrgreater thanMethods In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protege study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0.5 U/kg per day and glycated haemoglobin A(1c) (HbA(1c)) of less than 6-5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00385697. less thanbrgreater than less thanbrgreater thanFindings 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19.8% (41/207) in the 14-day full-dose group; 13.7% (14/102) in the 14-day low-dose group; 20.8% (22/106) in the 6-day full-dose group; and 20.4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0.03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group). less thanbrgreater than less thanbrgreater thanInterpretation Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in beta-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.
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