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Sökning: WFRF:(Gabriel Christoph)

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1.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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2.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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3.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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4.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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5.
  • Bott, Lukas Thomas, et al. (författare)
  • Coulomb dissociation of O-16 into He-4 and C-12
  • 2023
  • Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
  • Konferensbidrag (refereegranskat)abstract
    • We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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6.
  • Yi, Chuixiang, et al. (författare)
  • Climate control of terrestrial carbon exchange across biomes and continents
  • 2010
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
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8.
  • Arefalk, Gabriel, et al. (författare)
  • Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART Study
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundBased on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.MethodsData was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.ResultsA large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).ConclusionsIn this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.
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9.
  • Bachmaier, Hans, et al. (författare)
  • Bereal - method for pellet stoves : Field test and round robin
  • 2017
  • Ingår i: European Biomass Conf. Exhib. Proc.. - : ETA-Florence Renewable Energies. ; , s. 642-647
  • Konferensbidrag (refereegranskat)abstract
    • Recent pellet stoves perform excellently under type test conditions. In contrast, typical real life emissions show significantly higher values under usual operational conditions. Consequently, type testing procedures may not account for real life stove operation and, thus, do not allow to distinguish between low- and high-tech appliances. The EU-project beReal aimed at the development of a testing method for pellet stoves that reflects real life operations better and to support innovative pellet stoves that perform well under typical operational conditions. Based on an online survey and field observations, an advanced real life testing procedure for pellet stoves was established reflecting real life user behavior, e.g. regarding different load levels and the ignition phase. A field test was designed at the end of the project to demonstrate the applicability and practical relevance. The field test proved that emission values for beReal at the test stand and in the field stay within the same range. A Round Robin test proved the repeatability and reproducibility of the beReal testing procedure. The beReal method can be reproduced with the same statistical variability or performed even better than the type testing method with exception of PM between different laboratories. © 2017, ETA-Florence Renewable Energies. All rights reserved.
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10.
  • Baumeister, Hannah, et al. (författare)
  • A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
  • Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
  • Tidskriftsartikel (refereegranskat)abstract
    • Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
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11.
  • Birney, Ewan, et al. (författare)
  • Prepublication data sharing
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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12.
  • Bui, An H., et al. (författare)
  • Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial
  • 2016
  • Ingår i: Circulation. - 1941-3149 .- 1941-3084. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background- Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. Methods and Results- In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by approximate to 5 months after ACS. Conclusions- NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event.
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13.
  • Christiansen, Evald H, et al. (författare)
  • Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI.
  • 2017
  • Ingår i: The New England journal of medicine. - : Massachussetts Medical Society. - 1533-4406 .- 0028-4793. ; 376:19, s. 1813-1823
  • Tidskriftsartikel (refereegranskat)abstract
    • The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events.We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure.A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], -1.5 to 2.8; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure.Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months. (Funded by Philips Volcano; iFR SWEDEHEART ClinicalTrials.gov number, NCT02166736 .).
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14.
  • Dekkers, Koen, et al. (författare)
  • An online atlas of human plasma metabolite signatures of gut microbiome composition.
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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16.
  • Demurtas, Jacopo, et al. (författare)
  • Physical Activity and Exercise in Mild Cognitive Impairment and Dementia : An Umbrella Review of Intervention and Observational Studies
  • 2020
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 21:10, s. 1415-1422
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: The aim of this umbrella review was to determine the effect of physical activity/exercise on improving cognitive and noncognitive outcomes in people with MCI (mild cognitive impairment) and dementia.Design: Umbrella review of systematic reviews (SR), with or without meta-analyses (MAs), of randomized controlled trials (RCTs) and observational studies.Settings and Participants: People with MCI or dementia, confirmed through validated assessment measures. Any form of physical activity/exercise was included. As controls, we included participants not following any prespecified physical activity/exercise intervention or following the same standard protocol with the intervention group.Methods: The protocol was registered in PROSPERO (CDR 164197). Major databases were searched until December 31, 2019. The certainty of evidence of statistically significant outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. SRs' findings, without a formal MA, were reported descriptively.Results: Among 1160 articles initially evaluated, 27 SRs (all of RCTs, 9 without MA) for a total of 28,205 participants with MCI/dementia were included. In patients with MCI, mind-body intervention (standardized mean difference [SMD] = 0.36; 95% confidence intervals [CI] 0.20-0.52; low certainty) and mixed physical activity interventions (SMD = 0.30; 95% CI 0.11-0.49; moderate certainty) had a small effect on global cognition, whereas resistance training (SMD = 0.80; 95% CI 0.29-1.31; very low certainty) had a large effect on global cognition. In people affected by dementia, physical activity/exercise was effective in improving global cognition in Alzheimer disease (SMD = 1.10; 95% CI 0.65-1.64; very low certainty) and in all types of dementia (SMD = 0.48; 95% CI 0.22-0.74; low certainty). Finally, physical activity/exercise improved noncognitive outcomes in people with dementia including falls, and neuropsychiatric symptoms.Conclusions and Implications: Supported by very low-to-moderate certainty of evidence, physical activity/exercise has a positive effect on several cognitive and noncognitive outcomes in people with MCI and dementia, but RCTs, with low risk of bias/confounding, are still needed to confirm these relationships.
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17.
  • Dura, Alexandru, et al. (författare)
  • Clog : A Declarative Language for C Static Code Checkers
  • 2024
  • Ingår i: CC 2024 - Proceedings of the 33rd ACM SIGPLAN International Conference on Compiler Construction. - 9798400705076 ; , s. 186-197
  • Konferensbidrag (refereegranskat)abstract
    • We present Clog, a declarative language for describing static code checkers for C. Unlike other extensible state-of-the-art checker frameworks, Clog enables powerful interprocedural checkers without exposing the underlying program representation: Clog checkers consist of Datalog-style recursive rules that access the program under analysis via syntactic pattern matching and control flow edges only. We have implemented Clog on top of Clang, using a custom Datalog evaluation strategy that piggy-backs on Clang’s AST matching facilities while working around Clang’s limitations to achieve our design goal of representation independence. Our experiments demonstrate that Clog can concisely express a wide variety of checkers for different security vulnerabilities, with performance that is similar to Clang’s own analyses and highly competitive on real-world programs.
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18.
  • Ernst, Chantal, et al. (författare)
  • Direct Salmonella injection into enteroid cells allows the study of host-pathogen interactions in the cytosol with high spatiotemporal resolution
  • 2024
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 22:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Intestinal epithelial cells (IECs) play pivotal roles in nutrient uptake and in the protection against gut microorganisms. However, certain enteric pathogens, such as Salmonella enterica serovar Typhimurium (S. Tm), can invade IECs by employing flagella and type III secretion systems (T3SSs) with cognate effector proteins and exploit IECs as a replicative niche. Detection of flagella or T3SS proteins by IECs results in rapid host cell responses, i.e., the activation of inflammasomes. Here, we introduce a single-cell manipulation technology based on fluidic force microscopy (FluidFM) that enables direct bacteria delivery into the cytosol of single IECs within a murine enteroid monolayer. This approach allows to specifically study pathogen-host cell interactions in the cytosol uncoupled from preceding events such as docking, initiation of uptake, or vacuole escape. Consistent with current understanding, we show using a live-cell inflammasome reporter that exposure of the IEC cytosol to S. Tm induces NAIP/NLRC4 inflammasomes via its known ligands flagellin and T3SS rod and needle. Injected S. Tm mutants devoid of these invasion-relevant ligands were able to grow in the cytosol of IECs despite the absence of T3SS functions, suggesting that, in the absence of NAIP/NLRC4 inflammasome activation and the ensuing cell death, no effector-mediated host cell manipulation is required to render the epithelial cytosol growth-permissive for S. Tm. Overall, the experimental system to introduce S. Tm into single enteroid cells enables investigations into the molecular basis governing host-pathogen interactions in the cytosol with high spatiotemporal resolution.
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19.
  • Goodwin, Christopher M., 1989-, et al. (författare)
  • Operando Probing of the Surface Chemistry During the Haber-Bosch Process
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 282-286
  • Tidskriftsartikel (refereegranskat)abstract
    • The Haber-Bosch process produces NH3 from N2 and H21,2, typically with Fe and Ru3.  HB has been proposed as the most important scientific invention in the 20th century4. The chemical state during reaction has been proposed as oxides5, nitrides2, metallic, or surface nitride6. The proposed rate-limiting step has been the dissociation of  N27–9, reaction of adsorbed nitrogen10, or desorption of NH311. Due to the vacuum requirement for surface-sensitive techniques, studies at reaction conditions are limited to theory computations12–14. We determined the surface composition, during NH3 production, at pressures up to 1 bar and temperatures as high as 723 K on flat, stepped Fe, and stepped Ru single crystal surfaces using operando X-ray Photoelectron Spectroscopy15. We found that all surfaces remain metallic. On Fe only a small amount of adsorbed N remains, yet Ru’s surface is almost adsorbate free. At 523 K, high amines (NHx) coverages appear on the stepped Fe surface. The results show that the rate-limiting step on Ru is always N2 dissociation. Still, on Fe the hydrogenation step involving adsorbed N atoms is essential for the total rate, as predicted by theory13. If the temperature is lowered on Fe, the rate-limiting steps switch and become surface species’ hydrogenation.
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20.
  • Grossmann, Igor, et al. (författare)
  • Insights into the accuracy of social scientists' forecasts of societal change
  • 2023
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
  • Tidskriftsartikel (refereegranskat)abstract
    • How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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21.
  • Huber, Kurt, et al. (författare)
  • Antiplatelet and anticoagulation agents in acute coronary syndromes : What is the current status and what does the future hold?
  • 2014
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:5, s. 611-621
  • Tidskriftsartikel (refereegranskat)abstract
    • Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y(12) receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.
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22.
  • Johansson, Åsa, et al. (författare)
  • Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome
  • 2016
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:7, s. 1447-1456
  • Tidskriftsartikel (refereegranskat)abstract
    • N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of mortality in coronary artery disease and is widely employed as a prognostic biomarker. However, a causal relationship between NT-proBNP and clinical endpoints has not been established. We have performed a genome-wide association and Mendelian randomization study of NT-proBNP. We used a discovery set of 3740 patients from the PLATelet inhibition and patient Outcomes (PLATO) trial, which enrolled 18 624 patients with acute coronary syndrome (ACS). A further set of 5492 patients, from the same trial, was used for replication. Genetic variants at two novel loci (SLC39A8 and POC1B/GALNT4) were associated with NT-proBNP levels and replicated together with the previously known NPPB locus. The most significant SNP (rs198389, pooled P = 1.07 x 10(-15)) in NPPB interrupts an E-box consensus motif in the gene promoter. The association in SLC39A8 is driven by a deleterious variant (rs13107325, pooled P = 5.99 x 10(-10)), whereas the most significant SNP in POC1B/GALNT4 (rs11105306, pooled P = 1.02 x 10(-16)) is intronic. The SLC39A8 SNP was associated with higher risk of cardiovascular (CV) death (HR = 1.39, 95% CI: 1.08-1.79, P = 0.0095), but the other loci were not associated with clinical endpoints. We have identified two novel loci to be associated with NT-proBNP in patients with ACS. Only the SLC39A8 variant, but not the NPPB variant, was associated with a clinical endpoint. Due to pleotropic effects of SLC39A8, these results do not suggest that NT-proBNP levels have a direct effect on mortality in ACS patients. PLATO Clinical Trial Registration: ; NCT00391872.
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23.
  • Johansson, Åsa, et al. (författare)
  • NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO)
  • 2015
  • Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 8:3, s. 498-506
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined. Methods and Results Baseline plasma IL-18 levels were measured in 16633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (IL18, NLRC4, and MROH6) were identified (P<3.15x10(-8)) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum P=6.99x10(-72)). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in NLRC4 is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort. Conclusions Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (IL18) or close to genes that are involved in procaspase-1 activation (NLRC4 and CARD16, CARD17, and CARD18). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.
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24.
  • Jones, Benedict C, et al. (författare)
  • To which world regions does the valence-dominance model of social perception apply?
  • 2021
  • Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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25.
  • Kamundala, Gabriel (creator_code:cre_t)
  • Kamituga I Digital Gold
  • 2022
  • Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
    • This is one exhibition room within the larger "Planet Digital" exhibition (https://www.planetdigital.ch/en) hosted by the Museum für Gestaltung, Zürich, Switzerland (20.2.2022 to 6.6.2022).
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26.
  • Klauser, Franziska, et al. (författare)
  • Effect of Oxidizing Honeycomb Catalysts Integrated in a Firewood Room Heater on Gaseous and Particulate Emissions, Including Polycyclic Aromatic Hydrocarbons (PAHs)
  • 2018
  • Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 32:11, s. 11876-11886
  • Tidskriftsartikel (refereegranskat)abstract
    • Residential wood combustion is linked to a significant extent of emissions of polycyclic aromatic hydrocarbons (PAHs), which represent highly toxic, semivolatile pollutants. The use of catalysts reveals an effective measure to reduce emissions, especially gaseous flue gas compounds (carbon monoxide (CO) and organic gaseous compounds (OGC)). Their effect on toxicologically relevant PAHs is not clarified yet. In this work, the impact of two commercially available oxidizing platinum/palladium catalysts with either metallic or ceramic honeycomb carriers was examined under real-life operating conditions of a firewood room heater. The catalytic effect on CO and OGC, total suspended particles (TSP), total carbon (TC), elemental carbon (EC), organic carbon (OC), and 19 different PAHs, including 16 EPA PAHs (PAHs defined by the Environmental Protection Agency as priority pollutants) was evaluated by parallel measurements of catalytically treated and untreated flue gas from firewood combustion. The metallic catalyst, having a reaction surface that is 3.5 times greater than the ceramic catalyst, leads to a more-pronounced impact. Both types, the ceramic and the metallic catalyst, led to distinct reductions of CO (-69%, -88%) and OGC (-27%, -39%). In the test with the metallic catalyst, TSP increased (+17%) and PAHs were clearly reduced (-63%). This reduction was exclusively related to the higher-molecular-weight PAHs, such as the particularly toxic benzo(a)pyrene. Carbonaceous fractions (TC, EC, and OC) were not affected significantly. The toxicity of emissions arising from EPA PAHs can be clearly reduced by catalytic treatment. Moreover, the increase of TSP opens new questions, which must be clarified before the investigated catalysts are recommended as suitable secondary measure for emission abatement.
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27.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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28.
  • Kreisz, Philipp, et al. (författare)
  • S1 basic leucine zipper transcription factors shape plant architecture by controlling C/N partitioning to apical and lateral organs
  • 2024
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 121:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Plants tightly control growth of their lateral organs, which led to the concept of apical dominance. However, outgrowth of the dormant lateral primordia is sensitive to the plant's nutritional status, resulting in an immense plasticity in plant architecture. While the impact of hormonal regulation on apical dominance is well characterized, the prime importance of sugar signaling to unleash lateral organ formation has just recently emerged. Here, we aimed to identify transcriptional regulators, which control the trade-off between growth of apical versus lateral organs. Making use of locally inducible gain-of-function as well as single and higher-order loss-of-function approaches of the sugar-responsive S1-basic-leucine-zipper (S1-bZIP) transcription factors, we disclosed their largely redundant function in establishing apical growth dominance. Consistently, comprehensive phenotypical and analytical studies of S1-bZIP mutants show a clear shift of sugar and organic nitrogen (N) allocation from apical to lateral organs, coinciding with strong lateral organ outgrowth. Tissue-specific transcriptomics reveal specific clade III SWEET sugar transporters, crucial for long-distance sugar transport to apical sinks and the glutaminase GLUTAMINE AMIDO-TRANSFERASE 1_2.1, involved in N homeostasis, as direct S1-bZIP targets, linking the architectural and metabolic mutant phenotypes to downstream gene regulation. Based on these results, we propose that S1-bZIPs control carbohydrate (C) partitioning from source leaves to apical organs and tune systemic N supply to restrict lateral organ formation by C/N depletion. Knowledge of the underlying mechanisms controlling plant C/N partitioning is of pivotal importance for breeding strategies to generate plants with desired architectural and nutritional characteristics.
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29.
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30.
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31.
  • Lindholm, Daniel, et al. (författare)
  • Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization : results from the PLATO trial
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:31, s. 2083-2093
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown. We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization. Methods and results We performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding. Conclusion In patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.
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32.
  • Lopes, Renato D., et al. (författare)
  • Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy
  • 2017
  • Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:22, s. 2980-2987
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received >= 1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was >= 4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-termmorbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.
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33.
  • Lömker, Patrick, et al. (författare)
  • Operando XPS and SXRD study of the Fischer-Tropsch reaction on flat and stepped Co at up to around 1 bar
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The Fischer-Tropsch catalytic reaction on Co has still several unknows regarding the surface chemical state of the catalyst and presence of various adsorbed intermediates appearing under operando conditions. Here, we report an operando X-ray photoelectron spectroscopy study of the flat Co(0001) and stepped Co(10-14) model catalyst surfaces during Fischer-Tropsch synthesis conditions at 150 mbar – 975 mbar pressure and 406 K – 548 K temperature in a H2/CO gas mixture using X-ray photoelectron spectroscopy as well surface X-ray diffraction. We observe that the Co surface remains metallic at all conditions with only adsorbed species. There are a number of different intermediates on the surface such as adsorbed CO in only on-top position, C/-CH intermediates, -CH2- species and various longer hydrocarbon molecules. The coverage of the hydrocarbon species decreases with increasing temperature but increase strongly with pressure. The stepped surface shows a significant increase in adsorbed hydrocarbon species which is a clear indication of higher reactivity. There is no observation of any CHO or CH2O species indicating a direct CO dissociation pathway and that to our observation only hydrocarbon species participate in the chain growth. The relative high coverage of CO that is almost constant for the various conditions points to that CO dissociation is one of the rate-limiting steps. The rapid increase in the coverage of hydrocarbon species at high pressure conditions and on the stepped surface further indicates that the final hydrogen induced termination step is also rate-limiting. By following the time dependence of the C 1s region with rapid change in the flow of reactants, we demonstrate that the surface species are highly dynamic resulting in delays in reaching steady-state conditions. 
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34.
  • Milosevic, Jelena, et al. (författare)
  • PPM1D is a neuroblastoma oncogene and therapeutic target in childhood neural tumors
  • 2020
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Majority of cancers harbor alterations of the tumor suppressor TP53. However, childhood cancers, including unfavorable neuroblastoma, often lack TP53 mutations despite frequent loss of p53 function, suggesting alternative p53 inactivating mechanisms.Here we show that p53-regulating PPM1D at chromosome 17q22.3 is linked to aggressive tumors and poor prognosis in neuroblastoma. We identified that WIP1-phosphatase encoded by PPM1D, is activated by frequent segmental 17q-gain further accumulated during clonal evolution, gene-amplifications, gene-fusions or gain-of-function somatic and germline mutations. Pharmacological and genetic manipulation established WIP1 as a druggable target in neuroblastoma. Genome-scale CRISPR-Cas9 screening demonstrated PPM1D genetic dependency in TP53 wild-type neuroblastoma cell lines, and shRNA PPM1D knockdown significantly delayed in vivo tumor formation. Establishing a transgenic mouse model overexpressing PPM1D showed that these mice develop cancers phenotypically and genetically similar to tumors arising in mice with dysfunctional p53 when subjected to low-dose irradiation. Tumors include T-cell lymphomas harboring Notch1-mutations, Pten-deletions and p53-accumulation, adenocarcinomas and PHOX2B-expressing neuroblastomas establishing PPM1D as a bona fide oncogene in wtTP53 cancer and childhood neuroblastoma. Pharmacological inhibition of WIP1 suppressed the growth of neural tumors in nude mice proposing WIP1 as a therapeutic target in neural childhood tumors.
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35.
  • Motos, Ghislain, et al. (författare)
  • Aerosol and dynamical contributions to cloud droplet formation in Arctic low-level clouds
  • 2023
  • Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 23:21, s. 13941-13956
  • Tidskriftsartikel (refereegranskat)abstract
    • The Arctic is one of the most rapidly warming regions of the globe. Low-level clouds and fog modify the energy transfer from and to space and play a key role in the observed strong Arctic surface warming, a phenomenon commonly termed “Arctic amplification”. The response of low-level clouds to changing aerosol characteristics throughout the year is therefore an important driver of Arctic change that currently lacks sufficient constraints. As such, during the NASCENT campaign (Ny-Ålesund AeroSol Cloud ExperimeNT) extending over a full year from October 2019 to October 2020, microphysical properties of aerosols and clouds were studied at the Zeppelin station (475 m a.s.l.), Ny-Ålesund, Svalbard, Norway. Particle number size distributions obtained from differential mobility particle sizers as well as chemical composition derived from filter samples and an aerosol chemical speciation monitor were analyzed together with meteorological data, in particular vertical wind velocity. The results were used as input to a state-of-the-art cloud droplet formation parameterization to investigate the particle sizes that can activate to cloud droplets, the levels of supersaturation that can develop, the droplet susceptibility to aerosol and the role of vertical velocity. We evaluate the parameterization and the droplet numbers calculated through a droplet closure with in-cloud in situ measurements taken during nine flights over 4 d. A remarkable finding is that, for the clouds sampled in situ, closure is successful in mixed-phase cloud conditions regardless of the cloud glaciation fraction. This suggests that ice production through ice–ice collisions or droplet shattering may have explained the high ice fraction, as opposed to rime splintering that would have significantly reduced the cloud droplet number below levels predicted by warm-cloud activation theory. We also show that pristine-like conditions during fall led to clouds that formed over an aerosol-limited regime, with high levels of supersaturation (generally around 1 %, although highly variable) that activate particles smaller than 20 nm in diameter. Clouds formed in the same regime in late spring and summer, but aerosol activation diameters were much larger due to lower cloud supersaturations (ca. 0.5 %) that develop because of higher aerosol concentrations and lower vertical velocities. The contribution of new particle formation to cloud formation was therefore strongly limited, at least until these newly formed particles started growing. However, clouds forming during the Arctic haze period (winter and early spring) can be limited by updraft velocity, although rarely, with supersaturation levels dropping below 0.1 % and generally activating larger particles (20 to 200 nm), including pollution transported over a long range. The relationship between updraft velocity and the limiting cloud droplet number agrees with previous observations of various types of clouds worldwide, which supports the universality of this relationship.
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36.
  • Novik, Bengt, et al. (författare)
  • Association of Mesh and Fixation Options with Reoperation Risk after Laparoscopic Groin Hernia Surgery : A Swedish Hernia Registry Study of 25,190 Totally Extraperitoneal and Transabdominal Preperitoneal Repairs.
  • 2022
  • Ingår i: Journal of the American College of Surgeons. - 1072-7515 .- 1879-1190. ; 234:3, s. 311-325
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: International guidelines concerning mesh and mesh fixation options in laparoscopic totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) groin hernia repair are based on studies focusing on either mesh or fixation. We hypothesized that the value of such recommendations is limited by lacking knowledge on how mesh and fixation interact. The current registry-based nationwide cohort study compared different mesh/fixation combinations for relative risks for reoperation after TEP and TAPP groin hernia repair.STUDY DESIGN: All TEP and TAPP registered in the Swedish Hernia Registry 2005 to 2017 with standard polypropylene (StdPPM) or lightweight (LWM) flat mesh, having tack, fibrin glue, or no fixation, were included. The endpoint was reoperation due to recurrence as of December 31, 2018. Multivariable Cox regression rendered relative risk differences between the exposures, expressed as hazard ratios (HR) with 95% CIs.RESULTS: Of 25,190 repairs, 924 (3.7%) were later reoperated for recurrence. The lowest, mutually equivalent, reoperation risks were associated with StdPPM without fixation (HR 1), StdPPM with metal tacks (HR 0.8, CI 0.4 to 1.4), StdPPM with fibrin glue (HR 1.1, CI 0.7 to 1.6), and LWM with fibrin glue (HR 1.2, CI 0.97 to 1.6). Except for with fibrin glue, LWM correlated with increased risk, whether affixed with metal (HR 1.7, CI 1.1 to 2.7), or absorbable tacks (HR 2.4, CI 1.8 to 3.1), or deployed without fixation (HR 2.0, CI 1.6 to 2.6).CONCLUSIONS: With StdPPM, neither mechanical nor glue fixation seemed to improve outcomes. Thus, for this mesh category, we recommend nonfixation. With LWM, we recommend fibrin glue fixation, which was the only LWM alternative on par with nonaffixed StdPPM.
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37.
  • Nugroho, Ferry, 1986, et al. (författare)
  • Inverse designed plasmonic metasurface with parts per billion optical hydrogen detection
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasmonic sensors rely on optical resonances in metal nanoparticles and are typically limited by their broad spectral features. This constraint is particularly taxing for optical hydrogen sensors, in which hydrogen is absorbed inside optically-lossy Pd nanostructures and for which state-of-the-art detection limits are only at the low parts-per-million (ppm) range. Here, we overcome this limitation by inversely designing a plasmonic metasurface based on a periodic array of Pd nanoparticles. Guided by a particle swarm optimization algorithm, we numerically identify and experimentally demonstrate a sensor with an optimal balance between a narrow spectral linewidth and a large field enhancement inside the nanoparticles, enabling a measured hydrogen detection limit of 250 parts-per-billion (ppb). Our work significantly improves current plasmonic hydrogen sensor capabilities and, in a broader context, highlights the power of inverse design of plasmonic metasurfaces for ultrasensitive optical (gas) detection.
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38.
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39.
  • Ohlsson, Gabriel, 1982, et al. (författare)
  • A nanocell for quartz crystal microbalance and quartz crystal microbalance with dissipation-monitoring sensing
  • 2009
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 80:8, s. 083905-
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel device for nanometer-confinement of soft matter in one dimension (1D) is presented. This nanocell, with very large (up to 10(6):1) cell-radius to cell-height ratio, is tailored as an accessory for quartz crystal microbalance (QCM) and QCM with dissipation-monitoring (QCM-D). sensing to study internal and interfacial energy dissipation phenomena in highly confined (in 1D) soft matter and fluid films (patent pending). The cell consists of two macroscopic plates (diameter of 9 mm), a top (the "lid") and a bottom (the QCM-D sensor), separated by appropriate spacers with heights ranging from below 100 nm up to 10 mu m. The surfaces of both the lid and the bottom plate can be mechanically or/and chemically modified, prior to cell assembly, in order to tailor desired interfacial properties for the experiment. The cell is mounted on a standard QCM-D sensor, an AT-cut quartz crystal (the quartz crystal is cut at an angle of 35 degrees from its ZX-plane), forming the bottom plate. We illustrate theoretically and experimentally, as application examples, the use of this device for studies of dynamic mass loading and internal energy dissipation processes in thin films of ethylene glycol respective thin liquid crystal films around the nematic-isotropic phase transition.
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40.
  • Ohman, E. Magnus, et al. (författare)
  • 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
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10081, s. 1799-1808
  • 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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41.
  • Oldgren, Jonas, et al. (författare)
  • Risks for Stroke, Bleeding, and Death in Patients With Atrial Fibrillation Receiving Dabigatran or Warfarin in Relation to the CHADS(2) Score : A Subgroup Analysis of the RE-LY Trial
  • 2011
  • Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 155:10, s. 660-667
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: CHADS(2) is a simple, validated risk score for predicting the risk for stroke in patients with atrial fibrillation not treated with anticoagulants. There are sparse data on the risk for thrombotic and bleeding complications according to the CHADS(2) score in patients receiving anticoagulant therapy.Objective: To evaluate the prognostic importance of CHADS(2) risk score in patients with atrial fibrillation receiving oral anticoagulants, including the vitamin K antagonist warfarin and the direct thrombin inhibitor dabigatran.Design: Subgroup analysis of a randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00262600)Setting: Multinational study setting.Patients: 18 112 patients with atrial fibrillation who were receiving oral anticoagulants.Measurements: Baseline CHADS(2) score, which assigns 1 point each for congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and 2 points for stroke.Results: Distribution of CHADS(2) scores were as follows: 0 to 1-5775 patients; 2-6455 patients; and 3 to 6-5882 patients. Annual rates of the primary outcome of stroke or systemic embolism among all participants were 0.93% in patients with a CHADS(2) score of 0 to 1, 1.22% in those with a score of 2, and 2.24% in those with a score of 3 to 6. Annual rates of other outcomes among all participants with CHADS(2) scores of 0 to 1, 2, and 3 to 6, respectively, were the following: major bleeding, 2.26%, 3.11%, and 4.42%; intracranial bleeding, 0.31%, 0.40%, and 0.61%; and vascular mortality, 1.35%, 2.39%, and 3.68% (P < 0.001 for all comparisons). Rates of stroke or systemic embolism, major and intracranial bleeding, and vascular and total mortality each increased in the warfarin and dabigatran groups as CHADS(2) score increased. The rates of stroke or systemic embolism with dabigatran, 150 mg twice daily, and of intracranial bleeding with dabigatran, 150 mg or 110 mg twice daily, were lower than those with warfarin; there was no significant heterogeneity in subgroups defined by CHADS(2) scores.Limitation: These analyses were not prespecified and should be deemed exploratory.Conclusion: Higher CHADS(2) scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants.
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42.
  • Povsic, Thomas J., et al. (författare)
  • A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome : The design of the GEMINI-ACS-1 phase II study
  • 2016
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 174, s. 120-128
  • Tidskriftsartikel (refereegranskat)abstract
    • Dual antiplatelet therapy (DAPT), the combination of aspirin and a P2Y12 inhibitor, given for 12 months remains the standard of care after presentation with acute coronary syndrome (ACS) because it has been shown to be associated with a significant reduction in ischemic events compared with aspirin monotherapy. The factor Xa inhibitor rivaroxaban was shown to be associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, and stroke, and resulted in a nominal reduction in cardiovascular death, when added to background DAPT in the ATLAS ACS 2-TIMI 51 trial; however, there was excessive bleeding with this "triple-therapy" approach. The combination of rivaroxaban with P2Y12 inhibition in a "dual-pathway" approach may be an effective therapeutic regimen for the treatment of ACS, given the known importance of P2Y12 inhibition after stenting and intriguing data that the combination of an anticoagulant with clopidogrel after stenting in patients with atrial fibrillation appears an attractive option to this patient population. GEMINI-ACS-1 is a prospective, randomized, double-dummy, double-blind, active-controlled trial that will assess the safety of dual antithrombotic therapy (rivaroxaban [2.5 mg twice daily] + P2Y12 inhibitor) as compared with DAPT (aspirin [100 mg] + P2Y12 inhibitor) within 10 days of an ACS event in 3,000 patients. Patients will be randomized in a 1: 1 ratio stratified by intended P2Y12 inhibitor use (clopidogrel 75 mg daily or ticagrelor 90 mg twice daily), with 1500 patients expected in each P2Y12 inhibitor strata. The primary end point is Thrombolysis in Myocardial Infarction clinically significant bleeding (major, minor, or requiring medical attention). The exploratory efficacy determination will be a composite of cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis. GEMINI-ACS-1 will assess the safety and feasibility of dual antithrombotic therapy with rivaroxaban and a P2Y12 inhibitor compared with conventional DAPT for the treatment for patients with recent ACS.
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43.
  • Povsic, Thomas J., et al. (författare)
  • P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes
  • 2019
  • Ingår i: JAMA cardiology. - : AMER MEDICAL ASSOC. - 2380-6583 .- 2380-6591. ; 4:7, s. 680-684
  • 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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44.
  • Scholl, Ute I, et al. (författare)
  • Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:9, s. 1050-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • Adrenal aldosterone-producing adenomas (APAs) constitutively produce the salt-retaining hormone aldosterone and are a common cause of severe hypertension. Recurrent mutations in the potassium channel gene KCNJ5 that result in cell depolarization and Ca2+ influx cause ~40% of these tumors1. We identified 5 somatic mutations (4 altering Gly403 and 1 altering Ile770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 APAs without mutated KCNJ5. The altered residues lie in the S6 segments that line the channel pore. Both alterations result in channel activation at less depolarized potentials; Gly403 alterations also impair channel inactivation. These effects are inferred to cause increased Ca2+ influx, which is a sufficient stimulus for aldosterone production and cell proliferation in adrenal glomerulosa2. We also identified de novo germline mutations at identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities. These findings implicate gain-of-function Ca2+ channel mutations in APAs and primary aldosteronism.
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45.
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46.
  • Schweiker, Marcel, et al. (författare)
  • Evaluating assumptions of scales for subjective assessment of thermal environments – Do laypersons perceive them the way, we researchers believe?
  • 2020
  • Ingår i: Energy and Buildings. - : Elsevier BV. - 0378-7788. ; 211
  • Tidskriftsartikel (refereegranskat)abstract
    • People's subjective response to any thermal environment is commonly investigated by using rating scales describing the degree of thermal sensation, comfort, and acceptability. Subsequent analyses of results collected in this way rely on the assumption that specific distances between verbal anchors placed on the scale exist and that relationships between verbal anchors from different dimensions that are assessed (e.g. thermal sensation and comfort) do not change. Another inherent assumption is that such scales are independent of the context in which they are used (climate zone, season, etc.). Despite their use worldwide, there is indication that contextual differences influence the way the scales are perceived and therefore question the reliability of the scales’ interpretation. To address this issue, a large international collaborative questionnaire study was conducted in 26 countries, using 21 different languages, which led to a dataset of 8225 questionnaires. Results, analysed by means of robust statistical techniques, revealed that only a subset of the responses are in accordance with the mentioned assumptions. Significant differences appeared between groups of participants in their perception of the scales, both in relation to distances of the anchors and relationships between scales. It was also found that respondents’ interpretations of scales changed with contextual factors, such as climate, season, and language. These findings highlight the need to carefully consider context-dependent factors in interpreting and reporting results from thermal comfort studies or post-occupancy evaluations, as well as to revisit the use of rating scales and the analysis methods used in thermal comfort studies to improve their reliability.
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47.
  • Schweiker, Marcel, et al. (författare)
  • The Scales Project, a cross-national dataset on the interpretation of thermal perception scales
  • 2019
  • Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Thermal discomfort is one of the main triggers for occupants' interactions with components of the built environment such as adjustments of thermostats and/or opening windows and strongly related to the energy use in buildings. Understanding causes for thermal (dis-)comfort is crucial for design and operation of any type of building. The assessment of human thermal perception through rating scales, for example in post-occupancy studies, has been applied for several decades; however, long-existing assumptions related to these rating scales had been questioned by several researchers. The aim of this study was to gain deeper knowledge on contextual influences on the interpretation of thermal perception scales and their verbal anchors by survey participants. A questionnaire was designed and consequently applied in 21 language versions. These surveys were conducted in 57 cities in 30 countries resulting in a dataset containing responses from 8225 participants. The database offers potential for further analysis in the areas of building design and operation, psycho-physical relationships between human perception and the built environment, and linguistic analyses.
  •  
48.
  • Shipilin, Mikhail, et al. (författare)
  • In Situ Surface-Sensitive Investigation of Multiple Carbon Phases on Fe(110) in the Fischer-Tropsch Synthesis
  • 2022
  • Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 12:13, s. 7609-7621
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbide formation on iron-based catalysts is an integral and, arguably, the most important part of the Fischer–Tropsch synthesis process, converting CO and H2 into synthetic fuels and numerous valuable chemicals. Here, we report an in situ surface-sensitive study of the effect of pressure, temperature, time, and gas feed composition on the growth dynamics of two distinct iron–carbon phases with the octahedral and trigonal prismatic coordination of carbon sites on an Fe(110) single crystal acting as a model catalyst. Using a combination of state-of-the-art X-ray photoelectron spectroscopy at an unprecedentedly high pressure, high-energy surface X-ray diffraction, mass spectrometry, and theoretical calculations, we reveal the details of iron surface carburization and product formation under semirealistic conditions. We provide a detailed insight into the state of the catalyst’s surface in relation to the reaction.
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49.
  • Smirnova, Irina A., et al. (författare)
  • Isolation of yeast complex IV in native lipid nanodiscs
  • 2016
  • Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1858:12, s. 2984-2992
  • Tidskriftsartikel (refereegranskat)abstract
    • We used the amphipathic styrene maleic acid (SMA) co-polymer to extract cytochrome c oxidase (CytcO) in its native lipid environment from S. cerevisiae mitochondria. Native nanodiscs containing one CytcO per disc were purified using affinity chromatography. The longest cross-sections of the native nanodiscs were 11 nm x 14 nm. Based on this size we estimated that each CytcO was surrounded by similar to 100 phospholipids. The native nanodiscs contained the same major phospholipids as those found in the mitochondrial inner membrane. Even though CytcO forms a supercomplex with cytochrome bc(1) in the mitochondria! membrane, cyt.bc(1) was not found in the native nanodiscs. Yet, the loosely-bound Respiratory SuperComplex factors were found to associate with the isolated CytcO. The native nanodiscs displayed an O-2-reduction activity of similar to 130 electrons CytcO(-1) s(-1) and the kinetics of the reaction of the fully reduced CytcO with 02 was essentially the same as that observed with CytcO in mitochondrial membranes. The kinetics of CO-ligand binding to the CytcO catalytic site was similar in the native nanodiscs and the mitochondrial membranes. We also found that excess SMA reversibly inhibited the catalytic activity of the mitochondrial CytcO, presumably by interfering with cyt. c binding. These data point to the importance of removing excess SMA after extraction of the membrane protein. Taken together, our data shows the high potential of using SMA-extracted CytcO for functional and structural studies.
  •  
50.
  • Storey, Robert F, et al. (författare)
  • Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study
  • 2014
  • Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 25:7, s. 517-525
  • Tidskriftsartikel (refereegranskat)abstract
    • In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.
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