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1.
  • 2021
  • swepub:Mat__t
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2.
  • 2021
  • swepub:Mat__t
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3.
  • Maier, Hannes, et al. (author)
  • Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
  • 2022
  • In: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
  • Journal article (peer-reviewed)abstract
    • Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
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4.
  • Glasbey, JC, et al. (author)
  • 2021
  • swepub:Mat__t
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5.
  • Bravo, L, et al. (author)
  • 2021
  • swepub:Mat__t
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6.
  • Tabiri, S, et al. (author)
  • 2021
  • swepub:Mat__t
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7.
  • Abazajian, Kevork, et al. (author)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Journal article (peer-reviewed)abstract
    • CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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8.
  • Böhm, Felix, et al. (author)
  • FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
  • 2024
  • In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
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9.
  • Erlinge, D., et al. (author)
  • Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
  • 2017
  • In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142
  • Journal article (peer-reviewed)abstract
    • Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
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10.
  • Schosserer, Markus, et al. (author)
  • Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan
  • 2015
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6:1
  • Journal article (peer-reviewed)abstract
    • Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.
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11.
  • Ade, Peter, et al. (author)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Journal article (peer-reviewed)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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12.
  • Amendola, L., et al. (author)
  • Cosmology and fundamental physics with the Euclid satellite
  • 2018
  • In: Living Reviews in Relativity. - : Springer. - 1433-8351 .- 2367-3613. ; 21:1
  • Journal article (peer-reviewed)abstract
    • Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015–2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid’s Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
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  • Arvidsson, Niklas, et al. (author)
  • Cirkulära möbelflöden : Hur nya affärsmodeller kan bidra till hållbar utveckling inom offentliga möbler
  • 2017
  • Reports (other academic/artistic)abstract
    • Sverige har en stark möbelindustri och en stolt tradition av att tillverka tidlösa och högkvalitativa möbler, ofta av naturmaterial. 2016 producerade Sverige möbler för 22,8 miljarder SEK, varav kontorsmöbler stod för nästan en fjärdedel1. Det saknas idag statistik över vad som händer med dessa möbler när de inte längre används, men det står klart att många av dem slängs i förtid när verksamheter flyttar eller när deras behov ändras. Samtidigt syns en tydlig utveckling mot att kunder mer och mer efterfrågar återbrukade eller renoverade möbler som en del i sitt hållbarhetsarbete. Denna utveckling var startpunkten för projektet ”Affärsmodell-innovation för cirkulära möbelflöden”. Affärsmodellinnovation för cirkulära möbelflöden är ett Vinnovafinansierat projekt som under åren 2015-2017 arbetat med att utveckla och testa koncept för cirkulära affärsmodeller för i första hand offentliga möbler. I projektet har tjugo aktörer från hela värdekedjan, från underleverantörer, möbelproducenter, återförsäljare och användare till forskare och branschorgan, samarbetat kring affärsutveckling, kundincitament, produktdesign, logistik, hållbarhets- och certifieringsfrågor. Den här skriften belyser hur nya affärsmodeller för mer cirkulära möbelflöden kan bidra till en mer hållbar utveckling och ger smakprov på slutsatser från projektet. Skriften riktar sig framför allt till producenter och återförsäljare av möbler för offentliga miljöer, men även kunder och inköpare tror vi kan ha stor nytta av skriften. Vi hoppas att den även kan fungera som inspiration för andra industrier och branscher som funderar på en övergång till mer cirkulära affärsekosystem.
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15.
  • Bjurström, Martin F., et al. (author)
  • Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study
  • 2024
  • In: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576.
  • Journal article (peer-reviewed)abstract
    • BackgroundRandomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels.MethodsIn this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables.ResultsIn total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results.ConclusionsImplementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.
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16.
  • Boyer, Robert, et al. (author)
  • Three-dimensional product circularity
  • 2021
  • In: Journal of Industrial Ecology. - : John Wiley & Sons, Ltd. - 1088-1980 .- 1530-9290. ; 25:4, s. 824-
  • Journal article (peer-reviewed)abstract
    • Abstract Understanding product circularity as ?three-dimensional? could anchor the Circular Economy to common principles while affording its followers flexibility about how to measure it in their specific sectors and disciplines and within their organization's means. Inspired by a heuristic developed for the urban planning profession to cope with the inherent conflicts of Sustainable Development, this article argues that measuring product-level circularity should consider ways to achieve (1) high material recirculation, (2) high utilization, and (3) high endurance in products and service offerings. Achieving all three dimensions ensures that material flowing through the economy is recovered from prior use phases, that it is used intensely, and that it retains its value in spite of exogenous changes. The article argues further that these three dimensions ought to be measured and reported separately rather than as a composite metric and that certain applications will have opportunities to improve circularity through certain dimensions better than others. The article also explains how researchers at RISE (Research Institutes of Sweden AB) are working with industry and government partners to measure the three dimensions and how diverse actors interested in the Circular Economy can use the three dimensions to take the first steps in their transition to circularity.
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17.
  • Citrin, J., et al. (author)
  • Tractable flux-driven temperature, density, and rotation profile evolution with the quasilinear gyrokinetic transport model QuaLiKiz
  • 2017
  • In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 59:12
  • Journal article (peer-reviewed)abstract
    • Quasilinear turbulent transport models are a successful tool for prediction of core tokamak plasma profiles in many regimes. Their success hinges on the reproduction of local nonlinear gyrokinetic fluxes. We focus on significant progress in the quasilinear gyrokinetic transport model QuaLiKiz (Bourdelle et al 2016 Plasma Phys. Control. Fusion 58 014036), which employs an approximated solution of the mode structures to significantly speed up computation time compared to full linear gyrokinetic solvers. Optimisation of the dispersion relation solution algorithm within integrated modelling applications leads to flux calculations x 10(6-7) faster than local nonlinear simulations. This allows tractable simulation of flux-driven dynamic profile evolution including all transport channels: ion and electron heat, main particles, impurities, and momentum. Furthermore, QuaLiKiz now includes the impact of rotation and temperature anisotropy induced poloidal asymmetry on heavy impurity transport, important for W-transport applications. Application within the JETTO integrated modelling code results in 1 s of JET plasma simulation within 10 h using 10 CPUs. Simultaneous predictions of core density, temperature, and toroidal rotation profiles for both JET hybrid and baseline experiments are
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18.
  • Fisher, Jane, et al. (author)
  • The Dynamics of Circulating Heparin-Binding Protein : Implications for Its Use as a Biomarker
  • 2022
  • In: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 14:5, s. 447-460
  • Journal article (peer-reviewed)abstract
    • Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1-2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.
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21.
  • Hasper, Thomas Berg, et al. (author)
  • Water use by Swedish boreal forests in a changing climate
  • 2016
  • In: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 30:5, s. 690-699
  • Journal article (peer-reviewed)abstract
    • The rising levels of atmospheric carbon dioxide concentration ([CO2]) and temperature have the potential to substantially affect the terrestrial water and energy balance by altering the stomatal conductance and transpiration of trees. Many models assume decreases in stomatal conductance and plant water use under rising [CO2], which has been used as a plausible explanation for the positive global trend in river run-off over the past century. Plant water use is, however, also affected by changes in temperature, precipitation and land use, and there is yet no consensus about the contribution of different drivers to temporal trends of evapotranspiration (ET) and river run-off. In this study, we assessed water-use responses to climate change by using both long-term monitoring and experimental data in Swedish boreal forests. Historical trends and patterns in ET of large-scale boreal landscapes were determined using climate and run-off data from the past 50 years, while explicit tree water-use responses to elevated [CO2] and/or air temperature were examined in a whole-tree chamber experiment using mature Norway spruce (Picea abies (L.) Karst.) trees. The results demonstrated that ET estimated from water budgets at the catchment scale increased by 18% over the past 50 years while run-off did not significantly change. The increase in ET was related to increasing precipitation and a steady increase in forest standing biomass over time. The whole-tree chamber experiment showed that Norway spruce trees did not save water under elevated [CO2] and that experimentally elevated air temperature did not increase transpiration as decreased stomatal conductance cancelled the effect of higher vapour pressure deficit in warmed air. Our findings have important implications for projections of future water use of European boreal coniferous forests, indicating that changes in precipitation and standing biomass are more important than the effects of elevated [CO2] or temperature on transpiration rates.
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22.
  • Hofmann, Robin, et al. (author)
  • Oxygen therapy in ST-elevation myocardial infarction.
  • 2018
  • In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:29, s. 2730-2739
  • Journal article (peer-reviewed)abstract
    • Aims: To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes.Methods and results: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days.Conclusions: Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.
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23.
  • Hofmann, Robin, et al. (author)
  • Oxygen therapy in suspected acute myocardial infarction
  • 2017
  • In: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
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25.
  • Householder, John Ethan, et al. (author)
  • One sixth of Amazonian tree diversity is dependent on river floodplains
  • 2024
  • In: NATURE ECOLOGY & EVOLUTION. - 2397-334X. ; 8, s. 901-911
  • Journal article (peer-reviewed)abstract
    • Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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26.
  • Högberg, Peter, et al. (author)
  • High temporal resolution tracing of photosynthate carbon from the tree canopy to forest soil microorganisms
  • 2008
  • In: New Phytologist. - : New Phytologist Trust. - 0028-646X .- 1469-8137. ; 177:1, s. 220-228
  • Journal article (peer-reviewed)abstract
    • • Half of the biological activity in forest soils is supported by recent tree photosynthate, but no study has traced in detail this flux of carbon from the canopy to soil microorganisms in the field.• Using 13CO2, we pulse-labelled over 1.5 h a 50-m2 patch of 4-m-tall boreal Pinus sylvestris forest in a 200-m3 chamber.• Tracer levels peaked after 24 h in soluble carbohydrates in the phloem at a height of 0.3 m, after 2–4 d in soil respiratory efflux, after 4–7 d in ectomycorrhizal roots, and after 2–4 d in soil microbial cytoplasm. Carbon in the active pool in needles, in soluble carbohydrates in phloem and in soil respiratory efflux had half-lives of 22, 17 and 35 h, respectively. Carbon in soil microbial cytoplasm had a half-life of 280 h, while the carbon in ectomycorrhizal root tips turned over much more slowly. Simultaneous labelling of the soil with showed that the ectomycorrhizal roots, which were the strongest sinks for photosynthate, were also the most active sinks for soil nitrogen.• These observations highlight the close temporal coupling between tree canopy photosynthesis and a significant fraction of soil activity in forests.
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27.
  • Jocher, Georg, et al. (author)
  • Apparent Winter CO2 uptake by a boreal forest due to decoupling
  • 2017
  • In: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923 .- 1873-2240. ; 232, s. 23-34
  • Journal article (peer-reviewed)abstract
    • Net uptake of carbon dioxide (CO2) was observed during the winter when using the eddy covariance (EC) technique above a 90-year-old Scots pine (Pinus sylvestris L.) stand in northern Sweden. This uptake occurred despite photosynthetic dormancy. This discrepancy led us to investigate the potential impact of decoupling of below- and above-canopy air mass flow and accompanying below-canopy horizontal advection on these measurements. We used the correlation of above- and below-canopy standard deviation of vertical wind speed (sigma(w)), derived from EC measurements above and below the canopy, as the main mixing criterion. We identified 0.33 m s(-1) and 0.06 m s(-1) as site-specific o thresholds for above and below canopy, respectively, to reach the fully coupled state. Decoupling was observed in 45% of all cases during the measurement period (5.11.2014-25.2.2015). After filtering out decoupled periods the above-canopy mean winter NEE shifted from -0.52 mu mol m(-2) s(-1) to a more reasonable positive value of 0.31 mu mol m(-2) s(-1). None of the above-canopy data filtering criteria we tested (i.e., friction velocity threshold; horizontal wind speed threshold; single-level sigma(w) threshold) ensured sufficient mixing. All missed critical periods that were detected only by the two-level filtering approach. Tower-surrounding topography induced a predominant below-canopy wind direction and consequent wind shear between above- and below-canopy air masses. These processes may foster decoupling and below-canopy removal of CO2 rich air. To determine how broadly such a topographical influence might apply, we compared the topography surrounding our tower to that surrounding other forest flux sites worldwide. Medians of maximum elevation differences within 300m and 1000 m around 110 FLUXNET forest EC towers were 24 m and 66 m, respectively, compared to 24 m and 114 m, respectively, at our site. Consequently, below canopy flow may influence above-canopy NEE detections at many forested EC sites. Based on our findings we suggest below-canopy measurements as standard procedure at sites evaluating forest CO2 budgets.
  •  
28.
  • Jocher, Georg, et al. (author)
  • Impact of Canopy Decoupling and Subcanopy Advection on the Annual Carbon Balance of a Boreal Scots Pine Forest as Derived From Eddy Covariance
  • 2018
  • In: Journal of Geophysical Research: Biogeosciences. - 2169-8953 .- 2169-8961. ; 123:2, s. 303-325
  • Journal article (peer-reviewed)abstract
    • Apparent net uptake of carbon dioxide (CO 2 ) during wintertime by an ∼ 90 year old Scots pine stand in northern Sweden led us to conduct canopy decoupling and subcanopy advection investigations over an entire year. Eddy covariance (EC) measurements ran simultaneously above and within the forest canopy for that purpose. We used the correlation of above- and below-canopy standard deviation of vertical wind speed (σ w ) as decoupling indicator. We identified 0.33 m s -1 and 0.06 m s -1 as site-specific σ w thresholds for above- and below-canopy coupling during nighttime (global radiation < 20 W m -2 ) and 0.23 m s -1 and 0.06 m s -1 as daytime (global radiation > 20 W m -2 ) σ w thresholds. Decoupling occurred in 53% of the annual nighttime and 14% of the annual daytime. The annual net ecosystem exchange (NEE), gross ecosystem exchange (GEE), and ecosystem respiration (R eco ) derived via two-level filtered EC data were -357 g C m -2 , -1,138 g C m -2 , and 781 g C m -2 , respectively. In comparison, both single-level friction velocity (u * ) and quality filtering resulted in ~ 22% higher NEE, mainly caused by ~ 16% lower R eco . GEE remained similar among filtering regimes. Accounting for changes of CO 2 storage across the canopy in the single-level filtered data could only marginally decrease these discrepancies. Consequently, advection appears to be responsible for the major part of this divergence. We conclude that the two-level filter is necessary to adequately address decoupling and subcanopy advection at our site, and we recommend this filter for all forested EC sites.
  •  
29.
  • Khatri, C, et al. (author)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Journal article (peer-reviewed)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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30.
  • Kihlström Burenstam Linder, Lars, et al. (author)
  • Patient-Specific Titanium-Reinforced Calcium Phosphate Implant for the Repair and Healing of Complex Cranial Defects
  • 2019
  • In: World Neurosurgery. - : ELSEVIER SCIENCE INC. - 1878-8750 .- 1878-8769. ; 122, s. E399-E407
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The reconstruction of complex cranial defects is challenging and is associated with a high complication rate. The development of a patient-specific, titanium-reinforced, calcium phosphate-based (CaP-Ti) implant with bone regenerative properties has previously been described in 2 case studies with the hypothesis that the implant may improve clinical outcome. OBJECTIVE: To identify whether the introduction of CaP-Ti implant has the potential to improve clinical outcome. METHODS: A retrospective review of all patients having undergone CaP-Ti cranioplasty was conducted. Comprehensive clinical data were collected from the hospital computer database and patient records. Bone formation and osseointegration were analyzed in a single retrieval specimen. RESULTS: Fifty patients, with 52 cranial defects, met the inclusion criteria. The patient cohort displayed a previous failure rate of 64% (32/50) with autologous bone, alloplastic materials, or both. At a median follow-up time of 25 months, the explantation rate due to either early postoperative infection or persistent wound dehiscence was 1.9% (1/53) or 3.8% (2/53), respectively. Surgical intervention with local wound revision was required in 2 patients without the need of implant removal. One patient had a brain tumor recurrence, and the implant was explanted 31 months after implantation. Histologic examination showed that the entire implant was partly yet evenly transformed into vascularized compact bone. CONCLUSION: In the present study the CaP-Ti implant appears to have improved the clinical outcomes in a cohort of patients with a high rate of previous cranioplasty failures. The bone regenerative effect may in particular have an impact on the long-term success rate of the implant.
  •  
31.
  • Kollmer, Marius, et al. (author)
  • Electron tomography reveals the fibril structure and lipid interactions in amyloid deposits
  • 2016
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:20, s. 5604-5609
  • Journal article (peer-reviewed)abstract
    • Electron tomography is an increasingly powerful method to study the detailed architecture of macromolecular complexes or cellular structures. Applied to amyloid deposits formed in a cell culture model of systemic amyloid A amyloidosis, we could determine the structural morphology of the fibrils directly in the deposit. The deposited fibrils are arranged in different networks, and depending on the relative fibril orientation, we can distinguish between fibril meshworks, fibril bundles, and amyloid stars. These networks are frequently infiltrated by vesicular lipid inclusions that may originate from the death of the amyloid-forming cells. Our data support the role of nonfibril components for constructing fibril deposits and provide structural views of different types of lipid-fibril interactions.
  •  
32.
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33.
  • Lindahl, Bertil, et al. (author)
  • An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay
  • 2017
  • In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:2, s. 125-131
  • Journal article (peer-reviewed)abstract
    • Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.
  •  
34.
  • Linder, Gunnar Jinmei, 1959- (author)
  • Deconstructing Tradition in Japanese Music : A Study of Shakuhachi, Historical Authenticity and Transmission of Tradition
  • 2012
  • Doctoral thesis (other academic/artistic)abstract
    • In the present study I examine the vertical bamboo flute shakuhachi, as an example of how a tradition can be constructed. There are two main issues: the historical authenticity of the believed origins and development of the shakuhachi tradition, and how the transmission of this tradition is conducted.The first main issue is concerned with how a legendary origin, probably constructed in the late seventeenth century, was disproved in early twentieth-century studies. According to this legendary origin, the shakuhachi was connected to Chan (Zen) Buddhism in ninth-century China. It was replaced by a nowadays commonly accepted theory of an indigenous origin, found in both Japanese and English language contemporary writings. I discuss the legend, constructed by the so-called komusō monks of the Edo period (1603–1867), and suggest an alternative explanation of how they became connected to other kinds of medieval monks, so-called boro and komosō. The primary sources relating to the boro and the komosō are discussed. My analyses indicate that the twentieth-century studies created a connection to the boro and komosō as assumed devout Buddhist monks, probably for socio-political reasons.The second main issue concerns how the tradition is transmitted, and the constitutive elements of this transmission. Some Japanese studies discuss the notion of kata – fixed forms implicitly containing essential elements of the ‘tradition’ – as a special feature of Japanese arts. I investigate how transmission is conducted, and argue against the notion that the elements transmitted from teacher to student contain the essence of the tradition. I assert that the concept of fixed forms as a defining characteristic of Japanese traditional arts, should be modified to a more modest ‘character of the music’ on the level of individual transmitters. I discuss the elements that are transmitted, and investigate what it is that constitutes the ‘traditional’ aspects, if any, of this transmission.
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35.
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36.
  • Luize, Bruno Garcia, et al. (author)
  • Geography and ecology shape the phylogenetic composition of Amazonian tree communities
  • 2024
  • In: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699. ; 51:7, s. 1163-1184
  • Journal article (peer-reviewed)abstract
    • Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
  •  
37.
  • Lundgren, Sofie, et al. (author)
  • Deep brain stimulation of caudal zona incerta and subthalamic nucleus in patients with Parkinson’s disease : effects on voice intensity
  • 2011
  • In: Parkinson's Disease. - : Hindawi Publishing Corporation. - 2090-8083 .- 2042-0080. ; 2011, s. 658956-
  • Journal article (peer-reviewed)abstract
    • Deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson’s disease (PD) affects speech in small, inconsistent ways. However, voice intensity generally increases. Recently the caudal zona inserta (cZi) has been investigated as an alternate target in DBS treatment of PD. The effects of cZi-DBS on voice intensity have not yet been investigated. The aim of this study was to compare the voice intensity effects of cZi-DBS and STN-DBS in PD patients. Voice intensity during reading and intensity decay during rapid syllable repetition were measured for eight STN-DBS and eight cZi-DBS patients in a pre-surgical baseline and then on- and off-stimulation 12 months after surgery. Voice intensity on-stimulation was larger than off-stimulation for the STN-DBS patients, but smaller for the cZi-DBS patients. There were no significant changes in intensity decay. The results suggest that cZi and STN are involved differently in neuromuscular control of the speech respiratory subsystem.
  •  
38.
  • Mellhammar, Lisa, et al. (author)
  • Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching
  • 2021
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
  • Journal article (peer-reviewed)abstract
    • One can falsely assume that it is well known that bacteremia is associated with higher mortality in sepsis. Only a handful of studies specifically focus on the comparison of culture-negative and culture-positive sepsis with different conclusions depending on study design. The aim of this study was to describe outcome for critically ill patients with either culture-positive or -negative sepsis in a clinical review. We also aimed to identify subphenotypes of sepsis with culture status included as candidate clinical variables. Out of 784 patients treated in intensive care with a sepsis diagnosis, blood cultures were missing in 140 excluded patients and 95 excluded patients did not fulfill a sepsis diagnosis. Of 549 included patients, 295 (54%) had bacteremia, 90 (16%) were non-bacteremic but with relevant pathogens detected and in 164 (30%) no relevant pathogen was detected. After adjusting for confounders, 90-day mortality was higher in bacteremic patients, 47%, than in non-bacteremic patients, 36%, p = 0.04. We identified 8 subphenotypes, with different mortality rates, where pathogen detection in microbial samples were important for subphenotype distinction and outcome. In conclusion, bacteremic patients had higher mortality than their non-bacteremic counter-parts and bacteremia is more common in sepsis when studied in a clinical review. For reducing population heterogeneity and improve the outcome of trials and treatment for sepsis, distinction of subphenotypes might be useful and pathogen detection an important factor.
  •  
39.
  •  
40.
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41.
  • Memedi, Mevludin, et al. (author)
  • Self-assessments and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial
  • 2014
  • Other publication (other academic/artistic)abstract
    • Objective: The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression.Methods: Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales.Results: In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS, except at month 36 (P<0.01). The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59).Conclusions: PD symptoms can be remotely monitored over time with this test battery. The trends of the test scores were similar to the trends of clinical rating scores. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of the well-established scales.
  •  
42.
  • Memedi, Mevludin, 1983-, et al. (author)
  • Self-reported symptoms and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial
  • 2013
  • Conference paper (other academic/artistic)abstract
    • Objective: To determine if a home environment test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression.Background: Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study. On inclusion, 35 of them were treated with continuous intraduodenal administration of a levodopa-carbidopa intestinal gel (LCIG) and 30 patients were candidates for switching from conventional oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments and fine motor tests (tapping and spiral drawings), in their homes. Assessments were performed four times per day during week-long test periods. For the majority of these test periods, UPDRS and PDQ-39 ratings were performed at the start of the period.Methods: The test battery time series were summarized into scores for representing symptom severities over test periods. Six conceptual dimensions were defined; four subjectively-reported: ‘Walking’, ‘Satisfied’, ‘Dyskinesia’ and ‘Off’, and two objectively-measured: ‘Tapping’ and ‘Spiral’. In addition, an overall test score (OTS) was defined to represent the overall condition of a patient during a test period.Results: In LCIG-naïve patients, mean OTS improved startingf rom the first test period on LCIG treatment and this improvement remained statistically significant until month 24 (figure). In contrast to objectively-measured dimensions, mean scores of subjectively-reported dimensions improved significantly throughout the study. In LCIG-non-na€ıve patients, there were no significant changes in mean OTS, except at month 36 (p < 0.01). The OTS correlated adequately with total UPDRS (rho 5 0.59) and total PDQ-39 (0.59).Conclusions: Using the test battery it is possible to monitor PD symptoms over time. The trends of the test scores were strikingly similar to the trends of the clinical rating scores. Correlations between OTS and the rating scales were adequate indicating that the test battery contains important elements of the information of these well-established scales.
  •  
43.
  • Memedi, Mevludin, et al. (author)
  • Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease
  • 2015
  • In: IEEE journal of biomedical and health informatics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-2194 .- 2168-2208. ; 19:6, s. 1829-1834
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.
  •  
44.
  • Nilsson, Sven, et al. (author)
  • Densities of large living and dead trees in old-growth temperate and boreal forests
  • 2002
  • In: Forest Ecology and Management. - 1872-7042. ; 161:1-3, s. 189-204
  • Journal article (peer-reviewed)abstract
    • We recorded and reviewed densities and basal areas of large living and dead trees in old-growth forest in Europe. Recorded densities were similar to those reported from old-growth forests in eastern North America, but lower than in northwestem North America. Based on our results we suggest that, 10-20 living trees per ha with dbh > 70 cm may have been typical values for many central European and south Scandinavian virgin forests. In boreal forests, it was probably common with at least 20 living trees per ha with dbh > 40 cm. Basal areas of living trees in mixed old-growth forests in central Europe and southern Sweden were 34-40 m 2 per ha on dry ground and about 60 m(2) per ha in wet alder-ash-spruce forests. Densities of large trees (dbh > 40 cm) were twice as high in the latter forest type than on dry ground in Bialowieza forest, Poland. Based on our results, we propose the following generalizations to be further tested in other old-growth temperate and boreal forests: 1. Among all standing trunks (including high stumps) about 10% are dead. but this proportion increases for the largest trees. The proportion of standing trees that are dead seem to be independent of total basal areas. Based on this, we suggest that the volume of dead wood is directly proportional to the productivity of old-growth forests. 2. Standing dead trees (snags) are on average larger than downed dead trees. Trees with dbh >40 cm often dominate the basal area and volume of standing dead trees and living trees. 3. About 30% (20-40%) of the basal area and volume of dead trees is standing in old-growth forests. This proportion seems to be independent of total volume of dead wood. Large disturbances by fire, strong winds and insects may temporarily change these proportions considerably in individual stands. (C) 2002 Elsevier Science B.V. All rights reserved.
  •  
45.
  • Omar, Omar, et al. (author)
  • In situ bone regeneration of large cranial defects using synthetic ceramic implants with a tailored composition and design
  • 2020
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:43, s. 26660-26671
  • Journal article (peer-reviewed)abstract
    • The repair of large cranial defects with bone is a major clinical challenge that necessitates novel materials and engineering solutions. Three-dimensionally (3D) printed bioceramic (BioCer) implants consisting of additively manufactured titanium frames enveloped with CaP BioCer or titanium control implants with similar designs were implanted in the ovine skull and at s.c. sites and retrieved after 12 and 3 mo, respectively. Samples were collected for morphological, ultrastructural, and compositional analyses using histology, electron microscopy, and Raman spectroscopy. Here, we show that BioCer implants provide osteoinductive and microarchitectural cues that promote in situ bone regeneration at locations distant from existing host bone, whereas bone regeneration with inert titanium implants was confined to ingrowth from the defect boundaries. The BioCer implant promoted bone regeneration at nonosseous sites, and bone bonding to the implant was demonstrated at the ultrastructural level. BioCer transformed to carbonated apatite in vivo, and the regenerated bone displayed a molecular composition indistinguishable from that of native bone. Proof-of-principle that this approach may represent a shift from mere reconstruction to in situ regeneration was provided by a retrieved human specimen, showing that the BioCer was transformed into well-vascularized osteonal bone, with a morphology, ultrastructure, and composition similar to those of native human skull bone.
  •  
46.
  • Omerovic, Elmir, 1968, et al. (author)
  • Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction-Outcomes at two years
  • 2024
  • In: Cardiovascular Revascularization Medicine. - : Elsevier. - 1553-8389 .- 1878-0938. ; 66, s. 43-50
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years.METHODS: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here.RESULTS: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups.CONCLUSIONS: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin.REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02311231.
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47.
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48.
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49.
  • Pellegrini, Paola, et al. (author)
  • A drug screening assay on cancer cells chronically adapted to acidosis
  • 2018
  • In: Cancer Cell International. - : BMC. - 1475-2867. ; 18
  • Journal article (peer-reviewed)abstract
    • Background: Drug screening for the identification of compounds with anticancer activity is commonly performed using cell lines cultured under normal oxygen pressure and physiological pH. However, solid tumors are characterized by a microenvironment with limited access to nutrients, reduced oxygen supply and acidosis. Tumor hypoxia and acidosis have been identified as important drivers of malignant progression and contribute to multicellular resistance to different forms of therapy. Tumor acidosis represents an important mechanism mediating drug resistance thus the identification of drugs active on acid-adapted cells may improve the efficacy of cancer therapy. Methods: Here, we characterized human colon carcinoma cells (HCT116) chronically adapted to grow at pH 6.8 and used them to screen the Prestwick drug library for cytotoxic compounds. Analysis of gene expression profiles in parental and low pH-adapted cells showed several differences relating to cell cycle, metabolism and autophagy. Results: The screen led to the identification of several compounds which were further selected for their preferential cytotoxicity towards acid-adapted cells. Amongst 11 confirmed hits, we primarily focused our investigation on the benzoporphyrin derivative Verteporfin (VP). VP significantly reduced viability in low pH-adapted HCT116 cells as compared to parental HCT116 cells and normal immortalized epithelial cells. The cytotoxic activity of VP was enhanced by light activation and acidic pH culture conditions, likely via increased acid-dependent drug uptake. VP displayed the unique property to cause light-dependent cross-linking of proteins and resulted in accumulation of polyubiquitinated proteins without inducing inhibition of the proteasome. Conclusions: Our study provides an example and a tool to identify anticancer drugs targeting acid-adapted cancer cells.
  •  
50.
  • Pålhagen, Sven E., et al. (author)
  • Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinsons disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs
  • 2016
  • In: Parkinsonism & Related Disorders. - : ELSEVIER SCI LTD. - 1353-8020 .- 1873-5126. ; 29, s. 17-23
  • Journal article (peer-reviewed)abstract
    • Background: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinsons disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. Methods: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naive (N = 37), or had previous LCIG treatment for amp;lt;2 (N = 22), or amp;gt;= 2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinsons Disease Rating Scale (UPDRS), 39-item Parkinsons Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. Results: Mean monthly costs per patient ( 8226 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naive patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. Conclusions: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naive patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The longterm safety was consistent with the established LCIG profile. (C) 2016 AbbVie Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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