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Sökning: WFRF:(Bernasconi A)

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1.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)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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5.
  • De Angelis, A., et al. (författare)
  • Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
  • 2018
  • Ingår i: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
  • Tidskriftsartikel (refereegranskat)abstract
    • e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
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11.
  • Santoro, V., et al. (författare)
  • HighNESS conceptual design report: Volume I
  • 2024
  • Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 85-314
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Spallation Source, currently under construction in Lund, Sweden, is a multidisciplinary international laboratory. Once completed to full specifications, it will operate the world’s most powerful pulsed neutron source. Supported by a 3 million Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) has been completed to develop a second neutron source located below the spallation target. Compared to the first source, designed for high cold and thermal brightness, the new source has been optimized to deliver higher intensity, and a shift to longer wavelengths in the spectral regions of cold (CN, 2–20 Å), very cold (VCN, 10–120 Å), and ultracold (UCN, >500 Å) neutrons. The second source comprises a large liquid deuterium moderator designed to produce CN and support secondary VCN and UCN sources. Various options have been explored in the proposed designs, aiming for world-leading performance in neutronics. These designs will enable the development of several new instrument concepts and facilitate the implementation of a high-sensitivity neutron-antineutron oscillation experiment (NNBAR). This document serves as the Conceptual Design Report for the HighNESS project, representing its final deliverable.
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12.
  • Santoro, V., et al. (författare)
  • HighNESS conceptual design report: Volume II. the NNBAR experiment.
  • 2024
  • Ingår i: Journal of Neutron Research. - 1023-8166 .- 1477-2655. ; 25:3-4, s. 315-406
  • Tidskriftsartikel (refereegranskat)abstract
    • A key aim of the HighNESS project for the European Spallation Source is to enable cutting-edge particle physics experiments. This volume presents a conceptual design report for the NNBAR experiment. NNBAR would exploit a new cold lower moderator to make the first search in over thirty years for free neutrons converting to anti-neutrons. The observation of such a baryon-number-violating signature would be of fundamental significance and tackle open questions in modern physics, including the origin of the matter-antimatter asymmetry. This report shows the design of the beamline, supermirror focusing system, magnetic and radiation shielding, and anti-neutron detector necessary for the experiment. A range of simulation programs are employed to quantify the performance of the experiment and show how background can be suppressed. For a search with full background suppression, a sensitivity improvement of three orders of magnitude is expected, as compared with the previous search. Civil engineering studies for the NNBAR beamline are also shown, as is a costing model for the experiment.
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13.
  • Opheim, G., et al. (författare)
  • 7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice
  • 2021
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 96:7, s. 327-341
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.
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  • Kreins, AY, et al. (författare)
  • Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome
  • 2015
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:10, s. 1641-1662
  • Tidskriftsartikel (refereegranskat)abstract
    • Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
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  • Santoro, V., et al. (författare)
  • The HighNESS Project at the European Spallation Source : Current Status and Future Perspectives
  • 2024
  • Ingår i: Nuclear science and engineering. - 0029-5639 .- 1943-748X. ; 198:1, s. 31-63
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that, once completed at full specifications, will operate the world's most powerful pulsed neutron source. Supported by a 3 M Euro Research and Innovation Action within the European Union Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source located below the spallation target. Compared to the first source, which is located above the spallation target and designed for high cold and thermal brightness, the new source is being optimized to deliver higher intensity and a shift to longer wavelengths in the spectral regions of cold neutrons (CNs) (2 to 20 & Aring;), very cold neutrons (VCNs) (10 to 120 & Aring;), and ultracold neutrons (UCNs) (> 500 & Aring;). The second source consists of a large liquid deuterium moderator to deliver CNs and serve secondary VCN and UCN sources, for which different options are under study. These new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. The HighNESS project is now entering its last year, and we are working toward the Conceptual Design Report of the ESS upgrade. In this paper, results obtained in the first 2 years, ongoing developments, and future perspectives are described.
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  • Ammirati, Enrico, et al. (författare)
  • Acute Myocarditis Associated With Desmosomal Gene Variants
  • 2022
  • Ingår i: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 10:10, s. 714-727
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown.OBJECTIVES The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV.METHODS In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up.RESULTS In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk. (J Am Coll Cardiol HF 2022;10:714-727) (c) 2022 by the American College of Cardiology Foundation.
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  • Creary, Lisa E., et al. (författare)
  • Next-Generation Sequencing Identifies Extended HLA Class I and II Haplotypes Associated With Early-Onset and Late-Onset Myasthenia Gravis in Italian, Norwegian, and Swedish Populations
  • 2021
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic susceptibility to myasthenia gravis (MG) associates with specific HLA alleles and haplotypes at the class I and II regions in various populations. Previous studies have only examined alleles at a limited number of HLA loci that defined only broad serotypes or alleles defined at the protein sequence level. Consequently, genetic variants in noncoding and untranslated HLA gene segments have not been fully explored but could also be important determinants for MG. To gain further insight into the role of HLA in MG, we applied next-generation sequencing to analyze sequence variation at eleven HLA genes in early-onset (EO) and late-onset (LO) non-thymomatous MG patients positive for the acetylcholine receptor (AChR) antibodies and ethnically matched controls from Italy, Norway, and Sweden. For all three populations, alleles and haplotype blocks present on the ancestral haplotype AH8.1 were associated with risk in AChR-EOMG patients. HLA-B*08:01:01:01 was the dominant risk allele in Italians (OR = 3.28, P = 1.83E−05), Norwegians (OR = 3.52, P = 4.41E−16), and in Swedes HLA-B*08:01 was the primary risk allele (OR = 4.24, P <2.2E-16). Protective alleles and haplotype blocks were identified on the HLA-DRB7, and HLA-DRB13.1 class II haplotypes in Italians and Norwegians, whereas in Swedes HLA-DRB7 exhibited the main protective effect. For AChR-LOMG patients, the HLA-DRB15.1 haplotype and associated alleles were significantly associated with susceptibility in all groups. The HLA-DR13–HLA-DR–HLA-DQ haplotype was associated with protection in all AChR-LOMG groups. This study has confirmed and extended previous findings that the immunogenetic predisposition profiles for EOMG and LOMG are distinct. In addition, the results are consistent with a role for non-coding HLA genetic variants in the pathogenesis of MG.
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  • Santoro, V., et al. (författare)
  • DEVELOPMENT OF A HIGH INTENSITY NEUTRON SOURCE AT THE EUROPEAN SPALLATION SOURCE : THE HIGHNESS PROJECT
  • 2022
  • Ingår i: Proceedings of the 14th International Topical Meeting on Nuclear Applications of Accelerators, AccApp 2021, Embedded with the 2021 ANS Winter Meeting. - 9780894487842 ; , s. 11-20
  • Konferensbidrag (refereegranskat)abstract
    • The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that will operate the world’s most powerful pulsed neutron source. Supported by a 3M Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source below the spallation target. Compared to the first source, located above the spallation target and designed for high cold and thermal brightness, the new source will provide higher intensity, and a shift to longer wavelengths in the spectral regions of cold (2-20 Å), very cold (VCN, 10-120 Å), and ultra cold (UCN, > 500 Å) neutrons. The core of the second source will consist of a large liquid deuterium moderator to deliver a high flux of cold neutrons and to serve secondary VCN and UCN sources, for which different options are under study. The features of these new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. Part of the HighNESS project is also dedicated to the development of future instruments that will make use of the new source and will complement the initial suite of instruments in construction at ESS. The HighNESS project started in October 2020. In this paper, the ongoing developments and the results obtained in the first year are described.
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22.
  • Wienhues, Giulia, et al. (författare)
  • From desiccation to wetlands and outflow : rapid re-filling of Lake Victoria during the Latest Pleistocene 14–13 ka
  • 2023
  • Ingår i: Journal of Great Lakes research. - : Elsevier. - 0380-1330.
  • Tidskriftsartikel (refereegranskat)abstract
    • Reconstructing hydrological variability is critical for understanding Lake Victoria's ecosystem history, the evolution of its diverse endemic fish community, the dynamics of vegetation in the catchment, and the dispersal of aquatic and terrestrial fauna in the East African Rift system during Latest Pleistocene and Holocene times. Whereas consensus exists on widespread desiccation of Lake Victoria ∼18 – 17 ka, the re-filling history (16 – 13 ka) has remained highly controversial. Here, we present data from four new sediment cores along a depth transect. We use lithostratigraphic core correlation, sediment facies, XRF data, wetland vegetation analysis (Typha pollen), and 14C chronologies of unprecedented precision to document Latest Pleistocene lake-level variability. At our coring site in the central basin, local Typha wetlands existed >16.7 ka, alternating with periods of desiccation. Moisture increased slightly between ca. 16.7 – 14.5 ka and wetlands with permanent, shallow ponds established simultaneously in the center and the marginal, more elevated parts of the flat lake basin. After ca. 14.0 ka, lake levels increased; wetlands in the central basin were submerged and replaced by lacustrine environments and a >50 m deep lake established ca. 13.5 ka, likely with intermittent overflow most of the time. The lake reached modern or even above-modern levels around 10.8 ka. This lake-level history is consistent with regional terrestrial paleoenvironmental reconstructions, notably the expansion of Afromontane and rainforest. Our data suggest a complex picture of paleoclimatic conditions in Eastern Africa and teleconnections to the North-Atlantic and Indian Ocean domains.
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23.
  • Wienhues, Giulia, et al. (författare)
  • Latest pleistocene and holocene primary producer communities and hydroclimate in Lake Victoria, Eastern Africa
  • 2024
  • Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 330
  • Tidskriftsartikel (refereegranskat)abstract
    • The Lake Victoria ecosystem is emblematic of the catastrophic effects that human activities, particularly cultural eutrophication, can have on freshwater biodiversity. However, little is known about the long-term spatial and temporal pattern of aquatic primary paleo-production (PPaq) and producer communities in Lake Victoria and how these patterns relate to past climate variability, landscape evolution, lake hydrology, mixing regimes, nutrient cycling, and biodiversity dynamics in the past 17 kyr. We use sediments from four well-dated cores along a transect from offshore to nearshore sites, and exploit XRF element scanning and hyperspectral imaging data, TC, TN, bSi, δ13C and δ15N, and sedimentary pigments to investigate paleolimnological variability and change. Our findings demonstrate that changes in PPaq and algal communities during the past 17 kyr were closely related to hydroclimatic changes, lake mixing, and nutrient availability. During the wetland phase (16.7–14.5 cal ka BP), PPaq levels remained generally low, while chromophytes and chlorophytes dominated the algal community. Following the rapid lake level rise (∼14.2 cal ka BP) during the early African Humid Period (AHP), PPaq levels steadily increased, accompanied by a shift towards cyanobacteria and chromophytes. During the Holocene, our results suggest repeated short-lived arid intervals (∼10.5, ∼9, 7.8–7.2, ∼4, and 3.2–3.0 cal ka BP) and two distinct periods of enhanced lake mixing associated with high PPaq and high diatom productivity: the first one between 11 and 9 cal ka BP, which coincided with the maximum of the AHP (high precipitation, high wind, enhanced mixing), and the second, less pronounced one, between 7 and 4 cal ka BP. Between these two periods (i.e. 9–7 cal ka BP) we observe reduced diatom productivity, relatively low PPaq, and high C/N ratios, suggesting conditions with more stable lake stratification, likely associated with reduced wind strength, and some nutrient limitation (N and P). Finally, the drier conditions around the end of the AHP (ca. 4 cal ka BP) and during the late Holocene were associated with decreasing lake mixing and increasing dominance of cyanobacteria. Given our reconstruction of PPaq over the past 17 kyr, we conclude that the levels in the 20th century are unprecedentedly high, consistent with the massive human-mediated impact on the Lake Victoria ecosystem including biodiversity loss.
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24.
  • Wiesner, M., et al. (författare)
  • The electron-phonon interaction at deep Bi 2 Te3-semiconductor interfaces from Brillouin light scattering
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • It is shown that the electron-phonon interaction at a conducting interface between a topological insulator thin film and a semiconductor substrate can be directly probed by means of high-resolution Brillouin light scattering (BLS). The observation of Kohn anomalies in the surface phonon dispersion curves of a 50 nm thick Bi2Te3 film on GaAs, besides demonstrating important electron-phonon coupling effects in the GHz frequency domain, shows that information on deep interface electrons can be obtained by tuning the penetration depth of optically-generated surface phonons so as to selectively probe the interface region, as in a sort of quantum sonar.
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  • Bouamar, R., et al. (författare)
  • Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
  • 2013
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 13:5, s. 1253-1261
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac.
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27.
  • Cippà, Pietro E, et al. (författare)
  • Risk Stratification for Rejection and Infection after Kidney Transplantation.
  • 2015
  • Ingår i: Clinical Journal of the American Society of Nephrology. - 1555-905X. ; 10:12, s. 2213-2220
  • Tidskriftsartikel (refereegranskat)abstract
    • Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation.
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28.
  • Covey, Kristofer, et al. (författare)
  • Carbon and Beyond : The Biogeochemistry of Climate in a Rapidly Changing Amazon
  • 2021
  • Ingår i: Frontiers in Forests and Gobal Change. - : Frontiers Media S.A.. - 2624-893X. ; 4
  • Forskningsöversikt (refereegranskat)abstract
    • The Amazon Basin is at the center of an intensifying discourse about deforestation, land-use, and global change. To date, climate research in the Basin has overwhelmingly focused on the cycling and storage of carbon (C) and its implications for global climate. Missing, however, is a more comprehensive consideration of other significant biophysical climate feedbacks [i.e., CH4, N2O, black carbon, biogenic volatile organic compounds (BV0Cs), aerosols, evapotranspiration, and albedo] and their dynamic responses to both localized (fire, land-use change, infrastructure development, and storms) and global (warming, drying, and some related to El Nino or to warming in the tropical Atlantic) changes. Here, we synthesize the current understanding of (1) sources and fluxes of all major forcing agents, (2) the demonstrated or expected impact of global and local changes on each agent, and (3) the nature, extent, and drivers of anthropogenic change in the Basin. We highlight the large uncertainty in flux magnitude and responses, and their corresponding direct and indirect effects on the regional and global climate system. Despite uncertainty in their responses to change, we conclude that current warming from non-CO2 agents (especially CH4 and N2O) in the Amazon Basin largely offsets- and most likely exceeds-the climate service provided by atmospheric CO2 uptake. We also find that the majority of anthropogenic impacts act to increase the radiative forcing potential of the Basin. Given the large contribution of less-recognized agents (e.g., Amazonian trees alone emit similar to 3.5% of all global CH4), a continuing focus on a single metric (i.e., C uptake and storage) is incompatible with genuine efforts to understand and manage the biogeochemistry of climate in a rapidly changing Amazon Basin.
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  • Ekberg, Henrik, et al. (författare)
  • Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation.
  • 2009
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 9, s. 1876-1885
  • Tidskriftsartikel (refereegranskat)abstract
    • The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low-doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow-up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow-up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow-up, renal function remained stable (mean change: -0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). The MMF and low-dose tacrolimus arm continued to have the highest GFR (68.6 +/- 23.8 ml/min vs. 65.9 +/- 26.2 ml/min in the standard-dose cyclosporine, 64.0 +/- 23.1 ml/min in the low-dose cyclosporine and 65.3 +/- 26.2 ml/min in the low-dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair-wise tests). The MMF and low-dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. In the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low-dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.
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30.
  • Grdic Eliasson, Dubravka, et al. (författare)
  • M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection.
  • 2018
  • Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 11:1, s. 273-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-Ad restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A-/- mice were significantly less well protected compared with wild-type mice despite exhibiting comparable antibody levels. Similarly, poor protection was also observed in congenic Balb/B (H-2b) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69+ CD103low M2e-specific memory CD4 T cells were αβ TCR+ and 50% were Th17 cells that were associated with an early influx of neutrophils after virus challenge. Adoptively transferred M2e memory CD4 T cells were strong helper T cells, which accelerated M2e- but more importantly also hemagglutinin-specific IgG production. Thus, for the first time we demonstrate that M2e-specific memory CD4 T cells are broadly protective.Mucosal Immunology advance online publication 15 March 2017. doi:10.1038/mi.2017.14.
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31.
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32.
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33.
  • Hernández‑Morcillo, Monica, et al. (författare)
  • Scanning the solutions for the sustainable supply of forest ecosystem services in Europe
  • 2022
  • Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4057 .- 1862-4065. ; 17:5, s. 2013-2029
  • Tidskriftsartikel (refereegranskat)abstract
    • Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from diferent European regions. We identifed and prioritized ffteen major challenges hindering the balanced provision of multiple FES and identifed a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-orientedmanagement through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey,most solutions were assessed as highly efective, transferable, monitorable, and with potential for being economically efcient. The implementation of the solutions could have synergistic efects when applying the notion of leverage points. Sevenemerging pathways towards the sustainable supply of FES have been identifed. These pathways build on each other and areorganized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions betweenforest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparentknowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathwayscan contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES.
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34.
  • Iqbal, Z., et al. (författare)
  • Evidence for a solid phase of dodecahedral C-20
  • 2003
  • Ingår i: European Physical Journal B. - : Springer Science and Business Media LLC. - 1434-6028 .- 1434-6036. ; 31:4, s. 509-515
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence is presented for the formation of a solid phase based on the smallest fullerene, C-20, in thin diamond-like carbon films deposited by ultraviolet laser ablation from diamond onto nickel substrates at room temperature in the presence of 10(-4) torr of cyclohexane or benzene. Laser desorption mass spectrometry from the films shows the presence of C-20, C-21 and C-22 species, while micro-Raman spectroscopy and electron diffraction from selected particles together with first principle density-functional calculations, indicate a cubic solid with dodecahedral C-20 Cages as building blocks. Unlike solid C-60 and fully protonated C-20, which are bound by van der Waals forces, the proposed structure is stabilized by linking of the C-20 dodecahedra with bridging carbon atoms at interstitial tetrahedral sites to form a face-centered-cubic lattice with 22 carbon atoms per unit cell.
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35.
  • Kiess, W, et al. (författare)
  • Induction of puberty in the hypogonadal girl--practices and attitudes of pediatric endocrinologists in Europe
  • 2002
  • Ingår i: Hormone research. - : S. Karger AG. - 0301-0163. ; 57:1-2, s. 66-71
  • Tidskriftsartikel (refereegranskat)abstract
    • The management of children and adolescents with hypogonadism and in particular the induction of puberty in the hypogonadal girl is subject to controversy. Therefore, under the auspices and through organization of the Drugs and Therapeutics Committee of the European Society of Paediatric Endocrinology (ESPE), an interactive voting session and workshop was held at the 39th ESPE Annual Meeting in Brussels to discuss these topics. Common practice in Europe and attitudes of pediatric endocrinologists in Europe were questioned and recorded in the 1.5-hour program. We now report on some of the results of the questionnaires and discussions of that session to further the discussion on and knowledge of current concepts of induction of puberty in the hypogonadal girl in Europe. It became clear from the data accumulated here that the start of treatment, the aims of therapy and the modalities of how to treat the hypogonadal girl vary amongst pediatric endocrinologists in Europe. For example, a chronological age ≧11 years was considered appropriate for the start of estrogen therapy by 40.4% (out of 188 answers), while 47.8 and 7.5% felt that a chronological age ≧13 and ≧15 years respectively was appropriate. In respect to the form and route of estrogen administration, the audience was asked for their common estrogen replacement practice: 31.9% used oral 17β-estradiol treatment, while 10% would prescribe 17β-estradiol transdermal patches. Another 12.2% would recommend conjugated estrogens (e.g. Premarin<sup>®</sup>) orally, 4.8% use oral estradiol valerate and 39.3% ethinylestradiol orally. Only 1.8% out of 229 physicians answering were undecided. In addition, counseling of patients and their families is quite variable and perceptions for example regarding potential pregnancies in affected women are also not uniform. In this report the authors do not want to provide their own personal views but rather reflect current practice in Europe. It is hoped that a more uniform picture will emerge once European and international guidelines on how to treat the girl with hypogonadism will be available and even more discussions amongst doctors from different countries have been led.
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36.
  • Ross, Fiona M., et al. (författare)
  • Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders
  • 2012
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 97:8, s. 1272-1277
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing procedure; 3) most importantly, PCs must be purified or specifically identified; 4) positive cut-off levels should be relatively conservative: 10% for fusion or break-apart probes, 20% for numerical abnormalities; 5) informative probes should be combined to best effect; 6) in specialist laboratories, a single experienced analyst is considered adequate; 7) at least 100 PC should be scored; 8) essential abnormalities to test for are t(4;14), t(14;16) and 17p13 deletions; 9) suitable commercial probes should be available for clinically relevant abnormalities; 10) the clinical report should be expressed clearly and must state the percentage of PC involved and the method used for identification; 11) a retrospective European based FISH data bank linked to clinical data should be generated; and 12) prospective analysis should be centralized for upcoming trials based on the recommendations made. The European Myeloma Network aims to build on these recommendations to establish standards for a common European data base to define subgroups with prognostic significance.
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37.
  • Schouten, Stefan, et al. (författare)
  • An interlaboratory study of TEX86 and BIT analysis of sediments, extracts, and standard mixtures
  • 2013
  • Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 14:12, s. 5263-5285
  • Tidskriftsartikel (refereegranskat)abstract
    • Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility +/- 3-4 degrees C when translated to temperature) but a large spread in BIT measurements (reproducibility +/- 0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0 degrees C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the true (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values.
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38.
  • Újvári,, Gabor, et al. (författare)
  • Stadial-interstadial temperature variations in East Central Europe preceding the Last Glacial Maximum
  • 2021
  • Ingår i: Paleoceanography and Paleoclimatology. - : American Geophysical Union (AGU). - 2572-4517 .- 2572-4525. ; 36
  • Tidskriftsartikel (refereegranskat)abstract
    • Last glacial North Atlantic climate is characterized by abrupt, centennial-millennial scale climate oscillations, called Dansgaard-Oeschger (D-O) events. Understanding the cause and propagation of these D-O events into Eurasia is hampered by the scarcity of quantitative paleotemperature estimates from continental archives with precise, independent age models. Here, we present land snail shell carbonate clumped isotope-based active season paleotemperature estimates and δ13C/δ18O-based aridity reconstructions from Greenland stadial/interstadials (GS/GI) between 31 and 26.5 ka from the 14C-dated Dunaszekcső loess section (Hungary). This reconstruction is complemented with a new 230Th-dated flowstone stable isotope record covering 30-26 ka. Our snail shell clumped isotope (Δ47) data indicate growing season temperatures (GSTs) of 16°C–18°C and 7°C–14°C for the investigated interstadials and stadials, respectively. Stable carbon and oxygen stable isotope compositions of shells and flowstone calcite reveal milder interstadials with drier summers and more available moisture over the winter season, and colder stadials with annually/seasonally (winter) drier conditions, promoting increased loess/dust deposition. We propose that large-scale ocean-atmospheric variability, characterized by NAO phases, may have imparted a major control on transmitting abrupt North Atlantic climate event signals into continental Europe during the last glacial.
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39.
  • Van Hoovels, L., et al. (författare)
  • IgA rheumatoid factor in rheumatoid arthritis
  • 2022
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 60:10, s. 1617-1626
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context. Methods An international sample cohort consisting of samples from 398 RA patients and 1073 controls was tested for IgA RF with 3 commercial assays. For all RA patients and 100 controls essential clinical and serological data for ACR/EULAR classification were available. Results The sensitivity of IgA RF for diagnosing RA was lower than the sensitivity of IgM RF. Differences in numerical values between IgA RF assays were observed. With all assays, the highest IgA RF values were found in patients with primary Sjogren's syndrome. Double positivity for IgM RF and IgA RF had a higher specificity for RA than either IgM RF or IgA RF. The sensitivity of double positivity was lower than the sensitivity of either IgA RF or IgM RF. Single positivity for IgA RF was at least as prevalent in controls than in RA patients. Adding IgA RF to IgM RF and anti-citrullinated protein antibodies (ACPA) did not affect RA classification. However, combined positivity for IgA RF, IgM RF and IgG ACPA had a higher specificity and lower sensitivity for RA classification than positivity for either of the antibodies. Conclusions IgA RF showed a lower sensitivity than IgM RF. Combining IgA RF with IgM RF and ACPA did not improve sensitivity of RA classification. Combined positivity (IgA-RF/IgM-RF/ACPA) increased specificity.
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40.
  • Van Hoovels, L., et al. (författare)
  • Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results
  • 2022
  • Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays. MATERIALS AND METHODS: Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls. RESULTS: Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA. CONCLUSION: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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41.
  • Van Hoovels, L., et al. (författare)
  • Standardisation of ACPA tests: evaluation of a new candidate reference preparation
  • 2022
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:10, s. 1379-1384
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Commercial assays measuring antibodies to citrullinated protein/peptide (ACPA) show poor quantitative agreement. The diagnostic industry has never adopted the International Union of Immunological Societies-Centers for Disease Control and Prevention (IUIS-CDC) ACPA reference standard. Recently, the National Institute for Biological Standards and Control (NIBSC) prepared a new candidate ACPA standard (18/204). We evaluated both reference materials using different commercially available ACPA assays. Materials and methods This is an international study in which the NIBSC candidate ACPA standard and the IUIS-CDC ACPA reference material were analysed together with 398 diagnostic samples from individuals with rheumatoid arthritis (RA) and in 1073 individuals who did not have RA using nine commercial ACPA assays. Results For both reference materials and samples from individuals with RA and individuals who did not have RA, there were large differences in quantitative ACPA results between assays. For most assays, values for the IUIS-CDC standard were lower than values for NIBSC 18/204 and the IUIS-CDC/NIBSC ratio was comparable for several, but not all assays. When NIBSC 18/204 was used as a calibrator, an improvement in alignment of ACPA results across several of the evaluated assays was obtained. Moreover, NIBSC 18/204 could align clinical interpretation for some but not all assays. Conclusion Adoption of an international standard for ACPA determination is highly desirable. The candidate NIBSC 18/204 standard improved the standardisation and alignment of most ACPA assays and might therefore be recommended to be used as reference in commercial assays.
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