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Sökning: WFRF:(Bernhardt B.)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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3.
  • Grieser, M., et al. (författare)
  • Storage ring at HIE-ISOLDE Technical design report
  • 2012
  • Ingår i: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 207:1, s. 1-117
  • Forskningsöversikt (refereegranskat)abstract
    • We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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4.
  • Sha, ZQ, et al. (författare)
  • Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium
  • 2022
  • Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:4, s. 2114-2125
  • Tidskriftsartikel (refereegranskat)abstract
    • Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium’s ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.
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5.
  • Staude, I. R., et al. (författare)
  • Directional turnover towards larger-ranged plants over time and across habitats
  • 2022
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 466-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation.
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6.
  • Bernhardt, A. M., et al. (författare)
  • A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases
  • 2023
  • Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 89
  • Tidskriftsartikel (refereegranskat)abstract
    • A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi) genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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7.
  • Grieser, M., et al. (författare)
  • Storage ring at HIE-ISOLDE
  • 2012
  • Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 207:1, s. 1-117
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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9.
  • Lestinsky, M., et al. (författare)
  • Physics book: CRYRING@ESR
  • 2016
  • Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 225:5, s. 797-882
  • Forskningsöversikt (refereegranskat)abstract
    • The exploration of the unique properties of stored and cooled beams of highly-charged ions as provided by heavy-ion storage rings has opened novel and fascinating research opportunities in the realm of atomic and nuclear physics research. Since the late 1980s, pioneering work has been performed at the CRYRING at Stockholm (Abrahamsson et al. 1993) and at the Test Storage Ring (TSR) at Heidelberg (Baumann et al. 1988). For the heaviest ions in the highest charge-states, a real quantum jump was achieved in the early 1990s by the commissioning of the Experimental Storage Ring (ESR) at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt (Franzke 1987) where challenging experiments on the electron dynamics in the strong field regime as well as nuclear physics studies on exotic nuclei and at the borderline to atomic physics were performed. Meanwhile also at Lanzhou a heavy-ion storage ring has been taken in operation, exploiting the unique research opportunities in particular for medium-heavy ions and exotic nuclei (Xia et al. 2002).
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10.
  • Lindgren, Arne G., et al. (författare)
  • International stroke genetics consortium recommendations for studies of genetics of stroke outcome and recovery
  • 2022
  • Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 17:3, s. 260-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.
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11.
  • Staude, I. R., et al. (författare)
  • Replacements of small- by large-ranged species scale up to diversity loss in Europe's temperate forest biome
  • 2020
  • Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 4, s. 802-808
  • Tidskriftsartikel (refereegranskat)abstract
    • The loss of biodiversity at the global scale has been difficult to reconcile with observations of no net loss at local scales. Vegetation surveys across European temperate forests show that this may be explained by the replacement of small-ranged species with large-ranged ones, driven by nitrogen deposition. Biodiversity time series reveal global losses and accelerated redistributions of species, but no net loss in local species richness. To better understand how these patterns are linked, we quantify how individual species trajectories scale up to diversity changes using data from 68 vegetation resurvey studies of seminatural forests in Europe. Herb-layer species with small geographic ranges are being replaced by more widely distributed species, and our results suggest that this is due less to species abundances than to species nitrogen niches. Nitrogen deposition accelerates the extinctions of small-ranged, nitrogen-efficient plants and colonization by broadly distributed, nitrogen-demanding plants (including non-natives). Despite no net change in species richness at the spatial scale of a study site, the losses of small-ranged species reduce biome-scale (gamma) diversity. These results provide one mechanism to explain the directional replacement of small-ranged species within sites and thus explain patterns of biodiversity change across spatial scales.
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12.
  • Biberhofer, P, et al. (författare)
  • Joint CASE Report on Content and Methods for the Joint Master Program on Sustainability-driven Entrepreneurship
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The CASE project develops a joint master program on sustainability-driven entrepreneurship in a university-business knowledge alliance. However, it is not only for the development of the master program that university opens up to consider and integrate further stakeholder perspectives into the process. The future students shall learn in a transdisciplinary learning environment, steadily researching and integrating real-world needs and perspectives to develop competencies that enable them to solve complex sustainability-problems in their further careers. In the CASE project, we aim to avoid the indicated gap between sustainability-oriented, real-world contents and not corresponding pedagogical frameworks. We connect the development of contents and methods in the two interlinked work packages 3 and 4 in terms of process and outcomes (see Figure 1 for an overview of the WPs that contribute to the development of the master program). WP 3 is focusing on relevant content areas for the master program and WP 4 is analyzing innovative methods to foster competencies of sustainability-driven entrepreneurship. The output of the two WPs is this joint report describing the joint development process, giving background information on relevant content areas for sustainability-driven entrepreneurship and adequate teaching and learning approaches. In the course of the development process of WP 3 and WP 4 we considered different regional requirements and needs of the universities that are part of the CASE consortium and further stakeholders via participatory multi-stakeholder workshops. In chapter 1.3 we describe this process in detail and particularly elaborate on the multi-stakeholder approach chosen in the CASE project. This development process first covered clustering relevant topics to thematic areas, then structuring these into modules and courses with various teaching formats. Finally, we added recommendations for concrete teaching and learning methods. The report outlines modules for a master program that are designed to foster competencies of sustainability-driven entrepreneurship. Since the overarching aim of the CASE project is to develop a joint master program that can be adopted by various European universities, we are ambitious to create modules which are adaptable and can flexibly be implemented in different regional contexts and under differing conditions of universities. With this report, we are sharing our knowledge and experiences gained so far to make them accessible to HEIs, company partners and all other stakeholders interested in the topic of sustainability-driven entrepreneurship and in innovative teaching and learning methods.
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14.
  • Burstrom, B, et al. (författare)
  • Use of a historical register in social epidemiology: child mortality in Stockholm at the turn of the 19th century
  • 1998
  • Ingår i: Scandinavian journal of social medicine. - : SAGE Publications. - 0300-8037. ; 26:3, s. 166-172
  • Tidskriftsartikel (refereegranskat)abstract
    • This study describes the age- and cause-specific levels and social determinants of high child mortality in Stockholm around the turn of the century. The study is based on computerized individual level sociodemographic information and the death certificates of children aged 0-15 years residing in Maria parish in Stockholm during the years 1885, 1891 and 1910 (n=36 718) from a historical register (the Roteman archives). The usefulness of such data for further studies in social epidemiology is discussed. Age-specific rates and major causes of death compared well with other studies. Low social class and being born out of wedlock increased the overall risk of death in early childhood. Data appear valid and may be useful in social epidemiology. Further analyses of data from the Roteman archives may contribute to the understanding of causes behind high levels of cause- specific child mortality and trends in mortality in relation to societal change.
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18.
  • Båth, Magnus, et al. (författare)
  • OPTIMISATION in X-RAY and MOLECULAR IMAGING 2020
  • 2021
  • Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 195:3-4, s. 133-133
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Cumming, T. B., et al. (författare)
  • Early Mobilization After Stroke Is Not Associated With Cognitive Outcome Findings From AVERT
  • 2018
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 49:9, s. 2147-2154
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose We aimed to determine whether early mobilization after stroke affects subsequent cognitive function. Methods-AVERT (A Very Early Rehabilitation Trial) was an international, 56-site, phase 3 randomized controlled trial, conducted from 2006 to 2015. Participants were included if they were aged 18+, presented within 24 hours of stroke, and satisfied physiological limits for blood pressure, heart rate, and temperature. Participants were randomized to receive either usual stroke unit care or very early and more frequent mobilization in addition to usual stroke unit care. The Montreal Cognitive Assessment, scored 0 to 30, was introduced as a 3-month outcome during 2008. Results-Of the 2104 patients included in AVERT, 317 were assessed before the Montreal Cognitive Assessment's introduction. Of the remaining 1787, 1189 (66.5%) had complete Montreal Cognitive Assessment data, 456 (25.5%) had partially or completely missing data, 136 (7.6%) had died, and 6 (0.3%) were lost to follow-up. In surviving participants with complete data, adjusting for age and stroke severity, total Montreal Cognitive Assessment score was no different in the intervention (n=595; median, 23; interquartile range, 19-26; mean, 21.9; SD, 5.9) and usual care (n=594; median, 23; interquartile range, 19-26; mean, 21.8; SD, 5.9) groups (P=0.68). Conclusions-Exposure to earlier and more frequent mobilization in the acute stage of stroke does not influence cognitive outcome at 3 months. This stands in contrast to the primary outcome from AVERT (modified Rankin Scale), where the intervention group had less favorable outcomes than controls.
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21.
  • Cumming, Toby B, et al. (författare)
  • Hemispatial neglect and rehabilitation in acute stroke.
  • 2009
  • Ingår i: Archives of physical medicine and rehabilitation. - : Elsevier BV. - 1532-821X .- 0003-9993. ; 90:11, s. 1931-6
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To compare 2 methods for determining neglect in patients within 2 days of stroke, and to investigate whether early neglect was related to rehabilitation practice, and whether this relationship was affected by an early, intensive mobilization intervention. DESIGN: Data were collected from patients participating in a phase II randomized controlled trial of early rehabilitation after stroke. SETTING: Acute hospital stroke unit. PARTICIPANTS: Stroke patients (N=71). INTERVENTION: The 2 arms of the trial were very early mobilization (VEM) and standard care (SC). MAIN OUTCOME MEASURES: Neglect was assessed using the Star Cancellation Test and the National Institutes of Health Stroke Scale (NIHSS) inattention item within 48 hours of stroke onset, and therapy details were recorded during the hospital stay. RESULTS: Assessing neglect so acutely after stroke was difficult: 29 of the 71 patients were unable to complete the Star Cancellation Test, and agreement between this test and the NIHSS measure was only .42. Presence of neglect did not preclude early mobilization. SC group patients with neglect had longer hospital stays (median, 11d) than those without neglect (median, 4d); there was no difference in length of stay between patients with and without neglect in the VEM group (median, 6d in both). CONCLUSION: Early mobilization of patients with neglect was feasible and may contribute to a shorter acute hospital stay.
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22.
  • Cumming, T. B., et al. (författare)
  • Montreal Cognitive Assessment and Mini-Mental State Examination are both valid cognitive tools in stroke
  • 2013
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 128:2, s. 122-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective - To determine the validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) as screening tools for cognitive impairment after stroke. Materials and methods - Cognitive assessments were administered over 2 sessions (1 week apart) at 3 months post-stroke. Scores on the MoCA and MMSE were evaluated against a diagnosis of cognitive impairment derived from a comprehensive neuropsychological battery (the criterion standard). Results - Sixty patients participated in the study [mean age 72.1 years (SD = 13.9), mean education 10.5 years (SD = 3.9), median acute NIHSS score 5 (IQR 3-7)]. The MoCA yielded lower scores (median = 21, IQR = 17-24; mean = 20.0, SD = 5.4) than the MMSE (median = 26, IQR = 22-27; mean = 24.2, SD = 4.5). MMSE data were more skewed towards ceiling than MoCA data (skewness = -1.09 vs -0.73). Area under the receiver operator curve was higher for MoCA than for MMSE (0.87 vs 0.84), although this difference was not significant (chi(2) = 0.48, P = 0.49). At their optimal cut-offs, the MoCA had better sensitivity than the MMSE (0.92 vs 0.82) but poorer specificity (0.67 vs 0.76). Conclusions - The MoCA is a valid screening tool for post-stroke cognitive impairment; it is more sensitive but less specific than the MMSE. Contrary to the prevailing view, the MMSE also exhibited acceptable validity in this setting.
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23.
  • Cumming, T. B., et al. (författare)
  • The AVERT MoCA Data: Scoring Reliability in a Large Multicenter Trial
  • 2020
  • Ingår i: Assessment. - : SAGE Publications. - 1073-1911 .- 1552-3489. ; 27:5, s. 976-981
  • Tidskriftsartikel (refereegranskat)abstract
    • The Montreal Cognitive Assessment (MoCA) is a widely used cognitive screening tool in stroke. As scoring the visuospatial/executive MoCA items involves subjective judgement, reliability is important. Analyzing data on these items from A Very Early Rehabilitation Trial (AVERT), we compared the original scoring of assessors (n= 102) to blind scoring by a single, independent rater. In a sample of scoresheets from 1,119 participants, we found variable interrater reliability. The match between original assessors and the independent rater was the following: trail-making 97% (kappa = 0.94), cube copy 90% (kappa = 0.80), clock contour 92% (kappa = 0.49), clock numbers 89% (kappa = 0.67), and clock hands 72% (kappa = 0.46). For all items except clock contour, the independent rater was "stricter" than the original assessors. Discrepancies were typically errors in original scoring, rather than borderline differences in subjective judgement. In trials that include the MoCA, researchers should emphasize scoring rules to assessors and implement independent data checking, especially for clock hands, to maximize accuracy.
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  • Hysell, D. L., et al. (författare)
  • Heater-induced ionization inferred from spectrometric airglow measurements
  • 2014
  • Ingår i: Journal of Geophysical Research A: Space Physics. - 2169-9380. ; 119:3, s. 2038-2045
  • Tidskriftsartikel (refereegranskat)abstract
    • Spectrographic airglow measurements were made during an ionospheric modification experiment at High Frequency Active Auroral Research Program on 12 March 2013. Artificial airglow enhancements at 427.8, 557.7, 630.0, 777.4, and 844.6 nm were observed. On the basis of these emissions and using a methodology based on the method of Backus and Gilbert (1968, 1970), we estimate the suprathermal electron population and the subsequent equilibrium electron density profile, including contributions from electron impact ionization. We find that the airglow is consistent with heater-induced ionization in view of the spatial intermittency of the airglow.
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  • Kananen, L, et al. (författare)
  • Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
  • 2023
  • Ingår i: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 45:1, s. 85-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
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33.
  • Kananen, L, et al. (författare)
  • Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 6139-
  • Tidskriftsartikel (refereegranskat)abstract
    • Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual’s subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.
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34.
  • Kölby, Lars, 1963, et al. (författare)
  • A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
  • 2001
  • Ingår i: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
  • Tidskriftsartikel (refereegranskat)abstract
    • A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
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35.
  • Levin, Johannes, et al. (författare)
  • α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
  • 2024
  • Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:6, s. 4351-4365
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
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37.
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38.
  • Macassa, Gloria, et al. (författare)
  • Differentials in overall and cause-specific mortality among infants born in and out of wedlock, Stockholm 1878-1925
  • 2006
  • Ingår i: The History of the Family. - : Informa UK Limited. - 1081-602X .- 1873-5398. ; 11:1, s. 19-26
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates differentials in the decline of cause-specific infant mortality by marital status of the mother in Stockholm (1878-1925) and factors contributing to the explanation of these differentials using computerized records of individual entries from the Roteman Archives. Included in the analysis were 120,094 children less than 1 year of age who lived in Södermalm during this period. Cause-specific mortality rates were calculated for three time periods. Cox's regression analysis was used to study the relationship between overall and cause-specific risk of infant death and of being born in and out of wedlock in relation to a set of variables. Infant mortality rates and mortality risks were higher among children born out of rather than in wedlock. The most pronounced differentials in cause-specific mortality rates between these groups of children were seen in cases of diarrhea. The socioeconomic status of the household head and number of children in the household were statistically significant with infant mortality, but explain only part of the excess mortality risk of children born out of wedlock. In Stockholm at the turn of the 19th century being born out of wedlock was strongly associated with poor health outcomes, particularly in diarrheal diseases, pneumonia/ bronchitis, and immaturity/congenital causes.
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39.
  • Macassa, Gloria, et al. (författare)
  • Inequalities in child mortality in Mozambique : differentials by parental socio-economic position
  • 2003
  • Ingår i: Social Science and Medicine. - 0277-9536 .- 1873-5347. ; :57, s. 2255-2264
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates the relation between socio-economic parental position (education and occupation) and child death in Mozambique using data from the Mozambican Demographic and Health Survey carried out between March and July 1997. The analysis included 9142 children born within 10 years before the survey. In spite of the Western system of classification used in the study, the results partly showed a parental socio-economic gradient of infant and child mortality in Mozambique. Father's education seemed to reflect the family's social standing in the Mozambique context, showing a strong statistical association with postneonatal and child mortality. However, maternal education as a measure of socio-economic position was not statistically significantly associated with child mortality. This finding may partly be explained by the extreme hardships experienced by the country (civil war and natural disasters) and the implementation of the Economic Structural Adjustment Programme that have also affected the health of women and their children during the years covered by this study. Other measures of socio-economic position applicable to the rural African setting should be investigated.
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40.
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41.
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42.
  • Macassa, Gloria, et al. (författare)
  • Trends in infant and child mortality in Mozambique during and after a period ofconflict
  • 2003
  • Ingår i: Public Health. - 0033-3506 .- 1476-5616. ; 117:4, s. 221-227
  • Tidskriftsartikel (refereegranskat)abstract
    • This study describes urban and rural trends of infant, child and under-five mortality in Mozambique (1973–1997) by mother's place of residence. A direct method of estimation was applied to the 1997 Mozambican Demographic and Health Survey data. The levels of infant, child and under-five mortality were considerably higher in rural than in urban areas. The difference in mortality between urban and rural areas increased over time until 1988–1992 and thereafter diminished. Possible causes of the different trends (e.g. the impact of civil war, drought, migration, adjustment programme and HIV/AIDS) are discussed. The increase in mortality in urban areas during the last few years before the survey may have been related to the immigration to urban areas of mothers whose children had high levels of mortality. Higher levels of infant, child and under-five mortality still prevail, particularly in rural areas. Further studies are needed to investigate the differentials of infant and child mortality by mother's place of residence.
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43.
  • Mathey, Carina M, et al. (författare)
  • Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes
  • 2022
  • Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher's exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.
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44.
  • Nordblad, Erik, 1981- (författare)
  • Opening New Radio Windows and Bending Twisted Beams
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In ground based high frequency (HF) radio pumping experiments, absorption of ordinary (O) mode pump waves energises the ionospheric plasma, producing optical emissions and other effects. Pump-induced or natural kilometre-scale field-aligned density depletions are believed to play a role in self-focussing phenomena such as the magnetic zenith (MZ) effect, i.e., the increased plasma response observed in the direction of Earth's magnetic field. Using ray tracing, we study the propagation of ordinary (O) mode HF radio waves in an ionosphere modified by density depletions, with special attention to transmission through the radio window (RW), where O mode waves convert into the extraordinary (X, or Z) mode. The depletions are shown to shift the position of the RW, or to introduce RWs at new locations. In a simplified model neglecting absorption, we estimate the wave electric field strength perpendicular to the magnetic field at altitudes normally inaccessible. This field could excite upper hybrid waves on small scale density perturbations. We also show how transmission and focussing combine to give stronger fields in some directions, notably at angles close to the MZ, with possible implications for the MZ effect. In a separate study, we consider electromagnetic (e-m) beams with helical wavefronts (i.e., twisted beams), which are associated with orbital angular momentum (OAM). By applying geometrical optics to each plane wave component of a twisted nonparaxial e-m Bessel beam, we calculate analytically the shift of the beam's centre of gravity during propagation perpendicularly and obliquely to a weak refractive index gradient in an isotropic medium. In addition to the so-called Hall shifts expected from paraxial theory, the nonparaxial treatment reveals new shifts in both the transverse and lateral directions. In some situations, the new shifts should be significant also for nearly paraxial beams.
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45.
  • 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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46.
  • Powers, M. B., et al. (författare)
  • A Randomized Controlled Trial of Animated Versus Live Action Virtual Reality Therapy for Anxiety & Pain in a Level I Trauma Center
  • 2018
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • While virtual reality exposure therapy (VRET) shows promise as a treatment for anxiety and pain (Powers & Emmelkamp, 2008), many users complain that computer-generated virtual reality (VR) stimuli appear unrealistic, eccentric, and too much like a video game (Kwon, Powell, & Chalmers, 2013). Historically, programmers using video game assets and computer-generated imagery (CGI) created VR content. While CGI can be used to make intricate virtual environments, unless there is a team of expert digital artists, the virtual stimulus may look unrealistic and exhibit a number of graphical glitches that could prove distracting in therapy. Furthermore, CGI often suffers from the uncanny valley effect, where CGI representations of people are perceived as unsettling as the representations become more lifelike. Thus, the only method to overcome the uncanny valley effect is to present the VR as less realistic (CGI) or photorealistic. In addition, current CGI VR packages are expensive and difficult to implement in widespread medical settings. Recently, however, an exciting alternative to traditional computer-generated VR has emerged: 360-Degree 3-D HD Video VR (Live Action). The benefit of Live Action VR as opposed to CGI VR is that it is photorealistic and doesn’t cause the uncanny valley effect of CGI. In addition, the projected cost of the end product is approximately $500 and delivered using a portable VR headset. In this RCT, participants in a Level I Trauma Center reporting pain (N = 78) were randomized to waitlist, 10-minutes of CGI VR, or 10-minutes of Live Action VR. Consistent with prediction, both VR conditions showed greater reduction in anxiety relative to waitlist (p < .05). However, there was no difference between the conditions. The two VR conditions also showed significantly greater reductions in pain (p < .001) and pain interference (p < .001) relative to the waitlist with no differences between conditions. As expected, participants rated Live Action VR significantly more realistic than CGI VR (p < .001) and reported a greater sense of being in the virtual world (p < .05). Finally, 92% of participants in the waitlist preferred to view the Live Action VR.
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47.
  • Powers, Mark B., et al. (författare)
  • Nonpharmacologic Pain Management Among Hospitalized Inpatients : A Randomized Waitlist-Controlled Trial of Standard Virtual Reality (CGI VR) Versus Video Capture VR (360 degrees 3D/Stereoscopic Video Capture VR)
  • 2021
  • Ingår i: The Clinical Journal of Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0749-8047 .- 1536-5409. ; 37:9, s. 678-687
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Nonpharmacologic pain management strategies are needed because of the growing opioid epidemic. While studies have examined the efficacy of virtual reality (VR) for pain reduction, there is little research in adult inpatient settings, and no studies comparing the relative efficacy of standard animated computer-generated imagery (CGI) VR to Video Capture VR (360 degrees 3D/stereoscopic Video Capture VR). Here, we report on a randomized controlled trial of the relative efficacy of standard CGI VR versus Video Capture VR (matched for content) and also compared the overall efficacy of VR to a waitlist control group.Materials and Methods: Participants (N=103 hospitalized inpatients reporting pain) were randomized to 1 of 3 conditions: (1) waitlist control, (2) CGI VR, or (3) Video Capture VR. The VR and waitlist conditions were 10 minutes in length. Outcomes were assessed pretreatment, post-treatment, and after a brief follow-up.Results: Consistent with hypotheses, both VR conditions reduced pain significantly more relative to the waitlist control condition (d=1.60, P<0.001) and pain reductions were largely maintained at the brief follow-up assessment. Both VR conditions reduced pain by ∼50% and led to improvements in mood, anxiety, and relaxation. Contrary to prediction, the Video Capture VR condition was not significantly more effective at reducing pain relative to the CGI VR condition (d=0.25, P=0.216). However, as expected, patients randomized to the Video Capture VR rated their experience as more positive and realistic (d=0.78, P=0.002).Discussion: Video Capture VR was as effective as CGI VR for pain reduction and was rated as more realistic.
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48.
  • Schindler, L, et al. (författare)
  • Development of a Neurotensin-Derived 68Ga-Labeled PET Ligand with High In Vivo Stability for Imaging of NTS1 Receptor-Expressing Tumors
  • 2022
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Overexpression of the neurotensin receptor type 1 (NTS1R), a peptide receptor located at the plasma membrane, has been reported for a variety of malignant tumors. Thus, targeting the NTS1R with 18F- or 68Ga-labeled ligands is considered a straightforward approach towards in vivo imaging of NTS1R-expressing tumors via positron emission tomography (PET). The development of suitable peptidic NTS1R PET ligands derived from neurotensin is challenging due to proteolytic degradation. In this study, we prepared a series of NTS1R PET ligands based on the C-terminal fragment of neurotensin (NT(8–13), Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) by attachment of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an Nω-carbamoylated arginine side chain. Insertion of Ga3+ in the DOTA chelator gave potential PET ligands that were evaluated concerning NTS1R affinity (range of Ki values: 1.2–21 nM) and plasma stability. Four candidates were labeled with 68Ga3+ and used for biodistribution studies in HT-29 tumor-bearing mice. [68Ga]UR-LS130 ([68Ga]56), containing an N-terminal methyl group and a β,β-dimethylated tyrosine instead of Tyr11, showed the highest in vivo stability and afforded a tumor-to-muscle ratio of 16 at 45 min p.i. Likewise, dynamic PET scans enabled a clear tumor visualization. The accumulation of [68Ga]56 in the tumor was NTS1R-mediated, as proven by blocking studies.
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49.
  • Schmitz, G. J., et al. (författare)
  • Software Solutions for ICME
  • 2016
  • Ingår i: JOM. - : Springer. - 1047-4838 .- 1543-1851. ; 68:1, s. 70-76
  • Tidskriftsartikel (refereegranskat)abstract
    • The Integrated Computational Materials Engineering expert group (ICMEg), a coordination activity of the European Commission, aims at developing a global and open standard for information exchange between the heterogeneous varieties of numerous simulation tools. The ICMEg consortium coordinates respective developments by a strategy of networking stakeholders in the first International Workshop on Software Solutions for ICME, compiling identified and relevant software tools into the Handbook of Software Solutions for ICME, discussing strategies for interoperability between different software tools during a second (planned) international workshop, and eventually proposing a scheme for standardized information exchange in a future book or document. The present article summarizes these respective actions to provide the ICME community with some additional insights and resources from which to help move this field forward.
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50.
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