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1.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Zouganelis, I., et al. (författare)
  • The Solar Orbiter Science Activity Plan : Translating solar and heliospheric physics questions into action
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission's science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit's science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter's SAP through a series of examples and the strategy being followed.
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  • Armesto, N., et al. (författare)
  • Heavy-ion collisions at the LHC-Last call for predictions
  • 2008
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 35:5, s. 054001-
  • Forskningsöversikt (refereegranskat)abstract
    • This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from 14th May to 10th June 2007.
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  • Zhou, Wei, et al. (författare)
  • Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
  • 2022
  • Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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  • Haas, Jan, et al. (författare)
  • Atlas of the clinical genetics of human dilated cardiomyopathy
  • 2015
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 36:18, s. 1123-U43
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.
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  • Ashkir, Z., et al. (författare)
  • Novel insights into diminished cardiac reserve in non-obstructive hypertrophic cardiomyopathy from four-dimensional flow cardiac magnetic resonance component analysis
  • 2023
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : OXFORD UNIV PRESS. - 2047-2404 .- 2047-2412. ; 24:9, s. 1192-1200
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. Methods and results Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for >two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 +/- 9% vs. 39.4 +/- 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = -0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. Conclusion Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk in HCM.
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  • Krastev, DB, et al. (författare)
  • The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin
  • 2022
  • Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1476-4679 .- 1465-7392. ; 24:1, s. 62-
  • Tidskriftsartikel (refereegranskat)abstract
    • Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using wild-type and a trapping-deficient PARP1 mutant combined with rapid immunoprecipitation mass spectrometry of endogenous proteins and Apex2 proximity labelling, we delineated mass spectrometry-based interactomes of trapped and non-trapped PARP1. These analyses identified an interaction between trapped PARP1 and the ubiquitin-regulated p97 ATPase/segregase. We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. Small-molecule p97-complex inhibitors, including a metabolite of the clinically used drug disulfiram (CuET), prolonged PARP1 trapping and enhanced PARP inhibitor-induced cytotoxicity in homologous recombination-defective tumour cells and patient-derived tumour organoids. Together, these results suggest that p97 ATPase plays a key role in the processing of trapped PARP1 and the response of tumour cells to PARP inhibitors.
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  • Burdett, H. L., et al. (författare)
  • Effects of high temperature and CO2 on intracellular DMSP in the cold-water coral Lophelia pertusa
  • 2014
  • Ingår i: Marine Biology. - : Springer. - 0025-3162 .- 1432-1793. ; 161:7, s. 1499-1506
  • Tidskriftsartikel (refereegranskat)abstract
    • Significant warming and acidification of the oceans is projected to occur by the end of the century. CO2 vents, areas of upwelling and downwelling, and potential leaks from carbon capture and storage facilities may also cause localised environmental changes, enhancing or depressing the effect of global climate change. Cold-water coral ecosystems are threatened by future changes in carbonate chemistry, yet our knowledge of the response of these corals to high temperature and high CO2 conditions is limited. Dimethylsulphoniopropionate (DMSP), and its breakdown product dimethylsulphide (DMS), are putative antioxidants that may be accumulated by invertebrates via their food or symbionts, although recent research suggests that some invertebrates may also be able to synthesise DMSP. This study provides the first information on the impact of high temperature (12 A degrees C) and high CO2 (817 ppm) on intracellular DMSP in the cold-water coral Lophelia pertusa from the Mingulay Reef Complex, Scotland (56A degrees 49'N, 07A degrees 23'W), where in situ environmental conditions are meditated by tidally induced downwellings. An increase in intracellular DMSP under high CO2 conditions was observed, whilst water column particulate DMS + DMSP was reduced. In both high temperature treatments, intracellular DMSP was similar to the control treatment, whilst dissolved DMSP + DMS was not significantly different between any of the treatments. These results suggest that L. pertusa accumulates DMSP from the surrounding water column; uptake may be up-regulated under high CO2 conditions, but mediated by high temperature. These results provide new insight into the biotic control of deep-sea biogeochemistry and may impact our understanding of the global sulphur cycle, and the survival of cold-water corals under projected global change.
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  • Hennige, S. J., et al. (författare)
  • Hidden impacts of ocean acidification to live and dead coral framework
  • 2015
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : Royal Society Publishing. - 0962-8452 .- 1471-2954. ; 282:1813
  • Tidskriftsartikel (refereegranskat)abstract
    • Cold-water corals, such as Lophelia pertusa, are key habitat-forming organisms found throughout the world's oceans to 3000 m deep. The complex three-dimensional framework made by these vulnerable marine ecosystems support high biodiversity and commercially important species. Given their importance, a key question is how both the living and the dead framework will fare under projected climate change. Here, we demonstrate that over 12 months L. pertusa can physiologically acclimate to increased CO2, showing sustained net calcification. However, their new skeletal structure changes and exhibits decreased crystallographic and molecular-scale bonding organization. Although physiological acclimatization was evident, we also demonstrate that there is a negative correlation between increasing CO2 levels and breaking strength of exposed framework (approx. 20-30% weaker after 12 months), meaning the exposed bases of reefs will be less effective load-bearers', and will become more susceptible to bioerosion and mechanical damage by 2100.
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  • Hennige, S. J., et al. (författare)
  • Short-term metabolic and growth responses of the cold-water coral Lophelia pertusa to ocean acidification
  • 2014
  • Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645 .- 1879-0100. ; 99, s. 27-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Cold-water corals are associated with high local biodiversity, but despite their importance as ecosystem engineers, little is known about how these organisms will respond to projected ocean acidification. Since preindustrial times, average ocean pH has decreased from 8.2 to similar to 8.1, and predicted CO2 emissions will decrease by up to another 0.3 pH units by the end of the century. This decrease in pH may have a wide range of impacts upon marine life, and in particular upon calcifiers such as cold-water corals. Lophelia pertusa is the most widespread cold-water coral (CWC) species, frequently found in the North Atlantic. Here, we present the first short-term (21 days) data on the effects of increased CO2 (750 ppm) upon the metabolism of freshly collected L pertusa from Mingulay Reef Complex, Scotland, for comparison with net calcification. Over 21 days, corals exposed to increased CO2 conditions had significantly lower respiration rates (11.4 +/- 1.39 SE, gmol O-2 g(-1) tissue dry weight h(-1)) than corals in control conditions (28.6 +/- 7.30 SE mu mol O-2 g(-1) tissue dry weight h(-1)). There was no corresponding change in calcification rates between treatments, measured using the alkalinity anomaly technique and C-14 uptake. The decrease in respiration rate and maintenance of calcification rate indicates an energetic imbalance, likely facilitated by utilisation of lipid reserves. These data from freshly collected L pertusa from the Mingulay Reef Complex will help define the impact of ocean acidification upon the growth, physiology and structural integrity of this key reef framework forming species. 
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  • Hollander, Anna-Clara, et al. (författare)
  • Validation study of randomly selected cases of PTSD diagnoses identified in a Swedish regional database compared with medical records : is the validity sufficient for epidemiological research?
  • 2019
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: In Sweden, the patients' diagnoses are recorded in administrative registers. The research value of these registers is determined by their diagnostic validity, that is, if the diagnosis recorded meets the relevant diagnostic criteria. The aim of the study was to assess the validity of post-traumatic stress disorder (PTSD)-diagnoses as compared with case notes in medical records (MRs) and to test if there was a difference in validity by gender, migration status and those with and without psychotic symptoms. We hypothesised that the validity would be sufficient, using both Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and DSM-5 but higher according to DSM-IV than DSM-5, and that the validity would be the same for men and women, but different for Swedish-born and migrants, and for those with and without psychotic symptoms.DESIGN AND SETTING: A validation of the register-diagnoses using MRs from treatment centres within the Region of Stockholm to examine whether patients with a register-diagnosis of PTSD fulfilled DSM criteria of PTSD according to the case notes in their MRs.PARTICIPANTS: A random sample of 187 patients aged 18-64, who had been diagnosed with PTSD (F43.1 in the ICD-10) were drawn from the Region of Stockholm's MR database 2013-2015.PRIMARY OUTCOME MEASURE: Validity of the PTSD diagnoses according to DSM-IV and DSM-5 as proportions of true positives with 95% CI.RESULTS: The hypothesised sufficient validity of the PTSD diagnoses was confirmed. Although the point-estimates for DSM-IV were higher than for DSM-5, the hypothesis that there would be significant differences in validity between DSM-IV and DSM-5 was not confirmed. There were no significant validity differences by gender, migration status and for those with and without psychotic symptoms.CONCLUSIONS: This study has found that validity of the PTSD diagnoses in the register of the Region of Stockholm to be sufficient for epidemiological research.
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  • MacCabe, J. H., et al. (författare)
  • Decline in Cognitive Performance Between Ages 13 and 18 Years and the Risk for Psychosis in Adulthood A Swedish Longitudinal Cohort Study in Males
  • 2013
  • Ingår i: Jama Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 70:3, s. 261-270
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Clear evidence from many prospective, population-based studies indicates that patients who Objective: To assess the influence of cognitive developmental trajectories in adolescence and young Design: Longitudinal cohort study. Setting: Academic research. Population-Based Cohorts: Four population-based cohorts of adolescent boys and young men born in Exposure: Scores on tests of verbal, spatial, and inductive ability at age 13 years and in equivalent tests Main Outcome Measure: Hospital admissions for non-affective or affective psychoses in adulthood. Results: A relative decline (compared with the unaffected population) in verbal ability between ages 13 Conclusions: A relative decline in cognitive performance in adolescence and young adulthood
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  • McKinlay, Audrey, et al. (författare)
  • Service provision for children and young people with acquired brain injury : Practice recommendations
  • 2016
  • Ingår i: Brain Injury. - : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 30:13-14, s. 1656-1664
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Providing appropriate rehabilitation services for Acquired Brain Injury (ABI) in childhood presents a number of challenges for caregivers, health and education professionals and the young person as they develop. Primary objective: To record the challenges and possible creative solutions generated by an international group of professionals to address the needs of children with ABI. Review of information: Recommendations were generated from children's special interest group meetings of the International Brain Injury Association (Turin, Italy, 2001; Stockholm, Sweden, 2003; Melbourne, Australia, 2005; Lisbon, Portugal, 2008) and through meetings of the International Paediatric Brain Injury Society (IPBIS), formed in 2009. Delegates participating in the workshops were representative of nations from around the world and included The Netherlands, New Zealand, Australia, the UK, Finland, Germany, South Africa, the US, Canada, Sweden, Brazil and Italy. Outcomes: The information presented is based on a retrospective review of those meetings and the summaries of the topics considered.
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  • Nilsson, Ingeborg, et al. (författare)
  • Occupational engagement among community dwelling older people : a time-geographic perspective
  • 2015
  • Ingår i: Health Promotion International. - : Oxford University Press. - 0957-4824 .- 1460-2245. ; 30:3, s. 484-494
  • Tidskriftsartikel (refereegranskat)abstract
    • How older people spend their time in different occupations could contribute to our understanding of everyday life in healthy ageing. This study adopted a time-geographic method and occupational perspective to explore the occupational engagement of community dwelling older people. The term occupational engagement encompasses what people do, where and with whom they spend their time and the perceived level of competence and meaningfulness of their time use. Nineteen volunteers born between 1932 and 1933, living alone in an urban area in northern Sweden and receiving no home care services, completed open time-geographic diaries for 5 days in May 2010. The diary data were analyzed using Daily Life software program. The study revealed the complexity and the diversity of the older people's occupational engagement and that most of their time was spent alone in their home. The older people reported they were very good at doing almost half of the occupations in which they engaged and that their occupations were primarily either very meaningful or meaningful. While some methodological limitations were identified, time-geographic studies of community dwelling older people living independently are considered to have potential to contribute to community and social planning for older people as they can provide interesting insights to older persons' time use and occupational needs.
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  • Osby, U, et al. (författare)
  • Time trends in first admissions for schizophrenia and paranoid psychosis in Stockholm County, Sweden
  • 2001
  • Ingår i: Schizophrenia Research. - 0920-9964 .- 1573-2509. ; 47:2-3, s. 247-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have reported decreasing time trends in first diagnosed schizophrenia patients. The aim of this: study was to analyze time trends for first admissions with a diagnosis of schizophrenia or a diagnosis of either schizophrenia or paranoid psychosis during 1978-1994 in Stockholm County, Sweden, with a population of around 1.8 million. Information about first psychiatric admission with the diagnosis schizophrenia or paranoid psychosis for residents of Stockholm County was obtained from the Swedish population-based psychiatric inpatient register. Age-adjusted average yearly changes in first hospitalization rates were estimated in a Poisson regression model. Time trends in first admission rates were calculated from 1978 to 1994, while admissions during 1971 to 1977 were observed only to eliminate later re-admissions. First admissions for schizophrenia declined by 1.9% annually for females and by 1.3% for males, while first admissions for schizophrenia and paranoid psychosis together were unchanged over the study period for both genders. Our results indicate that the incidence of schizophrenia and paranoid psychosis taken together was essentially the same over the studied time period in Stockholm County, and that the apparent decline in first admission rates for schizophrenia may be an effect of changes in clinical diagnosis over time.
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  • Åhs, Jill, et al. (författare)
  • Trends in Inpatient Psychiatric Diagnoses in Sweden 1997-2011
  • 2017
  • Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 27:suppl_3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mental health service use has increased among the young.Trends in psychiatric hospitalizations might lend clues as to underlying causes influencing young peoples’ growing use ofpsychiatric services.Methods: We calculated population-adjusted rates for seven broadcategories of ICD-10 psychiatric diagnoses for Swedishinpatients discharged 1997- 2011. We computed rates forages 13-74 overall, as well as six age strata: 13-17, 18-24, 25-29,30-44, 45-64 and 65-74 years, utilizing data from nationalregisters.Results: The overall population-standardized rate of psychiatric hospitalizations did not change significantly over the 15-year period. Yet, children and young adults under age 30 sawnotable increases in inpatient psychiatric care, with ratesroughly doubling over the time period. Affective and anxietydisorders accounted for much of these increases, with curvi-linear increases in developmental and childhood behavioral disorders. Rates among older age groups were more stable,though all age groups saw increases in hospitalizations for anxiety disorders. Declines were seen for adults ages 30-44 for psychotic disorders. Adults ages 65-74 declined in hospitalizations for affective disorders while rising for all other age groupsduring this time.Conclusions: Young adults ages 18-29 years have become the age group withthe greatest proportion hospitalized for psychiatric care. Adolescents and young adults under age 30 saw rises in ratesof psychiatric inpatient care, while at the same time, older age groups did not. A large portion of this increase is due to affective and anxiety disorders, warranting investigation into changes in outpatient care practices, severity, or perceivedseverity of these disorders among this age group.
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