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Sökning: WFRF:(Jörgensen N)

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1.
  • Feroci, M., et al. (författare)
  • LOFT - The large observatory for x-ray timing
  • 2012
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
  • Konferensbidrag (refereegranskat)abstract
    • The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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2.
  • Feroci, M., et al. (författare)
  • The large observatory for x-ray timing
  • 2014
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
  • Konferensbidrag (refereegranskat)abstract
    • The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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3.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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4.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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5.
  • Vieira-Silva, S., et al. (författare)
  • Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581:7808, s. 310-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n=888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n=2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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6.
  • Walford, G. A., et al. (författare)
  • Genome-wide association study of the modified stumvoll insulin sensitivity index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci
  • 2016
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:10, s. 3200-3211
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci. © 2016 by the American Diabetes Association.
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7.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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8.
  • Mahajan, Anubha, et al. (författare)
  • Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus.
  • 2015
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.
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9.
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10.
  • Saxena, Richa, et al. (författare)
  • Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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11.
  • Aaldering, L. J., et al. (författare)
  • Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule
  • 2017
  • Ingår i: ChemBioChem. - : Wiley-VCH Verlag. - 1439-4227 .- 1439-7633. ; 18:8, s. 755-763
  • Tidskriftsartikel (refereegranskat)abstract
    • The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G-quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer-C3 introduction at the T7 loop position (TBA-SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA-SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties. 
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12.
  • Aghion, S., et al. (författare)
  • A moiré deflectometer for antimatter
  • 2014
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics—the moiré deflectometer—for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter.
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13.
  • Amole, C., et al. (författare)
  • The ALPHA antihydrogen trapping apparatus
  • 2014
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 735, s. 319-340
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.
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14.
  • Andresen, G. B., et al. (författare)
  • Search for trapped antihydrogen
  • 2011
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 695:1-4, s. 95-104
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 107 antiprotons with 1.3ï¿œ109 positrons to produce 6ï¿œ105 antihydrogen atoms, we have identified six antiproton annihilation events that are consistent with the release of trapped antihydrogen. The cosmic ray background, estimated to contribute 0.14 counts, is incompatible with this observation at a significance of 5.6 sigma. Extensive simulations predict that an alternative source of annihilations, the escape of mirror-trapped antiprotons, is highly unlikely, though this possibility has not yet been ruled out experimentally.
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15.
  • Ariga, T., et al. (författare)
  • Measuring GBAR with emulsion detector
  • 2014
  • Ingår i: International Journal of Modern Physics, Conference Series. - : World Scientific. - 2010-1945. ; 30
  • Tidskriftsartikel (refereegranskat)
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16.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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17.
  • Björkman, Anne, 1981, et al. (författare)
  • Plant functional trait change across a warming tundra biome
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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18.
  • Bruderer, S., et al. (författare)
  • Herschel/HIFI detections of hydrides towards AFGL 2591. Envelope emission versus tenuous cloud absorption
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L44-
  • Tidskriftsartikel (refereegranskat)abstract
    • The Heterodyne Instrument for the Far Infrared (HIFI) onboard the Herschel Space Observatory allows the first observations of light diatomic molecules at high spectral resolution and in multiple transitions. Here, we report deep integrations using HIFI in different lines of hydrides towards the high-mass star forming region AFGL 2591. Detected are CH, CH+, NH, OH+, H2O+, while NH+ and SH+ have not been detected. All molecules except for CH and CH+ are seen in absorption with low excitation temperatures and at velocities different from the systemic velocity of the protostellar envelope. Surprisingly, the CH(JF,P = 3/22,- - 1/21,+ ) and CH+(J = 1-0, J = 2-1) lines are detected in emission at the systemic velocity. We can assign the absorption features to a foreground cloud and an outflow lobe, while the CH and CH+ emission stems from the envelope. The observed abundance and excitation of CH and CH+ can be explained in the scenario of FUV irradiated outflow walls, where a cavity etched out by the outflow allows protostellar FUV photons to irradiate and heat the envelope at larger distances driving the chemical reactions that produce these molecules. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Apppendices and Table 1 (pages 6 to 7) are only available in electronic form at http://www.aanda.org
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19.
  • Coutens, A., et al. (författare)
  • The ALMA-PILS survey: First detection of nitrous acid (HONO) in the interstellar medium
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitrogen oxides are thought to play a significant role as a nitrogen reservoir and to potentially participate in the formation of more complex species. Until now, only NO, NO, and HNO have been detected in the interstellar medium. We report the first interstellar detection of nitrous acid (HONO). Twelve lines were identified towards component B of the low-mass protostellar binary IRAS 16293-2422 with the Atacama Large Millimeter/submillimeter Array, at the position where NO and NO have previously been seen. A local thermodynamic equilibrium model was used to derive the column density (∼9 × 1014 cm in a 0 .″5 beam) and excitation temperature (∼100 K) of this molecule. HNO, NO, NO+, and HNO3 were also searched for in the data, but not detected. We simulated the HONO formation using an updated version of the chemical code Nautilus and compared the results with the observations. The chemical model is able to reproduce satisfactorily the HONO, NO, and NO abundances, but not the NO, HNO, and NHOH abundances. This could be due to some thermal desorption mechanisms being destructive and therefore limiting the amount of HNO and NHOH present in the gas phase. Other options are UV photodestruction of these species in ices or missing reactions potentially relevant at protostellar temperatures.
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20.
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21.
  • Hellem, Marie N.N., et al. (författare)
  • Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients
  • 2022
  • Ingår i: Parkinsonism and Related Disorders. - : Elsevier BV. - 1353-8020. ; 99, s. 23-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Huntington's disease (HD) is an inherited neurodegenerative disease with motor, cognitive and psychiatric symptoms. Non-motor symptoms like depression and altered social cognition are proposed to be caused by dysfunction of the hypothalamus. We measured the hypothalamic neuropeptide oxytocin in plasma and cerebrospinal fluid (CSF) in a cohort of HD gene expansion carriers (HDGECs), compared the levels to healthy HD family controls and correlated oxytocin levels to disease progression and social cognition. Methods: We recruited 113 HDGECs and 33 controls. Psychiatric and cognitive symptoms were evaluated, and social cognition was assessed with the Emotion Hexagon test, Reading the Mind in the Eyes and The Awareness of Social Inference Test. The levels of oxytocin in CSF and blood were analyzed by radioimmunoassay. Results: We found the level of oxytocin in CSF to be significantly lower by 33.5% in HDGECs compared to controls (p = 0.016). When dividing the HDGECs into groups with or without cognitive impairment, we found the oxytocin level to be significantly lower by 30.3% in the HDGECs with cognitive symptoms (p = 0.046). We found a statistically significant correlation between the level of oxytocin and scores on social cognition (Reading the Mind in the Eyes p = 0.0019; Emotion Hexagon test: p = 0.0062; The Awareness of Social Inference Test: p = 0.002). Conclusions: This is the first study to measure oxytocin in the CSF of HDGECs. We find that HDGECs have a significantly lower level of oxytocin compared to controls, and that the level of oxytocin may represent an objective and comparable measure that could be used as a state biomarker for impairment of social cognition. We suggest treatment trials to evaluate a potential effect of oxytocin on social cognition in HD.
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22.
  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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23.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
  •  
24.
  • Lehmann, L., et al. (författare)
  • Linking hydrolysis performance to Trichoderma reesei cellulolytic enzyme profile
  • 2016
  • Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 113:5, s. 1001-1010
  • Tidskriftsartikel (refereegranskat)abstract
    • Trichoderma reesei expresses a large number of enzymes involved in lignocellulose hydrolysis and the mechanism of how these enzymes work together is too complex to study by traditional methods, for example, by spiking with single enzymes and monitoring hydrolysis performance. In this study, a multivariate approach, partial least squares regression, was used to see whether it could help explain the correlation between enzyme profile and hydrolysis performance. Diverse enzyme mixtures were produced by T. reesei Rut-C30 by exploiting various fermentation conditions and used for hydrolysis of washed pretreated corn stover as a measure of enzyme performance. In addition, the enzyme mixtures were analyzed by liquid chromatography-tandem mass spectrometry to identify and quantify the different proteins. A multivariate model was applied for the prediction of enzyme performance based on the combination of different proteins present in an enzyme mixture. The multivariate model was used for identification of candidate proteins that are correlated to enzyme performance on pretreated corn stover. A very large variation in hydrolysis performance was observed and this was clearly caused by the difference in fermentation conditions. Besides β-glucosidase, the multivariate model identified several xylanases, Cip1 and Cip2, as relevant proteins to study further.
  •  
25.
  • Lu, Yingchang, et al. (författare)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
  •  
26.
  • Madsen, N, et al. (författare)
  • Search for trapped antihydrogen in ALPHA
  • 2011
  • Ingår i: Canadian journal of physics (Print). - 0008-4204 .- 1208-6045. ; 89:1, s. 7-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Antihydrogen spectroscopy promises precise tests of the symmetry of matter and antimatter, and can possibly offer new insights into the baryon asymmetry of the universe. Antihydrogen is, however, difficult to synthesize and is produced only in small quantities. The ALPHA collaboration is therefore pursuing a path towards trapping cold antihydrogen to permit the use of precision atomic physics tools to carry out comparisons of antihydrogen and hydrogen. ALPHA has addressed these challenges. Control of the plasma sizes has helped to lower the influence of the multipole field used in the neutral atom trap, and thus lowered the temperature of the created atoms. Finally, the first systematic attempt to identify trapped antihydrogen in our system is discussed. This discussion includes special techniques for fast release of the trapped anti-atoms, as well as a silicon vertex detector to identify antiproton annihilations. The silicon detector reduces the background of annihilations, including background from antiprotons that can be mirror trapped in the fields of the neutral atom trap. A description of how to differentiate between these events and those resulting from trapped antihydrogen atoms is also included.
  •  
27.
  • Manigand, S., et al. (författare)
  • The ALMA-PILS survey: First detection of the unsaturated 3-carbon molecules Propenal (C2H3CHO) and Propylene (C3H6) towards IRAS 16293-2422 B
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Complex organic molecules with three carbon atoms are found in the earliest stages of star formation. In particular, propenal (C2H3CHO) is a species of interest due to its implication in the formation of more complex species and even biotic molecules. Aims. This study aims to search for the presence of C2H3CHO and other three-carbon species such as propylene (C3H6) in the hot corino region of the low-mass protostellar binary IRAS 16293-2422 to understand their formation pathways. Methods. We use ALMA observations in Band 6 and 7 from various surveys to search for the presence of C3H6 and C2H3CHO towards the protostar IRAS 16293-2422 B (IRAS 16293B). The identification of the species and the estimates of the column densities and excitation temperatures are carried out by modeling the observed spectrum under the assumption of local thermodynamical equilibrium. Results. We report the detection of both C3H6 and C2H3CHO towards IRAS 16293B, however, no unblended lines were found towards the other component of the binary system, IRAS 16293A. We derive column density upper limits for C3H8, HCCCHO, n-C3H7OH, i-C3H7OH, C3O, and cis-HC(O)CHO towards IRAS 16293B. We then use a three-phase chemical model to simulate the formation of these species in a typical prestellar environment followed by its hydrodynamical collapse until the birth of the central protostar. Different formation paths, such as successive hydrogenation and radical-radical additions on grain surfaces, are tested and compared to the observational results in a number of different simulations, to assess which are the dominant formation mechanisms in the most embedded region of the protostar. Conclusions. The simulations reproduce the abundances within one order of magnitude from those observed towards IRAS 16293B, with the best agreement found for a rate of 10-12 cm3 s-1 for the gas-phase reaction C3 + O → C2 + CO. Successive hydrogenations of C3, HC(O)CHO, and CH3OCHO on grain surfaces are a major and crucial formation route of complex organics molecules, whereas both successive hydrogenation pathways and radical-radical addition reactions contribute to the formation of C2H5CHO.
  •  
28.
  • Manigand, S., et al. (författare)
  • The ALMA-PILS survey: The first detection of doubly-deuterated methyl formate (CHD2OCHO) in the ISM
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746.
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of deuterated isotopologues of complex organic molecules can provide important constraints on their origin in regions of star formation. In particular, the abundances of deuterated species are very sensitive to the physical conditions in the environment where they form. Due to the low temperatures in regions of star formation, these isotopologues are enhanced to significant levels, making detections of multiply-deuterated species possible. However, for complex organic species, only the multiply-deuterated variants of methanol and methyl cyanide have been reported so far. The aim of this paper is to initiate the characterisation of multiply-deuterated variants of complex organic species with the first detection of doubly-deuterated methyl formate, CHD2OCHO. We use ALMA observations from the Protostellar Interferometric Line Survey (PILS) of the protostellar binary IRAS 16293-2422, in the spectral range of 329.1 GHz to 362.9 GHz. We report the first detection of doubly-deuterated methyl formate CHD2OCHO in the ISM. The D/H ratio of CHD2OCHO is found to be 2-3 times higher than the D/H ratio of CH2DOCHO for both sources, similar to the results for formaldehyde from the same dataset. The observations are compared to a gas-grain chemical network coupled to a dynamical physical model, tracing the evolution of a molecular cloud until the end of the Class 0 protostellar stage. The overall D/H ratio enhancements found in the observations are of the same order of magnitude as the predictions from the model for the early stages of Class 0 protostars. However, the higher D/H ratio of CHD2OCHO compared to the D/H ratio of CH2DOCHO is still not predicted by the model. This suggests that a mechanism is enhancing the D/H ratio of singly- and doubly-deuterated methyl formate that is not in the model, e.g. mechanisms for H-D substitutions.
  •  
29.
  • Qi, Qibin, et al. (författare)
  • FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
  • Tidskriftsartikel (refereegranskat)abstract
    • FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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30.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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31.
  • Stacey, Simon N, et al. (författare)
  • A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
  •  
32.
  • Taquet, V., et al. (författare)
  • Linking interstellar and cometary O2: A deep search for 16O18O in the solar-Type protostar IRAS 16293b-2422
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent measurements carried out at comet 67P/Churyumov-Gerasimenko (67P) with the Rosetta probe revealed that molecular oxygen, O2, is the fourth most abundant molecule in comets. Models show that O2 is likely of primordial nature, coming from the interstellar cloud from which our solar system was formed. However, gaseous O2 is an elusive molecule in the interstellar medium with only one detection towards quiescent molecular clouds, in the ρ Oph A core. We perform a deep search for molecular oxygen, through the 21-01 rotational transition at 234 GHz of its 16O18O isotopologue, towards the warm compact gas surrounding the nearby Class 0 protostar IRAS 16293-2422 B with the ALMA interferometer. We also look for the chemical daughters of O2, HO2, and H2O2. Unfortunately, the H2O2 rotational transition is dominated by ethylene oxide c-C2H4O while HO2 is not detected. The targeted 16O18O transition is surrounded by two brighter transitions at ± 1 km s-1 relative to the expected 16O18O transition frequency. After subtraction of these two transitions, residual emission at a 3σ level remains, but with a velocity offset of 0.3-0.5 km s-1 relative to the source velocity, rendering the detection "tentative". We derive the O2 column density for two excitation temperatures Tex of 125 and 300 K, as indicated by other molecules, in order to compare the O2 abundance between IRAS 16293 and comet 67P. Assuming that 16O18O is not detected and using methanol CH3OH as a reference species, we obtain a [O2]/[CH3OH] abundance ratio lower than 2-5, depending on the assumed Tex, a three to four times lower abundance than the [O2]/[CH3OH] ratio of 5-15 found in comet 67P. Such a low O2 abundance could be explained by the lower temperature of the dense cloud precursor of IRAS 16293 with respect to the one at the origin of our solar system that prevented efficient formation of O2 in interstellar ices.
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33.
  • Van Der Werf, D. P., et al. (författare)
  • Antimatter transport processes
  • 2010
  • Ingår i: AAPS Journal. - : IOP Publishing. - 1550-7416. ; 257:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A comparison of the 1S-2S transitions of hydrogen and antihydrogen will yield a stringent test of CPT conservation. Necessarily, the antihydrogen atoms need to be trapped to perform high precision spectroscopy measurements. Therefore, an approximately 0.75 T deep neutral atom trap, equivalent to about 0.5 K for ground state (anti)hydrogen atoms, has been superimposed on a Penning-Malmberg trap in which the anti-atoms are formed. The antihydrogen atoms are produced following a number of steps. A bunch of antiprotons from the CERN Antiproton Decelerator is caught in a Penning-Malmberg trap and subsequently sympathetically cooled and then compressed using rotating wall electric fields. A positron plasma, formed in a separate accumulator, is transported to the main system and also compressed. Antihydrogen atoms are then formed by mixing the antiprotons and positrons. The velocity of the anti-atoms, and their binding energies, will strongly depend on the initial conditions of the constituent particles, for example their temperatures and densities, and on the details of the mixing process. In this paper the complete lifecycle of antihydrogen atoms will be presented, starting with the production of the constituent antiparticles and the description of the manipulations necessary to prepare them appropriately for antihydrogen formation. The latter will also be described, as will the possible fates of the anti-atoms.
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34.
  • Vogel, N, et al. (författare)
  • Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
  • 2023
  • Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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35.
  • Allentoft, Morten E., et al. (författare)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
  •  
36.
  • Arsene, I. C., et al. (författare)
  • Rapidity and centrality dependence of particle production for identified hadrons in Cu + Cu collisions at s NN =200 GeV
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The BRAHMS collaboration has measured transverse momentum spectra of pions, kaons, protons, and antiprotons at rapidities 0 and 3 for Cu+Cu collisions at sNN=200 GeV. As the collisions become more central the collective radial flow increases while the temperature of kinetic freeze-out decreases. The temperature is lower and the radial flow weaker at forward rapidity. Pion and kaon yields with transverse momenta between 1.5 and 2.5 GeV/c are suppressed for central collisions relative to scaled p+p collisions. This suppression, which increases as the collisions become more central, is consistent with jet quenching models and is also present with comparable magnitude at forward rapidity. At such rapidities, initial state effects may also be present and persistence of the meson suppression to high rapidity may reflect a combination of jet quenching and nuclear shadowing. The ratio of protons to mesons increases as the collisions become more central and is largest at forward rapidities.
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37.
  •  
38.
  • Bollard, J., et al. (författare)
  • Early formation of planetary building blocks inferred from Pb isotopic ages of chondrules.
  • 2017
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The most abundant components of primitive meteorites (chondrites) are millimeter-sized glassy spherical chondrules formed by transient melting events in the solar protoplanetary disk. Using Pb-Pb dates of 22 individual chondrules, we show that primary production of chondrules in the early solar system was restricted to the first million years after the formation of the Sun and that these existing chondrules were recycled for the remaining lifetime of the protoplanetary disk. This finding is consistent with a primary chondrule formation episode during the early high-mass accretion phase of the protoplanetary disk that transitions into a longer period of chondrule reworking. An abundance of chondrules at early times provides the precursor material required to drive the efficient and rapid formation of planetary objects via chondrule accretion.
  •  
39.
  • Brogaard, K., et al. (författare)
  • Age and helium content of the open cluster NGC 6791 from multiple eclipsing binary members : III. Constraints from a subgiant
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Models of stellar structure and evolution can be constrained using accurate measurements of the parameters of eclipsing binary members of open clusters. Multiple binary stars provide the means to tighten the constraints and, in turn, to improve the precision and accuracy of the age estimate of the host cluster. In the previous two papers of this series, we have demonstrated the use of measurements of multiple eclipsing binaries in the old open cluster NGC 6791 to set tighter constraints on the properties of stellar models than was previously possible, thereby improving both the accuracy and precision of the cluster age. Aims. We identify and measure the properties of a non-eclipsing cluster member, V56, in NGC 6791 and demonstrate how this provides additional model constraints that support and strengthen our previous findings. Methods. We analyse multi-epoch spectra of V56 from FLAMES in conjunction with the existing photometry and measurements of eclipsing binaries in NGC6971. Results. The parameters of the V56 components are found to be Mp = 1.103 ± 0.008 Mpdbl and Ms = 0.974 ± 0.007 Mpdbl, Rp = 1.764 ± 0.099 Rpdbl and Rs = 1.045 ± 0.057 Rpdbl, Teff,p = 5447 ± 125 K and Teff,s = 5552 ± 125 K, and surface [Fe/H] = +0.29 ± 0.06 assuming that they have the same abundance. Conclusions. The derived properties strengthen our previous best estimate of the cluster age of 8.3 ± 0.3 Gyr and the mass of stars on the lower red giant branch (RGB), which is MRGB = 1.15 ± 0.02 Mpdbl for NGC 6791. These numbers therefore continue to serve as verification points for other methods of age and mass measures, such as asteroseismology.
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40.
  • Bönlökke, J. H., et al. (författare)
  • Upper-airway inflammation in relation to dust spiked with aldehydes or glucan
  • 2006
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 32:5, s. 374-382
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Organic dust is associated with adverse effects on human airways. This study was done to investigate whether the addition of β-(1,3)-D glucan or aldehydes to office dust causes enhanced inflammation in human airways. Methods Thirty-six volunteers were exposed randomly to clean air, office dust, dust spiked with glucan, and dust spiked with aldehydes. The three dust exposures contained between 332 and 379 µg dust/m3. Spiking with 1 gram of dust was done with 10 milligrams of glucan or 0.1 microliters of aldehydes. Acoustic rhinometry, rhinostereometry, nasal lavage, and lung function tests were applied. Results After the exposures to dust spiked with the glucan and aldehydes, the nasal volume decreased (–1.33 and –1.39 cm3 (mean), respectively) when compared with the –0.9 cm3 after clean air or office dust (P=0.036 for a difference in decrease between exposures). After 2–3 hours the aldehyde-spiked dust caused a 0.6-mm swelling of the inferior turbinate, and glucan-spiked dust produced a 0.7-mm swelling (P=0.039 for a difference in the swelling between the four exposures). The preexposure nasal lavage cleaned off the mucosa, and lower cytokine concentrations were found after all of the exposures. For interleukin-8, this decrease in concentration was smaller after the dust exposures spiked with glucan and aldehydes (–2.9 and –25.8 pg/ml, respectively) than after office dust or clean air (–65.9 and –74.1 pg/ml, respectively) (P=0.042). The nasal eosinophil cell concentration increased after exposure to dust spiked with glucan (P=0.045). Conclusions β-(1,3)-D glucan and aldehydes in office dust enhance the inflammatory effects of dust on the upper airways
  •  
41.
  • Casanueva, Felipe F., et al. (författare)
  • Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement
  • 2017
  • Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20, s. 489-498
  • Forskningsöversikt (refereegranskat)abstract
    • © 2017, The Author(s). Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
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42.
  • Chen, Wei-Min, et al. (författare)
  • Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
  • 2008
  • Ingår i: Journal of Clinical Investigation. - 0021-9738. ; Jun 2, s. 2620-2628
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.
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43.
  • Csengeri, D., et al. (författare)
  • Alcohol consumption and risk of atrial fibrillation - results from the BiomarCaRE Consortium
  • 2018
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39, s. 902-903
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Atrial fibrillation (AF) is an arrhythmia with high impact on public health. Among modifiable risk factors for the disease the role of alcohol consumption (AC) has remained inconsistent.Purpose: To assess the association between AC and incident AF across European cohorts.Methods: To study the association between self-reported AC and incident AF in N=107,845 community-based individuals from the BiomarCaRE consortium, 106,915 individuals free of AF at baseline were followed up for AF and stroke after AF. We assessed AC using validated questionnaires. Biomarkers N-terminal pro B-type natriuretic peptide (Nt-proBNP) and high sensitivity troponin I (hsTnI) were measured.Results: The median age of individuals was 47.8 years, 48.3% were men. The median of right-winsorized AC was 3 g/day. N=6,055 individuals developed AF (median follow-up time: 13.9 years). In a linear multivariable-adjusted Cox regression analyses, AC was linearly and positively associated with incident AF (Figure), hazard ratio (HR) per g/day 1.009, 95% confidence interval (CI) 1.007- 1.012, P<0.001. For one drink (12g) per day the HR was 1.15, CI 1.12–1.18, P<0.001. There was a high heterogeneity in associations across cohorts.No significant interactions of the association by Nt-proBNP and hsTnI were observed. AC was positively related to stroke risk after diagnosis of AF (HR 1.18, 95% CI 1.04–1.34, P=0.012).Conclusions: In contrast to other cardiovascular diseases, we did not observe a U-shaped association of alcohol with incident AF in the community, but a rather linearly increasing relation.
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44.
  • Grinderslev, Jakob B., et al. (författare)
  • Polymorphism and solid solutions of trimethylammonium monocarboranes
  • 2022
  • Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 51:41, s. 15806-15815
  • Tidskriftsartikel (refereegranskat)abstract
    • Metal closo-boranes have recently received significant attention as solid-state electrolytes due to their high thermal and electrochemical stability, and the weak interaction between the cat- and anion, facilitating fast ionic conductivity. Here we report a synthesis method for obtaining a novel mixed closo-carborane compound, [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08]. The crystal structures are investigated for [NH(CH3)3][CB9H10] and [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08], revealing that the latter forms a solid solution isostructural to [NH(CH3)3][CB9H10]. The compounds exhibit polymorphism as a function of temperature, and we report the discovery of four polymorphs of [NH(CH3)3][CB9H10] and four isostructural solid solution [NH(CH3)3][(CB8H9)0.26(CB9H10)0.66(CB11H12)0.08], along with a high-temperature decomposition intermediate of the latter. The α-polymorph is an ordered structure, with increasing amounts of disorder for the β- and γ-polymorphs, while the high temperature δ- and ϵ-polymorphs at T > 476 K are fully disordered on both the cation and anion site. These new compounds may be used as precursors for new types of solid-state ionic conductors.
  •  
45.
  • Gurholt, Tiril P., et al. (författare)
  • Intracranial and subcortical volumes in adolescents with early‐onset psychosis : A multisite mega‐analysis from the ENIGMA consortium
  • 2020
  • Ingår i: Human Brain Mapping. - Stockholm : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 373-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early-onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
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46.
  • Harsono, D., et al. (författare)
  • Missing water in Class i protostellar disks
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Water is a key volatile that provides insight into the initial stages of planet formation. The low water abundances inferred from water observations toward low-mass protostellar objects may point to a rapid locking of water as ice by large dust grains during star and planet formation. However, little is known about the water vapor abundance in newly formed planet-forming disks. Aims. We aim to determine the water abundance in embedded Keplerian disks through spatially-resolved observations of H218O lines to understand the evolution of water during star and planet formation. Methods. We present H218O line observations with ALMA and NOEMA millimeter interferometers toward five young stellar objects. NOEMA observed the 31,3-22,0 line (Eup? kB = 203.7 K) while ALMA targeted the 41,4-32,1 line (Eup? kB = 322.0 K). Water column densities were derived considering optically thin and thermalized emission. Our observations were sensitive to the emission from the known Keplerian disks around three out of the five Class I objects in the sample. Results. No H218O emission is detected toward any of our five Class I disks. We report upper limits to the integrated line intensities. The inferred water column densities in Class I disks are NH218O < 1015 cm-2 on 100 au scales, which include both the disk and envelope. The upper limits imply a disk-averaged water abundance of ? 10-6 with respect to H2 for Class I objects. After taking the physical structure of the disk into account, the upper limit to the water abundance averaged over the inner warm disk with T > 100 K is between ~10-7 and 10-5. Conclusions. Water vapor is not abundant in warm protostellar envelopes around Class I protostars. Upper limits to the water vapor column densities in Class I disks are at least two orders of magnitude lower than values found in Class 0 disk-like structures.
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47.
  • Hauge, Camilla, et al. (författare)
  • Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation.
  • 2007
  • Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 26:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth factor/insulin-stimulated AGC kinases share an activation mechanism based on three phosphorylation sites. Of these, only the role of the activation loop phosphate in the kinase domain and the hydrophobic motif (HM) phosphate in a C-terminal tail region are well characterized. We investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within the kinase domain, promoting zipper-like association of the tail with the kinase domain, serving to stabilize the HM in its kinase-activating binding site. We present a molecular model for allosteric activation of AGC kinases by the turn motif phosphate via HM-mediated stabilization of the alphaC helix. In S6K and MSK, the turn motif phosphate thereby also protects the HM from dephosphorylation. Our results suggest that the mechanism described is a key feature in activation of upto 26 human AGC kinases.
  •  
48.
  • Hedin, Charlotte Rose Hawkey, et al. (författare)
  • Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis
  • 2020
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:10, s. 2-2304
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. Methods: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. Results: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P =.035). Factors associated with lower ALP were normal ALP at baseline (P <.01), treatment with adalimumab (P =.090), and treatment in Europe (P =.083). Conclusions: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.
  •  
49.
  • Hirao, Yuki, et al. (författare)
  • OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
  • 2020
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
  •  
50.
  • Jakobsen, Lasse H., et al. (författare)
  • Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy : an international study of 264 real-world patients
  • 2020
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:4, s. 661-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: −0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.
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