| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 5. |
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| 6. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 7. |
- Tierney, W., et al.
(författare)
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A creative destruction approach to replication : Implicit work and sex morality across cultures
- 2021
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Ingår i: Journal of Experimental Social Psychology. - : Elsevier BV. - 0022-1031 .- 1096-0465. ; 93
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Tidskriftsartikel (refereegranskat)abstract
- How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures.
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| 8. |
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| 9. |
- Faatz, B., et al.
(författare)
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Simultaneous operation of two soft x-ray free-electron lasers driven by one linear accelerator
- 2016
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs-dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.
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| 10. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 11. |
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| 12. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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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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| 13. |
- Valassi, E., et al.
(författare)
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High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
- 2019
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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| 14. |
- Jentschel, M., et al.
(författare)
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EXILL - a high-efficiency, high-resolution setup for gamma-spectroscopy at an intense cold neutron beam facility
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- In the EXILL campaign a highly efficient array of high purity germanium (HPGe) detectors was operated at the cold neutron beam facility PF1B of the Institut Laue-Langevin (ILL) to carry out nuclear structure studies, via measurements of gamma-rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent flux of about 10(8) ns(-1)cm(2) at the target position and negligible neutron halo. The targetwas surrounded by an array of eight to ten anti-Compton shielded EXOGAMClover detectors, four to six anti-Compton shielded large coaxial GASP detectors and two standard Clover detectors. For a part of the campaign the array was combined with 16 LaBr3:(Ce) detectors from the FATIMA collaboration. The detectorswere arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The triggerless acquisition system allowed a signal collection rate of up to 6 x 10(5) Hz. The data allowed to set multi-fold coincidences to obtain decay schemes and in combination with the FATIMA array of LaBr3:(Ce) detectors to analyze half-lives of excited levels in the pico-to microsecond range. Precise energy and efficiency calibrations of EXILL were performed using standard calibration sources of Ba-133, Co-60 and Eu-152 as well as data from the reactions Al-27(n, gamma)Al-28 and Cl-35(n,gamma)Cl-36 in the energy range from 30 keV up to 10MeV.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Åsman, Barbro, et al.
(författare)
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The ATLAS Level-1 Calorimeter Trigger : PreProcessor implementation and performance
- 2012
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The PreProcessor system of the ATLAS Level-1 Calorimeter Trigger (L1Calo) receives about 7200 analogue signals from the electromagnetic and hadronic components of the calorimetric detector system. Lateral division results in cells which are pre-summed to so-called Trigger Towers of size 0.1 x 0.1 along azimuth (phi) and pseudorapidity (eta). The received calorimeter signals represent deposits of transverse energy. The system consists of 124 individual PreProcessor modules that digitise the input signals for each LHC collision, and provide energy and timing information to the digital processors of the L1Calo system, which identify physics objects forming much of the basis for the full ATLAS first level trigger decision. This paper describes the architecture of the PreProcessor, its hardware realisation, functionality, and performance.
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| 19. |
- Gaffney, L. P., et al.
(författare)
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Studies of pear-shaped nuclei using accelerated radioactive beams
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 497:7448, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on Rn-220 and Ra-224 show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.
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| 20. |
- Scheck, M., et al.
(författare)
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Do nuclei go pear-shaped? Coulomb excitation of Rn-220 and Ra-224 at REX-ISOLDE (CERN)
- 2015
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Ingår i: Cgs15 - Capture Gamma-ray Spectroscopy and Related Topics. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 93, s. 01038-01038
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Konferensbidrag (refereegranskat)abstract
- The IS475 collaboration conducted Coulomb-excitation experiments with post-accelerated radioactive Rn-220 and Ra-224 beams at the REX-ISOLDE facility. The beam particles (E-beam: 2.83 MeV/u) were Coulomb excited using Ni-60, Cd-14, and Sn-120 scattering targets. De-excitation gamma-rays were detected employing the Miniball array and scattered particles were detected in a silicon detector. Exploiting the Coulomb-excitation code GOSIA for each nucleus several matrix elements could be obtained from the measured gamma-ray yields. The extracted < 3 parallel to E3 parallel to 0(+)> matrix element allows for the conclusion that, while Rn-220 represents an octupole vibrational system, Ra-224 has already substantial octupole correlations in its ground state. This finding has i(m)plications for the search of CP-violating Schiff moments in the atomic systems of the adjacent odd-mass nuclei.
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| 21. |
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| 22. |
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| 23. |
- Liu, C, et al.
(författare)
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A DNA methylation biomarker of alcohol consumption.
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
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Tidskriftsartikel (refereegranskat)abstract
- The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
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| 24. |
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| 25. |
- Theuns, J., et al.
(författare)
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Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease
- 2014
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 83:21, s. 13-1906
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort. METHODS: C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia. RESULTS: A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.055%), all with a positive family history of neurodegenerative dementia, amyotrophic lateral sclerosis, or atypical parkinsonism, while no carriers were detected with typical sporadic or familial PD. Meta-analysis revealed a small increase in risk of PD with an increasing number of (G4C2)n repeats; however, we could not detect a robust association between the C9orf72 (G4C2)n repeat and PD, and the population attributable risk was low. CONCLUSIONS: Together, these findings indicate that expansions in C9orf72 do not have a major role in the pathogenesis of PD. Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease.
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| 26. |
- Allison, J, et al.
(författare)
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Geant4 developments and applications
- 2006
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Ingår i: IEEE TRANSACTIONS ON NUCLEAR SCIENCE. - 0018-9499. ; 53:1, s. 270-278
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 27. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 28. |
- Georgiadi, A, et al.
(författare)
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Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2999-
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Tidskriftsartikel (refereegranskat)abstract
- The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.
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| 29. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 30. |
- Pfeiffer, D., et al.
(författare)
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Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
- 2019
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:2, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods-Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/ GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of = 3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results-The study sample comprised 816 CADISP patients (age 44.2 +/- 10.3 years) and 2498 SiGN/GISCOME patients (age 67.7 +/- 14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions-Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
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| 31. |
- Jackson, Sarah S., et al.
(författare)
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Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:15, s. 3973-3982
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Tidskriftsartikel (refereegranskat)abstract
- Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m(2) increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. Significance: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.
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| 35. |
- Lahrouchi, Najim, et al.
(författare)
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Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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| 36. |
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| 37. |
- Lopes-Lima, M., et al.
(författare)
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Integrative phylogenetic, phylogeographic and morphological characterisation of the Unio crassus species complex reveals cryptic diversity with important conservation implications
- 2024
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Ingår i: Molecular Phylogenetics and Evolution. - : Academic Press Inc.. - 1055-7903 .- 1095-9513. ; 195
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Tidskriftsartikel (refereegranskat)abstract
- The global decline of freshwater mussels and their crucial ecological services highlight the need to understand their phylogeny, phylogeography and patterns of genetic diversity to guide conservation efforts. Such knowledge is urgently needed for Unio crassus, a highly imperilled species originally widespread throughout Europe and southwest Asia. Recent studies have resurrected several species from synonymy based on mitochondrial data, revealing U. crassus to be a complex of cryptic species. To address long-standing taxonomic uncertainties hindering effective conservation, we integrate morphometric, phylogenetic, and phylogeographic analyses to examine species diversity within the U. crassus complex across its entire range. Phylogenetic analyses were performed using cytochrome c oxidase subunit I (815 specimens from 182 populations) and, for selected specimens, whole mitogenome sequences and Anchored Hybrid Enrichment (AHE) data on ∼ 600 nuclear loci. Mito-nuclear discordance was detected, consistent with mitochondrial DNA gene flow between some species during the Pliocene and Pleistocene. Fossil-calibrated phylogenies based on AHE data support a Mediterranean origin for the U. crassus complex in the Early Miocene. The results of our integrative approach support 12 species in the group: the previously recognised Unio bruguierianus, Unio carneus, Unio crassus, Unio damascensis, Unio ionicus, Unio sesirmensis, and Unio tumidiformis, and the reinstatement of five nominal taxa: Unio desectus stat. rev., Unio gontierii stat. rev., Unio mardinensis stat. rev., Unio nanus stat. rev., and Unio vicarius stat. rev. Morphometric analyses of shell contours reveal important morphospace overlaps among these species, highlighting cryptic, but geographically structured, diversity. The distribution, taxonomy, phylogeography, and conservation of each species are succinctly described.
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| 38. |
- Mantzouki, Evanthia, et al.
(författare)
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Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
- 2018
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Ingår i: Toxins. - : MDPI. - 2072-6651. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
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| 39. |
- Maxwell, Tania L., et al.
(författare)
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Global dataset of soil organic carbon in tidal marshes
- 2023
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
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| 40. |
- Osterlund, P., et al.
(författare)
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Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
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Ingår i: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
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| 41. |
- Sabatelli, L., et al.
(författare)
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Burden of hospitalizations and outpatient visits associated with moderate and severe acute graft-versus-host disease in Finland and Sweden: a real-world data study
- 2022
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 30, s. 5125-5135
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to describe patient characteristics and quantify hospital stays and outpatient visits (H&OV) following diagnosis with moderate-to-severe acute graft-versus-host disease (aGVHD) in Finland and Sweden. Methods: A retrospective chart audit collected data from patient medical records of 3 specialized centers performing allogeneic hematopoietic stem cell transplantation (HSCT; Finland, n = 2; Sweden, n = 1). Eligible patients received allogeneic HSCT (January 1, 2016–June 30, 2017) from any donor source, were diagnosed with grade II–IV aGVHD (MAGIC or modified Glucksberg criteria) at any time from transplantation to 12months before data collection, and were ≥ 18years old at diagnosis.Criteria for comparing patients graded with modified Glucksberg and MAGIC severity scales were defined. Results: Fifty-five patients (Finland, n = 45; Sweden, n = 10) were included. Myeloablative conditioning was the most common conditioning regimen (81.8%); immunosuppression regimens were based on combinations of methotrexate (96.4%), in vivo T-cell depletion (80.0%), cyclosporine (63.6%), mycophenolate (40.0%), and tacrolimus (34.5%). Sixteen patients (29.1%) developed grade III/IV aGVHD; skin was the most common organ involved (80.0%). Most patients required ≥ 1 hospital stay (89.1%; median of 2 hospitalizations per patient); 7 patients (14.3%) required admission to an intensive care unit. Median hospitalization duration from HSCT to discharge was 26days. Most patients also required outpatient or emergency department visits (90.9%). Subgroup analyses showed longer hospital stays for patients receiving multiple treatment lines; no clear differences in H&OV were observed between prophylactic regimens. Conclusion: Based on this retrospective study, moderate-to-severe aGVHD is associated with considerable healthcare resource utilization in Finland and Sweden, particularly in patients who received multiple lines of therapy. © 2022, The Author(s).
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| 42. |
- Argirion, Ilona, et al.
(författare)
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Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies
- 2023
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:5, s. 687-696
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL).Methods: Anti-EBV IgG and IgA antibody responses target-ing 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their associ-ation with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies repre-senting the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models.Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glyco-protein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types.Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis.Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.
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| 43. |
- Christensen, M. J., et al.
(författare)
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Software-based data acquisition and processing for neutron detectors at European Spallation Source-early experience from four detector designs
- 2018
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- European Spallation Source (ESS) will deliver neutrons at high flux for use in diverse neutron scattering techniques. The neutron source facility and the scientific instruments will be located in Lund, and the Data Management and Software Centre (DMSC), in Copenhagen. A number of detector prototypes are being developed at ESS together with its European in-kind partners, for example: SoNDe, Multi-Grid, Multi-Blade and Gd-GEM. These are all position sensitive detectors but use different techniques for the detection of neutrons. Except for digitization of electronics readout, all neutron data is anticipated to be processed in software. This provides maximum flexibility and adaptability and allows deep inspection of the raw data for commissioning which will reduce the risk of starting up new detector technologies. But it also requires development of high performance software processing pipelines and optimized and scalable processing algorithms. This report provides a description of the ESS system architecture for the neutron data path. Special focus is on the interface between the detectors and DMSC which is based on UDP over Ethernet links. The report also describes the software architecture for detector data processing and the tools we have developed, which have proven very useful for efficient early experimentation, and can be run on a single laptop. Processing requirements for the SoNDe, Multi-Grid, Multi-Blade and Ge-GEM detectors are presented and compared to event processing rates archived so far.
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| 44. |
- Cohen, J., et al.
(författare)
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Divergent consensuses on Arctic amplification influence on midlatitude severe winter weather
- 2020
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 10, s. 20-29
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Forskningsöversikt (refereegranskat)abstract
- The Arctic has warmed more than twice as fast as the global average since the late twentieth century, a phenomenon known as Arctic amplification (AA). Recently, there have been considerable advances in understanding the physical contributions to AA, and progress has been made in understanding the mechanisms that link it to midlatitude weather variability. Observational studies overwhelmingly support that AA is contributing to winter continental cooling. Although some model experiments support the observational evidence, most modelling results show little connection between AA and severe midlatitude weather or suggest the export of excess heating from the Arctic to lower latitudes. Divergent conclusions between model and observational studies, and even intramodel studies, continue to obfuscate a clear understanding of how AA is influencing midlatitude weather.
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| 45. |
- Di Giglio, A., et al.
(författare)
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Towards the distributed core for ubiquitous superfast broadband optical access
- 2014
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Ingår i: 2014 European Conference on Networks and Communications (EuCNC). ; , s. 1-5
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Konferensbidrag (refereegranskat)abstract
- In this paper, we describe recent architectural and technological advances of the end to end optical network architecture proposed by the DISCUS project (the DIStributed Core for unlimited bandwidth supply for all Users and Services). The two main targets of DISCUS are the principle of equivalence in the access and the reduction of optical-to-electronic conversions in the metro-core network. Technological advances and techno-economic evaluation of Long-Reach Passive Optical Networks (LR-PON), as well as the optimal metro-core node architecture and the required network control plane framework are reported. Network infrastructure sharing challenges are also discussed.
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| 46. |
- Donis, Daphne, et al.
(författare)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Tidskriftsartikel (refereegranskat)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 47. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 48. |
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| 49. |
- Hultcrantz, M., et al.
(författare)
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Elevated risk of venous but not arterial thrombosis in Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma
- 2014
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:11, s. 1816-1821
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany malignancies, including multiple myeloma and its precursor, monoclonal gammopathy of unknown significant, are associated with an elevated risk of thromboembolism. There is limited information on the risk of thrombosis in patients with Waldenstrom macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL). ObjectivesTo assess the risk of venous and arterial thrombosis in WM/LPL patients in a large population-based cohort study in Sweden. Patients/methodsA total of 2190 patients with WM/LPL and 8086 matched controls were identified through Swedish registers between 1987 and 2005. Information on occurrence of venous and arterial thrombosis after the diagnosis of WM/LPL was obtained through the centralized Swedish Patient Register, with follow-up to 2006. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsPatients with WM/LPL had a significantly increased risk of venous thrombosis and the highest risk was observed during the first year following diagnosis (HR=4.0, 95% CI 2.5-6.4). The risk was significantly elevated 5 (HR=2.3, 95% CI 1.7-3.0) and 10years after diagnosis (HR=2.0, 95% CI 1.6-2.5). There was no increased risk of arterial thrombosis during any period of follow-up time (10-year HR=1.0, 95% CI 0.9-1.1). ConclusionsVenous thrombosis is a significant cause of morbidity in patients with WM/LPL. The potential role of thromboprophylaxis in WM/LPL, especially during the first year after diagnosis and in patients treated with thrombogenic agents, needs to be assessed to further improve outcome in WM/LPL patients.
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| 50. |
- Jhun, Mina-A, et al.
(författare)
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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.
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