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Sökning: WFRF:(Dalén L.)

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1.
  • Schael, S, et al. (författare)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Forskningsöversikt (refereegranskat)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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  • Bouyoucef, S E, et al. (författare)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Tidskriftsartikel (refereegranskat)
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  • Ferreira, Mjv, et al. (författare)
  • Poster Session 3 : Tuesday 5 May 2015, 08
  • 2015
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Tidskriftsartikel (refereegranskat)
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  • Palkopoulou, Eleftheria, et al. (författare)
  • A comprehensive genomic history of extinct and living elephants
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 115:11, s. E2566-E2574
  • Tidskriftsartikel (refereegranskat)abstract
    • Elephantids are the world's most iconic megafaunal family, yet there is no comprehensive genomic assessment of their relationships. We report a total of 14 genomes, including 2 from the American mastodon, which is an extinct elephantid relative, and 12 spanning all three extant and three extinct elephantid species including an similar to 120,000-y-old straight-tusked elephant, a Columbian mammoth, and woolly mammoths. Earlier genetic studies modeled elephantid evolution via simple bifurcating trees, but here we show that interspecies hybridization has been a recurrent feature of elephantid evolution. We found that the genetic makeup of the straight-tusked elephant, previously placed as a sister group to African forest elephants based on lower coverage data, in fact comprises three major components. Most of the straight-tusked elephant's ancestry derives from a lineage related to the ancestor of African elephants while its remaining ancestry consists of a large contribution from a lineage related to forest elephants and another related to mammoths. Columbian and woolly mammoths also showed evidence of interbreeding, likely following a latitudinal cline across North America. While hybridization events have shaped elephantid history in profound ways, isolation also appears to have played an important role. Our data reveal nearly complete isolation between the ancestors of the African forest and savanna elephants for similar to 500,000 y, providing compelling justification for the conservation of forest and savanna elephants as separate species.
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  • von Seth, J, et al. (författare)
  • Genomic insights into the conservation status of the world's last remaining Sumatran rhinoceros populations
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Small populations are often exposed to high inbreeding and mutational load that can increase the risk of extinction. The Sumatran rhinoceros was widespread in Southeast Asia, but is now restricted to small and isolated populations on Sumatra and Borneo, and most likely extinct on the Malay Peninsula. Here, we analyse 5 historical and 16 modern genomes from these populations to investigate the genomic consequences of the recent decline, such as increased inbreeding and mutational load. We find that the Malay Peninsula population experienced increased inbreeding shortly before extirpation, which possibly was accompanied by purging. The populations on Sumatra and Borneo instead show low inbreeding, but high mutational load. The currently small population sizes may thus in the near future lead to inbreeding depression. Moreover, we find little evidence for differences in local adaptation among populations, suggesting that future inbreeding depression could potentially be mitigated by assisted gene flow among populations.
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  • Cappellini, Enrico, et al. (författare)
  • Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny
  • 2019
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 574:7776, s. 103-
  • Tidskriftsartikel (refereegranskat)abstract
    • The sequencing of ancient DNA has enabled the reconstruction of speciation, migration and admixture events for extinct taxa(1). However, the irreversible post-mortem degradation(2) of ancient DNA has so far limited its recovery-outside permafrost areasto specimens that are not older than approximately 0.5 million years (Myr)(3). By contrast, tandem mass spectrometry has enabled the sequencing of approximately 1.5-Myr-old collagen type I-4. and suggested the presence of protein residues in fossils of the Cretaceous period(5)-although with limited phylogenetic use(6). In the absence of molecular evidence, the speciation of several extinct species of the Early and Middle Pleistocene epoch remains contentious. Here we address the phylogenetic relationships of the Eurasian Rhinocerotidae of the Pleistocene epoch(7-9), using the proteome of dental enamel from a Stephanorhinus tooth that is approximately 1.77-Myr old, recovered from the archaeological site of Dmanisi (South Caucasus, Georgia)(10). Molecular phylogenetic analyses place this Stephanorhinus as a sister group to the Glade formed by the woolly rhinoceros (Coelodonta antiquitatis) and Merck's rhinoceros (Stephanorhinus kirchbergensis). We show that Coelodonta evolved from an early Stephanorhinus lineage, and that this latter genus includes at least two distinct evolutionary lines. The genus Stephanorhinus is therefore currently paraphyletic, and its systematic revision is needed. We demonstrate that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA. Our approach also provides additional information about the sex and taxonomic assignment of other specimens from Dmanisi. Our findings reveal that proteomic investigation of ancient dental enamel-which is the hardest tissue in vertebrates(11), and is highly abundant in the fossil record-can push the reconstruction of molecular evolution further back into the Early Pleistocene epoch, beyond the currently known limits of ancient DNA preservation.
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  • Liu, Shanlin, et al. (författare)
  • Ancient and modem genomes unravel the evolutionary history of the rhinoceros family
  • 2021
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 184:19, s. 4874-4885.e16
  • Tidskriftsartikel (refereegranskat)abstract
    • Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses. This early Miocene (similar to 16 million years ago [mya]) split post-dates the land bridge formation between the Afro-Arabian and Eurasian landmasses. Our analyses also show that while rhinoceros genomes in general exhibit low levels of genome-wide diversity, heterozygosity is lowest and inbreeding is highest in the modern species. These results suggest that while low genetic diversity is a long-term feature of the family, it has been particularly exacerbated recently, likely reflecting recent anthropogenic-driven population declines.
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  • Schult, A. L., et al. (författare)
  • Detection of cancers and advanced adenomas in asymptomatic participants in colorectal cancer screening: a cross-sectional study
  • 2021
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To assess detection rates for colorectal cancer (CRC) and advanced adenomas in asymptomatic CRC screening participants and bowel symptoms in association with CRC and advanced adenoma. DESIGN: Cross-sectional study. SETTING: Two screening centres. PARTICIPANTS: 42 554 men and women, aged 50-74 years, participating in a randomised CRC screening trial. 36 059 participants underwent a sigmoidoscopy (and follow-up colonoscopy if positive sigmoidoscopy) and 6495 underwent a colonoscopy after a positive faecal immunochemical test (FIT). PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of asymptomatic participants diagnosed with CRC or advanced adenomas. Prevalence of bowel symptoms (rectal bleeding, change in bowel habits, diarrhoea, constipation, bloating, alternating bowel habits, general symptoms, other bowel symptoms) recorded by the endoscopist and their association with CRC and advanced adenomas. RESULTS: Among sigmoidoscopy participants, 7336 (20.3%) reported at least one symptom. 120 (60%) out of 200 individuals with screen-detected CRC and 1301 (76.5%) out of 1700 with advanced adenoma were asymptomatic. Rectal bleeding was associated with detection of CRC and advanced adenoma (OR 4.3, 95%CI 3.1 to 6.1 and 1.8, 95%CI 1.5 to 2.1, respectively), while change in bowel habits only with CRC detection (OR 3.8, 95%CI 2.4 to 6.1). Among the FIT positives, 2173 (33.5%) reported at least one symptom. Out of 299 individuals with screen-detected CRC and 1639 with advanced adenoma, 167 (55.9%) and 1 175 (71.7%) were asymptomatic, respectively. Detection of CRC was associated with rectal bleeding (OR 1.8, 95%CI 1.4 to 2.3), change in bowel habits (OR 2.2, 95%CI 1.4 to 3.5) and abdominal pain (OR 1.8, 95%CI 1.2 to 2.7). CONCLUSIONS: Some bowel symptoms increased the likelihood of being diagnosed with CRC or advanced adenoma. However, the majority of individuals with these findings were asymptomatic. Asymptomatic individuals should be encouraged to participate in CRC screening. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Identifier: NCT01538550. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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  • Xenikoudakis, G., et al. (författare)
  • Consequences of a demographic bottleneck on genetic structure and variation in the Scandinavian brown bear
  • 2015
  • Ingår i: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 24:13, s. 3441-3454
  • Tidskriftsartikel (refereegranskat)abstract
    • The Scandinavian brown bear went through a major decline in population size approximately 100 years ago, due to intense hunting. After being protected, the population subsequently recovered and today numbers in the thousands. The genetic diversity in the contemporary population has been investigated in considerable detail, and it has been shown that the population consists of several subpopulations that display relatively high levels of genetic variation. However, previous studies have been unable to resolve the degree to which the demographic bottleneck impacted the contemporary genetic structure and diversity. In this study, we used mitochondrial and microsatellite DNA markers from pre- and postbottleneck Scandinavian brown bear samples to investigate the effect of the bottleneck. Simulation and multivariate analysis suggested the same genetic structure for the historical and modern samples, which are clustered into three subpopulations in southern, central and northern Scandinavia. However, the southern subpopulation appears to have gone through a marked change in allele frequencies. When comparing the mitochondrial DNA diversity in the whole population, we found a major decline in haplotype numbers across the bottleneck. However, the loss of autosomal genetic diversity was less pronounced, although a significant decline in allelic richness was observed in the southern subpopulation. Approximate Bayesian computations provided clear support for a decline in effective population size during the bottleneck, in both the southern and northern subpopulations. These results have implications for the future management of the Scandinavian brown bear because they indicate a recent loss in genetic diversity and also that the current genetic structure may have been caused by historical ecological processes rather than recent anthropogenic persecution. 
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  • Ameen, Carly, et al. (författare)
  • Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
  • 2019
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
  • Tidskriftsartikel (refereegranskat)abstract
    • Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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  • Barlow, Axel, et al. (författare)
  • Middle Pleistocene genome calibrates a revised evolutionary history of extinct cave bears
  • 2021
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 31:8, s. 1771-1779
  • Tidskriftsartikel (refereegranskat)abstract
    • Palaeogenomes provide the potential to study evolutionary processes in real time, but this potential is limited by our ability to recover genetic data over extended timescales.1 As a consequence, most studies so far have focused on samples of Late Pleistocene or Holocene age, which covers only a small part of the history of many clades and species. Here, we report the recovery of a low coverage palaeogenome from the petrous bone of a 360,000 year old cave bear from Kudaro 1 cave in the Caucasus Mountains. Analysis of this genome alongside those of several Late Pleistocene cave bears reveals widespread mito-nuclear discordance in this group. Using the time interval between Middle and Late Pleistocene cave bear genomes, we directly estimate ursid nuclear and mitochondrial substitution rates to calibrate their respective phylogenies. This reveals postdivergence mitochondrial transfer as the dominant factor explaining their mito-nuclear discordance. Interestingly, these transfer events were not accompanied by large-scale nuclear introgression. However, we do detect additional instances of nuclear admixture among other cave bear lineages, and between cave bears and brown bears, which are not associated with mitochondrial exchange. Genomic data obtained from the Middle Pleistocene cave bear petrous bone has thus facilitated a revised evolutionary history of this extinct megafaunal group. Moreover, it suggests that petrous bones may provide a means of extending both the magnitude and time depth of palaeogenome retrieval over substantial portions of the evolutionary histories of many mammalian clades.
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  • Bergland, AK, et al. (författare)
  • Effects of Anthocyanin Supplementation on Serum Lipids, Glucose, Markers of Inflammation and Cognition in Adults With Increased Risk of Dementia - A Pilot Study
  • 2019
  • Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 10, s. 536-
  • Tidskriftsartikel (refereegranskat)abstract
    • Anthocyanins may protect against cardiovascular related cognitive decline and dementia.ObjectiveOpen-label study to measure changes in serum lipids, glucose, glycosylated hemoglobin (HbA1c), and markers of inflammation after anthocyanin supplementation in people with increased risk of dementia. As a secondary endpoint we examined potential changes in a battery of cognitive test in the anthocyanin group (AG). A total of 27 individuals with mild cognitive impairment (MCI) (n = 8) or stable non-obstructive coronary artery disease (CAD) (n = 19) consumed two Medox® capsules, each containing 80 mg of natural purified anthocyanins, twice daily for 16 weeks. They provided blood samples and performed a short battery of cognitive tests. Twenty healthy normal controls (NC) (n = 20) provided blood samples, but did not receive any intervention and did not perform cognitive tests.ResultsThere was a significant difference between groups for monocyte chemoattractant protein (MCP-1) and fasting glucose. In addition, total cholesterol and triglycerides were significantly increased in the AG. Improvements in memory and executive test scores were observed. No adverse effects were reported.ConclusionThe results of this pilot study were largely inconclusive with regard to the potential protective effects of anthocyanin supplementation. However, anthocyanins were well tolerated, and compliance was high. Larger, placebo-controlled studies to explore the potential effects of anthocyanins on dementia risk are encouraged.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT02409446
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  • Bhatta, L, et al. (författare)
  • Bone mineral density and risk of cardiovascular disease in men and women: the HUNT study
  • 2021
  • Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 36:11, s. 1169-1177
  • Tidskriftsartikel (refereegranskat)abstract
    • The association between bone mineral density (BMD) and cardiovascular disease (CVD) is not fully understood. We evaluated BMD as a risk factor for cardiovascular disease and specifically atrial fibrillation (AF), acute myocardial infarction (AMI), ischemic (IS) and hemorrhagic stroke (HS) and heart failure (HF) in men and women. This prospective population cohort utilized data on 22 857 adults from the second and third surveys of the HUNT Study in Norway free from CVD at baseline. BMD was measured using single and dual-energy X-ray absorptiometry in the non-dominant distal forearm and T-score was calculated. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from adjusted cox proportional hazards models. The analyses were sex-stratified, and models were adjusted for age, age-squared, BMI, physical activity, smoking status, alcohol use, and education level. Additionally, in women, we adjusted for estrogen use and postmenopause. During a mean follow-up of 13.6 ± 5.7 years, 2 928 individuals (12.8%) developed fatal or non-fatal CVD, 1 020 AF (4.5%), 1 172 AMI (5.1%), 1 389 IS (6.1%), 264 HS (1.1%), and 464 HF (2.0%). For every 1 unit decrease in BMD T-score the HR for any CVD was 1.01 (95% CI 0.98 to 1.04) in women and 0.99 (95% CI 0.94 to 1.03) in men. Point estimates for the four cardiovascular outcomes ranged from slightly protective (HR 0.95 for AF in men) to slightly deleterious (HR 1.12 for HS in men). We found no evidence of association of lower distal forearm BMD with CVD, AF, AMI, IS, HS, and HF.
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  • Boeskorov, G G, et al. (författare)
  • The Preliminary Analysis of Cave Lion Cubs Panthera spelaea (Goldfuss, 1810) from the Permafrost of Siberia
  • 2021
  • Ingår i: Quaternary. - : MDPI AG. - 2571-550X. ; 4:3
  • Tidskriftsartikel (refereegranskat)abstract
    • A preliminary description is presented of the well-preserved frozen mummies of two cubs of the extinct cave lion Panthera spelaea (finds of 2017–2018, Semyuelyakh River, Yakutia, eastern Siberia, Russia). The fossil lion cubs were found in close proximity, but they do not belong to the same litter, since their radiocarbon ages differ: the female (named ‘Sparta’) was dated to 27,962 ± 109 uncal years BP, and the male (named ‘Boris’) was dated to 43,448 ± 389 uncal years BP. The lion cubs have similar individual ages, 1–2 months. The general tone of the colour of the fur coat of Sparta is greyish to light brown, whereas, in Boris, the fur is generally lighter, greyish yellowish. It is, therefore, possible that light colouration prevailed with age in cave lions and was adaptive for northern snow-covered landscapes. The article discusses the results of computed tomography of cubs of the cave lion, the possible reasons for their death, and the peculiarities of their existence in the Siberian Arctic.
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  • Cappellini, Enrico, et al. (författare)
  • Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)
  • 2014
  • Ingår i: Zoological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4082 .- 1096-3642. ; 170:1, s. 222-232
  • Tidskriftsartikel (refereegranskat)abstract
    • The understanding of Earth's biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E.maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E.maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E.maximus. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium with the data set identifier PXD000423.
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  • Dalen, L, et al. (författare)
  • Identifying species from pieces of faeces
  • 2004
  • Ingår i: Conservation Genetics. - DORDRECHT : KLUWER ACADEMIC PUBL. - 1566-0621 .- 1572-9737. ; 5:1, s. 109-111
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  • De Baat, Esmée C., et al. (författare)
  • Risk Factors for Heart Failure among Pan-European Childhood Cancer Survivors : A PanCareSurFup and ProCardio Cohort and Nested Case-Control Study
  • 2023
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 41:1, s. 96-106
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines.METHODSThis study includes the PanCareSurFup and ProCardio cohort of ≥ 5-year childhood cancer survivors diagnosed between 1940 and 2009 in seven European countries (N = 42,361). We calculated the cumulative incidence of HF and conducted a nested case-control study to evaluate detailed treatment-related risk factors.RESULTSThe cumulative incidence of HF was 2% (95% CI, 1.7 to 2.2) by age 50 years. The case-control study (n = 1,000) showed that survivors who received a mean heart radiation therapy (RT) dose of 5 to < 15 Gy have an increased risk of HF (odds ratio, 5.5; 95% CI, 2.5 to 12.3), when compared with no heart RT. The risk associated with doses 5 to < 15 Gy increased with exposure of a larger heart volume. In addition, the HF risk increased in a linear fashion with higher mean heart RT doses. Regarding total cumulative anthracycline dose, survivors who received ≥ 100 mg/m2 had a substantially increased risk of HF and survivors treated with a lower dose showed no significantly increased risk of HF. The dose-response relationship appeared quadratic with higher anthracycline doses.CONCLUSIONSurvivors who received a mean heart RT dose of ≥ 5 Gy have an increased risk of HF. The risk associated with RT increases with larger volumes exposed. Survivors treated with < 100 mg/m2 total cumulative anthracycline dose have no significantly increased risk of HF. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.
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