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Sökning: WFRF:(Kane Y.)

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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Ovadia, C., et al. (författare)
  • Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis
  • 2021
  • Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 6:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 mu mol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67.8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0.7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0.6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1.04, 95% CI 0.35-3.07; p=0.95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0.29, 95% CI 0.04-2.42; p=0.25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1.28, 95% CI 0.86-1.91; p=0.22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0.60, 0.39-0.91; p=0.016). Interpretation Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Copyright (C) 2021 The Authors(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • Veronese, N., et al. (författare)
  • Inverse relationship between body mass index and mortality in older nursing home residents : a meta-analysis of 19,538 elderly subjects
  • 2015
  • Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:11, s. 1001-1015
  • Forskningsöversikt (refereegranskat)abstract
    • Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, 30kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI=1.26-1.58) for underweight, 0.85 (95% CI=0.73-0.99) for overweight and 0.74 (95% CI=0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR=1.65 [95% CI=1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
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  • Solmi, M, et al. (författare)
  • 2022
  • Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)
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  • Bouchy, F., et al. (författare)
  • WASP-21b : a hot-Saturn exoplanet transiting a thick disc star
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 519, s. A98-
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of WASP-21b, a new transiting exoplanet discovered by the Wide Angle Search for Planets ( WASP) Consortium and established and characterized with the FIES, SOPHIE, CORALIE and HARPS fiber-fed echelle spectrographs. A 4.3-d period, 1.1% transit depth and 3.4-h duration are derived for WASP-21b using SuperWASP-North and high precision photometric observations at the Liverpool Telescope. Simultaneous fitting to the photometric and radial velocity data with a Markov Chain Monte Carlo procedure leads to a planet in the mass regime of Saturn. With a radius of 1.07 R-Jup and mass of 0.30 M-Jup, WASP-21b has a density close to 0.24 rho(Jup) corresponding to the distribution peak at low density of transiting gaseous giant planets. With a host star metallicity [Fe/H] of -0.46, WASP-21b strengthens the correlation between planetary density and host star metallicity for the five known Saturn-like transiting planets. Furthermore there are clear indications that WASP-21b is the first transiting planet belonging to the thick disc.
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  • Chan, K. Y., et al. (författare)
  • Characterization of the Calcitonin Gene-Related Peptide Receptor Antagonist Telcagepant (MK-0974) in Human Isolated Coronary Arteries
  • 2010
  • Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0103 .- 0022-3565. ; 334:3, s. 746-752
  • Tidskriftsartikel (refereegranskat)abstract
    • The sensory neuropeptide calcitonin gene-related peptide (CGRP) plays a role in primary headaches, and CGRP receptor antagonists are effective in migraine treatment. CGRP is a potent vasodilator, raising the possibility that antagonism of its receptor could have cardiovascular effects. We therefore investigated the effects of the antimigraine CGRP receptor antagonist telcagepant (MK-0974) [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan- 3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)piperidine-1-c arboxamide] on human isolated coronary arteries. Arteries with different internal diameters were studied to assess the potential for differential effects across the coronary vascular bed. The concentration-dependent relaxation responses to human alpha CGRP were greater in distal coronary arteries (i.d. 600-1000 mu m; E-max = 83 +/- 7%) than proximal coronary arteries (i.d. 2-3 mm; E-max = 23 +/- 9%), coronary arteries from explanted hearts (i.d. 3-5 mm; E-max = 11 +/- 3%), and coronary arterioles (i.d. 200-300 mu m; E-max = 15 +/- 7%). Telcagepant alone did not induce contraction or relaxation of these coronary blood vessels. Pretreatment with telcagepant (10 nM to 1 mu M) antagonized alpha CGRP-induced relaxation competitively in distal coronary arteries (pA(2) = 8.43 +/- 0.24) and proximal coronary arteries and coronary arterioles (1 mu M telcagepant, giving pK(B) = 7.89 +/- 0.13 and 7.78 +/- 0.16, respectively). alpha CGRP significantly increased cAMP levels in distal, but not proximal, coronary arteries, and this was abolished by pretreatment with telcagepant. Immunohistochemistry revealed the expression and colocalization of the CGRP receptor elements calcitonin-like receptor and receptor activity-modifying protein 1 in the smooth muscle cells in the media layer of human coronary arteries. These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions.
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  • Hawthorn, F., et al. (författare)
  • TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
  • 2023
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
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  • Kane, Stephen R., et al. (författare)
  • Climate Modeling of a Potential ExoVenus
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 869:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The planetary mass and radius sensitivity of exoplanet discovery capabilities has reached into the terrestrial regime. The focus of such investigations is to search within the Habitable Zone where a modern Earth-like atmosphere may be a viable comparison. However, the detection bias of the transit and radial velocity methods lies close to the host star where the received flux at the planet may push the atmosphere into a runaway greenhouse state. One such exoplanet discovery, Kepler-1649b, receives a similar flux from its star as modern Venus does from the Sun, and so was categorized as a possible exo Venus. Here we discuss the planetary parameters of Kepler-1649b in relation to Venus to establish its potential as a Venus analog. We utilize the general circulation model ROCKE-3D to simulate the evolution of the surface temperature of Kepler-1649b under various assumptions, including relative atmospheric abundances. We show that in all our simulations the atmospheric model rapidly diverges from temperate surface conditions toward a runaway greenhouse with rapidly escalating surface temperatures. We calculate transmission spectra for the evolved atmosphere and discuss these spectra within the context of the James Webb Space Telescope Near-Infrared Spectrograph capabilities. We thus demonstrate the detectability of the key atmospheric signatures of possible runaway greenhouse transition states and outline the future prospects of characterizing potential Venus analogs.
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  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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  • Murgas, F., et al. (författare)
  • TOI-674b: An oasis in the desert of exo-Neptunes transiting a nearby M dwarf
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The NASA mission TESS is currently doing an all-sky survey from space to detect transiting planets around bright stars. As part of the validation process, the most promising planet candidates need to be confirmed and characterized using follow-up observations. Aims. In this article, our aim is to confirm the planetary nature of the transiting planet candidate TOI-674b using spectroscopic and photometric observations. Methods. We use TESS, Spitzer, ground-based light curves, and HARPS spectrograph radial velocity measurements to establish the physical properties of the transiting exoplanet candidate TOI-674b. We perform a joint fit of the light curves and radial velocity time series to measure the mass, radius, and orbital parameters of the candidate. Results. We confirm and characterize TOI-674b, a low-density super-Neptune transiting a nearby M dwarf. The host star (TIC 158588995, V = 14.2 mag, J = 10.3 mag) is characterized by its M2V spectral type with M = 0.420 ± 0.010 M , R = 0.420 ± 0.013 R , and Teff = 3514 ± 57 K; it is located at a distance d = 46.16 ± 0.03 pc. Combining the available transit light curves plus radial velocity measurements and jointly fitting a circular orbit model, we find an orbital period of 1.977143 ± 3 × 10-6 days, a planetary radius of 5.25 ± 0.17 R , and a mass of 23.6 ± 3.3 M implying a mean density of ρp =0.91 ± 0.15 g cm-3. A non-circular orbit model fit delivers similar planetary mass and radius values within the uncertainties. Given the measured planetary radius and mass, TOI-674b is one of the largest and most massive super-Neptune class planets discovered around an M-type star to date. It is found in the Neptunian desert, and is a promising candidate for atmospheric characterization using the James Webb Space Telescope.
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  • Panagopoulou, Paraskevi, et al. (författare)
  • Parental age and the risk of childhood acute myeloid leukemia : results from the Childhood Leukemia International Consortium
  • 2019
  • Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 59, s. 158-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent.Aim:To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies.Material/methods: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants < 1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period.Results:Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers >= 40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year.Conclusions:An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.
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  • Petridou, Eleni Th., et al. (författare)
  • Advanced parental age as risk factor for childhood acute lymphoblastic leukemia : results from studies of the Childhood Leukemia International Consortium
  • 2018
  • Ingår i: European Journal of Epidemiology. - : SPRINGER. - 0393-2990 .- 1573-7284. ; 33:10, s. 965-976
  • Tidskriftsartikel (refereegranskat)abstract
    • Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I (2) = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
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  • Roselli, Carolina, et al. (författare)
  • Multi-ethnic genome-wide association study for atrial fibrillation
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
  • Tidskriftsartikel (refereegranskat)abstract
    • Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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  • Strakova, A., et al. (författare)
  • Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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  • Wang, SPS, et al. (författare)
  • B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
  • 2022
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 31:5, s. 1103-1110
  • Tidskriftsartikel (refereegranskat)
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