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1.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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2.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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3.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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4.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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5.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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6.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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7.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t (peer-reviewed)
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8.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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9.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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10.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t
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11.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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12.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t
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13.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t (peer-reviewed)
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14.
  • Aad, G., et al. (author)
  • 2011
  • swepub:Mat__t
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15.
  • 2011
  • swepub:Mat__t
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16.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t
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17.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t
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18.
  • Schael, S., et al. (author)
  • Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
  • 2013
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
  • Research review (peer-reviewed)abstract
    • Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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19.
  • Schael, S, et al. (author)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Research review (peer-reviewed)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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21.
  • Sliz, E., et al. (author)
  • Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
  • 2023
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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22.
  • Snodgrass, C., et al. (author)
  • The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission
  • 2017
  • In: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2097
  • Journal article (peer-reviewed)abstract
    • We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/ Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies. This article is part of the themed issue 'Cometary science after Rosetta'.
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23.
  • Dey, Lankeswar, et al. (author)
  • Authenticating the Presence of a Relativistic Massive Black Hole Binary in OJ 287 Using Its General Relativity Centenary Flare : Improved Orbital Parameters
  • 2018
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 866:1
  • Journal article (peer-reviewed)abstract
    • Results from regular monitoring of relativistic compact binaries like PSR 1913+16 are consistent with the dominant (quadrupole) order emission of gravitational waves (GWs). We show that observations associated with the binary black hole (BBH) central engine of blazar OJ 287 demand the inclusion of gravitational radiation reaction effects beyond the quadrupolar order. It turns out that even the effects of certain hereditary contributions to GW emission are required to predict impact flare timings of OJ 287. We develop an approach that incorporates this effect into the BBH model for OJ 287. This allows us to demonstrate an excellent agreement between the observed impact flare timings and those predicted from ten orbital cycles of the BBH central engine model. The deduced rate of orbital period decay is nine orders of magnitude higher than the observed rate in PSR 1913+16, demonstrating again the relativistic nature of OJ 287's central engine. Finally, we argue that precise timing of the predicted 2019 impact flare should allow a test of the celebrated black hole no-hair theorem at the 10% level.
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26.
  • Frisk, U., et al. (author)
  • The Odin satellite - I. Radiometer design and test
  • 2003
  • In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 402:3, s. L27-L34
  • Journal article (peer-reviewed)abstract
    • The Sub-millimetre and Millimetre Radiometer (SMR) is the main instrument on the Swedish, Canadian, Finnish and French spacecraft Odin. It consists of a 1.1 metre diameter telescope with four tuneable heterodyne receivers covering the ranges 486-504 GHz and 541-581 GHz, and one fixed at 118.75 GHz together with backends that provide spectral resolution from 150 kHz to 1 MHz. This Letter describes the Odin radiometer, its operation and performance with the data processing and calibration described in Paper II.
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28.
  • Hilchenbach, M., et al. (author)
  • COMET 67P/CHURYUMOV-GERASIMENKO : CLOSE-UP on DUST PARTICLE FRAGMENTS
  • 2016
  • In: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 816:2
  • Journal article (peer-reviewed)abstract
    • The COmetary Secondary Ion Mass Analyser instrument on board ESA's Rosetta mission has collected dust particles in the coma of comet 67P/Churyumov-Gerasimenko. During the early-orbit phase of the Rosetta mission, particles and particle agglomerates have been imaged and analyzed in the inner coma at distances between 100 km and 10 km off the cometary nucleus and at more than 3 AU from the Sun. We identified 585 particles of more than 14 μm in size. The particles are collected at low impact speeds and constitute a sample of the dust particles in the inner coma impacting and fragmenting on the targets. The sizes of the particles range from 14 μm up to sub-millimeter sizes and the differential dust flux size distribution is fitted with a power law exponent of -3.1. After impact, the larger particles tend to stick together, spread out or consist of single or a group of clumps, and the flocculent morphology of the fragmented particles is revealed. The elemental composition of the dust particles is heterogeneous and the particles could contain typical silicates like olivine and pyroxenes, as well as iron sulfides. The sodium to iron elemental ratio is enriched with regard to abundances in CI carbonaceous chondrites by a factor from ∼1.5 to ∼15. No clear evidence for organic matter has been identified. The composition and morphology of the collected dust particles appear to be similar to that of interplanetary dust particles.
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29.
  • Kotseva, K, et al. (author)
  • Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry
  • 2019
  • In: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 26:8, s. 824-835
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice. Design A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries. Methods Patients (<80 years old) with verified coronary artery events or interventions were interviewed and examined ≥6 months later. Results A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m2), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active <30 min 5 times/week. Forty-two per cent had a blood pressure ≥140/90 mmHg (≥140/85 if diabetic), 71% had low-density lipoprotein cholesterol ≥1.8 mmol/L (≥70 mg/dL) and 29% reported having diabetes. Cardioprotective medication was: anti-platelets 93%, beta-blockers 81%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75% and statins 80%. Conclusion A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.
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31.
  • Hornung, K., et al. (author)
  • Electrical properties of cometary dust particles derived from line shapes of TOF-SIMS spectra measured by the ROSETTA/COSIMA instrument
  • 2019
  • In: Planetary and Space Science. - : Elsevier Ltd. - 0032-0633 .- 1873-5088. ; 182
  • Journal article (peer-reviewed)abstract
    • Between Aug. 2014 and Sept. 2016, while ESA's cornerstone mission Rosetta was operating in the vicinity of the nucleus and in the coma of comet 67P/Churyumov-Gerasimenko, the COSIMA instrument collected a large number of dust particles with diameters up to a millimeter. Positive or negative ions were detected by a time-of-flight secondary ion mass spectrometer (TOF-SIMS) and the composition of selected particles was deduced. Many of the negative ion mass spectra show, besides mass peaks at the correct position, an additional, extended contribution at the lower mass side caused by partial charging of the dust. This effect, usually avoided in SIMS applications, can in our case be used to obtain information on the electrical properties of the collected cometary dust particles, such as the specific resistivity (ρr>1.2⋅1010Ωm) and the real part of the relative electrical permittivity (εr<1.2). From these values a lower limit for the porosity is derived (P>0.8).
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32.
  • Sandholm, Niina, et al. (author)
  • New susceptibility loci associated with kidney disease in type 1 diabetes
  • 2012
  • In: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
  • Journal article (peer-reviewed)abstract
    • Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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  • Aarnio, K., et al. (author)
  • Cardiovascular events after ischemic stroke in young adults: A prospective follow-up study
  • 2016
  • In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 86:20, s. 1872-1879
  • Journal article (peer-reviewed)abstract
    • Objectives:To study the long-term risk of recurrent cardiac, arterial, and venous events in young stroke patients, and whether these risks differed between etiologic subgroups.Methods:The study population comprised 970 patients aged 15-49 years from the Helsinki Young Stroke Registry (HYSR) who had an ischemic stroke in 1994-2007. We obtained follow-up data until 2012 from the Finnish Care Register and Statistics Finland. Cumulative 15-year risks were analyzed with life tables, whereas relative risks and corresponding confidence intervals (CI) were based on hazard ratios (HR) from Cox regression analyses.Results:There were 283 (29.2%) patients with a cardiovascular event during the median follow-up of 10.1 years (range 0.1-18.0). Cumulative 15-year risk for venous events was 3.9%. Cumulative 15-year incidence rate for composite vascular events was 34.0 (95% CI 30.1-38.2) per 1,000 person-years. When adjusted for age and sex, patients with an index stroke caused by high-risk sources of cardioembolism had the highest HR for any subsequent cardiovascular events (3.7; 95% CI 2.6-5.4), whereas the large-artery atherosclerosis group had the highest HR (2.7; 95% CI 1.6-4.6) for recurrent stroke compared with patients with stroke of undetermined etiology.Conclusions:The risk for future cardiovascular events after ischemic stroke in young adults remains high for years after the index stroke, in particular when the index stroke is caused by high-risk sources of cardioembolism or large-artery atherosclerosis.
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34.
  • Coad, J. P., et al. (author)
  • Erosion/deposition in JET during the period 1999-2001
  • 2003
  • In: Journal of Nuclear Materials. - 0022-3115 .- 1873-4820. ; 313, s. 419-423
  • Journal article (peer-reviewed)abstract
    • Coated divertor and wall tiles exposed in JET for the 1999-2001 operations have been used to assess erosion/deposition. Deposited films of up to 90 mum thickness at the inner wall of the divertor tiles are, for the most part, enriched in beryllium and other metals, whilst carbon is probably chemically sputtered from these tiles and transported to shadowed regions of the inner divertor. However, from the composition at the surface of the tiles, it appears that the chemical erosion was 'switched off' by reducing the JET vessel wall temperature for the last part of the operations to 200 degreesC. Thick powdery deposits localised at the ion transport limit at each corner of the divertor may be due to physical sputtering. Erosion of the coatings is seen at the outer divertor wall, and on all the inner wall and outer limiter tiles.
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  • Martinez-Majander, N., et al. (author)
  • Embolic strokes of undetermined source in young adults: baseline characteristics and long-term outcome
  • 2018
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 25:3, s. 535-541
  • Journal article (peer-reviewed)abstract
    • Background and purposeEmbolic strokes of undetermined source (ESUS) are a recent entity, not yet thoroughly investigated in young stroke patients. The clinical characteristics and long-term risks of vascular events and all-cause mortality between young-onset ESUS and other aetiological subgroups were compared. MethodsPatients with ESUS were identified amongst the 1008 patients aged 15-49 years with first-ever ischaemic stroke in Helsinki Young Stroke Registry, and primary end-points were defined as recurrent stroke, composite vascular events and all-cause mortality. Cumulative 15-year risks for each end-point were analysed with life tables and adjusted risks were based on Cox proportional hazard analyses. ResultsOf the 971 eligible patients, 203 (20.9%) were classified as ESUS. They were younger (median age 40 years, interquartile range 32-46 vs. 45 years, 39-47), more often female (43.3% vs. 35.7%) and had fewer cardiovascular risk factors than other modified TOAST groups. With a median follow-up time of 10.1 years, ESUS patients had the second lowest cumulative risk of recurrent stroke and composite vascular events and lowest mortality compared to other TOAST groups. Large-artery atherosclerosis and small vessel disease carried significantly higher risk for recurrent stroke than did ESUS, whilst no difference appeared between cardioembolism from high-risk sources and ESUS. ConclusionsIn our cohort, ESUS patients were younger and had milder cardiovascular risk factor burden and generally better long-term outcome compared to other causes of young-onset stroke. The comparable risk of recurrent stroke between ESUS and high-risk sources of cardioembolism might suggest similarities in their pathophysiology.
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  • Martinez-Majander, N., et al. (author)
  • Endothelial Dysfunction is Associated With Early-Onset Cryptogenic Ischemic Stroke in Men and With Increasing Age
  • 2021
  • In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 10:14
  • Journal article (peer-reviewed)abstract
    • Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (+/- 5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients >= 41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.
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  • Martinez-Majander, N., et al. (author)
  • Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study
  • 2022
  • In: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 31:9
  • Journal article (peer-reviewed)abstract
    • Background and Purpose: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. Methods: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. Results: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). Conclusions: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS. © 2022 The Author(s)
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  • Mustanoja, S., et al. (author)
  • Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke
  • 2016
  • In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 47:6
  • Journal article (peer-reviewed)abstract
    • Background and Purpose-High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. Methods-The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. Results-Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n = 142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P < 0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP >= 160 mm Hg compared with those with SBP < 160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; P < 0.001) occurring earlier (13.9 years [13.0-14.6] versus 16.2 [15.8-16.6]; P < 0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. Conclusions-In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes.
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  • Ninou, AH, et al. (author)
  • PFKFB3 Inhibition Sensitizes DNA Crosslinking Chemotherapies by Suppressing Fanconi Anemia Repair
  • 2021
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
  • Journal article (peer-reviewed)abstract
    • Replicative repair of interstrand crosslinks (ICL) generated by platinum chemotherapeutics is orchestrated by the Fanconi anemia (FA) repair pathway to ensure resolution of stalled replication forks and the maintenance of genomic integrity. Here, we identify novel regulation of FA repair by the cancer-associated glycolytic enzyme PFKFB3 that has functional consequences for replication-associated ICL repair and cancer cell survival. Inhibition of PFKFB3 displays a cancer-specific synergy with platinum compounds in blocking cell viability and restores sensitivity in treatment-resistant models. Notably, the synergies are associated with DNA-damage-induced chromatin association of PFKFB3 upon cancer transformation, which further increases upon platinum resistance. FA pathway activation triggers the PFKFB3 assembly into nuclear foci in an ATR- and FANCM-dependent manner. Blocking PFKFB3 activity disrupts the assembly of key FA repair factors and consequently prevents fork restart. This results in an incapacity to replicate cells to progress through S-phase, an accumulation of DNA damage in replicating cells, and fork collapse. We further validate PFKFB3-dependent regulation of FA repair in ex vivo cultures from cancer patients. Collectively, targeting PFKFB3 opens up therapeutic possibilities to improve the efficacy of ICL-inducing cancer treatments.
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  • Randler, C., et al. (author)
  • Animal welfare attitudes : Effects of gender and diet in university samples from 22 countries
  • 2021
  • In: Animals. - : MDPI AG. - 2076-2615. ; 11:7
  • Journal article (peer-reviewed)abstract
    • Animal Welfare Attitudes (AWA) are defined as human attitudes towards the welfare of animals in different dimensions and settings. Demographic factors, such as age and gender are associated with AWA. The aim of this study was to assess gender differences among university students in a large convenience sample from twenty-two nations in AWA. A total of 7914 people participated in the study (5155 women, 2711 men, 48 diverse). Participants completed a questionnaire that collected demographic data, typical diet and responses to the Composite Respect for Animals Scale Short version (CRAS-S). In addition, we used a measure of gender empowerment from the Human Development Report. The largest variance in AWA was explained by diet, followed by country and gender. In terms of diet, 6385 participants reported to be omnivores, 296 as pescatarian, 637 ate a vegetarian diet and 434 were vegans (n = 162 without answer). Diet was related with CRAS-S scores; people with a vegan diet scored higher in AWA than omnivores. Women scored significantly higher on AWA than men. Furthermore, gender differences in AWA increased as gender inequality decreased. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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45.
  • van Dongen, M. M. E., et al. (author)
  • Use of antihypertensive medication after ischemic stroke in young adults and its association with long-term outcome
  • 2019
  • In: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 51:1, s. 68-77
  • Journal article (peer-reviewed)abstract
    • Background: Knowledge on the use of secondary preventive medication in young adults is limited. Methods: We included 936 first-ever ischemic stroke 30-day survivors aged 15-49, enrolled in the Helsinki Young Stroke Registry, 1994-2007. Follow-up data until 2012 came from Finnish Care Register, Statistics Finland, and Social Insurance Institution of Finland. Usage thresholds were defined as non-users, low (prescription coverage <30%), intermediate (30-80%) and high users (>80%). Adjusted Cox regression allowed assessing the association of usage with all-cause mortality and recurrent vascular events. Results: Of our patients, 40.5% were non-users, 7.8% had low usage, 11.8% intermediate usage and 40.0% high usage. Median follow-up was 8.3 years. Compared to non-users, risk of mortality and recurrent stroke or TIA was lower for patients with low-intermediate (HR 0.40, 95% CI 0.22-0.65; HR 0.31, 95% CI 0.18-0.53) and high usage (HR 0.25, 95% CI 0.15-0.42; HR 0.30, 95% CI 0.19-0.46), after adjustment for confounders. Conclusions: Use of antihypertensives was suboptimal in one-third of patients in whom antihypertensives were initially prescribed. Users were at lower risk of mortality and recurrent stroke or TIA compared to non-users.Key Messages The use of antihypertensive medication is suboptimal in one-third of patients in whom antihypertensive medication was initially prescribed after ischemic stroke at young age. The risk of mortality and recurrent stroke or TIA is lower for users of antihypertensive medication after ischemic stroke at young age compared to non-users, after adjustment for relevant confounders including pre-existing hypertension and prior use of antihypertensive medication. Specific guidelines on antihypertensive medication use after ischemic stroke at young age are lacking. However, our results may motivate doctors and patients in gaining better usage of antihypertensive medication, since better usage was associated with more favorable outcome in this study.
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47.
  • Ezzat, Kariem, et al. (author)
  • PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation
  • 2011
  • In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:12, s. 5284-5298
  • Journal article (peer-reviewed)abstract
    • Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne's muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine™ 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms.
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