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Sökning: WFRF:(Seppälä E.)

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  • Smith, Caren E., et al. (författare)
  • Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent
  • 2018
  • Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125. ; 62:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10−7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10−8) such that each serving of low-fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.
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  • McKeown, Nicola M., et al. (författare)
  • Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis
  • 2018
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:2, s. 317-330
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. Methods: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. Results: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10−3) and higher fasting insulin (0.030 ± 0.005 [loge pmol/l], p = 2.0 × 10−10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 loge pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. Conclusions/interpretation: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis. Trial registration: Trials related to this study were registered at clinicaltrials.govas NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses’ Health Study).
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  • Nivette, Amy E., et al. (författare)
  • A global analysis of the impact of COVID-19 stay-at-home restrictions on crime
  • 2021
  • Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 5, s. 868-877
  • Tidskriftsartikel (refereegranskat)abstract
    • The implementation of COVID-19 stay-at-home policies was associated with a considerable drop in urban crime in 27 cities across 23 countries. More stringent restrictions over movement in public space were predictive of larger declines in crime. The stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.
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  • Pappa, Irene, et al. (författare)
  • A genome-wide approach to children's aggressive behavior : The EAGLE consortium.
  • 2016
  • Ingår i: American Journal of Medical Genetics Part B. - : Wiley. - 1552-4841 .- 1552-485X. ; 171:5, s. 562-572
  • Tidskriftsartikel (refereegranskat)abstract
    • Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest sample exploring children's aggressive behavior to date (N = 18,988), with measures in two developmental stages (N = 15,668 early childhood and N = 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children's aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed sample and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total sample. GCTA quantified variance tagged by common SNPs (10-54%). The meta-analysis of the total sample identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P = 5.30 × 10(-8) ). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. © 2015 Wiley Periodicals, Inc.
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  • Buschmann, M. H., et al. (författare)
  • Correct interpretation of nanofluid convective heat transfer
  • 2018
  • Ingår i: International Journal of Thermal Sciences. - : Elsevier BV. - 1290-0729. ; 129, s. 504-531
  • Forskningsöversikt (refereegranskat)abstract
    • Engineers and scientist have a long tradition in trying to improve the thermophysical properties of convective heat carriers such as water and transformer oil. Technological developments of the last decades allow the dispersion of particle of sizes ranging between 10 and 100 nm in these liquids. In a large number of recent studies the resulting nanofluids have been reported to display anomalously high increase of convective heat transfer. The present study compiles experiments from five independent research teams investigating convective heat transfer in nanofluid flow in pipes, pipe with inserted twisted tape, annular counter flow heat exchanger, and coil and plate heat exchangers. The results of all these experiments unequivocally confirm that Newtonian nanofluid flow can be consistently characterized by employing Nusselt number correlations obtained for single-phase heat transfer liquids such as water when the correct thermophysical properties of the nanofluid are utilized. It is also shown that the heat transfer enhancement provided by nanofluids equals the increase in the thermal conductivity of the nanofluid as compared to the base fluid independent of the nanoparticle concentration or material. These results demonstrate that no anomalous phenomena are involved in thermal conduction and forced convection based heat transfer of nanofluids. The experiments are theoretically supported by a fundamental similarity analysis of nanoparticle motion in nanofluid flow.
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  • Buschmann, M. H., et al. (författare)
  • On the proper interpretation of nanofluid convective heat transfer
  • 2018
  • Ingår i: Proceeding: International Heat Transfer Conference 16. - 2377-424X. ; , s. 2855-2862
  • Konferensbidrag (refereegranskat)abstract
    • Technological developments of the last decades allow the production and the dispersion of particles of sizes ranging between 10 and 100 nm in liquids. In a large number of recent studies the resulting nanofluids have been reported to display anomalously high increase in convective heat transfer. The present study compiles experiments from five independent research teams investigating convective heat transfer in nanofluid flow in pipes (laminar and turbulent), pipe with inserted twisted tape, annular counter flow heat exchanger, and coil and plate heat exchangers. The results of all these experiments unequivocally confirm that Newtonian nanofluid flow can be consistently characterized by employing Nusselt number correlations obtained for single-phase heat transfer liquids such as water when the correct thermophysical properties of the nanofluid are utilized. It is also shown that the heat transfer enhancement provided by nanofluids equals the increase in the thermal conductivity of the nanofluid as compared to the base fluid independent of the nanoparticle concentration or material. These results demonstrate that no anomalous phenomena are involved in thermal conduction and forced convection based heat transfer of water based nanofluids. The experiments are theoretically supported by a fundamental similarity analysis of nanoparticle motion in nanofluid flow.
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  • Höglund, Katja, et al. (författare)
  • Effect of Breed on Plasma Endothelin-1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs
  • 2016
  • Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 30:2, s. 566-573
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are breed differences in several blood variables in healthy dogs.Objective: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration.Animals: Five-hundred and thirty-one healthy dogs of 9 breeds examined at 5 centers (2-4 breeds/center).Methods: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including blood pressure measurement, echocardiography, ECG, blood and urine analysis.Results: Median ET-1 concentration was 1.29 (interquartile range [IQR], 0.97-1.82) pg/mL, median cortisol concentration 46.0 (IQR, 29.0-80.8) nmol/L, and median renin activity 0.73 (IQR, 0.48-1.10) ng/mL/h in all dogs. Overall, breed differences were found in ET-1 and cortisol concentrations, and renin activity (P < .0001 for all). Pair-wise comparisons between breeds differed in 67% of comparisons for ET-1, 22% for cortisol, and 19% for renin activity, respectively. Within centers, breed differences were found at 5/5 centers for ET-1, 4/5 centers for cortisol, and 2/5 centers for renin activity. Newfoundlands had highest median ET-1 concentration, 3 times higher than Cavalier King Charles Spaniels, Doberman Pinschers, and Dachshunds. Median renin activity was highest in Dachshunds, twice the median value in Newfoundlands and Boxers. Median cortisol concentration was highest in Finnish Lapphunds, almost 3 times higher than in Boxers.Conclusions and Clinical Importance: Breed variation might be important to take into consideration when interpreting test results in clinical studies.
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  • Klütsch, Cornelya, et al. (författare)
  • Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia
  • 2011
  • Ingår i: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 42:1, s. 100-103
  • Tidskriftsartikel (refereegranskat)abstract
    • P>The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.
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  • Koivula, Lauri, et al. (författare)
  • Intensity-based dual model method for generation of synthetic CT images from standard T2-weighted MR images - Generalized technique for four different MR scanners
  • 2017
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 125:3, s. 411-419
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Recent studies have shown that it is possible to conduct entire radiotherapy treatment planning (RTP) workflow using only MR images. This study aims to develop a generalized intensity-based method to generate synthetic CT (sCT) images from standard T2-weighted (T2w) MR images of the pelvis. Materials and methods: This study developed a generalized dual model HU conversion method to convert standard T2w MR image intensity values to synthetic HU values, separately inside and outside of atlas-segmented bone volume contour. The method was developed and evaluated with 20 and 35 prostate cancer patients, respectively. MR images with scanning sequences in clinical use were acquired with four different MR scanners of three vendors. Results: For the generated synthetic CT (sCT) images of the 35 prostate patients, the mean (and maximal) HU differences in soft and bony tissue volumes were 16±6HUs (34HUs) and -46±56HUs (181HUs), respectively, against the true CT images. The average of the PTV mean dose difference in sCTs compared to those in true CTs was -0.6±0.4% (-1.3%). Conclusions: The study provides a generalized method for sCT creation from standard T2w images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences.
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  • Newnham, D. A., et al. (författare)
  • Observations and Modeling of Increased Nitric Oxide in the Antarctic Polar Middle Atmosphere Associated With Geomagnetic Storm-Driven Energetic Electron Precipitation
  • 2018
  • Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:7, s. 6009-6025
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitric oxide (NO) produced in the polar middle and upper atmosphere by energetic particle precipitation depletes ozone in the mesosphere and, following vertical transport in the winter polar vortex, in the stratosphere. Medium-energy electron (MEE) ionization by 30-1,000 keV electrons during geomagnetic storms may have a significant role in mesospheric NO production. However, questions remain about the relative importance of direct NO production by MEE at altitudes similar to 60-90 km versus indirect NO originating from auroral ionization above 90 km. We investigate potential drivers of NO variability in the southern-hemisphere mesosphere and lower thermosphere during 2013-2014. Contrasting geomagnetic activity occurred during the two austral winters, with more numerous moderate storms in the 2013 winter. Ground-based millimeter-wave observations of NO from Halley, Antarctica, are compared with measurements by the Solar Occultation For Ice Experiment (SOFIE) spaceborne spectrometer. NO partial columns over the altitude range 65-140 km from the two observational data sets show large day-to-day variability and significant disagreement, with Halley values on average 49% higher than the corresponding SOFIE data. SOFIE NO number densities, zonally averaged over geomagnetic latitudes -59 degrees to -65 degrees, are up to 3 x 10(8)/cm(3) higher in the winter of 2013 compared to 2014. Comparisons with a new version of the Whole Atmosphere Community Climate Model, which includes detailed D-region ion chemistry (WACCM-SIC) and MEE ionization rates, show that the model underestimates NO in the winter lower mesosphere whereas thermospheric abundances are too high. This indicates the need to further improve and verify WACCM-SIC with respect to MEE ionization, thermospheric NO chemistry, and vertical transport.
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  • Pyykkö, Okko T, et al. (författare)
  • Cerebrospinal fluid biomarker and brain biopsy findings in idiopathic normal pressure hydrocephalus
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e91974-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brain biopsy. Quantified Ab load in the brain biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.
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