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1.
  • Andrés, E., et al. (författare)
  • Observation of high-energy neutrinos using Čerenkov detectors embedded deep in Antarctic ice
  • 2001
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 410:6827, s. 441-443
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova2, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water3,4 or ice5. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations1.
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2.
  • Andrés, E., et al. (författare)
  • Recent results from AMANDA
  • 2001
  • Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 16:1C, s. 1013-1015
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope.
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3.
  • Andres, E., et al. (författare)
  • Results from the AMANDA high energy neutrino detector
  • 2000
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 91:1-3, s. 423-430
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper briefly summarizes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector. The complete data set from 1997 was analyzed. For Eμ > 10 TeV, the detector exceeds 10,000 m2 in effective area between declinations of 25 and 90 degrees. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the overall sensitivity of the detector. The absolute pointing accuracy and angular resolution has been confirmed by the analysis of coincident events between the SPASE air shower array and the AMANDA detector. Preliminary flux limits from point source candidates are presented. For declinations larger than +45 degrees, our results compare favorably to existing limits for sources in the Southern sky. We also present the current status of the searches for high energy neutrino emission from diffusely distributed sources, GRBs, and WIMPs from the center of the earth.
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4.
  • Wischnewski, R., et al. (författare)
  • The AMANDA neutrino detector : Status report
  • 2000
  • Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 85:1-3, s. 141-145
  • Tidskriftsartikel (refereegranskat)abstract
    • The first stage of the AMANDA High Energy Neutrino Detector at the South Pole, the 302 PMT array AMANDA-B10, is taking data since 1997. We describe results on atmospheric neutrinos, limits on indirect WIMP detection, seasonal muon flux variation, relativistic monopole flux limits, a search for gravitational collapse neutrinos, and a depth scan of the optical ice properties. The next stage 19-string detector AMANDA-II with ∼650 PMTs will be completed in spring 2000.
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5.
  • Bai, X., et al. (författare)
  • Status of the Neutrino Telescope AMANDA : Monopoles and WIMPS
  • 2001
  • Ingår i: Dark Matter in Astro- and Particle Physics. - Berlin, Heidelberg : Springer. - 9783642626081 ; , s. 699-706
  • Konferensbidrag (refereegranskat)abstract
    • The neutrino telescope AMANDA has been set up at the geographical South Pole as first step to a neutrino telescope of the scale of one cubic kilometer, which is the canonical size for a detector sensitive to neutrinos from Active Galactic Nuclei (AGN), Gamma Ray Bursts (GRB) and Topological Defects (TD). The location and depth in which the detector is installed is given by the requirement to detect neutrinos by the Cherenkov light produced by their reaction products and to keep the background due to atmospheric muons as small as possible. However, a detector optimized for this purpose is also capable to detect the bright Cherenkov light from relativistic Monopoles and neutrino signals from regions with high gravitational potential, where WIMPS are accumulated and possibly annihilate. Both hypothetical particles might contribute to the amount of dark matter. Therefore here a report about the status of the experiment (autumn 2000) and about the status of the search for these particles with the AMANDA B10 sub-detector is given.
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6.
  • Edsjö, Joakim, et al. (författare)
  • WIMP searches with AMANDA-B10
  • 2001
  • Ingår i: The Identification Of Dark Matter. - : World Scientific. - 9789810246020 ; , s. 499-505
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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7.
  • Kulmala, M., et al. (författare)
  • General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
  • 2011
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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8.
  • Andres, E., et al. (författare)
  • AMANDA : Status, results and future
  • 1999
  • Ingår i: Proceedings, 8th International Workshop, Venice, Italy, February 23-26, 1999. Vol. 1, 2. ; , s. 63-79
  • Konferensbidrag (refereegranskat)abstract
    • We review the status of the AMANDA neutrino telescope. We present resultsobtained from the four-string prototype array AMANDA-B4 and describe themethods of track reconstruction and neutrino event separation. We give also firstresults of the analysis of the 10-string detector AMANDA-B10, in particular onatmospheric neutrinos and the search for magnetic monopoles. We sketch thefuture schedule on the way to a cube kilometer telescope at the South Pole,ICECUBE.
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9.
  • Andres, E., et al. (författare)
  • The AMANDA neutrino telescope : Principle of operation and first results
  • 2000
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 13:1, s. 1-20
  • Tidskriftsartikel (refereegranskat)abstract
    • AMANDA is a high-energy neutrino telescope presently under construction at the geographical South Pole. In the Antarctic summer 1995/96, an array of 80 optical modules (OMs) arranged on 4 strings (AMANDA-B4) was deployed at depths between 1.5 and 2 km. In this paper we describe the design and performance of the AMANDA-B4 prototype, based on data collected between February and November 1996. Monte Carlo simulations of the detector response to down-going atmospheric muon tracks show that the global behavior of the detector is understood. We describe the data analysis method and present first results on atmospheric muon reconstruction and separation of neutrino candidates. The AMANDA array was upgraded with 216 OMs on 6 new strings in 1996/97 (AMANDA-B10), and 122 additional OMs on 3 strings in 1997/98.
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10.
  • Wischnewski, R., et al. (författare)
  • The AMANDA neutrino detector
  • 1999
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 75:1-2, s. 412-414
  • Tidskriftsartikel (refereegranskat)abstract
    • The first stage of the AMANDA High Energy Neutrino Detector at the South Pole, the 302 PMT array AMANDA-B with an expected effective area for TeV neutrinos of ∼ 104 m2, has been taking data since 1997. Progress with calibration, investigation of ice properties, as well as muon and neutrino data analysis are described. The next stage 20-string detector AMANDA-II with ∼800 PMTs will be completed in spring 2000.
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11.
  • Andrés, E. C., et al. (författare)
  • The AMANDA neutrino telescope
  • 1999
  • Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 77:1-3, s. 474-485
  • Tidskriftsartikel (refereegranskat)abstract
    • With an effective telescope area of order 104 m2 for TeV neutrinos, a threshold near ∼50 GeV and a pointing accuracy of 2.5 degrees per muon track, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe early results on the calibration of natural deep ice as a particle detector as well as on AMANDA's performance as a neutrino telescope.
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12.
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13.
  • Eriksson, Leif, 1971-, et al. (författare)
  • Secular trend, seasonality and effects of a community-based intervention on neonatal mortality : follow-up of a cluster-randomised trial in Quang Ninh province, Vietnam
  • 2018
  • Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 72:9, s. 776-782
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Little is know about whether the effects of community engagement interventions for child survival in low-income and middle-income settings are sustained. Seasonal variation and secular trend may blur the data. Neonatal mortality was reduced in a cluster-randomised trial in Vietnam where laywomen facilitated groups composed of local stakeholders employing a problem-solving approach for 3 years. In this analysis, we aim at disentangling the secular trend, the seasonal variation and the effect of the intervention on neonatal mortality during and after the trial.Methods: In Quang Ninh province, 44 communes were allocated to intervention and 46 to control. Births and neonatal deaths were assessed in a baseline survey in 2005, monitored during the trial in 2008–2011 and followed up by a survey in 2014. Time series analyses were performed on monthly neonatal mortality data.Results: There were 30 187 live births and 480 neonatal deaths. The intervention reduced the neonatal mortality from 19.1 to 11.6 per 1000 live births. The reduction was sustained 3 years after the trial. The control areas reached a similar level at the time of follow-up. Time series decomposition analysis revealed a downward trend in the intervention areas during the trial that was not found in the control areas. Neonatal mortality peaked in the hot and wet summers.Conclusions: A community engagement intervention resulted in a lower neonatal mortality rate that was sustained but not further reduced after the end of the trial. When decomposing time series of neonatal mortality, a clear downward trend was demonstrated in intervention but not in control areas.Trial registration number: ISRCTN44599712, Post-results.
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14.
  • Liao, X., et al. (författare)
  • Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?
  • 2016
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:11, s. 1165-1173
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions. © 2016 European Society of Cardiology.
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15.
  • Lorenz, M. W., et al. (författare)
  • Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration
  • 2018
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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16.
  • Andrés, E., et al. (författare)
  • Status of the AMANDA experiment
  • 1999
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 70:1-3, s. 448-452
  • Tidskriftsartikel (refereegranskat)abstract
    • The AMANDA high energy neutrino telescope has successfully been increased in size from four detector strings to ten detector strings during the 1996/1997 season. The first upward going muon-neutrino candidates have been reconstructed from the 1996 year's four-string data. Three new detector strings will be deployed during 1997/1998 to 2350 metres depth.
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17.
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18.
  • Bay, R. C., et al. (författare)
  • The AMANDA neutrino telescope and the indirect search for dark matter : AMANDA Colaboration
  • 1998
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 307:1-4, s. 243-252
  • Tidskriftsartikel (refereegranskat)abstract
    • With an effective telescope area of order 104m2, a threshold of ~50GeV and a pointing accuracy of 2.5°, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe its performance, focussing on the capability to detect halo dark matter particles via their annihilation into neutrinos.
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19.
  • Depledge, D. P., et al. (författare)
  • High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid from Cases of Varicella Zoster Virus Encephalitis
  • 2018
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:10, s. 1592-1601
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods. Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results. Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions. Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.
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20.
  • Guimond, S. E., et al. (författare)
  • Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
  • 2022
  • Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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21.
  • Jons, D., et al. (författare)
  • Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis
  • 2022
  • Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 86-87
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition  for  the development  of  multiple  sclerosis  (MS).  EBV  antibodies, predominantly anti-EBNA1, develop in the presymp-tomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV  seropositivity  preceded  the  first  expression  of  incipient  axonal lesions, serum Neurofilament Light (sNFL) .Objectives: To  determine  the  onset  and  individual  order  of  appearance  of EBV  seroreactivity  and  the  serum  neuroaxonal  injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients.Aims: To  characterize  the  presymptomatic  appearance  of  anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.Methods:  A nested  case-control  study  in  669  pre-symptomati-cally acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum lev-els of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were   measured   in   individual   presymptomatic   samples   and   expressed  as delta  scores  with  matched  controls  in  relation  to  time until MS onset.Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from  15-20  years  before  MS debut.  Significant  (p=0.001  and  p=0.002) from 10-15 years, with consistent delta-scores succes-sively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual sam-ples  negative  for  both EBNA1 and  VCA  IgG  antibodies  in  the  pre-MS group (n = 36) showed any elevation of the sNfL level.Conclusions: In  a  pre-MS  material,  the  seroreactivity  against  EBNA1  was followed  by  VCA  and  gp350,  before  increased  sNFL appeared, indicating incipient axonal injury. Together with its biological characteristics this temporal order confirms the role of EBV as a trigger of MS.
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22.
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23.
  • Lindberg, T., et al. (författare)
  • Distribution of15N in the soil-plant system during a four-year field lysimeter study with barley (Hordeum distichum L.) and perennial meadow fescue (Festuca pratensis Huds.)
  • 1989
  • Ingår i: Plant and Soil. - Dordrecht, Netherlands : Kluwer Academic Publishers. - 0032-079X .- 1573-5036. ; 119:1, s. 25-37
  • Tidskriftsartikel (refereegranskat)abstract
    • An annual cereal, barley, and a perennial grass ley, meadow fescue, were grown in field lysimeters in Sweden and fertilized with 12 and 20g Ca(NO3)2-N m-2 yr-1, respectively. Isotope-labeled (15N) fertilizer was added during year 1 of the study, whereafter similar amounts of unlabeled N were added during years 2 and 3. The grass ley lysimeters were ploughed after the growing season of year 3 and sown with barley during year 4. The barley harvest in year 1 removed 59% of the added fertilizer N, while the fertilizer N export by two meadow fescue harvests in year 1 was 65%. The labeled N export decreased rapidly after year 1, especially in the barley, but increased slightly after ploughing of the grass ley.The microbial biomass, measured with the chloroform fumigation method, incorporated a maximum of 1.4-1.7% of the labeled N during the first seven weeks after application. Later on, the incorporation stabilized at less than 1% in both cropping systems.The susceptibility of the residual labeled N to mineralization was evaluated three years after application by means of long-term laboratory incubations. The curves of cumulative mineralized N were described by a two-component first-order regression model that differentiated between an available and a more recalcitrant fraction of potentially mineralizable N. There was no difference in the amounts of potentially mineralizable N between the cropping systems. The labeled N comprised 5 and 2% of the amounts of potentially mineralizable N in the available and more recalcitrant fraction, respectively. The mineralization rate constants for the labeled N were almost twice as high as for the total potentially mineralizable N. The available fraction of the total potentially mineralizable N was 12%, while twice that proportion of the labeled N was available.It was concluded that the short-term ley did not differ from the annual crop with respect to the early disposition of the fertilizer N and the behaviour of the residual organic N.
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24.
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25.
  • Tschiderer, L., et al. (författare)
  • The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale
  • 2020
  • Ingår i: Gerontology. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 66:5, s. 447-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, ankle-brachial index, pulse wave velocity, and coronary artery calcium. The Prospective Studies of Atherosclerosis (Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences. (c) 2020 S. Karger AG, Basel
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26.
  • Uphoff, EP, et al. (författare)
  • Variations in the prevalence of childhood asthma and wheeze in MeDALL cohorts in Europe
  • 2017
  • Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 3:3
  • Tidskriftsartikel (refereegranskat)abstract
    • While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, individual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe.We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education, parental smoking, pets, parental asthma, doctor-diagnosed allergic rhinitis, doctor-diagnosed eczema and wheeze severity.At age 4 years, asthma prevalence varied from 1.72% in Germany to 13.48% in England and the prevalence of wheeze varied from 9.82% in Greece to 55.37% in Spain. Adjusted estimates of the proportion of 4-year-old children with wheeze diagnosed with asthma remained highest in England (38.14%, 95% CI 31.38–44.90%) and lowest in Spain (15.94%, 95% CI 6.16–25.71%).The large differences in prevalence rates of asthma, wheeze and wheeze with asthma at age 4 years between European cohorts may indicate that childhood asthma is more readily diagnosed in some countries while going unrecognised elsewhere.
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27.
  • Abdelmagid, N., et al. (författare)
  • Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
  • 2016
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
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28.
  • Askebjer, P., et al. (författare)
  • Optical properties of deep ice at the South Pole : Absorption
  • 1997
  • Ingår i: Applied Optics. - : Optical Society of America. - 0003-6935 .- 1539-4522. ; 36:18, s. 4168-4180
  • Tidskriftsartikel (refereegranskat)abstract
    • We discuss recent measurements of the wavelength-dependent absorption coefficients in deep South Pole ice. The method uses transit-time distributions of pulses from a variable-frequency laser sent between emitters and receivers embedded in the ice. At depths of 800-1000 m scattering is dominated by residual air bubbles, whereas absorption occurs both in ice itself and in insoluble impurities. The absorption coefficient increases approximately exponentially with wavelength in the measured interval 410-610 nm. At the shortest wavelength our value is approximately a factor 20 below previous values obtained for laboratory ice and lake ice; with increasing wavelength the discrepancy with previous measurements decreases. At ∼415 to ∼500 nm the experimental uncertainties are small enough for us to resolve an extrinsic contribution to absorption in ice: submicrometer dust particles contribute by an amount that increases with depth and corresponds well with the expected increase seen near the Last Glacial Maximum in Vostok and Dome C ice cores. The laser pulse method allows remote mapping of gross structure in dust concentration as a function of depth in glacial ice.
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29.
  • Ayukekbong, James A., et al. (författare)
  • Monitoring of seasonality of norovirus and other enteric viruses in Cameroon by real-time PCR : an exploratory study
  • 2014
  • Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 142:7, s. 1393-1402
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the seasonal fluctuation of norovirus and other enteric viruses in Cameroon. Two hundred participants aged between 1 and 69 years were prospectively followed up. Each participant provided monthly faecal samples over a 12-month period. A total of 2484 samples were tested using multiplex real-time PCR assay for the detection of norovirus, rotavirus and enterovirus. The effect of weather variables and risk factors were analysed by Pearson correlation and bivariate analysis. Overall, enterovirus was the most commonly detected virus (216% of specimens), followed by norovirus (39%) and rotavirus (04%). Norovirus and enterovirus were detected throughout the year with a peak of norovirus detection at the beginning of the rainy season and a significant alternation of circulation of norovirus genogroups from one month to the next. Age <5 years and consumption of tap water were risk factors for norovirus infection. Better understanding of factors influencing transmission and seasonality may provide insights into the relationship between physical environment and risk of infection for these viruses.
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30.
  • Bahls, M., et al. (författare)
  • Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium
  • 2020
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints. © The European Society of Cardiology 2019.
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31.
  • Benetou, V, et al. (författare)
  • Mediterranean diet and incidence of hip fractures in a European cohort
  • 2013
  • Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 24:5, s. 1587-1598
  • Tidskriftsartikel (refereegranskat)abstract
    • Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.
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32.
  • Bodda, C., et al. (författare)
  • HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
  • 2020
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 ΔDUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain. © 2020 Bodda et al.
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33.
  • Duong, Duc M., et al. (författare)
  • Exploring the influence of context in a community-based facilitation intervention focusing on neonatal health and survival in Vietnam : a qualitative study
  • 2015
  • Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; :15
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn the Neonatal health – Knowledge into Practice (NeoKIP) trial in Vietnam, local stakeholder groups, supported by trained laywomen acting as facilitators, promoted knowledge translation (KT) resulting in decreased neonatal mortality. In general, as well as in the community-based NeoKIP trial, there is a need to further understand how context influences KT interventions in low- and middle-income countries (LMICs). Thus, the objective of this study was to explore the influence of context on the facilitation process in the NeoKIP intervention.MethodsA secondary content analysis was performed on 16 Focus Group Discussions with facilitators and participants of the stakeholder groups, applying an inductive approach to the content on context through naïve understanding and structured analysis.ResultsThe three main-categories of context found to influence the facilitation process in the NeoKIP intervention were: (1) Support and collaboration of local authorities and other communal stakeholders; (2) Incentives to, and motivation of, participants; and (3) Low health care coverage and utilization. In particular, the role of local authorities in a KT intervention was recognized as important. Also, while project participants expected financial incentives, non-financial benefits such as individual learning were considered to balance the lack of reimbursement in the NeoKIP intervention. Further, project participants recognized the need to acknowledge the needs of disadvantaged groups.ConclusionsThis study provides insight for further understanding of the influence of contextual aspects to improve effects of a KT intervention in Vietnam. We suggest that future KT interventions should apply strategies to improve local authorities’ engagement, to identify and communicate non-financial incentives, and to make disadvantaged groups a priority. Further studies to evaluate the contextual aspects in KT interventions in LMICs are also needed.
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34.
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35.
  • Henmyr, Viktor, et al. (författare)
  • Characterization of genetic variation in TLR8 in relation to allergic rhinitis
  • 2015
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A previous investigation of all 10 TLR-genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations.METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR-associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared.RESULTS: Sequencing detected 13 polymorphisms (3 promotor, 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF <1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR-association tests made using the BAMSE cohort yielded 5 P-values < 0.05. Tests of IgE-levels yielded 4 significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects and response to different allergens in the different populations.CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.
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36.
  • Hober, Sophia, Professor, 1965-, et al. (författare)
  • Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
  • 2021
  • Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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37.
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38.
  • Kalenga, T. M., et al. (författare)
  • Modified ent-Abietane Diterpenoids from the Leaves of Suregada zanzibariensis
  • 2022
  • Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 85:9, s. 2135-2141
  • Tidskriftsartikel (refereegranskat)abstract
    • The leaf extract of Suregada zanzibariensis gave two new modified ent-abietane diterpenoids, zanzibariolides A (1) and B (2), and two known triterpenoids, simiarenol (3) and fi-amyrin (4). The structures of the isolated compounds were elucidated based on NMR and MS data analysis. Single-crystal X-ray diffraction was used to establish the absolute configurations of compounds 1 and 2. The crude leaf extract inhibited the infectivity of herpes simplex virus 2 (HSV-2, IC50 11.5 mu g/mL) and showed toxicity on African green monkey kidney (GMK AH1) cells at CC50 52 mu g/ mL. The isolated compounds 1-3 showed no anti-HSV-2 activity and exhibited insignificant toxicity against GMK AH1 cells at >= 100 mu M.
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39.
  • Karady, Julia, et al. (författare)
  • Coronary Plaque in People With HIV vs Non-HIV Asymptomatic Community and Symptomatic Higher-Risk Populations
  • 2024
  • Ingår i: JACC: Advances. - 2772-963X. ; 3:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification. Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH. Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence. Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001). Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.
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40.
  • Karady, Julia, et al. (författare)
  • Coronary plaque in people with HIV vs non-HIV asymptomatic community and symptomatic higher-risk populations
  • 2024
  • Ingår i: JACC: Advances. - : Elsevier. - 2772-963X. ; 3:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification.Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH.Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence.Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001).Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.
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41.
  • Lin, Audrey T., et al. (författare)
  • The history of Coast Salish "woolly dogs" revealed by ancient genomics and Indigenous Knowledge
  • 2023
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 382:6676, s. 1303-1308
  • Tidskriftsartikel (refereegranskat)abstract
    • Ancestral Coast Salish societies in the Pacific Northwest kept long-haired woolly dogs that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton", collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance.
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42.
  • Lorenz, M. W., et al. (författare)
  • Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration
  • 2015
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:10, s. 1921-1929
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
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43.
  • Mahambo, Emanuel T, et al. (författare)
  • Crotofolane Diterpenoids and Other Constituents Isolated from Croton kilwae.
  • 2023
  • Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 1520-6025 .- 0163-3864. ; 86:2, s. 380-389
  • Tidskriftsartikel (refereegranskat)abstract
    • Six new crotofolane diterpenoids (1-6) and 13 known compounds (7-19) were isolated from the MeOH-CH2Cl2 (1:1, v/v) extracts of the leaves and stem bark of Croton kilwae. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and mass spectrometric data. The structure of crotokilwaepoxide A (1) was confirmed by single-crystal X-ray diffraction, allowing for the determination of its absolute configuration. The crude extracts and the isolated compounds were investigated for antiviral activity against respiratory syncytial virus (RSV) and human rhinovirus type-2 (HRV-2) in HEp-2 and HeLa cells, respectively, for antibacterial activity against the Gram-positive Bacillus subtilis and the Gram-negative Escherichia coli, and for antimalarial activity against the Plasmodium falciparum Dd2 strain. ent-3β,19-Dihydroxykaur-16-ene (7) and ayanin (16) displayed anti-RSV activities with IC50 values of 10.2 and 6.1 μM, respectively, while exhibiting only modest cytotoxic effects on HEp-2 cells that resulted in selectivity indices of 4.9 and 16.4. Compounds 2 and 5 exhibited modest anti-HRV-2 activity (IC50 of 44.6 μM for both compounds), while compound 16 inhibited HRV-2 with an IC50 value of 1.8 μM. Compounds 1-3 showed promising antiplasmodial activities (80-100% inhibition) at a 50 μM concentration.
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44.
  • Merid, Simon Kebede, et al. (författare)
  • Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
  • 2020
  • Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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45.
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46.
  • Romania, P., et al. (författare)
  • Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion
  • 2017
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:4, s. 846-853
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 30 UTR, preserves ERAP1 from miR-UL1125p-mediated degradation. Specifically, HCMV miRUL112-5p binds the 30 UTR of ERAP1 A variant, but not the 30 UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant. Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly decreased HCMV seropositivity was detected among GG individuals suffering from multiple sclerosis, a disease model in which HCMV is negatively associated with adultonset disorder. Overall, our results identify a resistance mechanism to HCMV miR-UL112-5p-based immune evasion strategy with potential implications for individual susceptibility to infection and other diseases.
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47.
  • Strand, Tanja M, et al. (författare)
  • Highly Pathogenic Leptospira Found in Urban Brown Rats (Rattus norvegicus) in the Largest Cities of Sweden
  • 2015
  • Ingår i: Vector-Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1530-3667 .- 1557-7759. ; 15:12, s. 779-781
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptospirosis is an emerging zoonosis of global concern; however, its contemporary occurrence in Sweden, a European country partly located north of the Arctic Circle, is poorly known. Four out of 30 brown rats, captured within urban districts in Sweden, were found to be positive for antibodies to Leptospira interrogans serovar Icterohaemorrhagiae. This serovar causes Weil's disease in humans, a severe infection with jaundice, renal failure, and hemorrhage. Our study is the first finding of this highly pathogenic serovar in Swedish rats since the 1930s.
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48.
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49.
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50.
  • Studahl, Marie, 1957, et al. (författare)
  • Cytomegalovirus infection of the CNS in non-compromised patients.
  • 1994
  • Ingår i: Acta neurologica Scandinavica. - 0001-6314. ; 89:6, s. 451-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Six non-compromised patients with cytomegalovirus (CMV) associated meningoencephalitis are described. CMV was isolated from the cerebrospinal fluid (CSF) in 2/4 cases, while the diagnosis was based on an 8-fold rise in CMV-specific serum IgG antibodies and intrathecal antibody production against CMV in one case. By the polymerase chain reaction (PCR) CMV DNA was detected in the CSF in 5/5 cases and in serum in 3/4 cases. In one patient who had an Influenza A infection, both CMV and Epstein-Barr virus DNA were detected by PCR in the CSF. In 4 patients possible triggering events could be identified. Symptoms and signs indicating a multifocal brain involvement were present in 4 patients. The outcome was generally favourable except for sequelae in form of slight dysphasia in one case.
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