1. |
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2. |
- Leonov, A. A., et al.
(författare)
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Separation of electrons and protons in the GAMMA-400 gamma-ray telescope
- 2015
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 56:7, s. 1538-1545
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Tidskriftsartikel (refereegranskat)abstract
- The GAMMA-400 telescope will measure the fluxes of gamma rays and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV. These measurements will allow it to achieve the following scientific objectives: search for signatures of dark matter, investigation of gamma-ray point-like and extended sources, study of the energy spectrum of the Galactic and extragalactic diffuse emission, study of gamma-ray bursts and gamma-ray emission from the active Sun, together with high-precision measurements of the high-energy electrons and positrons spectra, protons and nuclei up to the knee. The bulk of cosmic rays are protons and helium nuclei, whereas the lepton component in the total flux is similar to 10(-3) at high energy. In the present paper, the simulated capability of the GAMMA-400 telescope to distinguish electrons and positrons from protons in cosmic rays is addressed. The individual contribution to the proton rejection from each detector system of GAMMA-400 is studied separately. The use of the combined information from all detectors allows us to reach a proton rejection of the order of similar to 4 x 10(5) for vertical incident particles and similar to 3 x 10(5) for particles with initial inclination of 30 degrees in the electron energy range from 50 GeV to 1 TeV. (C) 2015 COSPAR.
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3. |
- Kulmala, M., et al.
(författare)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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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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4. |
- Andrés, E., et al.
(författare)
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Observation of high-energy neutrinos using Čerenkov detectors embedded deep in Antarctic ice
- 2001
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 410:6827, s. 441-443
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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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5. |
- Andrés, E., et al.
(författare)
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Recent results from AMANDA
- 2001
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Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 16:1C, s. 1013-1015
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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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6. |
- Guimond, S. E., et al.
(författare)
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
- 2022
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
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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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7. |
- Tschiderer, L., et al.
(författare)
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Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies
- 2023
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Ingår i: Journal of the American Heart Association (JAHA). - 2047-9980. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and ResultsWe undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). ConclusionsOur large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
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8. |
- Andres, E., et al.
(författare)
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Results from the AMANDA high energy neutrino detector
- 2000
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Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 91:1-3, s. 423-430
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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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9. |
- Bai, X., et al.
(författare)
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Status of the Neutrino Telescope AMANDA : Monopoles and WIMPS
- 2001
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Ingår i: Dark Matter in Astro- and Particle Physics. - Berlin, Heidelberg : Springer. - 9783642626081 ; , s. 699-706
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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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10. |
- Edsjö, Joakim, et al.
(författare)
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WIMP searches with AMANDA-B10
- 2001
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Ingår i: The Identification Of Dark Matter. - : World Scientific. - 9789810246020 ; , s. 499-505
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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11. |
- Andrés, E., et al.
(författare)
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Status of the AMANDA experiment
- 1999
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Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 70:1-3, s. 448-452
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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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12. |
- Andres, E., et al.
(författare)
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The AMANDA neutrino telescope : Principle of operation and first results
- 2000
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 13:1, s. 1-20
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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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13. |
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14. |
- Wischnewski, R., et al.
(författare)
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The AMANDA neutrino detector : Status report
- 2000
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Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 85:1-3, s. 141-145
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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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15. |
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16. |
- Andres, E., et al.
(författare)
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AMANDA : Status, results and future
- 1999
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Ingår i: Proceedings, 8th International Workshop, Venice, Italy, February 23-26, 1999. Vol. 1, 2. ; , s. 63-79
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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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17. |
- Andrés, E. C., et al.
(författare)
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The AMANDA neutrino telescope
- 1999
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Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 77:1-3, s. 474-485
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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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18. |
- Bay, R. C., et al.
(författare)
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The AMANDA neutrino telescope and the indirect search for dark matter : AMANDA Colaboration
- 1998
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Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 307:1-4, s. 243-252
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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. |
- Lorenz, M. W., et al.
(författare)
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Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:10, s. 1921-1929
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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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20. |
- Askebjer, P., et al.
(författare)
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AMANDA : status report from the 1993-94 campaign and optical properties of the South Pole ice
- 1995
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Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 38:1-3, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- We report the first results of the AMANDA detector. During the antarctic summer 1993-94 four strings were deployed between 0.8 an 1 km depth, each equipped with 20 photomultiplier tubes (PMTs). A laser source was used to investigate the optical properties of the ice in situ. We find that the ice is intrinsically extremely transparent. The measured absorption length is 59 ± 3 m, i.e. comparable with the quality of the ultra-pure water used in the IMB and Kamiokande proton-decay and neutrino experiments [1,2] and more than two times longer than the best value reported for laboratory ice [3]. Due to a residual density of air bubbles at these depths, the motion of photons in the medium is randomized. For spherical, smooth bubbles we find that, at 1 km depth, the average distance between collisions is about 25 cm. The measured inverse scattering length on bubbles decreases linearly with increasing depth in the volume of ice investigated. © 1995 Elsevier Science B.V. All rights reserved.
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21. |
- Askebjer, P., et al.
(författare)
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Optical properties of deep ice at the South Pole : Absorption
- 1997
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Ingår i: Applied Optics. - : Optical Society of America. - 0003-6935 .- 1539-4522. ; 36:18, s. 4168-4180
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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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22. |
- Askebjer, P., et al.
(författare)
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Optical properties of the South Pole ice at depths between 0.8 and 1 kilometer
- 1995
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 267:5201, s. 1147-1150
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Tidskriftsartikel (refereegranskat)abstract
- The optical properties of the ice at the geographical South Pole have been investigated at depths between 0.8 and 1 kilometer. The absorption and scattering lengths of visible light (∼515 nanometers) have been measured in situ with the use of the laser calibration setup of the Antarctic Muon and Neutrino Detector Array (AMANDA) neutrino detector. The ice is intrinsically extremely transparent. The measured absorption length is 59 ± 3 meters, comparable with the quality of the ultrapure water used in the Irvine-Michigan-Brookhaven and Kamiokande proton-decay and neutrino experiments and more than twice as long as the best value reported for laboratory ice. Because of a residual density of air bubbles at these depths, the trajectories of photons in the medium are randomized. If the bubbles are assumed to be smooth and spherical, the average distance between collisions at a depth of 1 kilometer is about 25 centimeters. The measured inverse scattering length on bubbles decreases linearly with increasing depth in the volume of ice investigated.
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23. |
- Askebjer, P., et al.
(författare)
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UV and optical light transmission properties in deep ice at the South Pole
- 1997
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 24:11, s. 1355-1358
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Tidskriftsartikel (refereegranskat)abstract
- Both absorption and scattering of light at wavelengths 410 to 610 nanometers were measured in the South Pole ice at depths 0.8 to 1 kilometer with the laser calibration system of the Antarctic Muon And Neutrino Detector Array (AMANDA). At the shortest wavelengths the absorption lengths exceeded 200 meters - an order of magnitude longer than has been reported for laboratory ice. The absorption shows a strong wavelength dependence while the scattering length is found to be independent of the wavelength, consistent with the hypothesis of a residual density of air bubbles in the ice. The observed linear decrease of the inverse scattering length with depth is compatible with an earlier measurement by the AMANDA collaboration (at ∼515 nanometers).
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24. |
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25. |
- Liao, X., et al.
(författare)
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Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?
- 2016
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:11, s. 1165-1173
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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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26. |
- Lorenz, M. W., et al.
(författare)
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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
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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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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27. |
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28. |
- Tschiderer, L., et al.
(författare)
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The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale
- 2020
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Ingår i: Gerontology. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 66:5, s. 447-459
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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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29. |
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30. |
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31. |
- Wischnewski, R., et al.
(författare)
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The AMANDA neutrino detector
- 1999
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Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 75:1-2, s. 412-414
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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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32. |
- Abdelmagid, N., et al.
(författare)
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Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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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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33. |
- Adiels, Lars, 1952-, et al.
(författare)
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Test of CP violation with K0 and K‾0 at LEAR
- 1985
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Ingår i: Physics with antiprotons at LEAR in the ACOL era. - Gif sur Yvette : Editions Frontières. - 2863320351 ; , s. 467-482
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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34. |
- Bahls, M., et al.
(författare)
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Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium
- 2020
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:3
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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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35. |
- Finsterle, S., et al.
(författare)
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Conceptual uncertainties in modelling the interaction between engineered and natural barriers of nuclear waste repositories in crystalline rocks
- 2019
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Ingår i: Geological Society Special Publication. - 0305-8719. ; 482:1, s. 261-283
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear waste disposal in geological formations relies on a multi-barrier concept that includes engineered components – which, in many cases, include a bentonite buffer surrounding waste packages – and the host rock. Contrasts in materials, together with gradients across the interface between the engineered and natural barriers, lead to complex interactions between these two subsystems. Numerical modelling, combined with monitoring and testing data, can be used to improve our overall understanding of rock–bentonite interactions and to predict the performance of this coupled system. Although established methods exist to examine the prediction uncertainties due to uncertainties in the input parameters, the impact of conceptual model decisions on the quantitative and qualitative modelling results is more difficult to assess. A Swedish Nuclear Fuel and Waste Management Company Task Force project facilitated such an assessment. In this project, 11 teams used different conceptualizations and modelling tools to analyse the Bentonite Rock Interaction Experiment (BRIE) conducted at the Äspö Hard Rock Laboratory in Sweden. The exercise showed that prior system understanding along with the features implemented in the available simulators affect the processes included in the conceptual model. For some of these features, sufficient characterization data are available to obtain defensible results and interpretations, whereas others are less supported. The exercise also helped to identify the conceptual uncertainties that led to different assessments of the relative importance of the engineered and natural barrier subsystems. The range of predicted bentonite wetting times encompassed by the ensemble results were considerably larger than the ranges derived from individual models. This is a consequence of conceptual uncertainties, demonstrating the relevance of using a multi-model approach involving alternative conceptualizations.
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36. |
- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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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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37. |
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38. |
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39. |
- Torén, Kjell, 1952, et al.
(författare)
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Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2016
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 11:1, s. 927-933
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value <0.7 or below the lower limit of normal (LLN). Forced vital capacity (FVC) is a proxy for VC. The first aim was to compare the use of FVC and VC, assessed as the highest value of FVC or slow vital capacity (SVC), when assessing the FEV1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were investigated with FEV1, FVC, and SVC after bronchodilation. Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPDFVC was defined as FEV1/FVC <0.7, GOLDCOPD(VC) as FEV1/VC <0.7 using the maximum value of FVC or SVC, LLNCOPDFVC as FEV1/FVC below the LLN, and LLNCOPDVC as FEV1/VC below the LLN using the maximum value of FVC or SVC. Results: Prevalence of GOLDCOPD(FVC) was 10.0% (95% confidence interval [CI] 8.2-12.0) and the prevalence of LLNCOPDFVC was 9.5% (95% CI 7.8-11.4). When estimates were based on VC, the prevalence became higher; 16.4% (95% CI 14.3-18.9) and 15.6% (95% CI 13.5-17.9) for GOLDCOPD(VC) and LLNCOPDVC, respectively. The group of additional subjects classified as having COPD based on VC, had lower FEV1, more wheeze and higher residual volume compared to subjects without any COPD. Conclusion: The prevalence of COPD was significantly higher when the ratio FEV1/VC was calculated using the highest value of SVC or FVC compared with using FVC only. Subjects classified as having COPD when using the VC concept were more obstructive and with indications of air trapping. Hence, the use of only FVC when assessing airflow limitation may result in a considerable under diagnosis of subjects with mild COPD.
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40. |
- Udayappan, S. D., et al.
(författare)
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Intestinal Ralstonia pickettii augments glucose intolerance in obesity
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.
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41. |
- Wilson, A. N., et al.
(författare)
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Magnetic dipole bands in 190Hg : First evidence of excitations across the Z = 82 sub-shell in Hg nuclei
- 2001
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 505:1-4, s. 6-14
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Tidskriftsartikel (refereegranskat)abstract
- An experiment aimed at studying high-spin states in 190Hg was performed with the Eurogam II array. The data have revealed the presence of cascades of magnetic dipole transitions with some unexpected properties. Unlike the MI bands previously observed in the heavier Hg isotopes, these structures have extremely large B(M1)/B(E2) ratios, The observation of a third dipole band with much lower B(M1)/B(E2) values in the same spin/excitation energy regime suggests that the bands may represent configurations occurring in different minima in the potential energy surface. Configuration-dependent Cranked Nilsson-Strutinsky calculations predict the presence of a minimum in the nuclear potential energy surface at a deformation of ε ≅ 0.2, γ ≅ -90°, occurring when a proton is excited across the Z = 82 shell-gap into an h9/2 orbital. It is suggested that the bands exhibiting anomalously large B(M1)/B(E2) ratios may be associated with this minimum.
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42. |
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43. |
- Zheng, Hou-Feng, et al.
(författare)
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WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
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Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
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44. |
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45. |
- Alvebratt, Caroline, et al.
(författare)
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In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier
- 2020
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.
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46. |
- Benetou, V, et al.
(författare)
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Mediterranean diet and incidence of hip fractures in a European cohort
- 2013
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Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 24:5, s. 1587-1598
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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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47. |
- Berg, Staffan, et al.
(författare)
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In Vitro and In Vivo Evaluation of 3D Printed Capsules with Pressure Triggered Release Mechanism for Oral Peptide Delivery
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 110:1, s. 228-238
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Tidskriftsartikel (refereegranskat)abstract
- In this study a 3D printed capsule designed to break from the physiological pressures in the antropyloric region was evaluated for its ability to deliver the synthetic octapeptide octreotide in beagle dogs when co-formulated with the permeation enhancer sodium caprate. The pressure sensitive capsules were compared to traditional enteric coated hard gelatin capsules and enteric coated tablets. Paracetamol, which is completely absorbed in dogs, was included in the formulations and used as an absorption marker to give information about the in vivo performance of the dosage forms. The pressure sensitive capsules released drug in 50% of the dogs. In the cases where drug was released, there was no difference in octreotide bioavailability or C-max compared to the enteric coated dosage forms. When comparing all dosage forms, a correlation was seen between paracetamol C-max and octreotide bioavailability, suggesting that a high drug release rate may be beneficial for peptide absorption when delivered together with sodium caprate. (C) 2020 Published by Elsevier Inc.
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48. |
- Bergström, A., et al.
(författare)
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Physical activity and risk of renal cell cancer
- 2001
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Ingår i: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 92:1, s. 155-157
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Tidskriftsartikel (refereegranskat)abstract
- The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.
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49. |
- Bergström, I., et al.
(författare)
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Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone
- 2017
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:3, s. 1121-1131
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels. Introduction: Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone. Methods: Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure). Results: The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (−14 and −3%, p < 0.01, respectively) and crystallinity (−1.4 and −0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites. Conclusion: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.
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50. |
- Brough, H. A., et al.
(författare)
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Environmental peanut exposure increases the risk of peanut sensitization in high-risk children
- 2018
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 48:5, s. 586-593
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Tidskriftsartikel (refereegranskat)abstract
- Background: High household peanut consumption is associated with the development of peanut allergy, especially when peanut allergic cases are compared against atopic controls; thus, environmental peanut exposure (EPE) may be a risk factor for peanut sensitization and allergy. In this study, we explored the relationship between EPE and school-age peanut sensitization in a population-based cohort.Methods: Maternal bed dust was collected postnatally, and EPE was quantified using a polyclonal peanut ELISA. Peanut sensitization was assessed by specific IgE to peanut extract and sIgE to peanut protein component allergens Ara h 1, 2 or 3 >= 0.35kU/L (primary peanut sensitization). Initial nested case-control analysis was performed comparing peanut-sensitized cases against high-risk controls (matched for parental atopy) (n = 411) using a conditional regression analysis. This was followed by whole cohort analysis (n = 1878) comparing EPE against peanut sIgE sensitization at ages 4 and 8 years using generalized estimating equations and against primary peanut sensitization at age 8 years using a logistic regression model. Finally, a subgroup analysis was performed comparing the impact of EPE in peanut-sensitized vs egg-sensitized, peanut-tolerant individuals using logistic regression analysis. Levels of EPE were compared between groups using the Mann-Whitney U test.Results: In the nested case-control analysis, a higher level of EPE around birth was associated with peanut-specific IgE sensitization at age 4 years (OR=1.41, 95% CI:1.05-1.90) and primary peanut sensitization at age 8 years (OR=2.11, 95% CI:1.38-3.22) compared against high-risk controls. When the whole BAMSE cohort was assessed, EPE was no longer associated with peanut sensitization; however, on subgroup analysis, EPE was associated with primary peanut sensitization when compared against egg-sensitized peanut-tolerant controls with an adjusted odds ratio of 1.44 per unit EPE (95% CI:1.06-1.94). There was no significant interaction between EPE and FLG loss-of-function mutations, egg sensitization at age 4 years, infantile eczema or parental atopy on peanut sensitization.Conclusions: Higher levels of environmental exposure to peanut in the first few months of life appear to increase the probability of developing school-age peanut sensitization in atopic children (based on egg sensitization and parental atopy).
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