| 1. |
- Meech, K. J., et al.
(författare)
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EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
- 2011
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Ingår i: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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| 2. |
- Lis, D. C., et al.
(författare)
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Herschel/HIFI discovery of interstellar chloronium (H2Cl+)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of chloronium, H_2Cl^+, in the interstellar medium, using the HIFI instrument aboard the Herschel Space Observatory. The 2_12-1_01 lines of ortho-H\_2^35Cl^+ and ortho-H\_2^37Cl^+ are detected in absorption towards NGC 6334I, and the 1_11-0_00 transition of para-H\_2^35Cl^+ is detected in absorption towards NGC 6334I and Sgr B2(S). The H_2Cl^+ column densities are compared to those of the chemically-related species HCl. The derived HCl/H_2Cl^+ column density ratios, ~1-10, are within the range predicted by models of diffuse and dense photon dominated regions (PDRs). However, the observed H_2Cl^+ column densities, in excess of 10^13 cm^-2, are significantly higher than the model predictions. Our observations demonstrate the outstanding spectroscopic capabilities of HIFI for detecting new interstellar molecules and providing key constraints for astrochemical models.
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| 3. |
- Frisk, U., et al.
(författare)
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The Odin satellite - I. Radiometer design and test
- 2003
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 402:3, s. L27-L34
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Tidskriftsartikel (refereegranskat)abstract
- The Sub-millimetre and Millimetre Radiometer (SMR) is the main instrument on the Swedish, Canadian, Finnish and French spacecraft Odin. It consists of a 1.1 metre diameter telescope with four tuneable heterodyne receivers covering the ranges 486-504 GHz and 541-581 GHz, and one fixed at 118.75 GHz together with backends that provide spectral resolution from 150 kHz to 1 MHz. This Letter describes the Odin radiometer, its operation and performance with the data processing and calibration described in Paper II.
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| 4. |
- Goldsmith, Paul F., et al.
(författare)
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Herschel Measurements of Molecular Oxygen in Orion
- 2011
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 737:2, s. 96 (1-17)
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Tidskriftsartikel (refereegranskat)abstract
- We report observations of three rotational transitions of molecular oxygen (O2) in emission from the H2 Peak 1 position of vibrationally excited molecular hydrogen in Orion. We observed the 487 GHz, 774 GHz, and 1121 GHz lines using the Heterodyne Instrument for the Far Infrared on the Herschel Space Observatory, having velocities of 11 km s–1 to 12 km s–1 and widths of 3 km s–1. The beam-averaged column density is N(O2) = 6.5 × 1016 cm–2, and assuming that the source has an equal beam-filling factor for all transitions (beam widths 44, 28, and 19''), the relative line intensities imply a kinetic temperature between 65 K and 120 K. The fractional abundance of O2 relative to H2 is (0.3-7.3) × 10–6. The unusual velocity suggests an association with a ~5'' diameter source, denoted Peak A, the Western Clump, or MF4. The mass of this source is ~10 Msun and the dust temperature is ≥150 K. Our preferred explanation of the enhanced O2 abundance is that dust grains in this region are sufficiently warm (T ≥ 100 K) to desorb water ice and thus keep a significant fraction of elemental oxygen in the gas phase, with a significant fraction as O2. For this small source, the line ratios require a temperature ≥180 K. The inferred O2 column density sime5 × 1018 cm–2 can be produced in Peak A, having N(H2) sime 4 × 1024 cm–2. An alternative mechanism is a low-velocity (10-15 km s–1) C-shock, which can produce N(O2) up to 1017 cm–2.
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| 5. |
- Batty, J. A., et al.
(författare)
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An Investigation of CYP2D6 Genotype and Response to Metoprolol CR/XL During Dose Titration in Patients With Heart Failure: A MERIT-HF Substudy
- 2014
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Ingår i: Clinical Pharmacology & Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 95:3, s. 321-330
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Tidskriftsartikel (refereegranskat)abstract
- To explore the pharmacogenetic effects of the cytochrome P450 (CYP) 2D6 genotype in patients with systolic heart failure treated using controlled/extended-release (CR/XL) metoprolol, this study assessed the CYP2D6 locus for the nonfunctional * 4 allele (1846G> A; rs3892097) in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF; n = 605). Participants were characterized as extensive, intermediate, or poor metabolizers (EMs, IMs, or PMs, respectively), based on the presence of the CYP2D6* 4 allele (EM: * 1* 1, 60.4%; IM: * 1* 4, 35.8%; and PM: * 4* 4, 3.8%). Plasma metoprolol concentrations were 2.1-/4.6-fold greater in the IM/PM groups as compared with the EM group (P < 0.0001). Metoprolol induced significantly lower heart rates and diastolic blood pressures during early titration, indicating a CYP2D6* 4 allele dose-response effect (P < 0.05). These effects were not observed at maximal dose, suggesting a saturable effect. Genotype did not adversely affect surrogate treatment efficacy. CYP2D6 genotype modulates metoprolol pharmacokinetics/pharmacodynamics during early titration; however, the MERIT-HF-defined titration schedule remains recommended for all patients, regardless of genotype.
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| 6. |
- Chen, Jo-Hsin, et al.
(författare)
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HERSCHEL HIFI OBSERVATIONS OF O-2 TOWARD ORION: SPECIAL CONDITIONS FOR SHOCK ENHANCED EMISSION
- 2014
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 793:2, s. Article nr. 111 -
-
Tidskriftsartikel (refereegranskat)abstract
- We report observations of molecular oxygen (O-2) rotational transitions at 487 GHz, 774 GHz, and 1121 GHz toward Orion Peak A. The O-2 lines at 487 GHz and 774 GHz are detected at velocities of 10-12 km s(-1) with line widths similar to 3 km s(-1); however, the transition at 1121 GHz is not detected. The observed line characteristics, combined with the results of earlier observations, suggest that the region responsible for the O-2 emission is similar or equal to 9" (6 x 10(16) cm) in size, and is located close to the H-2 Peak 1 position (where vibrationally excited H-2 emission peaks), and not at Peak A, 23" away. The peak O-2 column density is similar to 1.1 x 10(18) cm(-2). The line velocity is close to that of the 621 GHz water maser emission found in this portion of the Orion Molecular Cloud, and having a shock with velocity vector lying nearly in the plane of the sky is consistent with producing maximum maser gain along the line of sight. The enhanced O-2 abundance compared to that generally found in dense interstellar clouds can be explained by passage of a low-velocity C shock through a clump with preshock density 2 x 10(4) cm(-3), if a reasonable flux of UV radiation is present. The postshock O-2 can explain the emission from the source if its line-of-sight dimension is similar or equal to 10 times larger than its size on the plane of the sky. The special geometry and conditions required may explain why O-2 emission has not been detected in the cores of other massive star-forming molecular clouds.
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| 7. |
- Liseau, René, 1949, et al.
(författare)
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Multi-line detection of O2 toward rho Ophiuchi A
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Context. Models of pure gas-phase chemistry in well-shielded regions of molecular clouds predict relatively high levels of molecular oxygen, O-2, and water, H2O. These high abundances imply high cooling rates, leading to relatively short timescales for the evolution of gravitationally unstable dense cores, forming stars and planets. Contrary to expectations, the dedicated space missions SWAS and Odin typically found only very small amounts of water vapour and essentially no O-2 in the dense star-forming interstellar medium. Aims. Only toward rho OphA did Odin detect a very weak line of O-2 at 119 GHz in a beam of size 10 arcmin. The line emission of related molecules changes on angular scales of the order of some tens of arcseconds, requiring a larger telescope aperture such as that of the Herschel Space Observatory to resolve the O-2 emission and pinpoint its origin. Methods. We use the Heterodyne Instrument for the Far Infrared (HIFI) aboard Herschel to obtain high resolution O-2 spectra toward selected positions in the rho Oph A core. These data are analysed using standard techniques for O2 excitation and compared to recent PDR-like chemical cloud models. Results. The N-J = 3(3)-1(2) line at 487.2 GHz is clearly detected toward all three observed positions in the rho Oph A core. In addition, an oversampled map of the 5(4)-3(4) transition at 773.8 GHz reveals the detection of the line in only half of the observed area. On the basis of their ratios, the temperature of the O-2 emitting gas appears to vary quite substantially, with warm gas (greater than or similar to 50 K) being adjacent to a much colder region, of temperatures lower than 30 K. Conclusions. The exploited models predict that the O-2 column densities are sensitive to the prevailing dust temperatures, but rather insensitive to the temperatures of the gas. In agreement with these models, the observationally determined O-2 column densities do not seem to depend strongly on the derived gas temperatures, but fall into the range N(O-2) = 3 to greater than or similar to 6 x 10(15) cm(-2). Beam-averaged O-2 abundances are about 5 x 10(-8) relative to H-2. Combining the HIFI data with earlier Odin observations yields a source size at 119 GHz in the range of 4 to 5 arcmin, encompassing the entire rho Oph A core. We speculate that one of the reasons for the generally very low detection rate of O-2 is the short period of time during which O-2 molecules are reasonably abundant in molecular clouds.
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| 8. |
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| 9. |
- Hjalmarson, A, et al.
(författare)
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The Göteborg metoprolol trial. Effects on mortality and morbidity in acute myocardial infarction
- 1983
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Ingår i: Circulation. - : SRDS. - 1539-3011. ; 67:suppl 1, s. 68-69
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Tidskriftsartikel (refereegranskat)abstract
- In the Göteborg Metoprolol Trial, 1395 patients with suspected acute myocardial infarction were, on admission, randomly allocated to double-blind treatment, 697 to placebo and 698 to metoprolol (15 mg i.v. + 200 mg/day) for 90 days. During this period, there were 62 deaths in the placebo group (8.9%) and 40 in the metoprolol group (5.7%), a mortality reduction of 36% (p less than 0.03). This effect persisted regardless of age, previous infarction or previous chronic beta blockade. All deaths were classified as cardiovascular. After 3 months, all patients were recommended open treatment with metoprolol, and the difference in mortality between the two groups was maintained after 1 year. Early institution of metoprolol (within 12 hours) influenced infarct development during the first 3 days (infarct diagnosis and indirect measures of infarct size). Metoprolol also reduced the incidence on fatal and nonfatal infarction during the next 4-90 days by 35%. Furthermore, fewer episodes of ventricular fibrillation were recorded in the metoprolol than in the placebo group (six vs 17 patients). The tolerance was judged to be very good. The same percentage of patients (19%) was withdrawn from the blind treatment in the two groups. Fewer patients in the metoprolol group used lidocaine, furosemide and analgesics. We conclude that metoprolol therapy instituted on admission in patients with suspected acute myocardial infarction reduced 3-month mortality and exerted beneficial clinical effects.
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| 10. |
- Kotecha, D., et al.
(författare)
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Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:24, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm. (C) 2017 by the American College of Cardiology Foundation.
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| 11. |
- Olberg, M., et al.
(författare)
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The Odin satellite. II. Radiometer data processing and calibration
- 2003
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L35-L38
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Tidskriftsartikel (refereegranskat)abstract
- The radiometer on-board the Odin satellite comprises four different sub-mm receivers covering the 486-581 GHz frequency range and one fixed frequency 119 GHz receiver. Two auto-correlators and one acousto-optical spectrometer serve as backends. This article gives an overview over the processing of the data delivered by these instruments and discusses calibration issues. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and the Centre National d'Études Spatiales (CNES, France). Odin is operated by the Swedish Space Corporation (SSC), the project's prime industrial contractor.
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| 12. |
- Pagani, L., et al.
(författare)
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Low upper limits on the O2 abundance from the Odin satellite
- 2003
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L77-L81
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Tidskriftsartikel (refereegranskat)abstract
- For the first time, a search has been conducted in our Galaxy for the 119 GHz transition connecting to the ground state of O2, using the Odin satellite. Equipped with a sensitive 3 mm receiver (Tsys(SSB) = 600 K), Odin has reached unprecedented upper limits on the abundance of O2, especially in cold dark clouds where the excited state levels involved in the 487 GHz transition are not expected to be significantly populated. Here we report upper limits for a dozen sources. In cold dark clouds we improve upon the published SWAS upper limits by more than an order of magnitude, reaching N(O2)/N(H2) <= 10-7 in half of the sources. While standard chemical models are definitively ruled out by these new limits, our results are compatible with several recent studies that derive lower O2 abundances. Goldsmith et al. (\cite{SWAS2002}) recently reported a SWAS tentative detection of the 487 GHz transition of O2 in an outflow wing towards rho Oph A in a combination of 7 beams covering approximately 10arcmin x 14arcmin . In a brief (1.3 hour integration time) and partial covering of the SWAS region (~65% if we exclude their central position), we did not detect the corresponding 119 GHz line. Our 3 sigma upper limit on the O2 column density is 7.3x 1015 cm-2. We presently cannot exclude the possibility that the SWAS signal lies mostly outside of the 9\arcmin Odin beam and has escaped our sensitive detector. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is operating Odin.
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| 13. |
- Richterova, A, et al.
(författare)
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Goteborg Metoprolol Trial : effects on chest pain
- 1984
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 53:13, s. 32-36
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Tidskriftsartikel (refereegranskat)abstract
- The effect of metoprolol on chest pain was compared with that of placebo in all randomized patients. The pain score before and 15 minutes after the injection of trial medication was registered and a reduction in chest pain was observed in the metoprolol group. Increasing chest pain after blind injection was observed in only 16 and 9 patients from the placebo and metoprolol groups, respectively. Comparison with the placebo as well as detailed analysis of clinical data revealed that in these patients the increasing pain could not be explained by coronary spasm evoked by beta-blockade. Similarly, metoprolol did not exhibit any unfavorable effect on the 14 patients who were withdrawn (together with the 28 patients given placebo) from blind treatment due to angina pectoris. Either metoprolol does not induce coronary vasospasm or spasm does not play a role in these patients with definite and suspected acute myocardial infarction as well as unstable angina pectoris. Metoprolol reduced the need for analgesics during the first 4 days and shortened the duration of pain. The effects were similar in patients with early and late treatment, but may depend on initial heart rate, blood pressure and site of infarction.
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| 14. |
- Sandqvist, Aa., et al.
(författare)
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Odin observations of H2O in the Galactic Centre
- 2003
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L63-L67
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Tidskriftsartikel (refereegranskat)abstract
- The Odin satellite has been used to detect emission and absorption in the 557-GHz H216O line in the Galactic Centre towards the Sgr Astar Circumnuclear Disk (CND), and the Sgr A +20 km s-1 and +50 km s-1 molecular clouds. Strong broad H2O emission lines have been detected in all three objects. Narrow H2O absorption lines are present at all three positions and originate along the lines of sight in the 3-kpc Spiral Arm, the -30 km s-1 Spiral Arm and the Local Sgr Spiral Arm. Broad H2O absorption lines near -130 km s-1 are also observed, originating in the Expanding Molecular Ring. A new molecular feature (the ``High Positive Velocity Gas'' - HPVG) has been identified in the positive velocity range of ~+120 to +220 km s-1, seen definitely in absorption against the stronger dust continuum emission from the +20 km s-1 and +50 km s-1 clouds and possibly in emission towards the position of Sgr Astar CND. The 548-GHz H218O isotope line towards the CND is not detected at the 0.02 K (rms) level. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is also responsible for the satellite operation.
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| 15. |
- Wilson, C. D., et al.
(författare)
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Submillimeter emission from water in the W3 region
- 2003
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L59-L62
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Tidskriftsartikel (refereegranskat)abstract
- Using the Odin satellite, we have mapped the submillimeter emission from the 110-101 transition of ortho-water in the W3 star-forming region. A 5arcminx 5arcmin map of the W3 IRS4 and W3 IRS5 region reveals strong water lines at half the positions in the map. The relative strength of the Odin lines compared to previous observations by SWAS suggests that we are seeing water emission from an extended region. Across much of the map the lines are double-peaked, with an absorption feature at -39 km s-1; however, some positions in the map show a single strong line at -43 km s-1. We interpret the double-peaked lines as arising from optically thick, self-absorbed water emission near the W3 IRS5, while the narrower blue-shifted lines originate in emission near W3 IRS4. In this model, the unusual appearance of the spectral lines across the map results from a coincidental agreement in velocity between the emission near W3 IRS4 and the blue peak of the more complex lines near W3 IRS5. The strength of the water lines near W3 IRS4 suggests we may be seeing water emission enhanced in a photon-dominated region. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is also responsible for the satellite operation.
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| 16. |
- Andersson, Bert, 1952, et al.
(författare)
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Changes in early and late diastolic filling patterns induced by long-term adrenergic beta-blockade in patients with idiopathic dilated cardiomyopathy.
- 1996
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Ingår i: Circulation. - 0009-7322. ; 94:4, s. 673-82
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Tidskriftsartikel (refereegranskat)abstract
- beta-Blockers have been used in patients with idiopathic dilated cardiomyopathy to improve cardiac performance and theoretically would be beneficial to diastolic function. However, there are few reports on changes in diastolic function during chronic pharmacological treatment of congestive heart failure.The present study was a substudy in the international Metoprolol in Dilated Cardiomyopathy Trial. Transmitral Doppler echocardiography was used to evaluate diastolic function in 77 patients randomly assigned to placebo (n = 37) or metoprolol (n = 40). The patients were treated for 12 months. Changes in Doppler flow variables in the metoprolol group implied a less restrictive filling pattern, expressed as an increase in E-wave deceleration time (placebo, 185 +/- 126 to 181 +/- 64 ms; metoprolol, 152 +/- 63 to 216 +/- 78 ms; P = .01, placebo versus metoprolol). Maximal increase in deceleration time had occurred by 3 months, whereas systolic recovery was achieved gradually and maximal effect was seen by 12 months of treatment. Although deceleration time was correlated to heart rate at baseline, changes in deceleration time were not significantly correlated to changes in heart rate during treatment.During the first 3 months of treatment, maximal effects on diastolic variables were reached, whereas the most prominent effect on systolic function was seen late in the study. It is suggested that effects on diastolic filling account for subsequent later myocardial systolic recovery. The E-wave deceleration time, which in recent studies has been shown to be a powerful predictor of survival, was significantly improved in the metoprolol-treated patients.
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| 17. |
- Blomström-Lundqvist, Carina, et al.
(författare)
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Effect of long term treatment with metoprolol and sotalol on ventricular repolarisation measured by use of transoesophageal atrial pacing
- 1986
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Ingår i: British Heart Journal. - 0007-0769. ; 55:2, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- The effects of long term (4 weeks) treatment with oral metoprolol (100 mg twice daily) and sotalol (160 mg twice daily) on ventricular repolarisation time were compared in a double blind crossover study in 20 patients post-infarction. For QT interval studies transoesophageal atrial pacing was performed at a cycle length of 800 ms. Sotalol prolonged the QT interval by 5-7% compared with metoprolol. The prolongation reflects a change in the repolarisation time because there was no change in the QS interval. Measurements of heart rate at rest and during bicycle exercise indicated that metoprolol and sotalol in the doses selected were equipotent as beta blockers. Transoesophageal atrial pacing is a simple non-invasive method with few and mild side effects that is well suited to drug studies.
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| 18. |
- Burda, P, et al.
(författare)
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Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment.
- 2015
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 38:5, s. 863-872
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Tidskriftsartikel (refereegranskat)abstract
- In the folate cycle MTHFD1, encoded by MTHFD1, is a trifunctional enzyme containing 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase activity. To date, only one patient with MTHFD1 deficiency, presenting with hyperhomocysteinemia, megaloblastic anaemia, hemolytic uremic syndrome (HUS) and severe combined immunodeficiency, has been identified (Watkins et al J Med Genet 48:590-2, 2011). We now describe four additional patients from two different families. The second patient presented with hyperhomocysteinemia, megaloblastic anaemia, HUS, microangiopathy and retinopathy; all except the retinopathy resolved after treatment with hydroxocobalamin, betaine and folinic acid. The third patient developed megaloblastic anaemia, infection, autoimmune disease and moderate liver fibrosis but not hyperhomocysteinemia, and was successfully treated with a regime that included and was eventually reduced to folic acid. The other two, elder siblings of the third patient, died at 9weeks of age with megaloblastic anaemia, infection and severe acidosis and had MTFHD1 deficiency diagnosed retrospectively. We identified a missense mutation (c.806C>T, p.Thr296Ile) and a splice site mutation (c.1674G>A) leading to exon skipping in the second patient, while the other three harboured a missense mutation (c.146C>T, p.Ser49Phe) and a premature stop mutation (c.673G>T, p.Glu225*), all of which were novel. Patient fibroblast studies revealed severely reduced methionine formation from [(14)C]-formate, which did not increase in cobalamin supplemented culture medium but was responsive to folic and folinic acid. These additional cases increase the clinical spectrum of this intriguing defect, provide in vitro evidence of disturbed methionine synthesis and substantiate the effectiveness of folic or folinic acid treatment.
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| 19. |
- Cavalie, T., et al.
(författare)
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Observation of water vapor in the stratosphere of Jupiter with the Odin space telescope
- 2008
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Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633. ; 56:12, s. 1573-1584
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Tidskriftsartikel (refereegranskat)abstract
- The water vapor line at 557 GHz has been observed with the Odin space telescope with a high signal-to-noise ratio and a high spectral resolution on November 8, 2002. The analysis of this observation as well as a re-analysis of previously published observations obtained with the submillimeter wavelength astronomy satellite seem to favor a cometary origin (Shoemaker-Levy 9) for water in the stratosphere of Jupiter, in agreement with the ISO observation results. Our model predicts that the water line should become fainter and broader from 2007. The observation of such a temporal variability would be contradictory with an IDP steady flux, thus supporting the SL9 source hypothesis. © 2008 Elsevier Ltd.
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| 20. |
- Cleland, J. G. F., et al.
(författare)
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Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials
- 2018
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:1, s. 26-35
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Tidskriftsartikel (refereegranskat)abstract
- Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >= 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 >= 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF >= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF >= 50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conculations Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
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| 21. |
- Crovisier, J., et al.
(författare)
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The chemical composition of 9P/tempel 1 from radio observations
- 2009
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Ingår i: ESO Astrophysics Symposia. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1431-2433 .- 1611-6143. - 9783540769583 ; 2009, s. 243-248
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Konferensbidrag (refereegranskat)abstract
- In 2005, as part of a world-wide multi-wavelength investigation of comet 9P/Tempel 1 in support to the Deep Impact mission, we conducted radio spectroscopic observations with the Nançay radio telescope, the Odin satellite, the CSO 10-m and the IRAM 30-m telescopes. We report here our results concerning the chemical composition of the comet. The relative abundances of the detected species (H2O, CH3OH, H2S, HCN) or their upper limits (CO, H2CO, CS) are comparable to the mean values observed in other comets. No significant changes of the outgassing rates (except possibly for CH3OH) or of the molecular abundances were observed following the impact.
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| 22. |
- Fu, Michael, 1963, et al.
(författare)
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Free radical scavenging enzymes and G protein mediated receptor signalling systems in ischaemically preconditioned porcine myocardium.
- 1993
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Ingår i: Cardiovascular research. - 0008-6363. ; 27:4, s. 612-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Increased antioxidant defence and altered G protein mediated receptor signalling systems could be expected in myocardial preconditioning. The myocardial antioxidant defence and the integrity of the G protein mediated receptor signalling systems were therefore examined in normal and preconditioned myocardium. METHODS: Preconditioning in the porcine heart was induced by two occlusions of the mid left anterior descending coronary artery for 10 min, with a 30 min reperfusion interval. Left ventricular biopsies were obtained from control and preconditioned regions 30 min after the last occlusion. RESULTS: In biopsies from the preconditioning region, neither the activities of superoxide dismutase of glutathione peroxidase, nor the content of malondialdehyde were changed. There were no alterations in either the number of receptors (beta adrenergic, muscarinic and endothelin receptors) or the amount of G proteins. Furthermore, the activity of adenylyl cyclase remained unchanged. CONCLUSIONS: No change in the antioxidant defence was demonstrated in preconditioned myocardium. This finding does not support the hypothesis that increased antioxidant defence could contribute to the cardioprotection of preconditioning. Additionally, an intact G protein mediated receptor signalling system was found in preconditioned myocardium with regard to beta adrenergic, muscarinic, and endothelin receptors.
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| 23. |
- Fu, Michael, 1963, et al.
(författare)
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Gi-mediated muscarinic adenylyl cyclase inhibition in timolol-treated stunned porcine myocardium.
- 1994
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Ingår i: Acta physiologica Scandinavica. - 0001-6772. ; 151:3, s. 291-9
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Tidskriftsartikel (refereegranskat)abstract
- The Gi-mediated muscarinic receptor-adenylyl cyclase system was examined in stunned myocardium induced by either three or five brief ischaemic periods after beta-adrenoceptor blockade by timolol (0.1 mg kg-1). The mid-left anterior descending coronary artery was occluded for 2, 10 and 2 min in four pigs, and for 2, 2, 5, 10 and 2 min in four other pigs. All the ischaemic periods were separated by 30 min of reperfusion and the biopsies were obtained 60 min after the last ischaemic period. Segment length function was measured in the ischaemic region and in the control region supplied by the left circumflex artery. In the two groups, the percentage systolic shortening was reduced equally, to 59 +/- 9 and 58 +/- 10% of control in the region subjected to ischaemia and only minimally in the control region. The biopsies from the stunned region from both groups showed: (1) no change in either the affinity for carbachol or the number of binding sites of the muscarinic receptors; (2) no alterations in messenger RNA encoding for the alpha subunit-2 of the inhibitory guanine nucleotide binding protein, as demonstrated by northern blot and solution hybridization; (3) no change in membrane-bound inhibitory guanine nucleotide binding protein, as shown by enzyme immunoassay utilizing a specific anti-peptide antibody, and (4) unchanged inhibition of stimulated adenylyl cyclase activity. These results suggest that there is an intact inhibitory guanine nucleotide binding protein-mediated muscarinic receptor adenylyl cyclase system in the stunned porcine myocardium.
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| 24. |
- Fu, Michael, 1963, et al.
(författare)
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Oxygen free radical injury and Gs mediated signal transduction in the stunned porcine myocardium.
- 1992
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Ingår i: Cardiovascular research. - 0008-6363. ; 26:5, s. 449-55
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to investigate involvement of oxygen free radicals and any changes in the Gs mediated beta adrenergic signalling system of stunned porcine myocardium. METHODS: Myocardial stunning was induced in eight pentobarbitone anaesthetised pigs by brief occlusions of the distal left anterior descending coronary artery for periods of up to 10 min. Segment length function was measured in the ischaemic region and in a control region supplied by the circumflex artery. Left ventricular biopsies were obtained from the two regions 1 h after the last occlusion for ultrastructural and biochemical studies. Timolol has been used to prevent arrhythmia during ischaemia. RESULTS: At the time when biopsies were obtained, percent systolic shortening was reduced to 58% in the region subjected to ischaemia and was only minimally reduced in the control region. In the biopsies from the stunned region: (1) electron microscopy showed mild and reversible intracellular changes in the stunned myocardium; (2) the activities of superoxide dismutase and glutathione peroxidase were decreased by 66% and 52%, respectively; (3) the content of malondialdehyde was increased by 49%; (4) neither density nor affinity of beta adrenoceptors showed any changes; (5) there were no alterations in messenger RNA encoding for the alpha subunit of the stimulatory guanine nucleotide binding protein (Gs), demonstrated by northern and dot-blot hybridisations; (6) ELISA technique utilising a specific antipeptide antibody showed no quantitative change in Gs; (7) the activity of adenyl cyclase was unchanged. CONCLUSIONS: Even though the stunned porcine myocardium showed substantial evidence of free radical injury, the beta adrenergic signalling system was intact.
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| 25. |
- Herlitz, Johan, et al.
(författare)
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Correlation between enzymatic estimation of infarct size and early mortality rate.
- 1983
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Ingår i: British Heart Journal. - : BMJ Group. - 0007-0769. ; 50:6, s. 520-524
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Tidskriftsartikel (refereegranskat)abstract
- In 585 patients with a first acute myocardial infarction the maximum activity of heat stable lactate dehydrogenase (EC 1.1.1.27) was correlated with mortality at three months. The patients participated in a double blind trial with metoprolol in acute myocardial infarction. In all patients not taking a beta blocker a highly significant correlation was found, but this was not evident in those who were. When patients with anterior or inferior infarctions treated with a placebo were analysed separately the correlation remained, as it did when the patients who were alive on the fourth day after the onset of pain were analysed separately. No correlation was observed between enzyme activity and three month mortality in these subgroups if only patients treated with metoprolol were included. In a subsample of only 171 patients it was found that the maximum activity of creatine kinase (EC 2.7.3.2) and creatine kinase subunit B did not correlate with three month mortality regardless of treatment. Thus it is concluded that when a sufficiently large number of patients are investigated there is a highly significant correlation between the enzymatic estimation of infarct size and early mortality in acute myocardial infarction. This relation did not persist when patients treated with beta blockade were analysed.
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