| 1. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Rauer, H., et al.
(författare)
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The PLATO 2.0 mission
- 2014
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 38:1-2, s. 249-330
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Tidskriftsartikel (refereegranskat)abstract
- PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s cadence) providing a wide field-of-view (2232 deg(2)) and a large photometric magnitude range (4-16 mag). It focuses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e. g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such a low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmospheres. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.
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| 3. |
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| 4. |
- Quanz, S. P., et al.
(författare)
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Large Interferometer For Exoplanets (LIFE) I. Improved exoplanet detection yield estimates for a large mid-infrared space-interferometer mission
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 664
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Tidskriftsartikel (refereegranskat)abstract
- Context. One of the long-term goals of exoplanet science is the atmospheric characterization of dozens of small exoplanets in order to understand their diversity and search for habitable worlds and potential biosignatures. Achieving this goal requires a space mission of sufficient scale that can spatially separate the signals from exoplanets and their host stars and thus directly scrutinize the exoplanets and their atmospheres.Aims. We seek to quantify the exoplanet detection performance of a space-based mid-infrared (MIR) nulling interferometer that measures the thermal emission of exoplanets. We study the impact of various parameters and compare the performance with that of large single-aperture mission concepts that detect exoplanets in reflected light.Methods. We have developed an instrument simulator that considers all major astrophysical noise sources and coupled it with Monte Carlo simulations of a synthetic exoplanet population around main-sequence stars within 20 pc of the Sun. This allows us to quantify the number (and types) of exoplanets that our mission concept could detect. Considering single visits only, we discuss two different scenarios for distributing 2.5 yr of an initial search phase among the stellar targets. Different apertures sizes and wavelength ranges are investigated.Results. An interferometer consisting of four 2 m apertures working in the 4–18.5 μ.m wavelength range with a total instrument throughput of 5% could detect up to ≈550 exoplanets with radii between 0.5 and 6 R⊕ with an integrated S/N ≥ 7. At least ≈160 of the detected exoplanets have radii ≤1.5 R⊕. Depending on the observing scenario, ≈25–45 rocky exoplanets (objects with radii between 0.5 and 1.5 R⊕) orbiting within the empirical habitable zone (eHZ) of their host stars are among the detections. With four 3.5 m apertures, the total number of detections can increase to up to ≈770, including ≈60–80 rocky eHZ planets. With four times 1 m apertures, the maximum detection yield is ≈315 exoplanets, including ≤20 rocky eHZ planets. The vast majority of small, temperate exoplanets are detected around M dwarfs. The impact of changing the wavelength range to 3–20 μm or 6–17 μm on the detection yield is negligible.Conclusions. A large space-based MIR nulling interferometer will be able to directly detect hundreds of small, nearby exoplanets, tens of which would be habitable world candidates. This shows that such a mission can compete with large single-aperture reflected light missions. Further increasing the number of habitable world candidates, in particular around solar-type stars, appears possible via the implementation of a multi-visit strategy during the search phase. The high median S/N of most of the detected planets will allow for first estimates of their radii and effective temperatures and will help prioritize the targets for a second mission phase to obtain high-S/N thermal emission spectra, leveraging the superior diagnostic power of the MIR regime compared to shorter wavelengths.
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| 5. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Friedman, R. J., et al.
(författare)
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Dabigatran etexilate and concomitant use of non-steroidal anti-inflammatory drugs or acetylsalicylic acid in patients undergoing total hip and total knee arthroplasty: No increased risk of bleeding
- 2012
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 108:1, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- Patients undergoing total hip or knee arthroplasty should receive anticoagulant therapy because of the high risk of venous thromboembolism. However, many are already taking non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) that can have antihaemostatic effects. We assessed the bleeding risk in patients treated with thromboprophylactic dabigatran etexilate, with and without concomitant NSAID or ASA. A post-hoc analysis was undertaken of the pooled data from trials comparing dabigatran etexilate (220 mg and 150 mg once daily) and enoxaparin. Major bleeding event (MBE) rates were determined and odds ratios (ORs) generated for patients who received study treatment plus NSAID (half-life <= 12 hours) or ASA (<= 160 mg/day) versus study treatment alone. Relative risks were calculated for comparisons between treatments. Overall, 4,405/8,135 patients (54.1%) received concomitant NSAID and 386/8,135 (4.7%) received ASA.ORs for the comparison with/without concomitant NSAID were 1.05 (95% confidence interval [Cl] 0.55-2.01) for 220 mg dabigatran etexilate; 1.19 (0.55-2.55) for 150 mg; and 1.32(0.67-2.57) for enoxaparin. ORs for the comparison with/without ASA were 1.14 (0.26-5.03); 1.64 (0.36-7.49); and 2.57 (0.83-7.94), respectively. For both NSAIDs and ASA there was no significant difference in bleeding between patients with and without concomitant therapy in any treatment arm. Patients concomitantly taking NSAIDs or ASA have a similar risk of MBE to those taking dabigatran etexilate alone. No significant differences in MBE were detected between dabigatran etexilate and enoxaparin within co-medication subgroups, suggesting that no increased major bleeding risk exists when dabigatran etexilate is administered with NSAID or ASA.
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| 7. |
- Ozgen, H, et al.
(författare)
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International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder
- 2020
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Ingår i: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 26:4-5, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. <b><i>Objective:</i></b> The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. <b><i>Method:</i></b> A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. <b><i>Results:</i></b> After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (<i>n</i> = 4), risk of developing SUD (<i>n</i> = 3), screening and diagnosis (<i>n</i> = 7), psychosocial treatment (<i>n</i> = 5), pharmacological treatment (<i>n</i> = 11), and complementary treatments (<i>n</i> = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. <b><i>Conclusion:</i></b> This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.
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| 8. |
- Ozgen, H, et al.
(författare)
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[International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder]
- 2022
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Ingår i: Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie. - : Hogrefe Publishing Group. - 1422-4917 .- 1664-2880. ; 50:1, s. 54-67
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Tidskriftsartikel (refereegranskat)abstract
- Zusammenfassung. Hintergrund: Eine Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Kindesalter stellt einen Risikofaktor für Substanzmissbrauch und Störungen durch Substanzgebrauch (Substance Use Disorder, SUD) in der Pubertät und dem (frühen) Erwachsenenalter dar. ADHS und SUD treten auch häufig bei therapiesuchenden Jugendlichen auf, was die Diagnosestellung und Therapie erschwert sowie mit schlechten Behandlungsergebnissen verbunden ist. Forschungsergebnisse über die Wirkung der Behandlung von ADHS im Kindesalter auf die Prävention von SUD im Jugendalter sind nicht eindeutig und Studien über die Diagnose und Behandlung von Jugendlichen mit ADHS und SUD sind selten. Daher reicht die verfügbare Evidenz allgemein nicht aus, um starke Behandlungsempfehlungen zu rechtfertigen. Fragestellung: Ziel dieser Arbeit war es, eine Konsenserklärung auf der Grundlage von wissenschaftlichen Daten und klinischen Erfahrungen zu erhalten. Methodik: Es wurde eine modifizierte Delphi-Studie durchgeführt, um basierend auf der Kombination von wissenschaftlichen Daten und klinischer Erfahrung mit einer multidisziplinären Gruppe von 55 Expert_innen aus 17 Ländern einen Konsens zu erzielen. Die Expert_innen wurden gebeten, eine Reihe von Aussagen über die Wirkung der Behandlung von ADHS im Kindesalter auf die SUD bei Jugendlichen sowie über das Screening, die Diagnostik und die Behandlung von Jugendlichen mit komorbidem ADHS und SUD zu bewerten. Ergebnisse: Nach drei iterativen Bewertungsrunden und der Anpassung von 37 Aussagen wurde ein Konsens über 36 dieser Aussagen erzielt, die sechs Bereiche repräsentieren: allgemein ( n = 4), Risiko der Entwicklung einer SUD ( n = 3), Screening und Diagnostik ( n = 7), psychosoziale Behandlung ( n = 5), pharmakologische Behandlung ( n = 11) und komplementäre Behandlungen ( n = 7). Der Einsatz von Routinescreenings auf ADHS wird bei adoleszenten Patient_innen in einer Suchtbehandlung ebenso wie Routinescreenings auf SUD bei jugendlichen Patient_innen mit ADHS in allgemeinpsychiatrischen Therapiesettings empfohlen. Langwirksame Stimulanzien werden als Behandlung der ersten Wahl von ADHS bei Jugendlichen mit gleichzeitiger ADHS und SUD empfohlen. Die Pharmakotherapie sollte vorzugsweise in psychosoziale Behandlung eingebettet werden. Die einzige nichtkonsentierte Aussage betraf die Notwendigkeit von Abstinenz vor Beginn einer pharmakologischen Behandlung bei Jugendlichen mit ADHS und gleichzeitigem SUD. Im Gegensatz zur Mehrheit verlangten einige Expert_innen eine vollständige Abstinenz vor Beginn einer pharmakologischen Behandlung, einige waren gegen die Verwendung von Stimulanzien bei der Behandlung dieser Patient_innen (unabhängig von Abstinenz), während einige sich gegen die alternative Anwendung von Bupropion aussprachen. Schlussfolgerungen: Diese internationale Konsenserklärung kann von Kliniker_innen und Patient_innen zusammen in einem gemeinsamen Entscheidungsprozess genutzt werden, um die besten Interventionen auszuwählen und die bestmöglichen Ergebnisse bei adoleszenten Patient_innen mit gleichzeitiger ADHS und SUD zu erzielen.
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| 9. |
- Gonzalez, RA, et al.
(författare)
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Onset and Severity of Early Disruptive Behavioral Disorders in Treatment-Seeking Substance Use Disorder Patients with and without Attention-Deficit/Hyperactivity Disorder
- 2020
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Ingår i: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 26:4-5, s. 211-222
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Aims:</i></b> This study addressed the age of onset of conduct disorder (CD) and oppositional defiant disorder (ODD) in treatment-seeking substance use disorder (SUD) patients with and without adult attention-deficit/hyperactivity disorder (ADHD) and its association with early onset of SUD. <b><i>Methods:</i></b> We examined data from the 2nd <i>International ADHD in Substance Use Disorders Prevalence Study</i>, including 400 adults in SUD treatment from Puerto Rico, Hungary, and Australia. ADHD, SUD, and CD/ODD were assessed with the <i>Conners Adult ADHD Diagnostic Interview for DSM-IV</i>, the <i>MINI International Neuropsychiatric Interview</i>, and the K-SADS, respectively. Cox regression analyses modeled time to emergence of CD/ODD separately for SUD patients with and without adult ADHD. Linear regression models examined associations between age of onset of SUD and presence of ADHD and adjusted for sex, age, and country. To assess the mediating role of CD/ODD on the association of ADHD with onset of SUD, adjusted regression models were estimated. <b><i>Results:</i></b> Treatment-seeking SUD patients with ADHD presented an earlier onset of CD/ODD compared with those without ADHD. CD/ODD symptom loads were higher among the SUD and ADHD group. Age of first substance use and SUD were significantly earlier in SUD patients with ADHD, and these findings remained significant after adjustment for demographics and coexisting CD/ODD. <b><i>Conclusions:</i></b> ADHD is associated with earlier onset of SUD as well as with an earlier onset of more frequent and more severe disruptive behavioral disorders. These findings may inform preventive interventions to mitigate adverse consequences of ADHD.
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| 10. |
- Johannes, A., et al.
(författare)
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Enhanced sputtering and incorporation of Mn in implanted GaAs and ZnO nanowires
- 2014
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Ingår i: Journal of Physics D: Applied Physics. - Bristol : IOP Publishing. - 1361-6463 .- 0022-3727. ; 47:39
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Tidskriftsartikel (refereegranskat)abstract
- We simulated and experimentally investigated the sputter yield of ZnO and GaAs nanowires, which were implanted with energetic Mn ions at room temperature. The resulting thinning of the nanowires and the dopant concentration with increasing Mn ion fluency were measured by accurate scanning electron microscopy (SEM) and nano-x-Ray Fluorescence (nanoXRF) quantification, respectively. We observed a clearly enhanced sputter yield for the irradiated nanowires compared to bulk, which is also corroborated by iradina simulations. These show a maximum if the ion range matches the nanowire diameter. As a consequence of the erosion thinning of the nanowire, the incorporation of the Mn dopants is also enhanced and increases non-linearly with increasing ion fluency.
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| 11. |
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| 12. |
- Chernitskiy, S. V., et al.
(författare)
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Neutronic Model Of A Fusion Neutron Source
- 2013
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Ingår i: Problems of Atomic Science and Technology. - 1562-6016. ; :1, s. 61-63
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Tidskriftsartikel (refereegranskat)abstract
- The MCNPX numerical code has been used to model a fusion neutron source based on a combined stellarator-mirror trap. Calculation results for the neutron spectrum near the inner wall and radial leakage of neutrons through the mantle surface of the fusion neutron source are presented.
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| 13. |
- Chernitskiy, S. V., et al.
(författare)
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Neutronic Model of a Stellarator-Mirror Fusion-Fission Hybrid
- 2012
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Ingår i: PROBL ATOM SCI TECH. - 1562-6016. ; :6, s. 58-60
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Tidskriftsartikel (refereegranskat)abstract
- The MCNPX numerical code has been used to model a compact concept for a fusion-fission reactor based on a combined stellarator-mirror trap. Calculation results for the radial leakage of neutrons through the mantle surface of the fission reactor are presented.
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| 14. |
- Chernitskiy, S. V., et al.
(författare)
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Static neutronic calculation of a subcritical transmutation stellarator-mirror fusion-fission hybrid
- 2014
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 72, s. 413-420
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Tidskriftsartikel (refereegranskat)abstract
- The MCNPX Monte-Carlo code has been used to model the neutron transport in a sub-critical fast fission reactor driven by a fusion neutron source. A stellarator-mirror device is considered as the fusion neutron source. The principal composition for a fission blanket of a mirror fusion-fission hybrid is devised from the calculations. Heat load on the first wall, the distribution of the neutron fields in the reactor, the neutron spectrum and the distribution of energy release in the blanket are calculated. The possibility of tritium breeding inside the installation in quantities that meet the needs of the fusion neutron source is analyzed. The portion of the plasma column generates fusion neutrons that mainly do not reach the fission reactor core is proposed to be surrounded by a vessel filled with borated water to absorb the flying out neutrons. The flux of the neutrons escaping from the device to surrounding space is also calculated.
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| 15. |
- Cockell, C.S., et al.
(författare)
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Habitability : a review
- 2016
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Ingår i: Astrobiology. - : Mary Ann Liebert Inc. - 1531-1074 .- 1557-8070. ; 16:1, s. 89-117
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Tidskriftsartikel (refereegranskat)abstract
- Habitability is a widely used word in the geoscience, planetary science, and astrobiology literature, but what does it mean? In this review on habitability, we define it as the ability of an environment to support the activity of at least one known organism. We adopt a binary definition of “habitability” and a “habitable environment.” An environment either can or cannot sustain a given organism. However, environments such as entire planets might be capable of supporting more or less species diversity or biomass compared with that of Earth. A clarity in understanding habitability can be obtained by defining instantaneous habitability as the conditions at any given time in a given environment required to sustain the activity of at least one known organism, and continuous planetary habitability as the capacity of a planetary body to sustain habitable conditions on some areas of its surface or within its interior over geological timescales. We also distinguish between surface liquid water worlds (such as Earth) that can sustain liquid water on their surfaces and interior liquid water worlds, such as icy moons and terrestrial-type rocky planets with liquid water only in their interiors. This distinction is important since, while the former can potentially sustain habitable conditions for oxygenic photosynthesis that leads to the rise of atmospheric oxygen and potentially complex multicellularity and intelligence over geological timescales, the latter are unlikely to. Habitable environments do not need to contain life. Although the decoupling of habitability and the presence of life may be rare on Earth, it may be important for understanding the habitability of other planetary bodies
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| 16. |
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| 17. |
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| 18. |
- Douketis, J D, et al.
(författare)
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Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure : Substudy of the RE-LY trial
- 2015
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 113:3, s. 625-632
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Tidskriftsartikel (refereegranskat)abstract
- In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain. We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders. Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p< 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs. 1.8 %, P< 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p< 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.
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| 19. |
- Ezekowitz, Michael D., et al.
(författare)
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Comparison of Dabigatran and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease The RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulant Therapy)
- 2016
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 134:8, s. 589-598
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant Therapy) compared dabigatran 150 and 110 mg twice daily with warfarin in 18 113 patients with atrial fibrillation. Those with prosthetic heart valves, significant mitral stenosis, and valvular heart disease (VHD) requiring intervention were excluded. Others with VHD were included. METHODS: This is a post hoc analysis of the RE-LY trial. RESULTS: There were 3950 patients with any VHD: 3101 had mitral regurgitation, 1179 with tricuspid regurgitation, 817 had aortic regurgitation, 471 with aortic stenosis, and 193 with mild mitral stenosis. At baseline, patients with any VHD had more heart failure, coronary disease, renal impairment, and persistent atrial fibrillation. Patients with any VHD had higher rates of major bleeds (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.16-1.5) but similar stroke or systemic embolism event rates (HR, 1.09; 95% CI, 0.88-1.33). For patients receiving dabigatran 110 mg, major bleed rates were lower than for patients taking warfarin (HR, 0.73; 95% CI, 0.56-0.95 with VHD; HR, 0.84; 95% CI, 0.71-0.99 without VHD), and major bleed rates for dabigatran 150 mg were similar to those for warfarin in patients with VHD (HR, 0.82; 95% CI, 0.64-1.06) or without VHD (HR, 0.98; 95% CI, 0.83-1.15). For dabigatran 150 mg, stroke/systemic embolic event rates were lower compared with warfarin in those with VHD (HR, 0.59; 95% CI, 0.37-0.93) and those without VHD (HR, 0.67; 95% CI, 0.52-0.86), and stroke/systemic embolic event rates were similar for warfarin and dabigatran 110 mg regardless of the presence of VHD (HR, 0.97; 95% CI, 0.65-1.45; and HR, 0.88; 95% CI, 0.70-1.10). Intracranial bleeds and death rates for dabigatran 150 and 110 mg were lower compared with warfarin independently of the presence of VHD. CONCLUSIONS: The presence of any VHD did not influence the comparison of dabigatran with warfarin.
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| 20. |
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| 21. |
- Ezekowitz, Michael D., et al.
(författare)
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Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation
- 2016
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:7, s. 973-978
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Tidskriftsartikel (refereegranskat)abstract
- Aims The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial allowed patients who completed the trial receiving their assigned dabigatran 150 mg (D150) or 110 mg (D110) twice a day to continue into the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. This permitted assessment of outcomes over a median of 4.6 and a maximum of 6.7 years, respectively. Methods and results The analysed population included only those patients who completed RE-LY on dabigatran and continued into RELYABLE without interruption of assigned dabigatran. Cumulative risk was expressed as Kaplan-Meier plots. Outcomes were compared using Cox proportional hazard modelling. Stroke or systemic embolization rates were 1.25 and 1.54% per year (D150 and D110, respectively); hazard ratio (HR) 0.81 [95% confidence interval (CI): 0.68-0.96] (P = 0.02). Ischaemic stroke was 1.03 (D150) and 1.29%/year (D110); HR 0.79 (95% CI: 0.66-0.95) (P = 0.01). Haemorrhagic stroke rates were 0.11 (D150) and 0.13%/year (D110); HR 0.91 (95% CI: 0.51-1.62) (P = 0.75). Rates of major haemorrhage were 3.34 (D150) and 2.76%/year (D110); HR 1.22 (95% CI: 1.08-1.37) (P = 0.0008). Intracranial haemorrhage rates were 0.32 (D150) and 0.23%/year (D110); HR 1.37 (95% CI: 0.93-2.01) (P = 0.11). Mortality was 3.43 (D150) and 3.55%/year (D110); HR 0.97 (95% CI: 0.87-1.08) (P = 0.54). Conclusion Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.
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| 22. |
- Georgiev, Valentin, et al.
(författare)
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A DFT Study on the Catalytic Reactivity of a Functional Model Complex for Intradiol-Cleaving Dioxygenases
- 2010
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:17, s. 5878-5885
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Tidskriftsartikel (refereegranskat)abstract
- The enzymatic ring cleavage of catechol derivatives is catalyzed by two groups of dioxygenases: extradiol- and intradiol-cleaving dioxygenases. Although having different oxidation state of their nonheme iron sites and different ligand coordinations, both groups of enzymes involve a common peroxy intermediate in their catalytic cycles. The factors that lead to either extradiol cleavage resulting in 2-hydroxymuconaldehyde or intradiol cleavage resulting in muconic acid are not fully understood. Well-characterized model compounds that mimic the functionality of these enzymes offer a basis for direct comparison to theoretical results. In this study the mechanism of a biomimetic iron complex is investigated with density functional theory (DFT). This complex catalyzes the ring opening of catecholate with exclusive formation of the intradiol cleaved product. Several spin states are possible for the transition metal system, with the quartet state found to be of main importance during the reaction course. The mechanism investigated provides an explanation for the observed selectivity of the complex. First, a bridging peroxide is formed, which decomposes to an alkoxy radical by O−O homolysis. In contrast to the subsequent barrier-free intradiol C−C bond cleavage, the extradiol pathway proceeds via the formation of an epoxide, which requires an additional activation barrier.
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| 29. |
- Noack, Holger, 1976-
(författare)
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Biomimetic Iron Complexes involved in Oxygenation and Chlorination : A Theoretical Study
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomimetic chemistry is directed towards the simulation of enzymatic reactivity with synthetic analogues. In this thesis a quantum chemical method has been employed to study the mechanism of highly reactive iron-oxo complexes involved in oxygenation and chlorination of organic substrates. The aim of this research is to gain greater understanding for the reactivity paradigm of the iron-oxo group. One reaction deals with the conversion of cyclohexane into adipic acid, a key chemical in industrial chemistry, catalyzed by an iron(II)-porphyrin complex in the presence of dioxygen. This process constitutes a ’green’ alternative to conventional adipic acid production, and is thus of great interest to synthetic chemistry. Another reaction investigated herein regards the selective chlorination observed for a new group of non-heme iron enzymes. With help of theoretical modeling it was possible to propose a mechanism that explains the observed selectivity. It is furthermore demonstrated how a biomimetic iron complex simulates the enzymatic reactivity by a different mechanism. Other topics covered in this thesis regard the structure-reactivity relationship of a binuclear iron complex and the intradiol C-C bond cleavage of catechol catalyzed by an iron(III) complex.
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| 30. |
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| 31. |
- Noack, Holger, et al.
(författare)
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Theoretical Insights into Heme Catalysed Oxidation of Cyclohexane to Adipic Acid
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Tidskriftsartikel (refereegranskat)abstract
- Adipic acid is a key compound in the chemical industry, where it is mainly used in the production of polymers. The conventional process of its generation requires vast amounts of energy, and moreover, pro- duces environmentally deleterious substances. Thus, there is interest in alternative ways to gain adequate amounts of adipic acid. Experimental reports on a one-pot iron catalyzed conversion of cyclohexane to adipic acid motivated a theoretical investigation based on DFT calculations. The process investigated is interesting because it requires less energy than contemporary methods and does not produce environmentally harmful side products. The aim of the present contribution is to gain insight into the mechanism of the iron catalyzed cyclohexane conversion to provide a basis for further development of this process. The rate limiting step along the reaction path is discussed. Furthermore, it is shown that the C-C bond breaks spontaneously after an initial hydrogen atom abstraction from one of the cylohexane-1,2-diol hydroxides.
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| 32. |
- Noack, Holger, et al.
(författare)
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Theoretical Insights into Heme-Catalyzed Oxidation of Cyclohexane to Adipic Acid
- 2011
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 50:4, s. 1194-1202
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Tidskriftsartikel (refereegranskat)abstract
- Adipic acid is a key compound in the chemical industry, where it is mainly used in the production of polymers. The conventional process of its generation requires vast amounts of energy and, moreover, produces environmentally deleterious substances. Thus, there is interest in alternative ways to gain adequate amounts of adipic acid. Experimental reports on a one-pot iron-catalyzed conversion of cyclohexane to adipic acid motivated a theoretical investigation based on density functional theory calculations. The process investigated is interesting because it requires less energy than contemporary methods and does not produce environmentally harmful side products. The aim of the present contribution is to gain insight into the mechanism of the iron-catalyzed cyclohexane conversion to provide a basis for the further development of this process. The rate-limiting step of the process is discussed, but considering the accuracy of the calculations, it is difficult to ensure whether the rate-limiting step is in the substrate oxidation or in the generation of the catalytically active species. It is shown that the slowest step in the substrate oxidation is the conversion of cyclohexanol to cyclohexane-1,2-diol. Hydrogen-atom transfer from one of the OH groups of cyclohexane-1,2-diol makes the intradiol cleavage occur spontaneously.
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| 33. |
- Noack, P., et al.
(författare)
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Family relations in adolescence
- 1999
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Ingår i: Journal of Adolescence. - : Elsevier BV. - 0140-1971 .- 1095-9254. ; 22:6, s. 713-717
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Tidskriftsartikel (refereegranskat)
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| 34. |
- Thuijs, Daniel J F M, et al.
(författare)
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Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.
- 2019
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Ingår i: Lancet (London, England). - 1474-547X. ; 394:10206, s. 1325-1334
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Tidskriftsartikel (refereegranskat)abstract
- The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results.The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050.From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 244 (27%) patients had died after PCI and 211 (24%) after CABG (hazard ratio 1·17 [95% CI 0·97-1·41], p=0·092). Among patients with three-vessel disease, 151 (28%) of 546 had died after PCI versus 113 (21%) of 549 after CABG (hazard ratio 1·41 [95% CI 1·10-1·80]), and among patients with left main coronary artery disease, 93 (26%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0·90 [0·68-1·20], pinteraction=0·019). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0·66) and no linear trend across SYNTAX score tertiles (ptrend=0·30).At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease.German Foundation of Heart Research (SYNTAXES study, 5-10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0-5-year follow-up).
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