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1.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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2.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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3.
  • Blanton, Michael R., et al. (författare)
  • Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
  • 2017
  • Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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4.
  • Lindblad-Toh, Kerstin, et al. (författare)
  • Genome sequence, comparative analysis and haplotype structure of the domestic dog.
  • 2005
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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5.
  • Akiyama, Kazunori, et al. (författare)
  • First M87 Event Horizon Telescope Results. IV. Imaging the Central Supermassive Black Hole
  • 2019
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of similar to 40 mu as, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions.
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6.
  • Akiyama, Kazunori, et al. (författare)
  • First M87 Event Horizon Telescope Results. V. Physical Origin of the Asymmetric Ring
  • 2019
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Event Horizon Telescope (EHT) has mapped the central compact radio source of the elliptical galaxy M87 at 1.3 mm with unprecedented angular resolution. Here we consider the physical implications of the asymmetric ring seen in the 2017 EHT data. To this end, we construct a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by general relativistic ray tracing. We compare the observed visibilities with this library and confirm that the asymmetric ring is consistent with earlier predictions of strong gravitational lensing of synchrotron emission from a hot plasma orbiting near the black hole event horizon. The ring radius and ring asymmetry depend on black hole mass and spin, respectively, and both are therefore expected to be stable when observed in future EHT campaigns. Overall, the observed image is consistent with expectations for the shadow of a spinning Kerr black hole as predicted by general relativity. If the black hole spin and M87's large scale jet are aligned, then the black hole spin vector is pointed away from Earth. Models in our library of non-spinning black holes are inconsistent with the observations as they do not produce sufficiently powerful jets. At the same time, in those models that produce a sufficiently powerful jet, the latter is powered by extraction of black hole spin energy through mechanisms akin to the Blandford-Znajek process. We briefly consider alternatives to a black hole for the central compact object. Analysis of existing EHT polarization data and data taken simultaneously at other wavelengths will soon enable new tests of the GRMHD models, as will future EHT campaigns at 230 and 345 GHz.
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7.
  • Akiyama, Kazunori, et al. (författare)
  • First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole
  • 2019
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 875:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to be
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8.
  • Akiyama, Kazunori, et al. (författare)
  • First M87 Event Horizon Telescope Results. VII. Polarization of the Ring
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2017 April, the Event Horizon Telescope (EHT) observed the near-horizon region around the supermassive black hole at the core of the M87 galaxy. These 1.3 mm wavelength observations revealed a compact asymmetric ring-like source morphology. This structure originates from synchrotron emission produced by relativistic plasma located in the immediate vicinity of the black hole. Here we present the corresponding linear-polarimetric EHT images of the center of M87. We find that only a part of the ring is significantly polarized. The resolved fractional linear polarization has a maximum located in the southwest part of the ring, where it rises to the level of similar to 15%. The polarization position angles are arranged in a nearly azimuthal pattern. We perform quantitative measurements of relevant polarimetric properties of the compact emission and find evidence for the temporal evolution of the polarized source structure over one week of EHT observations. The details of the polarimetric data reduction and calibration methodology are provided. We carry out the data analysis using multiple independent imaging and modeling techniques, each of which is validated against a suite of synthetic data sets. The gross polarimetric structure and its apparent evolution with time are insensitive to the method used to reconstruct the image. These polarimetric images carry information about the structure of the magnetic fields responsible for the synchrotron emission. Their physical interpretation is discussed in an accompanying publication.
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9.
  • Akiyama, Kazunori, et al. (författare)
  • First M87 Event Horizon Telescope Results. VIII. Magnetic Field Structure near The Event Horizon
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Event Horizon Telescope (EHT) observations at 230 GHz have now imaged polarized emission around the supermassive black hole in M87 on event-horizon scales. This polarized synchrotron radiation probes the structure of magnetic fields and the plasma properties near the black hole. Here we compare the resolved polarization structure observed by the EHT, along with simultaneous unresolved observations with the Atacama Large Millimeter/submillimeter Array, to expectations from theoretical models. The low fractional linear polarization in the resolved image suggests that the polarization is scrambled on scales smaller than the EHT beam, which we attribute to Faraday rotation internal to the emission region. We estimate the average density n(e) similar to 10(4-7) cm(-3), magnetic field strength B similar to 1-30 G, and electron temperature T-e similar to (1-12) x 10(10) K of the radiating plasma in a simple one-zone emission model. We show that the net azimuthal linear polarization pattern may result from organized, poloidal magnetic fields in the emission region. In a quantitative comparison with a large library of simulated polarimetric images from general relativistic magnetohydrodynamic (GRMHD) simulations, we identify a subset of physical models that can explain critical features of the polarimetric EHT observations while producing a relativistic jet of sufficient power. The consistent GRMHD models are all of magnetically arrested accretion disks, where near-horizon magnetic fields are dynamically important. We use the models to infer a mass accretion rate onto the black hole in M87 of (3-20) x 10(-4) M yr(-1).
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10.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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11.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. III. Imaging of the Galactic Center Supermassive Black Hole
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first event-horizon-scale images and spatiotemporal analysis of Sgr A* taken with the Event Horizon Telescope in 2017 April at a wavelength of 1.3 mm. Imaging of Sgr A* has been conducted through surveys over a wide range of imaging assumptions using the classical CLEAN algorithm, regularized maximum likelihood methods, and a Bayesian posterior sampling method. Different prescriptions have been used to account for scattering effects by the interstellar medium toward the Galactic center. Mitigation of the rapid intraday variability that characterizes Sgr A* has been carried out through the addition of a "variability noise budget" in the observed visibilities, facilitating the reconstruction of static full-track images. Our static reconstructions of Sgr A* can be clustered into four representative morphologies that correspond to ring images with three different azimuthal brightness distributions and a small cluster that contains diverse nonring morphologies. Based on our extensive analysis of the effects of sparse (u, v)-coverage, source variability, and interstellar scattering, as well as studies of simulated visibility data, we conclude that the Event Horizon Telescope Sgr A* data show compelling evidence for an image that is dominated by a bright ring of emission with a ring diameter of similar to 50 mu as, consistent with the expected "shadow" of a 4 x 10(6) M (circle dot) black hole in the Galactic center located at a distance of 8 kpc.
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12.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. IV. Variability, Morphology, and Black Hole Mass
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we quantify the temporal variability and image morphology of the horizon-scale emission from Sgr A*, as observed by the EHT in 2017 April at a wavelength of 1.3 mm. We find that the Sgr A* data exhibit variability that exceeds what can be explained by the uncertainties in the data or by the effects of interstellar scattering. The magnitude of this variability can be a substantial fraction of the correlated flux density, reaching similar to 100% on some baselines. Through an exploration of simple geometric source models, we demonstrate that ring-like morphologies provide better fits to the Sgr A* data than do other morphologies with comparable complexity. We develop two strategies for fitting static geometric ring models to the time-variable Sgr A* data; one strategy fits models to short segments of data over which the source is static and averages these independent fits, while the other fits models to the full data set using a parametric model for the structural variability power spectrum around the average source structure. Both geometric modeling and image-domain feature extraction techniques determine the ring diameter to be 51.8 +/- 2.3 mu as (68% credible intervals), with the ring thickness constrained to have an FWHM between similar to 30% and 50% of the ring diameter. To bring the diameter measurements to a common physical scale, we calibrate them using synthetic data generated from GRMHD simulations. This calibration constrains the angular size of the gravitational radius to be 4.8(-0.7)(+1.4) mu as, which we combine with an independent distance measurement from maser parallaxes to determine the mass of Sgr A* to be 4.0(-0.6)(+1.1) x 10(6) M-circle dot.
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13.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. V. Testing Astrophysical Models of the Galactic Center Black Hole
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we provide a first physical interpretation for the Event Horizon Telescope's (EHT) 2017 observations of Sgr A*. Our main approach is to compare resolved EHT data at 230 GHz and unresolved non-EHT observations from radio to X-ray wavelengths to predictions from a library of models based on time-dependent general relativistic magnetohydrodynamics simulations, including aligned, tilted, and stellar-wind-fed simulations; radiative transfer is performed assuming both thermal and nonthermal electron distribution functions. We test the models against 11 constraints drawn from EHT 230 GHz data and observations at 86 GHz, 2.2 mu m, and in the X-ray. All models fail at least one constraint. Light-curve variability provides a particularly severe constraint, failing nearly all strongly magnetized (magnetically arrested disk (MAD)) models and a large fraction of weakly magnetized models. A number of models fail only the variability constraints. We identify a promising cluster of these models, which are MAD and have inclination i <= 30 degrees. They have accretion rate (5.2-9.5) x 10(-9) M (circle dot) yr(-1), bolometric luminosity (6.8-9.2) x 10(35) erg s(-1), and outflow power (1.3-4.8) x 10(38) erg s(-1). We also find that all models with i >= 70 degrees fail at least two constraints, as do all models with equal ion and electron temperature; exploratory, nonthermal model sets tend to have higher 2.2 mu m flux density; and the population of cold electrons is limited by X-ray constraints due to the risk of bremsstrahlung overproduction. Finally, we discuss physical and numerical limitations of the models, highlighting the possible importance of kinetic effects and duration of the simulations.
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14.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein's equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A*). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A* to show that the observed image size is within similar to 10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass.
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15.
  • Algaba, Juan-Carlos, et al. (författare)
  • Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
  • Forskningsöversikt (refereegranskat)abstract
    • In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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16.
  • Bourantas, Christos V., et al. (författare)
  • Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery : An Analysis of the SYNTAX Study
  • 2015
  • Ingår i: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 85:2, s. 199-206
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation. BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG. MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5-year follow-up were collected and compared in the two groups. ResultsOne out of three patients exhibited severe lesion calcification (n=588). Patients with calcified coronaries had an increased mortality at 5-year follow-up (17.1% vs. 9.9%, P<0.001) and a higher event rate of death-myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P=0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P=0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all-cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02-1.89; P=0.037) but it was not an independent predictor of the combined end-points death-MI or MACE. ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death-MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. (c) 2014 Wiley Periodicals, Inc.
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17.
  • Broderick, Avery E., et al. (författare)
  • Characterizing and Mitigating Intraday Variability: Reconstructing Source Structure in Accreting Black Holes with mm-VLBI
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The extraordinary physical resolution afforded by the Event Horizon Telescope has opened a window onto the astrophysical phenomena unfolding on horizon scales in two known black holes, M87* and Sgr A*. However, with this leap in resolution has come a new set of practical complications. Sgr A* exhibits intraday variability that violates the assumptions underlying Earth aperture synthesis, limiting traditional image reconstruction methods to short timescales and data sets with very sparse (u, v) coverage. We present a new set of tools to detect and mitigate this variability. We develop a data-driven, model-agnostic procedure to detect and characterize the spatial structure of intraday variability. This method is calibrated against a large set of mock data sets, producing an empirical estimator of the spatial power spectrum of the brightness fluctuations. We present a novel Bayesian noise modeling algorithm that simultaneously reconstructs an average image and statistical measure of the fluctuations about it using a parameterized form for the excess variance in the complex visibilities not otherwise explained by the statistical errors. These methods are validated using a variety of simulated data, including general relativistic magnetohydrodynamic simulations appropriate for Sgr A* and M87*. We find that the reconstructed source structure and variability are robust to changes in the underlying image model. We apply these methods to the 2017 EHT observations of M87*, finding evidence for variability across the EHT observing campaign. The variability mitigation strategies presented are widely applicable to very long baseline interferometry observations of variable sources generally, for which they provide a data-informed averaging procedure and natural characterization of inter-epoch image consistency.
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18.
  • Dittrich, Christian, et al. (författare)
  • ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
  • 2016
  • Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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19.
  • Farah, Joseph, et al. (författare)
  • Selective Dynamical Imaging of Interferometric Data
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent developments in very long baseline interferometry (VLBI) have made it possible for the Event Horizon Telescope (EHT) to resolve the innermost accretion flows of the largest supermassive black holes on the sky. The sparse nature of the EHT's (u, v)-coverage presents a challenge when attempting to resolve highly time-variable sources. We demonstrate that the changing (u, v)-coverage of the EHT can contain regions of time over the course of a single observation that facilitate dynamical imaging. These optimal time regions typically have projected baseline distributions that are approximately angularly isotropic and radially homogeneous. We derive a metric of coverage quality based on baseline isotropy and density that is capable of ranking array configurations by their ability to produce accurate dynamical reconstructions. We compare this metric to existing metrics in the literature and investigate their utility by performing dynamical reconstructions on synthetic data from simulated EHT observations of sources with simple orbital variability. We then use these results to make recommendations for imaging the 2017 EHT Sgr A* data set.
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20.
  • Farooq, Vasim, et al. (författare)
  • Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients : development and validation of SYNTAX score II
  • 2013
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 381:9867, s. 639-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. Methods SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score >= 33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. Findings SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p(interaction) 0.0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p(interaction) 0.67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0.725 and for external (DELTA registry) validation of 0.716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0.567 and 0.612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. Interpretation Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score.
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21.
  • Farooq, Vasim, et al. (författare)
  • Incidence and multivariable correlates of long-term mortality in patients treated with surgical or percutaneous revascularization in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial.
  • 2012
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:24, s. 3105-3113
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The aim of this investigation was to determine the incidence and multivariable correlates of long-term (4-year) mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention (PCI) with TAXUS Express and Cardiac Surgery (SYNTAX) trial. Methods and results A total of 1800 patients were randomized to undergo coronary artery bypass graft (CABG) surgery (n = 897) or PCI (n = 903). Prospectively collected baseline and peri- and post-procedural data were used to determine independent correlates of 4-year all-cause death in the CABG and the PCI arms (Cox proportional hazards model). Four-year mortality rates in the CABG and the PCI arms were 9.0% [74 deaths (12 in-hospital)] and 11.8% [104 deaths (16 in-hospital)], respectively (log-rank P-value = 0.063). Censored data comprised 78 patients (8.7%) in the CABG arm, and 24 patients (2.7%) in the PCI arm (log-rank P-value < 0.001). Within the CABG arm, the strongest independent correlates of 4-year mortality were lack of discharge aspirin [hazard ratio (HR) 3.56; 95% CI: 2.04, 6.21; P < 0.001], peripheral vascular disease (PVD) (HR: 2.65; 95% CI: 1.49, 4.72; P = 0.001), chronic obstructive pulmonary disease, age, and serum creatinine. Within the PCI arm, the strongest independent correlate of 4-year mortality was lack of post-procedural anti-platelet therapy (HR: 152.16; 95% CI: 53.57, 432.22; P < 0.001), with 10 reported early (within 45 days) in-hospital deaths secondary to multifactorial causes precluding administration of anti-platelet therapy. Other independent correlates of mortality in the PCI arm included amiodarone therapy on discharge, pre-procedural poor left ventricular ejection fraction, a 'history of gastrointestinal bleeding or peptic ulcer disease', PVD (HR: 2.13; 95% CI: 1.26, 3.60; P = 0.005), age, female gender (HR: 1.60; 95% CI: 1.01, 2.56; P = 0.048), and the SYNTAX score (Per increase in 10 points: HR: 1.25; 95% CI: 1.06, 1.47; P = 0.007). Conclusion Independent correlates of 4-year mortality in the SYNTAX trial were multifactorial. Lack of discharge aspirin and lack of post-procedural anti-platelet therapy were the strongest independent correlates of mortality in the CABG and the PCI arms, respectively. Peripheral vascular disease is a common independent correlate of 4-year mortality and may be a marker of the severity of baseline coronary disease and risk of future native coronary disease (and extra-cardiac disease) progression.
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22.
  • Farooq, Vasim, et al. (författare)
  • Incidence, correlates, and significance of abnormal cardiac enzyme rises in patients treated with surgical or percutaneous based revascularisation : A substudy from the Synergy between Percutaneous Coronary Interventions with Taxus and Cardiac Surgery (SYNTAX) Trial
  • 2013
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 168:6, s. 5287-5292
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The aimof the present investigationwas to determine the long-termprognostic association of post-procedural cardiac enzyme elevation within the randomised Synergy between Percutaneous Coronary Intervention (PCI) with TAXUS and Cardiac Surgery (SYNTAX) Trial. Methods: 1800 patients with unprotected left main or de novo three-vessel coronary artery disease were randomised to undergo coronary artery bypass graft (CABG) surgery or PCI. Per protocol patients underwent post-procedural blood sampling with creatine kinase (CK), and the cardiac specific MB iso-enzyme (CK-MB) only if the preceding CK ratiowas = 2x the upper limit of normal (ULN). An independent chemistry laboratory evaluated all collected blood samples. Results: Post-procedural CK sampling was available in 1629 of 1800 patients (90.5%). As per protocol, CK-MB analyses were undertaken in 474 of 491 patients (96.5%) in the CABG arm, and 53 of 61 patients (86.9%) in the PCI arm. Within the CABG arm, despite the limitations of incomplete data, a post-procedural CK-MB ratio <3/>= 3 ULNseparated 4-year mortality into low-and high-risk groups (2.3% vs. 9.5%, p = 0.03). Additionally, in the CABG arm, a post-procedural CK-MB ratio = 3 ULN was associated with an increased frequency of a high SYNTAX Score (= 33) tertile (high [>= 33] SYNTAX Score: 39.5%, intermediate [23-32] SYNTAX Score 31.0%, low [>= 22] SYNTAX Score 29.5%, p = 0.02). Within the PCI arm, a post-procedural CK ratio of >2 or >= 2 ULN separated 4-year mortality into low-and high-risk groups (10.8% vs. 23.3%, p = 0.001). Notably, there was an early (within 6 months) and late (after 2 years) peak in mortality in patients with a post-PCI CK ratio of = 2 ULN. Lack of pre-procedural thienopyridine, carotid artery disease, type 1 diabetes, andpresenceof coronary bifurcationswere independent correlates of a CK ratio = 2 ULNpost-PCI. Conclusion: Cardiac enzyme elevations post-CABG or post-PCI are associatedwith an adverse long-termmortality; the causes of which are multifactorial.
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23.
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24.
  • Farooq, Vasim, et al. (författare)
  • Quantification of Incomplete Revascularization and its Association With Five-Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Trial Validation of the Residual SYNTAX Score
  • 2013
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:2, s. 141-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0-4, >4-8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4 +/- 11.5 and 4.5 +/- 6.9, respectively. The mean SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8 +/- 10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores 8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0-4, 8.7%; >4-8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization.
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25.
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26.
  • Farooq, Vasim, et al. (författare)
  • Short-Term and Long-Term Clinical Impact of Stent Thrombosis and Graft Occlusion in the SYNTAX Trial at 5 Years Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Trial
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:25, s. 2360-2369
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of this study was to report the short-term and long-term clinical impact of stent thrombosis (ST) and graft occlusion (GO) in the final 5-year outcomes of the SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial.Background The clinical effect of newer-generation drug-eluting stents and operative factors in complex coronary artery disease is uncertain.Methods The incidence of 5-year ST and GO, and their association with clinical outcomes, were analyzed in the randomized percutaneous coronary intervention and coronary artery bypass graft cohorts. ST and GO were defined by the SYNTAX protocol definitions (clinical presentation with acute coronary syndrome and angiographic/pathological evidence), the Academic Research Consortium (ARC) definition for ST, and the newly devised "ARC-like" definition of GO (i.e., definite, probable, or possible GO).Results At 5 years, 871 of 903 patients (96.5%) in the percutaneous coronary intervention cohort and 805 of 897 patients (89.7%) in the coronary artery bypass graft cohort completed follow-up. As compared with other vessel locations, protocol ST (72 lesions) occurred more frequently in the left main (14 of 72; 19%) and proximal coronary vasculature (37 of 72; 51%) and protocol GO (41 lesions) with grafts anastomosed to the distal right coronary artery (17 of 41; 42%). The incidence of 5-year ARC definite ST and ARC-like definite GO did not significantly differ (7%[n = 48] vs. 6% [n = 32], log rank p = 0.34); landmark analyses indicated significantly increased ARC definite ST within 30 days (3% [n = 19] vs. 1% [n = 6], log rank p = 0.033) but not >30 days to 5 years (4.2% [n = 29] vs. 4.5% [n = 26], log rank p = 0.78). At presentation, ARC definite ST (n = 48) and ARC-like definite GO (n = 32) were adjudicated to be linked to 4 (8%) and 0 deaths, respectively. At 5 years, ARC definite ST (n = 48) and ARC definite/probable ST (n = 75) were associated with 17 (17 of 48, 35.4%; median days to death: 0 days; interquartile range: 0 to 16 days; maximum: 321 days) and 31 (31 of 75, 41.3%; median: 0 days; interquartile range: 0 to 9 days; maximum: 721 days) cardiac deaths, respectively. At 5 years, ARC-like definite GO (n = 32) and ARC-like definite/probable GO (n = 53) were associated with 0 and 12 (12 of 52, 23.1%; median: 0 days; interquartile range: 0 to 14 days; maximum: 257 days) cardiac deaths, respectively.Conclusions Although the incidence of ST and GO was similar at 5 years, the clinical impact of ST appeared greater, with a negative impact on short-term to long-term mortality.
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27.
  • Farooq, Vasim, et al. (författare)
  • The CABG SYNTAX Score - an angiographic tool to grade the complexity of coronary disease following coronary artery bypass graft surgery : from the SYNTAX Left Main Angiographic (SYNTAX-LE MANS) substudy
  • 2013
  • Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 8:11, s. 1277-1285
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The SYNTAX Score (SXscore) has established itself as an important prognostic tool in patients undergoing percutaneous coronary intervention (PCI). A limitation of the SXscore is the inability to differentiate outcomes in patients who have undergone prior coronary artery bypass graft (CABG) surgery. The CABG SXscore was devised to address this limitation.METHODS AND RESULTS: In the SYNTAX-LE MANS substudy 115 patients with unprotected left main coronary artery disease (isolated or associated with one, two or three-vessel disease) treated with CABG were prospectively assigned to undergo a 15-month coronary angiogram. An independent core laboratory analysed the baseline SXscore prior to CABG. The 15-month CABG SXscore was calculated by a panel of three interventional cardiologists. The CABG SXscore was calculated by determining the standard SXscore in the "native" coronary vessels ("native SXscore") and deducting points based on the importance of the diseased coronary artery segment (Leaman score) that have a functioning bypass graft anastomosed distally. Points relating to intrinsic coronary disease, such as bifurcation disease or calcification, remain unaltered. The mean 15-month CABG SXscore was significantly lower compared to the mean baseline SXscore (baseline SXscore 31.6, SD 13.1; 15-month CABG SXscore 21.2, SD 11.1; p<0.001). Reproducibility analyses (kappa [k] statistics) indicated a substantial agreement between CABG SXscore measurements (k=0.70; 95% CI [0.50-0.90], p<0.001), with the points deducted to calculate the CABG SXscore the most reproducible measurement (k=0.74; 95% CI [0.53-0.95], p<0.001). Despite the limited power of the study, four-year outcome data (Kaplan-Meier curves) demonstrated a trend towards reduced all-cause death (9.1% vs. 1.8%, p=0.084) and death/CVA/MI (16.4% vs. 7.0%, p=0.126) in the low compared to the high CABG SXscore group.CONCLUSIONS: In this pilot study the calculation of the CABG SXscore appeared feasible, reproducible and may have a long-term prognostic role in patients with complex coronary disease undergoing surgical revascularisation. Validation of this new scoring methodology is required.
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28.
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29.
  • Farooq, Vasim, et al. (författare)
  • The Negative Impact of Incomplete Angiographic Revascularization on Clinical Outcomes and Its Association With Total Occlusions : The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) Trial
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:3, s. 282-294
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:The study sought to evaluate the clinical impact of angiographic complete (CR) and incomplete (ICR) revascularization and its association with the presence of total occlusions (TO), after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in the "all-comers" SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial.BACKGROUND:In patients with complex coronary artery disease undergoing PCI or CABG, the long-term prognostic implications of CR versus ICR is unsettled.METHODS:In this post hoc study, consisting of randomized (n = 1,800) and nested PCI (n = 198) and CABG (n = 649) registries, 4-year clinical outcomes were compared in groups, with and without angiographic CR, in the PCI and CABG arms. Clinical outcomes were analyzed with Kaplan-Meier estimates, log-rank comparisons, and Cox regression analyses. Multivariate predictors of ICR were determined. Similar analyses were undertaken in the TO and non-TO treated groups of both study arms.RESULTS:Angiographic CR was achieved in 52.8% of the PCI arm and 66.9% of the CABG arm. Within the PCI and CABG arms, ICR (compared with CR) seemed to be a surrogate marker of a greater burden of anatomical coronary complexity and clinical comorbidity and was associated with significantly higher frequencies of 4-year mortality, all-cause revascularization, stent thrombosis (PCI arm), and major adverse cardiac and cerebrovascular events. The presence of a TO was the strongest independent predictor of ICR after PCI (hazard ratio: 2.70, 95% confidence interval: 1.98 to 3.67, p < 0.001). Eight hundred and forty patients (PCI: 26.3%, CABG: 36.4%, p < 0.001) were identified to have 1,007 TOs, with 68.1% of TOs located in the proximal-mid coronary vasculature. The findings associating ICR (compared with CR) with higher frequencies of 4-year mortality and major adverse cardiac and cerebrovascular events remained consistent in the TO-treated groups in the PCI and CABG arms.CONCLUSIONS:Within the PCI and CABG arms of the all-comers SYNTAX trial, angiographically determined ICR has a detrimental impact on long-term clinical outcomes, including mortality. This effect remained consistent in patients with and without TOs.
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30.
  • Friedrich, Felix W., et al. (författare)
  • Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy
  • 2012
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 21:14, s. 3237-3254
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. HCM is caused by mutations in sarcomeric genes, but in 40 of patients, the mutation is not yet identified. We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct myopathies, sometimes associated with cardiomyopathy. We evaluated 121 HCM patients, devoid of a mutation in known disease genes. We identified three novel variants in FHL1 (c.134delA/K45Sfs, c.459CA/C153X and c.827GC/C276S). Whereas the c.459CA variant was associated with muscle weakness in some patients, the c.134delA and c.827GC variants were associated with isolated HCM. Gene transfer of the latter variants in C2C12 myoblasts and cardiac myocytes revealed reduced levels of FHL1 mutant proteins, which could be rescued by proteasome inhibition. Contractility measurements after adeno-associated virus transduction in rat-engineered heart tissue (EHT) showed: (i) higher and lower forces of contraction with K45Sfs and C276S, respectively, and (ii) prolonged contraction and relaxation with both mutants. All mutants except one activated the fetal hypertrophic gene program in EHT. In conclusion, this study provides evidence for FHL1 to be a novel gene for isolated HCM. These data, together with previous findings of proteasome impairment in HCM, suggest that FHL1 mutant proteins may act as poison peptides, leading to hypertrophy, diastolic dysfunction and/or altered contractility, all features of HCM.
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31.
  • Gau, Rémi, et al. (författare)
  • Brainhack : Developing a culture of open, inclusive, community-driven neuroscience
  • 2021
  • Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 109:11, s. 1769-1775
  • Tidskriftsartikel (refereegranskat)abstract
    • Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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32.
  • Goddi, Ciriaco, et al. (författare)
  • Polarimetric Properties of Event Horizon Telescope Targets from ALMA
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results from a full polarization study carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) during the first Very Long Baseline Interferometry (VLBI) campaign, which was conducted in 2017 April in the lambda 3 mm and lambda 1.3 mm bands, in concert with the Global mm-VLBI Array (GMVA) and the Event Horizon Telescope (EHT), respectively. We determine the polarization and Faraday properties of all VLBI targets, including Sgr A*, M87, and a dozen radio-loud active galactic nuclei (AGNs), in the two bands at several epochs in a time window of 10 days. We detect high linear polarization fractions (2%-15%) and large rotation measures (RM > 10(3.3)-10(5.5) rad m(-2)), confirming the trends of previous AGN studies at millimeter wavelengths. We find that blazars are more strongly polarized than other AGNs in the sample, while exhibiting (on average) order-of-magnitude lower RM values, consistent with the AGN viewing angle unification scheme. For Sgr A* we report a mean RM of (-4.2 0.3) x 10(5) rad m(-2) at 1.3 mm, consistent with measurements over the past decade and, for the first time, an RM of (-2.1 0.1) x 10(5) rad m(-2) at 3 mm, suggesting that about half of the Faraday rotation at 1.3 mm may occur between the 3 mm photosphere and the 1.3 mm source. We also report the first unambiguous measurement of RM toward the M87 nucleus at millimeter wavelengths, which undergoes significant changes in magnitude and sign reversals on a one year timescale, spanning the range from -1.2 to 0.3 x 10(5) rad m(-2) at 3 mm and -4.1 to 1.5 x 10(5) rad m(-2) at 1.3 mm. Given this time variability, we argue that, unlike the case of Sgr A*, the RM in M87 does not provide an accurate estimate of the mass accretion rate onto the black hole. We put forward a two-component model, comprised of a variable compact region and a static extended region, that can simultaneously explain the polarimetric properties observed by both the EHT (on horizon scales) and ALMA (which observes the combined emission from both components). These measurements provide critical constraints for the calibration, analysis, and interpretation of simultaneously obtained VLBI data with the EHT and GMVA.
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33.
  • Head, Stuart J., et al. (författare)
  • Coronary artery bypass grafting vs. percutaneous coronary intervention for patients with three-vessel disease : final five-year follow-up of the SYNTAX trial
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:40, s. 2821-2830
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Coronary artery bypass grafting (CABG) has been considered the standard of care for patients with three-vessel disease (3VD), but long-term comparative results from randomized trials of CABG vs. percutaneous coronary intervention (PCI) using drug-eluting stents (DES) remain limited. Methods and results Patients with de novo 3VD or left main disease were randomly assigned to PCI with the paclitaxel-eluting first-generation stent or CABG in the SYNTAX trial. This pre-specified analysis presents the 5-year outcomes of patients with 3VD (n = 1095). The rate of major adverse cardiac and cerebrovascular events (MACCE) was significantly higher in patients with PCI compared with CABG (37.5 vs. 24.2%, respectively; P < 0.001). Percutaneous coronary intervention as opposed to CABG resulted in significantly higher rates of the composite of death/stroke/myocardial infarction (MI) (22.0 vs. 14.0%, respectively; P < 0.001), all-cause death (14.6 vs. 9.2%, respectively; P = 0.006), MI (9.2 vs. 4.0%, respectively; P = 0.001), and repeat revascularization (25.4 vs. 12.6%, respectively; P < 0.001); however, stroke was similar between groups at 5 years (3.0 vs. 3.5%, respectively; P = 0.66). Results were dependent on lesion complexity (P for interaction = 0.12); in patients with a low (022) SYNTAX score, PCI vs. CABG resulted in similar rates of MACCE (33.3% vs. 26.8%, respectively; P = 0.21) but significantly more repeat revascularization (25.4% vs. 12.6%, respectively; P = 0.038), while in intermediate (2332) or high (>= 33) SYNTAX score terciles, CABG demonstrated clear superiority in terms of MACCE, death, MI, and repeat revascularization. Differences in MACCE between PCI and CABG were larger in diabetics [hazard ratio (HR) = 2.30] than non-diabetics (HR = 1.51), although the P for interaction failed to reach significance for MACCE (P for interaction = 0.095) or any of the other endpoints. Conclusion Five-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care as it resulted in significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar. For patients with low SYNTAX scores, PCI is an acceptable revascularization strategy, although at a price of significantly higher rates of repeat revascularization.
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34.
  • Hirsch, Jan-Mikael, et al. (författare)
  • A clinical evaluation of the Zygoma fixture: one year of follow-up at 16 clinics.
  • 2004
  • Ingår i: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 62:9 Suppl 2, s. 22-9
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To evaluate treatment outcome with Zygoma fixtures (Nobel Biocare, Göteborg, Sweden) with regard to fixture survival, patient satisfaction, and function of prosthesis replacement. MATERIALS AND METHODS: The treatment outcome of 76 patients treated with 145 Zygoma fixtures at 16 centers was evaluated. Patient's and dentist's evaluations of the functional and aesthetic outcome of the treatment were assessed at delivery of prosthesis and at the 1-year follow-up visit. At the 1-year follow-up visit, the status of the peri-implant mucosa around the abutments and the amount of plaque were registered. RESULTS: Sixty-six of the 76 patients, with 124 Zygoma fixtures supporting the prosthetic restorations, were evaluated at the 1-year follow-up. The overall survival rate for the Zygoma fixtures was 97.9% after 1-year of follow-up. Eighty percent of the patients were fully satisfied with both aesthetic and functional outcome at the time of prosthetic insertion and at the 1-year follow-up. All reported data from the dentists, with the exception of one restoration with several abutment screw loosenings, scored from acceptable to excellent for the aesthetic and functional outcome of the treatment. The status of peri-implant mucosa was recorded as normal in approximately 60% of the sites. Plaque, when present, was more often detected on the palatal surfaces compared with the buccal surfaces. CONCLUSION: This 1-year follow-up of Zygoma fixtures has shown good results with an acceptable number of minor complications and a majority of satisfied patients.
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35.
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36.
  • Hu, Zhicheng, et al. (författare)
  • Phenol-soluble modulin α and β display divergent roles in mice with staphylococcal septic arthritis.
  • 2022
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Phenol-soluble modulin α (PSMα) is identified as potent virulence factors in Staphylococcus aureus (S. aureus) infections. Very little is known about the role of PSMβ which belongs to the same toxin family. Here we compared the role of PSMs in S. aureus-induced septic arthritis in a murine model using three isogenic S. aureus strains differing in the expression of PSMs (Newman, Δpsmα, and Δpsmβ). The effects of PSMs on neutrophil NADPH-oxidase activity were determined in vitro. We show that the PSMα activates neutrophils via the formyl peptide receptor (FPR) 2 and reduces their NADPH-oxidase activity in response to the phorbol ester PMA. Despite being a poor neutrophil activator, PSMβ has the ability to reduce the neutrophil activating effect of PSMα and to partly reverse the effect of PSMα on the neutrophil response to PMA. Mice infected with S. aureus lacking PSMα had better weight development and lower bacterial burden in the kidneys compared to mice infected with the parental strain, whereas mice infected with bacteria lacking PSMβ strain developed more severe septic arthritis accompanied with higher IL-6 and KC. We conclude that PSMα and PSMβ play distinct roles in septic arthritis: PSMα aggravates systemic infection, whereas PSMβ protects arthritis development.
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37.
  • Iqbal, Javaid, et al. (författare)
  • Optimal Medical Therapy Improves Clinical Outcomes in Patients Undergoing Revascularization With Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting Insights From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial at the 5-Year Follow-Up
  • 2015
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 131:14, s. 1269-1277
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results-The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions-The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted.
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38.
  • Issaoun, Sara, et al. (författare)
  • Resolving the Inner Parsec of the Blazar J1924-2914 with the Event Horizon Telescope
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 934:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The blazar J1924-2914 is a primary Event Horizon Telescope (EHT) calibrator for the Galactic center's black hole Sagittarius A*. Here we present the first total and linearly polarized intensity images of this source obtained with the unprecedented 20 mu as resolution of the EHT. J1924-2914 is a very compact flat-spectrum radio source with strong optical variability and polarization. In April 2017 the source was observed quasi-simultaneously with the EHT (April 5-11), the Global Millimeter VLBI Array (April 3), and the Very Long Baseline Array (April 28), giving a novel view of the source at four observing frequencies, 230, 86, 8.7, and 2.3 GHz. These observations probe jet properties from the subparsec to 100 pc scales. We combine the multifrequency images of J1924-2914 to study the source morphology. We find that the jet exhibits a characteristic bending, with a gradual clockwise rotation of the jet projected position angle of about 90 degrees between 2.3 and 230 GHz. Linearly polarized intensity images of J1924-2914 with the extremely fine resolution of the EHT provide evidence for ordered toroidal magnetic fields in the blazar compact core.
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39.
  • Kappetein, Arie Pieter, et al. (författare)
  • Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease : 3-year follow-up of the SYNTAX trial
  • 2011
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:17, s. 2125-2134
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXUS Express stents. Methods and results: SYNTAX is an 85-centre randomized clinical trial (n = 1800). Prospectively screened, consecutive LM and/or 3VD patients were randomized if amenable to equivalent revascularization using either technique; if not, they were entered into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At 3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke, myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P < 0.001], repeat revascularization (10.7 vs. 19.7%, P < 0.001), and MI (3.6 vs. 7.1%, P = 0.002) were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0 vs. 14.1%, P = 0.21) and stroke alone (3.4 vs. 2.0%, P = 0.07) were not significantly different between treatment groups. Major adverse cardiac and cerebrovascular event rates were not significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P = 0.20) but were higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P < 0.001). Conclusions: At 3 years, MACCE was significantly higher in PCI-compared with CABG-treated patients. In patients with less complex disease (low SYNTAX scores for 3VD or low/intermediate terciles for LM patients), PCI is an acceptable revascularization, although longer follow-up is needed to evaluate these two revascularization strategies.
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40.
  • Lu, R.S., et al. (författare)
  • A ring-like accretion structure in M87 connecting its black hole and jet
  • 2023
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 616:7958, s. 686-690
  • Tidskriftsartikel (refereegranskat)abstract
    • The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
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41.
  • Mack, Michael J, et al. (författare)
  • Analysis of Stroke Occurring in the SYNTAX Trial Comparing Coronary Artery Bypass Surgery and Percutaneous Coronary Intervention in the Treatment of Complex Coronary Artery Disease
  • 2013
  • Ingår i: JACC. Cardiovascular interventions. - : Elsevier BV. - 1936-8798. ; 6:4, s. 344-354
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: This study sought to analyze stroke rates in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial's randomized and registry cohorts of patients being treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for treatment of complex coronary artery disease.BACKGROUND: The SYNTAX trial compared PCI to CABG in patients with de novo 3-vessel and/or left main coronary disease.METHODS: The SYNTAX randomized trial was conducted at 85 U.S. and European sites (n = 1,800). All strokes (up to 4 years) were independently adjudicated by a clinical events committee that included a neurologist. An additional 1,077 (of which 644 were followed for 5 years) and 198 patients were included in the CABG and PCI registries, respectively.RESULTS: In the randomized cohort, 31 CABG and 19 PCI patients experienced 33 and 20 strokes post-randomization at 4-year follow-up, respectively (p = 0.062). Three strokes occurred pre-procedurally but following randomization in CABG-treated patients. After CABG, a large proportion of strokes occurred acutely (0 to 30 days: 9 of 33), whereas in the PCI arm, most strokes occurred >30 days after the procedure (18 of 20). Stroke resulted in death in 3 patients in both the PCI and CABG groups. Of the patients who developed stroke, 68% (21 of 31) in the CABG group had residual deficits at discharge; in the PCI group, 47% (9 of 19) had residual deficits. In a multivariate analysis, treatment with CABG was not significantly associated with increased stroke rates (odds ratio: 1.67, 95% confidence interval: 0.93 to 3.01, p = 0.089). The incidence and outcomes of stroke were similar in the randomized trial and registries.CONCLUSIONS: There is a higher risk of periprocedural stroke in patients undergoing CABG versus PCI; however, the risk converges over the first 4 years of follow-up. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).
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42.
  • Manes, Martina, et al. (författare)
  • Closing Data Gaps and Paving the Way for Pan-European Fire Safety Efforts : Part I—Overview of Current Practices for Fire Statistics
  • 2023
  • Ingår i: Fire Technology. - 0015-2684. ; 59:4, s. 1925-1968
  • Tidskriftsartikel (refereegranskat)abstract
    • The analysis of the current state of fire statistics and data collection in Europe and other countries is needed to increase awareness of how fire incidents affect buildings and to support pan-European fire prevention and fire mitigation measures. The terminology and data collected regarding fire incidents in buildings in the EU Member States were mapped to obtain meaningful datasets to determine common terminology, collection methodology, and data interpretation system. An extensive literature review showed that fire data collection systems have been instrumental in informing firefighting strategies, evidence-based planning, prevention, and educational programmes. Differences and similarities between fire data collection systems were also investigated. The amount and quality of the information in fire statistical recording systems appear to be influenced by the complexity and structure with which the data are collected. The analysis also examined the existing fire statistics in the EU Member States and a few other countries. Finally, a detailed investigation of the number of fires, fire deaths, and injuries from 2009 to 2018 in several countries was examined based on data from a report by CTIF. The trends showed differences attributable to the existing fire statistical practices in terms of terminology and data collection, and interpretation. Part II proposes a common terminology for selected fire statistical variables. The results provide relevant information regarding fire safety at the European level and should be used to guide the development of more uniform fire statistics across Europe.
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43.
  •  
44.
  • Milojevic, Milan, et al. (författare)
  • Causes of Death Following PCI Versus CABG in Complex CAD 5-Year Follow-Up of SYNTAX
  • 2016
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 67:1, s. 42-55
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI). OBJECTIVES The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients. METHODS An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths. RESULTS In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores. CONCLUSIONS During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)
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45.
  •  
46.
  • Mohr, Friedrich W., et al. (författare)
  • Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease : 5-year follow-up of the randomised, clinical SYNTAX trial
  • 2013
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 381:9867, s. 629-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We report the 5-year results of the SYNTAX trial, which compared coronary artery bypass graft surgery (CABG) with percutaneous coronary intervention (PCI) for the treatment of patients with left main coronary disease or three-vessel disease, to confirm findings at 1 and 3 years. Methods The randomised, clinical SYNTAX trial with nested registries took place in 85 centres in the USA and Europe. A cardiac surgeon and interventional cardiologist at each centre assessed consecutive patients with de-novo three-vessel disease or left main coronary disease to determine suitability for study treatments. Eligible patients suitable for either treatment were randomly assigned (1: 1) by an interactive voice response system to either PCI with a first-generation paclitaxel-eluting stent or to CABG. Patients suitable for only one treatment option were entered into either the PCI-only or CABG-only registries. We analysed a composite rate of major adverse cardiac and cerebrovascular events (MACCE) at 5-year follow-up by Kaplan-Meier analysis on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00114972. Findings 1800 patients were randomly assigned to CABG (n=897) or PCI (n=903). More patients who were assigned to CABG withdrew consent than did those assigned to PCI (50 vs 11). After 5 years' follow-up, Kaplan-Meier estimates of MACCE were 26.9% in the CABG group and 37.3% in the PCI group (p<0.0001). Estimates of myocardial infarction (3.8% in the CABG group vs 9.7% in the PCI group; p<0.0001) and repeat revascularisation (13.7% vs 25.9%; p<0.0001) were significantly increased with PCI versus CABG. All-cause death (11.4% in the CABG group vs 13.9% in the PCI group; p=0.10) and stroke (3.7% vs 2.4%; p=0.09) were not significantly different between groups. 28.6% of patients in the CABG group with low SYNTAX scores had MACCE versus 32.1% of patients in the PCI group (p=0.43) and 31.0% in the CABG group with left main coronary disease had MACCE versus 36.9% in the PCI group (p=0.12); however, in patients with intermediate or high SYNTAX scores, MACCE was significantly increased with PCI (intermediate score, 25.8% of the CABG group vs 36.0% of the PCI group; p=0.008; high score, 26.8% vs 44.0%; p<0.0001). Interpretation CABG should remain the standard of care for patients with complex lesions (high or intermediate SYNTAX scores). For patients with less complex disease (low SYNTAX scores) or left main coronary disease (low or intermediate SYNTAX scores), PCI is an acceptable alternative. All patients with complex multivessel coronary artery disease should be reviewed and discussed by both a cardiac surgeon and interventional cardiologist to reach consensus on optimum treatment.
  •  
47.
  • Morice, Marie-Claude, et al. (författare)
  • Angiographic outcomes following stenting or coronary artery bypass surgery of the left main coronary artery : fifteen-month outcomes from the synergy between PCI with TAXUS express and cardiac surgery left main angiographic substudy (SYNTAX-LE MANS)
  • 2011
  • Ingår i: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - 1969-6213. ; 7:6, s. 670-679
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The SYNTAX-LE MANS substudy prospectively evaluated 15-month angiographic and clinical outcomes in patients with treated left main (LM) disease. METHODS AND RESULTS: In the SYNTAX trial, 1,800 patients with three-vessel and/or LM disease were randomised to either CABG or PCI; of these, 271 LM patients were prospectively assigned to receive a 15-month angiogram. The primary endpoint for the CABG arm was the ratio of ≥50% to <100% obstructed/occluded grafts bypassing LM lesions to the number placed. The primary endpoint for the PCI arm was the proportion of patients with ≤50% diameter stenosis ('patent' stents) of treated LM lesions. Per protocol, no formal comparison between CABG and PCI arms was intended based on the differing primary endpoints. Available 15-month angiograms were analysed for 114 CABG and 149 PCI patients. At 15 months, 9.9% (26/263) of CABG grafts were 100% occluded and an additional 5.7% (15/263) were ≥50% to <100% occluded. Overall, 27.2% (31/114) of patients had ≥1 obstructed/occluded graft. The 15-month CABG MACCE rate was 8.8% (10/114) and MACCE at 15 months was not significantly associated with graft obstruction/occlusion (p=0.85). In the PCI arm, 92.4% (134/145) of patients had ≤50% diameter LM stenosis at 15 months (89.7% [87/97] distal LM lesions and 97.9% [47/48] non-distal LM lesions). The 15-month PCI MACCE rate was 12.8% (20/156) and this was significantly associated with lack of stent patency at 15 months (p<0.001), mainly due to repeat revascularisation. CONCLUSIONS: At 15 months, 15.6% (41/263) of grafts were at least 50% obstructed but this was not significantly associated with MACCE; 92.4% (134/145) of patients had stents that remained patent at 15 months, and stent restenosis was significantly associated with MACCE, predominantly due to revascularisation.
  •  
48.
  • Morice, Marie-Claude, et al. (författare)
  • Five-Year Outcomes in Patients With Left Main Disease Treated With Either Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery Trial
  • 2014
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 129:23, s. 2388-2394
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Current guidelines recommend coronary artery bypass graft surgery (CABG) when treating significant de novo left main coronary artery (LM) stenosis; however, percutaneous coronary intervention (PCI) has a class IIa indication for unprotected LM disease in selected patients. This analysis compares 5-year clinical outcomes in PCI-and CABG-treated LM patients in the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) trial, the largest trial in this group to date. Methods and Results-The SYNTAX trial randomly assigned 1800 patients with LM or 3-vessel disease to receive either PCI (with TAXUS Express paclitaxel-eluting stents) or CABG. The unprotected LM cohort (N=705) was predefined and powered. Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9% in PCI patients and 31.0% in CABG patients (hazard ratio, 1.23 [95% confidence interval, 0.95-1.59]; P=0.12). Mortality rate was 12.8% and 14.6% in PCI and CABG patients, respectively (hazard ratio, 0.88 [95% confidence interval, 0.58-1.32]; P=0.53). Stroke was significantly increased in the CABG group (PCI 1.5% versus CABG 4.3%; hazard ratio, 0.33 [95% confidence interval, 0.12-0.92]; P=0.03) and repeat revascularization in the PCI arm (26.7% versus 15.5%; hazard ratio, 1.82 [95% confidence interval, 1.28-2.57]; P<0.01). Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores (>= 33). Conclusions-At 5 years, no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups. PCI-treated patients had a lower stroke but a higher revascularization rate versus CABG. These results suggest that both treatments are valid options for LM patients. The extent of disease should accounted for when choosing between surgery and PCI, because patients with high SYNTAX scores seem to benefit more from surgery compared with those in the lower tertiles.
  •  
49.
  • Morice, Marie-Claude, et al. (författare)
  • Outcomes in Patients With De Novo Left Main Disease Treated With Either Percutaneous Coronary Intervention Using Paclitaxel-Eluting Stents or Coronary Artery Bypass Graft Treatment in the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial
  • 2010
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 121:24, s. 2645-2653
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prospective, multinational, randomized Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial was designed to assess the optimal revascularization strategy between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), for patients with left main (LM) and/or 3-vessel coronary disease. Methods and Results: This observational hypothesis-generating analysis reports the results of a prespecified powered subgroup of 705 randomized patients who had LM disease among the 1800 patients with de novo 3-vessel disease and/or LM disease randomized to PCI with paclitaxel-eluting stents or CABG in the SYNTAX trial. Major adverse cardiac and cerebrovascular event rates at 1 year in LM patients were similar for CABG and PCI (13.7% versus 15.8%; Delta 2.1% [95% confidence interval -3.2% to 7.4%]; P = 0.44). At 1 year, stroke was significantly higher in the CABG arm (2.7% versus 0.3%; Delta-2.4% [95% confidence interval -4.2% to -0.1%]; P = 0.009]), whereas repeat revascularization was significantly higher in the PCI arm (6.5% versus 11.8%; Delta 5.3% [95% confidence interval 1.0% to 9.6%]; P = 0.02); there was no observed difference between groups for other end points. When patients were scored for anatomic complexity, those with higher baseline SYNTAX scores had significantly worse outcomes with PCI than did patients with low or intermediate SYNTAX scores; outcomes for patients with CABG did not correlate with baseline SYNTAX score, but baseline EuroSCORE significantly predicted outcomes for both treatments. Conclusions: Patients with LM disease who had revascularization with PCI had safety and efficacy outcomes comparable to CABG at 1 year; longer follow-up is required to determine whether these 2 revascularization strategies offer comparable medium-term outcomes in this group of complex patients.
  •  
50.
  • Narayan, Ramesh, et al. (författare)
  • The Polarized Image of a Synchrotron-emitting Ring of Gas Orbiting a Black Hole
  • 2021
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 912:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Synchrotron radiation from hot gas near a black hole results in a polarized image. The image polarization is determined by effects including the orientation of the magnetic field in the emitting region, relativistic motion of the gas, strong gravitational lensing by the black hole, and parallel transport in the curved spacetime. We explore these effects using a simple model of an axisymmetric, equatorial accretion disk around a Schwarzschild black hole. By using an approximate expression for the null geodesics derived by Beloborodov and conservation of the Walker-Penrose constant, we provide analytic estimates for the image polarization. We test this model using currently favored general relativistic magnetohydrodynamic simulations of M87*, using ring parameters given by the simulations. For a subset of these with modest Faraday effects, we show that the ring model broadly reproduces the polarimetric image morphology. Our model also predicts the polarization evolution for compact flaring regions, such as those observed from Sgr A* with GRAVITY. With suitably chosen parameters, our simple model can reproduce the EVPA pattern and relative polarized intensity in Event Horizon Telescope images of M87*. Under the physically motivated assumption that the magnetic field trails the fluid velocity, this comparison is consistent with the clockwise rotation inferred from total intensity images.
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