| 1. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 2. |
- Bernatsky, Sasha, et al.
(författare)
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Lymphoma risk in systemic lupus: effects of disease activity versus treatment
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:1, s. 138-142
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
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| 3. |
- Feroci, M., et al.
(författare)
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LOFT - The large observatory for x-ray timing
- 2012
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Konferensbidrag (refereegranskat)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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| 4. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 5. |
- Head, Stuart J., et al.
(författare)
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Coronary artery bypass grafting vs. percutaneous coronary intervention for patients with three-vessel disease : final five-year follow-up of the SYNTAX trial
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:40, s. 2821-2830
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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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| 6. |
- Roth, Lorenz, et al.
(författare)
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A phenomenological model of Io’s UV aurora based on HST/STIS observations
- 2014
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Ingår i: Icarus. - : Elsevier. - 0019-1035 .- 1090-2643. ; 228, s. 386-406
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Tidskriftsartikel (refereegranskat)abstract
- We have carried out a comprehensive analysis of a large set of spatially resolved observations of Io's OI 1304. Å, OI] 1356. Å, SI 1479. Å and SI] 1900. Å aurora taken by the Space Telescope Imaging Spectrograph (STIS) of the Hubble Space Telescope (HST) between 1997 and 2001. We find that the variability of the observed morphologies can be solely explained by the changes of the plasma and magnetic field environment of the Io torus and by the viewing perspective. The variations in brightness are strongly correlated with the periodic variations of the ambient electron density. Based on these findings we develop a phenomenological model for the spatial distribution of the oxygen and sulfur emissions in Io's vicinity. Taking into account Io's position with respect to the plasma torus, the orientation of Jupiter's magnetic field and the viewing perspective of the observation, the model calculates the auroral morphology and brightness. By fitting the model parameters to the observations we find that the model is able to reproduce the main features in all images obtained over a period of five years with one parameter set for each emission multiplet. The spatial distribution of the OI] 1356. Å, OI 1304. Å, SI 1479. Å, and SI] 1900. Å multiplets are shown to be very similar. In contrast to previous investigations, the model results reveal that the majority of the radiation from the bound atmosphere is emitted within 100. km above the surface. The equatorial aurora spots extend far into the wake region explaining observed features in the downstream region. The relative brightness of two the equatorial spots is best explained by our model if the emission on the day-side flank of Io is higher by a factor of ~1.5 with respect to the nightside flank. The measured brightness during an observation in eclipse is significantly lower than expected from the fitted model. The day-night asymmetry and the brightness decrease in eclipse support the idea of a wide collapse of Io's atmosphere in shadow. Since our phenomenological aurora model is able to reproduce the main features of the observed morphology by taking into account the variations of the magnetospheric parameters, it can be applied to predict the emission for future UV aurora observations for a given time and position of the observer.
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| 7. |
- Roth, Lorenz, et al.
(författare)
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Orbital apocenter is not a sufficient condition for HST/STIS detection of Europa's water vapor aurora
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:48, s. E5123-E5132
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Tidskriftsartikel (refereegranskat)abstract
- We report far-ultraviolet observations of Jupiter's moon Europa taken by Space Telescope Imaging Spectrograph (STIS) of the Hubble Space Telescope (HST) in January and February 2014 to test the hypothesis that the discovery of a water vapor aurora in December 2012 by local hydrogen (H) and oxygen (O) emissions with the STIS originated from plume activity possibly correlated with Europa's distance from Jupiter through tidal stress variations. The 2014 observations were scheduled with Europa near the apocenter similar to the orbital position of its previous detection. Tensile stresses on south polar fractures are expected to be highest in this orbital phase, potentially maximizing the probability for plume activity. No local H and O emissions were detected in the new STIS images. In the south polar region where the emission surpluses were observed in 2012, the brightnesses are sufficiently low in the 2014 images to be consistent with any H2O abundance from(0-5)x10(15) cm(-2). Large high-latitude plumes should have been detectable by the STIS, independent of the observing conditions and geometry. Because electron excitation of water vapor remains the only viable explanation for the 2012 detection, the new observations indicate that although the same orbital position of Europa for plume activity may be a necessary condition, it is not a sufficient condition. However, the December 2012 detection of coincident HI Lyman-alpha and OI 1304-angstrom emission surpluses in an similar to 200-km high region well separated above Europa's limb is a firm result and not invalidated by our 2014 STIS observations.
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| 8. |
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| 9. |
- Saur, Joachim, et al.
(författare)
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HUBBLE SPACE TELESCOPE/ADVANCED CAMERA FOR SURVEYS OBSERVATIONS OF EUROPA’S ATMOSPHERIC ULTRAVIOLET EMISSION AT EASTERN ELONGATION
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 738:2
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Tidskriftsartikel (refereegranskat)abstract
- We report results of a Hubble Space Telescope (HST) campaign with the Advanced Camera for Surveys to observe Europa at eastern elongation, i.e., Europa's leading side, on 2008 June 29. With five consecutive HST orbits, we constrain Europa's atmospheric OI 1304 angstrom and OI 1356 angstrom emissions using the prism PR130L. The total emissions of both oxygen multiplets range between 132 +/- 14 and 226 +/- 14 Rayleigh. An additional systematic error with values on the same order as the statistical errors may be due to uncertainties in modeling the reflected light from Europa's surface. The total emission also shows a clear dependence of Europa's position with respect to Jupiter's magnetospheric plasma sheet. We derive a lower limit for the O-2 column density of 6 x 10(18) m(-2). Previous observations of Europa's atmosphere with the Space Telescope Imaging Spectrograph in 1999 of Europa's trailing side show an enigmatic surplus of radiation on the anti-Jovian side within the disk of Europa. With emission from a radially symmetric atmosphere as a reference, we searched for an anti-Jovian versus sub-Jovian asymmetry with respect to the central meridian on the leading side and found none. Likewise, we searched for departures from a radially symmetric atmospheric emission and found an emission surplus centered around 90 degrees west longitude, for which plausible mechanisms exist. Previous work about the possibility of plumes on Europa due to tidally driven shear heating found longitudes with strongest local strain rates which might be consistent with the longitudes of maximum UV emissions. Alternatively, asymmetries in Europa's UV emission can also be caused by inhomogeneous surface properties, an optically thick atmospheric contribution of atomic oxygen, and/or by Europa's complex plasma interaction with Jupiter's magnetosphere.
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| 10. |
- Simonis, Helmut, et al.
(författare)
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A Generic Visualization Platform for CP
- 2010. - 7
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Konferensbidrag (refereegranskat)abstract
- In this paper we describe the design and implementation of CP-VIZ, a generic visualization platform for constraint programming. It provides multiple views to show the search tree, and the state of constraints and variables for a postmortem analysis of a constraint program. Different to most previous visualization tools, it is system independent, using a light-weight, intermediate XML format to exchange information between solvers and the visualization tools. CP-VIZ is available under an open-source licence, and has already been interfaced to four different constraint systems.
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