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| 5. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 6. |
- Fomalont, E. B., et al.
(författare)
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THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
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Tidskriftsartikel (refereegranskat)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 7. |
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| 8. |
- Aartsen, M. G., et al.
(författare)
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Constraints on Galactic Neutrino Emission with Seven Years of IceCube Data
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 849:1
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Tidskriftsartikel (refereegranskat)abstract
- The origins of high-energy astrophysical neutrinos remain a mystery despite extensive searches for their sources. We present constraints from seven years of IceCube Neutrino Observatory muon data on the neutrino flux coming from the Galactic plane. This flux is expected from cosmic-ray interactions with the interstellar medium or near localized sources. Two methods were developed to test for a spatially extended flux from the entire plane, both of which are maximum likelihood fits but with different signal and background modeling techniques. We consider three templates for Galactic neutrino emission based primarily on gamma-ray observations and models that cover a wide range of possibilities. Based on these templates and in the benchmark case of an unbroken E-2.5 power-law energy spectrum, we set 90% confidence level upper limits, constraining the possible Galactic contribution to the diffuse neutrino flux to be relatively small, less than 14% of the flux reported in Aartsen et al. above 1 TeV. A stacking method is also used to test catalogs of known high-energy Galactic gamma-ray sources.
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| 9. |
- Delabrouille, J., et al.
(författare)
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Exploring cosmic origins with CORE : Survey requirements and mission design
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology, including: what physical process gave birth to the Universe we see today? What are the dark matter and dark energy that seem to constitute 95% of the energy density of the Universe? Do we need extensions to the standard model of particle physics and fundamental interactions? Is the ACDM cosmological scenario correct, or are we missing an essential piece of the puzzle? In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the CORE space mission proposed to ESA in answer to the M5 call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. CORE has 19 frequency channels, distributed over a broad frequency range, spanning the 60-600 GHz interval, to control astrophysical foreground emission. The angular resolution ranges from 2' to 18', and the aggregate CMB sensitivity is about 2 mu K.arcmin. The observations are made with a single integrated focal-plane instrument, consisting of an array of 2100 cryogenically-cooled, linearly-polarised detectors at the focus of a 1.2-m aperture cross-Dragone telescope. The mission is designed to minimise all sources of systematic effects, which must be controlled so that no more than 10(-4) of the intensity leaks into polarisation maps, and no more than about 1% of E-type polarisation leaks into B-type modes. CORE observes the sky from a large Lissajous orbit around the Sun-Earth L2 point on an orbit that offers stable observing conditions and avoids contamination from sidelobe pick-up of stray radiation originating from the Sun, Earth, and Moon. The entire sky is observed repeatedly during four years of continuous scanning, with a combination of three rotations of the spacecraft over different timescales. With about 50% of the sky covered every few days, this scan strategy provides the mitigation of systematic effects and the internal redundancy that are needed to convincingly extract the primordial B-mode signal on large angular scales, and check with adequate sensitivity the consistency of the observations in several independent data subsets. CORE is designed as a near-ultimate CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation science and cannot be obtained by any other means than a dedicated space mission. It will provide well-characterised, highly-redundant multi-frequency observations of polarisation at all the scales where foreground emission and cosmic variance dominate the final uncertainty for obtaining precision CMB science, as well as 2' angular resolution maps of high-frequency foreground emission in the 300-600 GHz frequency range, essential for complementarity with future ground-based observations with large telescopes that can observe the CMB with the same beamsize.
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| 10. |
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| 11. |
- Finelli, F., et al.
(författare)
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Exploring cosmic origins with CORE : Inflation
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2018:4
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Tidskriftsartikel (refereegranskat)abstract
- We forecast the scientific capabilities to improve our understanding of cosmic inflation of CORE, a proposed CMB space satellite submitted in response to the ESA fifth call for a medium-size mission opportunity. The CORE satellite will map the CMB anisotropies in temperature and polarization in 19 frequency channels spanning the range 60-600 GHz. CORE will have an aggregate noise sensitivity of 1.7 mu K.arcmin and an angular resolution of 5' at 200 GHz. We explore the impact of telescope size and noise sensitivity on the inflation science return by making forecasts for several instrumental configurations. This study assumes that the lower and higher frequency channels suffice to remove foreground contaminations and complements other related studies of component separation and systematic effects, which will be reported in other papers of the series Exploring Cosmic Origins with CORE. We forecast the capability to determine key inflationary parameters, to lower the detection limit for the tensor-to-scalar ratio down to the 10(-3) level, to chart the landscape of single field slow-roll inflationary models, to constrain the epoch of reheating, thus connecting inflation to the standard radiation-matter dominated Big Bang era, to reconstruct the primordial power spectrum, to constrain the contribution from isocurvature perturbations to the 10(-3) level, to improve constraints on the cosmic string tension to a level below the presumptive GUT scale, and to improve the current measurements of primordial non-Gaussianities down to the f(NL)(local) < 1 level. For all the models explored, CORE alone will improve significantly on the present constraints on the physics of inflation. Its capabilities will be further enhanced by combining with complementary future cosmological observations.
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| 12. |
- Natoli, P., et al.
(författare)
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Exploring cosmic origins with CORE : Mitigation of systematic effects
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We present an analysis of the main systematic effects that could impact the measurement of CMB polarization with the proposed CORE space mission. We employ timeline to-map simulations to verify that the CORE instrumental set-up and scanning strategy allow us to measure sky polarization to a level of accuracy adequate to the mission science goals. We also show how the CORE observations can be processed to mitigate the level of contamination by potentially worrying systematics, including intensity-to-polarization leakage due to bandpass mismatch, asymmetric main beams, pointing errors and correlated noise. We use analysis techniques that are well validated on data from current missions such as Planck to demonstrate how the residual contamination of the measurements by these effects can be brought to a level low enough not to hamper the scientific capability of the mission, nor significantly increase the overall error budget. We also present a prototype of the CORE photometric calibration pipeline, based on that used for Planck, and discuss its robustness to systematics, showing how CORE can achieve its calibration requirements. While a fine-grained assessment of the impact of systematics requires a level of knowledge of the system that can only be achieved in a future study phase, the analysis presented here strongly suggests that the main areas of concern for the CORE mission can be addressed using existing knowledge, techniques and algorithms.
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| 13. |
- Osborn, H. P., et al.
(författare)
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The PDS 110 observing campaign - photometric and spectroscopic observations reveal eclipses are aperiodic
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 485:2, s. 1614-1625
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Tidskriftsartikel (refereegranskat)abstract
- PDS 110 is a young disc-hosting star in the Orion OB1A association. Two dimming events of similar depth and duration were seen in 2008 (WASP) and 2011 (KELT), consistent with an object in a closed periodic orbit. In this paper, we present data from a ground-based observing campaign designed to measure the star both photometrically and spectroscopically during the time of predicted eclipse in 2017 September. Despite high-quality photometry, the predicted eclipse did not occur, although coherent structure is present suggesting variable amounts of stellar flux or dust obscuration. We also searched for radial velocity (RV) oscillations caused by any hypothetical companion and can rule out close binaries to 0.1Ms. Asearch of Sonneberg plate archive data also enabled us to extend the photometric baseline of this star back more than 50 yr, and similarly does not re-detect any deep eclipses. Taken together, they suggest that the eclipses seen in WASP and KELT photometry were due to aperiodic events. It would seem that PDS 110 undergoes stochastic dimmings that are shallower and of shorter duration than those of UX Ori variables, but may have a similar mechanism.
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| 14. |
- De Zotti, G., et al.
(författare)
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Exploring cosmic origins with CORE : Extragalactic sources in cosmic microwave background maps
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the potential of a next generation space-borne Cosmic Microwave Background (CMB) experiment for studies of extragalactic sources. Our analysis has particular bearing on the definition of the future space project, CORE, that has been submitted in response to ESA's call for a Medium-size mission opportunity as the successor of the Planck satellite. Even though the effective telescope size will be somewhat smaller than that of Planck, CORE will have a considerably better angular resolution at its highest frequencies, since, in contrast with Planck, it will be diffraction limited at all frequencies. The improved resolution implies a considerable decrease of the source confusion, i.e. substantially fainter detection limits. In particular, CORE will detect thousands of strongly lensed high-z galaxies distributed over the full sky. The extreme brightness of these galaxies will make it possible to study them, via follow-up observations, in extraordinary detail. Also, the CORE resolution matches the typical sizes of high-z galaxy proto-clusters much better than the Planck resolution, resulting in a much higher detection efficiency; these objects will be caught in an evolutionary phase beyond the reach of surveys in other wavebands. Furthermore, CORE will provide unique information on the evolution of the star formation in virialized groups and clusters of galaxies up to the highest possible redshifts. Finally, thanks to its very high sensitivity, CORE will detect the polarized emission of thousands of radio sources and, for the first time, of dusty galaxies, at mm and sub-mm wavelengths, respectively.
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| 15. |
- Di Valentino, E., et al.
(författare)
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Exploring cosmic origins with CORE : Cosmological parameters
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We forecast the main cosmological parameter constraints achievable with the CORE space mission which is dedicated to mapping the polarisation of the Cosmic Microwave Background (CMB). CORE was recently submitted in response to ESA's fifth call for medium-sized mission proposals (M5). Here we report the results from our pre-submission study of the impact of various instrumental options, in particular the telescope size and sensitivity level, and review the great, transformative potential of the mission as proposed. Specifically, we assess the impact on a broad range of fundamental parameters of our Universe as a function of the expected CMB characteristics, with other papers in the series focusing on controlling astrophysical and instrumental residual systematics. In this paper, we assume that only a few central CORE frequency channels are usable for our purpose, all others being devoted to the cleaning of astrophysical contaminants. On the theoretical side, we assume ACDM as our general framework and quantify the improvement provided by CORE over the current constraints from the Planck 2015 release. We also study the joint sensitivity of CORE and of future Baryon Acoustic Oscillation and Large Scale Structure experiments like DESI and Euclid. Specific constraints on the physics of inflation are presented in another paper of the series. In addition to the six parameters of the base ACDM, which describe the matter content of a spatially flat universe with adiabatic and scalar primordial fluctuations from inflation, we derive the precision achievable on parameters like those describing curvature, neutrino physics, extra light relics, primordial helium abundance, dark matter annihilation, recombination physics, variation of fundamental constants, dark energy, modified gravity, reionization and cosmic birefringence. In addition to assessing the improvement on the precision of individual parameters, we also forecast the post-CORE overall reduction of the allowed parameter space with figures of merit for various models increasing by as much as similar to 10(7) as compared to Planck 2015, and 10(5) with respect to Planck 2015 + future BAO measurements.
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| 16. |
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| 17. |
- Burigana, C., et al.
(författare)
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Exploring cosmic origins with CORE : Effects of observer peculiar motion
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the effects on the cosmic microwave background (CMB), cosmic infrared background (CIB), and thermal Sunyaev-Zeldovich effect due to the peculiar motion of an observer with respect to the CMB rest frame, which induces boosting effects. After a brief review of the current observational and theoretical status, we investigate the scientific perspectives opened by future CMB space missions, focussing on the Cosmic Origins Explorer (CORE) proposal. The improvements in sensitivity offered by a mission like CORE, together with its high resolution over a wide frequency range, will provide a more accurate estimate of the CMB dipole. The extension of boosting effects to polarization and cross-correlations will enable a more robust determination of purely velocity-driven effects that are not degenerate with the intrinsic CMB dipole, allowing us to achieve an overall signal-to-noise ratio of 13; this improves on the Planck detection and essentially equals that of an ideal cosmic variance-limited experiment up to a multipole l similar or equal to 2000. Precise inter-frequency calibration will offer the opportunity to constrain or even detect CMB spectral distortions, particularly from the cosmological reionization epoch, because of the frequency dependence of the dipole spectrum, without resorting to precise absolute calibration. The expected improvement with respect to COBE-FIRAS in the recovery of distortion parameters (which could in principle be a factor of several hundred for an ideal experiment with the CORE configuration) ranges from a factor of several up to about 50, depending on the quality of foreground removal and relative calibration. Even in the case of similar or equal to 1% accuracy in both foreground removal and relative calibration at an angular scale of 1 degrees, we find that dipole analyses for a mission like CORE will be able to improve the recovery of the CIB spectrum amplitude by a factor similar or equal to 17 in comparison with current results based on COBE-FIRAS. In addition to the scientific potential of a mission like CORE for these analyses, synergies with other planned and ongoing projects are also discussed.
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| 18. |
- Challinor, A., et al.
(författare)
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Exploring cosmic origins with CORE : Gravitational lensing of the CMB
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- Lensing of the cosmic microwave background (CMB) is now a well-developed probe of the clustering of the large-scale mass distribution over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission will allow production of a clean map of the lensing deflections over nearly the full-sky. The number of high-SAN modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that will follow from its power spectrum and the cross-correlation with other clustering data. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous measurements of the baryon acoustic oscillation feature in the clustering of galaxies, three times smaller than the minimum total mass allowed by neutrino oscillation measurements. Lensing has applications across many other science goals of CORE, including the search for B-mode polarization from primordial gravitational waves. Here, lens-induced B-modes will dominate over instrument noise, limiting constraints on the power spectrum amplitude of primordial gravitational waves. With lensing reconstructed by CORE, one can delens the observed polarization internally, reducing the lensing B-mode power by 60 %. This can be improved to 70 % by combining lensing and measurements of the cosmic infrared background from CORE, leading to an improvement of a factor of 2.5 in the error on the amplitude of primordial gravitational waves compared to no delensing (in the null hypothesis of no primordial B-modes). Lensing measurements from CORE will allow calibration of the halo masses of the tens of thousands of galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. The 19 frequency channels proposed for CORE will allow accurate removal of Galactic emission from CMB maps. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE.
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| 19. |
- Remazeilles, M., et al.
(författare)
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Exploring cosmic origins with CORE : B-mode component separation
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that, for the baseline design of the CORE satellite mission, the polarized foregrounds can be controlled at the level required to allow the detection of the primordial cosmic microwave background (CMB) B-mode polarization with the desired accuracy at both reionization and recombination scales, for tensor-to-scalar ratio values of r greater than or similar to 5 x 10(-3). We consider detailed sky simulations based on state-of-the-art CMB observations that consist of CMB polarization with tau = 0.055 and tensor-to-scalar values ranging from r = 10(-2) to 10(-3), Galactic synchrotron, and thermal dust polarization with variable spectral indices over the sky, polarized anomalous microwave emission, polarized infrared and radio sources, and gravitational lensing effects. Using both parametric and blind approaches, we perform full component separation and likelihood analysis of the simulations, allowing us to quantify both uncertainties and biases on the reconstructed primordial B-modes. Under the assumption of perfect control of lensing effects, CORE would measure an unbiased estimate of r = (5 +/- 0.4) x 10(-3) after foreground cleaning. In the presence of both gravitational lensing effects and astrophysical foregrounds, the significance of the detection is lowered, with CORE achieving a 4 sigma-measurement of r = 5 x 10(-3) after foreground cleaning and 60% de lensing. For lower tensor-to-scalar ratios (r = 10(-3)) the overall uncertainty on r is dominated by foreground residuals, not by the 40% residual of lensing cosmic variance. Moreover, the residual contribution of unprocessed polarized point-sources can be the dominant foreground contamination to primordial B-modes at this r level, even on relatively large angular scales, l similar to 50. Finally, we report two sources of potential bias for the detection of the primordial B-modes by future CMB experiments: (i) the use of incorrect foreground models, e.g. a modelling error of Delta beta(s) = 0.02 on the synchrotron spectral indices may result in an excess in the recovered reionization peak corresponding to an effective Delta r > 10(-3); (ii) the average of the foreground line-of-sight spectral indices by the combined effects of pixelization and beam convolution, which adds an effective curvature to the foreground spectral energy distribution and may cause spectral degeneracies with the CMB in the frequency range probed by the experiment.
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| 20. |
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| 21. |
- Hills, M. J., et al.
(författare)
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A compact 4 K cooling system for superconducting nanowire single photon detectors
- 2019
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Ingår i: 27TH INTERNATIONAL CRYOGENICS ENGINEERING CONFERENCE AND INTERNATIONAL CRYOGENIC MATERIALS CONFERENCE 2018 (ICEC-ICMC 2018). - : IOP PUBLISHING LTD.
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Konferensbidrag (refereegranskat)abstract
- Compact, low power, robust closed-cycle cooling platforms are a key requirement for emerging low temperature quantum technologies. We have repurposed a 4 K Stirling/Joule-Thomson cooler built for the Planck space mission into a flexible demonstration system. We have verified a cooling power of 4mW at 4.7K. We have installed a fibre-coupled superconducting nanowire single-photon detector in this platform and deployed it for two key advanced infrared photon counting applications: single-photon LIDAR and dosimetry for laser cancer treatment. We discuss proposed improvements to the Stirling cooler design for increased cooling power, manufacturability and turn-key operation.
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| 22. |
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| 23. |
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| 24. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 25. |
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| 26. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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| 27. |
- Gallardo, P. A., et al.
(författare)
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Optical design concept of the CMB-S4 large-Aperture telescopes and cameras
- 2022
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 12190
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4-the next-generation ground-based cosmic microwave background (CMB) experiment-will significantly advance the sensitivity of CMB measurements and improve our understanding of the origin and evolution of the universe. CMB-S4 will deploy large-Aperture telescopes fielding hundreds of thousands of detectors at millimeter wavelengths. We present the baseline optical design concept of the large-Aperture CMB-S4 telescopes, which consists of two optical configurations: (i) a new off-Axis, three-mirror, free-form anastigmatic design and (ii) the existing coma-corrected crossed-Dragone design. We also present an overview of the optical configuration of the array of silicon optics cameras that will populate the focal plane with 85 diffraction-limited optics tubes covering up to 9 degrees of field of view, up to 1.1 mm in wavelength. We describe the computational optimization methods that were put in place to implement the families of designs described here and give a brief update on the current status of the design effort.
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| 28. |
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| 29. |
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| 30. |
- Wiedner, M.C., et al.
(författare)
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Heterodyn receiver for the Origins Space Telescope concept 2
- 2018
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
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Konferensbidrag (refereegranskat)abstract
- The Origins Space Telescope (OST) is a NASA study for a large satellite mission to be submitted to the 2020 Decadal Review. The proposed satellite has a fleet of instruments including the HEterodyne Receivers for OST (HERO). HERO is designed around the quest to follow the trail of water from the ISM to disks around protostars and planets. HERO will perform high-spectral resolution measurements with 2x9 pixel focal plane arrays at any frequency between 468GHz to 2,700GHz (617 to 111 μm). HERO builds on the successful Herschel/HIFI heritage, as well as recent technological innovations, allowing it to surpass any prior heterodyne instrument in terms of sensitivity and spectral coverage.
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| 31. |
- Wiedner, M.C., et al.
(författare)
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Heterodyne Receiver for Origins
- 2021
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Ingår i: Journal of Astronomical Telescopes, Instruments, and Systems. - 2329-4221 .- 2329-4124. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The Heterodyne Receiver for Origins (HERO) is the first detailed study of a heterodyne focal plane array receiver for space applications. HERO gives the Origins Space Telescope the capability to observe at very high spectral resolution (R = 107) over an unprecedentedly large far-infrared (FIR) wavelengths range (111 to 617 μm) with high sensitivity, with simultaneous dual polarization and dual-frequency band operation. The design is based on prior successful heterodyne receivers, such as Heterodyne Instrument for the Far-Infrared/Herschel, but surpasses it by one to two orders of magnitude by exploiting the latest technological developments. Innovative components are used to keep the required satellite resources low and thus allowing for the first time a convincing design of a large format heterodyne array receiver for space. HERO on Origins is a unique tool to explore the FIR universe and extends the enormous potential of submillimeter astronomical spectroscopy into new areas of astronomical research.
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| 32. |
- Freedman, Ben, et al.
(författare)
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Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 135:19, s. 1851-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country-and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
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| 33. |
- Gemmell, Nathan R., et al.
(författare)
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A miniaturized 4K platform for superconducting infrared photon counting detectors
- 2017
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Ingår i: Superconductors Science and Technology. - : Institute of Physics Publishing (IOPP). - 0953-2048 .- 1361-6668. ; 30:11
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Tidskriftsartikel (refereegranskat)abstract
- We report on a miniaturized platform for superconducting infrared photon counting detectors. We have implemented a fibre-coupled superconducting nanowire single photon detector in a Stirling/Joule-Thomson platform with a base temperature of 4.2 K. We have verified a cooling power of 4 mW at 4.7 K. We report 20% system detection efficiency at 1310 nm wavelength at a dark count rate of 1 kHz. We have carried out compelling application demonstrations in single photon depth metrology and singlet oxygen luminescence detection.
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| 34. |
- Meyer, Esther, et al.
(författare)
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Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
- 2017
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49, s. 223-237
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Tidskriftsartikel (refereegranskat)abstract
- Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.
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