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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 10. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 11. |
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| 12. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 13. |
- Amati, L., et al.
(författare)
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The THESEUS space mission concept : science case, design and expected performances
- 2018
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Ingår i: Advances in Space Research. - : ELSEVIER SCI LTD. - 0273-1177 .- 1879-1948. ; 62:1, s. 191-244
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Tidskriftsartikel (refereegranskat)abstract
- THESEUS is a space mission concept aimed at exploiting Gamma-Ray Bursts for investigating the early Universe and at providing a substantial advancement of multi-messenger and time-domain astrophysics. These goals will be achieved through a unique combination of instruments allowing GRB and X-ray transient detection over a broad field of view (more than 1 sr) with 0.5-1 arcmin localization, an energy band extending from several MeV down to 0.3 keV and high sensitivity to transient sources in the soft X-ray domain, as well as on-board prompt (few minutes) follow-up with a 0.7 m class IR telescope with both imaging and spectroscopic capabilities. THESEUS will be perfectly suited for addressing the main open issues in cosmology such as, e.g., star formation rate and metallicity evolution of the inter-stellar and intra-galactic medium up to redshift similar to 10, signatures of Pop III stars, sources and physics of re-ionization, and the faint end of the galaxy luminosity function. In addition, it will provide unprecedented capability to monitor the X-ray variable sky, thus detecting, localizing, and identifying the electromagnetic counterparts to sources of gravitational radiation, which may be routinely detected in the late '20s/early '30s by next generation facilities like aLIGO/ aVirgo, eLISA, KAGRA, and Einstein Telescope. THESEUS will also provide powerful synergies with the next generation of multi-wavelength observatories (e.g., LSST, ELT, SKA, CTA, ATHENA).
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| 14. |
- Feroci, M., et al.
(författare)
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The Large Observatory for X-ray Timing (LOFT)
- 2012
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
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Tidskriftsartikel (refereegranskat)abstract
- High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
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| 15. |
- Belli, LS, et al.
(författare)
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COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:10, s. 1914-
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Tidskriftsartikel (refereegranskat)abstract
- Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.DesignData from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.ResultsFrom 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).ConclusionsIncreased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).
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| 16. |
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| 17. |
- Donnarumma, I., et al.
(författare)
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Multiwavelength Observations of 3C 454.3. II. The AGILE 2007 December Campaign
- 2009
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Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 707:2, s. 1115-1123
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Tidskriftsartikel (refereegranskat)abstract
- We report on the second Astrorivelatore Gamma a Immagini Leggero (AGILE) multiwavelength campaign of the blazar 3C 454.3 during the first half of 2007 December. This campaign involved AGILE, Spitzer, Swift, Suzaku, the Whole Earth Blazar Telescope (WEBT) consortium, the Rapid Eye Mount (REM), and the Multicolor Imaging Telescopes for Survey and Monstrous Explosions (MITSuME) telescopes, offering a broadband coverage that allowed for a simultaneous sampling of the synchrotron and inverse Compton (IC) emissions. The two-week AGILE monitoring was accompanied by radio to optical monitoring by WEBT and REM, and by sparse observations in mid-infrared and soft/ hard X-ray energy bands performed by means of Target of Opportunity observations by Spitzer, Swift, and Suzaku, respectively. The source was detected with an average flux of similar to 250 x 10(-8) photons cm(-2) s(-1) above 100 MeV, typical of its flaring states. The simultaneous optical and gamma-ray monitoring allowed us to study the time lag associated with the variability in the two energy bands, resulting in a possible <= one-day delay of the gamma-ray emission with respect to the optical one. From the simultaneous optical and gamma-ray fast flare detected on December 12, we can constrain the delay between the gamma-ray and optical emissions within 12 hr. Moreover, we obtain three spectral energy distributions (SEDs) with simultaneous data for 2007 December 5, 13, and 15, characterized by the widest multifrequency coverage. We found that a model with an external Compton on seed photons by a standard disk and reprocessed by the broad-line regions does not describe in a satisfactory way the SEDs of 2007 December 5, 13, and 15. An additional contribution, possibly from the hot corona with T = 10(6) K surrounding the jet, is required to account simultaneously for the softness of the synchrotron and the hardness of the IC emissions during those epochs.
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| 18. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Tavani, M., et al.
(författare)
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Detection of Gamma-Ray Emission from the Eta-Carinae Region
- 2009
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Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 698:2, s. L142-L146
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of extensive observations by the gamma-ray AGILE satellite of the Galactic region hosting the Carina nebula and the remarkable colliding wind binary Eta Carinae (eta Car) during the period 2007 July-2009 January. We detect a gamma-ray source (1AGL J1043-5931) consistent with the position of eta Car. If 1AGL J1043-5931 is associated with the Car system, our data provide the long sought first detection above 100 MeV of a colliding wind binary. The average gamma-ray flux above 100 MeV and integrated over the preperiastron period 2007 July-2008 October is F(gamma) = (37 +/- 5) x 10(-8) ph cm(-2) s(-1) corresponding to an average gamma-ray luminosity of L(gamma) = 3.4 x 10(34) erg s(-1) for a distance of 2.3 kpc. We also report a two-day gamma-ray flaring episode of 1AGL J1043-5931 on 2008 October 11-13 possibly related to a transient acceleration and radiation episode of the strongly variable shock in the system.
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| 20. |
- Tavani, M., et al.
(författare)
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Direct Evidence for Hadronic Cosmic-Ray Acceleration in the Supernova Remnant IC 443
- 2010
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Ingår i: The Astrophysical Journal. Letters. - 2041-8205. ; 710:2, s. L151-L155
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Tidskriftsartikel (refereegranskat)abstract
- The supernova remnant (SNR) IC 443 is an intermediate-age remnant well known for its radio, optical, X-ray, and gamma-ray energy emissions. In this Letter, we study the gamma-ray emission above 100 MeV from IC 443 as obtained by the AGILE satellite. A distinct pattern of diffuse emission in the energy range 100 MeV-3 GeV is detected across the SNR with its prominent maximum (source "A") localized in the northeastern shell with a flux F = (47 +/- 10) x 10(-8) photons cm(-2) s(-1) above 100 MeV. This location is the site of the strongest shock interaction between the SNR blast wave and the dense circumstellar medium. Source "A" is not coincident with the TeV source located 0.4. away and associated with a dense molecular cloud complex in the SNR central region. From our observations, and from the lack of detectable diffuse TeV emission from its northeastern rim, we demonstrate that electrons cannot be the main emitters of gamma rays in the range 0.1-10 GeV at the site of the strongest SNR shock. The intensity, spectral characteristics, and location of the most prominent gamma-ray emission together with the absence of cospatial detectable TeV emission are consistent only with a hadronic model of cosmic-ray acceleration in the SNR. A high-density molecular cloud (cloud "E") provides a remarkable "target" for nucleonic interactions of accelerated hadrons; our results show enhanced gamma-ray production near the molecular cloud/shocked shell interaction site. IC 443 provides the first unambiguous evidence of cosmic-ray acceleration by SNRs.
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| 21. |
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| 22. |
- de Graaf, Nine, et al.
(författare)
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Minimally invasive versus open pancreatoduodenectomy for pancreatic and peri-ampullary neoplasm (DIPLOMA-2) : study protocol for an international multicenter patient-blinded randomized controlled trial
- 2023
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Ingår i: Trials. - : BioMed Central Ltd. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design: The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion: The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration: ISRCTN27483786. Registered on August 2, 2023. © 2023, BioMed Central Ltd., part of Springer Nature.
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| 23. |
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| 24. |
- Feroci, M., et al.
(författare)
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Monitoring the hard X-ray sky with SuperAGILE
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 510, s. A9-
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Tidskriftsartikel (refereegranskat)abstract
- Context SuperAGILE is the hard X-ray monitor of the AGILE gamma ray mission, in orbit since 23 April 2007. It is an imaging experiment based on a set of four independent silicon strip detectors, equipped with one-dimensional coded masks, operating in the nominal energy range 18-60 keV. Aims. The main goal of SuperAGILE is the observation of cosmic sources simultaneously with the main gamma-ray AGILE experiment, the Gamma Ray Imaging Detector (GRID). Given its similar to steradian-wide field of view and its similar to 15 mCrab day-sensitivity, SuperAGILE is also well suited to the long-term monitoring of Galactic compact objects and the detection of bright transients. Methods. The SuperAGILE detector properties and design allow for a 6 arcmin angular resolution in each of the two independent orthogonal projections of the celestial coordinates. Photon by photon data are continuously available by means of experiment telemetry, and are used to derive images and fluxes of individual sources, with integration times depending on the source intensity and position in the field of view. Results. We report on the main scientific results achieved by SuperAGILE over its first two years in orbit, until April 2009. The scientific observations started in mid-July 2007, with the science verification phase, continuing during the complete AGILE Cycle 1 and the first similar to half of Cycle 2. Despite the largely non-uniform sky coverage, due to the pointing strategy of the AGILE mission, a few tens of Galactic sources were monitored, sometimes for unprecedently long continuous periods, leading to the detection also of several bursts and outbursts. Approximately one gamma ray burst per month was detected and localized, allowing for prompt multi-wavelength observations. A few extragalactic sources in bright states were occasionally detected as well. The light curves of sources measured by SuperAGILE are made publicly available on the web in almost real-time. To enable a proper scientific use of these, we provide the reader with the relevant scientific and technical background.
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| 25. |
- Jin, Shoko, et al.
(författare)
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The wide-field, multiplexed, spectroscopic facility WEAVE : Survey design, overview, and simulated implementation
- 2024
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 530:3, s. 2688-2730
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Tidskriftsartikel (refereegranskat)abstract
- WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959nm at R similar to 5000, or two shorter ranges at . After summarizing the design and implementation of WEAVE and its data systems, we present the organization, science drivers, and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for similar to 3 million stars and detailed abundances for similar to 1.5 million brighter field and open-cluster stars; (ii) survey similar to 0.4 million Galactic-plane OBA stars, young stellar objects, and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey similar to 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionized gas in z < 0.5 cluster galaxies; (vi) survey stellar populations and kinematics in field galaxies at 0.3 less than or similar to z less than or similar to 0.7; (vii) study the cosmic evolution of accretion and star formation using >1 million spectra of LOFAR-selected radio sources; and (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.
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