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- 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. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Greiner, J., et al.
(författare)
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GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 551-582
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Tidskriftsartikel (refereegranskat)abstract
- We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range (COMPTEL, INTEGRAL; see Fig. 1). These gamma-ray observations will be complemented by observations in the soft X-ray and (near-)infrared region with the corresponding telescopes placed on a separate satellite. The Gamma-Ray Imaging, Polarimetry and Spectroscopy ("GRIPS") mission with its three instruments Gamma-Ray Monitor (GRM), X-Ray Monitor (XRM) and InfraRed Telescope (IRT) addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate γ-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.
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| 9. |
- De Falco, V., et al.
(författare)
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The transitional millisecond pulsar IGR J18245-2452 during its 2013 outburst at X-rays and soft gamma-rays
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 603
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Tidskriftsartikel (refereegranskat)abstract
- IGR J18245-2452/PSR J1824-2452I is one of the rare transitional accreting millisecond X-ray pulsars, showing direct evidence of switches between states of rotation-powered radio pulsations and accretion-powered X-ray pulsations, dubbed transitional pulsars. IGR J18245-2452 with a spin frequency of ∼ 254.3 Hz is the only transitional pulsar so far to have shown a full accretion episode, reaching an X-ray luminosity of ∼ 1037 erg s-1 permitting its discovery with INTEGRAL in 2013. In this paper, we report on a detailed analysis of the data collected with the IBIS/ISGRI and the two JEM-X monitors on-board INTEGRAL at the time of the 2013 outburst. We make use of some complementary data obtained with the instruments on-board XMM-Newton and Swift in order to perform the averaged broad-band spectral analysis of the source in the energy range 0.4-250 keV. We have found that this spectrum is the hardest among the accreting millisecond X-ray pulsars. We improved the ephemeris, now valid across its full outburst, and report the detection of pulsed emission up to ∼ 60 keV in both the ISGRI (10.9σ) and Fermi/GBM (5.9σ) bandpass. The alignment of the ISGRI and Fermi GBM 20-60 keV pulse profiles are consistent at a ∼ 25 μs level. We compared the pulse profiles obtained at soft X-rays with XMM-Newton with the soft γ-ray ones, and derived the pulsed fractions of the fundamental and first harmonic, as well as the time lag of the fundamental harmonic, up to 150 μs, as a function of energy. We report on a thermonuclear X-ray burst detected with INTEGRAL, and using the properties of the previously type-I X-ray burst, we show that all these events are powered primarily by helium ignited at a depth of yign ≈ 2.7 × 108 g cm-2. For such a helium burst the estimated recurrence time of Δtrec ≈ 5.6 d is in agreement with the observations.
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| 10. |
- Glasbey, James, et al.
(författare)
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The impact of conversion on the risk of major complication following laparoscopic colonic surgery : an international, multicentre prospective audit
- 2018
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910. ; 2020 Suppl 6, s. 69-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laparoscopy has now been implemented as a standard of care for elective colonic resection around the world. During the adoption period, studies showed that conversion may be detrimental to patients, with poorer outcomes than both laparoscopic completed or planned open surgery. The primary aim of this study was to determine whether laparoscopic conversion was associated with a higher major complication rate than planned open surgery in contemporary, international practice.METHODS: Combined analysis of the European Society of Coloproctology 2017 and 2015 audits. Patients were included if they underwent elective resection of a colonic segment from the caecum to the rectosigmoid junction with primary anastomosis. The primary outcome measure was the 30-day major complication rate, defined as Clavien-Dindo grade III-V.RESULTS: Of 3980 patients, 64% (2561/3980) underwent laparoscopic surgery and a laparoscopic conversion rate of 14% (359/2561). The major complication rate was highest after open surgery (laparoscopic 7.4%, converted 9.7%, open 11.6%, P < 0.001). After case mix adjustment in a multilevel model, only planned open (and not laparoscopic converted) surgery was associated with increased major complications in comparison to laparoscopic surgery (OR 1.64, 1.27-2.11, P < 0.001).CONCLUSIONS: Appropriate laparoscopic conversion should not be considered a treatment failure in modern practice. Conversion does not appear to place patients at increased risk of complications vs planned open surgery, supporting broadening of selection criteria for attempted laparoscopy in elective colonic resection.
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| 11. |
- Hermsen, W., et al.
(författare)
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Synchronous X-ray and Radio Mode Switches: A Rapid Global Transformation of the Pulsar Magnetosphere
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6118, s. 436-439
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Tidskriftsartikel (refereegranskat)abstract
- Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.
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| 14. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 15. |
- Amofah, H. A., et al.
(författare)
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Factors affecting in-hospital sleep-wake pattern in octogenarians during the early postoperative phase after transcutaneous aortic valve replacement
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:Suppl. 1, s. S53-S53
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Tidskriftsartikel (refereegranskat)abstract
- Background: Octogenarian patients are an increasing group admitted for advanced cardiac treatment. Little is known about factors disturbing their sleep-wake pattern in the early postoperative phase after transcutaneous aortic valve replacement (TAVI), as current knowledge is based upon studies on younger age groups treated for surgical aortic valve replacement.Aim: To determine factors affecting the in-hospital sleep wake pattern in octogenarian patients after TAVI.Methods: This is a prospective cohort study in a tertiary university hospital. Inclusion criteria were age > 80 years with severe aortic stenosis accepted for TAVI. Actigraphy was used to identify sleep-wake pattern (sleep time night and sleep time day), and the Minimal Insomnia Symptom Scale (MISS) to measure self-reported insomnia daily during the first five postoperative days. Charlson`s comorbidity index was used as a measure of comorbidities and the Visual Analog Scale (VAS) to rate pain severity. Information regarding duration of anesthesia, blood transfusion and parenteral administration of morphine equivalents were derived from the patients’ medical journals. Multiple regression analysis was used to test associations between variables.Results: In all, 65 patients (41 women) were included. Mean age was 85 years (SD 2.8). No significant associations were found between age, comorbidities, blood transfusion and morphine equivalents and sleep. Gender was significantly associated with sleep time night and sleep efficiency as men had shortest duration of sleep from the third to the fifth postoperative night (p < .001, and adjusted R2=.230 to .283). Duration of anesthesia had a significant association with sleep time night and sleep efficiency from the third to the fifth postoperative night (p=.013 to p < .001, and adjusted R2=.230 to .283), where longer duration gave less total sleep and lower sleep efficiency. VAS score correlated with wake time night the third night, where a higher VAS score gave more wake time (p=.006 and adjusted R2 .236).Conclusion: Male gender, longer duration of perioperative anesthesia and postoperative pain were associated with disturbances in the postoperative sleep-wake pattern in octogenarian patients in the early postoperative phase after TAVI. This knowledge is important and relevant and should have implications in improving patient care.
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| 16. |
- Amofah, H. A., et al.
(författare)
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Factors associated with disturbances in sleep-wake pattern in octogenarian patients in the early postoperative phase after surgical aortic valve replacement
- 2017
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Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 16:Suppl. 1, s. S63-S64
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disturbances of the sleep-wake pattern are known phenomenon in the postoperative phase after aortic valve replacement (SAVR) that have negative impact on the morbidity, quality of life and mortality. Octogenarian patients are an increasing group admitted for cardiac surgery, however knowledge is based on younger patients.Aims: To determine factors associated with disturbances in postoperative sleep-wake pattern in octogenarian patients after SAVR.Methods: A prospective cohort study of octogenarian patients in a single center university hospital. Inclusion criteria were age > 80 years, severe aortic stenosis, accepted for SAVR. Actigraphy was used to identify the sleep-wake pattern (sleep-time, sleep efficiency and wake time night and sleep- and wake-time day) for the five first postoperative days, and the sleep questionnaires Minimal Insomnia Symptom scale (MISS) to measure the selfreported insomnia at baseline and daily for the five first postoperative days. Charlsons comorbidity index was used to score comorbidities and the Visual Analog Scale (VAS), was used to rate pain severity. The patients’ medical journals were used to record duration of anesthesia, duration of cardiopulmonary by-pass, blood transfusions and parenteral administration of morphine equivalents. Multiple regression analysis was used to test associations between variables.Results: In all, 78 patients were included (40 women). Mean age was 82 years (SD 2.0). For the sleep-wake pattern first to fifth postoperative night, mean sleep-time night was 330-370 minutes (SD 32-124). Mean sleep efficiency was 68-77% (SD 21-26). Mean sleep-time day was 545-712 minutes (SD 146-169). Mean insomnia score was 1,8-5,3 (SD 2,6-3,8). On the first postoperative night the pain VAS score correlated with wake time night, where a higher VAS indicated more wake time (p=.014, adjusted R2=.213). No other variable; age, gender, duration of anesthesia, duration of cardiopulmonary by-pass, blood transfusion or morphine equivalents showed significant association with the sleep-wake pattern or insomnia.Conclusion: Postoperative pain was associated with disturbances in sleep-wake pattern in octogenarian patients in the early postoperative phase after SAVR. This indicates that pain management may be inadequate for patients after SAVR. More research on this issue is needed to establish data needed to improve treatment and care.
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| 18. |
- Benavente, ED, et al.
(författare)
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Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Women presenting with coronary artery disease (CAD) more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid atherosclerotic tissue. Prioritization of these networks identified two main SMC GRNs in late-stage atherosclerosis. Single-cell RNA-sequencing mapped these GRNs to two SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like GRN was mostly expressed in plaques that were vulnerable in females. Finally, mice orthologs of the female myofibroblast-like genes showed retained expression in advanced plaques from female mice but were downregulated in male mice during atherosclerosis progression. Female atherosclerosis is driven by GRNs that promote a fibrous vulnerable plaque rich in myofibroblast-like SMCs.
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