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- 2019
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Journal article (peer-reviewed)
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3. |
- Abdellaoui, G., et al.
(author)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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In: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Journal article (peer-reviewed)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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- Abdellaoui, G., et al.
(author)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Journal article (peer-reviewed)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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7. |
- Abellán, C., et al.
(author)
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Challenging Local Realism with Human Choices
- 2018
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
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Journal article (peer-reviewed)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
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8. |
- De Paolis, L., et al.
(author)
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Kaonic atoms measurement at DA Φ NE : SIDDHARTA and SIDDHARTA-2
- 2019
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In: Basic Concepts in Nuclear Physics : Theory, Experiments and Applications - 2018 La Rábida International Scientific Meeting on Nuclear Physics - Theory, Experiments and Applications - 2018 La Rábida International Scientific Meeting on Nuclear Physics. - Cham : Springer International Publishing. - 9783030222031 ; 225, s. 191-195
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Conference paper (peer-reviewed)abstract
- Light kaonic atoms studies provide the unique opportunity to perform experiments equivalent to scattering at threshold, being their atomic binding energies in the keV range. High precision atomic X-rays spectroscopy ensures that the energy shift and broadening of the lowest-lying states of the kaonic atoms, induced by the strong interaction between the kaon and nucleus, can be detected. Kaonic hydrogen and kaonic deuterium are the lightest atomic systems and their study deliver the isospin-dependent kaon-nucleon scattering lengths. The SIDDHARTA collaboration was able to perform the most precise kaonic hydrogen measurement to date, together with an exploratory measurement of kaonic deuterium. The measurement of the kaonic deuterium will be realized in the near future by a major upgrade of SIDDHARTA: SIDDHARTA-2. In this paper an overview of the main results obtained by SIDDHARTA together with the future plans are presented.
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9. |
- Curceanu, C., et al.
(author)
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Low-energy kaon-nuclei interaction studies at DAΦNE : Siddharta-2 and amadeus
- 2017
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In: Acta Physica Polonica B. - 0587-4254. ; 48:10, s. 1855-1860
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Journal article (peer-reviewed)abstract
- The DAΦNE electron-positron collider of the Laboratori Nazionali di Frascati of INFN has made available a unique quality low-energy negatively charged kaons "beam", which is being used to study the kaon-nucleon/nuclei interactions by the SIDDHARTA-2 experiment and the AMADEUS Collaboration. The dynamics of the strong interaction processes in the nonperturbative regime is approached by lattice calculations and effective field theories (ChPT) which are still lacking experimental results in the lowenergy regime, fundamental for their good understanding. The studies of kaonic atoms and of the kaonic nuclear processes performed by SIDDHARTA- 2 and AMADEUS play in this context a key-role.
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10. |
- Curceanu, C., et al.
(author)
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The kaonic atoms research program at DAΦNE : Overview and perspectives
- 2018
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1138:1
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Journal article (peer-reviewed)abstract
- The interaction of antikaons with nucleons and nuclei in the low-energy regime represents an active research field in hadron physics with still many important open questions. The investigation of light kaonic atoms is, in this context, a unique tool to obtain precise information on this interaction. The energy shift and broadening of the lowest-lying states of such atoms, induced by the kaon-nucleus strong interaction, can be determined with high precision from atomic X-ray spectroscopy. This experimental method provides unique information to understand the low energy kaon-nucleus interaction at threshold. The lightest atomic systems, kaonic hydrogen and kaonic deuterium, deliver the isospin-dependent kaon-nucleon scattering lengths. The most precise kaonic hydrogen measurement to date, together with an exploratory measurement of kaonic deuterium, were carried out by the SIDDHARTA collaboration at the DAΦNE electron-positron collider of LNF-INFN, by combining the excellent quality kaon beam delivered by the collider with new experimental techniques, as fast and precise X-ray detectors: Silicon Drift Detectors. The measurement of kaonic deuterium will be realized in the near future by SIDDHARTA-2, a major upgrade of SIDDHARTA. In this paper an overview of the main results obtained by SIDDHARTA together with the future plans, are given.
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11. |
- Marton, J., et al.
(author)
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Spectroscopy of kaonic atoms at DAFNE and J-PARC
- 2019
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In: Proceedings - 15th International Workshop on Meson Physics, MESON 2018. - : EDP Sciences.
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Conference paper (peer-reviewed)abstract
- The interaction of antikaons (K) with nucleons and nuclei in the low-energy regime represents a very active research field in hadron physics. A unique and rather direct experimental access to the antikaon-nucleon scattering lengths is provided by precision X-ray spectroscopy of transitions in low-lying states in the lightest kaonic atoms (i.e. kaonic hydrogen and deuterium). In the SIDDHARTA experiment at the electron-positron collider DAFNE of LNFINFN we measured the most precise values of the strong interaction observables in conic hydrogen. The strong interaction on the 1s ground state of the electromagnetically bound K-p atom causes an energy shift and broadening of the 1s state. SIDDHARTA will extend the spectroscopy to kaonic deuterium to get access to the antikaon-neutron interaction and thus the isospin dependent scattering lengths. At J-PARC a kaon beam is used in a complementary experiment with a different setup for spectroscopy of kaonic deuterium atoms. The talk will give an overview of the of the upcoming experiments SIDDHARTA and the complementary experiment at J-PARC.Furthermore, the implications of the experiments for the theory of low-energy strong interaction with strangeness will be discussed.
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12. |
- Scordo, A., et al.
(author)
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The kaonic atoms research program at DAΦNE : From SIDDHARTA to SIDDHARTA-2
- 2018
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In: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 181
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Journal article (peer-reviewed)abstract
- The interaction of antikaons with nucleons and nuclei in the low-energy regime represents an active research field in hadron physics with still many important open questions. The investigation of light kaonic atoms, in which one electron is replaced by a negatively charged kaon, is a unique tool to provide precise information on this interaction; the energy shift and the broadening of the low-lying states of such atoms, induced by the kaon-nucleus hadronic interaction, can be determined with high precision from the atomic X-ray spectroscopy, and this experimental method provides unique information to understand the low energy kaon-nucleus interaction at the production threshold. The lightest atomic systems, like the kaonic hydrogen and the kaonic deuterium deliver, in a model-independent way, the isospin-dependent kaon-nucleon scattering lengths. The most precise kaonic hydrogen measurement to-date, together with an exploratory measurement of kaonic deuterium, were carried out in 2009 by the SIDDHARTA collaboration at the DAΦNE electron-positron collider of LNF-INFN, combining the excellent quality kaon beam delivered by the collider with new experimental techniques, as fast and very precise X-ray detectors, like the Silicon Drift Detectors. The SIDDHARTA results triggered new theoretical work, which achieved major progress in the understanding of the low-energy strong interaction with strangeness reflected by the antikaon-nucleon scattering lengths calculated with the antikaon-proton amplitudes constrained by the SIDDHARTA data. The most important open question is the experimental determination of the hadronic energy shift and width of kaonic deuterium; presently, a major upgrade of the setup, SIDDHARTA-2, is being realized to reach this goal. In this paper, the results obtained in 2009 and the proposed SIDDHARTA-2 upgrades are presented.
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13. |
- Sirghi, D., et al.
(author)
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Experiments with low-energy kaons at the DAΦNE Collider
- 2019. - 1
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In: XIII International Conference on Beauty, Charm and Hyperon Hadrons (BEACH 2018) 17–23 June 2018, Peniche, Portugal. - : IOP Publishing. - 1742-6588. ; 1137
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Conference paper (peer-reviewed)abstract
- The investigations of light kaonic atoms offer the unique opportunity to perform experiments equivalent to scattering at vanishing relative energies, being their atomic binding energies in the keV range. This allows the determination of the hadron-nucleus interaction at threshold without the need of an extrapolation to zero relative energy. The energy shift and broadening of the lowest-lying states of such atoms, induced by the kaon-nucleus strong interaction, can be determined with high precision from atomic X-ray spectroscopy. The lightest atomic systems, kaonic hydrogen and kaonic deuterium, deliver the isospin-dependent kaon-nucleon scattering lengths. The most precise kaonic hydrogen measurement to date, together with an exploratory measurement of kaonic deuterium, were carried out by the SIDDHARTA collaboration at the DAΦNE electron-positron collider of LNF-INFN. The measurement of kaonic deuterium will be realized in the near future by SIDDHARTA-2, a major upgrade of SIDDHARTA. A correlated study of the kaon-nuclei interaction at momenta below 130 MeV/c is carried out by the AMADEUS collaboration, using the KLOE detector and dedicated targets inserted near the collider interaction point. In this paper an overview of the main results obtained by SIDDHARTA together with the future plans, the SIDDHARTA-2 experiment and with the preliminary results of the study of charged antikaons interacting with nuclei by the AMADEUS collaboration, are shown.
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14. |
- Sirghi, D., et al.
(author)
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Kaonic atoms measurements at the DAΦNE Collider
- 2018
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In: Proceedings of Science. - 1824-8039. ; 336
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Conference paper (peer-reviewed)abstract
- The DAΦNE electron-positron collider of the Laboratori Nazionali di Frascati of INFN is a worldwide unique low-energy kaon source, which is being used to produce and to study kaonic atoms by the SIDDHARTA collaboration. The X-ray measurements of kaonic atoms play an important role for understanding the low-energy QCD in the strangeness sector. Significant achievements have been obtained by the SIDDHARTA experiment, among which: the most precise kaonic hydrogen measurement of the 1s level shift and width induced by the presence of the strong interaction; an upper limit of the X-ray yield for kaonic deuterium K-series; the accurate measurement of the 2p level shift and width of kaonic helium-4 and kaonic helium-3; yields of various light kaonic atoms transitions. Using the experience gained with SIDDHARTA experiment, the first kaonic deuterium measurement is in preparation in the framework of the SIDDHARTA-2 experiment, with the goal to determine the antikaon-nucleon isospin dependent scattering lengths, which is possible only by combining the K−p and the upcoming K−d results. An overview of the experimental results of SIDDHARTA and an outlook to SIDDHARTA-2 experiments are given in this paper.
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15. |
- Freitag, Daniel F., et al.
(author)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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In: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Journal article (peer-reviewed)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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17. |
- Strosberg, J., et al.
(author)
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Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors
- 2017
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 376:2, s. 125-135
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Journal article (peer-reviewed)abstract
- BACKGROUND Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials. gov number, NCT01578239; EudraCT number 2011-005049-11.)
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18. |
- Divakar, Pradeep K., et al.
(author)
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Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi
- 2015
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 208:4, s. 1217-1226
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Journal article (peer-reviewed)abstract
- We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes, Ascomycota), one of the largest families of lichen-forming fungi with complex and variable morphologies, also including several lichenicolous fungi. We assembled a six-locus data set including nuclear, mitochondrial and low-copy protein-coding genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle originated independently three times in lichenized ancestors within Parmeliaceae, and a new generic name is introduced for one of these fungi. In all cases, the independent origins occurred c. 24 million yr ago. Further, we show that the Paleocene, Eocene and Oligocene were key periods when diversification of major lineages within Parmeliaceae occurred, with subsequent radiations occurring primarily during the Oligocene and Miocene. Our phylogenetic hypothesis supports the independent origin of lichenicolous fungi associated with climatic shifts at the Oligocene-Miocene boundary. Moreover, diversification bursts at different times may be crucial factors driving the diversification of Parmeliaceae. Additionally, our study provides novel insight into evolutionary relationships in this large and diverse family of lichen-forming ascomycetes.
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22. |
- Walsh, Louise, et al.
(author)
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BET Inhibition as a Rational Therapeutic Strategy for Invasive Lobular Breast Cancer
- 2019
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 25:23, s. 7139-7150
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Journal article (peer-reviewed)abstract
- PURPOSE: Invasive lobular carcinoma (ILC) is a subtype of breast cancer accounting for 10% of breast tumors. The majority of patients are treated with endocrine therapy; however, endocrine resistance is common in estrogen receptor-positive breast cancer and new therapeutic strategies are needed. Bromodomain and extraterminal inhibitors (BETi) are effective in diverse types of breast cancer but they have not yet been assessed in ILC.EXPERIMENTAL DESIGN: We assessed whether targeting the BET proteins with JQ1 could serve as an effective therapeutic strategy in ILC in both 2D and 3D models. We used dynamic BH3 profiling and RNA-sequencing (RNA-seq) to identify transcriptional reprograming enabling resistance to JQ1-induced apoptosis. As part of the RATHER study, we obtained copy-number alterations and RNA-seq on 61 ILC patient samples.RESULTS: Certain ILC cell lines were sensitive to JQ1, while others were intrinsically resistant to JQ1-induced apoptosis. JQ1 treatment led to an enhanced dependence on antiapoptotic proteins and a transcriptional rewiring inducing fibroblast growth factor receptor 1 (FGFR1). This increase in FGFR1 was also evident in invasive ductal carcinoma (IDC) cell lines. The combination of JQ1 and FGFR1 inhibitors was highly effective at inhibiting growth in both 2D and 3D models of ILC and IDC. Interestingly, we found in the RATHER cohort of 61 ILC patients that 20% had FGFR1 amplification and we showed that high BRD3 mRNA expression was associated with poor survival specifically in ILC.CONCLUSIONS: We provide evidence that BETi either alone or in combination with FGFR1 inhibitors or BH3 mimetics may be a useful therapeutic strategy for recurrent ILC patients.
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23. |
- Currow, D. C., et al.
(author)
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Chronic breathlessness associated with poorer physical and mental health-related quality of life (SF-12) across all adult age groups
- 2017
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 72:12, s. 1151-1153
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Journal article (peer-reviewed)abstract
- Little is known about the impact of chronic breathlessness (modified Medical Research Council (mMRC) score ≥2 for most days, at least three of the last six months) on health-related quality of life (Short Form-12 (SF-12)). 3005 adults from randomly selected households were interviewed face-to-face in South Australia. mMRC ≥2 community prevalence was 2.9%. Adjusted analyses showed clinically meaningful and statistically significant decrements of physical and mental components of SF-12 (mean SF-12 summary scores in physical (-13.0 (-16.0 to -10.2)) and mental (-10.7 (-13.7 to -7.8)) components compared with people with mMRC=0) as chronic breathlessness severity increased, across five age groupings.
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24. |
- Gilani, Sarwat I, et al.
(author)
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Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in Preeclampsia
- 2017
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In: Journal of the American Society of Nephrology: JASN. - 1533-3450. ; 28:11, s. 3363-3372
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Journal article (peer-reviewed)abstract
- Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and α1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of HbF in podocyte injury was studied in pregnant rabbits. Compared with urine from women with normotensive pregnancies, urine from women with preeclamptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podocin(+) EVs-to-nephrin(+) EVs ratio) and increased nephrinuria, both of which correlated with proteinuria. Plasma levels of hemopexin, which were decreased in women with preeclampsia, negatively correlated with proteinuria, urinary podocin(+) EVs-to-nephrin(+) EVs ratio, and nephrinuria. Administration of HbF to pregnant rabbits increased the number of urinary EVs of podocyte origin. These findings provide evidence that urinary EVs are reflective of preeclampsia-related altered podocyte protein expression. Furthermore, renal injury in preeclampsia associated with an elevated urinary podocin(+) EVs-to-nephrin(+) EVs ratio and may be mediated by prolonged exposure to cellfree HbF.
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25. |
- Bonnin, CM, et al.
(author)
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Lifetime Psychotic Symptoms, Subthreshold Depression and Cognitive Impairment as Barriers to Functional Recovery in Patients with Bipolar Disorder
- 2019
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In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:7
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Journal article (peer-reviewed)abstract
- (1) Background: bipolar disorder (BD) is a chronic disease that often leads to functional impairment. The objective of this study is to elucidate which variables are associated with better functional outcomes in a sample of euthymic patients with BD. (2) Methods: patients were recruited at the Hospital Clinic of Barcelona and they underwent a clinical interview, a functional assessment, and a comprehensive neuropsychological evaluation. After that, patients were divided into two groups according to the Functioning Assessment Short Test total score: functionally remitted vs. functionally impaired. Following this, a multivariate logistic regression was run in order to identify clinical, demographic and cognitive factors associated with functional remission. (3) Results: a total of 420 euthymic patients with BD were assessed for this study, distributed as follows: functionally remitted (n = 221) and functionally impaired (n = 199). Finally, the multivariate logistic regression revealed that only five variables significantly contributed to the model, including: lifetime history of psychotic symptoms (the variable that contributed the most to the model), followed by the Hamilton Depression total score, and cognitive performance (executive functions and verbal memory). (4) Conclusions: treatments to ensure a good functional outcome in BD should specially prevent psychosis, target subthreshold depressive symptoms and enhance cognition, more specifically executive functions and verbal memory.
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