| 1. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 2. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 3. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 4. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t
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| 5. |
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| 6. |
- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 7. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 8. |
- Schael, S., et al.
(författare)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 9. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 10. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 11. |
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| 12. |
- Tinetti, Giovanna, et al.
(författare)
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The EChO science case
- 2015
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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| 13. |
- Spina, L., et al.
(författare)
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The Gaia-ESO Survey: Metallicity of the Chamaeleon I star-forming region
- 2014
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568
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Tidskriftsartikel (refereegranskat)abstract
- Context. Recent metallicity determinations in young open clusters and star-forming regions suggest that the latter may be characterized by a slightly lower metallicity than the Sun and older clusters in the solar vicinity. However, these results are based on small statistics and inhomogeneous analyses. The Gaia-ESO Survey is observing and homogeneously analyzing large samples of stars in several young clusters and star-forming regions, hence allowing us to further investigate this issue. Aims. We present a new metallicity determination of the Chamaeleon I star forming region. based on the products distributed in the first internal release of the Gaia-ESO Survey. Methods. The 48 candidate members of Chamaeleon I have been observed with the high-resolution, spectrograph UVES. We use the surface gravity, lithium line equivalent width, and position in the Hertzsprimg-Russell diagram to confirm the cluster members, and we use the iron abundance to derive the mean metallicity of the region. Results. Out of the 48 targets. we confirm 15 high probability members. Considering the metallicity measurements for nine of them. we find that the iron abundance of Chamaeleon I is slightly subsolar with a mean value [Fe/H] = -0.08 +/- 0.04 dex, This result agrees with the metallicity determination of other nearby star-forming regions and suggests that the chemical pattern of the youngest stars in the solar neighborhood is indeed more metal-poor than the Sun. We argue that this evidence may be related to the chemical distribution of the Gould Belt that contains most of the nearby star-forming regions and young clusters.
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| 14. |
- Spina, L., et al.
(författare)
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The Gaia-ESO Survey: the first abundance determination of the pre-main-sequence cluster gamma Velorum
- 2014
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 567
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Tidskriftsartikel (refereegranskat)abstract
- Context. Knowledge of the abundance distribution of star forming regions and young clusters is critical to investigate a variety of issues, from triggered star formation and chemical enrichment by nearby supernova explosions to the ability to form planetary systems. In spite of this, detailed abundance studies are currently available for relatively few regions. Aims. In this context, we present the analysis of the metallicity of the gamma Velorum cluster, based on the products distributed in the first internal release of the Gaia-ESO Survey. Methods. The gamma Velorum candidate members have been observed with FLAMES, using both UVES and Giraffe, depending on the target brightness and spectral type. In order to derive a solid metallicity determination for the cluster, membership of the observed stars must be first assessed. To this aim, we use several membership criteria including radial velocities, surface gravity estimates, and the detection of the photospheric lithium line. Results. Out of the 80 targets observed with UVES, we identify 14 high-probability members. We find that the metallicity of the cluster is slightly subsolar, with a mean [Fe/H] = -0.057 +/- 0.018 dex. Although J08095427-4721419 is one of the high-probability members, its metallicity is significantly larger than the cluster average. We speculate about its origin as the result of recent accretion episodes of rocky bodies of similar to 60 M-circle plus hydrogen-depleted material from the circumstellar disk.
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| 15. |
- Spina, L., et al.
(författare)
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The Gaia-ESO Survey: chemical signatures of rocky accretion in a young solar-type star
- 2015
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that newly formed planetary systems undergo processes of orbital reconfiguration and planetary migration. As a result, planets or protoplanetary objects may accrete onto the central star, being fused and mixed into its external layers. If the accreted mass is sufficiently high and the star has a sufficiently thin convective envelope, such events may result in a modification of the chemical composition of the stellar photosphere in an observable way, enhancing it with elements that were abundant in the accreted mass. The recent Gaia-ESO Survey observations of the 10-20 Myr old Gamma Velorum cluster have enabled identifying a star that is significantly enriched in iron with respect to other cluster members. In this Letter we further investigate the abundance pattern of this star, showing that its abundance anomaly is not limited to iron, but is also present in the refractory elements, whose overabundances are correlated with the condensation temperature. This finding strongly supports the hypothesis of a recent accretion of rocky material.
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| 16. |
- da Silva, R., et al.
(författare)
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Oxygen, sulfur, and iron radial abundance gradients of classical Cepheids across the Galactic thin disk
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 678, s. A195-A195
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Tidskriftsartikel (refereegranskat)abstract
- Context. Classical Cepheids (CCs) are solid distance indicators and tracers of young stellar populations. Dating back to the beginning of the 20th century, they have been safely adopted to trace the rotation, kinematics, and chemical enrichment history of the Galactic thin disk.Aims. The main aim of this investigation is to provide iron, oxygen, and sulfur abundances for the largest and most homogeneous sample of Galactic CCs analyzed so far (1118 spectra of 356 objects). The current sample, containing 70 CCs for which spectroscopic metal abundances are provided for the first time, covers a wide range in galactocentric distances, pulsation modes, and pulsation periods.Methods. Optical high-resolution spectra with a high signal-to-noise ratio that were collected with different spectrographs were adopted to provide homogeneous estimates of the atmospheric parameters (effective temperature, surface gravity, and microturbulent velocity) that are required to determine the abundance. Individual distances were based either on trigonometric parallaxes by the Gaia Data Release 3 (Gaia DR3) or on distances based on near-infrared period-luminosity relations.Results. We found that iron and α-element radial gradients based on CCs display a well-defined change in the slope for galactocentric distances larger than ~12 kpc. We also found that logarithmic regressions account for the variation in [X/H] abundances from the inner to the outer disk. Radial gradients for the same elements, but based on open clusters covering a wide range in cluster ages, display similar trends. This means that the flattening in the outer disk is an intrinsic feature of the radial gradients because it is independent of age. Empirical evidence indicates that the S radial gradient is steeper than the Fe radial gradient. The difference in the slope is a factor of two in the linear fit (−0.081 vs. −0.041 dex kpc−1) and changes from −1.62 to −0.91 in the logarithmic distance. Moreover, we found that S (explosive nucleosynthesis) is underabundant on average when compared with O (hydrostatic nucleosynthesis). The difference becomes clearer in the metal-poor regime and for the [O/Fe] and [S/Fe] abundance ratios. We performed a detailed comparison with Galactic chemical evolution models and found that a constant star formation efficiency for galactocentric distances larger than 12 kpc accounts for the flattening observed in both iron and α-elements. To further constrain the impact of the predicted S yields for massive stars on radial gradients, we adopted a toy model and found that the flattening in the outermost regions requires a decrease of a factor of four in the current S predictions.Conclusions. CCs are solid beacons for tracing the recent chemical enrichment of young stellar populations. Sulfur photospheric abundances, when compared with other α-elements, have the key advantage of being a volatile element. Therefore, stellar S abundances can be directly compared with nebular sulfur abundances in external galaxies.
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| 17. |
- Madonna, G, et al.
(författare)
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Clinical Categorization Algorithm (CLICAL) and Machine Learning Approach (SRF-CLICAL) to Predict Clinical Benefit to Immunotherapy in Metastatic Melanoma Patients: Real-World Evidence from the Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:16
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Tidskriftsartikel (refereegranskat)abstract
- The real-life application of immune checkpoint inhibitors (ICIs) may yield different outcomes compared to the benefit presented in clinical trials. For this reason, there is a need to define the group of patients that may benefit from treatment. We retrospectively investigated 578 metastatic melanoma patients treated with ICIs at the Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale” of Napoli, Italy (INT-NA). To compare patients’ clinical variables (i.e., age, lactate dehydrogenase (LDH), neutrophil–lymphocyte ratio (NLR), eosinophil, BRAF status, previous treatment) and their predictive and prognostic power in a comprehensive, non-hierarchical manner, a clinical categorization algorithm (CLICAL) was defined and validated by the application of a machine learning algorithm—survival random forest (SRF-CLICAL). The comprehensive analysis of the clinical parameters by log risk-based algorithms resulted in predictive signatures that could identify groups of patients with great benefit or not, regardless of the ICI received. From a real-life retrospective analysis of metastatic melanoma patients, we generated and validated an algorithm based on machine learning that could assist with the clinical decision of whether or not to apply ICI therapy by defining five signatures of predictability with 95% accuracy.
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| 18. |
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| 19. |
- Almoosawi, Suzana, et al.
(författare)
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Chronotype : Implications for Epidemiologic Studies on Chrono-Nutrition and Cardiometabolic Health
- 2019
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Ingår i: Advances in Nutrition. - : Oxford University Press. - 2161-8313 .- 2156-5376. ; 10:1, s. 30-42
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Forskningsöversikt (refereegranskat)abstract
- Chrono-nutrition is an emerging research field in nutritional epidemiology that encompasses 3 dimensions of eating behavior: timing, frequency, and regularity. To date, few studies have investigated how an individual's circadian typology, i.e., one's chronotype, affects the association between chrono-nutrition and cardiometabolic health. This review sets the directions for future research by providing a narrative overview of recent epidemiologic research on chronotype, its determinants, and its association with dietary intake and cardiometabolic health. Limited research was found on the association between chronotype and dietary intake in infants, children, and older adults. Moreover, most of the evidence in adolescents and adults was restricted to cross-sectional surveys with few longitudinal cohorts simultaneously collecting data on chronotype and dietary intake. There was a gap in the research concerning the association between chronotype and the 3 dimensions of chrono-nutrition. Whether chronotype modifies the association between diet and cardiometabolic health outcomes remains to be elucidated. In conclusion, further research is required to understand the interplay between chronotype, chrono-nutrition, and cardiometabolic health outcomes.
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| 20. |
- Almoosawi, Suzana, et al.
(författare)
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Long Sleep Duration and Social Jetlag Are Associated Inversely with a Healthy Dietary Pattern in Adults : Results from the UK National Diet and Nutrition Survey Rolling Programme Y1-4
- 2018
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Limited observational studies have described the relationship between sleep duration and overall diet. The present study investigated the association between sleep duration on weekdays or social jetlag and empirically derived dietary patterns in a nationally representative sample of UK adults, aged 19-64 years old, participating in the 2008-2012 UK National Diet and Nutrition Survey Rolling Programme. Survey members completed between three to four days of dietary records. Sleep duration on weekdays was categorized into tertiles to reflect short, normal, and long sleep duration. Social jetlag was calculated as the difference between sleep duration on weekends and weekdays. The association between sleep duration/social jetlag and dietary patterns, derived by principal components analysis, was assessed by regressing diet on sleep, whilst accounting for the complex survey design and adjusting for relevant confounders. Survey members in the highest tertile of sleep duration had on average a 0.45 (95% Confidence Interval (CI) -0.78, -0.12) lower healthy dietary pattern score, compared to middle tertile (p = 0.007). There was an inverted u-shaped association between social jetlag and the healthy dietary pattern, such that when sleep on weekends exceeded weekday sleep by 1 h 45 min, scores for indicating a healthy dietary pattern declined (p = 0.005). In conclusion, long sleep duration on weekdays and an increased social jetlag are associated with a lower healthy dietary pattern score. Further research is required to address factors influencing dietary patterns in long sleepers.
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| 21. |
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| 22. |
- Ekelund, U., et al.
(författare)
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Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women : the EPIC-InterAct Study
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 55:7, s. 1944-1952
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Tidskriftsartikel (refereegranskat)abstract
- We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.
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| 23. |
- Ho, Andrew T. V., et al.
(författare)
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Prostaglandin E2 is essential for efficacious skeletal muscle stem-cell function, augmenting regeneration and strength
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:26, s. 6675-6684
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC expansion. An acute treatment with PGE2 suffices to robustly augment muscle regeneration by either endogenous or transplanted MuSCs. Loss of PGE2 signaling by specific genetic ablation of the EP4 receptor in MuSCs impairs regeneration, leading to decreased muscle force. Inhibition of PGE2 production through nonsteroidal anti-inflammatory drug (NSAID) administration just after injury similarly hinders regeneration and compromises muscle strength. Mechanistically, the PGE2 EP4 interaction causes MuSC expansion by triggering a cAMP/phosphoCREB pathway that activates the proliferation-inducing transcription factor, Nurr1. Our findings reveal that loss of PGE2 signaling to MuSCs during recovery from injury impedes muscle repair and strength. Through such gain-or loss-of-function experiments, we found that PGE2 signaling acts as a rheostat for muscle stem-cell function. Decreased PGE2 signaling due to NSAIDs or increased PGE2 due to exogenous delivery dictates MuSC function, which determines the outcome of regeneration. The markedly enhanced and accelerated repair of damaged muscles following intramuscular delivery of PGE2 suggests a previously unrecognized indication for this therapeutic agent.
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| 24. |
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| 25. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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