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| 2. |
- Mlecnik, B, et al.
(författare)
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Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.
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| 5. |
- Mlecnik, B, et al.
(författare)
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Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I–III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I–III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10–4.55) p = 0.0269) of the patient’s gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.
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| 6. |
- Rodriguez, D., et al.
(författare)
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MATS and LaSpec : High-precision experiments using ion traps and lasers at FAIR
- 2010
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Ingår i: The European physical journal. Special topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 183, s. 1-123
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Forskningsöversikt (refereegranskat)abstract
- Nuclear ground state properties including mass, charge radii, spins and moments can be determined by applying atomic physics techniques such as Penning-trap based mass spectrometry and laser spectroscopy. The MATS and LaSpec setups at the low-energy beamline at FAIR will allow us to extend the knowledge of these properties further into the region far from stability. The mass and its inherent connection with the nuclear binding energy is a fundamental property of a nuclide, a unique ""fingerprint"". Thus, precise mass values are important for a variety of applications, ranging from nuclear-structure studies like the investigation of shell closures and the onset of deformation, tests of nuclear mass models and mass formulas, to tests of the weak interaction and of the Standard Model. The required relative accuracy ranges from 10(-5) to below 10(-8) for radionuclides, which most often have half-lives well below 1 s. Substantial progress in Penning trap mass spectrometry has made this method a prime choice for precision measurements on rare isotopes. The technique has the potential to provide high accuracy and sensitivity even for very short-lived nuclides. Furthermore, ion traps can be used for precision decay studies and offer advantages over existing methods. With MATS (Precision Measurements of very short-lived nuclei using an Advanced Trapping System for highly-charged ions) at FAIR we aim to apply several techniques to very short-lived radionuclides: High-accuracy mass measurements, in-trap conversion electron and alpha spectroscopy, and trap-assisted spectroscopy. The experimental setup of MATS is a unique combination of an electron beam ion trap for charge breeding, ion traps for beam preparation, and a high-precision Penning trap system for mass measurements and decay studies. For the mass measurements, MATS offers both a high accuracy and a high sensitivity. A relative mass uncertainty of 10(-9) can be reached by employing highly-charged ions and a non-destructive Fourier-Transform Ion-Cyclotron-Resonance (FT-ICR) detection technique on single stored ions. This accuracy limit is important for fundamental interaction tests, but also allows for the study of the fine structure of the nuclear mass surface with unprecedented accuracy, whenever required. The use of the FT-ICR technique provides true single ion sensitivity. This is essential to access isotopes that are produced with minimum rates which are very often the most interesting ones. Instead of pushing for highest accuracy, the high charge state of the ions can also be used to reduce the storage time of the ions, hence making measurements on even shorter-lived isotopes possible. Decay studies in ion traps will become possible with MATS. Novel spectroscopic tools for in-trap high-resolution conversion-electron and charged-particle spectroscopy from carrier-free sources will be developed, aiming e. g. at the measurements of quadrupole moments and E0 strengths. With the possibility of both high-accuracy mass measurements of the shortest-lived isotopes and decay studies, the high sensitivity and accuracy potential of MATS is ideally suited for the study of very exotic nuclides that will only be produced at the FAIR facility. Laser spectroscopy of radioactive isotopes and isomers is an efficient and model-independent approach for the determination of nuclear ground and isomeric state properties. Hyperfine structures and isotope shifts in electronic transitions exhibit readily accessible information on the nuclear spin, magnetic dipole and electric quadrupole moments as well as root-mean-square charge radii. The dependencies of the hyperfine splitting and isotope shift on the nuclear moments and mean square nuclear charge radii are well known and the theoretical framework for the extraction of nuclear parameters is well established. These extracted parameters provide fundamental information on the structure of nuclei at the limits of stability. Vital information on both bulk and valence nuclear properties are derived and an exceptional sensitivity to changes in nuclear deformation is achieved. Laser spectroscopy provides the only mechanism for such studies in exotic systems and uniquely facilitates these studies in a model-independent manner. The accuracy of laser-spectroscopic-determined nuclear properties is very high. Requirements concerning production rates are moderate; collinear spectroscopy has been performed with production rates as few as 100 ions per second and laser-desorption resonance ionization mass spectroscopy (combined with beta-delayed neutron detection) has been achieved with rates of only a few atoms per second. This Technical Design Report describes a new Penning trap mass spectrometry setup as well as a number of complementary experimental devices for laser spectroscopy, which will provide a complete system with respect to the physics and isotopes that can be studied. Since MATS and LaSpec require high-quality low-energy beams, the two collaborations have a common beamline to stop the radioactive beam of in-flight produced isotopes and prepare them in a suitable way for transfer to the MATS and LaSpec setups, respectively.
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| 7. |
- Yang, B., et al.
(författare)
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Exploring high-energy doubly excited states of NH by dissociative recombination of NH
- 2014
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 47:3, s. 035201-
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated electron capture by NH+ resulting in dissociative recombination (DR). The impact energies studied of similar to 4-12 eV extend over the range below the two lowest predicted NH+ dissociative states in the Franck-Condon (FC) region of the ion. Our focus has been on the final state populations of the resulting N and H atoms. The neutral DR fragments are detected downstream of a merged electron and ion beam interaction zone in the TSR storage ring, which is located at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. Transverse fragment distances were measured on a recently developed high count-rate imaging detector. The distance distributions enabled a detailed tracking of the final state populations as a function of the electron collision energy. These can be correlated with doubly excited neutral states in the FC region of the ion. At low electron energy of similar to 5 eV, the atomic product final levels are nitrogen Rydberg states together with ground-state hydrogen. In a small electron energy interval near 7 eV, a significant part of the final state population forms hydrogen Rydberg atoms with nitrogen atoms in the first excited (D-2) term, showing the effect of Rydberg doubly excited states below the predicted 2(2)Pi ionic potential. The distance distributions above similar to 10 eV are compatible with nitrogen Rydberg states correlating to the doubly excited Rydberg state manifold below the ionic 2(4) Sigma(-) level.
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| 8. |
- Novotny, O., et al.
(författare)
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DISSOCIATIVE RECOMBINATION MEASUREMENTS OF HCl+ USING AN ION STORAGE RING
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 777:1, s. 54-
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Tidskriftsartikel (refereegranskat)abstract
- We have measured dissociative recombination (DR) of HCl+ with electrons using a merged beams configuration at the TSR heavy-ion storage ring located at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. We present the measured absolute merged beams recombination rate coefficient for collision energies from 0 to 4.5 eV. We have also developed a new method for deriving the cross section from the measurements. Our approach does not suffer from approximations made by previously used methods. The cross section was transformed to a plasma rate coefficient for the electron temperature range from T = 10 to 5000 K. We show that the previously used HCl+ DR data underestimate the plasma rate coefficient by a factor of 1.5 at T = 10 K and overestimate it by a factor of three at T = 300 K. We also find that the new data may partly explain existing discrepancies between observed abundances of chlorine-bearing molecules and their astrochemical models.
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| 9. |
- Novotný, O., et al.
(författare)
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DISSOCIATIVE RECOMBINATION MEASUREMENTS OF NH+ USING AN ION STORAGE RING
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 792:2
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated dissociative recombination (DR) of NH+ with electrons using a merged beams configuration at the TSR heavy-ion storage ring located at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. We present our measured absolute merged-beams recombination rate coefficient for collision energies from 0 to 12 eV. From these data, we have extracted a cross section, which we have transformed to a plasma rate coefficient for the collisional plasma temperature range from T-p1 = 10 to 18,000 K. We show that the NH+ DR rate coefficient data in current astrochemical models are underestimated by up to a factor of approximately nine. Our new data will result in predicted NH+ abundances lower than those calculated by present models. This is in agreement with the sensitivity limits of all observations attempting to detect NH+ in interstellar clouds.
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| 10. |
- Richardson, V., et al.
(författare)
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The reactivity of methanimine radical cation (H2CNH.+) and its isomer aminomethylene (HCNH2.+) with methane
- 2021
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 775
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and theoretical studies are presented on the reactions of the isomeric radical cations H2CNH+ and HCNH2+ with CH4. Ionic isomers were generated selectively by VUV dissociative photoionization of azetidine and cyclopropylamine precursors respectively. Both exclusively give H2CNH2+ plus CH3 as products, but differences are observed related to a competition between stripping and complex-mediated H-transfer. Astrochemical implications for Titan’s atmosphere are briefly discussed, where the presence of methanimine (H2CNH), a key prebiotic molecule and a potential precursor for tholins, is proposed on the basis of atmospheric models and the observation of CH2NH2+ ions in Cassini mass spectrometric data.
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