| 1. |
- Pingel, Jessica, et al.
(författare)
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Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.
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| 2. |
- Aad, G., et al.
(författare)
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Commissioning of the ATLAS Muon Spectrometer with cosmic rays
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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| 3. |
- Aad, G, et al.
(författare)
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Determination of spin and parity of the Higgs boson in the [Formula: see text] decay channel with the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Tidskriftsartikel (refereegranskat)abstract
- Studies of the spin and parity quantum numbers of the Higgs boson in the [Formula: see text] final state are presented, based on proton-proton collision data collected by the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 20.3 fb[Formula: see text] at a centre-of-mass energy of [Formula: see text] TeV. The Standard Model spin-parity [Formula: see text] hypothesis is compared with alternative hypotheses for both spin and CP. The case where the observed resonance is a mixture of the Standard-Model-like Higgs boson and CP-even ([Formula: see text]) or CP-odd ([Formula: see text]) Higgs boson in scenarios beyond the Standard Model is also studied. The data are found to be consistent with the Standard Model prediction and limits are placed on alternative spin and CP hypotheses, including CP mixing in different scenarios.
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| 4. |
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| 5. |
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| 6. |
- Aad, G, et al.
(författare)
-
Measurements of fiducial cross-sections for [Formula: see text] production with one or two additional b-jets in pp collisions at [Formula: see text]=8 TeV using the ATLAS detector.
- 2016
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
-
Tidskriftsartikel (refereegranskat)abstract
- Fiducial cross-sections for [Formula: see text] production with one or two additional b-jets are reported, using an integrated luminosity of 20.3 fb[Formula: see text] of proton-proton collisions at a centre-of-mass energy of 8 TeV at the Large Hadron Collider, collected with the ATLAS detector. The cross-section times branching ratio for [Formula: see text] events with at least one additional b-jet is measured to be 950 [Formula: see text] 70 (stat.) [Formula: see text] (syst.) fb in the lepton-plus-jets channel and 50 [Formula: see text] 10 (stat.) [Formula: see text] (syst.) fb in the [Formula: see text] channel. The cross-section times branching ratio for events with at least two additional b-jets is measured to be 19.3 [Formula: see text] 3.5 (stat.) [Formula: see text] 5.7 (syst.) fb in the dilepton channel ([Formula: see text], [Formula: see text], and ee) using a method based on tight selection criteria, and 13.5 [Formula: see text] 3.3 (stat.) [Formula: see text] 3.6 (syst.) fb using a looser selection that allows the background normalisation to be extracted from data. The latter method also measures a value of 1.30 [Formula: see text] 0.33 (stat.) [Formula: see text] 0.28 (syst.)% for the ratio of [Formula: see text] production with two additional b-jets to [Formula: see text] production with any two additional jets. All measurements are in good agreement with recent theory predictions.
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| 7. |
- Aad, G, et al.
(författare)
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Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at [Formula: see text] and 8 TeV in the ATLAS experiment.
- 2016
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
-
Tidskriftsartikel (refereegranskat)abstract
- Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the [Formula: see text] and [Formula: see text] decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 [Formula: see text] at [Formula: see text] TeV and 20.3 [Formula: see text] at [Formula: see text] TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is [Formula: see text]. The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered.
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| 8. |
- Aad, G, et al.
(författare)
-
Observation and measurements of the production of prompt and non-prompt [Formula: see text] mesons in association with a [Formula: see text] boson in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Tidskriftsartikel (refereegranskat)abstract
- The production of a [Formula: see text] boson in association with a [Formula: see text] meson in proton-proton collisions probes the production mechanisms of quarkonium and heavy flavour in association with vector bosons, and allows studies of multiple parton scattering. Using [Formula: see text] of data collected with the ATLAS experiment at the LHC in [Formula: see text] collisions at [Formula: see text], the first measurement of associated [Formula: see text] production is presented for both prompt and non-prompt [Formula: see text] production, with both signatures having a significance in excess of [Formula: see text]. The inclusive production cross-sections for [Formula: see text] boson production (analysed in [Formula: see text] or [Formula: see text] decay modes) in association with prompt and non-prompt [Formula: see text] are measured relative to the inclusive production rate of [Formula: see text] bosons in the same fiducial volume to be [Formula: see text] and [Formula: see text] respectively. Normalised differential production cross-section ratios are also determined as a function of the [Formula: see text] transverse momentum. The fraction of signal events arising from single and double parton scattering is estimated, and a lower limit of [Formula: see text] at [Formula: see text] confidence level is placed on the effective cross-section regulating double parton interactions.
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| 9. |
- Aad, G, et al.
(författare)
-
Search for a new resonance decaying to a W or Z boson and a Higgs boson in the [Formula: see text] final states with the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:6
-
Tidskriftsartikel (refereegranskat)abstract
- A search for a new resonance decaying to a W or Z boson and a Higgs boson in the [Formula: see text] final states is performed using 20.3 fb[Formula: see text] of pp collision data recorded at [Formula: see text] 8 TeV with the ATLAS detector at the Large Hadron Collider. The search is conducted by examining the WH / ZH invariant mass distribution for a localized excess. No significant deviation from the Standard Model background prediction is observed. The results are interpreted in terms of constraints on the Minimal Walking Technicolor model and on a simplified approach based on a phenomenological Lagrangian of Heavy Vector Triplets.
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| 10. |
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| 11. |
- Aad, G, et al.
(författare)
-
Search for direct pair production of a chargino and a neutralino decaying to the 125 GeV Higgs boson in [Formula: see text] TeV [Formula: see text] collisions with the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Tidskriftsartikel (refereegranskat)abstract
- A search is presented for the direct pair production of a chargino and a neutralino [Formula: see text], where the chargino decays to the lightest neutralino and the [Formula: see text] boson, [Formula: see text], while the neutralino decays to the lightest neutralino and the 125 GeV Higgs boson, [Formula: see text]. The final states considered for the search have large missing transverse momentum, an isolated electron or muon, and one of the following: either two jets identified as originating from bottom quarks, or two photons, or a second electron or muon with the same electric charge. The analysis is based on 20.3 [Formula: see text] of [Formula: see text] proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations, and limits are set in the context of a simplified supersymmetric model.
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| 12. |
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| 13. |
- Aad, G, et al.
(författare)
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Search for heavy long-lived multi-charged particles in pp collisions at [Formula: see text] TeV using the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:8
-
Tidskriftsartikel (refereegranskat)abstract
- A search for heavy long-lived multi-charged particles is performed using the ATLAS detector at the LHC. Data collected in 2012 at [Formula: see text] TeV from pp collisions corresponding to an integrated luminosity of 20.3 fb[Formula: see text]are examined. Particles producing anomalously high ionisation, consistent with long-lived massive particles with electric charges from [Formula: see text] to [Formula: see text] are searched for. No signal candidate events are observed, and 95 % confidence level cross-section upper limits are interpreted as lower mass limits for a Drell-Yan production model. The mass limits range between 660 and 785 GeV.
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| 14. |
- Aad, G, et al.
(författare)
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Search for Higgs boson pair production in the [Formula: see text] final state from pp collisions at [Formula: see text] TeVwith the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:9
-
Tidskriftsartikel (refereegranskat)abstract
- A search for Higgs boson pair production [Formula: see text] is performed with 19.5 fb[Formula: see text] of proton-proton collision data at [Formula: see text] TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum [Formula: see text] system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall-Sundrum model with a warped extra dimension as well as the two-Higgs-doublet model. An upper limit on the cross-section for [Formula: see text] of 3.2 (2.3) fb is set for a Kaluza-Klein graviton [Formula: see text] mass of 1.0 (1.5) TeV, at the 95 % confidence level. The search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section [Formula: see text] of 202 fb, compared to a Standard Model prediction of [Formula: see text] fb.
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| 15. |
- Aad, G, et al.
(författare)
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Search for Higgs Boson Pair Production in the γγbb[over ¯] Final State Using pp Collision Data at sqrt[s]=8 TeV from the ATLAS Detector.
- 2015
-
Ingår i: Physical Review Letters. - 1079-7114. ; 114:8
-
Tidskriftsartikel (refereegranskat)abstract
- Searches are performed for resonant and nonresonant Higgs boson pair production in the γγbb[over ¯] final state using 20 fb^{-1} of proton-proton collisions at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the CERN Large Hadron Collider. A 95% confidence level upper limit on the cross section times branching ratio of nonresonant production is set at 2.2 pb, while the expected limit is 1.0 pb. The difference derives from a modest excess of events, corresponding to 2.4 standard deviations from the background-only hypothesis. The limit observed in the search for a narrow X→hh resonance ranges between 0.7 and 3.5 pb as a function of the resonance mass.
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| 16. |
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| 17. |
- Aad, G, et al.
(författare)
-
Search for production of [Formula: see text] resonances decaying to a lepton, neutrino and jets in [Formula: see text] collisions at [Formula: see text] TeV with the ATLAS detector.
- 2015
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Tidskriftsartikel (refereegranskat)abstract
- A search is presented for narrow diboson resonances decaying to [Formula: see text] or [Formula: see text] in the final state where one [Formula: see text] boson decays leptonically (to an electron or a muon plus a neutrino) and the other [Formula: see text] boson decays hadronically. The analysis is performed using an integrated luminosity of 20.3 fb[Formula: see text] of [Formula: see text] collisions at [Formula: see text] TeV collected by the ATLAS detector at the large hadron collider. No evidence for resonant diboson production is observed, and resonance masses below 700 and 1490 GeV are excluded at 95 % confidence level for the spin-2 Randall-Sundrum bulk graviton [Formula: see text] with coupling constant of 1.0 and the extended gauge model [Formula: see text] boson respectively.
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| 18. |
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| 19. |
- Aad, G, et al.
(författare)
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Searches for scalar leptoquarks in pp collisions at [Formula: see text] = 8 TeV with the ATLAS detector.
- 2016
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
-
Tidskriftsartikel (refereegranskat)abstract
- Searches for pair-produced scalar leptoquarks are performed using 20 fb[Formula: see text] of proton-proton collision data provided by the LHC and recorded by the ATLAS detector at [Formula: see text] TeV. Events with two electrons (muons) and two or more jets in the final state are used to search for first (second)-generation leptoquarks. The results from two previously published ATLAS analyses are interpreted in terms of third-generation leptoquarks decaying to [Formula: see text] and [Formula: see text] final states. No statistically significant excess above the Standard Model expectation is observed in any channel and scalar leptoquarks are excluded at 95 % CL with masses up to [Formula: see text] 1050 GeV for first-generation leptoquarks, [Formula: see text] 1000 GeV for second-generation leptoquarks, [Formula: see text] 625 GeV for third-generation leptoquarks in the [Formula: see text] channel, and 200 [Formula: see text] 640 GeV in the [Formula: see text] channel.
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| 20. |
- Aad, G., et al.
(författare)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
-
Tidskriftsartikel (refereegranskat)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 21. |
- Aad, G, et al.
(författare)
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Study of the [Formula: see text] and [Formula: see text] decays with the ATLAS detector.
- 2016
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
-
Tidskriftsartikel (refereegranskat)abstract
- The decays [Formula: see text] and [Formula: see text] are studied with the ATLAS detector at the LHC using a dataset corresponding to integrated luminosities of 4.9 and 20.6 fb[Formula: see text] of pp collisions collected at centre-of-mass energies [Formula: see text] TeV and 8 TeV, respectively. Signal candidates are identified through [Formula: see text] and [Formula: see text] decays. With a two-dimensional likelihood fit involving the [Formula: see text] reconstructed invariant mass and an angle between the [Formula: see text] and [Formula: see text] candidate momenta in the muon pair rest frame, the yields of [Formula: see text] and [Formula: see text], and the transverse polarisation fraction in [Formula: see text] decay are measured. The transverse polarisation fraction is determined to be [Formula: see text], and the derived ratio of the branching fractions of the two modes is [Formula: see text], where the first error is statistical and the second is systematic. Finally, a sample of [Formula: see text] decays is used to derive the ratios of branching fractions [Formula: see text] and [Formula: see text], where the third error corresponds to the uncertainty of the branching fraction of [Formula: see text] decay. The available theoretical predictions are generally consistent with the measurement.
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| 22. |
- Aad, G., et al.
(författare)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 23. |
- Aad, G., et al.
(författare)
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The ATLAS Simulation Infrastructure
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Tidskriftsartikel (refereegranskat)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 24. |
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| 25. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 26. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 27. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 28. |
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| 29. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 30. |
- Asleh, Karama, et al.
(författare)
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Predictive Biomarkers for Adjuvant Capecitabine Benefit in Early-Stage Triple-Negative Breast Cancer in the FinXX Clinical Trial
- 2020
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 26:11, s. 2603-2614
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Recent studies have demonstrated a benefit of adjuvant capecitabine in early breast cancer, particularly in patients with triple-negative breast cancer (TNBC). However, TNBC is heterogeneous and more precise predictive biomarkers are needed. Experimental Design: Tumor tissues collected from TNBC patients in the FinXX trial, randomized to adjuvant anthracycline-taxane-based chemotherapy with or without capecitabine, were analyzed using a 770-gene panel targeting multiple biological mechanisms and additional 30-custom genes related to capecitabine metabolism. Hypothesis-generating exploratory analyses were performed to assess biomarker expression in relation to treatment effect using the Cox regression model and interaction tests adjusted for multiplicity. Results: One hundred eleven TNBC samples were evaluable (57 without capecitabine and 54 with capecitabine). The median follow-up was 10.2 years. Multivariate analysis showed significant improvement in recurrence-free survival (RFS) favoring capecitabine in four biologically important genes and metagenes, including cytotoxic cells [hazard ratio (HR) = 0.38; 95% confidence intervals (CI), 0.16-0.86, P-interaction = 0.01], endothelial (HR = 0.67; 95% CI, 0.20-2.22, P-interaction = 0.02), mast cells (HR = 0.78; 95% CI, 0.49-1.27, P-interaction = 0.04), and PDL2 (HR = 0.31; 95% CI, 0.12- 0.81, P- interaction = 0.03). Furthermore, we identified 38 single genes that were significantly associated with capecitabine benefit, and these were dominated by immune response pathway and enzymes involved in activating capecitabine to fluorouracil, including TYMP. However, these results were not significant when adjusted for multiple testing. Conclusions: Genes and metagenes related to antitumor immunity, immune response, and capecitabine activation could identify TNBC patients who are more likely to benefit from adjuvant capecitabine. Given the reduced power to observe significant findings when correcting for multiplicity, our findings provide the basis for future hypothesis- testing validation studies on larger clinical trials.
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| 31. |
- Biörserud, Christina, et al.
(författare)
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Sahlgrenska Excess Skin Questionnaire (SESQ): A reliable questionnaire to assess the experience of excessive skin after weight loss.
- 2013
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 47:1, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- Abstract There is a lack of knowledge and reliable measurement instruments to assess excess skin after massive weight loss. The purpose of this study was to test the reliability of a new self-administered questionnaire. A self-administered questionnaire, the Sahlgrenska Excess Skin Questionnaire (SESQ) was designed to assess excess skin after weight loss. The questionnaire includes 30 questions about demographic data, activity and daily life and excess skin on specific body parts and the body as a whole. Forward and backward translations were made by two independent professional translators, from Swedish to English and then back to Swedish. The questionnaire was tested on 10 patients from Sweden and England and was followed by an interview with each patient. Minor corrections were made. A test-retest was carried out to evaluate the reliability by sending the Swedish questionnaire to 46 subjects with weight loss after obesity surgery, dieting, or medication. The test-retest reliability of questions concerning activity and daily life between the two occasions had a Percentage Of Agreement (POA) of 49%-76% and a weighted Kappa of 0.44-0.78. The questions about the degree of excess skin on specific body parts had a POA of 50%-76% and a weighted Kappa of 0.53-0.81. Excess skin perceived as causing problems had a POA of 32%-57 %, an adjusted POA of 63%-87%, and an Intra-Class Correlation of 0.72-0.92. The SESQ is reliable for evaluating patients' experience of excess skin after massive weight loss.
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| 32. |
- Boras, Dominik, et al.
(författare)
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Determining internal porosity in Prussian blue analogue cathode materials using positron annihilation lifetime spectroscopy
- 2023
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Ingår i: Journal of Materials Science. - : Springer Nature. - 0022-2461 .- 1573-4803. ; 58:42, s. 16344-16356
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Tidskriftsartikel (refereegranskat)abstract
- Prussian blue analogues (PBAs), AxM[M’(CN)6]1–y·zH2O, are a highly functional class of materials with use in a broad range of applications, such as energy storage, due to their porous structure and tunable composition. The porosity is particularly important for the properties and is deeply coupled to the cation, water, and [M’(CN)6]n– vacancy content. Determining internal porosity is especially challenging because the three compositional parameters are dependent on each other. In this work, we apply a new method, positron annihilation lifetime spectroscopy (PALS), which can be employed for the characterization of defects and structural changes in crystalline materials. Four samples were prepared to evaluate the method’s ability to detect changes in internal porosity as a function of the cation, water, and [M’(CN)6]n– vacancy content. Three of the samples have identical [M’(CN)6]n– vacancy content and gradually decreasing sodium and water content, while one sample has no sodium and 25% [M’(CN)6]n– vacancies. The samples were thoroughly characterized using inductively coupled plasma-optical emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Mössbauer spectroscopy as well as applying the PALS method. Mössbauer spectroscopy, XRD, and TGA analysis revealed the sample compositions Na1.8(2)Fe2+0.64(6)Fe2.6+0.36(10)[Fe2+(CN)6]·2.09(2)H2O, Na1.1(2)Fe2+0.24(6)Fe2.8+0.76(6)[Fe2.3+(CN)6]·1.57(1)H2O, Fe[Fe(CN)6]·0.807(9)H2O, and Fe[Fe(CN)6]0.75·1.5H2O, confirming the absence of vacancies in the three main samples. It was shown that the final composition of PBAs could only be unambiguously confirmed through the combination of ICP, XRD, TGA, and Mössbauer spectroscopy. Two positron lifetimes of 205 and 405 ps were observed with the 205 ps lifetime being independent of the sodium, water, and/or [Fe(CN)6]n– vacancy content, while the lifetime around 405 ps changes with varying sodium and water content. However, the origin and nature of the 405 ps lifetime yet remains unclear. The method shows promise for characterizing changes in the internal porosity in PBAs as a function of the composition and further development work needs to be carried out to ensure the applicability to PBAs generally.
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| 33. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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| 34. |
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| 35. |
- Gonzalez-Ericsson, Paula, et al.
(författare)
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The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers into breast cancer clinical trials and daily practice
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 250:5, s. 667-684
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Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
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| 36. |
- Gopalakrishnan, Shyam, et al.
(författare)
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The population genomic legacy of the second plague pandemic
- 2022
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 32:21, s. 4743-4751.e6
-
Tidskriftsartikel (refereegranskat)abstract
- Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.
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| 37. |
- Hudeček, Jan, et al.
(författare)
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Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
- 2020
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1
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Forskningsöversikt (refereegranskat)abstract
- Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.
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| 38. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Kos, Zuzana, et al.
(författare)
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Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
- 2020
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.
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| 40. |
- Krause, Torsten, et al.
(författare)
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Not Seeing the Forest for the Trees: The Oversight of Defaunation in REDD+ and Global Forest Governance
- 2019
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Ingår i: Forests. - : MDPI AG. - 1999-4907. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade, countries have strived to develop a global governance structure to halt deforestation and forest degradation, by achieving the readiness requirements for Reducing Emissions from Deforestation and forest Degradation (REDD+). Nonetheless, deforestation continues, and seemingly intact forest areas are being degraded. Furthermore, REDD+ may fail to consider the crucial ecosystem functions of forest fauna including seed dispersal and pollination. Throughout the tropics, forest animal populations are depleted by unsustainable hunting to the extent that many forests are increasingly devoid of larger mammals—a condition referred to as empty forests. Large mammals and birds, who often disperse seeds of larger more carbon-rich tree species, are preferentially targeted by hunters and the first to be depleted. Such defaunation has cascading ecosystem effects, changing forest structure and composition with implications for carbon storage capacity. Failure to address defaunation would therefore be a major oversight in REDD+, compromising its long-term viability. We carried out a desktop study reviewing REDD+ documents and national implementation efforts in Colombia, Ecuador, Nigeria, Tanzania, and Indonesia to assess the extent to which they address hunting and acknowledged the ecosystem functions of fauna. We also assessed sub-national REDD+ projects to determine whether they recognized hunting and if and how they incorporated hunting management and wildlife monitoring at the project level. Moreover, we assessed to what extent sub-national REDD+ projects addressed the long-term impacts of the sustainability of hunting on forest ecosystem function including carbon storage. We found that hunting, the risk of defaunation, and its effects have been ignored in the REDD+ policy process at both the international and national levels. At the project level, we found some reference to hunting and the risks posed by the loss of forest fauna, albeit only addressed superficially. Our results underline the fact that forest ecosystems are being reduced to their carbon content and that, despite the rhetoric of biodiversity co-benefits, fauna is not treated as a functional component of forests. This neglect threatens to undermine forest ecosystem function and service delivery as well as long-term forest carbon assimilation capacity and hence, ultimately, to compromise REDD+ objectives
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| 41. |
- Krause, Torsten, et al.
(författare)
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The legitimacy of incentive-based conservation and a critical account of social safeguards.
- 2014
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011. ; 41, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Incentive-based conservation has become a significant part of how tropical forests are being governed. Reducing emissions from deforestation and forest degradation (REDD+) is a mechanism to mitigate climate change that many countries have started to implement. REDD+, however, is criticized for its potential negative impacts on local populations and Indigenous people. To prevent and mitigate the negative impacts, safeguards are increasingly being used to prevent and shift the focus toward 'non-carbon' elements of forest conservation. We discuss the legitimacy of these types of projects from a stakeholder perspective. Using a normative framework, we assess the Ecuadorian Socio Bosque conservation program, concentrating more specifically on the level of input and output legitimacy. Results show that Socio Bosque in its current form has shortcomings in both input and output legitimacy. We argue that an encompassing conception of legitimacy, including input and output criteria, particularly from a local stakeholder perspective, is essential for the future success of incentive-based conservation and particularly for REDD+ projects. (C) 2014 Elsevier Ltd. All rights reserved.
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| 42. |
- Krause, Torsten, et al.
(författare)
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What future for primates? Conservation struggles in the forests of Cross River State, Nigeria
- 2019
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 14:6, s. 1515-1529
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Tidskriftsartikel (refereegranskat)abstract
- While deforestation and forest degradation have gained attention in recent years not least at the UN climate negotiations, a third “de”, i.e., defaunation, has to a great extent been overlooked. Human-induced faunal loss does not only reduce tree species diversity, but also significantly erodes key ecosystem services and functions and further disadvantages local communities. In this article, we analyze these impacts, and the associated multi-level governance gaps, through a case study of Nigeria’s Cross River State and make suggestions for more encompassing conservation approaches that take defaunation into account. To this end, we analyze the interplay between current forest governance and REDD+ in Cross River State and local hunting of forest fauna. Drawing on Ostrom’s social-ecological systems framework and a mixed-methods approach, we identify shortcomings and gaps of international and domestic forest governance, for instance, the ongoing expansion of agriculture in forest areas, a lack of collective action on forest fauna conservation at the local level, as well as conflicts amongst key actors at the sub-national level. Current REDD+ governance in Cross River State largely fails to address fauna loss and local hunting practices, but also affect allocation and access of environmental benefits and burdens for local people.
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| 43. |
- Leung, Samuel CY, et al.
(författare)
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Analytical validation of a standardized scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicenter collaboration
- 2019
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 75:2, s. 225-235
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections.Methods and results: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot‐spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799–0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot‐spot method (0.83; 95% CI = 0.74–0.90) did not. Visually, interobserver concordance in location of selected hot‐spots varies between cases. The median times for scoring were 9 and 6 min for global and hot‐spot methods, respectively.Conclusions: The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.
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| 44. |
- Nielsen, Torsten O, et al.
(författare)
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Abstract P2-03-01: Analytical validation of a standardized scoring protocol for Ki67 assessed on breast excision whole sections: An international multicenter collaboration
- 2018
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Ingår i: Cancer research. Supplement. - 1538-7445. ; 78:4
-
Konferensbidrag (refereegranskat)abstract
- Aims: (i) Determine whether between-observer reproducibility for Ki67 when assessed on whole sections according to a standardized scoring protocol is adequate for clinical application. (ii) Compare between-observer reproducibility of Ki67 scores assessed on hot-spots to scores using a global method that averages across a tissue section.Background: The nuclear proliferation biomarker Ki67 has multiple potential roles in breast cancer, including aiding decisions based on prognosis, but unacceptable levels of between-laboratory variability have been observed. The International Ki67 in Breast Cancer Working Group has undertaken a systematic program to determine whether Ki67 measurement can be analytically validated and standardized across labs. In phase 1, variability in visual interpretation was identified as an important source of variability. Phases 2 and 3a showed that adherence to defined scoring methods substantially improved reproducibility in scoring tissue microarrays and core-cut biopsies. We now assess whether acceptable reproducibility can be achieved on whole sections.Methods: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 to assemble 4 sets of 30 stained tumor sections, circulated around 23 labs in 12 countries. Ki67 was scored by 2 methods by all labs: (a) global: 4 fields of 100 tumor cells each were selected to reflect observed heterogeneity in nuclear staining (b) hot-spot: the field with highest Ki67 percentage of tumor cells with nuclear staining was selected and up to 500 cells scored. Ki67 scores were log2-transformed for statistical analyses and back-transformed for presentation. The primary objective was to assess whether either method could achieve an intraclass correlation coefficient (ICC) significantly greater than 0.8, considered substantial to almost-perfect reproducibility. Secondary objectives were to assess which method had highest observed ICC and to assess whether observers identified the same “hot-spots”.Results: ICC for the global method was 0.87 (95%CI: 0.799-0.93), marginally meeting the prespecified success criterion. The ICC for the hot-spot method was 0.83 (95%CI: 0.74-0.90) and had a CI extending below the success criterion. Across the 23 labs, geometric mean value of the 30 scores ranged from 8.5 to 19.6 for the global method and from 12.8 to 30.3 for the hot-spot method. The overall mean (95% CI) of these values was 12.9 (11.9-14.0) and 20.9 (19.1-22.8), respectively. Visually, between-laboratory agreement in location of selected hot-spot varies between cases. The median times for scoring were 9 and 6 minutes for global and hot-spot methods respectively.Conclusions: The global method marginally met the prespecified criterion of success; it should now be evaluated for clinical validity in appropriate cohorts of cases. The hot-spot method was observed to have slightly less reproducibility between labs. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between labs further
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| 45. |
- Polley, Mei-Yin C, et al.
(författare)
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An international study to increase concordance in Ki67 scoring.
- 2015
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Ingår i: Modern Pathology. - : Elsevier BV. - 1530-0285 .- 0893-3952. ; 28:6, s. 778-786
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Tidskriftsartikel (refereegranskat)abstract
- Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.Modern Pathology advance online publication, 20 February 2015; doi:10.1038/modpathol.2015.38.
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| 46. |
- Schistad, Elina Iordanova, et al.
(författare)
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A population-based study of inflammatory mechanisms and pain sensitivity
- 2020
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 161:2, s. 338-350
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Tidskriftsartikel (refereegranskat)abstract
- Two recent studies suggest that experimental pain sensitivity is associated with low-grade systemic inflammation. However, only 2 biomarkers have been identified, and the studies were conducted in adult individuals where confounding effects of comorbid diseases cannot be excluded. We therefore tested associations between pain sensitivity and 119 inflammation-related serum biomarkers in 827 healthy adolescents (15-19 years) in the population-based Tromso Study: Fit Futures. The main outcome measure was cold-pressor pain tolerance (CPT), tested by placing the dominant hand in circulating cold (3 degrees C) water for a maximum of 105 seconds. Secondary outcomes were heat and pressure pain threshold and tolerance. Twelve proteins and 6 fatty acids were significantly associated with CPT after adjustment for possible confounding factors and correction for multiple comparisons. Of these, all fatty acids and 10 proteins were protective, ie, higher biomarkers levels were associated with increased CPT, whereas 2 biomarkers were associated with lower tolerance. Taken together, these biomarkers predicted completion of the tolerance test with a C-statistic of 0.65. Results for heat and pressure pain tolerance were remarkably similar, strengthening the generalizability of our findings. In this cohort of young healthy individuals, we found a relationship between inflammation-related biomarkers and pain tolerance and thresholds. Biomarkers with anti-inflammatory and analgesic effects predominated, suggesting that the development of prophylactic dietary or pharmaceutical treatments may be possible.
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| 47. |
- Stebbins, Amanda, et al.
(författare)
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A Model for Predicting Mortality in Acute ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention : Results From the Assessment of Pexelizumab in Acute Myocardial Infarction Trial
- 2010
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Ingår i: Circulation: Cardiovascular Interventions. - 1941-7640. ; 3:5, s. 414-422
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Tidskriftsartikel (refereegranskat)abstract
- Background-Accurate models to predict mortality are needed for risk stratification in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods and Results-We examined 5745 patients with STEMI undergoing primary PCI in the Assessment of Pexelizumab in Acute Myocardial Infarction Trial within 6 hours of symptom onset. A Cox proportional hazards model incorporating regression splines to accommodate nonlinearity in the log hazard ratio (HR) scale was used to determine baseline independent predictors of 90-day mortality. At 90 days, 271 (4.7%) of 5745 patients died. Independent correlates of 90-day mortality were (in descending order of statistical significance) age (HR, 2.03/10-y increments; 95% CI, 1.80 to 2.29), systolic blood pressure (HR, 0.86/10-mm Hg increments; 95% CI, 0.82 to 0.90), Killip class (class 3 or 4 versus 1 or 2) (HR, 4.24; 95% CI, 2.97 to 6.08), heart rate (>70 beats per minute) (HR, 1.45/10-beat increments; 95% CI, 1.31 to 1.59), creatinine (HR, 1.23/10-mu mol/L increments >90 mu mol/L; 95% CI, 1.13 to 1.34), sum of ST-segment deviations (HR, 1.25/10-mm increments; 95% CI, 1.11 to 1.40), and anterior STEMI location (HR, 1.47; 95% CI, 1.12 to 1.93) (c-index, 0.82). Internal validation with bootstrapping confirmed minimal overoptimism (c-index, 0.81). Conclusions-Our study provides a practical method to assess intermediate-term prognosis of patients with STEMI undergoing primary PCI, using baseline clinical and ECG variables. This model identifies key factors affecting prognosis and enables quantitative risk stratification that may be helpful in guiding clinical care and for risk adjustment for observational analyses. (Circ Cardiovasc Interv. 2010;3:414-422.)
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| 48. |
- Tremaroli, Valentina, 1978, et al.
(författare)
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Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation
- 2015
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 22:2, s. 228-238
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls. By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery.
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