| 1. |
- Aad, G., et al.
(författare)
-
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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| 2. |
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| 3. |
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| 4. |
- Aad, G., et al.
(författare)
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Readiness of the ATLAS Tile Calorimeter for LHC collisions
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
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Tidskriftsartikel (refereegranskat)abstract
- The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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| 5. |
- 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
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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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| 6. |
- 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
-
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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| 7. |
- 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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| 8. |
- Liwing, Johan, et al.
(författare)
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Improved survival in myeloma patients : starting to close in on the gap between elderly patients and a matched normal population
- 2014
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 164:5, s. 684-693
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Tidskriftsartikel (refereegranskat)abstract
- The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2.8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4.9 years) compared to conventional treatment (2.3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6.9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.
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| 9. |
- Lund, Johan, et al.
(författare)
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Addition of thalidomide to melphalan and prednisone treatment prolongs survival in multiple myeloma - a retrospective population based study of 1162 patients.
- 2014
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 92:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- The combination of melphalan and prednisone (MP) has been the standard treatment of multiple myeloma (MM). Since the introduction of novel agents, the clinical outcome in MM has improved. Several prospective studies with thalidomide combined with MP (MPT) compared to MP have been performed, most of them showing that MPT gives a better response rate and median overall survival (OS). Among 1843 MM patients admitted to 15 Swedish centres, we selected all patients treated with MP and MPT in 1(st) , 2(nd) , 3(rd) or 4(th) line of therapy, in total 888 patients treated with MP and 274 with MPT. Patients were evaluated for response rate, OS and TTNT. Multivariate Cox model analysis was made to adjust for different criteria at time for MM-diagnosis. The median OS from beginning of 1(st) line of treatment was 2.2/4.2 years after MP/MPT respectively, and in 2(nd) , 3(rd) and 4(th) line of treatment 1.8/2.9, 1.4/1.6 and 1.1/1.9 years (P<0.0001, 0.003, 0.74 and 0.235). The relative risk for death in the MPT group vs. the MP group was 0.61 (95% CI: 0.45-0.84) in 1(st) and 0.55 (0.38-0.83), p<0.01) in 2(nd) line. Treatment with MPT gave a significantly better overall survival rate after both 1(st) and 2(nd) line of therapy compared to treatment with MP only. This article is protected by copyright. All rights reserved.
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| 10. |
- Uttervall, Katarina, et al.
(författare)
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A Combination Regimen of Bortezomib, Cyclophosphamide and Betamethasone Gives Quicker, Better and More Durable Response than VAD/CyBet Regimens : Results from a Swedish Retrospective Analysis
- 2013
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Ingår i: Acta Haematologica. - : S. Karger AG. - 0001-5792 .- 1421-9662. ; 130:1, s. 7-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Induction therapy for multiple myeloma (MM) and remission status before high-dose treatment (HDT) have been shown to be prognostic factors for survival outcome, although the optimal induction therapy is yet to be defined. Methods: We conducted a retrospective analysis of the impact of induction therapy on survival outcome before and after HDT in MM patients. The study included 236 consecutive patients who underwent HDT. Results: One hundred and forty-two patients (62%) were treated with vincristine, doxorubicin and dexamethasone (VAD) or cyclophosphamide and betamethasone (CyBet) and 94 (38%) were treated with bortezomib, cyclophosphamide and betamethasone (VCB) as induction. Time to first and time to best response was faster in the VCB group than in the VAD/CyBet group, with 42 versus 75 (p < 0.001) and 54 versus 88 days (p < 0.001), respectively. After induction therapy, 49% of the patients in the VCB group and 38% in the VAD/CyBet group achieved a very good partial response or better. Multivariate analysis revealed younger age, lower International Staging System stage and induction treatment with VCB as variables associated with favourable time to progression. Conclusions:Outcome measured as response and time to progression before and after HDT in MM differs depending on type of induction treatment and suggests that VCB is a highly effective induction regimen that confers a post-HDT advantage.
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| 11. |
- Aad, G., et al.
(författare)
-
- 2011
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Aad, G., et al.
(författare)
-
- 2012
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Ingår i: Nuclear Physics, Section B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 864:3, s. 341-381
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Borgegard, Tomas, et al.
(författare)
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Alzheimers Disease: Presenilin 2-Sparing gamma-Secretase Inhibition Is a Tolerable A beta Peptide-Lowering Strategy
- 2012
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Secretase inhibition represents a major therapeutic strategy for lowering amyloid beta (A beta) peptide production in Alzheimers disease (AD). Progress toward clinical use of gamma-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The gamma-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between A beta production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1(PS1) over PS2 subclass of gamma-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain A beta levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious gamma-secretase targeting strategy for AD.
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| 14. |
- Borgegård, Tomas, et al.
(författare)
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Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
- 2012
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
-
Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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| 15. |
- Hegmar, Hannes, et al.
(författare)
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Liver stiffness predicts progression to liver-related events in patients with chronic liver disease - A cohort study of 14 414 patients
- 2024
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Ingår i: Liver international. - : WILEY. - 1478-3223 .- 1478-3231.
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterogenous populations. Methods: This Swedish multi-centre cohort study included patients (n = 14 414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C-index was used to measure discrimination of VCTE. Results: Included patients had a median age of 46 (interquartile range 34-57), median LSM of 5.9 kPa (4.6-8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow-up of 5.9 (4.3-8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM >= 25 kPa, 28.7% developed cirrhosis with portal hypertension within 5 years of follow-up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval = 37.6-62.0). VCTE had a high discriminative ability, with C-indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC. Conclusions: Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow-up and treatment decisions.
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| 16. |
- Liin, Sara, et al.
(författare)
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Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors
- 2018
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Ingår i: The Journal of General Physiology. - : ROCKEFELLER UNIV PRESS. - 0022-1295 .- 1540-7748. ; 150:8, s. 1215-1230
-
Tidskriftsartikel (refereegranskat)abstract
- Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels. However, because they inactivate voltage-gated sodium channels by promoting activation of one voltage sensor, we suggest that, despite different effects on the channel gates, the biaryl-sulfonamide motif is a general ion-channel activator motif. Because these compounds block action potential-generating sodium and calcium channels and open an action potential-dampening potassium channel, they should have a high propensity to reduce excitability. This opens up the possibility to build new excitability-reducing pharmaceutical drugs from the biaryl-sulfonamide scaffold.
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| 17. |
- Lund, Line Naomi, et al.
(författare)
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Novel peptide ligand with high binding capacity for antibody purification
- 2012
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1225, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Small synthetic ligands for protein purification have become increasingly interesting with the growing need for cheap chromatographic materials for protein purification and especially for the purification of monoclonal antibodies (mAbs). Today, Protein A-based chromatographic resins are the most commonly used capture step in mAb down stream processing; however, the use of Protein A chromatography is less attractive due to toxic ligand leakage as well as high cost. Whether used as an alternative to the Protein A chromatographic media or as a subsequent polishing step, small synthetic peptide ligands have an advantage over biological ligands; they are cheaper to produce, ligand leakage by enzymatic degradation is either eliminated or significantly reduced, and they can in general better withstand cleaning in place (CIP) conditions such as 0.1 M NaOH. Here, we present a novel synthetic peptide ligand for purification of human IgG. Immobilized on WorkBeads, an agarose-based base matrix from Bio-Works, the ligand has a dynamic binding capacity of up to 48 mg/mL and purifies IgG from harvest cell culture fluid with purities and recovery of >93%. The binding affinity is similar to 10(5) M-1 and the interaction is favorable and entropy-driven with an enthalpy penalty. Our results show that the binding of the Fc fragment of IgG is mediated by hydrophobic interactions and that elution at low pH is most likely due to electrostatic repulsion. Furthermore, we have separated aggregated IgG from non-aggregated IgG, indicating that the ligand could be used both as a primary purification step of IgG as well as a subsequent polishing step. (C) 2012 Elsevier B.V. All rights reserved.
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| 18. |
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| 19. |
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| 20. |
- Watz, Johan, 1977-, et al.
(författare)
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Atlantic salmon in regulated rivers: Understanding river management through the ecosystem services lens
- 2022
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Ingår i: Fish and Fisheries. - : John Wiley & Sons. - 1467-2960 .- 1467-2979. ; 23:2, s. 478-491
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Tidskriftsartikel (refereegranskat)abstract
- Known as the “king of fishes”, the Atlantic salmon (Salmo salar, Salmonidae) is an iconic freshwater species whose contribution to human wellbeing has long been recognized, as have widespread declines in its abundance, partly due to river regulation. To understand how salmon conservation has been addressed within the ecosystem services (ES) framework, we synthesized the peer-reviewed literature on ES provided by salmon in regulated rivers. We developed a search string to capture allusions to provisioning, regulating, supporting and cultural ES and assessed the results to identify knowledge gaps. The effects of hydropower on fisheries catches and on modelled populations were shown is several publications. Overall, few studies focused explicitly on ES from salmon and hydropower; this is surprising given the considerable body of literature on salmon in regulated rivers. Wild salmon as a food source and other provisioning services are less important today than historically. Because predators such as salmon are important for facilitating biodiversity by cycling nutrients and controlling food webs, there is a scope of work for future assessments of these regulating and supporting services. Few papers explicitly addressed cultural ES, despite the salmon’s longstanding iconic status; this is a knowledge gap for future ES assessments in relation to hydropower. The influence of ES assessments for policy makers is growing through the Intergovernmental Panel for Biodiversity and Ecosystem Services (IPBES) and the post-2020 biodiversity strategy. Explicitly addressing ES poses an opportunity for river managers to raise awareness of aquatic conservation efforts and well-informed decision-making for sustaining ES.
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| 21. |
- Aad, G., et al.
(författare)
-
- 2011
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swepub:Mat__t (refereegranskat)
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| 22. |
- Aad, G., et al.
(författare)
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The ATLAS Collaboration
- 2009
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 830:1-4, s. 925c-940c
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Aad, G., et al.
(författare)
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The ATLAS Experiment at the CERN Large Hadron Collider
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
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Forskningsöversikt (refereegranskat)abstract
- The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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| 24. |
- Abat, E., et al.
(författare)
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Combined performance studies for electrons at the 2004 ATLAS combined test-beam
- 2010
-
Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 5, s. P11006-
-
Tidskriftsartikel (refereegranskat)abstract
- In 2004 at the ATLAS (A Toroidal LHC ApparatuS) combined test beam, one slice of the ATLAS barrel detector (including an Inner Detector set-up and the Liquid Argon calorimeter) was exposed to particles from the H8 SPS beam line at CERN. It was the first occasion to test the combined electron performance of ATLAS. This paper presents results obtained for the momentum measurement p with the Inner Detector and for the performance of the electron measurement with the LAr calorimeter (energy E linearity and resolution) in the presence of a magnetic field in the Inner Detector for momenta ranging from 20 GeV/c to 100 GeV/c. Furthermore the particle identification capabilities of the Transition Radiation Tracker, Bremsstrahlungs-recovery algorithms relying on the LAr calorimeter and results obtained for the E/p ratio and a way how to extract scale parameters will be discussed.
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| 25. |
- Abat, E., et al.
(författare)
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Photon reconstruction in the ATLAS Inner Detector and Liquid Argon Barrel Calorimeter at the 2004 Combined Test Beam
- 2011
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- The reconstruction of photons in the ATLAS detector is studied with data taken during the 2004 Combined Test Beam, where a full slice of the ATLAS detector was exposed to beams of particles of known energy at the CERN SPS. The results presented show significant differences in the longitudinal development of the electromagnetic shower between converted and unconverted photons as well as in the total measured energy. The potential to use the reconstructed converted photons as a means to precisely map the material of the tracker in front of the electromagnetic calorimeter is also considered. All results obtained are compared with a detailed Monte-Carlo simulation of the test-beam setup which is based on the same simulation and reconstruction tools as those used for the ATLAS detector itself.
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| 26. |
- Abat, E., et al.
(författare)
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Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
- 2009
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
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Tidskriftsartikel (refereegranskat)abstract
- A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
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| 27. |
- Agarwal, Anubha, et al.
(författare)
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Toward a Universal Definition of Etiologies in Heart Failure : Categorizing Causes and Advancing Registry Science
- 2024
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Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 17:4
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Forskningsöversikt (refereegranskat)abstract
- Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.
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| 28. |
- Agudo, Antonio, et al.
(författare)
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Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 34:6, s. 1244-1250
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.
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| 29. |
- Agudo, Antonio, et al.
(författare)
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Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition
- 2006
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 15:12, s. 2427-2434
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C > A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G > A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.
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| 30. |
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| 31. |
- Aharrouche, M., et al.
(författare)
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Measurement of the response of the ATLAS liquid argon barrel calorimeter to electrons at the 2004 combined test-beam
- 2010
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 614:3, s. 400-432
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Tidskriftsartikel (refereegranskat)abstract
- During summer and fall 2004, the response of a full slice of the ATLAS barrel detector to different particles was studied in controlled beam. One module of the ATLAS liquid argon barrel calorimeter identical to the production modules and read out by the final front-end and back-end electronics was used for electromagnetic calorimetry. This paper presents and discusses the electron performance of the LAr barrel calorimeter, including linearity, uniformity, and resolution with different amounts of material upstream the calorimeter and energies ranging from 1 to 250 GeV.
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| 32. |
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| 33. |
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| 34. |
- Arana, Alejandro, et al.
(författare)
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Long-Term Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus and Pimecrolimus : Final Results from the Extension of the Cohort Study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE)
- 2021
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Ingår i: Clinical Epidemiology. - : Dove Medical Press. - 1179-1349. ; 13, s. 1141-1153
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Evidence is insufficient to infer whether topical calcineurin inhibitors (TCIs; tacrolimus and pimecrolimus) cause malignancy. The study objective was to estimate the long-term risk of skin cancer and lymphoma associated with topical TCI use in adults and children, separately.Patients and Methods: A cohort study in Denmark, Sweden, UK, and the Netherlands was conducted. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for nonmelanoma skin cancer (NMSC), melanoma, cutaneous T-cell lymphoma (CTCL), non-Hodgkin lymphoma (NHL) excluding CTCL, and Hodgkin lymphoma (HL) in new users of TCIs versus users of moderate/high-potency topical corticosteroids.Results: The study included 126,908/61,841 adults and 32,605/27,961 children initiating treatment with tacrolimus/pimecrolimus, respectively. Follow-up was ≥10 years for 19% of adults and 32% of children. Incidence rate ratios and (95% confidence intervals) for tacrolimus versus corticosteroid users in adults were <1 for melanoma, non-Hodgkin lymphoma, and Hodgkin lymphoma; and 1.80 (1.25-2.58) for cutaneous T-cell lymphoma. For pimecrolimus, IRRs in adults were <1 for non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and Hodgkin's lymphoma; and 1.21 (1.03-1.41) for melanoma; and 1.28 (1.20-1.35) for nonmelanoma skin cancer. In children, results were inconclusive due to few events. In adults, incidence rate ratios ≥5 years after first topical calcineurin inhibitor exposure were not higher than in overall analyses.Conclusion: Overall, we found little evidence associating use of topical calcineurin inhibitors with skin cancer and lymphoma; confounding by indication, surveillance bias, and reverse causation may have influenced these results. Even if causal, the public health impact of these excess risks would be low and confined to the first years of exposure.
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| 35. |
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| 36. |
- Balassiano, Karen, et al.
(författare)
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Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
- 2011
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Ingår i: Cancer Letters. - Amsterdam : Elsevier BV. - 1872-7980 .- 0304-3835. ; 311:1, s. 85-95
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological subtype and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 37. |
- Bandak, Ghassan, et al.
(författare)
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Hyperkalemia After Initiating Renin-Angiotensin System Blockade : The Stockholm Creatinine Measurements (SCREAM) Project
- 2017
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score.Methods and Results: We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new beta-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new beta-blocker and ACEI/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m(2) were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration.Conclusions: Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m(2), but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.
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| 38. |
- Bergenfeldt, Henrik, et al.
(författare)
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Time-dependent prognostic effects of recipient and donor age in adult heart transplantation
- 2019
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 38:2, s. 174-183
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recipient age and donor age are well-known prognostic factors in adult heart transplantation. However, the association between donor age and recipient age and their interaction and short- and long-term mortality is unknown. METHODS: We studied 64,354 heart transplants to adult recipients between 1988 and 2013 in the ISHLT Registry. Donor age and recipient age were analyzed as continuous and categorical variables and restricted cubic spline functions to assess non-linear associations and interactions. The end-point was all-cause mortality. RESULTS: In the multivariable analysis, the odds ratio for 30-day mortality per 10-year increase in recipient age was 1.05 (95% confidence interval [CI] 1.01 to 1.08, p = 0.009) compared with 1.19 (95% CI 1.15 to 1.22, p < 0.001) for donor age. In the first year, the hazard ratio for mortality was 1.05 (95% CI 1.02 to 1.07, p < 0.001) for a 10-year increase in recipient age and 1.16 (1.14 to 1.18, p < 0.001) for donor age. In Years 1 to 3, 3 to 5, and 5 to 10 post-transplant, the hazard ratio was 0.89 (95% CI 0.86 to 0.92, p < 0.001), 0.98 (95% CI 0.94 to 1.02, p = 0.266), and 1.14 (95% CI 1.11 to 1.17, p < 0.001) for recipient age, and 1.12 (95% CI 1.08 to 1.14, p < 0.001), 1.07 (95% CI 1.03 to 1.10, p < 0.001), and 1.07 (95% CI 1.05 to 1.10, p < 0.001) for donor age, respectively. There was no interaction of recipient age and donor age with survival at any follow-up time-point. CONCLUSIONS: At 30 days, both higher donor age and recipient age were associated with higher mortality. At 1 to 10 years, older donor age was associated with higher mortality at all follow-up time-points, but the hazard was greater in the short term, and recipient age was associated only with longer term mortality. The risk from donor age appears equal across recipient age groups.
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| 39. |
- Boezio, M., et al.
(författare)
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The space experiment PAMELA
- 2004
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Ingår i: Nuclear Physics B - Proceedings Supplements. - : Elsevier BV. ; , s. 39-46
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Konferensbidrag (refereegranskat)abstract
- We present in this paper a status report of the space experiment PAMELA. PAMELA is a satellite-borne experiment which primarily aims to measure the antiproton and positron spectra in the cosmic radiation over a large energy range (from 80 MeV up to 190 GeV for antiprotons and from 50 MeV up to 270 GeV for positrons) and to search for antinuclei with a sensitivity of the order of 10(-8) in the antihelium/ helium ratio. In addition, it will measure the light nucleax component of cosmic rays and investigate phenomena connected with Solar and Earth physics. The apparatus will be installed onboard the polar orbiting Resurs DK1 satellite, which will be launched into space by a Soyuz TM2 rocket in 2004 from Baikonur cosmodrome in Kazakhstan, for a 3 year long mission. PAMELA consists of: a time of flight system, a transition radiation detector, a magnetic spectrometer, an anticoincidence detector, an electromagnetic imaging calorimeter, a shower tail catcher scintillator and a neutron detector.
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| 40. |
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Borgerlighet
- 2007
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Ingår i: Fronesis. - 1404-2614. ; :24
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Annan publikation (refereegranskat)abstract
- Lyxkonsumtion, Stureplansbrats, medelklass och överklass diskuteras allt mer. Samtidigt har den partipolitiska borgerligheten tagit över regeringsmakten. Men vad innebär det att tala om borgerlighet i dagens Sverige? Vilka tillhör denna sociala kategori och vad utmärker den? I Fronesis nr 24 dissekeras gårdagens såväl som dagens borgerlighet.
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| 41. |
- Braun, Oscar Ö., et al.
(författare)
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Continuous-flow LVADs in the Nordic countries : complications and mortality and its predictors
- 2019
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 53:1, s. 14-20
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries.Design: This was a retrospective, international, multicenter cohort study.Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p < .001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively.Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.
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| 42. |
- Caldenby, Claes, 1946, et al.
(författare)
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Architecture and Engineering - 10 Years Anniversary Book
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A Jubilee Book will tell our story, a common share of moments and activities, thoughts and reflections, from 10 years of Architecture and Engineering, in short AT. A creative mixture of strong professional cultures, a desire and an enthusiasm for searching out and taking on the challanges of the future in architecture and engineering of the built environment.
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| 43. |
- Carneiro, Fatima, et al.
(författare)
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Pathology findings and validation of gastric and esophageal cancer cases in a European cohort (EPIC/EUR-GAST)
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 42:5, s. 618-627
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trends and etiological factors. However, the available information is not always collected in population cancer registries, and heterogeneous criteria have been applied for the histopathological classification of tumors. We describe the pathological features of incident gastric and esophageal cancers identified within the European Prospective Investigation into Cancer and Nutrition (EPIC). Material and methods. In an investigation on gastric and esophageal cancer (EUR-GAST) in the EPIC project, a validation study of diagnoses reported by EPIC centers was conducted by a European panel of pathologists. Original pathology reports, stained slides of tumors and the respective paraffin blocks were requested from the centers. Results. The whole series encompassed 467 cancer cases (gastric and esophageal cancers). Material was available for histopathological validation in 263 cases (56%); in the remaining cases, information was retrieved from the original reports (n = 110; 24%) or codes provided by the EPIC centers (n = 94; 20%). Among cases submitted to histopathological validation reported originally as unknown histotype or unknown site, a specific diagnosis was made in 95% and 74% of the cases, respectively. In cases for which only the original reports were available, the respective percentages were 46% and 67%. Gastric adenocarcinomas were classified according to site (cardia (29.4%), non-cardia (48.2%) and unknown (22.4%)) and histological type (intestinal (33.4%), diffuse (33.7%) and mixed, unclassified or unknown (32.9%)). Frequency of cardia was higher in Northern countries (35%) than in Mediterranean countries (18%). Conclusions. In addition to providing epidemiological data within the EPIC cohort on gastric and esophageal adenocarcinomas, the results reported here confirm the relevance of a validation study, notably for multicenter studies.
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| 44. |
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| 45. |
- Casolino, M., et al.
(författare)
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Cosmic-ray observations of the heliosphere with the PAMELA experiment
- 2006
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Ingår i: Astrophysics. - : Elsevier BV. ; , s. 1848-1852
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Konferensbidrag (refereegranskat)abstract
- The PAMELA experiment is a multi-purpose apparatus built around a permanent magnet spectrometer, with the main goal of studying in detail the antiparticle component of cosmic rays. The apparatus will be carried in space by means of a Russian satellite, due to launch in 2005, for a three year-long mission. The characteristics of the detectors composing the instrument, alongside the long lifetime of the mission and the orbital characteristics of the satellite, will allow to address several items of cosmic-ray physics. In this paper, we will focus on the solar and heliospheric observation capabilities of PAMELA.
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| 46. |
- Cermakova, Pavla, et al.
(författare)
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Cardiovascular Diseases in similar to 30,000 Patients in the Swedish Dementia Registry
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 48:4, s. 949-958
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular diseases are leading causes of death and patients with dementia are often affected by them. Objective: Investigate associations of cardiovascular diseases with different dementia disorders and determine their impact on mortality. Methods: This study included 29,630 patients from the Swedish Dementia Registry (mean age 79 years, 59% women) diagnosed with Alzheimer's disease (AD), mixed dementia, vascular dementia, dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD), or unspecified dementia. Records of cardiovascular diseases come from the Swedish National Patient Register. Multinomial logistic regression and cox proportional hazard models were applied. Results: Compared to AD, we found a higher burden of all cardiovascular diseases in mixed and vascular dementia. Cerebrovascular diseases were more associated with DLB than with AD. Diabetes mellitus was less associated with PDD and DLB than with AD. Ischemic heart disease was less associated with PDD and FTD than AD. All cardiovascular diseases predicted death in patients with AD, mixed, and vascular dementia. Only ischemic heart disease significantly predicted death in DLB patients (HR = 1.72; 95% CI = 1.16-2.55). In PDD patients, heart failure and diabetes mellitus were associated with a higher risk of death (HR = 3.06; 95% CI = 1.74-5.41 and HR = 3.44; 95% CI = 1.31-9.03). In FTD patients, ischemic heart disease and atrial fibrillation or flutter significantly predicted death (HR = 2.11; 95% CI = 1.08-4.14 and HR= 3.15; 95% CI = 1.60-6.22, respectively). Conclusion: Our study highlights differences in the occurrence and prognostic significance of cardiovascular diseases in several dementia disorders. This has implications for the care and treatment of the different dementia disorders.
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| 47. |
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| 48. |
- Delcoigne, Benedicte, et al.
(författare)
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Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs : Results from four Nordic countries
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 81:6, s. 789-797
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.Methods: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.Results: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.Conclusion: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.
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| 49. |
- Dellgren, Goeran, et al.
(författare)
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Effect of once-per-daytacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial
- 2024
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Ingår i: LANCET RESPIRATORY MEDICINE. - 2213-2600. ; 12:1, s. 34-44
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Tidskriftsartikel (refereegranskat)abstract
- Background Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. Methods ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (005-01 mg/kg before transplantation and 01-02 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). Findings Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 552 years (SD 102), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 028 [95% CI 015-052], log-rank p<00001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 072 [95% CI 041-127], log-rank p=025). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 049 [95% CI 026-091], log-rank p=0021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. Interpretation Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation.
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| 50. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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