| 11. |
- Lane, J. C. E., et al.
(författare)
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Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
- 2020
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Ingår i: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 2:11, s. E698-E711
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Tidskriftsartikel (refereegranskat)abstract
- Background Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I-2 value was less than 0.4. Findings The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Selfcontrolled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1.65 [95% CI 1.12-2.44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2.19 [95% CI 1.22-3.95]), chest pain or angina (1.15 [1.05-1.26]), and heart failure (1.22 [1.02-1.45]). Interpretation Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.
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| 14. |
- Grimsholm, O., et al.
(författare)
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The Interplay between CD27(dull) and CD27(brig)(ht) B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 30:9, s. 2963-
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Tidskriftsartikel (refereegranskat)abstract
- Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27(dull) and CD27(bright) MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27(du)(ll) and CD27(bright) MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27(du)(ll) into the CD27(bright) MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27(du)(ll) MBCs transit to the more differentiated CD27 bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27(du)(ll) clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27(du)(ll) MBCs that expand and differentiate in response to change.
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| 15. |
- Lebedev, A.A., et al.
(författare)
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Amplification of the signal in triode structures of ion detectors based on 6H-SIC epitaxial films
- 2001
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 79:26, s. 4447-4449
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of about 50 times the inneramplification of signals in SiC-based detectors of short-range ions is shown. The detector has an n-p-n+-like structure, where the p-type base was grown epitaxially on a 6H n+-SiC substrate. To complete the structure a Schottky barrier was made on top. Detector parameters were investigated in a "floating base" regime. Alpha particles from 244Cm were used and the augmentation of signal (E) with increasing applied voltage (U) was investigated. A superlinear increase of E was observed with a significant (tens of times) amplification of the introduced by the alpha particle nonequilibrium charge. It was also found that the nonuniformity of the diffusion-drift carrier transport parameters in the films does not exceed 10%. © 2001 American Institute of Physics.
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| 16. |
- Shubina, T. V., et al.
(författare)
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III-nitride microcrystal cavities with quasi whispering gallery modes grown by molecular beam epitaxy
- 2016
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Ingår i: Physica status solidi. B, Basic research. - : WILEY-V C H VERLAG GMBH. - 0370-1972 .- 1521-3951. ; 253:5, s. 845-852
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Tidskriftsartikel (refereegranskat)abstract
- This paper analyzes current trends in fabrication of III-nitride microresonators exploiting whispering gallery modes. Novel cup-cavities are proposed and their fabrication from GaN and InN by molecular beam epitaxy on patterned substrates is described. These cup-cavities can concentrate the mode energy in a subwavelength volume. Their mode energies are stable up to room temperature, being identical in large microcrystals. In these cavities, mode switching can be realized by means of refractive index variation. Cup-cavity modes, being inferior to plasmonic resonances in the respect of integral emission enhancement, have advantages for spectrally selective amplification of quantum transitions in site-controlled nano-emitters. (C) 2016 WILEY-VCH Verlag GmbH amp; Co. KGaA, Weinheim
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| 17. |
- Shubina, T. V., et al.
(författare)
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III-nitride tunable cup-cavities supporting quasi whispering gallery modes from ultraviolet to infrared
- 2015
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 5:17970
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Tidskriftsartikel (refereegranskat)abstract
- Rapidly developing nanophotonics needs microresonators for different spectral ranges, formed by chip-compatible technologies. In addition, the tunable ones are much in demand. Here, we present site-controlled III-nitride monocrystal cup-cavities grown by molecular beam epitaxy. The cup-cavities can operate from ultraviolet to near-infrared, supporting quasi whispering gallery modes up to room temperature. Besides, their energies are identical in large ripened crystals. In these cavities, the refractive index variation near an absorption edge causes the remarkable effect of mode switching, which is accompanied by the spatial redistribution of electric field intensity with concentration of light into a subwavelength volume. Our results shed light on the mode behavior in semiconductor cavities and open the way for single-growth-run manufacturing the devices comprising an active region and a cavity with tunable mode frequencies.
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