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- Abramson, JS, et al.
(författare)
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Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:14, s. 1675-1684
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Tidskriftsartikel (refereegranskat)abstract
- This global, phase 3 study compared lisocabtagene maraleucel (liso-cel) with standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT) were randomized 1:1 to liso-cel (100×106 CAR+ T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS) by independent review. A total of 184 patients were randomized. In this primary analysis with a median follow-up of 17.5 months, median EFS was not reached (NR) for liso-cel versus 2.4 months for SOC (hazard ratio [HR] = 0.356; 95% confidence interval [CI]: 0.243‒0.522). Complete response (CR) rate was 74% for liso-cel versus 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel versus 6.2 months for SOC (HR = 0.400; 95% CI: 0.261‒0.615; P < .0001). Median overall survival was NR for liso-cel versus 29.9 months for SOC (HR = 0.724; 95% CI: 0.443‒1.183; P = .0987). When adjusted for crossover from SOC to liso-cel, median overall survival was NR for liso-cel and SOC (HR = 0.415; 95% CI: 0.251‒0.686). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4/5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel over SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. (ClinicalTrials.gov; NCT03575351.)
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- Gunnarsson, S., et al.
(författare)
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Effects of short-day treatment on long-term growth performance and maturation of farmed Arctic charr Salvelinus alpinus reared in brackish water
- 2014
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Ingår i: Journal of Fish Biology. - : Wiley. - 0022-1112. ; 85:4, s. 1211-1226
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Tidskriftsartikel (refereegranskat)abstract
- The effects of a 6 week short-day photoperiod followed by continuous light, applied during the juvenile phase of Arctic charr Salvelinus alpinus in fresh water on smoltification and on the long-term growth andmaturity following transfer to brackish water (BW) (constant salinity of either 17 and 27 or increasing salinity in steps from 17 to 27) were investigated. Prior to salinity transfer, the juveniles were either reared at continuous light (C group) or reared for 6 weeks on a short day (8L: 16D, S group) followed by continuous light (24L: 0D). Increased salinity had negative effect on growth, with female fish reared at 17 salinity weighing 19 and 27% more than the salinity-step group (17-27) and the 27 salinity group, respectively. The stepwise acclimation to salinity had limited advantage in terms of growth rate. Short photoperiod for 6 weeks (November to January) followed by continuous light improved growth, but not seawater (SW) tolerance. Gill Na+, K+-ATPase activity and plasma Na+ levels changed with time, indicating some variation in osmoregulatory capacity during the experimental period. Overall, there appear to be interactive effects on maturation from applying short-day photoperiod followed by rearing at higher salinities. Plasma leptin varied with time and may be linked to stress caused by the observed variations in osmoregulatory ability. It is concluded that changes in growth rates observed in this study are mainly related to rearing salinity with higher growth rates at lower salinities. Short-day photoperiod has some growth-inducing effects but did not improve SW tolerance. Farmers of S. alpinus using BW for land-based rearing should keep salinity at moderate and stable levels according to these results to obtain best growth.
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- Kutschera, Verena E., et al.
(författare)
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High genetic variability of vagrant polar bears illustrates importance of population connectivity in fragmented sea ice habitats
- 2016
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Ingår i: Animal Conservation. - : Wiley. - 1367-9430 .- 1469-1795. ; 19:4, s. 337-349
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Tidskriftsartikel (refereegranskat)abstract
- Projections by the Intergovernmental Panel on Climate Change (IPCC) and sea ice forecasts suggest that Arctic sea ice will decline markedly in coming decades. Expected effects on the entire ecosystem include a contraction of suitable polar bear habitat into one or few refugia. Such large-scale habitat decline and fragmentation could lead to reduced genetic diversity. Here we compare genetic variability of four vagrant polar bears that reached Iceland with that in recognized subpopulations from across the range, examining 23 autosomal microsatellites, mitochondrial control region sequences and Y-chromosomal markers. The vagrants' genotypes grouped with different genetic clusters and showed similar genetic variability at autosomal microsatellites (expected heterozygosity, allelic richness, and individual heterozygosity) as individuals in recognized subpopulations. Each vagrant carried a different mitochondrial haplotype. A likely route for polar bears to reach Iceland is via Fram Strait, a major gateway for the physical exportation of sea ice from the Arctic basin. Vagrant polar bears on Iceland likely originated from more than one recognized subpopulation, and may have been caught in sea ice export during long-distance movements to the East Greenland area. Although their potentially diverse geographic origins might suggest that these vagrants encompass much higher genetic variability than vagrants or dispersers in other regions, the four Icelandic vagrants encompassed similar genetic variability as any four randomly picked individuals from a single subpopulation or from the entire sample. We suggest that this is a consequence of the low overall genetic variability and weak range-wide genetic structuring of polar bears - few dispersers can represent a large portion of the species' gene pool. As predicted by theory and our demographic simulations, continued gene flow will be necessary to counteract loss of genetic variability in increasingly fragmented Arctic habitats. Similar considerations will be important in the management of other taxa that utilize sea ice habitats.
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