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- Usmani, SZ, et al.
(författare)
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Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma
- 2022
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 107:10, s. 2408-2417
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Tidskriftsartikel (refereegranskat)abstract
- In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) μg/mL for DARA SC and 496 (SD, 231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice. (Clinicaltrials gov. Identifier: NCT03277105.
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- Krickov, Ivan V., et al.
(författare)
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Sizable carbon emission from the floodplain of Ob River
- 2021
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Ingår i: Ecological Indicators. - : Elsevier. - 1470-160X .- 1872-7034. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- The Ob River floodplain is the second largest floodplain in the world. Despite its vast area, estimates of carbon (C) emissions from the Ob River floodplain are largely absent. Here we present seasonal C emission and water area extent from the main channel and the floodplain along a ~4 km reach in the boreal zone of the Ob River. We found strong seasonality in water area extent of the Ob main channel (~1.8 km2) and floodplain (~3 km2) with water covering 34% of land during flood and subsequently declining to ~16% and ~14% during summer and autumn baseflow, respectively. The C emissions also varied seasonally over the open water period, ranging from −0.1 to 0.6 g C m−2 d−1 for the Ob main channel and from 0 to 9 g C m−2 d−1 for the floodplain. The dissolved organic carbon positively affected CO2 concentrations and fluxes in the floodplain during all seasons, whereas pH and oxygen concentration negatively impacted CO2 concentrations and fluxes. Some nutrients (ammonia and phosphate) positively correlated with CO2 and CH4 concentrations in summer. The total C emission from the study reach (1.8 km2 main channel, 3 km2 floodplain) during moderate flooding was 236 ± 51 tons C yr−1 (>99% CO2, <1% CH4) with the floodplain accounting for ~65%. The contribution of the floodplain to the net river C evasion may be even greater during years of high flooding and in northern regions of the Ob River basin, where floodplain soils are more C-rich and are underlain by permafrost, and in years with more extensive flooding.
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- Lim, Artem G., et al.
(författare)
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Carbon emission and export from the Ket River, western Siberia
- 2022
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Ingår i: Biogeosciences. - : Copernicus Publications. - 1726-4170 .- 1726-4189. ; 19:24, s. 5859-5877
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent progress in the understanding of the carbon (C) cycle of Siberian permafrost-affected rivers, spatial and seasonal dynamics of C export and emission from medium-sized rivers (50 000-300 000 km2 watershed area) remain poorly known. Here we studied one of the largest tributaries of the Ob River, the Ket River (watershed Combining double low line 94 000 km2), which drains through pristine taiga forest of the boreal zone in the West Siberian Lowland (WSL). We combined continuous and discrete measurements of carbon dioxide (CO2) concentration using submersible CO2 sensor and floating chamber flux (FCO2), with methane (CH4), dissolved organic and inorganic C (DOC and DIC, respectively), particulate organic C and total bacterial concentrations over an 800 km transect of the Ket River main stem and its 26 tributaries during spring flood (May 2019) and 12 tributaries during summer baseflow (end of August-beginning of September 2019). The partial pressure of CO2 (pCO2) was lower and less variable in the main stem (2000 to 2500 μatm) compared to that in the tributaries (2000 to 5000 μatm). In the tributaries, the pCO2 was 40 % higher during baseflow compared to spring flood, whereas in the main stem, it did not vary significantly across the seasons. The methane concentration in the main stem and tributaries was a factor of 300 to 1900 (flood period) and 100 to 150 times lower than that of CO2 and ranged from 0.05 to 2.0 μmol L-1. The FCO2 ranged from 0.4 to 2.4 g C m-2 d-1 in the main channel and from 0.5 to 5.0 g C m-2 d-1 in the tributaries, being highest during August in the tributaries and weakly dependent on the season in the main channel. During summer baseflow, the DOC aromaticity, bacterial number, and needleleaf forest coverage of the watershed positively affected CO2 concentrations and fluxes. We hypothesize that relatively low spatial and seasonal variability in FCO2 of the Ket River is due to a flat homogeneous landscape (bogs and taiga forest) that results in long water residence times and stable input of allochthonous dissolved organic matter (DOM), which dominate the FCO2. The open water period (May to October) C emission from the fluvial network (main stem and tributaries) of the Ket River was estimated to 127 ± 11 Gg C yr-1, which is lower than the downstream dissolved and particulate C export during the same period. The estimated fluvial C emissions are highly conservative and contain uncertainties linked to ignoring hotspots and hot moments of emissions, notably in the floodplain zone. This stresses the need to improve the temporal resolution of FCO2 and water coverage across seasons and emphasizes the important role of WSL rivers in the release of CO2 into the atmosphere.
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- Vorobyev, Sergey N., et al.
(författare)
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Floodplain carbon dioxide emissions strongly exceed those of the main river stem : a case study of the Ob river, western Siberia
- 2024
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Ingår i: Journal of Hydrology. - : Elsevier. - 0022-1694 .- 1879-2707. ; 638
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Tidskriftsartikel (refereegranskat)abstract
- The importance of floodplains in carbon (C) evasion from the lotic systems is especially important in continental plains of low runoff such as the organic-rich Western Siberian Lowland (WSL). To quantify the relative importance of the floodplain compared to main stem CO2 emissions, we monitored a large region of the Ob River's middle course (permafrost-free zone) over 3 months from spring to summer. We calculated seasonal water coverage using remote sensing, GIS and hydrologically-based approaches and measured CO2 emissions using floating chambers. There was a strongly pronounced seasonality in the water area's extent of the floodplain with water covering > 40 % of land during the ∼ 30 days of the most intensive spring flood (May – June) and subsequently declining to ≤ 10 % during summer (July-August). Maximal CO2 emissions were recorded in most shallow water bodies of the floodplain, notably in temporary flooded fens and birch forests. The CO2 emissions during the study period ranged from 0.2 ± 0.2 to 0.9 ± 0.2 g Cm−2 d−1 for the floodplain and 0.03 ± 0.34 g C m−2 d−1 for the Ob's main channel.CO2 emissions from the floodplain were ∼ 163 ± 20 t C per km for the river's main stem during the 95 day study period. The partial contributions of temporary flooded zones, main stem, and permanent lakes / secondary channels to total emissions (1820 km² area) were 70, 16, and 14 %, respectively. Over spring and summer seasons, contributions from flooded zones ranged from 43 to 99 % of total CO2 emissions from water surfaces of the Ob River's middle course. Extrapolation of obtained results to the entire territory of the Ob River floodplain indicates that not accounting for the floodplain emissions may sizably—up to an order of magnitude—underestimate the CO2 emissions from riverine systems in Western Siberia during open water period. Future work on the Ob River floodplain in the permafrost-bearing zone should be prioritized and would allow adequate upscaling of C emission from this environmentally important territory.
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