| 1. |
- d'Amore, Francesco, et al.
(författare)
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Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:5, s. 565-573
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.
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| 2. |
- Faucherre, Samuel, et al.
(författare)
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Short and Long-Term Controls on Active Layer and Permafrost Carbon Turnover Across the Arctic
- 2018
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Ingår i: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 123:2, s. 372-390
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Tidskriftsartikel (refereegranskat)abstract
- Decomposition of soil organic matter (SOM) in permafrost terrain and the production of greenhouse gases is a key factor for understanding climate change-carbon feedbacks. Previous studies have shown that SOM decomposition is mostly controlled by soil temperature, soil moisture, and carbon-nitrogen ratio (C:N). However, focus has generally been on site-specific processes and little is known about variations in the controls on SOM decomposition across Arctic sites. For assessing SOM decomposition, we retrieved 241 samples from 101 soil profiles across three contrasting Arctic regions and incubated them in the laboratory under aerobic conditions. We assessed soil carbon losses (Closs) five times during a 1 year incubation. The incubated material consisted of near-surface active layer (ALNS), subsurface active layer (ALSS), peat, and permafrost samples. Samples were analyzed for carbon, nitrogen, water content, δ13C, δ15N, and dry bulk density (DBD). While no significant differences were observed between total ALSS and permafrost Closs over 1 year incubation (2.3 ± 2.4% and 2.5 ± 1.5% Closs, respectively), ALNS samples showed higher Closs (7.9 ± 4.2%). DBD was the best explanatory parameter for active layer Closs across sites. Additionally, results of permafrost samples show that C:N ratio can be used to characterize initial Closs between sites. This data set on the influence of abiotic parameter on microbial SOM decomposition can improve model simulations of Arctic soil CO2 production by providing representative mean values of CO2 production rates and identifying standard parameters or proxies for upscaling potential CO2 production from site to regional scales.
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| 3. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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