| 11. |
- Clayton, Aled, et al.
(författare)
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Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
- 2018
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Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
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| 12. |
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| 13. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 Trial.
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:4
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD).To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD.Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851).Clinics in 17 countries.Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial.Patients were randomized 2:2:1 to once-weekly somapacitan, daily GH, or once-weekly placebo for 34 weeks (main period). During the 52-week extension period, patients continued treatment with somapacitan or daily GH.Body composition measured using dual-energy x-ray absorptiometry (DXA). The primary endpoint was change in truncal fat percentage to week 34. Insulin-like growth factor 1 (IGF-I) standard deviation score (SDS) values were used to dose titrate.At 34 weeks, somapacitan significantly reduced truncal fat percentage (estimated difference: -1.53% [-2.68; -0.38]; P = 0.0090), demonstrating superiority compared with placebo, and it improved other body composition parameters (including visceral fat and lean body mass) and IGF-I SDS. At 86 weeks, improvements were maintained with both somapacitan and daily GH. Somapacitan was well tolerated, with similar adverse events (including injection-site reactions) compared with daily GH.In AGHD patients, somapacitan administered once weekly demonstrated superiority over placebo, and the overall treatment effects and safety of somapacitan were in accordance with known effects and safety of GH replacement for up to 86 weeks of treatment. Somapacitan may provide an effective alternative to daily GH in AGHD. A short visual summary of our work is available (1).
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| 14. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Safety and convenience of once-weekly somapacitan in adult GH deficiency: A 26-week randomized, controlled trial
- 2018
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 178:5, s. 491-499
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design: 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (NCT02382939). Methods: Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n=61) or once-daily Norditropin (n=31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results: Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P=0.0171). Conclusions: In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 European Society of Endocrinology Printed in Great Britain.
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| 15. |
- Tran, C. -T, et al.
(författare)
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A study on transient heat transfer of the EU-ABWR external core catcher using the Phase-change Effective Convectivity Model
- 2015
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Ingår i: International Topical Meeting on Nuclear Reactor Thermal Hydraulics 2015, NURETH 2015. - : American Nuclear Society. - 9781510811843 ; , s. 6821-6834
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Konferensbidrag (refereegranskat)abstract
- In advanced designs of Nuclear Power Plants (NPPs), for mitigation of severe accident consequences, on the one hand, the In-Vessel Retention (IVR) concept has been implemented. On the other hand in other new NPP designs (Generation HI and III+) with large power reactors, the External Core Catcher (ECC) has been widely adopted. Assessment of ECC design robustness is largely based on analysis of heat transfer of a melt pool formed in the ECC. Transient heat transfer analysis of an ECC is challenging due to (i) uncertainty in the in-vessel accident progression and subsequent vessel failure modes; (ii) long transient, (iii) high Rayleigh number and complex flows involving phase change of the melt pool formed in an ECC. The present paper is concerned with analysis of transient melt pool heat transfer in the ECC of new Advanced Boiling Water Reactor (ABWR) designed by Toshiba Corporation (Japan). According to the ABWR severe accident management strategy, the ECC is initially dry. In order to prevent steam explosion flooding is initiated after termination of melt relocation from the vessel. The ECC full of melt is cooled from the top directly by water and from the bottom through the ECC walls. In order to assess sustainability of the ECC, heat transfer simulation of a stratified melt pool formed in the ECC is carried out. The problem addressed in this work is heat flux distribution at ECC boundaries when cooling is applied (i) from the bottom, (ii) from the top and from the bottom. To perform melt pool heat transfer simulation, we employ Phase-change Effective Convectivity Model (PECM) which was originally developed as a computationally efficient, sufficiently accurate, 2D/3D accident analysis tools for simulation of transient melt pool heat transfer in the reactor lower plenum. Thermal loads from the melt pool to ECC boundaries are determined for selected ex-vessel accident scenarios. Performance of the ECC, efficiency of severe accident management (SAM) measures and procedures are evaluated based on results of PECM simulation and severe accident analysis.
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