Weinreichstevens6452

INTRODUCTION Extended half-life factor IX concentrates (EHL-FIX) can be administered weekly to prevent bleeding for persons with severe haemophilia B. We report the experience of a large UK haemophilia comprehensive care centre using low dose EHL-FIX for persons with severe haemophilia B. AIM The low doses used in real world are approximately half of the doses used in clinical trials. We aim to assess the efficacy and safety of low dose EHL-FIX. METHODS Data from a cohort of 13 patients who were switched from standard half-life factor IX (SHL-FIX) to Alprolix® (mean dose 31.5 IU/kg) and seven patients who switched from standard half-life factor IX to Idelvion® (mean dose 20.2 IU/kg) were included. RESULTS The median annualized bleeding rate was similar for SHL-FIX (median 3, interquartile range [IQR] 1-5) and EHL-FIX (median 3, IQR 1-5.25). Quality of life scores, measured using the European Quality of Life 5 Dimensions assessment were similar for SHL-FIX (median 0.76, IQR 0.63-0.84) and EHL-FIX (median 0.79, IQR 0.58-0.88). CONCLUSION This study shows that EHL-FIX given at low doses can be effective for prevention of bleeding for persons with severe haemophilia B. © 2020 John Wiley & Sons Ltd.RATIONALE In 2015, Queen's University embarked on an institution-wide transition to a competency-based medical education (CBME) curriculum for all 29 postgraduate medical education programmes. On 1 July 2017, this goal was accomplished. With this mass transition came the requirement to assess the efficacy of implementation through a programme evaluation process, which included the use of outcome harvesting (Wilson-Grau). Outcome harvesting identified the intended and unintended outcomes of CBME implementation, which helped us understand how the intervention was achieved and how the relationship between behaviours and stakeholders contributed to the successful transition. METHODS A systematic approach to document analysis was used to categorize the eight identified areas of implementation governance, scholarship, faculty development, resident leadership, curriculum, assessment, communications, and technology. Documents (N = 443) were organized per project area and then coded thematically. Documents were then categorized for attribution to outcomes using the outcome harvesting approach. Outcomes were validated via interrater reliability and substantiated by stakeholders to verify accuracy of formulation and plausibility of its influence on the outcome. RESULTS The harvest produced 38 outcomes, either intended or unintended, that can be attributed to CBME implementation at Queen's University. CONCLUSION Using outcome harvesting to assess the efficacy of CBME implementation produced a robust set of themes and resultant outcomes that can be categorized as requirements for success of implementation of any curricular innovation. Emergent themes included collaboration, community of practice, and stakeholder commitment. More unique observations noted through the harvest process included new policy development, creation of learner ownership, and an increase in the output of scholarly activity involving CBME. © 2020 John Wiley & Sons, Ltd.Peptides have important biological functions. However, peptides' susceptibility to proteolysis is a big hurdle to their application. We demonstrated, for the first time, that poly(2-oxazoline) can work as functional mimics of peptides. Using host defense peptide as a model, we showed poly(2-oxazoline) based glycine pseudopeptides can mimic host defense peptide and have potent in vitro and in vivo activities against methicillin-resistant Staphylococcus aureus that cause formidable infections. CP-673451 research buy The poly(2-oxazoline) showed potent activity against persister cells that are highly resistant to antibiotics. S taphylococcus aureus were unable to acquire resistance upon poly(2-oxazoline), owning to the reactive oxygen species related antimicrobial mechanism. Poly(2-oxazoline) treated Staphylococcus aureus were still sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross-resistance in using antimicrobial poly(2-oxazoline). Our study highlighted poly(2-oxazoline) as a new type of functional mimics of peptides and opened up new avenues in designing and exploring peptide mimetics for biological functions and applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND The role of postoperative radiotherapy in pathological T2-3N0M0 esophageal squamous cell carcinoma is unknown. We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma. MATERIALS AND METHODS Patients aged 18-72 years with pathological stage T2-3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible. Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over 6 weeks. The primary endpoint was disease-free survival. The secondary endpoints were local-regional recurrence rate, overall survival, and radiation-related toxicities. RESULTS From October 2012 to February 2018, 167 patients were enrolled in this study. We analyzed 157 patients whose follow-up time was more than 1 year or who had died. The median follow-up time was 45.6 monthesults of this phase III study indicated that postoperative radiotherapy significantly improved disease-free survival and decreased local-regional recurrence rate in patients with pathological T2-3N0M0 thoracic esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. The distant metastasis rates and overall survival rates were not different between the two groups. Adjuvant radiotherapy should be considered for pathologic T2-3N0M0 thoracic esophageal squamous cell carcinoma. Prospective trials to identify high-risk subgroups are needed. © AlphaMed Press 2020.Human adipose-derived stem/stromal cells (hASCs) can differentiate into specialized cell types and thereby contribute to tissue regeneration. As such, hASCs have drawn increasing attention in cell therapy and regenerative medicine, not to mention the ease to isolate them from donors. Culture conditions are critical for expanding hASCs while maintaining optimal therapeutic capabilities. Here, we identified a role for transforming growth factor β1 (TGFβ1) in culture medium in influencing the fate of hASCs during in vitro cell expansion. Human ASCs obtained after expansion in standard culture medium (Standard-hASCs) and in endothelial cell growth medium 2 (EGM2-hASCs) were characterized by high-throughput transcriptional studies, Gene Set Enrichment Analysis and functional properties. EGM2-hASCs exhibited enhanced multipotency capabilities and an immature phenotype compared with Standard-hASCs. Moreover, the adipogenic potential of EGM2-hASCs was enhanced, including toward beige adipogenesis, compared with Standard-hASCs.