Clinical Trial Readiness for Spinal Muscular Atrophy: Experience of an International Educational-Training Initiative.

Several successful clinical trials have been conducted in spinal muscular atrophy (SMA) over recent years which have led to the approval of splicing modifiers and gene transfer therapies. With an increasing number of other agents progressing through pre-clinical and clinical development, increasing worldwide clinical trial readiness is becoming essential.SMA Europe initiated a clinical trial readiness project, which included the development of a pilot face-to-face educational-training initiative for clinical specialists and physiotherapists involved in SMA, with an emphasis on the patient perspective. Participants were selected through two surveys and, ahead of the meeting, a mock protocol with specific questions was provided. The initiative involved a series of presentations, role-play and interactive exercises. We describe here our experience and evaluation of this educational-training initiative, emphasising scientific aspects, psychosocial implications and level of satisfaction.From a participant, patient and industry perspective, such training was considered successful and met the objective, which was to improve clinical trial readiness in emerging sites. Resource planning, ethical considerations and communication with patients were identified as three important topics for future training. This initiative highlights the need to develop a training programme to achieve clinical trial readiness across Europe and showcases a collaborative effort with different stakeholders, clinicians, patient advocacy groups and sponsors to address an important issue.

Freeze-Thaw Resistance and Air-Void Analysis of Concrete with Recycled Glass-Pozzolan Using X-ray Micro-Tomography.

Recent studies have shown promising potential for using Glass Pozzolan (GP) as an alternative supplementary cementitious material (SCM) due to the scarcity of fly ash and slag in the United States. However, comprehensive studies on the freeze-thaw (FT) resistance and air void system of mixtures containing GP are lacking. Therefore, this study aimed to evaluate GP's effect on FT resistance and characterize mixtures with different GP contents, both macro- and microscopically. In this study, six concrete mixes were considered: Three mixes with 20%, 30% and 40% GP as cement replacements and two other comparable mixes with 30% fly ash and 40% slag, as well as a mix with 100% Ordinary Portland cement (OPC) as a reference. Concrete samples were prepared, cured and tested according to the ASTM standards for accelerated FT resistance for 1000 cycles and corresponding dynamic modulus of elasticity (Ed). All the samples showed minimal deterioration and scaling and high F/T resistance with a durability factor of over 90%. The relationships among FT resistance parameters, air-pressured method measurements of fresh concretes and air void analysis parameters of hardened concretes were examined in this study. X-ray micro-tomography (micro-CT scan) was used to evaluate micro-cracks development after 1000 freeze-thaw cycles and to determine spatial parameters of air voids in the concretes. Pore structure properties obtained from mercury intrusion porosimetry (MIP) and N2 adsorption method showed refined pore structure for higher cement replacement with GP, indicating more gel formation (C-S-H) which was verified by thermogravimetric analysis (TGA).