Understanding and controlling the glass transition of HTPB oligomers

In this paper, we use a combination of experiment and simulation to achieve enhanced levels of synthetic control on the microstructure of the much-used binder material hydroxyl terminated polybutadiene (HTPB). Specifically, we determine the appropriate combination of initiator, temperature and solvent required to dial in the relative contents of trans, cis and vinyl monomeric units. When an alkylithium initiator (TBDMSPLi) is used, the vinyl content increases from 18% to >90% as the polymerization solvent is switched from non-polar to polar. Further, in non-polar solvents, the vinyl content increases from 18% to 40% with decreasing polymerization temperature. The glass transition temperature, Tg, is shown to be strongly affected by the microstructure, covering the very wide range of −95 °C to −25 °C. The Tg values of HTPB oligomers with high vinyl content are exceptionally high (−25 °C) and can be associated with their aliphatic backbones with pendant side-groups structures. The experimental indications that intramolecular degrees of freedom have a dominant effect on Tg are confirmed by Molecular Dynamics simulations. These simulations identify crankshaft flips of main-chain sub-sections as the key mechanism and relate this to the vinyl content; the frequency of these rotations increases by an order of magnitude, as the vinyl content is reduced from 90% to 20%. The generic mechanistic understanding gained here into what constitutes a “good binder” material is readily transferrable to the potential identification of future candidate systems with very different chemistries

Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): Study protocol for a randomised controlled trial

Background: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall. Methods/design: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers. Discussion: At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12612001226897. Registered on 20 November 2012. © 2017 The Author(s)

A Randomised Controlled Trial Assessing the Effects of Peri-operative Fenofibrate Administration on Abdominal Aortic Aneurysm Pathology: Outcomes From the FAME Trial

Objective: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. Methods: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. Results: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. Conclusion: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs

Additional file 1: of Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): study protocol for a randomised controlled trial

SPIRIT 2013 Checklist. (DOC 122 kb

Additional file 2: of Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): study protocol for a randomised controlled trial

SPIRIT figure. Schedule of enrolment, interventions and assessments. (DOC 60 kb