Vitrification and plastic flow in transient elastomer networks

We investigate how the crossover temperature of the elastic-plastic transition, the ‘vitrification point’ Tv, changes under load for isotropic vitrimers and exchangeable liquid crystal elastomers (xLCEs), using the thermoplastic SIS triblock polymer as a reference. In all these cases, the elastic network cross-links are transient: physical micro-phase separation in SIS and covalent transesterification bonds in vitrimers. From the analysis of SIS we define Tv as the point when entropic rubber-elasticity contraction due to heating under load turns into the irreversible plastic extension due to cross-links breaking and reforming. In xLCEs, the response to mechanical stress is heavily influenced by the smectic liquid-crystalline order, which makes the material much stiffer than normal rubbery networks, and also leads to the shape-memory effect across the smectic-isotropic transition point. The vitrification in the isotropic phase of xLCE, and in isotropic vitrimers, was found to be independent of stress, which can be attributed to the thermal activity of the catalyst determining Tv and it not being mechanically coupled to the elastic network. Beyond Tv, with increasing stress the plastic extension rapidly increases with temperature, as cross-link dynamics becomes more apparent.This work was funded by the EPSRC (EP/J017639), the Ernest Oppenheimer Trust in Cambridge, and by China Scholarship Council.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.polymer.2016.04.06

Postoperative pain management in children: Guidance from the pain committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative)

The main remit of the European Society for Paediatric Anaesthesiology (ESPA) Pain Committee is to improve the quality of pain management in children. The ESPA Pain Management Ladder is a clinical practice advisory based upon expert consensus to help to ensure a basic standard of perioperative pain management for all children. Further steps are suggested to improve pain management once a basic standard has been achieved. The guidance is grouped by the type of surgical procedure and layered to suggest basic, intermediate, and advanced pain management methods. The committee members are aware that there are marked differences in financial and personal resources in different institutions and countries and also considerable variations in the availability of analgesic drugs across Europe. We recommend that the guidance should be used as a framework to guide best practice

Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts

Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts.Project ON.2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000021), co-funded by North Portugal Regional Operational Program (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund (ERDF) and also supported by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)info:eu-repo/semantics/publishedVersio