EMBRACE (EMbedding Repositories And Consortial Enhancement) project: final report

EMBRACE (EMBedding Repositories And Consortial Enhancement) was an 18-month project led by UCL on behalf of the SHERPA-LEAP (London Eprints Access Project) Consortium, a group of 13 University of London institutions with institutional repositories. The project had two strands, technical and strategic. In its technical strand, EMBRACE aimed to implement a number of technical improvements to enhance the functionality of the SHERPA-LEAP repositories. In a concurrent strategic strand, EMBRACE set out to investigate the challenges of embedding repositories of digital assets in institutional strategy to ensure repository sustainability. The technical work of the project resulted in the successful enhancement of the partner repositories, and a cover page generating tool has been released on an open source basis. The strategic work delivered two main outputs: a full report on the work of RAND in drawing on stakeholder interviews which identifies drivers for, and barriers to, repository sustainability; and a supplementary, "briefing paper" digest of the main report, concentrating on the interventions which can be taken by repository managers and champions to address the challenges of embedding repositories. Both documents are in the public domain. The Briefing Paper is explicitly designed for adaptation and local customisation by HEIs. The RAND report emphasises the importance of establishing a clear vision for the repository, and of close communication with stakeholders, if a repository is to succeed

SHERPA-LEAP: a consortial model for the creation and support of academic institutional repositories

Purpose: To introduce SHERPA-LEAP, a model for the consortial development, population and support of eprints repositories. Design/methodology/approach: The organisational and technical structures of the consortium are described, including a brief summary of central and local resource responsibilities. Some positive and negative aspects of a consortial approach to institutional repository development, and of the SHERPA-LEAP model in particular, are identified. Outstanding issues and future plans for the consortium are outlined. Findings: SHERPA-LEAP is found to be succeeding in its aims of developing and supporting eprints repositories within the federal University of London. Some lessons learned from the SHERPA-LEAP approach are identified, but the SHERPA-LEAP consortial model is found to have been mostly beneficial to the participating institutions. In particular, the networking and experience-sharing opportunities which any consortial solution will facilitate are highly valued by the SHERPA-LEAP partners. Value: The case study is intended to help to inform the decision-making of institutions and consortia which are considering consortial solutions to the establishment and maintenance of institutional repositories

Evidence that avian reovirus σNS is an RNA chaperone: implications for genome segment assortment.

Reoviruses are important human, animal and plant pathogens having 10-12 segments of double-stranded genomic RNA. The mechanisms controlling the assortment and packaging of genomic segments in these viruses, remain poorly understood. RNA-protein and RNA-RNA interactions between viral genomic segment precursors have been implicated in the process. While non-structural viral RNA-binding proteins, such as avian reovirus σNS, are essential for virus replication, the mechanism by which they assist packaging is unclear. Here we demonstrate that σNS assembles into stable elongated hexamers in vitro, which bind single-stranded nucleic acids with high affinity, but little sequence specificity. Using ensemble and single molecule fluorescence spectroscopy, we show that σNS also binds to a partially double-stranded RNA, resulting in gradual helix unwinding. The hexamer can bind multiple RNA molecules and exhibits strand-annealing activity, thus mediating conversion of metastable, intramolecular stem-loops into more stable heteroduplexes. We demonstrate that the ARV σNS acts as an RNA chaperone facilitating specific RNA-RNA interactions between genomic precursors during segment assortment and packaging

Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA–coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology

A Performance Study of Select Choral Literature for Two-Part Women\u27s Chorus

When searching for appropriate literature for any choral group, there are many considerations to take into account: the musical abilities of the singers, the type of accompaniment, the vocal ranges and tessitura in the parts, the language of the text, etc. One primary consideration would be the divisi or number of parts within a piece, which can sometimes be a good measure of the piece’s difficulty. Put simply, more divisi generally means that the singers must be able to sing more complex chords with more independence. So it might seem that pieces with a great deal of divisi would be a poor choice for very small groups with limited musical abilities. However, more divisi in a piece does not automatically render it more harmonically complex, but often functions to thicken the sound through doubling of notes in other voices or the accompaniment. Conversely, a piece of choral music that comprises just two vocal parts might seem to be too simple for a group with strong musical ability. Actually, there is a wide variety of two-part music that can not only prove musically challenging to such a group, but also provides ample teaching opportunities in rehearsal as well as a satisfying musical experience for both ensemble and audience. I will discuss five such pieces for two-part women’s chamber ensemble, all of varying levels of difficulty, and address them regarding several points: history, form and structure, conducting and performance considerations, and reviews on available recordings

It's more than just physical therapy: reported utilization of physiotherapy services for adults with neuromuscular disorders attending a specialist centre.

PURPOSE: The purpose of this study is to evaluate service users' perceptions of their utilization of the physiotherapy service at a specialist Neuromuscular Centre and to identify their reasons for and barriers to attending. METHOD: A prospective survey design, consisting of a 13-item questionnaire was completed by 104 registered users of a physiotherapy service at a Neuromuscular Centre in northwest England. Descriptive statistics was employed to analyse data from Likert style questions and thematic analysis conducted on responses to open-ended questions. RESULTS: Over 79% of respondents were satisfied with the frequency and duration of their treatment. Respondents attended physiotherapy to obtain physical therapy, for general wellbeing and to access specialized resources. Barriers to attendance included work commitments, travel cost and time, and lack of Centre resources. Clients attending physiotherapy valued the specialist service including advice from therapists, perceived benefit from social interaction with other clients and physical therapy. CONCLUSION: Adults with neuromuscular disorders identified psychosocial as well as physical benefits from attending physiotherapy at the Neuromuscular Centre. The findings highlight the importance of service users' views in service provision and suggest that a collaborative commitment to patient management could by advantageous when developing physiotherapy services

Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement

Objectives To assess the Gram-positive-specific antibiotic linezolid and the broad-spectrum antibiotic tigecycline for use in local antibiotic delivery via antibiotic-loaded bone cement. Methods Linezolid and tigecycline were added to Biomet bone cement at varying concentrations. Antibiotic elution over 1 week was quantified by HPLC-MS. The effect of wear on elution over 51 h was determined using a modified TE-66 wear tester. Eluted antibiotics were used to determine the MICs for a panel of clinically relevant bacteria. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. Cytotoxicity of eluted antibiotics against MG-63 cells was evaluated using an MTT assay. Results Linezolid and tigecycline eluted from bone cement to clinically relevant levels within 1 h and retained activity over 1 week. Mechanical wear significantly reduced elution of tigecycline, but had little effect on elution of linezolid. Linezolid showed low cytotoxicity towards MG-63 cells with ≤300 mg/mL resulting in >50% cell activity. Cytotoxicity of tigecycline was higher, with an IC50 of 5–10 mg/L. Conclusions Linezolid and tigecycline retain activity after elution from bone cement. The concentration of tigecycline may need to be carefully controlled due to cytotoxicity. The effect of wear on bone cement may need to be considered if tigecycline is to be used for local delivery. Up to 10% linezolid can be added without affecting the impact strength of the bone cement. These results are promising indications for future investigation of these antibiotics for use in local antibiotic delivery strategies

Molecular frustration: a hypothesis for regulation of viral infections

The recent revolution in imaging techniques and results from RNA footprinting in situ reveal how the bacteriophage MS2 genome regulates both particle assembly and genome release. We have proposed a model in which multiple packaging signal (PS) RNA-coat protein (CP) contacts orchestrate different stages of a viral life cycle. Programmed formation and release of specific PS contacts with CP regulates viral particle assembly and genome uncoating during cell entry. We hypothesize that molecular frustration, a concept introduced to understand protein folding, can be used to better rationalize how PSs function in both particle assembly and genome release. More broadly this concept may explain the directionality of viral life cycles, for example, the roles of host cofactors in HIV infection. We propose that this is a universal principle in virology that explains mechanisms of host-virus interaction and suggests diverse therapeutic interventions

Cardiovascular disease in Alpha 1 antitrypsin deficiency:an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools

Background: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development. Results: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment. Conclusion: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD

Using rhythm for rehabilitation: evaluation of a novel haptic device

This project explored how new and novel approaches to stroke rehabilitation could improve physical function and the confidence of stroke survivors to remain active and engaged in the community. The innovation trialed was a ‘Haptic bracelet/cueing device’, developed at The Open University. An overview of the Haptic device, its development and role in stroke rehabilitation can be viewed at: https://www.youtube.com/watch?v=S4ZxN6H6XGk The Haptic bracelets provide a physical (embodied) beat that someone can walk to as an alternative to existing audio cuing ways of working. The haptic device provides a non-invasive, relatively cheap way of facilitating people after stroke to continue to maintain or even improve their mobility after intensive rehabilitation has finished. This research explored the impact of the haptic device to gains in mobility. The project had two key aims: 1. To develop a usable and practical prototype of a haptic device to restore gait symmetry after stroke. 2. To investigate the feasibility and acceptability of the prototype in stroke patients. Summary of findings and recommendations When introduced to the Haptic Bracelets participants hoped the product would provide them with: • More confidence and make them feel safer when walking. • Greater ability to take bigger strides rather than little steps. • A way to combat the silly mistakes participants reported making due to tiredness. • Reduced pain (knees, hips) The physiotherapists saw potential for the Haptic devices as part of post stroke rehabilitation, but expressed concern about their lack of access to mobile technologies when out in community practice settings. There were also concerns about use with some stroke survivors because of issues of cognition; and the sensation from the Haptic beat. In the Haptic gait testing • All the participants demonstrated good mobility performance prior to the study (high score on the Rivermead mobility scale) • 4/7* (57.1%) participants who were the most asymmetrical at baseline improved their gait symmetry whilst wearing the haptic device • 3/7* (42%) participant’s gait symmetry continued to improve in the post off condition. • All the participants walked quicker in post-op condition. However, gait speed varied between participants when they were wearing the haptic bracelets. • Participants were had had their strokes between 3-10 years ago, but there was still an indication that the Haptic bracelets were having some impact on mobility. • Syncing of the Haptic device and more mobile Inertial Measurement Unit (IMU) to the fixed gait laboratory (gold standard) system has improved the potential for more community based rehabilitation and commercialisation of the Haptic bracelets. • Post Haptic interviews identified that there were mixed participant feelings about the bracelets. However, some did express positive experiences from testing the Haptic bracelets, including a carry over effect after the devices were removed. Recommendations As this was a pilot study more work is now required to explore the: • use of the Haptic bracelets in community rehabilitation settings • feasibility of the using Haptic bracelets in community settings, particularly looking at staff access to new technologies • potential for the Haptic bracelets to be used in the home as part of ongoing rehabilitation • benefits of Haptic bracelets in the context of longer term stroke rehabilitation • future design needs to improve the look, size and ease of application • cost benefits of using Haptic bracelets as part of an overall program of stroke rehabilitation