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

The RNA-binding protein hnRNPA2 regulates β-catenin protein expression and is overexpressed in prostate cancer

The RNA-binding protein hnRNPA2 (HNRNPA2B1) is upregulated in cancer, where it controls alternative pre-mRNA splicing of cancer-relevant genes. Cytoplasmic hnRNPA2 is reported in aggressive cancers, but is functionally uncharacterized. We explored the role of hnRNPA2 in prostate cancer (PCa). Methods: hnRNPA2 function/localization/expression in PCa was determined using biochemical approaches (colony forming/proliferation/luciferase reporter assays/flow cytometry/immunohistocytochemistry). Binding of hnRNPA2 within cancer-relevant 3′-UTR mRNAs was identified by bioinformatics. Results: RNAi-mediated knockdown of hnRNPA2 reduced colony forming and proliferation, while hnRNPA2 overexpression increased proliferation of PCa cells. Nuclear hnRNPA2 is overexpressed in high-grade clinical PCa, and is also observed in the cytoplasm in some cases. Ectopic expression of a predominantly cytoplasmic variant hnRNPA2-ΔRGG also increased PCa cell proliferation, suggesting that cytoplasmic hnRNPA2 may also be functionally relevant in PCa. Consistent with its known cytoplasmic roles, hnRNPA2 was associated with 3′-UTR mRNAs of several cancer-relevant mRNAs including β-catenin (CTNNB1). Both wild-type hnRNPA2 and hnRNPA2-ΔRGG act on CTNNB1 3′-UTR mRNA, increasing endogenous CTNNB1 mRNA expression and β-catenin protein expression and nuclear localization. Conclusion: Nuclear and cytoplasmic hnRNPA2 are present in PCa and appear to be functionally important. Cytoplasmic hnRNPA2 may affect the cancer cell phenotype through 3′-UTR mRNA-mediated regulation of β-catenin expression and other cancer-relevant genes

TNF- α Autocrine Feedback Loops in Human Monocytes:The Pro- and Anti-Inflammatory Roles of the TNF- α Receptors Support the Concept of Selective TNFR1 Blockade in Vivo

Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy. We studied the roles of the two TNF-α receptors, TNFR1 and TNFR2, in human monocytes, the principal producer of TNF-α and central to many TNF-α driven diseases. We hypothesised that TNF-α has pro- and anti-inflammatory effects on monocytes, occurring differentially via TNFR1 and TNFR2. Monocytes were isolated from healthy human subjects and exposed to LPS, plus/minus the addition of blocking antibodies to TNF-α or its receptors. Pro- and anti-inflammatory cytokine production was quantified using real-time PCR and ELISAs. Cell surface expression of TNFR1/2 was measured by flow cytometry. We demonstrated that monocytes vary in the expression patterns of TNFR1 and TNFR2. Autocrine binding of TNF-α led to sustained upregulation of proinflammatory cytokines via TNFR1. In contrast, autocrine binding via TNFR2 upregulated the anti-inflammatory cytokine, IL-10, without proinflammatory effect. TNFR2 was responsible for binding soluble TNF-α secreted by monocytes, clearing the cytokine from the pericellular environment. TNFR1 blockade did not change the cell surface expression of TNFR2, leaving this receptor free to upregulate IL-10. These novel results support the concept of selective TNFR1 blockade in vivo in order that positive anti-inflammatory effects of TNF-α can be retained via TNFR2 ligation

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

Alpha-1 antitrypsin deficiency; Emphysema; PrevalenceDeficiència d'alfa-1 antitripsina; Emfisema; PrevalençaDeficiencia de alfa-1 antitripsina; Enfisema; PrevalenciaBackground Although bronchiectasis has been recognised as a feature of some patients with Alpha1-Antitrypsin deficiency the prevalence and characteristics are not widely known. We wished to determine the prevalence of bronchiectasis and patient characteristics. The first cohort of patients recruited to the EARCO (European Alpha1 Research Collaboration) International Registry data base by the end of 2021 was analysed for radiological evidence of both emphysema and bronchiectasis as well as baseline demographic features. Results Of the first 505 patients with the PiZZ genotype entered into the data base 418 (82.8%) had a reported CT scan. There were 77 (18.4%) with a normal scan and 38 (9.1%) with bronchiectasis alone. These 2 groups were predominantly female never smokers and had lung function in the normal range. The remaining 303 (72.5%) ZZ patients all had emphysema on the scan and 113 (27%) had additional evidence of bronchiectasis. Conclusions The data indicates the bronchiectasis alone is a feature of 9.1% of patients with the PiZZ genotype of Alpha1-antitrypsin deficiency but although emphysema is the dominant lung pathology bronchiectasis is also present in 27% of emphysema cases and may require a different treatment strategy.The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS)

Assessing uncertainties in scattering correction algorithms for reflective tube absorption measurements made with a WET Labs ac-9

In situ absorption measurements collected with a WET Labs ac-9 employing a reflective tube approach were scatter corrected using several possible methods and compared to reference measurements made by a PSICAM to assess performance. Overall, two correction methods performed best for the stations sampled: one using an empirical relationship between the ac-9 and PSICAM to derive the scattering error (ε) in the nearinfrared (NIR), and one where ε was independently derived from concurrent measurements of the volume scattering function (VSF). Application of the VSF-based method may be more universally applicable, although difficult to routinely apply because of the lack of commercially available VSF instrumentation. The performance of the empirical approach is encouraging as it relies only on the ac meter measurement and may be readily applied to historical data, although there are inevitably some inherent assumptions about particle composition that hinder universal applicability. For even the best performing methods, residual errors of 20% or more were commonly observed for many water types. For clear ocean waters, a conventional baseline subtraction with the assumption of negligible near-IR absorption performed as well or better than the above methods because propagated uncertainties were lower than observed with the proportional method

Polyandrous females avoid costs of inbreeding

Why do females typically mate with more than one male? Female mating patterns have broad implications for sexual selection, speciation and conflicts of interest between the sexes, and yet they are poorly understood. Matings inevitably have costs, and for females, the benefits of taking more than one mate are rarely obvious. One possible explanation is that females gain benefits because they can avoid using sperm from genetically incompatible males, or invest less in the offspring of such males. It has been shown that mating with more than one male can increase offspring viability, but we present the first clear demonstration that this occurs because females with several mates avoid the negative effects of genetic incompatibility. We show that in crickets, the eggs of females that mate only with siblings have decreased hatching success. However, if females mate with both a sibling and a non-sibling they avoid altogether the low egg viability associated with sibling matings. If similar effects occur in other species, inbreeding avoidance may be important in understanding the prevalence of multiple mating

The Acute Physiological and Perceptual Responses to Blood-flow Restriction Applied During Un-resisted Knee Exercise: A Potential Treatment Adjunct for Physiotherapists

Purpose: Blood-flow restriction [BfR] training involves the temporary, artificial reduction of blood flow through a limb. Evidence suggests that BfR combined with low-intensity resistance exercise can minimise the loss of thigh muscle size and strength during periods of impaired weight-bearing. However, evidence is scarce as to the specific utility of adding BfR to un-resisted or ‘no-load’ exercise during injury rehabilitation. Therefore, this case series examined the effects of applying BfR during a no-load lower-limb knee exercise completed by athletes recovering from significant lower limb injuries. Methods: Three professional rugby players provided consent to incorporate BfR training into their injury rehabilitation programmes. (Case one; four weeks post tibia and fibula fracture. Case two; five weeks post Achilles tendon rupture. Case three; immediately following MRI diagnosis of an osseous stress injury of the knee). During the control exercise session, players performed three sets of a seated, un-resisted, single-leg knee-extension exercise. At subsequent sessions, a 21.5 cm wide blood-pressure cuff was used to superimpose BfR over the same exercise. BfR was applied intermittently or continuously across the upper thigh via 100 mmHg or 120 mmHg cuff pressure. Near infra-red spectroscopy [NIRS] monitored tissue oxygen saturation [SmO2] and total haemoglobin mass [tHb] of the vastus lateralis muscle before and during the exercise of each lower-limb. The relative change in SmO2 and tHb generated during each exercise session was then calculated. Session rate of perceived exertion [RPE] was monitored via a 10-point visual scale. Descriptive statistics were then used to indicate trends among these variables. Results: BfR training was delivered four to five times per week for periods of 4 to 12 weeks. NIRS data from thirty BfRT sessions (five sessions per leg, per player) were obtained. Mean resting values for vastus lateralis SmO2 and tHb were 54.3% and 12.72 g/dL respectively. During the control exercise session, SmO2 increased by a mean of 4.68 points, whilst tHb decreased slightly (-0.04 g/dL). In contrast, the addition of continuous BfR at 120 mmHg generated a mean drop in SmO2 of 22.31 points, whilst tHb increased (+0.23 g/dL). No adverse events or pain occurred during any exercise session. The control session generated a mean session RPE of 0.94 out of 10. Session RPE during BfR training ranged between 3.6 and 4.9. Conclusion(s): In a case series of injured athletes, data indicated that adding BfR to a ‘no-load’ knee extension exercise generated oxygen desaturation of the vastus lateralis muscle and increased perceptual exertion. Lower-limb BfR training was delivered in a safe, tolerable way as part of a multi-modal, intensive injury rehabilitation programme. Implications: BfR training may provide Physiotherapists with a novel Method of generating exercise-induced physiological stress within muscle tissue during exercise, without the need to add any external resistance. Achieving sufficient physiological stress during the very early stages of injury rehabilitation via no-load BfR training may promote a muscular response that limits the longitudinal muscle disuse atrophy seen during periods of impaired weight-bearing. Further research is warranted to substantiate this and to explore the utility of no-load BfR training within non-athletic, clinical populations. Funding acknowledgements: This study was funded via a PhD studentship awarded by Manchester Metropolitan University

Reported fatigue in people after Guillain-Barré Syndrome: a retrospective national survey in the UK

Aim. Despite continuing functional recovery over time, fatigue remains a persistent feature of post-acute GuillainBarré Syndrome (GBS). The aim of this study was to determine the prevalence of fatigue in people after GBS and investigate its associations with other factors after GBS. Methods. Validated questionnaires including the SF-36 and fatigue severity scale were sent to members of the GBS support group, a UK wide patient and carer organisation. Results. A total of 884 questionnaires were returned (58% response rate). Respondents’ answers demonstrated that those with severe fatigue following GBS had spent longer in hospital than those who were not severely fatigued (P=0.003). Poorer mental health was also associated with more severe fatigue. A strong predictor of prolonged fatigue was discharge from hospital in a wheelchair (OR=2.37, 95% CI 1.52 to 3.71, P<0.001) but the severity of fatigue appeared to be independent of recovery of mobility (Kendall’s taub=0.03, P=0.2). Conclusion. This survey is the largest study of fatigue in people after GBS. Its findings demonstrate that fatigue remains a persistent problem for many people after GBS. More severe fatigue was associated with decreased health related quality of life and increased levels of depression and anxiety in people after GBS. Whilst the severity of fatigue was significantly associated with poorer mobility on discharge, there was no association between the recovery of mobility after discharge and fatigue severity. This indicates that whilst other impairments and activity limitations improved over time, fatigue did not and implies that more severe fatigue is not simply an indicator of a more severe presentation of GBS. Whilst the reasons for persistent severe fatigue remain unclear, this study indicates that further investigations of mobility, mental health and fatigue are warranted so that targeted interventions can be put in place to manage this debilitating complication. (It J Physiotherapy 2013;3:154-60