Using digital content to build audiences for live opera

Purpose The purpose of this paper is to report on audience response to selected digital content produced by English Touring Opera (ETO) in support of the company’s Autumn 2015 tour. Methodology This study was conducted collaboratively between ETO and the Guildhall School of Music and Drama. The research team used focus groups to explore audience reactions to five items of supporting material produced by ETO. Through a qualitative analysis of the transcribed sessions, this report investigates how the items function, both individually and in general. Research Limitations As this is a qualitative study with a small sample group (23 individuals; 8 sessions), the results do not take the form of statistical conclusions. Future research might test the findings and hypotheses using a large-scale, quantitative study. Findings Viewers use online materials such as trailers, interviews, and rehearsal footage to appropriately align their expectations of a live performance, and to increase their familiarity with both the producing company and with specific productions. Viewers want the clips to feature music and imagery from the productions. In order to function well, the online materials must clearly demonstrate their relationship to the company and to the production. If successful in performing these functions, the online materials are likely to increase anticipation and thereby enhance the impact of attendance at a live performance. Practical Implications Digital content should help audiences know what to expect from a production, and encourage them to feel anticipation about attending. Content should be carefully contextualised so that viewers know what to expect from it and can decide whether or not (and when) to engage with it. Value The originality of this study lies both in its collaborative methodology and in the newness of the subject under investigation. Arts companies are increasingly interested in producing digital content, and this study could help inform strategies to ensure that those materials effectively enhance the audience experience.This research was supported by the Arts and Humanities Research Council [grant Number AH/J005142/1

Intermittent attendance at breast cancer screening

Background. To determine why women skip rounds and factors influencing return of previous non attenders (PNAs) to breast screening. Design and methods. Retrospective, quantitative, structured questionnaire posted to 2500 women. First PNAs did not attend their first screening appointment in 2007/2008 but then attended in 2010; First Controls first attended in 2010 without missed previous appointments. Women who attended screening in 2006 or earlier then skipped a round but returned in 2010 were Subsequent PNAs; Subsequent Controls attended all appointments.Results. More First Controls than First PNAs had family history of cancer (72.7% vs 63.2%; P=0.003); breast cancer (31.3% vs 24.8%; P=0.04). More PNAs lived rurally; more First PNAs had 3rd level education (33.2% vs 23.6%; P=0.002) and fewer had private insurance than First Controls (57.7% vs 64.8%; P=0.04). Excellent/good health was reported in First PNAs and First Controls (82.9% vs 83.2%), but fewer Subsequent PNAs than Subsequent Controls (72.7% vs 84.9%; P=0.000). Common considerations at time of missed appointment were had mammogram elsewhere (33% First PNA) and postponed to next round (16% First PNA, 18.8% Subsequent PNA). Considerations when returning to screening were similar for First PNAs and Subsequent PNAs: I am older (35.4%, 29.6%), I made sure I remembered (29%, 23.6%), could reschedule (17.6%, 20.6%), illness of more concern (16.5%, 19%). More First PNAs stated my family/friends advised (22.3% vs 15.2%) or my GP (12.6% vs 4.6%) advised me to attend, heard good things about BreastCheck (28.8% vs 13.6%).Conclusions. Intermittent attenders do not fit socio-demographic patterns of non-attenders; GP recommendation and word of mouth were important in women’s return to screening. Fear and anxiety seem to act as a screening facilitator rather than an inhibitor

Promoting healthier communities through adult education: Learning Connections in action

This presentation will highlight an Adult Education initiative delivered in Cork City through collaboration between members of the Cork Learning Neighbourhoods Project. It will outline the outreach provision of the Certificate in the Mental Health in the Community and how this is delivered in non-traditional settings to achieve successful collaboration, support accessible participation in lifelong learning and build capacity in communities. The process of creating a learning space to achieve transformative learning will be outlined as well as how this programme serves to enable students to address mental health issues on a personal level, community level and beyond

Improved Performance of Near infrared Excitation Raman Spectroscopy Using Reflective Thin-film Gold on Glass Substrates for Cytology Samples

Confocal near-infrared Raman spectroscopy has been shown to have applications in the area of clinical biology. A source wavelength in the near infrared is preferred over visible wavelengths for inspecting biological samples due to superior wave number resolution and reduced photo damage. However, these excitation sources have a number of drawbacks when compared to lasers in the visible wavelength region, including the requirement to use expensive highly pure crystal substrates such as Raman grade calcium fluoride as well as long acquisition times due to the lower Raman scattering efficiency. This paper investigates the use of a reflective substrate comprising a low cost 100 nm thin-film gold on glass substrate, as an alternative. Similar to recent work that used stainless steel substrates, it is demonstrated that the thin-film gold coated substrates, which are relatively inexpensive, produce cell spectra with 1.65 times the signal to noise ratio when compared with spectra obtained from calcium fluoride under identical conditions, with no apparent background signal in the fingerprint region. Two prostate cell lines are examined having been deposited on glass, calcium fluoride, and thin-film gold on glass substrates using the Thin Prep standard. Background spectra from, and cell adhesion on, these three substrates are compared. A comparison of the intensities and signal to noise ratios of the resulting spectra, and their viability for classification using principle components analysis is performed, which further demonstrates the benefit of reflective substrates

Secretory leucoprotease inhibitor binds to NF-κB binding sites in monocytes and inhibits p65 binding

Secretory leucoprotease inhibitor (SLPI) is a nonglycosylated protein produced by epithelial cells. In addition to its antiprotease activity, SLPI has been shown to exhibit antiinflammatory properties, including down-regulation of tumor necrosis factor α expression by lipopolysaccharide (LPS) in macrophages and inhibition of nuclear factor (NF)-κB activation in a rat model of acute lung injury. We have previously shown that SLPI can inhibit LPS-induced NF-κB activation in monocytic cells by inhibiting degradation of IκBα without affecting the LPS-induced phosphorylation and ubiquitination of IκBα. Here, we present evidence to show that upon incubation with peripheral blood monocytes (PBMs) and the U937 monocytic cell line, SLPI enters the cells, becoming rapidly localized to the cytoplasm and nucleus, and affects NF-κB activation by binding directly to NF-κB binding sites in a site-specific manner. SLPI can also prevent p65 interaction with the NF-κB consensus region at concentrations commensurate with the physiological nuclear levels of SLPI and p65. We also demonstrate the presence of SLPI in nuclear fractions of PBMs and alveolar macrophages from individuals with cystic fibrosis and community-acquired pneumonia. Therefore, SLPI inhibition of NF-κB activation is mediated, in part, by competitive binding to the NF-κB consensus-binding site

Improved performance of near infrared excitation Raman spectroscopy using reflective thin-film gold on glass substrates for cytology samples

Confocal near-infrared Raman spectroscopy has been shown to have applications in the area of clinical biology. A source wavelength in the near infrared is preferred over visible wavelengths for inspecting biological samples due to superior wavenumber resolution and reduced photodamage. However, these excitation sources have a number of drawbacks when compared to lasers in the visible wavelength region, including the requirement to use expensive highly pure crystal substrates such as Raman grade calcium fluoride as well as long acquisition times due to the lower Raman scattering efficiency. This paper investigates the use of a reflective substrate comprising a low cost 100 nm thin-film gold on glass substrate, as an alternative. Similar to recent work that used stainless steel substrates, it is demonstrated that the thin-film gold coated substrates, which are relatively inexpensive, produce cell spectra with 1.65 times the signal to noise ratio when compared with spectra obtained from calcium fluoride under identical conditions, with no apparent background signal in the fingerprint region. Two prostate cell lines are examined having been deposited on glass, calcium fluoride, and thin-film gold on glass substrates using the ThinPrep standard. Background spectra from, and cell adhesion on, these three substrates are compared. A comparison of the intensities and signal to noise ratios of the resulting spectra, and their viability for classification using principle components analysis is performed, which further demonstrates the benefit of reflective substrates

A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins

Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4−/− and Myd88−/−, but not TRIF−/− mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Defining Disease Phenotypes in Primary Care Electronic Health Records by a Machine Learning Approach: A Case Study in Identifying Rheumatoid Arthritis.

OBJECTIVES: 1) To use data-driven method to examine clinical codes (risk factors) of a medical condition in primary care electronic health records (EHRs) that can accurately predict a diagnosis of the condition in secondary care EHRs. 2) To develop and validate a disease phenotyping algorithm for rheumatoid arthritis using primary care EHRs. METHODS: This study linked routine primary and secondary care EHRs in Wales, UK. A machine learning based scheme was used to identify patients with rheumatoid arthritis from primary care EHRs via the following steps: i) selection of variables by comparing relative frequencies of Read codes in the primary care dataset associated with disease case compared to non-disease control (disease/non-disease based on the secondary care diagnosis); ii) reduction of predictors/associated variables using a Random Forest method, iii) induction of decision rules from decision tree model. The proposed method was then extensively validated on an independent dataset, and compared for performance with two existing deterministic algorithms for RA which had been developed using expert clinical knowledge. RESULTS: Primary care EHRs were available for 2,238,360 patients over the age of 16 and of these 20,667 were also linked in the secondary care rheumatology clinical system. In the linked dataset, 900 predictors (out of a total of 43,100 variables) in the primary care record were discovered more frequently in those with versus those without RA. These variables were reduced to 37 groups of related clinical codes, which were used to develop a decision tree model. The final algorithm identified 8 predictors related to diagnostic codes for RA, medication codes, such as those for disease modifying anti-rheumatic drugs, and absence of alternative diagnoses such as psoriatic arthritis. The proposed data-driven method performed as well as the expert clinical knowledge based methods. CONCLUSION: Data-driven scheme, such as ensemble machine learning methods, has the potential of identifying the most informative predictors in a cost-effective and rapid way to accurately and reliably classify rheumatoid arthritis or other complex medical conditions in primary care EHRs

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes