Treatment of retinopathy of prematurity in Northern Ireland, 2000-2011: a population-based study

Purpose To evaluate the incidence of treatment-requiring retinopathy of prematurity (ROP) over a 12-year-period in Northern Ireland. Methods The medical records of all infants treated for ROP from January 2000 to December 2011were retrospectively reviewed and cross-referenced with the Neonatal Intensive Care Outcomes Research and Evaluation (NICORE) database. Results The Northern Ireland population data showed an increase in the number of live births from 2000 to 2011. The proportion of babies born with a birth weight <1501 g and/or <32 weeks’ gestational age remained constant (χ2 trend = 3.220, P = 0.0727), although the proportion of these babies who died prior to 42 weeks’ gestation decreased from 2000 to 2011 (P = 0.0196 using χ2 for trend = 5.445; P = 0.0354 using χ2 = 20.809). The prevalence of treatment-requiring ROP in these infants increased from 1.05% in 2000 to 5.78% in 2011 (P < 0.001 using χ2 trend = 16.309; P < 0.001 using χ2 = 31.378). Conclusions The present population-based study highlights that the incidence of treatment- requiring ROP is increasing in Northern Ireland. The increasing number of infants requiring treatment will need to be taken into consideration in the commissioning process for ROP services in Northern Ireland.

Development of a Novel Assay for the Detection of Active Neutrophil Elastase in Patients with Chronic Obstructive Pulmonary Disease

Neutrophil elastase (NE), a biomarker of infection and inflammation, correlates with the severity of several respiratory diseases including chronic obstructive pulmonary disease (COPD). However, it’s detection and quantification in biological samples is confounded by a lack of reliable and robust methodologies. Standard assays using chromogenic or fluorogenic substrates are not specific when added to complex clinical samples containing multiple proteolytic and hydrolytic enzymes which have the ability to hydrolyse the substrate, thereby resulting in an over-estimation of the target protease. Furthermore, ELISA systems measure total protease levels which can be a mixture of latent, active and protease-inhibitor complexes. Therefore, we have developed a novel immunoassay (ProteaseTag™ Active NE Immunoassay) which is selective and specific for the capture of active NE in sputum and Bronchoalveolar Lavage (BAL) in patients with COPD. The objective of this study was to clinically validate ProteaseTag™ Active NE Ultra Immunoassay for the detection of NE in sputum from COPD patients. 20 matched sputum sol samples were collected from 10 COPD patients (M=6, F=4; 73 ± 6 years) during stable and exacerbation phases. Samples were assayed for NE activity utilising both ProteaseTag™ Active NE Ultra Immunoassay and a fluorogenic substrate-based kinetic activity assay. Both assays detected elevated levels of NE in the majority of patients (n=7) during an exacerbation (mean=217.2 μg/ml ±296.6) compared to their stable phase (mean=92.37 μg/ml ±259.8). However, statistical analysis did not show this difference to be significant (p=0.07, ProteaseTag™ Active NE Ultra Immunoassay; p=0.06 kinetic assay), most likely due to the low study number. A highly significant correlation was found between the 2 assay types (p≤0.0001, r=0.996). NE as a primary efficacy endpoint in clinical trials or as a marker of inflammation within the clinic has been hampered by the lack of a robust and simple to use assay. ProteaseTag™ Active NE Immunoassay specifically measures only active NE in clinical samples, is quick and easy to use (< 3 hours) and has no dependency on a kinetic readout. ProteaseTag™ technology is currently being transferred to a lateral flow device for use at Point of Care.

A novel inhibitor of channel activating proteases: Putting the CAP on ENaC

Background: Excessive activation of epithelial sodium channels (ENaC) contributes to CF lung pathophysiology due to the resultant dehydration of the airway surface liquid (ASL) and impaired mucociliary clearance. Regulated proteolysis of the endogenous α and γ subunits of ENaC by apical membrane-bound Channel Activating Proteases (CAPs) is a fundamental regulatory mechanism for channel activity. In the CF lung a stark imbalance between the levels of CAPs and their natural inhibitors drives the activation of normally inactive ENaC. On this basis inhibition of CAPs-ENaC signalling represents a potential therapeutic intervention. To this end we have developed a novel cell impermeable active-site directed compound (QUB-TL1) designed to inactivate key trypsin-like CAPs highly relevant in this regard. Objectives & Methods: Utilize differentiated non-CF and CF human airway epithelial cells to assess the impact of QUB-TL1 on a range of parameters including surface CAP activities, ENaC subunit processing/channel activity, ASL height and mucociliary clearance. Results: Treatment of airway epithelial cells with QUB-TL1 results in the significant downregulation of key endogenous CAP activities found to be excessively active at the surface of CF cultures. QUB-TL1-mediated CAP inhibition subsequently causes the internalisation of a pool of processed (active) ENaCγ prominent at the apical surface of CF cultures which correlates with a decline in channel activity. This downregulation of ENaC activity results in an increase in ASL height and improved mucociliary clearance in CF cells. We further find QUB-TL1 uniquely inhibits the ENaC activating enzyme furin, which is in contrast to the alternate trypsin-like CAP inhibitors camostat mesylate and aprotinin. QUB-TL1-mediated furin inhibition correlates with a reduction in neutrophil elastase-induced ENaC activation. Moreover we find QUB-TL1 treatment protects CF cultures from Pseudomonas aeruginosa exotoxin A-induced cytotoxicity. Pseudomonas aeruginosa exotoxin A is a major toxic product activated by furin and positively associated with mortality. Conclusion: The novel inhibitor (QUB-TL1) dampens CAPs-ENaC signalling which improves hydration status mucociliary clearance in CF airway epithelial cell cultures. Moreover this compound provides additional benefit by preventing Pseudomonas aeruginosa exotoxin A-induced cytotoxicity.

Utilisation of a novel ProteaseTag™ activity immunoassay for the specific measurement of neutrophil elastase in BAL from children with cystic fibrosis

Introduction: Neutrophil elastase (NE) is a serine protease implicated in the pathogenesis of several respiratory diseases including cystic fibrosis (CF). The presence of free NE in BAL is a predictor of subsequent bronchiectasis in children with CF (Sly et al, 2013, NEJM 368: 1963-1970). Furthermore, children with higher levels of sputum NE activity (NEa) tend to experience a more rapid decline in FEV1 over time even after adjusting for age, gender and baseline FEV1 (Sagel et al, 2012, AJRCCM 186: 857-865). Its detection and quantification in biological samples is however confounded by a lack of robust methodologies. Standard assays using chromogenic or fluorogenic substrates are not specific when added to complex samples containing multiple proteolytic and hydrolytic enzymes. ELISA systems measure total protein levels which can be a mixture of latent, active and protease-inhibitor complexes. We have therefore developed a novel assay (ProteaseTag™ Active NE Immunoassay), which couples an activity dependent NE-Tag with a specific antibody step, resulting in an assay which is both selective and specific for NEa. Aims: To clinically validate ProteaseTag™ Active NE for the detection of free NEa in BAL from children with CF. Methods: A total of 95 paediatric BAL samples [CF (n=76; 44M, 32F) non-CF (n=19; 12M, 7F)] collected through the Study of Host Immunity and Early Lung Disease in CF (SHIELD CF) were analysed for NEa using ProteaseTag™ Active NE (ProAxsis Ltd) and a fluorogenic substrate-based assay utilising Suc-AAPV-AMC (Sigma). IL-8 was measured by ELISA (R&D Systems). Results were analysed to show comparisons in free NEa between CF and non-CF samples alongside correlations with a range of clinical parameters. Results: NEa measured by ProteaseTag™ Active NE correlated significantly with age (r=0.3, p=0.01) and highly significantly with both IL-8 (r=0.4, p=<0.0001) and the absolute neutrophil count (ANC) (r=0.4, p=<0.0001). These correlations were not observed when NEa was measured by the substrate assay even though a significant correlation was found between the two assays (r=0.8, p<0.0001). A trend towards significance was found between NEa in the CF and non-CF groups when measured by ProteaseTag™ Active NE (p=0.07). Highly significant differences were found with the other inflammatory parameters between the 2 groups (IL-8: p=0.0002 and ANC: p=0.006). Conclusion: NEa as a primary efficacy endpoint in clinical trials or as a marker of inflammation within the clinic has been hampered by the lack of a robust and simple to use assay. ProteaseTag™ Active NE has been shown to be a specific and superior tool in the measurement of NEa in paediatric CF BAL samples (supporting data from previous studies using adult CF expectorated samples). The technology is currently being transferred to a lateral flow device for use at Point of Care. Acknowledgements: This work was supported by the National Children’s Research Centre, Dublin (SHIELD CF) and grants from the Medical Research Council and Cystic Fibrosis Foundation Therapeutics.

The perceived impact of interprofessional information sharing on young people about their sexual health care

This article presents the results from an analysis of data from service providers and young adults who were formerly in state care about how information about the sexual health of young people in state care is managed. In particular, the analysis focuses on the perceived impact of information sharing between professionals on young people. Twenty-two service providers from a range of professions including social work, nursing and psychology, and 19 young people aged 18–22 years who were formerly in state care participated in the study. A qualitative approach was employed in which participants were interviewed in depth and data were analysed using modified analytical induction (Bogdan & Biklen, 2007). Findings suggest that within the care system in which service provider participants worked it was standard practice that sensitive information about a young person’s sexual health would be shared across team members, even where there appeared to be no child protection issues. However, the accounts of the young people indicated that they experienced the sharing of information in this way as an invasion of their privacy. An unintended outcome of a high level of information sharing within teams is that the privacy of the young person in care is compromised in a way that is not likely to arise in the case of young people who are not in care. This may deter young people from availing themselves of the sexual health services.

The role of knowledge in the contraceptive behaviour of sexually active young people in state care

Aim: To analyse the role of sex-focused knowledge in the contraceptive behaviour of sexually active young people in state care.

Methods: The sample consisted of 19 care leavers (young people previously in state care) aged 18-22 years, 16 females and 3 males. In-depth interviewing was the method of data collection, and a qualitative strategy resembling modified analytical induction was used to analyse data.

Findings: Findings indicated that a lack of information was not the sole, or even the primary reason for engaging in unsafe sexual practices. Other factors such as ambivalence to becoming pregnant also featured in participants’ accounts. Several participants conveyed a relatively weak sense of agency about consistently using contraception. A small number of participants expressed a strong determination to avoid pregnancy, and these appeared to have a level of anxiety about becoming pregnant that motivated them to engage with knowledge about contraception and its use.

Conclusion: Lack of sex-focused information is just one aspect of a myriad of complex factors, including socioeconomic disadvantage and/or emotional deprivation, that influences contraceptive behaviour.

Christianity as a Vocation: The Rostrevor Benedictines and the Renewal of Faith in Ireland

This chapter explores how the Benedictine monks at Holy Cross Monastery in Rostrevor, Northern Ireland, have re-introduced the idea of vocation into the minds of a range of Christians on the island of Ireland. A picture of this new vision of the church in Ireland is painted through sections devoted to 'living ecumenism' and 'creating safe spaces'. The work of the Rostrevor Benedictines may seem limited because of the small scale of the changes among individuals. But Holy Cross is just one of multiple 'extra-institutional' spaces in Ireland's changing religious landscape. From their strategic positions on the margins, extra-institutional expressions of religion may prompt more significant changes in religious practice than initially seem possible.

Inhibition of protease-ENaC signaling improves mucociliary function in cystic fibrosis airways

Rationale: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height
compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of ENaC have therapeutic potential in CF airways to reduce the hyperstimulated sodium and fluid absorption to levels which can restore airways hydration.

Objectives: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function.

Methods: Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy) and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured by LDH assay.

Measurements and Results: QUB-TL1 inhibits extracellularly-located CAPs, including prostasin, matriptase and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells (AECs). QUB-TL1-mediated CAPs inhibition results in diminished ENaC-mediated Na+ absorption in CF AECs due to internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A induced cell death.

Conclusions: QUB-TL1 corrects aberrant CAP activities providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.

Étude de l'ajustement de pratiques vers une gestion différenciée de l'activité éducative par des directions d'établissement expérimentation d'un modèle d'accompagnement collectif

Les résultats de l'étude viennent réaffirmer la complexité des responsabilités éducatives d'une direction d'établissement. Pour répondre aux particularités du milieu, la direction est appelée à sortir des cadres habituels, à se questionner et à innover avec les membres de l'équipe-école, et ce, selon un savoir-agir situé guidant une gestion différenciée des activités éducatives. Huit balises viennent guider l'ajustement de ces pratiques.Les résultats permettent aussi d'expliciter en quoi le modèle d'accompagnement collectif devient une façon pour la direction d'établissement de prendre du recul, de sortir du sentiment d'isolement et de développer ses compétences. Ces résultats permettent de répondre à la question de recherche : en quoi un modèle d'accompagnement collectif est apte à soutenir l'ajustement de pratiques vers une gestion différenciée de l'activité éducative chez des directions d'établissement? Trois objectifs en découlent : 1) décrire et mettre en oeuvre un modèle d'accompagnement collectif 2) décrire et analyser les pratiques de gestion différenciée de l'activité éducative et 3) expliciter en quoi un modèle d'accompagnement collectif est apte à soutenir l'ajustement de pratiques vers une gestion différenciée de l'activité éducative chez des directions d'établissement. La démarche méthodologique rend compte de la double posture qu'occupe la personne accompagnatrice-chercheure et accompagnatrice-formatrice ayant accompagné et travaillé avec deux cohortes de neuf directions ou directions adjointes d'établissement de l'ordre d'enseignement primaire et secondaire, au sein de deux commissions scolaires de caractéristiques sociogéographiques différentes, sur une période de 15 mois. À partir d'une expérimentation, la démarche méthodologique donne la parole aux membres acteurs-praticiens et cochercheurs, les directions d'établissement. Chaque direction était alors invitée à conduire un projet professionnel d'intervention (PPI) selon la réalité éducative de son milieu. C'est donc à partir de l'analyse des PPI et des dires des membres acteurs-praticiens et cochercheurs que l'étude met en lumière des savoirs théoriques, praxéologiques et expérientiels de cette recherche-action.

Jazz Innovations I, March 10, 2010

Concert Program for Jazz Innovations I, March 10, 2010

Inventário das minas de água da área do Mosteiro de Tibães: proposta preliminar de hidrogeo‐itinerários

O Mosteiro de São Martinho de Tibães localiza‐se próximo de Braga (Norte de Portugal) e foi a Casa‐mãe da Ordem Beneditina em Portugal. Este Mosteiro foi abastecido durante séculos por numerosas minas de água, a maioria das quais se encontra actualmente abandonada. Este trabalho enfatiza a importância da combinação de diferentes matérias científicas nos processos de recuperação do património mineiro abandonado, bem como de sítios geo‐arqueológicos de relevância cultural, como um exemplo do processo transformador de uma organização, no sentido de promover um segundo ciclo de vida. O objectivo deste trabalho é apresentar uma abordagem metodológica, sob o ponto de vista da geoconservação e da geodiversidade. Subsequentemente, acções específicas serão desenvolvidas para reabilitar determinadas área, com o intuito de facilitar a sua inclusão em hidrogeo‐itinerários classificados. Esta perspectiva reflecte uma importante medida para a sustentabilidade, quer para o promotor quer para o meio ambiente envolvente.

The presence of Taeniodonta (Mammalia) in the Early Eocene of Europe

The first representative of the extinct mammalian order Taeniodonta in Europe is described, Eurodon silveirinhensis n. gen., n. sp., from the early Eocene locality of Silveirinha, Portugal. A formerly enigmatic form, Lessnessina Hooker, 1979, from Abbey Wood, England, and approximately contemporary, is also referred to the Taeniodonta.

The development of a knowledge-based society - Challenges for e-learning and adult students in higher education

This chapter appears in Encyclopaedia of Distance Learning 2nd Edition edit by Rogers, P.; Berg, Gary; Boettecher, Judith V.; Howard, Caroline; Justice, Lorraine; Schenk, Karen D.. Copyright 2009, IGI Global, www.igi-global.com. Posted by permission of the publisher. URL: http://www.igi-global.com/reference/ details.asp?ID=9703&v=tableOfContents