Chronic inflammation in CF airways - a persistent issue for A20

Cystic Fibrosis (CF) is characterised by prolonged and exaggerated airways inflammation. Despite recent developments to overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to reduce the inflammatory response. The NF-kB regulator A20 is a key target to normalise the inflammatory response and is reduced in CF. Here, we describe the plethora of functions of A20 as they apply to innate immune function within the airways. Pharmacological compounds can enhance A20 mRNA and protein expression, but we observed a blunted effect in CF primary epithelial cells. In CF cells pre-treatment with gibberellic acid (GA3) shows anti-inflammatory effects only in some patients. We show that cells with higher basal p38 expression respond with an increase in pro-inflammatory cytokines. Furthermore, all CF PNECs show increased p38 mRNA when stimulated in the presence of GA3. Our results suggest that those patients may benefit from therapeutics targeting p38.

Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol

Introduction Emerging evidence suggests that patient-reported outcome (PRO)-specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best-practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported. Hypothesis: Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points.

Methods and analysis Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO-specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion.

Ethics and dissemination The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r).

Migrating Borders and Moving Times:Temporality and the Crossing of Borders in Europe

Edited book, with 12,000 word contributed authored chapter 'Crossing borders, changing times'

Företags potentiella manipulation av tillväxttakt i goodwillnedskrivningstestet : En kvantitativ studie av svenska och finska börsnoterade företag

Bakgrund och problem: I och med den nya standarden IAS 36 ska företagen göra uppskattningar angående den långsiktiga tillväxttakten i goodwillnedskrivningstestet. Detta innebär en möjlighet att manipulera tillväxttakten för att på så vis undvika eller framkalla nedskrivning av goodwill. Problemformulering: Hur påverkar utvalda variabler företags potentiella manipulation av angiven tillväxttakt? Syfte: Syftet med studien är att bidra med förklaringar till vad som påverkar att företag redovisar för höga respektive för låga tillväxttakter i goodwillnedskrivningstestet. Metod: Denna studie bygger på en kvantitativ metod där urvalet består av samtliga svenska och finska börsnoterade företag med redovisad goodwill. Utifrån existerade kunskap formuleras fyra hypoteser som testas mot empirin. Resultat och slutsats: Resultatet av denna studie visar inga signifikanta samband mellan den beroende variabeln manipulation och de oberoende variablerna storlek, skuldsättningsgrad, bransch och redovisningstillsyn. Den deskriptiva statistiken visar att i stort sett hälften av företagen manipulerar tillväxttakten.

Kvinnor i styrelser : Att lyckas i en mansdominerad värld

Kvinnor har länge varit exkluderade från ledarpositioner, såsom styrelser, men utvecklingen mot en mer jämställd könsfördelning går långsamt framåt. Syftet med uppsatsen är att skapa förståelse för hur kvinnor i styrelser kan bidra till utvecklingen mot en jämnare könsfördelning. Genom att intervjua fem kvinnliga styrelseledamöter har vi fått en inblick i deras upplevelser och erfarenheter av styrelsearbete och könsroller. Kvinnorna i undersökningen har, genom många års styrelsearbete i olika former samt genom gedigna arbetserfarenheter, arbetat sig fram till ledande positioner inom olika branscher och företag. Även om de överlag inte anser sig ha behandlats annorlunda i styrelsen på grund av sitt kön kan vissa av kvinnorna ändå uppleva att de ibland förväntas ansvara för specifika uppgifter just för att de är kvinnor, att de behöver tuffa till sig eller att de måste vara mer pålästa och duktigare än männen. De anser att kvotering kan vara det enda sättet att få jämställda styrelser men understryker att det bör vara kompetensen som avgör vem som får uppdraget. För att lyckas bra som ledamot krävs, enligt respondenterna, en viss baskunskap om ekonomi och ledarskap samt ett visst mått av självsäkerhet och att våga stå för sina åsikter. Kravbilden på styrelsemedlemmar i bolagsstyrelser har ökat under de senaste årtiondena och det krävs att medlemmarna som individer har en hög kompetens och att styrelsen i sin helhet besitter en bred kunskapsbas. Denna utveckling kan ha en positiv effekt på könsfördelningen då det är fler kvinnor än män som har universitetsutbildning och eftersom en mer heterogen grupp ger ett bredare spektrum av kunskaper. Kvinnorna i undersökningen har genom sina positioner bidragit till brytandet av normer och gör det därför lättare för andra kvinnor att följa i deras spår. Det råder ingen brist på kompetenta kvinnor men utmaningen ligger i att kartlägga och synliggöra dessa kvinnor och ge dem samma möjlighet som männen att nå ledande positioner.

Processo de planejamento estratégico em universidade pública: o caso da Universidade Federal do Pará

The goal of this research is to check if the strategic planning developed between 2001 and 2009 into the State University of Para (Universidade Federal do Pará - UFPA) was consolidated into its Academic Centers as a management practice. To this end, we identified the planning formalization degree of the Academic Centers, the conceived tools for the planning, the conception and the methodological process used in the tools elaboration, as also its implementation. The research used a qualitative approach: it is descriptive and it uses the case study technique. The data were gathered from primary and secondary sources, through bibliography, documents, and field researches through semi-structure interviews. The analysis and data interpretation were done by each investigated Academic Center from the analytics categories guided by the specifics goals. We used theoretic fundamental based principles and the university as a study empiric reference based on its structure analysis, organizational processes and institutional strategic plan. We inspected how the strategic planning process was developed throughout the fixed period and how the investigated Academic Centers are from the collected documents and interviews. The theoretical foundation was built from three axis: the Brazilian undergraduate and posgraduate education system; the university itself including its singularity and complexity as an organization; and the planning as a strategic management process. The main results show us that the UFPA has updated regulatory milestones, presenting organizational structure, laws, instructions, manuals and deployed management model that give the strategic planning development conditions beyond its administration, i. e., into its Academic Centers. The centers also present those established milestones and develop the basic planning processes of the institution. Those processes are conceived based on the institutional strategic planning and the managers mainly use the procedural orientation defined by the university management, from where the conceptual foundation is originated and propagated. According to the literature and to the research done in this work, we can conclude that the Academic Centers from the UFPA developed the strategic planning practice. This planning is organized and founded and guided the plans and decisions which avoided the disordered management and, according to the managers, allowed the advances and performance improvement. We can conclude that the UFPA built an important foundation with respect to the management professionalization. On the other hand, we can not conclude that the management practice is consolidated since there are weaknesses into the structuring of the technical teams and there is not any management tool for the implementation of the elaborated plans

Relier les mesures d'atténuation et d'adaptation aux changements climatiques : la situation des régions côtières du Québec

Les conséquences associées aux changements climatiques peuvent déjà être perçues dans différents secteurs socio-économiques. Tel est le cas des zones côtières. Afin d’assurer la pérennité des populations dans les régions insulaires, différentes mesures d’adaptation côtières peuvent être utilisées. Or, ces mesures peuvent parfois manquer de vision à long terme et d’intégration de l’autre type de réaction aux changements climatiques soit l’atténuation. La difficulté à relier adaptation et atténuation est présente dans plusieurs secteurs, dont les zones côtières. La situation dans les territoires Québécois maritimes (plus précisément les côtes de la Côte-Nord, du Bas- Saint-Laurent et de la Gaspésie-Îles-de-la-Madeleine) est semblable à celle observée ailleurs, mais demeure unique étant donné la composition de ses côtes, l’évolution démographique de ces municipalités et son économie fortement basée sur le tourisme et l’industrie des pêches. Les principaux enjeux retrouvés dans ces territoires sont associés au tourisme, à l’industrie de la pêche, à la densité humaine et aux infrastructures qui en découlent ou au milieu naturel. Ces enjeux présentent différentes vulnérabilités face au changement climatique côtier auxquelles les municipalités doivent s’adapter. Les mesures d’adaptation côtières implantées au Québec peuvent être divisées en deux grandes catégories : les mesures techniques et les mesures règlementaires et politiques. Or, afin de s’adapter adéquatement les municipalités doivent faire preuve de multidisciplinarité et combiner les différentes techniques disponibles, ceci peut présenter une difficulté notable. La situation canadienne à l’extérieur du Québec est similaire pour les territoires Atlantiques Canadiens. Du côté du Pacifique, les types de menaces surviennent dans des proportions différentes à celles de l’Est. De façon générale, les provinces les plus à risques de la hausse du niveau des mers sont aussi celles qui utilisent principalement des mesures de protection d’urgence, optant pour une vision à court terme, ceci incluant le Québec. Le cadre législatif encadrant les territoires côtiers québécois du Golfe est complexe. En effet, il s’agit d’une combinaison de lois et règlements fédéraux et provinciaux qui s’entrecoupent, étant donné l’entrecroisement des compétences gouvernemental dans ce secteur. Ceci peut compliquer d’avantages le travail des municipalités québécoises. Afin de faciliter l’implantation de mesures d’adaptation considérant l’atténuation, les municipalités côtières québécoises pourraient développer un cadre d’évaluation des différentes mesures.

Entre liberté et contrainte : les praticiens de l’art face au métier d’artiste

Ce mémoire trouve son origine dans le questionnement que nous avons posé par rapport à nos propres représentations concernant la pratique de l’art lorsque nous avons pris connaissance du plan d’action Québec horizon culture et en particulier du programme de mentorat qu’il offre aux artistes et qui consistent à les jumeler avec des gens d’affaires. Dans ce mémoire, nous avons cherché à comprendre comment les individus qui aspirent à faire de l’art subissent les injonctions du milieu artistique et les valeurs qu’il véhicule, de même que les exigences à propos de l’art véhiculées plus généralement dans la société. Notre intérêt s’est porté sur les représentations endossées par les artistes en lien avec la façon de subvenir à leurs besoins matériels. Plus particulièrement, nous avons cherché à savoir comment les programmes de mentorat auxquels prennent part des artistes participent de cet agencement et si les artistes qui manifestent de l’intérêt pour ces programmes ont une façon différente des autres d’envisager cet agencement. Pour répondre à ce questionnement, nous avons interrogé par des entretiens semi-dirigés des praticiens de l’art mentorés et non mentorés provenant de différents milieux artistiques. Il résulte de notre enquête qu’ils n’accordent pas tous la même place à l’activité artistique dans leur vie et que seulement certains cherchent à subvenir à leurs besoins matériels par l’activité artistique. De ces deux dimensions de la pratique artistique, nous avons conclu que le sens de la pratique artistique varie d’un répondant à l’autre. Nous avons finalement dégagé quatre types de finalité de la pratique artistique : intégrée, récréative, désintéressée et instrumentale.

Encountering the Spectre of Painting

When thinking what paintings are, I am continually brought back to my memory of a short sequence in Alfred Hitchcock’s Vertigo. In the scene, Kim Novak’s Madeleine is seated on a bench in an art gallery. She is apparently transfixed by a painting, Portrait of Carlotta. Alongside James Stewart, we watch her looking intently. Madeleine is pretending to be a ghost. At this stage she does not expect us to believe she is a ghost, but simply to immerse ourselves in the conceit, to delight in the shudder. Madeleine’s back is turned away from us, and as the camera draws near to show that the knot pattern in her hair mirrors the image in the portrait, I imagine Madeleine suppressing a smile. She resolutely shows us her back, though, so her feint is not betrayed. Madeleine’s stillness in this scene makes her appear as an object, a thing in the world, a rock or a pile of logs perhaps. We are not looking at that thing, however, but rather a residual image of something creaturely, a spectre. This after-image is held to the ground both by the gravity suggested by its manifestation and by the fine lie - the camouflage - of pretending to be a ghost. Encountering a painting is like meeting Madeleine. It sits in front of its own picture, gazing at it. Despite being motionless and having its back to us, there is a lurching sensation the painting brings about by pretending to be the ghost of its picture, and, at the same time, never really anticipating your credulity.

Origin of an enigmatic regional Mio-Pliocene unconformity on the Demerara plateau

The Demerara plateau, located offshore French Guiana and Suriname, is part of a passive transform continental margin particularly prone to develop slope instabilities, probably in relation to the presence of a free distal border along its steep continental slope. Slope failure occurred at different periods (Cretaceous to Neogene) and shows an overall retrogressive evolution through time. Upslope these failure headscarp, an enigmatic regional MioPliocene unconformity has been discovered through the interpretation of new academic and industrial datasets. The aim of this work is to describe and understand the origin of this surface. Our analysis shows that this unconformity is made of a series of valleys that cross-cut sedimentary strata. Each one of these valleys has a short lateral extent and is closed along two perpendicular directions, which suggests that it could correspond to a highly meandering system, or to some sub-circular depressions. The infill of these features is equivalent to the regional stratigraphic strata found outside the structures, but in a subdued position. This seems to imply that the structures have originated by a local loss of sediments at their base or by sliding processes. Furthermore, these depressions intersect each other through time, while migrating progressively downslope. We discuss a series of hypotheses that try to explain the onset and evolution of these depressions forming the Mio-Pliocene unconformity (Canyons? Slope failures? Contourite moats? Hydrate pockmarks?). Having established that these structures are depressions formed by collapse, and have many similarities with structures recently described in the literature as pockmarks associated with gas hydrate dissolution, we favor this hypothesis. We propose that these hydrate pockmarks form with a mass failure that was triggered by fluid-overpressure development at the base of the hydrate stability zone.

Processo de planejamento estratégico em universidade pública: o caso da Universidade Federal do Pará

The goal of this research is to check if the strategic planning developed between 2001 and 2009 into the State University of Para (Universidade Federal do Pará - UFPA) was consolidated into its Academic Centers as a management practice. To this end, we identified the planning formalization degree of the Academic Centers, the conceived tools for the planning, the conception and the methodological process used in the tools elaboration, as also its implementation. The research used a qualitative approach: it is descriptive and it uses the case study technique. The data were gathered from primary and secondary sources, through bibliography, documents, and field researches through semi-structure interviews. The analysis and data interpretation were done by each investigated Academic Center from the analytics categories guided by the specifics goals. We used theoretic fundamental based principles and the university as a study empiric reference based on its structure analysis, organizational processes and institutional strategic plan. We inspected how the strategic planning process was developed throughout the fixed period and how the investigated Academic Centers are from the collected documents and interviews. The theoretical foundation was built from three axis: the Brazilian undergraduate and posgraduate education system; the university itself including its singularity and complexity as an organization; and the planning as a strategic management process. The main results show us that the UFPA has updated regulatory milestones, presenting organizational structure, laws, instructions, manuals and deployed management model that give the strategic planning development conditions beyond its administration, i. e., into its Academic Centers. The centers also present those established milestones and develop the basic planning processes of the institution. Those processes are conceived based on the institutional strategic planning and the managers mainly use the procedural orientation defined by the university management, from where the conceptual foundation is originated and propagated. According to the literature and to the research done in this work, we can conclude that the Academic Centers from the UFPA developed the strategic planning practice. This planning is organized and founded and guided the plans and decisions which avoided the disordered management and, according to the managers, allowed the advances and performance improvement. We can conclude that the UFPA built an important foundation with respect to the management professionalization. On the other hand, we can not conclude that the management practice is consolidated since there are weaknesses into the structuring of the technical teams and there is not any management tool for the implementation of the elaborated plans

Utilidad de los criterios de predicción clínica y del test rápido antigénico para el manejo de la faringitis aguda en un servicio de urgencias

Objetivo: Validar los criterios de CENTOR modificados (CENTOR-m) y los tests rápidos de detección del antígeno de Estreptococo del Grupo A (SGA) en la faringitis aguda. Diseño: Estudio de validación de pruebas diagnósticas. Emplazamiento y participantes: Ciento un pacientes elegibles, que consultaron al departamento de urgencias de un hospital de tercer nivel con cuadro clínico compatible con faringitis aguda. Mediciones Principales: Se obtuvieron muestras de hisopados faríngeos para la realización del test rápido antigénico para SGA (FAMR) y para cultivo, respectivamente. Se calculó en cada caso los criterios de CENTOR-m. Resultados: La edad media de los pacientes incluidos en el estudio fue de 22,6 años (DE:13,8). El 48,5 % eran varones. El SGA fue el patógeno aislado en el 20,79 % de los casos. El CENTOR-m presentó una sensibilidad del 83,3 % (50,9 %-97,1 %), especificidad del 45,5 % (30,7 %-61,0 %) valor predictivo positivo (VPP) del 29,4 % (15,7 %-47,7 %) y valor predictivo negativo (VPN) del 90,9 % (69,4 %-98,4 %). El FAMR presento una sensibilidad del 81,5 % (61,3 %-93,0 %) especificidad del 98,6 % (91,4 %-99,9 %), VPP del 95,7 % (76,0 %-99,8 %) y VPN del 93,3 % (84,5 %-97,5 %). El 49,5 % de los pacientes recibieron antibióticos basándose en el juicio médico, lo que resultó en una proporción de sobreindicación de antimicrobianos del 62 %. Conclusiones: Los criterios de CENTOR-m demostraron adecuado valor pronóstico negativo y el FAMR buena sensibilidad, especificidad y valor pronóstico positivo para faringitis por SGA. La utilización de ambos métodos en la atención urgente podría optimizar el manejo de la patología y la adecuación antibiótica.