Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

Vaclav Havel's Legacy of Freedom

Vaclav Havel changed history as an advocate of freedom and universal human rights. A playwright, essayist, poet, dissident, and politician, Havel became a symbol of the civic opposition to the communist government in Czechoslovakia. After the Prague “Velvet Revolution” that toppled the communist regime, Havel became president of Czechoslovakia, and later the first president of the Czech Republic. Ten years ago, on September 21, 2002, President Vaclav Havel came to FIU and delivered memorable remarks about freedom and in support of a peaceful transition to democracy in Cuba. Madeleine K. Albright is Chair of Albright Stonebridge Group, a global strategy firm, and Chair of Albright Capital Management LLC, an investment advisory firm focused on emerging markets. She was the 64th Secretary of State of the United States. On May 29, 2012, Dr. Albright received the Presidential Medal of Freedom, the nation’s highest civilian honor, from President Obama. She received an honorary degree from FIU in 1996. Dr. Albright is a Professor in the Practice of Diplomacy at the Georgetown University School of Foreign Service. The panel discussion includes: Thomas Dine, President of the American Friends of the Czech Republic The Honorable Petr Gandalovic, Ambassador of the Czech Republic to the U.S. Carl Gershman, President of the National Endowment for Democracy Martin Palous, Director, Vaclav Havel Library, SIPA Senior Fellow Marifeli Perez-Stable, Interim Director, Latin American and Caribbean Center

Compilation of downward flux observations from sediment trap deployments in the Atlantic Ocean - Contribution to EURO-BASIN's Data integration

We provide a compilation of downward fluxes (total mass, POC, PON, BSiO2, CaCO3, PIC and lithogenic/terrigenous fluxes) from over 6000 sediment trap measurements distributed in the Atlantic Ocean, from 30 degree North to 49 degree South, and covering the period 1982-2011. Data from the Mediterranean Sea are also included. Data were compiled from different sources: data repositories (BCO-DMO, PANGAEA), time series sites (BATS, CARIACO), published scientific papers and/or personal communications from PI's. All sources are specifed in the data set. Data from the World Ocean Atlas 2009 were extracted to provide each flux observation with contextual environmental data, such as temperature, salinity, oxygen (concentration, AOU and percentage saturation), nitrate, phosphate and silicate.

Caractérisation des infections à Chlamydia trachomatis persistantes induites par l'action des antibiotiques

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Prévalence et facteurs de risques des infections sexuellement transmises chez des prostituées malgaches

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Caractérisation des infections à Chlamydia trachomatis persistantes induites par l'action des antibiotiques

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

El interés de la audiencia por las intervenciones televisivas de Pablo Iglesias: estrategia comunicativa de Podemos

Este artículo analiza la eclosión mediática y política del partido político Podemos durante sus primeros meses de vida tras las elecciones europeas. Comprobaremos si el interés que despierta el partido en sus inicios, en intención de voto, se traslada a las audiencias de televisión con dos hipótesis que muestran la estrategia comunicativa de Podemos y su repercusión: la H1 afirma que los programas en los que participa Pablo Iglesias obtienen mayor audiencia de la habitual y la H2 plantea que la apuesta del líder de Podemos por el medio televisivo es muy superior y con mejores resultados con respecto a los partidos clásicos. Los resultados demuestran que los programas en los que participa (N=14) crecen un 62% y baten récord de audiencia. Concluimos que la estrategia comunicativa de Podemos da importancia a la televisión, además de continuar con la estrategia en redes aprendida en el 15M.

The puppet as a tool for working in Art Therapy

This article aims to investigate the possibilities of building puppets in art therapy workshop, for this it realizes a tour of the primitive use of the puppet as a magical twin and potential towards the study of authors who have used the puppets as a therapeutic tool from the first half of the twentieth century. It’s raised an own theoretical organization, which includes the consideration of the significance of the body in the construction and management of the puppet and the puppet transitional perspective, halfway of external reality and psychic reality as an object that makes fantasy and reality arises built.

Connectivity Mapping (ssCMap) To Predict A20 Inducing Drugs: Anti-inflammatory Action In Cystic Fibrosis

Cystic Fibrosis (CF) lung disease is characterised by a chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to also normalise the inflammatory response. The prolonged and heightened inflammatory response in CF is in part mediated by a lack of intrinsic downregulation of the pro-inflammatory NF-kB pathway. We have previously identified reduced expression of the NF-kB down-regulator A20 in CF as a key target to normalise the inflammatory response. Here we have used publically available gene array expression data together with sscMap (statistically significant connections’map)to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NFkB (p65) expression (mRNA) as well as pro-inflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o-, CFBE41o-) and in primary nasal epithelial cells (PNECs) from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with TNFAIP3 (A20) knockdown (siRNA). We also show that the A20 inducing effect of ikarugamycin and quercetin is lower in CF derived airway epithelial cells than in non-CF cells.

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