The glycoprotein gp350 of EBV - an in vivo antigen and a promising druggable target molecule

Epstein-Barr virus (EBV) infects more than 90% of the human population worldwide. The virus is directly responsible for acute infectious mononucleosis (IM), and is related to several malignancies like Hodgkin lymphoma (HL), Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and posttransplant lymphoproliferative diseases (PTLD). EBV is also associated with various autoimmune diseases like Multiple Sclerosis (MS). The present work aimed at investigating the biology of EBV in long-term infected healthy carriers, thereby focusing on the expression of the lytic envelope glycoprotein gp350. The protein is well known for its crucial role for the viral infection of human B cells and is therefore considered an attractive target for therapeutic approaches, and also a vaccine candidate. The first part of this thesis was dedicated to investigating the presence of gp350 and its potential role in vivo. Since gp350-specificic antibodies can be detected life-long in EBV seropositive individuals, there might be a constant trigger of the immune system by gp350. This hypothesis was corroborated by my observation that certain latently EBV infected cell lines express significant amounts of gp350 on the cell surface and/or release it via extracellular vesicles (EVs). Moreover, I could show for the first time that the gp350 protein is present on a subset of B cells from healthy EBV-seropositive donors, and that the protein is also present in sera. Intriguingly, I could observe a direct correlation between antibody and protein titers. Moreover, I could show that gp350 carrying vesicles isolated from donors reactivate autologous gp350-specific CD4+ T cells, implicating a potential immunological function, e.g., in maintaining viral latency and stable co-existence with the host. This is the first time that gp350 was detected in the blood of healthy donors. Additional studies are needed to elucidate its origin, exact status and biological function. Therapeutic monoclonal antibodies are a success story in modern medicine. Of particular potential are fully human IgG antibodies which combine the unprecedented specificities of antibodies with a very low immunogenicity. However, fully human antibodies targeting gp350 are not existent. In the second part of this thesis, we therefore developed a new technique to generate fully human IgG antibodies in humanized mice in collaboration with Prof. R. Stripecke (Med. Hochschule Hannover). These humanized mice were immunized with Epstein-Barr-virus like particles (EB-VLPs), and splenocytes were then immortalized with EBV in vitro. The supernatants of the EBV immortalized B cells were tested for human gp350-specific antibodies with neutralizing potential. The most promising antibody from the biological and neutralization assays was cloned. The immunoglobulin sequence was obtained, and classified the antibody as human IgG3, an Ig class strongly related with infectious diseases. The collaboration with the Stripecke lab resulted in the first fully human IgG antibodies generated in humanized mice. In summary, the present study showed for the first time that gp350 is present in sera from EBV-positive healthy carriers without previous viral reactivation. Moreover, this protein is able to reactivate specific cellular immune responses. Finally, a fully human IgG3 gp350-specific antibody was produced, that may be developed into a therapeutic tool for the treatment of EBV-associated diseases

The effect of extramural English on Secondary-school learners'oral proficiency

El objetivo de este estudio es analizar la relación entre la exposición extracurricular al inglés y el aprendizaje en la destreza oral. Más concretamente, las preguntas de investigación que vertebraron el estudio fueron: ¿A qué tipo de inglés extracurricular, y en qué medida, se exponen los estudiantes de secundaria? y ¿cómo afecta la exposición al inglés fuera del aula a la destreza oral de los estudiantes de secundaria? Los participantes fueron estudiantes de inglés de 14-15 años de un instituto de secundaria de Navarra (España), quienes completaron un cuestionario online sobre sus hábitos de inglés fuera de la enseñanza reglada y una tarea oral basada en la narración de seis imágenes. El nivel oral de los participantes fue evaluado por dos calificadoras a través de una escala holística. Los resultados del cuestionario online revelaron grandes variaciones en cuanto a tipo y horas de exposición. En general, esta exposición tuvo un efecto positivo en la competencia oral de los alumnos, aunque las actividades más eficaces resultaron ser las que requieren que los alumnos tengan rol activo, a menudo facilitado por inputs multimodales, incluso cuando esta exposición no fue demasiado elevada. Además, no sólo la cantidad de exposición, sino también la combinación de distintos tipos influyó en el rendimiento oral de los participantes.The purpose of this study is to empirically combine data on extramural English (EE) with learning outcomes in the oral skill. More specifically, the research questions that guided the study were: (RQ 1) What type of EE, and how much, do secondary-school students make use of? and (RQ 2) How does EE affect the oral proficiency of secondary-school students? Data were collected from 16 English learners aged 14-15 in a secondary school in Navarre (Spain) through an online questionnaire about frequency and types of EE habits and an oral task based on the narration of a picture story. Participants’ oral performance was assessed by two raters using a holistic scale. The results from the online questionnaire revealed profound varying levels of engagement outside the regular school curriculum. In general, extramural exposure had a positive effect on students’ oral proficiency. The most effective types of activities were those which require learners to have an active participation, often triggered or facilitated through multimodal sources of input, even when this exposure was not too high. Another interesting result was that not only the amount of exposure, but also the combination of different types of activities influenced oral performance.Máster Universitario en Profesorado de Educación Secundaria por la Universidad Pública de NavarraBigarren Hezkuntzako Irakasletzako Unibertsitate Masterra Nafarroako Unibertsitate Publikoa

Signifying the In-Between: Race and Identity in Lawrence Hill’s Any Known Blood and Black Berry Sweet Juice: On Being Black and White in Canada

Trabajo de fin de Grado. Grado en Estudios Ingleses. Curso académico 2021-2022En su novela Any Known Blood y su libro de no ficción “Black Berry Sweet Juice: On Being Black and White in Canada” Lawrence Hill presenta la ambivalencia de ser mestizo en Canadá. Este espacio liminal que caracteriza al sujeto birracial permite a Hill defender nociones de nacionalidad y cultura que refutan ideas preconcebidas e idealizadas sobre el sentido de identidad, especialmente la de los sujetos negros. Al exponer los vínculos históricos entre los negros de Canadá y Estados Unidos, el autor expone las grietas de la política del multiculturalismo y desafía la metanarrativa canadiense que establece Canadá como un lugar libre de racismo, en contraposición con los Estados Unidos.In his novel Any Known Blood and his non-fiction book Black Berry Sweet Juice: On Being Black and White in Canada Lawrence Hill presents the ambivalence of being neither white nor Black in Canada. This in-between space which characterises the mixed-race subject allows Hill to propose a notion of nationhood and culture which contests fixed, idealized preconceptions around the sense of identity, particularly that of Black people. By exposing the historical links between Blacks in Canada and the United States as well as Canadian on-going racism in spite of multicultural policies, the author challenges the Canadian metanarrative which constructs Canada as a place where race does not matter, in contrast with its Southern neighbour

Value efficiency analysis of health systems: does public financing play a role?

Aims/Background: This study measures the performance of the health system in 165 countries and its relationship with public financing. Methods: We use value efficiency analysis (VEA), a refinement of data envelopment analysis (DEA), to measure the efficiency of the health systems using data on healthy life expectancy and disability adjusted life years as health outcomes. Expenditure on health and education are used as inputs to the health system. Results: The group of high income OECD countries shows the largest indexes of efficiency and also the lowest dispersion. In contrast, low income countries also have the most inefficient health systems, which implies that there are more opportunities for improvement. The average efficiency score is 0.96 for high income countries, 0.83 for upper-middle income countries, 0.86 for lower-middle income countries and only 0.76 for low income countries. Only 17 countries have a score equal to 1 and therefore are completely efficient and can be taken as referents. The index of efficiency is found to be positively associated with government expenditure on health as a percentage of total expenditure on health. Conclusions: The analysis of the results shows that the public share in health expenditure and the weight of health expenditure in public budgets are two factors positively associated with the performance of the health systems. The study also highlights the advantages of using VEA over DEA in the measurement of performance

25F VALUE EFFICIENCY ASSESSMENT OF QUALITY OF LIFE IN SPANISH MUNICIPALITIES

Área temática: F) Sector Público Palabras clave: calidad de vida, bienestar, municipios, DEA, VEA Keywords: quality of life, welfare, municipalities, DEA, VEA Clasificación JEL: R00, O18, H75, C60 1 VALUE EFFICIENCY ASSESSMENT OF QUALITY OF LIFE IN SPANISH MUNICIPALITIES Resumen En este trabajo se utiliza la metodología VEA-Value Efficiency Analysis para evaluar la calidad de vida de los 643 municipios españoles de mayor tamaño, utilizando 19 indicadores. El VEA es un refinamiento del DEA que impone consistencia sobre los pesos de los indicadores. Estos indicadores cubren aspectos relacionados con el consumo, servicios sociales, vivienda, transporte, medio ambiente, mercado laboral, salud, cultura, educación y seguridad. También se calculan índices VEA de supereficiencia para construir un ranking completo de calidad de vida. Los resultados muestran que la parte norte y centro de España obtiene los niveles mayores de calidad de vida. Abstrac

Long-term augmentation therapy with Alpha-1 Antitrypsin in an MZ-AAT severe persistent asthma

A young Caucasian female with severe bronchial asthma and Alpha1-antitrypsin (AAT) deficiency, MZ phenotype, experienced a quick and severe limitation of her physical capacity, which negatively affected her psychological state and social life, though she was under a strong antiasthmatic treatment. Given her declining health status and the significant chronic corticoid administration- related side-effects (including high reduction of muscle mass and bone density), a clinical trial with commercial intravenous AAT was proposed by the patient’s doctors, and accepted by the Spanish Ministry of Health, although it this therapy was not approved for MZ phenotypes yet. This new therapy quickly stopped lung function decline rate, dramatically reduced the number of hospital admissions of the patient, suppressed the oral administration of prednisone, reversed the corticosteroid-related health adverse effects, significantly improving her quality of life. Thus, although AAT replacement therapy is not approved nor indicated for the treatment of bronchial asthma in MZ patients, its favourable effects observed in this isolated case support the hypothesis that bronchial asthma could be due to pathogenic mechanisms related to a protease- antiprotease imbalance, what which could open new perspectives for future research on the field