Analysis of immunogenicity data in the product information of biological drugs: A need to report immunogenicity data systematically

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019Objetivo: Analisar se a prática contemporânea de avaliação fármaco a fármaco resulta na inclusão suficiente de informação (relativa à imunogenicidade) nos Resumos de Características do Medicamentos (RCMs) de produtos biológicos aprovados no Espaço Económico Europeu. Métodos: Informação relacionada com imunogenicidade foi identificada e extraída de um grupo de 73 medicamentos biológicos que cumpriam com critérios de seleção definidos à priori. Posteriormente, treze questões dicotómicas relacionadas com imunogenicidade foram propostas para avaliar se há assuntos que estão atualmente a ser negligenciados pelos RCMs destes produtos. Resultados: A maioria dos RCMs (92%) não inclui recomendações direcionadas para médicos e/ou doentes sobre como reportar Reações Adversas ao Medicamento possivelmente causadas por imunogenicidade. Adicionalmente, 80% dos RCMs não identifica o método utilizado para determinar as taxas de imunogenicidade reportadas nestes documentos e 81% dos RCMs não possui informação quanto ao impacto que a imunogenicidade pode ter (ou não) na farmacocinética destes fármacos. Foi também identificado um fator de grupo em que RCMs de fármacos mais antigos poderão estar a influenciar como abordar e quais os assuntos abordados por RCMs de medicamentos mais recentes. Para transformar os RCMs de produtos biológicos em documentos úteis a consultar quando uma resposta imunogénica ocorre, é avançada uma proposta sobre como reportar sistematicamente informação relativa à imunogenicidade nestes documentos. Conclusões: Com base nestes resultados, uma estratégia de avaliação fármaco a fármaco não resulta em RCMs com informação suficiente pelo que é necessário repensar esta abordagem e reportar estes dados de forma sistemática. Orientações futuras sobre como reportar informação relacionada com imunogenicidade serão necessárias, caso contrário os RCMs não serão a fonte base de informação, para profissionais de saúde, sobre como usar um produto biológico de forma segura e eficaz.Objective: To evaluate whether the current case-by-case practice leads to sufficient reporting of immunogenicity-related information in the Summary of Product Characteristics (SmPCs) of biological products approved in the European market. Methods: Immunogenicity-related information was identified and extracted from a group of 73 biological drugs that complied with drug-selection criteria. Afterwards, thirteen dichotomous questions were proposed to evaluate whether any issues are being commonly neglected. Results: Most SmPCs (92%) do not have any recommendations to patients or healthcare professionals on how to report immunogenicity-related adverse drug reactions. Furthermore, 80% of SmPCs do not identify the assay used to assess the reported immunogenicity rates and 81% of SmPCs do not address the possible impact of immunogenicity on their drug’s pharmacokinetics. It was also hypothesized based on these results that a group factor (i.e. SmPCs from older drugs) could be influencing how and which issues were being addressed by newer-drugs’ SmPCs. To transform these documents into useful tools capable of providing answers when an immunogenic response occurs, a decision-tree addressing how to systematically report immunogenicity-related information in the SmPCs of biological products is proposed. Conclusions: Based on these results, a case-by-case strategy does not yield sufficient reporting across SmPCs and thus reporting immunogenicity-related information should be reconsidered in order to report this information in a systematic way. Further guidance about reporting immunogenicity-related information is therefore required, otherwise SmPCs will not become the basis of information for healthcare professionals on how to use a biological product safely and effectively

Purification of cellulosic pulp by hot water extraction

Hot water extraction (HWE) of pulp in a flow-through reactor was evaluated as a method to purify paper-grade pulps. About 50–80 % of the xylan and up to 50 % of the lignin in unbleached birch Kraft pulp was extracted by the HWE without losses in cellulose yield. The residual xylan content in the extracted pulps was predominantly too high for dissolving-grade applications, but some of the pulps with a xylan content of 5–7 % might still be suitable as rayon-grade pulps. Increasing extraction temperature lowered the xylan content at which cellulose yield started to decrease. Furthermore, at any given xylan content, increasing extraction temperature resulted in cellulosic pulp with higher degree of polymerization. The extracted xylan was recovered almost quantitatively as xylo-oligosaccharides. The results suggest that HWEs at elevated temperatures may be applied to purify cellulosic pulps, preferably containing a low xylan content, and to recover the extracted sugars.Finnish Bioeconomy Cluster FIBIC OyTechnology Development Centre (Finland

Cell Wall Porosity in Norway Spruce Wood as Affected by High-Temperature Drying

In this study, pore size distribution in wood after high-temperature drying followed by rewetting was investigated by differential scanning calorimetry. Nonfreezing water content of wood was lower than previously indicated considering the effect of phase change on specific heat capacity of water. High-temperature drying appeared to close cavities of the largest size in earlywood, particularly with increasing drying temperature and time. Pore closure by irreversible hydrogen bonding dominated the eventual creation of cavities by degradation of wood structural components. Stress relaxation within wood elements, favored by slow high-temperature drying, decreased the extent of drying microcracks in earlywood, manifested in lower nonfreezing water content

AnCoraPipe: A tool for multilevel annotation

AnCoraPipe is a corpus annotation tool which allows different linguistic levels to be annotated simultaneously and efficiently, since it uses a single format for all stages. In this way, the required annotation time is reduced and the integration of the work of all annotators is made easier

Tout ce qui n’est pas dit par Madeleine Bourdouxhe. L’affirmation féminine de Sept Nouvelles à travers le silence

After several years in the background, the work of Madeleine Bourdouxhe (1906-1996) has been rediscovered, and critics have found in her stories a message of feminine identity affirmation, ahead of her time. Sept nouvelles brings together some of the short novels written by the author during her lifetime, presenting different women, contemporary to the author, who suffer from the lack of identity to which they are subjected by society and that forces them to be conditioned by their husbands. Through these stories, the writer expresses the need of women in the mid-20th century to achieve their own identity. However, this message is not explicitly presented in the short novels but it is developed through different literary and linguistic resources that will succeed in conveying to the reader the emptiness felt by her characters. The brief interventions of the women, their characteristics and, mostly, their silences will form the focus of our analysis.Tras varios años en un segundo plano, la obra de Madeleine Bourdouxhe (1906-1996) ha sido redescubierta y la crítica ha encontrado en sus relatos un mensaje de afirmación identitario femenino, precoz para su época. Sept nouvelles recupera algunas de las novelas cortas escritas por la autora durante su vida que presentan a diferentes mujeres, contemporáneas a la escritora, que sufren la falta de identidad a las que las somete la sociedad y que les obliga a estar condicionadas por sus maridos. A través de estas historias, la escritora expresa la necesidad de las mujeres de la mitad del siglo XX de alcanzar su identidad propia. Sin embargo, este mensaje no se presenta de manera explícita en la obra, sino que se desarrolla a través de diferentes recursos literarios y lingüísticos que conseguirán transmitir al lector el vacío que sienten sus personajes. Las breves intervenciones de las mujeres, sus características y, especialmente, sus silencios conformarán el centro de nuestro análisis.Après des années dans un arrière-plan, l'œuvre de Madeleine Bourdouxhe (1906-1996) a été redécouverte et la critique a trouvé dans ses récits un message d'affirmation de l'identité féminine, précoce pour son époque. Sept nouvelles rassemble certaines des nouvelles écrits par l'auteure tout au long de sa vie, qui mettent en scène différentes femmes, contemporaines à l'écrivaine, qui souffrent du manque d'identité auquel elles sont soumises par la société et qui les contraint à être conditionnées par leurs maris.À travers ces histoires, l'auteur exprime le besoin des femmes de la moitié du XXe siècle d'atteindre leur propre identité. Toutefois, ce message n'est pas présenté explicitement dans l'œuvre, mais il est développé à travers différentes ressources littéraires et linguistiques qui parviendront à transmettre au lecteur le vide ressenti par ses personnages. Les brèves interventions des femmes, leurs caractéristiques et, surtout, leurs silences constitueront le point central de notre analyse

Finanzas Descentralizadas

[ES] Las criptomonedas y la tecnología blockchain han tenido un gran auge este último año y con ello la sección de las Finanzas Descentralizadas (DeFi). Sin embargo, la atención a las mismas no ha sido acorde. A pesar de que las DeFi han crecido exponencialmente, los materiales para ayudar a las personas a comprenderlas han quedado a su vez rezagados. Con objeto de acelerar la adopción de esta alternativa a las finanzas tradicionales, este trabajo busca simplificar los diseños complejos de esta idea para que sean entendibles y accesibles para el público, y que éste puedaadentrarse en este fenómeno actual. Esta investigación tratará los conceptos más comunes para entender cómo esta nueva tecnología va a beneficiar de múltiples maneras a la sociedad y cómo puede cambiar las diversas formas de observar el sector financiero. El desarrollo de este proyecto no ha sido aislado, dado que nos ha conducido a la búsqueda de oportunidades para conseguir rentabilidad dentro de las DeFi, y a la creación de una empresa para atender a la gran demanda que generaban estos conocimientos. El objetivo principal es explicar una simple idea, que ha terminado siendo un mercado financiero activo descentralizado funcionando paralelamente con el tradicional. El trabajo se desarrolla en base a los diferentes proyectos construidos en la red Ethereum, aunque el concepto se puede aplicar a toda la tecnología y a cualquier red. El trabajo explica los proyectos más importantes que hay actualmente en el sector, qué arquitectura interna tienen y cómo han tenido tanto impacto. Por último, se desarrollan los problemas latentes hoy en día y se plantean soluciones a los mismos, finalizando con una reflexión y una conclusión sobre el análisis realizado.[EN] Cryptocurrencies and blockchain technology have had a huge boom this last year and with it the Decentralized Finance (DeFi) section, although it is not given the attention it requires. DeFi has grown exponentially, but the materials to help people understand this concept have lagged behind. To accelerate the adoption of this great alternative to traditional finance, this work seeks to make the complex designs of this great idea simple for the public to understand and accessible so that they can delve into this great phenomenon of today. This research will deal with the most common concepts to understand how this new technology is going to bring a large number of benefits to society and how the various ways of seeing the financial sector can change. Everything that will be explained in this project has led me to dedicate myself partially to the search for opportunities to achieve profitability within the DeFi, to the point of having to create a company due to the great demand generated by this knowledge. The main objective is to explain a simple idea, which has ended up being a decentralized active financial market working in parallel with the traditional one. The work is developed based on the different projects built on the Ethereum network, but the concept can be applied to all technology and to any network. The most important projects currently in the sector will be explained, what internal architecture they have and how they have had such an impact. Finally, the problems that are latent today will be developed and in what way they will be solved, ending with a reflection and a conclusion on everything that was previously discussed.Borrega Langa, R. (2021). Finanzas Descentralizadas. Universitat Politècnica de València. http://hdl.handle.net/10251/172618TFG

Variación somatológica de poblaciones autóctonas de la Antigua Guinea Ecuatorial Española

En 1948 una expedición científica recorrió los territorios españoles del Golfo de Guinea, bajo el patrocinio del Instituto de Estudios Africanos del CSIC y de la Dirección General de Marruecos y Colonias. Dos de sus componentes, Alcobé y Fernández Cabeza, dedicaron sus actividades al estudio antropológico somático de los indígenas. En el presente estudio se analiza la variación somática poblacional de una muestra de datos inéditos de aquella expedición consistente en 120 individuos de cada una de las muestras recolectadas de varones y mujeres Pamue; varones Combe; y varones y mujeres Bubi. Nuestro estudio analiza el dimorfismo sexual, así como la variación intra e intergrupal. Adicionalmente, y debido a que las etnias guineanas se mezclaron con los antiguos pigmeos occidentales de la etnia Biaka (o Baka), se comparan aquéllas con otras de la cubeta congoleña compuesta por Pigmeos del Ituri, así como mestizos entre éstos y melanoafricanos, conocidos como Waldneger. Dar a conocer esta amplia información, creemos, será una aportación valiosa al conocimiento de la rica diversidad somatológica de los pueblos africanos

Albert Camus y la filosofía del límite (lectura casi nietzscheana de "El hombre rebelde")

El presente artículo tiene como objetivo la aproximación a un autor, y en concreto a uno de sus textos, que no suele aparecer en los manuales de filosofia, ni siquiera en los libros monográficos que hablan del existencialismo. Hablamos de Albert Camus (1913-1960) y de su obra El hombre rebelde (1951)