Defining response to anti-VEGF therapies in neovascular AMD

The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient’s age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as ‘responder status’ after treatment for n-AMD, ‘tachyphylaxis’ and ‘recalcitrant’ n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there is resolution of fluid (intraretinal fluid; IRF, subretinal fluid; SRF and retinal thickening), and/or improvement of >5 letters, subject to the ceiling effect of good starting VA. Poor response is defined as <25% reduction from the baseline in the central retinal thickness (CRT), with persistent or new IRF, SRF or minimal or change in VA (that is, change in VA of 0+4 letters). Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently. Poor or non-response to anti-VEGF may be due to clinical factors including suboptimal dosing than that required by a particular patient, increased dosing intervals, treatment initiation when disease is already at an advanced or chronic stage), cellular mechanisms, lesion type, genetic variation and potential tachyphylaxis); non-clinical factors including poor access to clinics or delayed appointments may also result in poor treatment outcomes. In eyes classified as good responders, treatment should be continued with the same agent when disease activity is present or reactivation occurs following temporary dose holding. In eyes that show partial response, treatment may be continued, although re-evaluation with further imaging may be required to exclude confounding factors. Where there is persistent, unchanging accumulated fluid following three consecutive injections at monthly intervals, treatment may be withheld temporarily, but recommenced with the same or alternative anti-VEGF if the fluid subsequently increases (lesion considered active). Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT). Idiopathic polypoidal choroidopathy may require treatment with PDT monotherapy or combination with anti-VEGF. A committee comprised of retinal specialists with experience of managing patients with n-AMD similar to that which developed the Royal College of Ophthalmologists Guidelines to Ranibizumab was assembled. Individual aspects of the guidelines were proposed by the committee lead (WMA) based on relevant reference to published evidence base following a search of Medline and circulated to all committee members for discussion before approval or modification. Each draft was modified according to feedback from committee members until unanimous approval was obtained in the final draft. A system for categorising the range of responsiveness of n-AMD lesions to anti-VEGF therapy is proposed. The proposal is based primarily on morphological criteria but functional criteria have been included. Recommendations have been made on when to consider discontinuation of therapy either because of success or futility. These guidelines should help clinical decision-making and may prevent over and/or undertreatment with anti-VEGF therapy.

Mundos prohibidos: El poder en el discurso epistolar de Gertrudis Gómez de Avellaneda y Juana Borrero

This dissertation analyses, through a theoretical framework and a critical approach, letters of Cuban writers Gertrudis Gómez de Avellaneda and Juana Borrero. While love letters have captured the interest of some scholars, such as Claudio Guillén, Cintio Vitier and Alexander Roselló Selimov, the conflict that the analysis of non-literary texts poses has prevented further research in this field. Therefore, I propose a systematic method of analysis encompassing but not limited to evaluating letters based on their purpose, intent, interpretation, and temporal and spatial composition; analyzing the perspective and function of epistolary entities, and examining the textual signs that distinguish the epistolary forms from the literary forms. With this analytical tool, I examine a selection of letters of Gómez de Avellaneda and demonstrate that the writer displaces her identify from the autobiographic self to the epistolary self, in order to manipulate the perspective of her addressee. Caught between the Neoclassical way of thinking and the Romantic aesthetics, her assertive discourse, also reflected in her epistolary work, contributed to the incursion of women writers into the social and professional life of the nineteen century. Following the same method of investigation, an analysis of letters written by Borrero proves that, by building a world of delusion, hallucination and fantasy the writer brings to prose what first generation of female modernistas had done in poetry. In both cases, my focus is on the strategies that turn these letters into instruments of power, process that transformed the love-letter paradigm and forever renovated the women epistolary genre. This dissertation further explores the possibility of initiating a cycle in the study of personal letters to uncover a forgotten genre, mission that might build a bridge to embrace the new forms of written communication that scholars have already begun to explore in contemporary literature.

Análise textual-interativa das Cartas dos Sertões do Seridó: em busca de efeitos estético-estilísticos

This work takes as its object of study a specific set of texts, designated letters about Sertões do Seridó (interstate region in the Brazilian northeastern), written by Paulo Bezerra, whose main approach is the backcountry universe. For its unique character, mainly because of a strong poetic appeal, we infer that these letters can also contain natural phenomena related to discourse-compositional structure, which may be responsible for creating specific effects, particularly aesthetical. In order to discuss and develop the issue, we set the theoretical assumptions of Textual-Interactive Perspective whose base is the concept of language as interaction, such as verbal activity impregnated with the space-time social and historical context in which the interlocutors are related, we chose the analytical category discursive topic and analyse introduction, sequencing and change of topic mechanisms. The goal is to determine the functionality of these mechanisms, noting how correlate the structural and interactional aspects are, and how this movement can be used to explain some of the aesthetic and stylistic effects of these letters. The result shows that it is used different topic organizational patterns according to the nature of the central topic. These different mechanisms express an aesthetic intention and feature a style. This result gives rise to more general conclusions about the texts: their discursive-compositional structure is related to the creation of aesthetics and stylistics effects.

Entre cartas e contos na sala de aula: diálogos e afetos em textos de Mário de Andrade e Câmara Cascudo

Specific educational material production for a group of level IV – 8th and 9th years of Youth and Adults Education, having as starting point the reading of a series of letter of correspondence between Câmara Cascudo and Mário de Andrade in the 1920s, and the verification of the way the dialog between the two authors reveals elements that transpire themselves in the tale entitled “Piá não sofre? Sofre”, from the book Os contos de Belazarte, de Mário de Andrade. The educational material production was preceded by the analysis of the selected tale, which will be studied along with some of the letters, in an analysis of the textual, discursive and semantic features of the text in representation of these both genres: letter and tale. The selected tale was written between 1923 and 1926, dates close to the years when the author came by Rio Grande do Norte state, in the years from 1927 to 1929, accompanied by Câmara Cascudo, being also this period that there are records of letters in the set of correspondence between them. To the reading of the selected material, it was used theoretical references from literature and literary historiography, especially the history of Brazilian modernist movement. To the production of the educational material, it was chosen as theoretical reference the accumulated knowledge in the area of literature teaching, literacy and the recommendations of the Brazilian National Curriculum Parameters. The methodology in this study was constructed from the theoretical references and had as basic support the study of didactic sequences from which a specific thematic unit got its shape from, required by the analyzed material and tested in a classroom.

Entre cartas e contos na sala de aula: diálogos e afetos em textos de Mário de Andrade e Câmara Cascudo

Specific educational material production for a group of level IV – 8th and 9th years of Youth and Adults Education, having as starting point the reading of a series of letter of correspondence between Câmara Cascudo and Mário de Andrade in the 1920s, and the verification of the way the dialog between the two authors reveals elements that transpire themselves in the tale entitled “Piá não sofre? Sofre”, from the book Os contos de Belazarte, de Mário de Andrade. The educational material production was preceded by the analysis of the selected tale, which will be studied along with some of the letters, in an analysis of the textual, discursive and semantic features of the text in representation of these both genres: letter and tale. The selected tale was written between 1923 and 1926, dates close to the years when the author came by Rio Grande do Norte state, in the years from 1927 to 1929, accompanied by Câmara Cascudo, being also this period that there are records of letters in the set of correspondence between them. To the reading of the selected material, it was used theoretical references from literature and literary historiography, especially the history of Brazilian modernist movement. To the production of the educational material, it was chosen as theoretical reference the accumulated knowledge in the area of literature teaching, literacy and the recommendations of the Brazilian National Curriculum Parameters. The methodology in this study was constructed from the theoretical references and had as basic support the study of didactic sequences from which a specific thematic unit got its shape from, required by the analyzed material and tested in a classroom.

Os possessivos de segunda pessoa em cartas de leitores de jornais brasileiros dos séculos XIX e XX

Based on the theoretical and methodological presuppositions of the theory of language variation and change (cf. WEINREICH; LABOV; HERZOG, 2006 [1968]), it is described and analyzed in this article the process of variation/change concerning the second person possessive pronouns in letters from readers of Brazilian newspapers from the XIX and XX centuries. These letters feature a portrait of the Brazilian press from the South (Santa Catarina), Southeast (Rio de Janeiro) and Northeast (Bahia and Rio Grande do Norte) regions in each century and are part of the Project for Brazilian Portuguese History‘s (PHPB) printed common minimal corpus. The point of departure of this work is the idea that the use of variant forms of expressing second person possessive pronouns – teu and seu – results from the interaction characterizing the varied social roles performed by the letters‘ senders. Arranging communicative units, which gather elements/features denoting time and space, conditioned and determined by socio-historical and cultural aspects, the readers‘ letters, turn out to be a promising research field under the light of this paper. More specifically, In the row of presented results in studies about the pronominal system in the diachroneity of/in Brazilian Portuguese (PB) (FARACO, 2002; LORENGIAN-PENKAL, 2007; CALLOU; LOPES, 2003; LOPES; DUARTE, 2003; MENON, 2005; ARDUIN; COELHO, 2006; LOPES, 2009; MARCOTULIO, 2010), the results featured in here point at different usages of the possessives, noticing the coexistence of the forms teu/tua and seu/sua strongly conditioned by the socio-discursive nature of the readers‘ letters in the course of the centuries and through different regions.

Os possessivos de segunda pessoa em cartas de leitores de jornais brasileiros dos séculos XIX e XX

Based on the theoretical and methodological presuppositions of the theory of language variation and change (cf. WEINREICH; LABOV; HERZOG, 2006 [1968]), it is described and analyzed in this article the process of variation/change concerning the second person possessive pronouns in letters from readers of Brazilian newspapers from the XIX and XX centuries. These letters feature a portrait of the Brazilian press from the South (Santa Catarina), Southeast (Rio de Janeiro) and Northeast (Bahia and Rio Grande do Norte) regions in each century and are part of the Project for Brazilian Portuguese History‘s (PHPB) printed common minimal corpus. The point of departure of this work is the idea that the use of variant forms of expressing second person possessive pronouns – teu and seu – results from the interaction characterizing the varied social roles performed by the letters‘ senders. Arranging communicative units, which gather elements/features denoting time and space, conditioned and determined by socio-historical and cultural aspects, the readers‘ letters, turn out to be a promising research field under the light of this paper. More specifically, In the row of presented results in studies about the pronominal system in the diachroneity of/in Brazilian Portuguese (PB) (FARACO, 2002; LORENGIAN-PENKAL, 2007; CALLOU; LOPES, 2003; LOPES; DUARTE, 2003; MENON, 2005; ARDUIN; COELHO, 2006; LOPES, 2009; MARCOTULIO, 2010), the results featured in here point at different usages of the possessives, noticing the coexistence of the forms teu/tua and seu/sua strongly conditioned by the socio-discursive nature of the readers‘ letters in the course of the centuries and through different regions.

La idea de América en las cartas de Thomas Merton a escritores argentinos

Este artículo, que forma parte de una investigación sobre la poética de traducción y las ideas americanistas de Thomas Merton, explora estos temas a través del análisis de la correspondencia de Thomas Merton con sus cuatro corresponsales argentinos: Victoria Ocampo, Miguel Grinberg, Rafael Squirru y Alejandro Vignati. Si bien en las cartas intercambiadas con estos cuatro actores culturales argentinos los intereses particulares son variados, subyace en todas el ideal americanista que Merton manifiesta a lo largo de sus escritos y su percepción de la poesía sudamericana.

La idea de América en las cartas de Thomas Merton a escritores argentinos

Este artículo, que forma parte de una investigación sobre la poética de traducción y las ideas americanistas de Thomas Merton, explora estos temas a través del análisis de la correspondencia de Thomas Merton con sus cuatro corresponsales argentinos: Victoria Ocampo, Miguel Grinberg, Rafael Squirru y Alejandro Vignati. Si bien en las cartas intercambiadas con estos cuatro actores culturales argentinos los intereses particulares son variados, subyace en todas el ideal americanista que Merton manifiesta a lo largo de sus escritos y su percepción de la poesía sudamericana.

El género epistolar en la prensa como visión ciudadana de la esfera pública en Colombia

A partir de un análisis temático inductivo, este artículo explora la visión ciudadana sobre la esfera pública expresada en las cartas de los lectores de los diarios El Tiempo y El Heraldo de Colombia. Los resultados muestran cómo la identidad colectiva de los lectores apareció en forma transversal en las cartas, para dar cuenta de una comunidad de adultos que se autodefine como “colombianos de bien”. El análisis reveló dos unidades de significado: posturas sobre la administración de lo público y antagonismos en la esfera pública, centrada en el conflicto político con las guerrillas. A través de estas se pudieron hacer visibles los llamamientos vívidos de los lectores al gobierno, funcionarios públicos, actores al margen de la ley y a sus compatriotas, para movilizarse para exigir cambios sociales largamente esperados.

Посланието на патриарх Фотий до българския княз Борис-Михаил и неговият славянски превод

Статията разглежда славянския превод на Посланието на патриарх Фотий до българския княз Борис- Михаил, запазен само в руски преписи от началото на XVI до началото на XX в. Специално внимание се отделя на езика на славянския превод (правопис, морфосинтаксис, лексика и словообразуване), чрез който става възможно датирането на превода, тъй като липсват всякакви други (литературни, исторически, палеографски, кодикологични) сведения за това. Изследването на езика позволява пре- водът да се отнесе към книжовната продукция на XIV в. и по-точно към школата на Евтимий Търновски. Причината за появата на славянския превод на Фотиевия трактат трябва да се търси в основното послание на съчинението – запазване устоите на християнската вяра и въплъщаването й в държавното управление.

Avaliação breve do défice executivo em pessoas idosas com Acidente Vascular Cerebral: Validação da Bateria de Avaliação Frontal

RESUMO Objetivos: O Acidente Vascular Cerebral (AVC) potencia o desenvolvimento de disfunção executiva, conduzindo a défice no desempenho das tarefas do quotidiano. A avaliação neuropsicológica das funções executivas é importante para desenvolver estratégias de reabilitação adequadas. Assim, são objetivos descrever os dados normativos, precisão de diagnóstico, propriedades psicométricas e análise fatorial da Bateria de Avaliação Frontal (FAB), instrumento breve e de rápida administração, numa amostra de idosos com AVC. Métodos: Inserida no projeto Trajetórias do Envelhecimento de Idosos em Resposta Social, esta investigação conta com uma amostra de 112 pessoas idosas com diagnóstico médico de AVC e 157 pessoas idosas de um subgrupo de controlo sem AVC. Os sujeitos apresentam idades compreendidas entre os 60 e os 100 anos (M = 78,20; DP = 7,57) sendo maioritariamente do sexo feminino (n = 194). A avaliação inclui entrevistas e testes neuropsicológicos agrupados em medidas de funcionamento executivo, medidas cognitivas de referência e medidas clínicas de controlo. Resultados: As variáveis idade e escolaridade interferiram nas pontuações obtidas na amostra clínica, não sendo verificado impacto da variável sexo. Para um ponto de corte de 7, a FAB teve uma sensibilidade de 83,4% e especificidade de 66,1 % (AUC = 0,64); revelou um alfa de Cronbach de 0,79 e correlações fortes com os testes executivos (teste de Stroop, Figura Complexa de Rey, fator Atencional-Executivo do Montreal Cognitive Assessment e Alternância nos testes de Fluência verbal). A análise fatorial confirmatória apontou uma estrutura com um fator. Conclusões: A FAB apresenta boa consistência interna, validade convergente e validade de constructo, aparentando ser uma escala útil para avaliar o défice executivo em pessoas idosas com AVC. Dadas algumas limitações do estudo, que poderão explicar a fraca precisão diagnóstica da FAB, são incentivadas investigações futuras pois a FAB revelou-se um instrumento com propriedades psicométricas promissoras. ABSTRACT Goals: Stroke potentiates the development of executive dysfunction, leading to impairment in performance of daily activities. The neuropsychological assessment of executive functions is important to develop adequate rehabilitation strategies. Thus, describing the normative data, diagnostic accuracy, psychometric properties and factor analysis of the Frontal Assessment Battery (FAB), a brief and easy to administer instrument, in a clinical sample with stroke are objectives of this study. Methods: Being part of the Aging Trajectories of Institutionalized Elderly, this research has a sample 112 elderly people with a medical diagnosis of stroke and a control subgroup of 157 elderly people. The subjects have ages between 60 and 100 years old (M = 78.20, SD = 7.57), mostly females (n = 194). The measurements used include interviews and neuropsychological tests grouped in executive functioning measures, cognitive measures of reference and clinical measures of control. Results: The variables age and education affect the scores obtained in the clinical subgroup, having the variable gender no impact on these. Using a cutoff score of 7, the FAB had a sensitivity of 83.4% and a specificity of 66.1% for screening stroke (AUC = 0.64); showed a Cronbach's α of 0.79, and strong correlations with executive tests (Stroop test, Rey Complex Figure, Attentional-Executive factor of Montreal Cognitive Assessment and Switching in the verbal fluency tests). The confirmatory factor analysis supported a one-factor structure. Conclusions: The FAB presents good internal consistency, convergent, and construct when used for elderly with stroke. Due to some limitations of the study, which may explain the weak discriminant validity, further investigations are encouraged because FAB has showed promising psychometric properties.

"Je ne vous dirai point, mon très cher fils" Correspondance de Catherine de Charrière de Sévery 1780-1783

This dissertation examines the principles of education imbued in a three year correspondence between an eighteenth century woman and her teenage son from the French speaking region of Vaud, current day Switzerland. Despite her great respect for the literature and ideas of the new pedagogues of the Enlightenment, especially J.J. Rousseau and Mme de Genlis, Catherine de Charrière de Sévery maintained the traditional perspective of education of the Ancien Régime. To explore the concepts of education and instruction through the epistolary practice, this research is based on the corpus of 107 letters that Mme de Sévery wrote to her son Vilhelm between 1780 and 1783. Additional documents - among them Mme de Sévery’s diaries - from the particularly rich archival holdings of this aristocratic family have been used to complement her correspondence. Most previous studies on family correspondence have dealt with mothers to daughters, or fathers to sons, whereas this research is centered on letters between a mother and her son. The location of this family – Lausanne and the Pays de Vaud – provides a particular regional perspective due to two factors: immersion into a region uniformly Protestant, and the dual-influence of Germanic and French cultures. The study analyzes the educational principles that appear throughout Mme de Sévery’s letters by comparison with three literary works of the 18th century: a familiar correspondence, the Lettres du Lord Chesterfield à son fils (1776); the fundamental education treatise by J.J. Rousseau, Émile, ou de l’Éducation (1762); and a pedagogical treatise written by Mme de Genlis as an epistolary novel, Adèle et Théodore, ou lettres sur l’éducation. Using letters as the main tool to guide her son’s upbringing, Mme de Sévery highlights the moral and family values that are most important to her and leads him to find his place in society.

Avaliação de um programa de intervenção sobre leitura e escrita numa escola de intervenção prioritária

Dissertação de Mestrado apresentada ao Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Educacional.

Caixa dos estímulos para o ensino pré-escolar

Dissertação de Mestrado para obtenção do grau de Mestre em Design de Comunicação, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.