Localization and regulation by GABA of anion transporter present in pollen grain protoplasts and tube of Arabidopsis thaliana

Tese de doutoramento, Biologia (Biologia do Desenvolvimento), Universidade de Lisboa, Faculdade de Ciências, 2015

Review of survey techniques used in urban freight studies

Report produced as part of the Green Logistics project (EPSRC and Department for Transport funded). This report is based on a review of studies in which data has been collected to obtain an understanding of road-based urban freight transport activities and patterns of operation. Studies from the UK and other countries have been included in this review. While it may be thought that relatively few such studies have been conducted, approximately 60 such studies have been identified as taking place in the UK and approximately 100 elsewhere since the 1960s. In addition, other studies have been carried out in order to assess industry and policy maker opinions about urban freight transport , however this type of study and survey work is not the focus of this report. Gaining an understanding of road-based urban freight transport activities is an important element in determining the current sustainability of such activity (in economic, social and environmental terms) and how best to go about enhancing its sustainability. By reviewing the existing survey work in this subject it has been possible to draw together the methodologies developed and implemented. This should therefore be of help in understanding which techniques are most commonly used, the strengths and limitations of the various techniques, and in assessing the most suitable urban freight survey techniques for a given study.

Review of UK urban freight studies

Report produced as part of the Green Logistics project (EPSRC and Department for Transport funded). This report is based on a review of UK studies in which data has been collected to obtain an understanding of road-based urban freight transport activities and patterns of operation. Urban freight remains relatively under researched by comparison with passenger transport both in the UK and worldwide. However, in the UK there have been a number of studies that have attempted to investigate road-based freight operations since the 1960s. But no attempt has been made to draw together the results of these various studies and compare them. This is what is presented in this report. The report has studied the results of 30 UK urban freight studies carried out in the last decade in order to attempt to provide insight into urban freight activities in our towns and cities. It presents this current knowledge about urban freight transport activities in the UK from these studies, and compares the similarities and differences between study findings.

The Consequences of Gender in Homogamic Couples

In studies which analyse the social distance between spouses at the moment a couple is formed, and which attempt to understand the role of the family, and in particular of marriage, in crystallising social divisions, the concept of homogamy has often been purely descriptive. This article questions this static approach and seeks to pinpoint the changes which social homogamy undergoes in the course of conjugal life, addressing women’s decisions on work–family articulation. Drawing on a critical approach to the concept of rational choice, the article intends to demonstrate the merit of an interpretative approach by analysing how members of a sample of 27 university-educated Portuguese partnered mothers take their decisions in the context of an interdependency framework in which the dynamics of family interaction tend to thwart individual career path development, rendering spouses dependent on each other.

Analysing the results of UK urban freight studies

The paper is based on work carried out as part of the Green Logistics project1. The paper provides a review of urban freight studies that have taken place in the UK over approximately a thirty year period from the early 1970 s to the present (this is the first attempt at such a review in the UK as far as the authors are aware). Coverage of both goods collection and delivery vehicle activity and service vehicle activity is included. This review covers the survey techniques used, as well as the survey results obtained. Comparisons are made between the results of studies from the 1970 s and those carried out in the last decade in order to gain insight to changes in urban freight transport operations. The data provided in the studies reviewed is extremely important as it provides insight into urban freight operations that is unavailable from any other data source, including national freight surveys conducted by government. However, until now, the results of these studies have not been widely disseminated or compared.

The importance of qualitative methodology in management empirical research

Purpose: The aim of this paper is to highlight the importance of qualitative research within the scope of management scientific studies, referring to its philosophy, nature and instruments. It also confronts it with quantitative methodology, approaching its differences as well as its complementariness and synergies, with the purpose of explaining, from a more analytic point of view, the relevance of qualitative methodology in the course of an authentic and real research despite its complexity. Design/methodology/approach: Regardless of its broad application, one may attest the scarcity literature that focuses on qualitative research applied to the management scientific area, as opposed to the large amount that refers to quantitative research. Findings: The paper shows the influence that qualitative research has on management scientific research. Originality/value:. Qualitative research assumes an important role within qualitative research by allowing for the study and analysis of certain types of phenomena that occur inside organisations, and in respect of which quantitative studies cannot provide an answer.

Sound levels and risk perceptions of music students during classes

It is well recognized that professional musicians are at risk of hearing damage due to the exposure to high sound pressure levels during music playing. However, it is important to recognize that the musicians’ exposure may start early in the course of their training as students in the classroom and at home. Studies regarding sound exposure of music students and their hearing disorders are scarce and do not take into account important influencing variables. Therefore, this study aimed to describe sound level exposures of music students at different music styles, classes, and according to the instrument played. Further, this investigation attempted to analyze the perceptions of students in relation to exposure to loud music and consequent health risks, as well as to characterize preventive behaviors. The results showed that music students are exposed to high sound levels in the course of their academic activity. This exposure is potentiated by practice outside the school and other external activities. Differences were found between music style, instruments, and classes. Tinnitus, hyperacusis, diplacusis, and sound distortion were reported by the students. However, students were not entirely aware of the health risks related to exposure to high sound pressure levels. These findings reflect the importance of starting intervention in relation to noise risk reduction at an early stage, when musicians are commencing their activity as students.

Comprehensive treatments for social cognitive deficits in schizophrenia: A critical review and effect-size analysis of controlled studies

Recent advances in psychosocial treatments for schizophrenia have targeted social cognitive deficits. A critical literature review and effect-size (ES) analysis was conducted to investigate the efficacy of comprehensive programs of social cognitive training in schizophrenia. Results revealed 16 controlled studies consisting of seven models of comprehensive treatment with only three of these treatment models investigated in more than one study. The effects of social cognitive training were reported in 11/15 studies that included facial affect recognition skills (ES=.84) and 10/13 studies that included theory-of-mind (ES=.70) as outcomes. Less than half (4/9) of studies that measured attributional style as an outcome reported effects of treatment, but effect sizes across studies were significant (ESs=.30-.52). The effect sizes for symptoms were modest, but, with the exception of positive symptoms, significant (ESs=.32-.40). The majority of trials were randomized (13/16), selected active control conditions (11/16) and included at least 30 participants (12/16). Concerns for this area of research include the absence of blinded outcome raters in more than 50% of trials and low rates of utilization of procedures for maintaining treatment fidelity. These findings provide preliminary support for the broader use of comprehensive social cognitive training procedures as a psychosocial intervention for schizophrenia.

Interaction of malaria parasites with host late endocytic and autophagic pathways is essential for Plasmodium liver stage development

RESUMO: A Malária é causada por parasitas do género Plasmodium, sendo a doença parasitária mais fatal para o ser humano. Apesar de, durante o século passado, o desenvolvimento económico e a implementação de diversas medidas de controlo, tenham permitido erradicar a doença em muitos países, a Malária continua a ser um problema de saúde grave, em particular nos países em desenvolvimento. A Malária é transmitida através da picada de uma fêmea de mosquito do género Anopheles. Durante a picada, os esporozoítos são injetados na pele do hospedeiro, seguindo-se a fase hepática e obrigatória do ciclo de vida. No fígado, os esporozoítos infetam os hepatócitos onde se replicam, dentro de um vacúolo parasitário (VP) e de uma forma imunitária silenciosa, em centenas de merozoitos. Estas novas formas do parasita são as responsáveis por infetar os eritrócitos, iniciando a fase sanguínea da doença, onde se os primeiros sintomas se manifestam, tais como a característica febre cíclica. A fase hepática da doença é a menos estudada e compreendida. Mais ainda, as interações entre o VP e os organelos da células hospedeira estão ainda pouco caracterizados. Assim, neste estudo, as interações entre os organelos endocíticos e autofágicos da célula hospedeira e o VP foram dissecados, observando-se que os anfisomas, que são organelos resultantes da intersecção do dois processos de tráfego intracelular, interagem com o parasita. Descobrimos que a autofagia tem também uma importante função imunitária durante a fase hepática inicial, ao passo, que durante o desenvolvimento do parasita, já numa fase mais tardia, o parasita depende da interação com os endossomas tardios e anfisomas para crescer. Vesiculas de BSA, EGF e LC3, foram, também, observadas dentro do VP, sugerindo que os parasitas são capazes de internalizar material endocítico e autofágico do hospedeiro. Mais ainda, mostramos que esta interação depende da cinase PIKfyve, responsável pela conversão do fosfoinositidio-3-fosfato no fosfoinositidio-3,5-bifosfato, uma vez que inibindo esta cinase o parasita não é capaz de crescer normalmente. Finalmente, mostramos que a proteína TRPML1, uma proteína efetora do fosfoinositidio-3,5-bifosfato, e envolvida no processo de fusão das membranas dos organelos endocíticos e autofágicos, também é necessária para o crescimento do parasita. Desta forma, o nosso estudo sugere que a membrana do VP funde com vesiculas endocíticas e autofágicas tardias, de uma forma dependente do fositidio-3,5-bifosfato e do seu effetor TRPML1, permitindo a troca de material com a célula hospedeira. Concluindo, os nossos resultados evidenciam que o processo autofágico que ocorre na célula hospedeira tem um papel duplo durante a fase hepática da malaria. Enquanto numa fase inicial os hepatócitos usam o processo autofágico como forma de defesa contra o parasita, já durante a fase de replicação o VP funde com vesiculas autofágicas e endocíticas de forma a obter os nutrientes necessários ao seu desenvolvimento.--------- ABSTRACT: Malaria, which is caused by parasites of the genus Plasmodium, is the most deadly parasitic infection in humans. Although economic development and the implementation of control measures during the last century have erradicated the disease from many areas of the world, it remains a serious human health issue, particularly in developing countries. Malaria is transmitted by female mosquitoes of the genus Anopheles. During the mosquito blood meal, Plasmodium spp. sporozoites are injected into the skin dermis of the vertebrate host, followed by an obligatory liver stage. Upon entering the liver, Plasmodium parasites infect hepatocytes and silently replicate inside a host cell-derived parasitophorous vacuole (PV) into thousands of merozoites. These new parasite forms can infect red blood cells initiating the the blood stage of the disease which shows the characteristic febrile malaria episodes. The liver stage is the least characterized step of the malaria infection. Moreover, the interactions between the Plasmodium spp. PV and the host cell trafficking pathways are poorly understood. We dissected the interaction between Plasmodium parasites and the host cell endocytic and autophagic pathways and we found that both pathways intersect and interconnect in the close vicinity of the parasite PV, where amphisomes are formed and accumulate. Interestingly, we observed a clearance function for autophagy in hepatocytes infected with Plasmodium berghei parasites at early infection times, whereas during late liver stage development late endosomes and amphisomes are required for parasite growth. Moreover, we found the presence of internalized BSA, EGF and LC3 inside parasite vacuoles, suggesting that the parasites uptake endocytic and autophagic cargo. Furthermore, we showed that the interaction between the PV and host traffic pathways is dependent on the kinase PIKfyve, which converts the phosphoinositide PI(3)P into PI(3,5)P2, since PIKfyve inhibition caused a reduction in parasite growth. Finally, we showed that the PI(3,5)P2 effector protein TRPML1, which is involved in late endocytic and autophagic membrane fusion, is also required for parasite development. Thus, our studies suggest that the parasite parasitophorous vacuole membrane (PVM) is able to fuse with late endocytic and autophagic vesicles in a PI(3,5)P2- and TRPML1-dependent manner, allowing the exchange of material between the host cell and the parasites, necessary for the rapid development of the latter that is seen during the liver stage of infection. In conclusion, we present evidence supporting a specific and essential dual role of host autophagy during the course of Plasmodium liver infection. Whereas in the initial hours of infection the host cell uses autophagy as a cell survival mechanism to fight the infection, during the replicative phase the PV fuses with host autophagic and endocytic vesicles to obtain nutrients required for parasite growth.

Key-elements of family interventions for psychosis : a qualitative research

RESUMO:As perturbações psicóticas são doenças mentais complexas sendo influenciadas na sua etiologia e prognóstico por factores biológicos e psicossociais. A interferência do ambiente familiar na evolução da doença espelha bem esta realidade. Quando em 1962 George Brown e colaboradores descobriram que ambientes familiares com elevada Emoção Expressa (EE) contribuíam para um aumento significativo do número de recaídas de pessoas com esquizofrenia (Brown et al., 1962), estava aberto o caminho para o desenvolvimento de novas intervenções familiares. A EE inclui cinco componentes: três componentes negativos, i.e. criticismo, hostilidade e envolvimento emocional excessivo; e dois componentes positivos, i.e. afectividade e apreço (Amaresha & Venkatasubramanian, 2012; Kuipers et al., 2002). No final dos anos 1970 surgiram os primeiros trabalhos na área das intervenções familiares nas psicoses (IFP). Dois grupos em países diferentes, no Reino Unido e nos Estados Unidos da América, desenvolveram quase em simultâneo duas abordagens distintas. Em Londres, a equipa liderada por Julian Leff desenhava uma intervenção combinando sessões unifamiliares em casa, incluindo o paciente, e sessões em grupo, apenas para os familiares (Leff et al., 1982). Por seu turno, em Pittsburgh, Gerard Hogarty e colaboradores desenvolviam uma abordagem que compreendia a dinamização de sessões educativas em grupo (Anderson e tal., 1980). Para designar este trabalho, Hogarty e colaboradores propuseram o termo “psicoeducação”. As IFP começaram a ser conhecidas por esta designação que se generalizou até aos dias de hoje. Neste contexto a educação era vista como a partilha de informação acerca da doença, dos profissionais para os familiares. Nas sessões os profissionais eram informados acerca das manifestações, etiologia, tratamento e evolução das psicoses, bem como de formas para lidar com as situações difíceis geradas pela doença, e.g. risco de recaída. Os trabalhos pioneiros das IFP foram rapidamente sucedidos pelo desenvolvimento de novos modelos e a proliferação de estudos de eficácia. Para além dos modelos de Leff e Hogarty, os modelos IFP que ficaram mais conhecidos foram: (1) a Terapia Familiar-Comportamental, desenvolvida por Ian Falloon e colaboradores (Falloon et al., 1984); e (2) a Terapia Multifamiliar em Grupo, desenvolvida por William McFarlane e colaboradores (McFarlane, 1991). O incremento de estudos de eficácia contribuiu rapidamente para as primeiras meta-análises. Estas, por sua vez, resultaram na inclusão das IFP nas normas de orientação clínica mais relevantes para o tratamento das psicoses, nomeadamente da esquizofrenia (e.g. PORT Recomendations e NICE Guidelines). No geral os estudos apontavam para uma diminuição do risco de recaída na esquizofrenia na ordem dos 20 a 50% em dois anos (Pitschel-Walz et al., 2001). No final dos anos 1990 as IFP atingiam assim o apogeu. Contudo, a sua aplicação prática tem ficado aquém do esperado e as barreiras à implementação das IFP passaram a ser o foco das atenções (Gonçalves-Pereira et al., 2006; Leff, 2000). Simultaneamente, alguns autores começaram a levantar a questão da incerteza sobre quais os elementos-chave da intervenção. O conhecimento sobre o processo das IFP era reduzido e começaram a surgir as primeiras publicações sobre o assunto (Lam, 1991). Em 1997 foi dinamizada uma reunião de consenso entre os três investigadores mais relevantes do momento, Falloon, Leff e McFarlane. Deste encontro promovido pela World Schizophrenia Fellowship for Schizophrenia and Allied Disorders surgiu um documento estabelecendo dois objectivos e quinze princípios para as IFP (WFSAD, 1997). Não obstante os contributos que foram feitos, continua a existir uma grande falta de evidência empírica acerca do processo das IFP e dos seus elementos-chave (Cohen et al., 2008; Dixon et al., 2001; Lam, 1991; Leff, 2000; McFarlane et al., 2003). Também em Portugal, apesar da reflexão teórica nesta área e do registo de ensaios de efectividade de grupos para familiares – estudo FAPS (Gonçalves-Pereira, 2010), os componentes fundamentais das IFP nunca foram analisados directamente. Assim, o projecto de investigação descrito nesta tese teve como objectivo identificar os elementos-chave das IFP com base em investigação qualitativa. Para tal, conduzimos três estudos que nos permitiriam alcançar dados empíricos sobre o tema. O primeiro estudo (descrito no Capítulo 2) consistiu na realização de uma revisão sistemática da literatura científica acerca das variáveis relacionadas com o processo das IFP. A nossa pesquisa esteve focada essencialmente em estudos qualitativos. Contudo, decidimos não restringir demasiado os critérios de inclusão tendo em conta as dificuldades em pesquisar sobre investigação qualitativa nas bases de dados electrónicas e também devido ao facto de ser possível obter informação sobre as variáveis relacionadas com o processo a partir de estudos quantitativos. O método para este estudo foi baseado no PRISMA Statement para revisões sistemáticas da literatura. Depois de definirmos os critérios de inclusão e exclusão, iniciámos várias pesquisas nas bases de dados electrónicas utilizando termos booleanos, truncações e marcadores de campo. Pesquisámos na PubMed/MEDLINE, Web of Science e nas bases de dados incluídas na EBSCO Host (Academic Search Complete; Education Research Complete; Education Source; ERIC; and PsycINFO). As pesquisas geraram 733 resultados. Depois de serem removidos os duplicados, 663 registos foram analisados e foram seleccionados 38 artigos em texto integral. No final, 22 artigos foram incluídos na síntese qualitativa tendo sido agrupados em quatro categorias: (1) estudos examinando de forma abrangente o processo; (2) estudos acerca da opinião dos participantes sobre a intervenção que receberam; (3) estudos comparativos que individualizaram variáveis sobre o processo; e (4) estudos acerca de variáveis mediadoras. Os resultados evidenciaram um considerável hiato na investigação em torno do processo das IFP. Identificámos apenas um estudo que abordava de forma abrangente o processo das IFP (Bloch, et al., 1995). Este artigo descrevia uma análise qualitativa de um estudo experimental de uma IFP. Contudo, as suas conclusões gerais revelaramse pobres e apenas se podia extrair com certeza de que as IFP devem ser baseadas nas necessidades dos participantes e que os terapeutas devem assumir diferentes papéis ao longo da intervenção. Da revisão foi possível perceber que os factores terapêuticos comuns como a aliança terapêutica, empatia, apreço e a “aceitação incondicional”, podiam ser eles próprios um elemento isolado para a eficácia das IFP. Outros estudos enfatizaram a educação como elemento chave da intervenção (e.g. Levy-Frank et al., 2011), ao passo que outros ainda colocavam a ênfase no treino de estratégias para lidar com a doença i.e. coping (e.g. Tarrier et al., 1988). Com base nesta diversidade de resultados e tendo em conta algumas propostas prévias de peritos (McFarlane, 1991; Liberman & Liberman, 2003), desenvolvemos a hipótese de concebermos as IFP como um processo por etapas, de acordo com as necessidades dos familiares. No primeiro nível estariam as estratégias relacionadas com os factores terapêuticos comuns e o suporte emocional,no segundo nível a educação acerca da doença, e num nível mais avançado, o foco seria o treino de estratégias para lidar com a doença e diminuir a EE. Neste estudo concluímos que nem todas as famílias iriam precisar de IFP complexas e que nesses casos seria possível obter resultados favoráveis com IFP pouco intensas. O Estudo 2 (descrito no Capítulo 3) consistiu numa análise qualitativa dos registos clínicos do primeiro ensaio clínico da IFP de Leff e colaboradores (Leff et al., 1982). Este ensaio clínico culminou numa das evidências mais substanciais alguma vez alcançada com uma IFP (Leff et al., 1982; Leff et al., 1985; Pitschel-Walz et al., 2001). Este estudo teve como objectivo modular a EE recorrendo a um modelo misto com que compreendia sessões familiares em grupo e algumas sessões unifamiliares em casa, incluindo o paciente. Os resultados mostraram uma diminuição das recaídas em nove meses de 50% no grupo de controlo para 8% no grupo experimental. Os registos analisados neste estudo datam do período de 1977 a 1982 e podem ser considerados como material histórico de alto valor, que surpreendentemente nunca tinha sido analisado. Eram compostos por descrições pormenorizadas dos terapeutas, incluindo excertos em discurso directo e estavam descritos segundo uma estrutura, contendo também os comentários dos terapeutas. No total os registos representavam 85 sessões em grupo para familiares durante os cinco anos do ensaio clínico e 25 sessões unifamiliares em casa incluindo o paciente. Para a análise qualitativa decidimos utilizar um método de análise dedutivo, com uma abordagem mecânica de codificação dos registos em categorias previamente definidas. Tomámos esta decisão com base na extensão apreciável dos registos e porque tínhamos disponível informação válida acerca das categorias que iríamos encontrar nos mesmos, nomeadamente a informação contida no manual da intervenção, publicado sob a forma de livro, e nos resultados da 140 nossa revisão sistemática da literatura (Estudo 1). Deste modo, foi construída uma grelha com a estrutura de codificação, que serviu de base para a análise, envolvendo 15 categorias. De modo a cumprir com critérios de validade e fidelidade rigorosos, optámos por executar uma dupla codificação independente. Deste modo dois observadores leram e codificaram independentemente os registos. As discrepâncias na codificação foram revistas até se obter um consenso. No caso de não ser possível chegar a acordo, um terceiro observador, mais experiente nos aspectos técnicos das IFP, tomaria a decisão sobre a codificação. A análise foi executada com recurso ao programa informático NVivo® versão 10 (QSR International). O número de vezes que cada estratégia foi utilizada foi contabilizado, especificando a sessão e o participante. Os dados foram depois exportados para uma base de dados e analisados recorrendo ao programa informático de análise estatística SPSS® versão 20 (IBM Corp.). Foram realizadas explorações estatísticas para descrever os dados e obter informação sobre possíveis relações entre as variáveis. De modo a perceber a significância das observações, recorremos a testes de hipóteses, utilizando as equações de estimação generalizadas. Os resultados da análise revelaram que as estratégias terapêuticas mais utilizadas na intervenção em grupo foram: (1) a criação de momentos para ouvir as necessidades dos participantes e para a partilha de preocupações entre eles – representando 21% de todas as estratégias utilizadas; (2) treino e aconselhamento acerca de formas para lidar com os aspectos mais difíceis da doença – 15%; (3) criar condições para que os participantes recebam suporte emocional – 12%; (4) lidar com o envolvimento emocional excessivo 10%; e (5) o reenquadramento das atribuições dos familiares acerca dos comportamentos dos pacientes – 10%. Nas sessões unifamiliares em casa, as estratégias mais utilizadas foram: (1) lidar com o envolvimento emocional excessivo – representando 33% de todas as estratégias utilizadas nas sessões unifamiliares em casa; (2) treino e aconselhamento acerca de formas para lidar com os aspectos desafiadores da doença – 22%; e (3) o reenquadramento das atribuições dos familiares acerca dos comportamentos dos pacientes, juntamente com o lidar com a zanga, o conflito e a rejeição – ambas com 10%. A análise longitudinal mostrou que a criação de momentos para ouvir as necessidades dos familiares tende a acontecer invariavelmente ao longo do programa. Sempre que isso acontece, são geralmente utilizadas estratégias para ajudar os familiares a lidarem melhor com os aspectos difíceis da doença e estratégias para fomentar o suporte emocional. Por sua vez, foi possível perceber que o trabalho para diminuir o envolvimento emocional excessivo pode acontecer logo nas primeiras sessões. O reenquadramento e o lidar com a zanga/ conflito/ rejeição tendem a acontecer a partir da fase intermédia até às últimas sessões. A análise das diferenças entre os familiares com baixa EE e os de elevada EE, mostrou que os familiares com elevada EE tendem a tornar-se o foco da intervenção grupal. Por sua vez, os familiares com baixa EE recebem mais estratégias relacionadas com aliança terapêutica, comparativamente com os familiares com elevada EE. São de realçar os dados relativamente às estratégias educativas. Foi possível observar que estas tendem a acontecer mais no início dos grupos, não estando associadas a outras estratégias. Contudo é de notar a sua baixa utilização, a rondar apenas os 5%.O Estudo 3 (descrito no Capítulo 4) surgiu como uma forma de completar a análise do Estudo 2, permitindo uma visão mais narrativa do processo e focando, adicionalmente, as mudanças que ocorrem nos participantes. Com base nos mesmos registos utilizados no Estudo 2, codificámos de forma secundária os registos em duas categorias i.e. marcadores de mudança e marcadores emocionais. Os marcadores de mudança foram cotados sempre que um participante exibia comportamentos ou pensamentos diferentes dos anteriores no sentido de uma eventual redução na EE. Os marcadores emocionais correspondiam à expressão intensa de sentimentos por parte dos participantes nas sessões e que estariam relacionados com assuntos-chave para essas pessoas. Os excertos que continham a informação destes marcadores foram posteriormente revistos e articulados com notas e comentários não estruturados que recolhemos durante a codificação do Estudo 2. Com base nesta informação os registos foram revistos e, utilizando um método indutivo, elaborámos uma narrativa acerca da intervenção. Os resultados da narrativa foram discutidos com dados de que dispúnhamos, referentes a reuniões com os terapeutas envolvidos na intervenção em análise (Elizabeth Kuipers, Ruth Berkowitz e Julian Leff; Londres, Novembro de 2011). Reconhecemos que, pela sua natureza não estruturada e indutiva, a avaliação narrativa está mais sujeita ao viés de observador. Não obstante, os resultados deste Estudo 3 parecem revestir uma consistência elevada. O mais relevante foi a evidência de que na intervenção em análise ocorreram mudanças emocionais significativas nos familiares ao longo das sessões em grupo. Numa fase inicial os familiares tenderam a expressar sentimentos de zanga. Seguidamente, os terapeutas iam nterrompendo o discurso de reminiscências, direccionavam o discurso para as suas preocupações actuais e os familiares pareciam ficar mais calmos. Contudo, à medida que os 143 participantes “mergulhavam” nos problemas com que se confrontavam na altura, os sentimentos de zanga davam lugar a sentimentos de perda e angústia. Nessa altura os terapeutas enfatizavam o suporte emocional e introduziam progressivamente técnicas de reenquadramento para ajudar os participantes a avaliar de forma mais positiva as situações. Este trabalho dava lugar a sentimentos mais positivos, como a aceitação, apreço e a sensação de controlo. O Estudo 3 evidenciou também o que designamos como o “Efeito de Passagem de Testemunho”. Este efeito aconteceu sempre que um membro novo se juntava ao grupo. Os membros antigos, que estavam a ser o alvo das atenções e naturalmente a receber mais intervenção, mudam de papel e passam eles próprios a focar as suas atenções nos membros mais recentes do grupo, contribuindo para a dinâmica do grupo com as mesmas intervenções que os ajudaram previamente. Por exemplo, alguns membros antigos que eram altamente críticos nos grupos em relação aos seus familiares passavam a fazer comentários de reenquadramento dirigidos para os novos membros. Por fim, o Capítulo 5 resume as conclusões gerais deste projecto de investigação. Os estudos apresentados permitiram um incremento no conhecimento acerca do processo das IFP. Anteriormente esta informação era baseada sobretudo na opinião de peritos. Com este projecto aumentámos o nível de evidência ao apresentar estudos com base em dados empíricos. A análise qualitativa do Estudo 2 permitiu pela primeira vez, tanto quanto é do nosso conhecimento, perceber de forma aprofundada o processo subjacente a uma IFP (no contexto de um ensaio clínico que se revelou como um dos mais eficazes de sempre). Identificámos as estratégias mais utilizadas, as relações entre elas e a sua diferente aplicação entre familiares com baixa EE e familiares com alta EE.O Estudo 3 completou a informação incluindo aspectos relacionados com as mudanças individuais durante o programa. No final foi possível perceber que as IFP devem ser um programa por etapas. Nos Estudo 2 e 3, evidenciámos que numa fase inicial, os terapeutas dedicaram especial atenção para que os familiares tivessem espaço para partilharem as suas necessidades, disponibilizando logo de seguida estratégias para promover o suporte emocional e estratégias de coping. Num nível subsequente do programa, o trabalho terapêutico avançou para estratégias mais direccionadas para regular a EE, mantendo sempre as estratégias iniciais ao longo das sessões. Assim apesar de a educação ter sido um componente importante na IFP em análise, houve outras estratégias mais relevantes no processo. A evidência gerada pelos Estudos 2 e 3 baseou-se em registos históricos de elevado valor, sendo que os constructos subjacentes na época, nomeadamente a EE, continuam a ser a base da investigação e prática das IFP a nível mundial em diferentes culturas (Butzlaff & Hooley, 1998). Concluímos que as IFP são um processo complexo com diferentes níveis de intervenção, podendo gerar mudanças emocionais nos participantes durante as sessões. No futuro será importante replicar o nosso trabalho (nomeadamente o Estudo 2) com outras abordagens de IFP, de modo a obter informação acerca do seu processo. Esse conhecimento será fundamental para uma possível evolução do paradigma das IFP. ----------- ABSTRACT: Background: Psychotic-spectrum disorders are complex biopsychosocial conditions and family issues are important determinants of prognosis. The discovery of the influence of expressed emotion on the course of schizophrenia paved the road to the development of family interventions aiming to lower the “emotional temperature” in the family. These treatment approaches became widely recognised. Effectiveness studies showed remarkable and strong results in relapse prevention and these interventions were generalised to other psychotic disorders besides schizophrenia. Family interventions for psychosis (FIP) prospered and were included in the most important treatment guidelines. However, there was little knowledge about the process of FIP. Different FIP approaches all led to similar outcomes. This intriguing fact caught the attention of authors and attempts were made to identify the key-elements of FIP. Notwithstanding, these efforts were mainly based on experts’ opinions and the conclusions were scanty. Therefore, the knowledge about the process of FIP remains unclear. Aims: To find out which are the key-elements of FIP based on empirical data. Methods: Qualitative research. Three studies were conducted to explore the process of FIP and isolate variables that allowed the identification of the key-elements of FIP. Study 1 consisted of a systematic literature review of studies evaluating process-related variables of FIP. Study 2 subjected the intervention records of a formerly conducted effective clinical trial of FIP to a qualitative analysis. Records were analysed into categories and the emerging data were explored using descriptive statistics and generalised estimating equations. Study 3 consisted of a narrative evaluation using an inductive qualitative approach, examining the same data of Study 2. Emotional markers and markers of change were identified in the records and the content of these excerpts was synthesised and discussed. Results: On Study 1, searches revealed 733 results and 22 papers were included in the qualitative synthesis. We found a single study comprehensively exploring the process of FIP. All other studies focused on particular aspects of the process-related variables. The key-elements of FIP seemed to be the so-called “common therapeutic factors”, followed by education about the illness and coping skills training. Other elements were also identified, as the majority of studies evidenced a multiple array of components. Study 2,revealed as the most used strategies in the intervention programme we analysed: the addressing of needs; sharing; coping skills and advice; emotional support; dealing with overinvolvement; and reframing relatives’ views about patients’ behaviours. Patterns of the usefulness of the strategies throughout the intervention programme were identified and differences between high expressed emotion and low expressed emotion relatives were elucidated. Study 3 accumulated evidence that relatives experience different emotions during group sessions, ranging from anger to grief, and later on, to acceptance and positive feelings. Discussion: Study 1 suggested a stepped model of intervention according to the needs of the families. It also revealed a gap in qualitative research of FIP. Study 2 demonstrated that therapists of the trial under analysis often created opportunities for relatives to express and share their concerns throughout the entire treatment programme. The use of this strategy was immediately followed by coping skills enhancement, advice and emotional support. Strategies aiming to deal with overinvolvement may also occur early in the treatment programme. Reframing was the next most used strategy, followed by dealing with anger, conflict and rejection. This middle and later work seems to operate in lowering criticism and hostility, while the former seems to diminish overinvolvement. Single-family sessions may be used to augment the work developed in the relatives groups. Study 3 revealed a missing part of Study 2. It demonstrated that the process of FIP promotes emotional changes in the relatives and therapists must be sensitive to the emotional pathway of each participant in the group.

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.

Treatment-dependent loss of polyfunctional CD8+ T-cell responses in HIV-infected kidney transplant recipients is associated with herpesvirus reactivation.

Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases.

Pulmonary hypertension in Switzerland: treatment and clinical course.

The prognosis of pulmonary hypertension (PH), especially idiopathic pulmonary arterial hypertension (IPAH), has improved during the recent years. The Swiss Registry for PH represents the collaboration of the various centres in Switzerland dealing with PH and serves as an important tool in quality control. The objective of the study was to describe the treatment and clinical course of this orphan disease in Switzerland. We analyzed data from 222 of 252 adult patients, who were included in the registry between January 1999 and December 2004 and suffered from either PAH, PH associated with lung diseases or chronic thromboembolic PH (CTEPH) with respect to the following data: NYHA class, six-minute walking distance (6-MWD), haemodynamics, treatments and survival. If compared with the calculated expected figures the one, two and three year mean survivals in IPAH increased from 67% to 89%, from 55% to 78% and from 46% to 73%, respectively. Most patients (90%) were on oral or inhaled therapy and only 10 patients necessitated lung transplantation. Even though pulmonary endarterectomy (PEA) was performed in only 7 patients during this time, the survival in our CTEPH cohort improved compared with literature data and seems to approach outcomes usually seen after PEA. The 6-MWD increased maximally by 52 m and 59 m in IPAH and CTEPH, respectively, but in the long term returned to or below baseline values, despite the increasing use of multiple specific drugs (overall in 51% of IPAH and 29% of CTEPH). Our national registry data indicate that the overall survival of IPAH and presumably CTEPH seems to have improved in Switzerland. Although the 6-MWD improved transiently, it decreased in the long term despite specific and increasingly combined drug treatment. Our findings herewith underscore the progressive nature of the diseases and the need for further intense research in the field.

Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities. BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited. METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism. RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF. CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

Mentorships and co-op placements as a means of heightening the need for a secondary school diploma to the education of at-risk students.--

Both educators and politicians appear to be quite concerned about a dropout rate in Ontario's public schools of some 30 percent. With the basic understanding that a high dropout rate is costly both in economic terms and in human terms, something quite obviously needs to be done to reduce the dropout rate in Ontario schools and, in doing so, ensuring Ontario and its graduates an active role in a growing global economy. This study is an exploratory pilot study in that it examined mentoring and the role that mentoring can play in assisting a student in staying in school and graduating from secondary school. Also incorporated in this is co-operative education and the role it can play, through mentoring, in making students aware of lifestyle level of employment, and of the skills necessary to obtain gainful, meaningful employment. In order to gain information on student attitudes, needs and expectations of a mentoring situation, a series of three questionnaires was used. Also, a questionnaire was distributed to the various co-operative education employers. The intent of this questionnaire was to probe the attitudes, needs and expectations of a mentoring situation from the perspective of an employer. The findings of this study indicated that co-operative education and mentoring are a very valuable and useful component in education. There exist certain factors in a co-operative education setting that serve to enhance and to augment the traditional or "theoretical" setting of the classroom. In addition, a mentoring situation tends to add a sense of relevance to education that students seem to require. Also, an opportunity is offered that allows a student to practice and further refine the skills that have been taught over the course of the student's academic life. Results from this study suggested that a mentoring situation, occurring through a co-operative education situation, adds relevance and a sense of "application" to the traditional or classroom schooling situation. The whole idea of mentoring bodes well for the future of education and of the student. Many advantages are identified in a mentoring situation. One of the advantages is that the schools are able to work quite closely with the community and business in order to stay current and informed on the needs and expected needs of the business community. Co-operative education has now gone beyond being an "experimental" mode of education. All students can benefit from being involved in the program. Certainly at-risk students are aided with staying in school. Those students who are said to be not at-risk can also benefit from being enrolled in the program by gaining hands-on work experience and some of the necessary skills to ensure a place in a growing world economy.