Rozprawy doktorskie na temat „Prospective studies”

The overarching goal of this thesis was to examine aspects of childhood amnesia in children, adolescents, and adults, and to evaluate theoretical explanations for the phenomenon. The research addressed three main questions. First, at what age does the boundary of childhood amnesia occur in adults, and what is the shape of the boundary? Second, is it possible for children to verbally express preverbal aspects of their memories after a 6-year delay? Third, is maternal narrative style during early childhood related to the age of adolescents� earliest autobiographical memories? In Experiment 1A, I examined whether the way in which we ask adults to sample their memories alters estimates of the offset of childhood amnesia. Independent groups of adults were asked to describe and date one memory from any time in their lives associated with each of six cue words (Lifespan Condition), one childhood memory associated with each of six cue words (Childhood Condition), or their earliest memory associated with each of six cue words (Cued Earliest Condition). A fourth group of adults was asked to describe and date their six earliest memories (Uncued Earliest Condition). As predicted, participants in the Cued Earliest and Uncued Earliest Conditions reported earlier memories than participants in the Childhood Condition, who in turn reported earlier memories than participants in the Lifespan Condition. Consistent with prior research, when adults were asked to report their earliest memories, with or without the use of cue words, the mean age of the earliest memory reported was between 3 and 4 years. In Experiment 1B, I examined the distribution of the early memories reported by six individual adults by asking them to report all the memories that they could recall from each year of childhood, until they had reported at least their 20 earliest memories. When the number of memories recalled was plotted as a function of age at event, the distributions looked like step functions, with the step occurring at ages 4-6 years. Participants also reported some early memories for events that occurred before this age. In Experiment 2, I examined children�s and parents� verbal and non-verbal recall for a specific event - the Magic Shrinking Machine - after a 6-year delay. The children were aged 27-51 months when they originally played with the machine. After a 6-year delay, nine of 46 children and 26 of 42 parents verbally recalled the event. There were no age-related differences in the amount or accuracy of the information that participants reported about the event. When children�s reports were compared to their task-relevant vocabulary measured at the time of the event, there were just two instances in which a child used a word to describe the event that had not been part of his or her productive vocabulary at the time of the event. Children showed no non-verbal recall of the event, relative to a group of age-matched controls. In Experiment 3, I tested the hypothesis that the way that parents talk about the past with their children during early childhood will influence the age of these children�s earliest autobiographical memories when they are older. Conversations about past events between 17 mother-child dyads were recorded on multiple occasions between the children�s 2nd and 4th birthdays. When these children were between the ages of 12-13 years, they were asked to describe their earliest autobiographical memory. Adolescents whose mothers used a greater ratio of elaborations to repetitions when discussing the past with their child during early childhood had earlier first memories than did adolescents whose mothers used a smaller ratio of elaborations to repetitions. The present findings on adults� earliest memories are consistent with a two-stage model of childhood amnesia. Theories that draw on multiple cognitive developments provide a more complete account of childhood amnesia than theories that focus on a single developmental milestone. I propose that neurological maturation and language acquisition set the stage for subsequent language-related developments that contribute to the emergence of autobiographical memory and, ultimately, the offset of childhood amnesia.

Prospective memory refers to remembering to carry out an intended or planned action, such as keeping a doctor's appointment or telling a friend about an upcoming party. Despite its importance in everyday life, prospective memory has received little empirical or theoretical attention. Rather, much of the literature has focused on retrospective memory, that is, memory for information learnt in the past. The current literature on prospective memory addresses five aspects that are necessary for carrying out an intended action. These are (a) formulating the plan; (b) having the knowledge necessary to carry out the plan; (c) remembering the plan at the appropriate time; (d) carrying out the plan; and (e) remembering that the plan has been performed. The literature also raises three fundamental questions. Namely, whether prospective and retrospective memory involve different processes, whether self-report and behavioral measures of prospective memory are correlated, and whether prospective memory performance varies as a function of age. These questions were the focus of the exploratory studies presented in this dissertation. The first three studies involved the development of a memory diary, a memory questionnaire, and a metamemory questionnaire, respectively. These instruments were used in the fourth and fifth studies. Studies 4 and 5 also included behavioral measures of prospective memory and objective measures of retrospective memory. The fourth study examined how community-dwelling adults feel about, and use, their memory on a daily basis. In accordance with previous research, no age differences were observed on the behavioral measures of prospective memory. Moreover, performance on the self-report measures did not differ as a function of age. As hypothesized, age was correlated with performance on a retrospective memory task. The fifth study involved an extension and replication of Study 4, with the major addition being the use of several standard laboratory tests to assess retrospective memory. This study revealed several interesting findings. First, in contrast to previous studies, performance on some retrospective memory tasks was related to performance on some prospective memory tasks. Second, by and large, self-report and behavioral measures of prospective memory were not correlated. Third, performance on the prospective memory tasks (both self-report and behavioral) did not vary as a function of age, although performance ' on the retrospective memory tasks was clearly age related. The implications of this research are discussed.
Arts, Faculty of
Psychology, Department of
Graduate

Nesta pesquisa foi estudada a prática de prospecção do futuro (estudos do futuro) como suporte à busca de informações para a decisão empresarial. Dentre os objetivos da pesquisa se encontram a busca de associações entre os métodos de prospecção e as diferentes categorias de informação, a avaliação da importância atribuída à atividade de prospecção, a identificação da frequência de uso e dos horizontes de tempo para os quais os métodos são utilizados, bem como a obtenção do grau de satisfação percebida com os resultados obtidos. A pesquisa é realizada por metodologia mista, quantitativa e qualitativa. Foram feitos levantamento de dados quantitativos e estudos de casos, e os resultados foram analisados de forma complementar. Na amostra de respondentes foi identificado que há associação entre a categoria da informação que está sendo prospectada e os métodos de estudos do futuro. Determinados métodos são mais utilizados para algumas categorias de informação, a exemplo do método de Cenários para buscar informações sobre Política e Sociedade. Por outro lado, determinadas combinações apresentaram menor uso, como o método Roadmap Tecnológico para buscar informação sobre Tecnologia. É atribuída elevada importância para a prospecção do futuro. Tal avaliação depende do tipo de decisão ser estratégico ou tático, e este último fator também influencia a frequência em que a atividade é praticada. O horizonte de tempo da prospecção também está associado aos métodos, sendo que Cenários apresenta maior uso para horizontes de mais de cinco anos. Há métodos que apresentam maior satisfação dos respondentes da amostra, sendo eles: Cenários, Previsões e Projeções de Executivos e Pesquisas de Mercado. Os métodos mais praticados são os que apresentam a possibilidade de interatividade pessoal, como Cenários e Previsões e Projeções de Executivos. Por outro lado, os métodos mais objetivos, como os que utilizam modelos matemáticos e os que possuem metodologia mais estruturada, não figuraram entre os mais praticados. Nos casos estudados foi identificado que os métodos mais praticados são baseados em opinião e julgamento e utilizam a interatividade pessoal como principal forma de condução. Houve também preocupação manifestada sobre a necessidade de estruturação da atividade nas empresas e sobre a prática da mesma seguindo recomendações metodológicas.
The use of future studies methodologies to provide information for decision making has been studied in this research. The objectives of the research are to analyze the association of methods to different information categories, to evaluate the importance of future studies, to identify the frequency of use of future studies and the time horizon in which the methods are used in searching information, and to gather users perceived satisfaction with the results. The research is implemented through a mixed-methods methodology, quantitative and qualitative. Quantitative survey and case studies have been made and combined results have been analyzed in a complementary approach. Results from the sample indicate that there is an association of methods with information categories. Some methods are more used to deal with some information categories, e.g. Scenario method with Political and Social information. On the other hand, some method-information category combinations are less used, e.g. Technology Roadmap method with Technology. Evaluation of the importance of future studies is high and depends on the decision type to be strategic or tactical. These types of decision influence the frequency of use of future studies methodologies. Time horizon is associated to methods, as in Scenario method to time horizons greater than five years ahead. There are methods with higher satisfaction ratings: Scenario, jury of Executive Opinion and Market Survey. The most used methods are the ones with high personal interaction possibility, e.g. Scenario and jury of Executive Opinion. On the other hand, objective methods, as those that make use of mathematical techniques or more structured methodologies are not among the most used. In the case studies results, methods based on judgment and opinion with high personal interaction are the most used. There were concerns about the need for more structure to deal with future studies in the company and also about its practice in accordance with methodological recommendations.

Neste trabalho foi proposto o estudo prospectivo de gestações após a 40a semana, objetivando: a) verificar os índices de morbidade e mortalidade perinatais; b) identificar os testes de avaliação da vitalidade fetal mais adequados para a vigilância destas gestações; c) comparar os resultados dos testes de avaliação da vitalidade fetal com os resultados perinatais na 1a e 2a semana, após a 40a semana de gestação, para testar o protocolo do Serviço. Para a realização do estudo, selecionaram-se 52, gestantes divididas em 2 grupos: GI (1a semana) com 32 gestantes e GIl (2a semana) com 20 gestantes. Acompanhou-se a vitalidade fetal com a Cardiotocografia de Repouso e Intraparto, Teste da Estimulação Sônica, Avaliação do Volume do Líquido Amniótico através da Técnica dos Quatro Quadrantes, Perfil Biofisico Fetal e Dopplerfluxometria Uterina e Umbilical, realizados 2 vezes na semana. Os resultados neonatais e os índices de morbidade foram: Índices de Apgar no 10 e 50 minutos (alterados < 7), pH da artéria umbilical (alterado < 7,20), peso dos recém-nascidos, tempo de internação dos recém-nascidos, oligoidrâmnia, líquido amniótico meconial, alterações na cardiotocografia com presença de desacelerações e índices de cesárea. O estudo permitiu como resultados e conclusões: a) a incidência de oligoidrâmnio foi de 44,23%, líquido meconial de 28,85%, cardiotocografia alterada, 50,00% e partos cesáreos, 57,70%, não havendo óbito fetal ou neonatal. Não houve alterações significativas nos índices de Apgar, pH da artéria umbilical e tempo de internação dos recém-nascidos. b) A cardiotocografia e, principalmente, a avaliação do volume do líquido amniótico, pelo índice de líquido amniótico, foram os métodos mais adequados na detecção de alterações verificadas neste grupo de gestantes. Do parâmetro ultra-sonográfico do Perfil Biofisico Fetal, apenas o Volume do Líquido Amniótico demonstrou ser importante. A Dopplerfluxometria (uterina e umbilical) não revelou nenhuma utilidade na vigilância destas gestações. c) A distribuição dos casos com oligoidramnia, líquido meconial, cardiotocografia alterada, índices de cesárea e pH da artéria umbilical < 7,20, semelhante na 41a semana (GI) e 42a semana (GIl), valida o protocolo do Serviço. d) Adicionalmente, este estudo permite ainda as seguintes observações: 1) importância da oligoidrâmnia e líquido meconial na determinação dos elevados índices de cesáreas; 2) incidência elevada (50,00) de nulíparas nesta casuística.
This study proposed pros.pectively the evaluation of the gestations after 40 weeks with these objectives: a) Analysis of the perinatal outcome. b) Identification of the proper test for fetal well-being assessment for this gestation. c) Comparation of these tests results with perinatal outcome at the first and second weeks after 40 weeks, therefore, testing the protocol of this Service. It recruited 52 patients divided in two groups: GI (1st week) with 32 patients and Gil (2nd week) with 20 patients. The fetal surveillance was assessed by antepartum and intrapartum cardiotocography, acoustic stimulation test, amniotic fluid volume assessment by the ultrasonographic four quadrant technique (amniotic fluid index), fetal biophysical profile and umbilical and uterine doppler velocimetry, ali tests were performed twice weekly. The neonatal outcome results and morbidity parameters were: Apgar index in 1st and s\" minutes (alterated < 7), umbilical artery pH (alterated < 7,20), the new born weight, oligohydramnios, meconium stained, deceleration (DIP 11 or umbilical deceleration) and cesarean section rates. The study permitted these results and conclusions: a) The oligohydramnios, meconium stained, cardiotocography alterations and cesarean section incidences were 44,23%, 28,85%, 50,00% and 57,70%, respectively. There was no fetal death. b) The cardiotocography and amniotic fluid assessment by the amniotic fluid index, were the best tests to detect the alterations verified. The amniotic fluid volume was the most important parameter in the fetal biophysical profile. Doppler (uterine and umbilical) revealed no utility. c) The equal distribution of the oligohydramnios, meconium stained, altereted cardiotocography, cesarean section and umbilical artery pH < 7,20 cases in the group studied reassure the Service protocol. d) In addition this study also permitted observation of: 1) The importance of the meconium stained in the cesarean section rate. 2) The nuliparus elevated incidence (50,00%) in this group.

Le concept d’anthropologie prospective élaboré dans les années 1950 par Gaston Berger, fondateur de la prospective en France, n’a pas eu la postérité qu’il mérite. Il a été contourné par les prospectivistes, qui ont conduit la prospective dans les parages du marketing, et oublié par les philosophes, qui font trop rarement de l’avenir un véritable sujet de réflexion. Or au début du XXIe siècle, après la prise de conscience de l’entrée de l’humanité dans l’ère de l’anthropocène, ce concept représente peut-être le meilleur fil conducteur pour l’élaboration de la toute nouvelle responsabilité prospective qui pourrait faire contrepoids aux stratégies suicidaires des principaux acteurs de la civilisation occidentale – stratégies exclusivement guidées par les objectifs de puissance technologique ou militaire, de croissance économique ou de recherche de profit à court terme – stratégies qui sacrifient ostensiblement l’avenir de l’humanité au bénéfice du présent ou du court terme. La présente thèse cherche à dessiner l’infrastructure conceptuelle de cette responsabilité prospective qui reste à imaginer et à structurer. La Table des Situations Stratégiques esquissée ici représente un premier pas dans cette direction. Elle ambitionne d’aboutir à une grille d’analyse et d’évaluation des stratégies déployées par les principaux acteurs de la civilisation occidentale sur la surface du globe. Elle vise à consolider l’idée d’un « permis d’engager l’avenir de l’humanité », c’est-à-dire l’idée d’un contrôle démocratique de la pertinence des stratégies des entreprises transnationales ou des gouvernements, sur tous les sujets qui concernent l’avenir à long terme de l’humanité
The anthropological concept of perspective futures developed in the 1950’s by Gaston Berger (the founder of future studies in France) was not accorded the posterity it deserves. It was overlooked by prospectivists that led future studies into marketing gimmicks and forgotten by philosophers that rarely engage in true reflection on the subject. Or during the beginning of the 21st century, after becoming aware of the human’s entry into Anthropocene era this concept represent possibly the best guide in preparing all the new prospective responsibility that could counter dangerous strategies of major actors of western civilization-strategies that are exclusively guided by military force or technological advancement, economic growth or the pursuit of short term profit-strategies that sacrifices ostensible the future of humanity or the benefit of the present or of the short term. The present thesis attempts to design conceptual framework of this prospective responsibility that rest on imagination. The foundation of the strategic situation initially sketched out here represents the first step in that direction. It attempts to develop analysis and evaluation of strategies employed by the principle actors of western civilization in the world. It attempts to consolidate ideas on one hand, that enable one to engaged in the future of mankind, that is the idea of a democratic control of series of strategies of transnational firms or of governments, particularly, the subjects that concern the future of humanity

This thesis focuses on the role of different psychosocial factors in the course of pain over time in a general population sample of women in Sweden. The main aim was to identify and quantify such factors as predictors of pain, pain-related disability and quality of life within a biopsychosocial framework for the understanding of the pain experience over time.  The studies were based on baseline (BL) and follow-up (FU) measures with 12 months apart among 2,300 women living in Sweden, and included physical and psychological health and socio-economic status. Study I investigated associations between socio-economic status (SES) at baseline and pain and pain-related disability at follow-up, and additionally a possible mediating role of depressive symptoms in such associations. The results indicated that educational level, financial strain and occupational level were associated with pain over time. Symptoms of depression were related to all pain-and SES factors, and might be understood as a mediating factor within this context. The results of Study II showed a link between symptoms of burnout at baseline and several pain-locations. Additionally, among women with pain, the characteristics of the pain experience and pain-related disability were associated with level of burnout over time. Study III focused on the sub sample of women reporting pain at follow-up, and examined possible predictors of their perceptions of quality of life (QOL). Several psychosocial factors were associated with QOL, and seemed to be more important predictors than the characteristics of pain in terms of intensity and frequency. These factors were burnout, emotional distress, and social support. Study IV was an attempt to sum up the results of the previous studies by analysing predictors of the course of pain, i.e. by comparing women that developed pain from BL to FU with those that remained pain-free and to compare women with sustained pain with those who recovered from pain during the assessment period. These analyses showed symptoms of posttraumatic stress (PTSD) to be associated with reporting emerging pain, while pain variables, educational level and social support were related to sustained pain. The results of the four studies in this thesis indicate that psychosocial factors and their interplay with the characteristics of pain can be identified and described in a female sample, with a broad definition of pain, and that these factors play a central role in the experience of pain and its impact on the everyday life of these women. There may be several possible paths leading to the development of persistent pain among women and the identification of risk factors is complicated by never-ending interactions between biological, psychological and social processes. At an early stage, prior to pain development, several risk factors may cluster together (e.g. SES, depression), and work as indicators of, e.g. dysfunctional coping in relation to pain. In the first contact with health care and among primary care personnel the identification of such indicators is crucial so as to find women at risk for prolonged pain conditions. General indicators might then be more easily distinguishable than certain individual behaviour characteristics widely accepted as risk factors for pain and disability (e.g. fear-avoidance). To spread the knowledge of general factors in the first line of health care is therefore of great importance in preventive work. Finally, the results demonstrated that many women report pain with characteristics that to a great extent affect their lives and through interactions with psychological and social health might have grave consequences for perceptions of quality of life.

This article is intended to explain core ideas resulting from processes of which Peruvian environmental legal system is derived; it is morean overview rather than a system characterization, as well as a perspective or sampling foresight representing Río +20 process meaning. In that sense, it examines the modern environmental regulations rising context and provides a brief retrospective of Peruvian environmental legal system development and prospective studies within the frame of green economy paradigms and the environmental governance, presenting only three prospective references aschallenges and trends on: Climate and Energy Law, a new legal Framework for a Green Economy and Sustainable Enterprise, and finally, stressing emphatically on mega-cities, Conurbation and Land use Planning issues given little attention usually law renders to this matters.
El ensayo pretende explicar las ideas fuerza de los procesos quedan origen al sistema jurídico ambiental peruano, una reseña antes que una caracterización del sistema, así como una perspectiva o prospectiva muestral a resultas de lo que representa el proceso denominado Río + 20. En ese sentido, da cuenta del contexto en que surge la normativa ambiental nacional moderna, igualmente ofrece una breve retrospectiva del desarrollo del sistema jurídico ambiental peruano y las prospectivas en el marco de los paradigmas de la economía verde y la gobernanza ambiental, mostrando solo tres referentes proyectivos a modo de desafíos y tendencias sobre el derecho climático y derecho energético, el imperativo de un nuevo marco legal parauna economía verde y empresa sostenible; y un gran énfasis al tema de las megaciudades, conurbación y ordenamiento territorial, con énfasis, debido a la poca atención que le suele brindar el derecho.

Cadmium and lead accumulate in humans and can have toxic effects. Exposure to cadmium is well known to cause kidney damage. Cadmium binds to metallothioneins, proteins that play a role in cadmium transport. Lead exposure’s main effect is on the central nervous system, but associations with kidney disease have also been found, although it is unknown if the latter is a causal association. The main source of both metals within the non-smoking population is from the diet. This thesis aims to 1) compare the biomarkers lead and cadmium concentration in whole-blood, plasma and urine with regard to their ability to discriminate between individuals with different mean concentrations, and to describe the effect of urinary dilution, 2) estimate the association between end-stage renal disease and blood concentrations of cadmium, lead and mercury, using prospectively collected samples for exposure evaluation, 3) use longitudinal data on kidney function makers to evaluate kidney recovery after a substantial decrease in cadmium exposure, and 4) assess the influence of metallothionein polymorphisms (MT1A rs11076161, MT2A rs10636 and MT2A rs28366003) on cadmium-associated kidney toxicity and recovery due to a reduction in Cd exposure. Repeated sampling of whole-blood, plasma and urine was conducted on 48 occupationally lead-exposed men and 20 individuals under normal environmental lead exposure, for estimation of the day-to-day and between individual-variation. Prospective samples were obtained for 118 cases that later in life developed end-stage renal disease, and 378 matched controls. Erythrocyte cadmium, lead, and mercury concentrations were determined and the risk of developing end-stage renal disease associated with metal concentrations was estimated. For evaluation of kidney recovery after a reduction in cadmium exposure and to test for gene-environment interactions, follow-up data on N-acetyl-β‑d-glucosaminidase, β2‑microglobulin, albumin, and gene polymorphisms were obtained for 412 individuals within the Chinese population and the relation to blood and urinary cadmium was assessed. The concentration of lead in blood was found to be the biomarker with the largest fraction of the total variance attributable to between-individual variation, and was therefore the biomarker with the best ability to discriminate between individuals with different mean concentrations, both for individuals under occupational and normal environmental exposure (91 and 95%, respectively). Adjusting for urinary dilution had a great effect on the fraction of the total variance attributable to between-individual variation among individuals with normal lead exposure but only a minor effect among those who were occupationally exposed. Variance analysis showed that blood concentrations were also the best discriminating biomarker for cadmium. Erythrocyte lead was, in a univariate model, associated with an increased risk of developing end-stage renal disease [odds ratio (OR) = 1.54 for an interquartile range increase, with a 95% confidence interval (CI) = 1.18-2.00], while erythrocyte mercury was negatively associated (OR = 0.75 for an interquartile range increase, with a 95% CI = 0.56-0.99). For erythrocyte cadmium, the OR was 1.15 with a 95% CI of 0.99-1.34. Associations with lead and cadmium were only seen among men. In the study on kidney recovery, the proportion of individuals with albumin level above the 95th percentile decreased between baseline and follow up, but no decrease was found for the tubular markers N-acetyl-β‑d-glucosaminidase and β2-microglobulin. Metallothionein polymorphisms modified cadmium-associated effects on N-acetyl-β‑d-glucosaminidase and β2-microglobulin levels but did not modify cadmium-associated change in any of the kidney function markers between baseline and follow up after a substantial decrease in exposure. Blood concentrations of lead and cadmium are the biomarkers with the best ability to discriminate between individuals with different mean concentrations. Adjustment for urinary dilution has great influence on the fraction of the total variance attributed to between individual variation among urine samples with low lead concentrations, but only a small influence on samples with high lead concentrations. This suggests a difference in excretion. The association between end-stage renal disease and low-level lead exposure, as assessed through prospective erythrocyte samples, gives reason for concern, although further studies are needed to determine causality. A cadmium-associated increase in albumin is reversible after a substantial reduction in exposure, but this is not the case for the observed tubular effects. The tubular kidney effects of cadmium might be modified by the MT1A rs11076161 polymorphism.
För att bedöma exponering för kadmium och bly mäts ofta deras koncentrationer i blod eller urin. Dessa studerades i longitudinella data för 48 blyarbetare och 20 individer med normal miljömässig exponering. Blod- och urinprover togs var annan till var tredje månad. Kadmium- och blykoncentrationer mättes sedan i helblod, plasma och urin. Koncentrationer av bly i blod var den biomarkör som hade den största andelen av den totala variationen som kunde förklaras av skillnader mellan individer, och var därför den biomarkör med den bästa förmågan att särskilja på individer med olika medelkoncentration, både för individer med yrkesexponering och normal miljömässig exponering (91 respektive 95% av variansen berodde på vilken individ blodprovet kom ifrån). Justering för urinens utspädning av bly i urin förbättrar oftast urins användbarhet som biomarkör. För bly stämde detta bara hos dem som inte var blyarbetare. Blodkoncentrationer var också den biomarkör med störst andel av den totala variation som kunde förklaras med skillnader mellan individer för kadmium. Kadmium och bly ackumuleras i njure respektive ben och kan ha toxikologiska effekter. Det är välkänt att höga exponeringsnivåer av kadmium orsakar njurskada och även vid lägre exponeringsnivåer har studier funnit samband med markörer för njurfunktion. Exponering för bly påverkar i första hand det centrala nervsystemet. Studier har dock funnit samband mellan koncentrationer av bly i blod och njurens glomerulära filtrationshastighet. Det är oklart både om dessa associationer, vid låga exponeringsnivåer, är viktiga för hälsan och om de verkligen beror på att kadmium och bly orsakar njurskada. För att studera end-stage renal disease användes prospektiva kohorter där personer lämnat blodprov för forskning: Västerbottens interventionsprogram med prover som tagits vid Västerbottens hälsoundersökningar, MONICA-undersökningar i Norr- och Västerbotten, mammografiundersökningarna i Västerbotten och Malmö kost cancer. Sammanlagt ingick över ett hundra tusen individer i dessa kohorter. Med hjälp av det Svenska njurregistret identifierades sedan 118 personer som senare i livet fått end-stage renal disease. Dessa jämfördes med 378 kontroller. För dessa 496 personer tinades blodprovet (närmare bestämt röda blodkroppar) upp och analyserades för kadmium och bly. För att undersöka njurens förmåga till återhämtning studerades tre områden i Kina varav ett tidigare varit kraftigt kadmiumexponerat. Erytrocytkoncentrationer av bly var, utan att ta hänsyn till några andra variabler, associerat med en ökad risk för att utveckla end-stage renal disease (med oddskvoten 1.54 för en interquartile range ökning av erytrocytbly, med ett 95% konfidensintervall 1.18-2.00). Sambanden kvarstod också efter att ha tagit hänsyn till övriga variabler. För erytrocytkadmium var oddskvoten 1.15 med 95% konfidensintervall 0.99-1.34, och sambandet försvagades när hänsyn togs till andra variabler. Associationerna sågs bland män men inte bland kvinnor. Eftersom kadmium vid höga nivåer orsakar njurskada är det också av intresse att studera om påverkan på njuren går över om exponeringen minskas. Totalt följdes 412 individer upp med mätningar av markörer för njurfunktion och kadmiumkoncentrationer i blod och urin. Första undersökningen gjordes 1998, då man just hade slutat äta kadmiumförorenat ris. En andra undersökning gjordes 2006. Andelen individer med avvikande albuminvärde i urin var lägre vid uppföljningen jämfört med vid baslinjen, men ingen minskning sågs för markörer för tubulär förmåga att återta proteiner. Åttioprocent av kadmium i celler är bundet till proteinet metallotheonin, vilket skyddar mot cellskada, men har också en roll i transporten av kadmium från levern till njurarna. En tidigare studie har visat att njurens känslighet för kadmiumexponering var associerad med genetiska skillnader i detta protein. För att studera genetiska associationer studerades de 412 personerna i den kinesiska studien [då också individernas genotyper av metallotheonin-polymorfierna MT1A rs11076161 (G/A), MT2A rs10636 (G/C) och MT2A rs28366003 (A/G) bestämdes]. Genetiken spelade roll för sambandet mellan förmåga att återta proteiner och kadmium men påverkade inte förändring av njurfunktion efter att man slutat äta kadmiumförorenat ris. Kadmium- och blykoncentrationer i blod är de biomarkörer, av koncentrationer i blod, plasma och urin, med den bästa förmågan att skilja på individer med olika medelkoncentrationer. Justering för urinutspädning påverkade andelen av den totala variationen som kunde förklaras av skillnader mellan individer i stor utsträckning för individer med normal miljömässig exponering men inte bland yrkesexponerade, vilket tyder på en skillnad i hur utsöndringen går till. Associationen mellan end-stage renal disease och låg exponering för bly, uppmätta i prospektiva erytrocytprover, ger orsak till oro, men ytterligare studier behövs för att kunna utvärdera om detta är ett kausalt samband. En kadmiumrelaterad skada av den glomerulära filtrationen är reversibel efter en kraftig reducering i exponering, men detta är inte fallet för tubulär skada. De tubulära njureffekterna av kadmiumexponering kan påverkas av metallotheonin-polymorfier.

Background: Androgens are important in prostate cancer development but how circulating levels of androgens affect risk of prostate cancer of different aggressiveness is not clear. Being childless has been associated with a lower risk of prostate cancer, but it is not clear if this association is causal or a result of residual confounding. Fathering of dizygotic twins, a marker of high fertility, has not been studied in relation to risk of prostate cancer. Another marker of life-long hormonal exposure is height, which has been associated with increased risk of cancer and cancer death. However, the association to separate cancer sites has not been consistent. The aims of this thesis were to study hormonal factors (paper I), and proxies of hormonal factors (paper II and III), and risk of prostate cancer; as well as height and risk of cancer and cancer death by separate sites (paper IV). Methods: Study designs were i) case-control studies, nested within the Västerbotten Intervention Project (paper I), and in Prostate Cancer database Sweden 2.0 (PCBaSe 2.0) (paper II and III), and ii) cohort study, in the Metabolic Syndrome and Cancer project (Me-Can) (paper IV). Results, prostate cancer: In paper I, increasing levels of serum androgens were not associated with risk of prostate cancer overall or in tumor risk categories. In paper II, childless men had a lower risk of prostate cancer, overall and in all risk categories, compared to fathers, an association which was in part explained by differences in marital status and educational level.  In paper III, fathers of dizygotic twins did not have an increased risk of prostate cancer, either overall or in risk categories, when compared to fathers of singletons. Results, cancer overall: In paper IV, height was associated with an increased risk of cancer and cancer death overall in both women and men. The strongest association for cancer was to malignant melanoma in both women and men, and for cancer death to post-menopausal breast cancer in women and renal cell carcinoma in men. Conclusions: These studies indicate that hormonal factors, when studied as serum levels or when studied using proxies of fertility, do not have a major impact on the risk of prostate cancer. The association between height and an increased risk of cancer appears robust for total cancer and cancer death, as well as for several separate cancer sites.

The management of women with mild and moderate dyskaryosis remains controversial. Any strategy must aim to be safe, efficient and cost effective. Two alternative strategies consist of immediate colposcopy for all women or a policy of cytological surveillance with colposcopy reserved for women with persistent dyskaryosis. Instead of a blanket policy for all women, selective approaches might be useful if accurate predictors of underlying high grade cervical intraepithelial neoplasia (CIN) were identified. Finally the effective treatment of women is important to prevent the development of invasive cancer. Large Loop Excision of the Transformation Zone or LLETZ is a relatively new treatment modality which has rapidly been established as the preferred treatment for women with CIN but it's efficacy has not been studied beyond a period of six months. The core of the thesis is description of a large prospective randomised study carried out in the University of Aberdeen. This was a four year project sponsored by the charity Birthright (now Well-being). Nine hundred and two women with a single smear showing mild or moderate dyskaryosis were recruited and allocated in a random fashion to either an immediate treatment group and one of three surveillance groups with periods of up to 24 months before treatment. Outcome measurements included the cytological and histological results. The cost effectiveness of two alternate management strategies for women with mild dyskaryosis is also described. The use of social factors and virological tests as secondary screening techniques is examined to determine if they might select women with high grade disease. Finally, the outcome of treatment of women including 400 women from the Birthright study using large loop excision of the transformation zone (LLETZ) is assessed.

Intentions are things we want to do in the future (e.g. post a letter). The ability that allows us to form, maintain and execute delayed intentions is referred to as prospective memory. The first aim of my research was to explore whether the lateral increase and medial decrease in prefrontal cortex activity associated with prospective memory, as demonstrated in previous neuroimaging studies, can be replicated using functional-near infrared spectroscopy (fNIRS). Study 1 only found neural difference between intentions related to objects (non-social cues) and intentions related to faces (social cues). Study 2 also failed to replicate the lateral-medial dissociation, and was thus adapted in Study 3 to include additional within-subject factor of posture (laying down versus sitting), to account for potential differences between fMRI and fNIRS findings. The findings from Study 3 provided the first demonstration of increased lateral and decreased medial prefrontal cortex activation pattern using fNIRS. The second aim was to explore the effects of value of intentions: our motivation to fulfill delayed intentions is presumably related to the value attached to those intentions. In Experiment 1 prospective memory performance was modulated as a function of monetary value attached to two concurrent intentions. Participants performed better for high-value intentions, when compared to low- value intentions. Experiment 2 examined two other properties of value: monetary (Gain/Loss) and social framing (Self/Other). Participants either received a reward for fulfilling intentions (Gain), or incurred deductions when they failed to execute intentions (Loss). Also, participants either earned rewards for themselves (Self), or for their partner (Other). In the GainSelf and GainOther conditions, performance was better for high- versus low-value intentions, while in the LossSelf and LossOther conditions there was no difference. In sum, this dissertation showed the feasibility of using fNIRS in prospective memory research, and explored how value underlies our intentions.

Introdução: A hiperplasia prostática benigna (HPB), uma das doenças mais comuns do homem idoso, pode estar associada com sintomas do trato urinário inferior que afetam sua qualidade de vida. A prostatectomia aberta é uma das opções de tratamento. O antígeno prostático específico (PSA) pode estar aumentado em pacientes com HPB, reduzindo sua especificidade diagnóstica para câncer de próstata. O objetivo do estudo é avaliar o comportamento do PSA após a prostatectomia aberta, particularmente, em pacientes com o exame aumentado no pré-operatório. Método: Foi realizado um estudo prospectivo com 130 pacientes submetidos à prostatectomia aberta no HCFMUSP de julho de 2000 a setembro de 2003. Os pacientes foram divididos em dois grupos de estudo. O grupo caso foi composto por pacientes com PSA > = 4,0ng/ml e o grupo controle formado por pacientes com PSA < 4,0ng/ml. Após seis a doze meses das operações foram realizados exame digital retal e PSA. Os pacientes com exame digital retal anormal ou PSA após a prostatectomia > = 4,0ng/ml ou queda percentual do PSA < 70% do valor inicial foram biopsiados. Resultados: Em média, os pacientes apresentaram 71,18 anos e 10,81ng/ml de nível sérico de PSA total. O tamanho da próstata e o peso do adenoma foram, em média, de 122,91cm³ e 76,54g, respectivamente. A necessidade da sonda vesical foi vista em 42,31% (55/130) dos pacientes. O exame digital retal foi anormal em 11,54% (15/130) dos pacientes. A presença de prostatite crônica ocorreu em 49,23% (64/130) das análises histológicas dos espécimes cirúrgicos. Apresentaram PSA aumentado 76,15% (99/130) dos pacientes, formando o grupo caso. Não se encontrou variável que apresentasse diferença estatisticamente significativa entre os grupos para justificar o aumento do PSA. Câncer de próstata incidental foi verificado em 6,51% (8/130) dos pacientes. Em média, a queda percentual do PSA foi de 81,13% do valor inicial após 10,1 meses da operação. Pacientes do grupo caso apresentaram queda de 85,16% e pacientes do grupo controle queda de 67,01% (p = 0,004). Em média, o PSA após a prostatectomia aberta foi de 1,38ng/ml. Pacientes do grupo caso apresentaram média de 1,56ng/ml enquanto que os pacientes do grupo controle tiveram média de 0,73ng/ml (p = 0,001). Observou-se PSA > = 4,0ng/ml após a prostatectomia aberta em 6,56% (8/122) dos pacientes. Houve correlação positiva entre a variação do PSA e o peso do adenoma (r = 0,262, p = 0,004). Foi diagnosticado câncer de próstata em 4,1% (5/122) dos pacientes. Todos pacientes pertenciam ao grupo caso e tiveram PSA > = 4,0ng/ml após a operação. Conclusão: A maioria dos pacientes apresentou PSA pré-operatório aumentado. O comportamento do PSA se caracterizou por queda percentual acentuada após 10,1 meses da prostatectomia aberta. Os pacientes com PSA préoperatório aumentado apresentaram queda mais expressiva, porém com valores mais elevados de PSA após a prostatectomia aberta em relação aos pacientes com PSA pré-operatório normal.
INTRODUCTION: Benign prostatic hyperplasia (BPH), a common aging male disease, is associated with lower urinary tract symptoms that may affect overall quality of life. Open prostatectomy is one of the treatment options. Prostate-specific antigen (PSA) specificity for prostate cancer is impaired because patients with BPH may have elevated PSA. The PSA evolution after open prostatectomy is the objective of this study, particularly, in patients with elevated PSA before operation. Methods: A prospective study was made with 130 patients undergoing open prostatectomy for BPH from July 2000 to September 2003 at HCFMUSP. Patients were divided into two study groups by PSA cut-off value. Patients with PSA > = 4,0 ng/ml integrated case group. Patients with PSA < 4,0ng/ml integrated control group. Digital rectal examination and PSA were repeated after six to 12 months after operation. Biopsy was performed in patients with altered digital rectal examination, PSA > = 4,0ng/ml or PSA reduction less than 70%. Results: Mean patient age was 71,18 years. Total PSA average value was 10,81ng/ml. The mean prostatic volume and adenoma weight was 122,91cm³ and 76,54g, respectively. 42,31% (55/130) of patients had an indwelling catheter. Digital rectal examination was altered in 11,54% (15/130) of patients. Pathologic examinations of the prostatic specimens showed chronic prostatitis in 49,23% (64/130) of them. PSA was elevated in 76,15% (99/130) of patients. They composed the case group. It was not found any factor between study groups that showed significant difference to justify the elevated PSA. Incidental prostate cancer was detected in 6,15% (8/130) of patients. The mean PSA reduction was 81,13% 10,1 months after open prostatectomy. The mean PSA reduction was 85,16% and 67,01% for case group and control group patients, respectively (p = 0,004). PSA average value was 1,38ng/ml 10,1 months after open prostatectomy. PSA average value was 1,56ng/ml and 0,73ng/ml for case group and control group patients, respectively (p = 0,001). Only 6,56% (8/122) of patients had PSA > = 4,0ng/ml after open prostatectomy. It was observed statistical correlation between adenoma weight and PSA change (r = 0,262, p = 0,004). Prostate cancer was detected in 4,1% (5/122) of patients. All of them had elevated PSA after operation and belonged to case group. Conclusions: Most of patients had preoperative elevated PSA. It was observed an important PSA reduction 10,1 months after open prostatectomy. Patients with preoperative elevated PSA had more important reduction but higher postoperative PSA values than patients with preoperative normal PSA.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Urban Studies and Planning, 2018.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 263-270).
To assist policy makers with evaluating urban development policies and anticipating trends in the evolution of cities, researchers have significantly improved modem urban land-use-and-transportation (LUT) simulations. Despite extensive studies regarding the interdependency of household life cycle stages and moving decisions in demography, most existing LUT simulations do not address households changing life cycle stages when modeling residential relocation behavior. The reasons include 1) the data that capture households and housing transitions is hard to obtain, and 2) the analysis methods are mainly for cross-sectional datasets. This dissertation focuses on these issues and contributes to the literature in three respects: behavior exploration, methodology, and applications to housing and transportation policy analysis. The ultimate goal of this study is to have a better understanding of the relationship between household life cycle stages and their moving decisions when the housing market is heavily regulated with incentives based on age, family structure, and income. This research focuses on the housing market in Singapore as a case and utilizes a new dataset of recent movers. First, this study generates sampling weights both at the individual and household levels to correct sample bias. Then, this study uses discrete choice models to identify key household and housing factors that influence households' moving behavior at the household-level. In order to capture household characteristics at the time of decision-making, the household characteristics for those households that changed structure when moving had to be reconstructed. The results show that household moving decisions are mainly influenced by three sets of factors: life cycle stages, tenure choices and housing submarkets. Finally, this research adopts a Markov Chain Model (MCM) approach to estimate a set of forward-looking moving and tenure transition rates accounting for various issues, such as sample bias and "missing-move" problems. The final results improve the estimate of moving and tenure transition rates in several ways: adding more demographic factors, handling household structure changes, and relaxing the memoryless assumption to accommodate a special feature of the public housing sector in Singapore. I expect that this study will have important implications for LUT microsimulations as well as housing and transportation policymaking. It demonstrates a method to analyze a retrospective dataset of recent movers in order to obtain detailed forward-looking moving and tenure transition rates (which are required for microsimulations). It also demonstrates a way to model household structure changes at the household level without introducing a full set of demographic models at the individual level. This study shows that with detailed moving and tenure transition rates, researchers can better capture the critical interactions between households' moving decisions and government intervention on the housing market. This can improve the current LUT simulations in a way that they can be more sensitive to government housing regulation and support long-term policymaking regarding the spatial distribution of housing and transportation infrastructure.
by Jingsi Xu Shaw.
Ph. D.

This research was initiated due to the popularity brand community phenomenon is gaining among companies through last several years. Growing number of companies on the market and shortening of the life cycle of products, make companies work hard in order to retain existing customers and gain new ones. Brand communities may provide many benefits to companies such as ability to build customer loyalty, increase of the marketing efficiency and enhancement of a brand. We wish to explore brand communities from two perspectives: inside, factors that may influence brand community members in particular purchase of augmented products and word of mouth communication and outside, the perception of brand communities as a future value by prospective customers.Due to our philosophical considerations and non-geographical nature of brand communities, the research method that we have chosen is quantitative. In order to collect a large amount of primary raw data we have used a survey approach. Therefore the self-administered questionnaire was designed. Two sampling techniques were used in data collection process – convenience and snowball. The survey was distributed via e-mail and Internet. The predetermined respondents were asked to answer questionnaires and distribute them further. During the data collection period 258 respondents were surveyed.The findings of this research suggest that prospective customers, who have a favorite brand, see brand community as a future value, hence may have an incentive to buy products or services of a particular brand. A managerial implication in this case is that brand communities are a good opportunity for a company to build long term relations with existing customers by involving them in brand community activities. Brand community events such as meetings, festivals, and promotional activities also influence an incentive of consumers to buy augmented products or services of a company; hence giving a firm an opportunity to earn additional profits by selling more additional products, paid services or accessories. Word of mouth communication is another valuable asset that companies may use. In our research we have proved that word of mouth inside brand communities may influence its members to buy products or services of another brand under the influence of an opinion leader or the majority. So managers of companies that sell related or supplemented products may jointly organize events, and reach more consumers.

Avaliou-se prospectivamente 19 pacientes com obstrução infravesical por hiperplasia prostática benigna selecionados pra prostatectomia transvesical. Obteve-se um fragmento da parede da bexiga e quantificou-se o colágeno no epimísio, perimísio e endomísio do detrusor. Amostra vesicais de oito doadores cadavéricos de órgãos serviram como controles. Observou-se padrão focal de aumento do colágeno na camada muscular da bexiga dos pacientes com obstrução. Demonstrou-se que a idade correlaciona-se positivamente com o aumento da quantidade de colágeno com a diminuição da complacência vesical, o aumento da prevalência de hiperatividade detrusora e a maior chance de retenção urinária
We prospectively evaluated 19 patients with bladder outlet obstruction by benign prostatic hyperplasia selected for transvesical prostatectomy. A sample of the bladder wall was obtained and the collagen was measured at the level of epimysium, premysium and endomysium. Bladder samples from eight cadaveric organ donors were used as controls. A focal pattern of collagen increase was observed at the bladder smooth muscle layer of obstructed patients. Age was shown to correlate with increased collagen quantity. Increased collagen quantity also correlated with decreased bladder compliance, higher prevalence of detrusor overactivity and of urinary retention

Background: Associations between dietary fats and mortality are unclear. Methods: We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999–2010. We added our results to a meta-analysis based on searches until November 2018. Results: In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78–0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04–1.11). In the meta-analysis of 29 prospective cohorts (n = 1,148,117) we found a significant inverse association between total fat (0.89, 0.82–0.97), MUFA (0.93, 0.87–0.99) and PUFA (0.86, 0.80–0.93) consumption and all-cause mortality. No association was observed between total fat and CVD (0.92, 0.79–1.08) or CHD mortality (1.03 0.99–1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01–1.20) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67–0.96) and PUFA (0.84, 0.80–0.90) intakes and stroke mortality. Conclusions: We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes.
European Society of Cardiology
Revisión por pares

Background: A large number of prospective studies have shown that overweight and diabetes are related to an increased risk of many cancers, including colorectal cancer. In contrast, diabetes has been related to a decreased risk of prostate cancer, and overweight has been related to an increased risk of fatal, but not of incident, prostate cancer. Data from studies on metabolic factors related to overweight and diabetes, and the association with cancer risk, are limited.  Aim: The aim of this thesis was to study metabolic factors in relation to risk of prostate cancer (paper I and III), colorectal cancer (paper II and V), and cancer overall (paper VI).  Methods: Study designs were i) case-control studies, nested within the Northern Sweden Health and Disease Cohort (paper I and II), and ii) cohort studies of the Swedish Construction Workers cohort (paper III), and the Metabolic syndrome and Cancer project (Me-Can) comprising seven European cohorts (paper V and VI). Paper IV was a descriptive paper of Me-Can.  Results, prostate cancer: In paper I, increasing levels of several factors related to insulin resistance (insulin, insulin resistance index, leptin, HbA1c, and glucose) were associated with a decreased risk of overall incident prostate cancer, and the associations were stronger for non-aggressive tumours. In paper III, increasing levels of blood pressure was associated with a significant decreased risk of overall incident prostate cancer and of non-aggressive tumours. Body mass index (BMI) was significantly positively related to fatal prostate cancer.   Results, colorectal cancer: In paper II, obesity, hypertension, and hyperglycaemia, were associated with an increased risk of colorectal cancer, and presence of two or three of these factors was associated with a higher risk than the presence of one single factor. In paper V, BMI was associated with a significant linear positive association with risk of colorectal cancer in men and women, and significant positive associations were also found in men for blood pressure and triglycerides. A high metabolic syndrome score, based on levels of BMI, blood pressure, glucose, cholesterol, and triglycerides, was associated with a significant increased risk of colorectal cancer in men and women. The association was stronger than for any of the factors in single, but there was no evidence of a positive interaction between these metabolic factors.  Results, cancer overall: Blood glucose was significantly positively associated with risk of incident and fatal cancer overall, and at several specific sites. The associations were stronger in women than in men, and for fatal than for incident cancer.  Conclusions: Results from these studies indicate that elevated blood glucose is related to an increased risk of cancer overall and at several specific sites, and further, that overweight and metabolic aberrations increase the risk of colorectal cancer in an additive way. The association with prostate cancer seems to be more complex; insulin resistance and high blood pressure were in our studies related to a decreased risk of overall incident prostate cancer and of non-aggressive tumours, whereas overweight increased the risk of fatal prostate cancer.

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Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished

Prevention of cardiovascular disease (CVD), a leading cause of death in men and women, is both a global and national public health priority. Prevention efforts have generally focused on well-known lifestyle (e.g., physical inactivity, unhealthy diet, smoking) and metabolic (e.g., overweight/obesity, hypertension, hyperlipidaemia) risk factors. It is also important for public health strategies to consider emerging risk factors, innovative approaches to risk factors, and evidence in middle-aged men and women, to develop effective prevention strategies. This thesis explored innovative aspects of cardiovascular risk in a large cohort of middle-aged and older Australian men and women (“the 45 and Up Study”) by examining: 1) emerging or lesser known risk factors such as raw vegetable intake (Chapter 3), sedentary behaviour (Chapter 4, Appendix 1) and psychological distress (Chapter 5); 2) the single versus joint influence of lifestyle risk factors on incident type 2 diabetes (Chapter 4, Appendix 1) and hypertension (Chapter 5); 3) potential gender differences (Chapters 3-5, Appendix 1), and female-specific behaviours such as breastfeeding (Chapters 6-7). Overall, findings support Australian recommendations for fruit and vegetable intake, physical activity, alcohol intake and infant breastfeeding. While the importance of reducing known risk factors for CVD prevention was evident, the role of raw vegetable intake, sedentary behaviour and psychological distress was inconclusive. Breastfeeding was associated with a lower maternal risk of CVD. Findings confirmed that adopting a cluster of healthy lifestyle behaviours can reduce CVD risk in the middle-aged and older population. Potential gender differences were explored and identified. This thesis contributes to the literature by exploring innovative aspects of cardiovascular risk that are relevant to middle-aged adults, particularly women, as well as informs health care providers, researchers and policy makers.

O objetivo primário do presente estudo foi quantificar e comparar as alterações do posicionamento da pálpebra superior nos olhos testados e nos olhos contralaterais de portadores de ptose palpebral senil submetidos à instilação de colírio de fenilefrina a 10% em um dos olhos e ao teste do levantamento manual da pálpebra ptótica. Como objetivo secundário, verificar a influência da dominância ocular, da intensidade e da uni ou bilateralidade da ptose nas respostas palpebrais frente aos dois testes. Métodos: Estudo clínico prospectivo transversal, que avaliou o efeito da ação tópica do colírio de fenilefrina a 10% e da manobra de levantamento manual da pálpebra no posicionamento palpebral de indivíduos portadores de ptose palpebral involucional unilateral ou bilateral. Os pacientes foram filmados antes e 5, 10 e 15 minutos após a instilação do colírio. A distância margem reflexo (DMR1) foi medida com a utilização do software Image J e os resultados foram analisados com o modelo linear de efeitos mistos. Resultados: Na pesquisa foram incluídos 70 indivíduos entre 44-86 anos, 64 destes do sexo feminino (91.43%), divididos em três grupos: indivíduos com ptose unilateral; com ptose bilateral e controles. O olho submetido à instilação do colírio de fenilefrina apresentou aumento da DMR1 nos primeiros 10 minutos: de 1,33±0,66 mm para 2,06±0,89 mm (grupo ptose unilateral), de 1,26 ± 0.63 mm para 2,29±0,86 mm (grupo ptose bilateral) e de 3,12 ± 0,68 mm para 4,06 ± 0,92 mm (grupo controle). A DMR1 diminuiu nos olhos contralaterais dos pacientes portadores de ptose, mais significativamente após a instilação do colírio de fenilefrina: teste de fenilefrina vs. levantamento manual da pálpebra = 18.9% vs. 17.2% de redução no grupo com ptose unilateral, e 13.6% vs. 10.7% de redução no grupo com ptose bilateral. Os fatores: dominância ocular, uni ou bilateralidade da ptose e a sua intensidade não influenciaram na resposta aos testes. Conclusões: O aumento da DMR1 ocorreu nos olhos testados de todos os grupos. Tanto o levantamento manual da pálpebra como a instilação do colírio de fenilefrina 10% agiram na pálpebra superior do olho contralateral, porém a resposta foi mais significativa após o teste da fenilefrina e nos grupos com ptose, unilateral e bilateral
Purpose: The primary aim of this study is quantify and compare the effect of 10% phenylephrine instillation and manual elevation (ME) on the upper eyelid position of the tested eye and the contralateral eye in patients with involutional blepharoptosis (IB). The secondary objective is to correlate the eye dominance, severity and laterality of ptosis with eyelid position changes after these two tests. Methods: This is a prospective transversal study conducted in involutional ptosis patients, submitted to two tests followed by observation of the effect on the contralateral eyelid: 1) ME of the more ptotic eyelid, and 2) instillation of two drops of 10% PE (phenylephrine test) in the more ptotic eye. The patients were filmed before and 5, 10 and 15 minutes after instillation. The upper eyelid margin reflex distance (MRD1) was measured using the software Image J, and the results were analyzed with the linear mixed-effects model. Results: The study included 70 patients aged 44- 86 years, 64 of whom were female (91.43%), divided into three groups: subjects with unilateral ptosis, subjects with bilateral ptosis and controls. The eye submitted to instillation with 10% PE displayed significant elevation during the first 10 min: from 1.33±0.66mm to 2.06 ± 0.89mm (unilateral group), from 1.26 ± 0.63mm to 2.29 ± 0.86mm (bilateral group) and from 3.12 ± 0.68mm to 4.06±0.92mm (control group). MRD1 decreased in the contralateral eye in IB patients, significantly more so after the phenylephrine test: PE vs. ME = 18.9% vs. 17.2% reduction in the unilateral group, and 13.6% vs. 10.7% reduction in the bilateral group. The outcome was not influenced by IB severity and the concurrence of IB and eye dominance. Conclusion: MRD1 elevation in tested eyes in all groups. Both Manual elevation and phenylephrine tests affected the contralateral upper eyelid, but the response was significantly better with the latter

INTRODUÇÃO: O dispositivo endoscópico temporário de exclusão duodenojejunal (DETEDJ) promove exclusão funcional do duodeno e da porção inicial do jejuno, impedindo seu contato com o quimo. Em estudos prévios, mostrou-se eficaz na perda de peso e apresentou resultados promissores no controle do diabetes mellitus tipo 2 (DMT2). O objetivo deste estudo foi avaliar a eficácia e a segurança do DETEDJ, mantido por 12 meses, na perda de peso e controle do DMT2. MÉTODOS: realizou-se estudo de coorte prospectivo, aberto, incluindo 22 pacientes com obesidade (IMC 35 kg/m²) e DMT2, candidatos a cirurgia bariátrica, os quais foram submetidos a colocação do DETEDJ, mantido por 12 meses, e com seguimento por mais 6 meses após sua retirada. RESULTADOS: o DETEDJ foi implantado com sucesso em todos os pacientes. Treze indivíduos completaram 12 meses com o dispositivo e 12 retornaram 6 meses após a retirada. Na análise por intenção de tratamento foram estudados todos os pacientes com o dispositivo implantado (n = 22). Comparando o momento inicial com a última aferição antes da retirada do dispositivo, houve redução significativa do peso (119,4 ± 23 kg vs. 102,1 ± 18,7 kg p < 0,001), do IMC (45,3 ± 7,1 kg/m2 vs. 38,7 ± 5,7 kg/m2 p < 0,001), da glicemia de jejum (179,4 ± 68,8 vs. 139 ± 58,1 mg/dL p < 0,001) e da HbA1c (8,9 ± 1,7% vs. 6,9 ± 1,2% - p < 0,001). Dezesseis pacientes apresentavam HbA1c controlada ( 7%) no momento da retirada, contra apenas um no início do estudo. Na análise por protocolo, foram estudados os 12 pacientes que completaram o seguimento de 6 meses após a retirada. A perda de peso e o controle glicêmico obtidos com o DETEDJ estavam mantidos no final do acompanhamento (peso, IMC e HbA1c p < 0,001 comparado com tempo basal; glicemia de jejum p = 0,001 comparado com tempo basal). Houve redução significativa dos níveis de triglicerídeos, colesterol, insulina e peptídeo C ao término do tratamento com o DETEDJ (análise por intenção de tratamento). CONCLUSÃO: o DETEDJ mantido por um ano é seguro e eficaz para perda de peso e controle do DMT2. O seguimento por um período de seis meses após sua retirada demonstra manutenção dos benefícios obtidos
BACKGROUND: endoscopic duodeno-jejunal bypass liner (DJBL) promotes functional exclusion of duodenum and initial jejunum, preventing mucosal contact with chyme. Previous studies have shown effective weight loss and promising results on type 2 diabetes mellitus (T2D) improvement. The aim of this study was to evaluate efficacy and safety of DJBL, maintained for 12 months on weight loss and T2D control. METHODS: open-label, cohort, prospective study, including 22 patients with obesity (BMI 35 kg/m²) and T2D, candidates for bariatric surgery, submitted to DJBL implant maintained for 12 months, and with 6-months follow-up after removal. RESULTS: DJBL was successfully implanted in all patients. Thirteen patients completed 12 months with device and 12 returned 6 moths after removal. Intention-to-treat analysis was done including all patients with device implanted (n = 22). Comparing baseline with last observation carried forward (LOCF), there was significant reduction of weight (119,4 ± 23 kg vs. 102,1 ± 18,7 kg p < 0,001), BMI (45,3 ± 7,1 kg/m2 vs. 38,7 ± 5,7 kg/m2 p < 0,001), fasting glucose (179,4 ± 68,8 vs. 139 ± 58,1 mg/dL p < 0,001) and HbA1c (8,9 ± 1,7% vs. 6,9 ± 1,2% - p < 0,001). Sixteen patients had HbA1c controlled ( 7%) at LOCF (just one controlled at baseline). On per protocol analysis, the 12 patients who returned 6 months after device removal were considered. Weight loss and glycemic control obtained with DJBL were maintained at the end of follow-up (weight, BMI and HbA1c p < 0,001 compared with baseline; fasting glucose p= 0,001 compared with baseline). There was significant reduction of triglycerides, cholesterol, insulin and C-peptide at the LOCF (ITT analysis). CONCLUSION: DJBL maintained for one year is safe and efficient for weight loss and T2D control. Benefits are maintained 6- months after removal

OBJECTIVES: To estimate the incidence and risk of childhood overweight and obesity according to socioeconomic status in Peruvian and Vietnamese school-aged children. METHODS: Longitudinal data from the Young Lives study were analyzed. Exposure was wealth index in tertiles. Outcome was overweight and obesity. Cumulative incidence per 100 children-years, relative risks (RR), and 95 % confidence intervals (95 % CI) were calculated. A hierarchical approach, including child- and family-related variables, was followed to construct multivariable models. RESULTS: The cumulative incidence of overweight and obesity was 4.8 (95 % CI 4.1-5.5) and 1.7 (95 % CI 1.3-2.2) in the younger and older Peruvian cohort, respectively; and in Vietnam 1.5 (95 % CI 1.2-1.8) and 0.3 (95 % CI 0.2-0.5), respectively. The incidence of overweight and obesity was higher at the top wealth index tertile in all samples. In the older cohorts, comparing highest versus bottom wealth index tertile, RR of overweight and obesity was four to nine times higher: 4.25 in Peru (95 % CI 2.21-8.18) and 9.11 in Vietnam (95 % CI 1.07-77.42). CONCLUSIONS: The results provide important information for childhood obesity prevention in countries moving ahead with economic, epidemiological and nutritional transitions.
Revisión por pares

Forekomst, dødelighet og risikofaktorer for subaraknoidalblødning Prospektive analyser av HUNT og Tromsøundersøkelsen Subaraknoidalblødning (SAB) utgjør omtrent 1-7 % av alle hjerneslag. Forekomsten har blitt estimert til å ligge mellom 7 og 10 per 100.000 personår. Det virker som forekomsten er relativt stabil over tid og mellom land, unntatt i Finland og Japan, hvor forekomsten er høyere. Noen studier har antydet at forekomsten har gått noe ned de senere tiår, mens sykeligheten og dødeligheten etter SAB fortsatt er høy. Siden blødningen er relativt sjelden, har det vært vanskelig å påvise risikofaktorer i prospektive studier, men røyking, høyt blodtrykk, høyt alkoholinntak og det å være kvinne er kjent å øke risikoen. Det er mer usikkerhet vedrørende kroppsmasseindeks (KMI) og serumlipider. Det er også lite kunnskap om hvilke kjennetegn ved pasientene som fører til økt risiko for død etter SAB. Vi registrerte alle som fikk SAB etter deltakelse i befolkningsundersøkelsene HUNT 1 og 2 (1984-86 og 1995-97) og Tromsø 3 og 4 (1985-87og 1994-95) ved hjelp av diagnoseregistrene på sykehusene som populasjonene sogner til og Dødsårsaksregisteret. Vi identifiserte til sammen 214 pasienter. Vi estimerte forekomst og overlevelse, og studerte effekten av risikofaktorer ved hjelp av Cox og Poisson regresjonsanalyser. De fire artiklene omhandler forekomst og dødelighet av SAB (artikkel I, HUNT 1 og 2 og Tromsø 3 og 4), risikofaktorer for SAB (artikkel II, HUNT 1), KMI og serum lipider og risiko for SAB (artikkel III, HUNT 2 og Tromsø 4) og kjønnsforskjeller i risikofaktorer for SAB (artikkel IV, HUNT 2 og Tromsø 4). Vi fant at forekomsten av SAB fra 1984 til 2007 var 10,3 per 100.000 personår, 13,3 hos kvinner og 7,1 hos menn. Insidensen kan ha økt litt siden 1984, noe som kan skyldes endring i diagnostikk, men den har vært stabil siden 1995. 30 dagers letalitet var 36 % og tenderte til å øke med alder, men forble stabil over de 23 årene i oppfølgningen. Vi fant en lineær og positiv sammenheng mellom systolisk og diastolisk blodtrykk og risiko for SAB. Røykere hadde høyere risiko for SAB enn dem som aldri hadde røykt, og det kan virke som om risikoen assosiert med røyking er høyere hos kvinner enn hos menn. Det kan også virke som om overvekt (KMI 25-29.9) er negativt assosiert med risiko for SAB. Derimot fant vi ingen sammenheng mellom totalkolesterol, HDL-kolesterol eller triglyserider og risiko for SAB i totalpopulasjonen, men hos deltakere under 50 år var HDL-kolesterol negativt assosiert med risiko.

Accidental falls remain an important healthcare issue for older people. We report on three studies examining risk predictors for further falls, falls-related hospital attendances and mortality, and then test the effectiveness of a hospital-based falls prevention intervention. A prospective study of 498 older people who attended an Emergency Department (E.D.) with a fall showed that age 80 years and older was the greatest predictor of further falls, with a 2-fold increased adjusted risk by 5 years (HR 2.00; 95% C.I. 1.42 – 2.82). Mortality following an E.D. presentation with a fall was 19% at 1 year, increasing to 52% by 5 years. Increasing age and assistance with ADLs predicted both ED re-presentation and mortality. Being female and falls due to syncope were protective. The Concord Health and Ageing in Men (CHAMP), is a longitudinal study of 1705 men. Previous history of falls was the most significant predictor of future falls (IRR 3.12; 95% C.I. 2.49 – 3.91) and falls injury hospitalisations at 10 years (HR 1.48; 95% C.I. 1.09 – 1.99) in this cohort. Risk factors for falls included increasing age, disability in ADLs, being single, dementia, having 3 or more comorbidities, polypharmacy and reduced visual acuity. Dementia was associated with 2-fold increased risk of falls injury hospitalisation at 10 years (HR 2.67; 95% C.I. 1.69 – 4.22). Men born in a non-English-speaking country and men who were still working were less likely to be hospitalised die to a fall injury. A randomised controlled trial (n = 81) of a specialist-led CONFABs clinic versus enhanced G.P. coordinated care, showed an increased rate of falls (IRR 2.39; 95% C.I. 1.09 – 5.27) and risk of falls (RR 1.79; 95% C.I. 1.10 – 2.96) at 1 year with the CONFABS clinic intervention. There was no significant difference in the rate of injurious falls or in the number of fractures between the interventions. Compliance with recommendations was similar in both groups, although more falls prevention strategies were recommended to the falls clinic participants. There are shared risk factors for falls, fall hospitalisations and mortality, with increasing age, functional disability and dementia the most important to consider. Falls prevention strategies may be successfully provided in General Practice, supported by specialist risk assessment and recommendations.

Thesis (PhD)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: Prospective, longitudinal clinical studies in first-episode schizophrenia have become relatively commonplace over the past two decades or more and have provided a wealth of useful information regarding the clinical presentation, treatment, course and outcome of the illness. However, there remain several unanswered questions. The majority of the studies have been conducted in upper income countries using often costly medication with heterogeneous samples. While the overall outcome of patients showed some progress, there is room for improvement yet. The overall aim of the dissertation was to study the clinical, biological and functional aspects of outcome in first episode schizophrenia in a resource constrained setting. We conducted a prospective, non-comparative, longitudinal study over 12 months assessing the efficacy and tolerability of a cost effective, long-acting injectable antipsychotic (LAI; flupenthixol decanoate) combined with an assertive monitoring program (AMP) among first-episode schizophrenia patients. Efficacy was measured by examining rates of response, remission and relapse, as well as quality of life and social and occupational functioning. Tolerability of our intervention was assessed by measuring extrapyramidal symptoms, and weight and metabolic changes. We also examined the evolution of treatment refractoriness by studying the rates of non-response, and other associated predictor and outcome features. We found high rates of acceptance and adherence to the LAI and AMP. Seventy percent of our patients completed the 12 months of treatment. Treatment response was achieved by 82% of the participants and 60% achieved remission. Although 19% of our patients relapsed, the majority of the relapses were mild and did not require hospitalisation. Patients experienced significant quality of life and social and occupational functioning improvements. We found mild rates of extrapyramidal effects, present in only a third of our cohort. The majority of the extrapyramidal effects were treated with anticholinergics or propranolol. Only 3% of our patients developed transient dyskinesia over the duration of the study. However, our cohort gained considerable weight, with statistically significant increases in BMI (p< .0001) and waist circumference (p=0.0006). Our cohort also experienced significant deleterious changes to their lipid profiles. Of particular concern was the increase in triglycerides (p=0.03) and a significant decrease in high density lipoprotein (p=0.005) leading to a 91% increase in the triglyceride/high density lipoprotein ratio. With regards to emerging treatment refractoriness, 12% of our patients met our pre-defined criteria for non-response. Non-responders were younger and at baseline showed more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS), and lower BMI. At endpoint the non-responders were characterised by higher levels of symptomatology in all domains; poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and a lower BMI. The strongest predictors of non-response were prominent baseline NSS and poor early (7 weeks) treatment response. In conclusion, the combination of an LAI with an AMP may be an effective and safe intervention in firstepisode schizophrenia, and may be particularly suitable for resource-constrained settings. The risk of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics and low-potency first-generation antipsychotics. Ensuring effective treatment for first episode schizophrenia patients is a global problem, and likely to be under-recognised in LMICs.
AFRIKAANSE OPSOMMING: Oor die afgelope twee dekades het toenemend meer longitudinale kliniese studies, wat eerste episode skisofrenie bestudeer, die lig gesien. Die studies het ‘n magdom van waardevolle inligtng oor die kliniese voorkoms, behandeling, verloop en uitkomste van die siekte opgelewer. Die meerderheid van die studies is egter in hoë inkomste ontwikkelde lande gedoen met pasiënte wat duur medikasie gebruik en hoofsaaklik in heterogene steekproewe. Alhoewel dit blyk uit hierdie studies dat daar oor die algemeen vordering gemaak word ten opsigte van die behandeling van pasiënte is daar steeds ‘n gebrek aan voldoende inligting oor die onderwerp veral in minder gegoede, ontwikkelende lande. Die oorhoofse doel van hierdie proefskrif is om binne ‘n hulpbron beperkte konteks die kliniese, biologiese en funksionele aspekte van pasiënt -uitkomste in eerste episode skisofrenie te ondersoek. Ons het ‘n longitudinale studie gedoen waarin ons die effektiwiteit en toleransie van ‘n enkele antipsigotiese medikasie vir 12 maande nagevors het. Die medikasie wat ons ondersoek het, is flupenthixol decanoate en word deur ‘n inspuiting gegee en die medikasie word dan geleidelik deur die liggaam geabsorbeer. As deel van die behandeling het ons pasiënte ook streng gemonitor. Ons het die effektiwiteit van die behandeling gemeet nagelang van hoe pasiënte reageer op die behandeling, hoeveel pasiënte in remissie gaan en terugval, en ook pasiënte se kwaliteit van lewe en hulle sosiale en beroepsfunksionering. Ons het toleransie gemeet nagelang van pasiënte se gewig en metaboliese verandering sowel as die voorkoms van medikasie geïnduseerde newe-effekte. Verder het ons pasiënte wat nie op medikasie gereageer het nie ondersoek sowel as die aspekte wat moontlik hiernee verband hou. Ons het bevind dat die meerderheid van pasiënte hulle medikasie getrou geneem het en ook die streng monitering aanvaar het. Sewentig persent van die pasiënte het hulle 12 maande behandeling voltooi, 82% het op die medikasie gereageer en 60% het in remissie ingegaan. Alhoewel 19% van die pasiënte teruggeval het, was dit nie so ernstig dat ons hulle moes hospitaliseer nie. Pasiënte het beduidende verbetering ten opsigte van hulle kwaliteit van lewe en sosiale en beroepsfunksionering getoon. Ons het slegs ‘n gematigde mate van medikasie geïnduseerde newe-effekte opgemerk en alleenlik by ‘n derde van die kohort. In die meerderheid van gevalle het ons die newe-effekte met anticholinergics of propranolol behandel. Slegs 3% van die pasiënte het gedurende die verloop van 12 maande die kondisie transient dyskinesia ontwikkel. Ongelukkig het ons kohort geweldig baie gewig opgetel en die toename in pasiënte se BMI (p< .0001) en middellyf omtrek (p=0.0006) was statisties beduidend. Ons het ook bevind dat veranderinge in ons kohort se lipied profiele kommerwekkend is veral as in ag geneem word dat die toename in trigliseriede (p = 0,03) en die beduidende afname in die hoë digtheid lipoproteïen (p = 0,005) gelei het tot ‘n 91% verhoging in trigliseriede: hoë digtheid lipoproteïen verhouding.

Este estudo compara dois protocolos de reabilitação fisioterapêutica - um com três meses de duração (protocolo padrão IOT) e outro com dois meses (protocolo avançado) - para evidenciar a real necessidade de um tempo prolongado de reabilitação em 31 pacientes submetidas a artroplastia total do joelho. O estudo é prospectivo e randomizado e a faixa etária avaliada está entre 60 e 76 anos. As pacientes são avaliadas no pré-operatório e após o tratamento com avaliação clínica (escala de dor, Knee Society Score, SF-36 e goniometria) e avaliação de força (avaliação isocinética) para comparação dos protocolos. A análise estatística dos valores da escala de dor, do Knee Society Score, da amplitude de movimento, do pico de torque muscular e da avaliação da qualidade de vida (SF-36) demonstra que todas as pacientes obtêm melhora quando comparamos o pré e pós-operatório, independente do grupo. Conclui-se que o protocolo de reabilitação fisioterapêutica com dois meses de duração para o pós-operatório de artroplastia total do joelho mostra ser eficaz, alcançando os mesmos objetivos e resultados que o protocolo com três meses de duração
The present study compares two physiotherapeutic rehabilitation protocols - one lasting three months (standard IOT protocol), the other lasting two months (advanced protocol) - to assert the actual need of a prolonged rehabilitation period in 31 cases of patients who went through total knee arthroplasty. The study is prospective and randomized; the age group of evaluated patients is between 60 and 76 years-old. In order to compare the two protocols, patients are evaluated before surgery and after treatment, by means of clinical evaluation (pain scale, Knee Society Score, SF-36 and goniometry) and isokinetic strength test. Statistical analyses of results from pain scale, Knee Society Score, movement amplitude, muscular torque peak and quality of life show improvement for all patients between pre- and post-operation, regardless of group. The study concludes the two months physiotherapeutic rehabilitation protocol for total knee arthroplasty is as effective as the three months protocol, as both reached the same goals and results

Introdução: Neurocisticercose (NCC) é a principal causa evitável de epilepsia adquirida no mundo. NCC, além de ser, a doença parasitária mais comum do SNC, representa um importante problema de saúde pública, especialmente em países em desenvolvimento. Estudos de neuroimagem são cruciais no diagnóstico e planejamento terapêutico da NCC. Apesar da ressonância magnética (RM) fornecer maior número e detalhe de informações sobre a doença, a tomografia computadorizada (TC) ainda é o método mais sensível na detecção de calcificação intracraniana, o achado radiológico mais comum da NCC. Objetivo: Comparar performance das sequências de RM ponderadas em suscetibilidade magnética na identificação de calcificações intracranianas em pacientes com NCC. Métodos: Estudo prospectivo, unicêntrico, no qual 57 indivíduos foram submetidos a TC e RM de crânio. Todos os indivíduos foram provenientes do Ambulatório de Doenças Infecciosas do Departamento de Neurologia do Hospital das Clínicas - Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), com diagnóstico confirmado de NCC. O protocolo de RM incluiu uma sequência convencional 2D gradiente eco (2D-GRE) e duas relativamente novas sequências de suscetibilidade magnética: susceptibilityweighted imaging (SWI) e principles of echo shifting with a train of observations (PRESTO). A TC foi considerada método padrão de referência. Dois neurorradiologistas, cegos para os dados clínicos e demais achados radiológicos, analisaram independentemente as sequências 2D-GRE, SWI e PRESTO quanto à presença, número e localizações de calcificações intracranianas atribuídas a NCC. Resultados: Foram identificadas, pela TC, 739 lesões calcificadas relacionadas a NCC em 50 dos 57 indivíduos incluídos no estudo. A média de lesões calcificadas por paciente foi de 12,9 (± 19,8). A médias de lesões encontradas pelas sequências de suscetibilidade magnética, obtido através da média dos resultados dos observadores, foi de 10,8 (± 17,5) para PRESTO, 10,6 (± 17,3) para SWI e 8,3 (± 13,6) para 2D-GRE. Neste quesito não houve diferença estaticamente significativa entre PRESTO e SWI (p = 0,359) e ambos foram superiores a 2D-GRE (p < 0,05). A concordância foi fraca a moderada, provavelmente devido ao alto número de lesões falso-positivas encontradas (490), das quais 53,9% representavam lesões relacionadas a NCC em estágios não calcificados. A sensibilidade e especificidade das sequências estudadas em identificar corretamente indivíduos com NCC em estágio calcificado foi respectivamente de 85% e 100% para 2D-GRE, 90% e 100% para SWI e 93% e 100% para PRESTO. Conclusão: As sequências SWI, PRESTO e 2D-GRE apresentam boa sensibilidade na identificação de lesões calcificadas em pacientes com NCC. As sequências SWI e PRESTO tiveram melhor performance do que 2D-GRE. Todas as sequências estudadas mostrarem-se apropriadas para identificar indivíduos com NCC no estágio de calcificação. Sequências ponderadas em suscetibilidade magnética podem ajudar no entendimento da história natural, fisiopatologia e achados de imagem da NCC
Background: Neurocysticercosis (NCC) is the main preventable cause of acquired epilepsy. NCC, besides being the most common parasitic disease of the CNS, is an important public health problem, mainly in developing countries. Neuroimaging studies are crucial in the diagnosis and therapeutic planning of NCC. Although magnetic resonance imaging (MRI) provides countless and more detailed information about the disease, computed tomography (CT) is still the most sensitive method for detecting intracranial calcification, the most common radiological finding of NCC. Purpose: To compare the diagnostic performance of susceptibility-weighted MRI sequences in identification of intracranial calcifications in patients with NCC. Methods: A prospective study with 57 subjects who underwent CT and MRI of the brain. All individuals came from Department of Neurology of the Hospital das Clínicas - Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), with a stablished diagnosis of NCC. The MRI protocol included a conventional 2D gradient echo sequence (2D-GRE) and two relatively new susceptibility-weighted sequences: susceptibility-weighted imaging (SWI) and principles of echo shifting with a train of observations (PRESTO). CT was considered the standard reference method. Two neuroradiologists, blinded to clinical data and other radiological findings, independently analyzed the 2D-GRE, SWI and PRESTO sequences on behalf to presence, number and sites of intracranial calcifications attributed to NCC. Results: A total of 739 NCC-related calcified lesions were identified by CT in 50 of the 57 subjects included in the study. The mean number of calcified lesions per patient was 12.9 (± 19.8). The mean number of lesions found by the susceptibility-weighted MRI sequences, obtained through the mean of the observers\' results, was 10.8 (± 17.5) for PRESTO, 10.6 (± 17.3) for SWI and 8.3 (± 13.6) for 2D-GRE. There was no statistically significant difference between PRESTO and SWI (p = 0.359) and both were superior to 2D-GRE (p < 0.05). The concordance was weak to moderate, probably due to the high number of false-positive lesions found (490), of which 53.9% represented NCC-related lesions in non-calcified stages. The sensitivity and specificity of the sequences studied in correctly identifying individuals with calcified NCC were 85% and 100% respectively for 2D-GRE, 90% and 100% for SWI and 93% and 100% for PRESTO. Conclusion: SWI, PRESTO and 2D-GRE sequences have good sensitivity in the identification of calcified lesions in patients with NCC. SWI and PRESTO performed better than 2DGRE. All sequences studied are suitable for identifying individuals with NCC in the calcified stage. The new susceptibility-weighted MRI sequences may help in understanding the natural history, pathophysiology and imaging findings of NCC

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Os acidentes de trânsito (AT) se constituem em um importante problema de saúde pública mundial devido a sua magnitude crescente e ao alto custo humano e material que acarreta a qualquer sociedade. Embora as estatísticas de óbito e internação por AT no Brasil mostrem números alarmantes de vítimas, é consenso que elas revelam parte do problema, pois refletem os casos de maior gravidade que são registrados nos sistemas de informação em saúde. Assim, são escassas as pesquisas epidemiológicas sobre o envolvimento da população em acidentes de trânsito no Brasil, que tenham utilizado dados primários oriundos de base populacional, e inexistem investigações prospectivas que tenham estimado o risco de sofrer AT e seus padrões de ocorrência segundo características diversas das pessoas, incluindo os comportamentos no trânsito. Desse modo, o presente estudo foi concebido com o intuito de contribuir para ampliar o conhecimento sobre o tema. A Tese é composta por três artigos com os seguintes objetivos: Artigo 1 - Estimar a incidência cumulativa de envolvimento autorreferido em AT entre condutores de veículos terrestres a motor e descrever as características desses eventos segundo variáveis sociodemográficas, circunstâncias dos acidentes, lesões produzidas e utilização de serviços de saúde; Artigo 2 - Identificar fatores associados ao envolvimento em AT entre condutores por meio de uma abordagem analítica hierarquizada; Artigo 3 -Estimar a densidade de incidência (DI) geral de envolvimento em AT, autorreferido por condutores de veículos a motor, e DI estrato-específicas segundo características sociodemográficas e comportamentos no trânsito, por meio de abordagem prospectiva.Foi conduzida uma pesquisa longitudinal prospectiva, de base comunitária, que ocorreu entre os anos 2013 e 2014, e incluiu condutores de veículos motorizados terrestres residentes no município de Jequié, Bahia. Na linha de base (LB) do estudo foram recrutados 1.407 participantes por meio de amostragem por conglomerado em único estágio, para a qual foram selecionados 35 setores censitários. Durante a LB foram realizadas entrevistas domiciliares, após obtenção do consentimento informado, com aplicação de formulário estruturado por equipe de entrevistadores treinados, composta por estudantes de graduação da área da saúde de uma universidade pública.Ao fim das entrevistas, a equipe de coleta informou aos participantes sobre a fase de acompanhamento do estudo, na qual foram realizados três contatos telefônicos quadrimestrais para saber se houve envolvimento em AT, perfazendo o período completo do seguimento. A análise dos dados foi feita com estatística descritiva univariada, estimação de medidas epidemiológicas de frequência, medidas de associação e de impacto potencial, e modelo de regressão logística multinível para identificação de fatores associados ao envolvimento em AT enquanto dirigiam veículo (variável desfecho, definida segundo a Classificação Internacional de Doenças, 10ª revisão, com modificações). Para isso,foi elaborado um modelo conceitual hierarquizado composto por quatro blocos de fatores de exposição de acordo com as relações proximais-distais entre estes e o desfecho, estimando-se Odds Ratio (OR) ajustado e Intervalos de Confiança a 95% (IC95%).Estabeleceu-se valor de p≤0,05 como critério de significância estatística. Além disso, o delineamento amostral foi considerando durante a análise. Os dados produzidos na LB compuseram os dois primeiros artigos, enquanto o terceiro utilizoudados da etapa longitudinal. Dos 1.407 condutores entrevistados, 10,6% referiram envolvimento em AT enquanto estavam dirigindo veículo nos 12 meses anteriores à entrevista. A maioria dos envolvidos foi do sexo masculino (72,1%), entre 15 e 29 anos de idade (42,2%) e que estavam conduzindo motocicleta (52,4%). O tipo de acidente mais frequente foi colisão entre automóvel e moto (31,3%). Este último veículo esteve presente em 65,4% das ocorrências. O acidente interrompeu as atividades habituais de 23,8% dos envolvidos e 40,1% sofreram lesão física. Entre os envolvidos em AT, 25,2% foram atendidos em emergências hospitalares e 8,2% foram hospitalizados. Quanto aos fatores associados,observou-se maior chance de envolvimento em AT entre condutores de 15 a 29 anos (OR=3,56; IC95% 1,42-8,94); de cor da pele preta ou parda (OR=1,55; IC95% 1,03-2,33); motociclistas (OR=1,73; IC95% 1,16-2,57); com antecedentes de multa no trânsito (OR=1,77; IC95% 1,05-2,97); que referiram beber e dirigir (OR=1,67; IC95% 1,11-2,51) e usar telefone celular durante a condução (OR=1,66; IC95% 1,11-2,47). Os fatores proximais modificaram as medidas de associação das exposições dos níveis superiores de determinação do modelo hierarquizado, principalmente da associação com a variável sexo. No tocante à etapa prospectiva, no período de um ano, 110 condutores se envolveram em AT enquanto dirigiam veículos. A taxa geral de DI situou-se em 8,4 envolvidos por 100 condutores-ano. As taxas específicas apresentaram diferenças entre categorias de algumas variáveis. O risco de se envolver em AT foi maior entre condutores do sexo masculino, com idade entre 15 e 29 anos, solteiros, sem filhos, que conduziam, mais frequentemente, motocicletas, já tendo sofrido pelo menos um acidente anteriormente e que referiram se engajar em alguns comportamentos de risco, como gostar de velocidades altas ao dirigir e andar em veículo cujo condutor ingeriu bebidas alcoólicas. Os Riscos Atribuíveis Proporcionais variaram de 12,2% a 49,0%, sendo os de maior magnitude aqueles concernentes aos comportamentos sobre velocidade na condução. Os resultados foram, no geral, coerentes com as informações publicadas em literatura científica sobre o tema de estudo, ressalvado as diferentes abordagens metodológicas. As informações obtidas nesse estudo, de base populacional e prospectivamente, indicam um quadro mais preciso e completo sobre a magnitude dos AT e sobre grupos de risco em área urbana, que podem subsidiar políticas públicas e programas de prevenção de causas externas e de promoção da saúde e segurança no trânsito.

BACKGROUND: Folate, a B-vitamin found primarily in fruits and vegetables, especially leafy greens, and other B-vitamins involved in folate metabolism are believed to protect against cancer and cardiovascular disease. Maintaining an adequate folate status ensures availability of methyl groups for DNA synthesis and for all methylation reactions in the body, and prevents the accumulation of homocysteine, a sulphur-containing amino acid that has been linked to cardiovascular disease. The aim of this thesis was to relate factors involved in folate metabolism to the risk of developing colorectal cancer (CRC), prostate cancer (PCa), stroke (ischemic and hemorrhagic), and acute myocardial infarction (AMI). SUBJECTS AND METHODS: These were nested case-referent studies, with 226 CRC, 254 PCa, 396 stroke (334 ischemic and 62 hemorrhagic), and 571 AMI cases, and double, matched referents from the population-based Northern Sweden Health and Disease Study. CRC RESULTS: A bell-shaped association was observed between plasma folate concentrations and the risk of CRC [multivariate odds ratio (OR) for the middle versus lowest quintile, 2.00 (95% CI 1.13-3.56)]. Homocysteine was not associated with CRC risk. A reduced risk was observed for the MTHFR 677C>T polymorphism [OR for TT versus CC, 0.41 (95% CI 0.19-0.85), Ptrend=0.062] that was independent of plasma folate status. Prediagnostic plasma folate concentrations were higher in cases with promoter hypermethylation in the p16 and/or hMLH1 tumor suppressor genes in CRC tissue compared to cases without promoter hypermethylation in these genes (P=0.025). PCa RESULTS: Increasing plasma levels of folate and vitamin B12 were associated with increased risk of PCa [OR for the highest versus lowest quartile, 1.60 (95% CI 1.03-2.49), Ptrend=0.02 for folate, and 2.63 (95% CI 1.61-4.29), Ptrend<0.001 for vitamin B12]. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance. In multivariate analyses, the risk estimate remained statistically significant only for vitamin B12. STROKE RESULTS: Plasma folate concentrations were associated with the risk of hemorrhagic stroke in an inverse linear manner after adjustment for conventional risk factors including hypertension [multivariate OR for the highest versus lowest quartile, 0.21 (95% CI 0.06-0.71), Ptrend=0.008]. Risk estimates were attenuated by the inclusion of homocysteine in the model [OR 0.34 (95% CI 0.08-1.40), Ptrend=0.088]. Similar results were obtained for folate intake. Neither plasma folate levels nor folate intake demonstrated a clear association with the risk of ischemic stroke, and neither plasma nor dietary vitamin B12 was associated with the risk of either type of stroke. AMI RESULTS: Plasma folate concentrations demonstrated an inverse association with risk of AMI that was independent of other risk factors, including homocysteine [multivariate OR for the highest versus lowest quintile, 0.56 (95% CI 0.34-0.90), Ptrend=0.080]. For vitamin B12, no clear risk relationships were apparent. None of the risk estimates for dietary intake of folate, vitamin B12, vitamin B6, or vitamin B2 were statistically significant, although the results for folate and vitamin B12 intake were in line with those for the plasma variables. CONCLUSIONS: The results of these population-based, prospective studies suggest that although a high folate status may be associated with a reduced risk of cardiovascular diseases, the relationship with cancer risk seems to be more complicated. The possibility of a detrimental component to the role of folate and vitamin B12 in carcinogenesis may have implications in the ongoing debate concerning mandatory folate fortification of foods.

Objective: Prospective study designs ideally allow patients to be followed from the first manifestations of the illness or even from an at-risk stage. It can thus provide data on the predictive value of changes in clinical symptomatology, cognition or further biological markers to broaden our understanding of the etiopathology and symptomatic trajectory of bipolar disorders. The scope of this narrative review is to summarize evidence from prospectively collected data on psychopathological and other clinical and biological changes in the early developmental course of bipolar disorders. Methods: The narrative review was based on a literature search conducted in February 2016 within the PubMed library for prospective study data of persons in antecedent and early manifest stages of manifest bipolar disorder published within the last 15 years. Results: A total of 19 prospective studies were included. Regarding psychopathological features; personality, temperament and character traits as well as changes in sleep and circadian rhythm, the evidence suggests that risk factors for the development of bipolar disorder can already be described and should be studied further to understand their interaction, mediation with other factors and timing in the developmental process of bipolar disorder. Apart from the positive family history, childhood anxiety, sleep problems, subthreshold (hypo)manic symptoms and certain character traits/emotionality should be identified and monitored already in clinical practice as their presence likely increases risk of bipolar disorder. Up to date no substantiated evidence was found from prospective studies addressing cognitive features, life events, immunological parameters and morphological central nervous system changes as potential risk factors for bipolar disorder. Conclusion: For an improved understanding of episodic disorders, longitudinal data collection is essential. Since the etiology of bipolar disorders is complex, a number of potential risk factors have been proposed. Prospective studies addressing this spectrum and resilience factors are critical and will be best conducted within multi-site research networks or initiatives.

Previous studies on nonnative English speaker teachers (NNESTs) (Reyes & Medgyes, 1994; Samimy & Brutt-Griffler, 1999; Llurda, 2008; Rajagopalan, 2005) and publications in World Englishes (WEs), English as a Lingua Franca (ELF) and English as an international language (EIL), have analyzed and documented how prevailing ideologies rooted in "the myth of the native speaker" (Pennycook, 1994; Canagarajah, 1999; Kramsch, 2000), "the native speaker fallacy" (Phillipson, 1992) and associated ideologies generate discrimination and affect students and teachers' sense of self-worth.

By making use of telecollaboration to determine how L1 Spanish speaking Colombian EFL pre-service teachers' interactions with U.S. heritage Spanish speakers (HSSs) influence the Colombian future teachers' self-perceptions as (non) native speakers and future teachers, this study responds to scholars' concerns to diversify the scope of explorations on NNESTs. Examining the ideological side of the native vs. non-native speaker dichotomy in telecollaboration, this research seeks to reverse the tendency to study interactants' exchanges mainly as a language feedback process through which "native speakers" support those who are not native speakers.

Under an overarching qualitative phenomenological case study research design, the first article's pre-assessment of participants' self-perceptions of (non) nativeness found that the myth of the native speaker, the native speaker fallacy and associated ideologies permeated participants' self-images as language speakers and prospective teachers. Nevertheless, their ongoing education and the perceived benefits of becoming skillful language users contrasted with the harmful effects of these ideologies.

The second study determined that in adopting meaning making abilities as their center of interest in telecollaboration, most participants focused less on the achievement of idealized native speaker abilities. Their interaction with U.S. peers generated confidence in their use of English, self-criticism of their skills in Spanish and a tendency to embrace the idea that they could succeed as English teachers. The third article suggests that the cooperative relationships that participants established with U.S. peers provided them affective and knowledge-based resources to build more favorable views of themselves, attitudes to confront the detrimental effects of nativespeakership ideologies, and informed judgments to dismantle them.

Background Serious liver disease in infancy causes significant morbidity. Up to 80% of children will eventually require transplantation. This study aims to investigate parent and family responses to the diagnosis of serious liver disease in infancy and to identify family factors that are predictive of the infants’ emotional and behavioural outcomes. Methods The study uses quantitative and qualitative methods. Parents of infants recently diagnosed with serious liver disease completed validated measures of parent stress, family function, impact of the illness on the family, and father engagement, as well as an interview about their experience of the infants’ illness. The measures were repeated after one year, with the addition of the Child Behavior Checklist (CBCL). Results Parents of 42 infants enrolled, and parents of 37 infants completed the study. Illness severity, liver diagnosis other than Biliary Atresia and parent perceptions of greater impact of the infants’ illness on the family predicted poorer infant outcomes. For mothers, the final best-fit model explained 32% of the variation in CBCL (P = .001). Fathers’ best-fit model explained 44% of the variation in CBCL (P < .001). Thematic analysis of the parent interviews revealed six major themes: uncertainty; awareness of the infant’s vulnerability; feelings of isolation; dealing with other aspects of life; the importance of shared experience; and adjustment. The integrated data analysis demonstrated that lack of extended family support, poor family adjustment to the illness, and financial stress are related to greater impact of the illness on the family. Conclusions The study identifies early risk factors for poor emotional and behavioural outcomes for infants with serious liver disease, providing an opportunity for early intervention. Parents who lack support from extended family, who have financial stress, or who report a high impact of the illness on the family, should be referred for psychosocial assessment.

Osteoporotic fractures are a major and increasing clinical and public health concern internationally. Identification of individuals at high risk for fragility fractures may enable us to target preventive interventions more effectively. In this thesis, I aimed to evaluate novel risk factors for osteoporosis and develop a fracture risk assessment model among the middle-aged and older people. I used data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, which is a large population-based prospective study started in 1993. About 25,000 men and women were assessed at baseline and about 15,000 of them returned for a second examination 4 years later. All participants are followed up to the present for clinical events including fractures. My work is in two parts. For the first part, I examined the risk of fracture associated with some novel or less well studied risk factors. These risk factors included change in height over time, respiratory function, physical activity and body fat mass. We found that men and women with annual height loss >0.5 cm are at increased risk of hip and any fracture (relative risk=1.9 (95% CI 1.3-2.7) per cm/year height loss). One litre lower forced expiratory volume in 1 second (FEV1) was associated with a 2-fold risk of hip fracture in men and women. We also observed a non-linear association, independent of body mass index, between increasing body fat mass and lower fracture risk in women but not in men. I performed a systematic review and meta-analysis of studies evaluating the association between physical activity and hip fractures. Using a new validated questionnaire in EPIC-Norfolk, we observed varying relationships between physical activity in different domains of life and fracture risk in men and women. For the second part of the thesis, I developed a biostatistical model to calculate 10-year risk of developing a fracture among EPIC-Norfolk study participants. This model incorporates clinical and radiological assessments known to be associated with fractures and can be extended to other risk factors assessed in other prospective cohorts. This helps clinicians to achieve a better estimate of the prospective risk of fracture in their patients. I applied this model to compare the predictive value of two different clinical assessment methods for osteoporosis, namely dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS). We found that that the predictive power of QUS is comparable to, and independent of, predictive power of DXA. In summary, my studies have added to our knowledge about some novel and easy-to-use risk factors of osteoporosis and proposed a practical method to merge and utilise data from different risk factors for estimation of fracture risk in individuals.