58 resultados para Revealed preference methods


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21th Annual Conference of the International Group for Lean Construction (IGLC 21), July 2013, Fortaleza, Brazil

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A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

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Dissertação para obtenção do Grau de Mestre em Biotecnologia

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Dissertation submitted in Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa for the degree of Master of Biomedical Engineering

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Dissertação apresentada para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

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RESUMO: A operação de Nissen, por laparoscopia, é considerada a cirurgia antirefluxo mais adequada por ser a que melhor replica a fisiologia normal da válvula gastresofágica na maioria dos doentes com sintomas típicos de doença do refluxo gastresofágico (DRGE). São critérios técnicos o encerramento seguro dos pilares do diafragma e a criação de fundoplicatura completa (360 graus), curta (inferior a dois centímetros), lassa e sem tensão – desiderando para o qual a laqueação proximal dos vasos curtos gástricos é crucial. Realizei a operação de Nissen, por laparoscopia, em sessenta mulheres e quarenta homens com DRGE, sem mortalidade operatória, no Serviço de Cirurgia 6 do Hospital dos Capuchos, CHLC, EPE. Os cem doentes apresentavam média etária de 46 anos e queixas, com tempo de evolução entre 1 e 43 anos, de pirose (90%), regurgitação (80%), azia (73%), epigastralgias (54%). A endoscopia alta revelou esofagite de grau Savary-Miller 0-I (62%), II (23%), III (8%), IV (7%); hérnia de deslizamento (71%), hérnia paraesofágica (8%), sem hérnia (21%); a pHmetria de 24h diagnosticou padrão misto (38%), levantado (20%), deitado (20%), inconclusiva (22%) e a manometria diagnosticou EEI hipotónico (35%), peristálise esofágica normal (88%), hipomotilidade ligeira (5%) e foi omissa (7%). Hérnia hiatal, esofagite grave, ineficácia do controlo sintomático com inibidor da bomba de protões e desejo de descontinuidade terapêutica constituíram as indicações para tratamento cirúrgico. Por celioscopia, efetuei laqueação dos vasos curtos gástricos (70%), cruroplastia e fundoplicatura total (seda 2/0), curta (dimensão média 1,5-2 cm), lassa, sem tensão e sem calibração intraoperatória do esófago. A fundoplicatura de Nissen laparoscópica mostrou-se segura e eficaz no tratamento da DRGE. A sua idoneidade foi ainda comprovada pela normalização da pHmetria de 24 horas e da manometria pós-operatórias, com significado estatístico, num grupo de catorze voluntários assintomáticos. Em catamnese com recuo médio 30,7 meses 94% dos indivíduos persistem assintomáticos. Interrogando-me acerca das repercussões desta operação sobre a microcirculação do fundo gástrico coloquei, como premissa, a possibilidade de na operação de Nissen a laqueação dos vasos curtos poder induzir modificação no diâmetro arteriolar da parede do fundo gástrico. Para pesquisar a influência da laqueação dos vasos curtos gástricos e da fundoplicatura total sobre o calibre arteriolar da parede do estômago no cárdia, no fundo e na região dos vasos curtos gástricos, idealizei um Projeto de investigação experimental em cobaias. O Projeto foi desenvolvido no Centro de Investigação do Departamento de Anatomia da FCM-UNL. Para a sua realização obtive autorização da Comissão Científica e Pedagógica da FCM-UNL, requeri a acreditação como investigador à Direção Geral de Veterinária e, por recorrer à utilização de animais, submeti-o à Comissão de Ética da FCM-UNL, que o aprovou por unanimidade. Para limitar o número de animais utilizados ao mínimo necessário, calculei, por método estatístico, a quantidade de cobaias necessárias. Subdividindo-as num grupo de ensaio (GE), onde realizei a operação de Nissen, e num grupo de controlo (GC), onde apenas procedi a tração gástrica, defini e apliquei protocolos de anestesia, de cirurgia e de eutanásia, segundo os princípios dos 3R – Replacement, Reduction, Refinement da técnica de experimentação humana de Russell e Burch (1959) – uma estrutura ética amplamente aceite para a realização de experimentação científica humanizada com animais. A utilização das técnicas de estudo angiomorfológico permitiu-me analisar e descrever a anatomia normal, a vascularização arterial macroscópica, a microangioarquitetura, por microscopia eletrónica de varrimento de moldes de corrosão vascular, e a histologia da parede do estômago da cobaia. Procedi, também, à definição dos critérios morfológicos que considerei suscetíveis de validação deste modelo animal para o estudo proposto. Por razões académicas, foi necessário abreviar o Projeto encurtando, em cerca de dois anos, o prazo disponível para conclusão do estudo. Apreciando-o com o Gabinete de Análise Epidemiológica e Estatística do Centro de Investigação do CHLC, EPE, optou-se, perante a escassez de elementos após já terem sido recrutados 46 animais, por uma amostra, suplementar, de dimensão de conveniência de oito cobaias (quatro em cada grupo), condicionada pelo limite temporal universitário e pelo respeito pela dignidade dos animais. Neste subgrupo procedi, por microscopia eletrónica de varrimento, à medição dos calibres arteriolares nos moldes vasculares do cárdia, do fundo e da zona dos vasos curtos gástricos tanto no GC como no GE efetuando 469 medições no primeiro e 461 no último. Os dados foram enviados ao Centro de Investigação do CHLC, EPE que procedeu à sua análise estatística (ANOVA). A referida análise revelou que as arteríolas do plexo mucoso e as do plexo submucoso do cárdia, do fundo e da região dos vasos curtos gástricos, mostraram aumento de calibre no GE. O aumento foi, estatisticamente, significativo por ser superior a 50% do calibre do GC. Nos vasos curtos, a diferença foi mais pequena, mas persistiu sendo, estatisticamente, significativa. Os vasos retos dilataram na base, na sua emergência do plexo seroso, apenas no fundo gástrico. Na cobaia a operação de Nissen – fundoplicatura total com laqueação dos vasos curtos gástricos –, provocou vasodilatação arteriolar do fundo gástrico. Considero que essa vasodilatação constituiu acomodação à modificação introduzida e infiro que o mesmo possa acontecer no ser humano. Admito, assim, que também ocorra vasodilatação no ser humano, na sequência da laqueação dos vasos curtos gástricos, pela analogia microvascular entre as duas espécies e que essa vasodilatação corresponda, igualmente, a um mecanismo de adaptação arteriolar visando, por exemplo, suprir a perda incorrida pela laqueação. A associação experimental entre laqueação dos vasos curtos gástricos e realização de fundoplicatura total, que exerce aumento inerente de pressão sobre a JEG, não só não provocou défice da microcirculação do esófago distal ou do estômago proximal como desencadeou um mecanismo de vasodilatação fúndica que reforça o conceito de segurança da operação de Nissen para tratamento da DRGE. -------------- ABSTRACT: The laparoscopic Nissen operation is considered to be the most appropriate antirefluxsurgery because it suitably replicates the standard physiology of the gastroesophageal valve in most patients with typical symptoms of gastroesophageal reflux disease (GERD). The technical criteria includes the safe shutdown of the diafragmatic crura(cruroplasty) and the creation of a complete fundoplication (360 degrees), short (lesser than two inches), floppy and without tension – a goal for which the proximal ligation of the gastric short vessels is crucial. The laparoscopic Nissen operation was performed in sixty women and forty men with GERD, without any operative mortality, at the Surgical Department of the Hospital dos Capuchos, CHLC, EPE. The one hundred patients, averaged 46 years old, complained of heartburn (90%), regurgitation (80%) and upper abdominal pain (54 %). The endoscopy process revealed Savary-Miller esophagitis of grade 0-I (62%), II (23%), III (8%), IV (7%), sliding hernia (71%), paraesophageal hernia (8%) or no herniation (21%). The pHmetry/24h diagnosed mixed pattern (38%), raised (20%), lying (20%) or inconclusive (22%). The manometry diagnosed hypotensive LES (35%), normal esophageal peristalsis (88%), mild hypomotility (5%) and was absent (7%). Hiatal hernia, severe esophagitis, ineffective symptomatic control with proton pump inhibitor and request for treatment discontinuation were the signs for surgical action. A laparoscopic ligation of short gastric vessels (70%), cruroplasty and fundoplication (silk 2/0), short (average size 1.5–2 cm) and floppy, without tension and without intraoperative calibration of the esophagus were thus performed. The laparoscopic Nissen fundoplication behaved safe and effective in treating GERD. In a group of 14 asymptomatic volunteers its reputation was confirmed with statistical significance by normalization of postoperative pHmetry/24h and manometry. 94% of the individuals remained asymptomatic up to 30.7 months (average) in the follow-up. Interrogating myself about the impact of this operation on the microcirculation of the gastric fundus I put premised on the possibility of the ligation of the short gastric vessels in the Nissen procedure can induce changes in the arteriolar diameter in the Wall of the gastric fundus. To explore the influence of ligation of the short gastric vessels and the fundoplication at the arteriolar caliber of the cardia, the fundus and the region of the short vessels of the gastric wall, I designed a project of experimental research in guinea pigs with two interdependent components: one veterinary and another technical where I applied angiomorphological studies. The project was developed at the Research Centre of the Department of Anatomy FCMUNL. For its accomplishment I got permission from the Scientific and Pedagogical Committee of the FCM-UNL, I requested for accreditation as a researcher at the General Directorate of Veterinary and, by resorting to the use of animals I submitted it to the Ethics Committee of the FCM-UNL, which approved it unanimously. The guinea pigs were divided into two experimental groups: an experimental group (EG), in which the Nissen procedure was performed and a control group (CG) in which only a gastric traction was done. Protocols of anesthesia, surgery and euthanasia were applied according to the 3Rs – Replacement, Reduction, Refinement of the technique of human experimentation of Burch and Russell (1959) – a widely accepted ethical framework for conducting scientific experiments using animals humanely. Using histological and angiomorphological techniques, I performed the analysis and the description of the normal, macro and microvascular, anatomy of the guinea pig stomach and I defined the morphological criteria that I considered susceptible for validation of this animal model for the proposed study. By means of scanning electron microscopy I measured the arteriolar calibers of the vascular casts of the cardia, of the fundus and of the short gastric vessels in both CG and EG, making 469 measurements in the former and 461 in the latter. The data were sent to the Research Center of the CHLC which conducted the statistical analysis (ANOVA). The data were sent to the Centre for Research of the CHLC, EPE which proceeded to statistical analysis (ANOVA). This analysis revealed that the arterioles plexus of the mucosal and submucosal plexus of the cardia, fundus and region of the short gastric vessels, showed increased caliber in EG. The increase was statistically significant for being greater than 50% CG gauge. In the short gastric vessels, the difference was smaller, but persisted and statistically significant. Straight vessels were dilated at the base, on its emergence of the plexus serous only in the fundus. In the guinea pig, the Nissen procedure - complete fundoplication with ligation of the short gastric vessels - caused arteriolar vasodilation on the gastric fundus. I believe that this vasodilation constituted some accommodation to the modification introduced and infer that the same might happen in humans. I admit therefore that vasodilation also occurs in humans following the ligation of the short gastric vessels by microvascular analogy between the two species and that this vasodilation corresponds also to na adaptation mechanism arteriolar, for example, to compensate the loss incurred by ligation. The association of experimental ligation of the short gastric vessels with conducting complete fundoplication, which exerts increased pressure on the EGJ, not only did not cause a microcirculation deficit of the distal esophagus or proximal stomach as triggered a mechanism of fundic vasodilation which reinforces the security concept of the Nissen procedure for treatment of GERD.

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RESUMO: Os circuitos fronto-estriatais constituem um sistema em ansa fechada que une diversas regiões do lobo frontal aos gânglios da base, participando, com outras áreas cerebrais, no controlo do movimento, cognição e comportamento. As Distonias Primárias, a Doença de Parkinson e a Hidrocefalia de Pressão Normal, são doenças do movimento caracterizadas por disfunção do circuito fronto-estriatal motor. A conectividade funcional entre as diversas ansas do sistema fronto-estriatal, permite prever que as doenças do movimento possam também acompanhar-se de sintomas da esfera cognitiva e comportamental, cuja avaliação seria importante no manejo diagnóstico e terapêutico dos doentes. Objectivos Os nossos objectivos foram avaliar, por estudos clínicos, a relação entre sintomas motores, cognitivos e comportamentais em três doenças do movimento com fisiopatologias diversas - distonias Primárias, Doença de Parkinson e Hidrocefalia de Pressão Normal - analisando os dados sob a perspectiva teórica fornecida pelo conhecimentos dos vários circuitos frontoestriatais. Os nossos objectivos específicos para cada doença foram: a) Distonias Primárias: avaliação de disfunção executiva em doentes com Distonia Primária e relação com a gravidade dos sintomas motores b) Doença de Parkinson: 1. avaliação breve das funções mentais nas fases iniciais da doença, incluindo análise longitudinal para determinação de factores preditivos para declínio cognitivo; 2. relação entre a função motora e cognitiva e a Perturbação do Comportamento do sono REM, incluindo análise longitudinal; 3.avaliação de sintomas psiquiátricos, de um ponto de vista global e especificamente com incidência sobre as Perturbações do Controlo do Impulso (PCI). c) Hidrocefalia de Pressão Normal: 1. caracterização das alterações da marcha, incluindo comparação com a Doença de Parkinson; 2. caracterização das alterações cognitivas e da relação entre estas e a disfunção da marcha; 3. estudo evolutivo das alterações da marcha e cognitiva em doentes submetido a cirurgia e doentes não submetidos a cirurgia. Métodos: A Distonia Primária, a Doença de Parkinson e a Hidrocefalia de Pressão Normal foram diagnosticadas segundo critérios clínicos validados. Sempre que justificado, foram recrutados grupos de controlo, com indivíduos sem doença, emparelhados para idade, sexo e grau de escolaridade. Os doentes foram avaliados com instrumentos de aplicação clinica directa, incluindo escalas de função motora, testes neuropsicológicos globais e dirigidos às funções executivas e escalas de avaliação psiquiátrica. Testes aplicados nas Distonias Primárias: Unified Dystonia Rating Scale, Wisconsin Card Sorting Test, teste de Stroop, teste de cubos da WAIS, Teste de Retenção Visual de Benton; na Doença de Parkinson: Unified Parkinson's Disease Rating Scale, Frontal Assessment Battery (FAB), Mini-Mental State Examination (MMSE), REM-sleep behaviour disorder Questionnaire; Symptom Chek-list 90-R, Brief Psychiatric Rating Scale, FAS (fluência verbal lexical) Nomeação de Animais (Fluência verbal semântica), prova de repetição de dígitos (WAIS), Rey auditory verbal learning test, teste de Stroop, matrizes progressivas de Raven, Questionnaire for Impulsive-Compulsive Disorders; na HPN: prova cronometrada de marcha,MMSE, prova de memória imediata da WAIS, prova de repetição de dígitos (WAIS), FAB, desenho complexo de Rey, teste de Stroop, cancelamento de letras, teste Grooved Pegboard. Os doentes com HPN foram também submetidos a estudo imagiológico. A avaliação estatística foi adaptada às características de cada um dos estudos.Resultados Distonias Primárias: encontrámos défices de função executiva, envolvendo dificuldade na mudança entre sets cognitivos, bem como correlação significativa entre as pontuações nos testes cronometrados e a gravidade dos sintomas motores. Doença de Parkinson: os doentes com DP obtiveram pontuações significativamente inferiores na FAB e em sub-testes do MMSE (memória e função visuo-espacial). A pontuação no MMSE encontrava-se significativamente correlacionada com itens da função motora não relacionados com o tremor. A disfunção da marcha, a disartria, o fenótipo não tremorígeno, a presença de alucinações e pontuação abaixo do ponto de corte na MMSE, foram factores preditivos de demência na avaliação longitudinal. A rigidez e a disartria foram factores preditivos de declínio nas funções frontais. A disfunção frontal foi factor preditivo de declínio na pontuação do MMSE. Encontrámos uma prevalência elevada de RBD nas fases iniciais da DP, que o estudo longitudinal mostrou ser factor preditivo de declínio motor, nomeadamente por agravamento da bradicinésia. Encontrámos também uma prevalência elevada de sintomas psiquiátricos, nomeadamente psicose, depressão, ansiedade, somatização e sintomas obsessivo-compulsivos. As PCI não se encontravam relacionadas com o fenótipo motor, com as complicações motoras do tratamento dopaminérgico ou com a disfunção cognitiva. HPN: os doentes com HPN e os DP apresentaram um padrão disfunção da marcha semelhante, caraterizado por passos curtos, lentidão e dificuldades de equilíbrio, sendo os sintomas mais graves na HPN. Os doentes de Parkinson com maior duração de doença, maior dose de dopaminérgicos e fenótipo motor acinético-rígido apresentaram um padrão de disfunção da marcha de gravidade semelhante ao encontrado na HPN. As alterações vasculares da substância branca, em particular as encontradas na região frontal, encontravam-se negativamente correlacionadas com a melhoria da marcha após PL. O estudo das funções cognitivas mostrou um padrão de atingimento global, com valores mais baixos na cópia do desenho complexo de Rey. Os resultados nas provas de função cognitiva não se encontravam significativamente correlacionados com os resultados na prova da marcha. A progressão na disfunção da marcha encontrava-se relacionada com o tratamento não cirúrgico, idade superior na primeira avaliação, presença de lesões da substância branca, e presença de factores de risco vascular, ao passo que não foram encontrados factores que predissessem de modo significativo o agravamento da função cognitiva. Conclusões: Os resultados dos diversos estudos, evidenciam a presença de alterações cognitivas e comportamentais nas três doenças de movimento. O padrão destas alterações e o modo como estas se relacionaram com os sintomas motores variou de doença para doença. Nas Distonias primárias, a perseveração cognitiva poderá ser o sintoma correspondente à perseveração motora própria da doença, sugerindo disfunção no circuito dorso-lateral frontoestriatal. A correlação entre a gravidade motora da doença e o resultado nos testes cognitivos cronometrados, poderá ser o efeito da relação entre bradicinésia e bradifrenia. Na Doença de Parkinson, o espectro de alterações é mais acentuado, espelhando a disseminação do processo degenerativo no SNC. Para além dos sintomas de disfunção executiva, sugerindo disfunção das tês ansas não motoras, existem sinais de disfunção cognitiva global, estas com uma influência mais significativa no desenvolvimento da demência. A relação entre os diferentes sintomas motores e cognitivos é também complexa, embora se evidencie uma dissociação significativa entre o tremor, sem relação com os sintomas não motores, e os sintomas motores não tremorígenos, relacionados com o declínio cognitivo. Enquanto que a presença de RBD parece ser um factor preditivo de agravamento motor, os sintomas psiquiátricos, também muito frequentes, apresentam uma relação menos clara com a função motora. Destes, os sintomas obsessivo-compulsivos são aqueles que com mais frequência se atribuem a disfunção do sistema fronto-estriatal, nomeadamente da ansa orbito-frontal. As PCI também não mostraram ter relação com os sintomas motores ou cognitivos. Na HPN, é patente o carácter fronto-estriatal das alterações da marcha, demonstrado tanto na sua caracterização quanto no efeito deletério das lesões vasculares da substância branca do lobo frontal na recuperação da marcha após PL. As alterações cognitivas parecem ter um padrão mais difuso, o que talvez explique a falta de correlação com os sintomas motores - esta dissociação pode ser causada quer por diferença nos mecanismos fisiopatológicos quer por presença de comorbilidades cognitivas. --------- ABSTRACT: Fronto-striatal circuits constitute a closed loop system which connects different parts of the frontal lobes to the basal ganglia. They are engaged in motor, cognitive and behavioural control. Primary Dystonia, Parkinson's Disease and Normal-Pressure Hydrocephalus are movement disorders caused by disturbance of the motor fronto-striatal circuit. The existence of cognitive and behavioural dysfunction in these movement disorders is predictable, given the functional connectivity between the several distinct loops of the circuit. Evaluation of cognitive and behavioural dysfunction in these three disorders is thus both of clinical and theoretical relevance. Objectives Our objectives were to evaluate, by clinical means, the relation between motor, cognitive and behavioural symptoms in three movement disorders with different pathophysiological backgrounds - Primary Dystonia, Parkinson's Disease and Normal-Pressure Hydrocephalus - and to analyse the study results under the theoretical framework formed by present knowledge of the fronto-estriatal system. Specific objectives: a) Primary Dystonia: executive dysfunction assessment and correlation analysis with motor dysfunction severity; b) Parkinson's Disease: 1. brief cognitive assessment in the early stages of disease, including a longitudinal analysis for determination of predictive factors for cognitive decline; 2. to investigate the relation between RBD and cognitive and motor dysfunction, including a longitudinal analysis; 3. psychiatric symptom assessment, with particular incidence on Impulse Control Disorders; c) Normal-Pressure Hydrocephalus: 1. gait dysfunction characterization and comparison with Parkinson's Disease patients; 2. determination of cognitive dysfunction profile and its relation with gait dysfunction; 3. follow-up study of cognitive and motor outcome in patients submitted and not submitted to shunt surgery. Methods: Primary Dystonia, Parkinson's Disease and Normal Pressure Hydrocephalus were diagnosed according to clinically validate criteria. Where warranted, we recruited control groups formed by healthy individuals, matched for age, sex and educational level. Patients were evaluated with instruments of direct clinical application, including motor function scales, neuropsychological tests aimed at global and executive functions and psychiatric rating scales. Tests used in Primary Dystonia: Unified Dystonia Rating Scale, Wisconsin Card Sorting Test, Stroop Test, Cube Assembly test (WAIS), Benton’s Visual Retention Test; in Parkinson's Disease: Unified Parkinson's Disease Rating Scale, Frontal Assessment Battery (FAB) , Mini-mental State Examination (MMSE), REM-sleep behavior disorder Questionnaire, Symptom Check-list 90- R, Brief Psychiatric Rating Scale, FAS (phonetic verbal fluency), semantic verbal fluency test, digit span test (WAIS), auditory verbal learning test,Stroop test, Raven's progressive Matrices, Questionnaire for Impulsive-Compulsive Disorders; in NPH: timed walking test, MMSE, immediate memory task (WAIS), digit span test (WAIS), FAB, Rey’s Complex Figure test, Stroop test, letter cancellation test, Perdue Pegboard test. NPH patients were also subjected to an imaging study. Statistics were adapted to the characteristics of each study.Results: Primary Dystonia: we found set-shifting deficits as well as significant correlation between timed neuropsychological tests and dystonia severity. Parkinson's Disease: PD patients had significantly lower scores on the FAB and on the memory and visuo-spatial tests of the MMSE; MMSE scores were significantly correlated to non-tremor motor scores; gait dysfunction and speech scores, non-tremor motor phenotype, hallucinations and scores bellow cut-off on the MMSE were predictive of dementia at follow-up; speech and rigidity scores were predictive of frontal type decline; frontal dysfunction was predictivy of decline in MMSE scores; RBD bradykinesia worsening; psychiatric symptoms were prevalent, particularly Psychosis, Depression, Anxiety, Somatisation and Obsessive-Compulsive Symptoms; Impulse Control Disorders were unrelated to motor phenotype,motor side effects of dopamine treatment and executive function; NPH: gait dysfunction was worse in NPH when compared to PD patients, although the pattern was similarly characterized by slowness, short steps and disequilibrium; PD patients whose gait disturbance was as severe as that of NPH patients were characterized by longer disease duration, predominance of non-tremor motor scores, more advanced disease stage and higher dopamine dose; frontal white matter lesions correlated negatively with improvement after LP; cognitive function assessment revealed wide spread deficits, with lower results on the drawing of the complex figure of Rey, which were not significantly correlated to gait dysfunction; older age, white matter lesions and the presence of vascular risk factors were predictive factors for motor but not cognitive function worsening. Conclusion: Results from our studies highlight the presence of cognitive and behavioural dysfunction in all three movement disorders. Symptom pattern and the relation with ovement derangement varied according to the disease. In Primary Dystonia, set-shifting difficulties could be the cognitive counterpart of motor perseveration characteristic of this disorder, suggesting dysfunction of the dorso-lateral circuit. The relation between timed tests and dystonia severity could suggest a relation between bradyphrenia and bradykinesia in Primary Dystonia. In Parkinson's Disease patients, the spectrum of non-motor symptoms is wider, probably reflecting the spread of neurodegeneration beyond the fronto-striatal circuits. While frontal type deficits predominate, suggestive of dorso-lateral and orbito-frontal dysfunction, non-frontal deficits were also apparent in the initial stages of disease, and were predictive of dementia at follow-up. The relationship between cognitive and motor symptoms is complex, although the results strongly suggest a dissociation between tremor symptoms, which bore no relation with non-motor symptoms, and non-tremor symptoms,whichwas frequent, and a predictive factor for which were related with cognitive decline. While RBD was found to be a predictive factor for bradykinesia worsening, psychiatric symptoms, which were also frequent, showed no apparent relation with motor dysfunction. Relevant to our theoretical consideration was the high prevalence of OCS, which have been attributed to orbito-frontal dysfunction. As to the particular case of ICD, we found no relation either with motor or cognitive dysfunction. The fronto-striatal nature of gait dysfunction in NPH is suggest by the clinical characterization study and by the effects of frontal white matter lesions on gait recovery after LP, whereas cognitive dysfunction presented a more diffuse pattern, which could explain the lack or relation with gait assessment results and also the different outcome on the longitudinal study - this dissociation could be caused by a real difference in pathophysiological mechanisms or, in alternative, be due to the existence of cognitive comorbidities.

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As an introduction to a series of articles focused on the exploration of particular tools and/or methods to bring together digital technology and historical research, the aim of this paper is mainly to highlight and discuss in what measure those methodological approaches can contribute to improve analytical and interpretative capabilities available to historians. In a moment when the digital world present us with an ever-increasing variety of tools to perform extraction, analysis and visualization of large amounts of text, we thought it would be relevant to bring the digital closer to the vast historical academic community. More than repeating an idea of digital revolution introduced in the historical research, something recurring in the literature since the 1980s, the aim was to show the validity and usefulness of using digital tools and methods, as another set of highly relevant tools that the historians should consider. For this several case studies were used, combining the exploration of specific themes of historical knowledge and the development or discussion of digital methodologies, in order to highlight some changes and challenges that, in our opinion, are already affecting the historians' work, such as a greater focus given to interdisciplinarity and collaborative work, and a need for the form of communication of historical knowledge to become more interactive.

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Dissertation presented to obtain the Ph.D degree in Chemistry.

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Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

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Dissertação para obtenção do Grau Mestre em Engenharia Civil – Perfil de Construção

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Fundação para a Ciência e a Tecnologia - SFRH/BD/27914/2006

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This study focuses on the assessment of the fermentation conditions required to modulate the metabolic flux in the osmotolerant yeast Candida magnoliae and evaluate its potential to produce low-alcoholic and low-caloric fermented beverages. For that purpose, two strains, PYCC 2903 and PYCC 3191, were used and fermentation conditions as oxygenation, sugar concentration and the ratio of glucose to fructose were studied using synthetic culture media. Candida magnoliae PYCC 2903 was subsequently used to ferment real industrial fructose-rich substrates such as fruit juices. Sugar consumption profiles for C.magnoliae PYCC 2903 incubated aerobically in the presence of high fructose and glucose concentrations (15%, 10% and 5%) showed a selective utilization of fructose, denoting a preference for this sugar over glucose. The lower ratio between ethanol and sugar alcohols yield was obtained for both strains incubated under oxygen limitation simulating industrial fructose-rich substrates, confirming the ability of this yeast to direct fermentation towards alternative products. Enzymatic assays for hexokinase activity in terms of capacity and affinity for glucose and fructose were performed, aiming to elucidate its contribution to the fructophilic behaviour of this yeast. Enzymatic assays for both strains showed that the Vmax is two to threefold higher for fructose than for glucose but Km is also 10-20-fold higher for this sugar than for glucose. Hence, hexokinase kinetic properties do not explain fructophily in C.magnoliae. This indicates that fructose transport is probably determining in this respect, as observed for other fructophilic yeasts. Fruit juice fermentations with C.magnoliae PYCC 2903 revealed a potential for the production of beverages with interesting sensorial properties. Pear and peach fermentations exhibited the best results with the lowest ratio between ethanol and sugar alcohols yield and the most pleasant organoleptic features.

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Three different treatments were applied on several specimens of dolomitic and calcitic marble, properly stained with rust to mimic real situations (the stone specimens were exposed to the natural environment for about six months in contact with rusted iron). Thirty six marble specimens, eighteen calcitic and eighteen dolomitic, were characterized before and after treatment and monitored throughout the cleaning tests. The specimens were characterized by SEM-EDS (Scanning Electron Microscopy coupled with Energy Dispersion System), XRD (XRay Diffraction), XRF (X-Ray Fluorescence), FTIR (Fourier Transform Infrared Spectroscopy) and color measurements. It was also made a microscopic and macroscopic analysis of the stone surface along with the tests of short and long term capillary absorption. A series of test trials were conducted in order to understand which concentrations and contact times best suits to this purpose, to confirm what had been written to date in the literature. We sought to develop new methods of treatment application, skipping the usual methods of applying chemical treatments on stone substrates, with the use of cellulose poultice, resorting to the agar, a gel already used in many other areas, being something new in this area, which possesses great applicability in the field of conservation of stone materials. After the application of the best methodology for cleaning, specimens were characterized again in order to understand which treatment was more effective and less harmful, both for the operator and the stone material. Very briefly conclusions were that for a very intense and deep penetration into the stone, a solution of 3.5% of SDT buffered with ammonium carbonate to pH around 7 applied with agar support would be indicated. For rust stains in its initial state, the use of Ammonium citrate at a concentration of 5% buffered with ammonium to pH 7 could be applied more than once until satisfactory results appear.

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Egéria was a 4th century A.D. nun who undertook a long journey from her homeland, the roman province of Gallaecia, to the Near East. Her itinerary, which described the segment between Mount Sinai and Constantinople, revealed the enthusiasm which graced her original decision to embark on the journey, and the determination with which she faced every stage. She kept a Diary throughout her journey. Probably, it constitutes one of the first known Travel Diaries. Her reports describe her observations and the splendor of the Christian cult sites. Her text is affectionately dedicated to her fellow nuns that remained in the West of the Empire, keeping their uniting bond strong. Our study aims to search all references to visited sites in Egéria’s text, as the information contained therein serves as a precious descriptor of their locations, spatial organization and environment. Egéria visits unique, historical sites, which will influence her writing style. She is, in fact, a pilgrim to a recently created historical site, The Holy Land. Egéria lived during a fundamental historical and artistic Framework, that of the architectural forms of expression of the First Christianity. Her words can be translated into images, as a partitions script, a visualization of lights and ambiences, and a testimonial of places that no longer exist. We hope to see, in Egéria’s written work, the images she observed, for her words are images. We expect a complementary approach among the research methods given by Archeology, composed by Architecture and explained by the sensible text from Egéria’s journey - a religious and artistic journey written from a powerful feminine point of view.