Automatic learning for the classification of chemical reactions and in statistical thermodynamics

This Thesis describes the application of automatic learning methods for a) the classification of organic and metabolic reactions, and b) the mapping of Potential Energy Surfaces(PES). The classification of reactions was approached with two distinct methodologies: a representation of chemical reactions based on NMR data, and a representation of chemical reactions from the reaction equation based on the physico-chemical and topological features of chemical bonds. NMR-based classification of photochemical and enzymatic reactions. Photochemical and metabolic reactions were classified by Kohonen Self-Organizing Maps (Kohonen SOMs) and Random Forests (RFs) taking as input the difference between the 1H NMR spectra of the products and the reactants. The development of such a representation can be applied in automatic analysis of changes in the 1H NMR spectrum of a mixture and their interpretation in terms of the chemical reactions taking place. Examples of possible applications are the monitoring of reaction processes, evaluation of the stability of chemicals, or even the interpretation of metabonomic data. A Kohonen SOM trained with a data set of metabolic reactions catalysed by transferases was able to correctly classify 75% of an independent test set in terms of the EC number subclass. Random Forests improved the correct predictions to 79%. With photochemical reactions classified into 7 groups, an independent test set was classified with 86-93% accuracy. The data set of photochemical reactions was also used to simulate mixtures with two reactions occurring simultaneously. Kohonen SOMs and Feed-Forward Neural Networks (FFNNs) were trained to classify the reactions occurring in a mixture based on the 1H NMR spectra of the products and reactants. Kohonen SOMs allowed the correct assignment of 53-63% of the mixtures (in a test set). Counter-Propagation Neural Networks (CPNNs) gave origin to similar results. The use of supervised learning techniques allowed an improvement in the results. They were improved to 77% of correct assignments when an ensemble of ten FFNNs were used and to 80% when Random Forests were used. This study was performed with NMR data simulated from the molecular structure by the SPINUS program. In the design of one test set, simulated data was combined with experimental data. The results support the proposal of linking databases of chemical reactions to experimental or simulated NMR data for automatic classification of reactions and mixtures of reactions. Genome-scale classification of enzymatic reactions from their reaction equation. The MOLMAP descriptor relies on a Kohonen SOM that defines types of bonds on the basis of their physico-chemical and topological properties. The MOLMAP descriptor of a molecule represents the types of bonds available in that molecule. The MOLMAP descriptor of a reaction is defined as the difference between the MOLMAPs of the products and the reactants, and numerically encodes the pattern of bonds that are broken, changed, and made during a chemical reaction. The automatic perception of chemical similarities between metabolic reactions is required for a variety of applications ranging from the computer validation of classification systems, genome-scale reconstruction (or comparison) of metabolic pathways, to the classification of enzymatic mechanisms. Catalytic functions of proteins are generally described by the EC numbers that are simultaneously employed as identifiers of reactions, enzymes, and enzyme genes, thus linking metabolic and genomic information. Different methods should be available to automatically compare metabolic reactions and for the automatic assignment of EC numbers to reactions still not officially classified. In this study, the genome-scale data set of enzymatic reactions available in the KEGG database was encoded by the MOLMAP descriptors, and was submitted to Kohonen SOMs to compare the resulting map with the official EC number classification, to explore the possibility of predicting EC numbers from the reaction equation, and to assess the internal consistency of the EC classification at the class level. A general agreement with the EC classification was observed, i.e. a relationship between the similarity of MOLMAPs and the similarity of EC numbers. At the same time, MOLMAPs were able to discriminate between EC sub-subclasses. EC numbers could be assigned at the class, subclass, and sub-subclass levels with accuracies up to 92%, 80%, and 70% for independent test sets. The correspondence between chemical similarity of metabolic reactions and their MOLMAP descriptors was applied to the identification of a number of reactions mapped into the same neuron but belonging to different EC classes, which demonstrated the ability of the MOLMAP/SOM approach to verify the internal consistency of classifications in databases of metabolic reactions. RFs were also used to assign the four levels of the EC hierarchy from the reaction equation. EC numbers were correctly assigned in 95%, 90%, 85% and 86% of the cases (for independent test sets) at the class, subclass, sub-subclass and full EC number level,respectively. Experiments for the classification of reactions from the main reactants and products were performed with RFs - EC numbers were assigned at the class, subclass and sub-subclass level with accuracies of 78%, 74% and 63%, respectively. In the course of the experiments with metabolic reactions we suggested that the MOLMAP / SOM concept could be extended to the representation of other levels of metabolic information such as metabolic pathways. Following the MOLMAP idea, the pattern of neurons activated by the reactions of a metabolic pathway is a representation of the reactions involved in that pathway - a descriptor of the metabolic pathway. This reasoning enabled the comparison of different pathways, the automatic classification of pathways, and a classification of organisms based on their biochemical machinery. The three levels of classification (from bonds to metabolic pathways) allowed to map and perceive chemical similarities between metabolic pathways even for pathways of different types of metabolism and pathways that do not share similarities in terms of EC numbers. Mapping of PES by neural networks (NNs). In a first series of experiments, ensembles of Feed-Forward NNs (EnsFFNNs) and Associative Neural Networks (ASNNs) were trained to reproduce PES represented by the Lennard-Jones (LJ) analytical potential function. The accuracy of the method was assessed by comparing the results of molecular dynamics simulations (thermal, structural, and dynamic properties) obtained from the NNs-PES and from the LJ function. The results indicated that for LJ-type potentials, NNs can be trained to generate accurate PES to be used in molecular simulations. EnsFFNNs and ASNNs gave better results than single FFNNs. A remarkable ability of the NNs models to interpolate between distant curves and accurately reproduce potentials to be used in molecular simulations is shown. The purpose of the first study was to systematically analyse the accuracy of different NNs. Our main motivation, however, is reflected in the next study: the mapping of multidimensional PES by NNs to simulate, by Molecular Dynamics or Monte Carlo, the adsorption and self-assembly of solvated organic molecules on noble-metal electrodes. Indeed, for such complex and heterogeneous systems the development of suitable analytical functions that fit quantum mechanical interaction energies is a non-trivial or even impossible task. The data consisted of energy values, from Density Functional Theory (DFT) calculations, at different distances, for several molecular orientations and three electrode adsorption sites. The results indicate that NNs require a data set large enough to cover well the diversity of possible interaction sites, distances, and orientations. NNs trained with such data sets can perform equally well or even better than analytical functions. Therefore, they can be used in molecular simulations, particularly for the ethanol/Au (111) interface which is the case studied in the present Thesis. Once properly trained, the networks are able to produce, as output, any required number of energy points for accurate interpolations.

A Classificação Internacional de Funcionalidade, Incapacidade e Saúde : um modelo multidimensional e multideterminado da funcionalidade em idosos assistidos na Rede

RESUMO: Os estudos sobre a funcionalidade da população idosa têm uma representação importante naquilo que é o atual conhecimento da demografia do mundo. Portugal posiciona-se e perspetiva-se como pertencendo aos países mais envelhecidos, possuindo uma rede de cuidados pós-agudos – a Rede Nacional de Cuidados Continuados Integrados (RNCCI)– que assiste uma parcela importante dessa população. Os aspetos conceptuais da funcionalidade de acordo com a OMS e operacionalizados pela Classificação Internacional de Funcionalidade (CIF), não mereceram até agora suficiente aplicabilidade no nosso país, inviabilizando a possibilidade de oferecermos contributos para a sua operacionalização. Da mesma forma, também os Core Sets da Classificação não têm sido sujeitos a processos de validação que contemplem amostras portuguesas, mantendo-se desconhecimento da especificidade dos fatores contextuais na nossa população. O presente estudo tem como objetivos conhecer a evolução da funcionalidade dos idosos assistidos na RNCCI na região do Algarve nas unidades de convalescença e média duração, validar o Core Set Geriátrico da OMS e propor uma versão abreviada da sua modalidade abrangente, no contexto destes cuidados. A amostra constituída por 451 idosos, dos quais 62,1% eram mulheres, revelou na pré-morbilidade níveis favoráveis de funcionalidade, com exceção para as Atividades Domésticas. Contudo, os mais idosos (≥ 85 anos), os indivíduos sem escolaridade, as mulheres e os viúvos/solteiros apresentaram mais casos desfavoráveis quando comparados com os seus pares. Na evolução da funcionalidade observámos melhorias significativas em todos os domínios avaliados, com diferenças relativamente à idade e à escolaridade; apesar dos resultados positivos os mais idosos e os indivíduos sem escolaridade apresentaram níveis inferiores de evolução. No entanto, a funcionalidade alcançada revelou ficar com resultados significativamente inferiores na comparação com aquela que os indivíduos possuíam na pré-morbilidade. Os modelos de regressão revelaram que as Funções Mentais, a Perceção do Estado de Saúde e a atividade Usar o Telefone, foram as variáveis que melhor explicaram os outcomes da funcionalidade alcançada. A validação do Core Set Geriátrico foi possível na maioria das categorias, sendo que foi no componente das Funções do Corpo onde esse processo revelou maior fragilidade. As Funções Neuromusculoesqueléticas e Relacionadas com o Movimento foram aquelas que registaram em ambos os momentos avaliativos frequências mais elevadas de deficiência, enquanto no componente Atividades & Participação isso ocorreu na atividade Utilização dos Movimentos Finos da Mão. Os capítulos Apoios e Relacionamentos e Atitudes foram considerados os Fatores Ambientais mais Facilitadores mas também com maior impacto Barreira. A proposta para o Core Set Geriátrico Abreviado resultou das categorias independentes que explicaram os modelos da funcionalidade alcançada e cujo resultado engloba um conjunto de 27 categorias, com um enfoque importante no componente Atividades/Participação de onde se destacam os domínios da Mobilidade e dos Auto Cuidados. A funcionalidade dos indivíduos e das populações deve ser considerada uma variável incontornável da Saúde Pública, cuja avaliação deve refletir uma abordagem biopsicossocial, apoiada na Classificação Internacional de Funcionalidade. A operacionalização da Classificação a partir dos Core Sets necessita de pesquisa mais aprofundada relativamente às caraterísticas psicométricas dos seus qualificadores e dos seus processos de validação.-----------ABSTRACT: The studies about the functioning of the elderly play an important role on what the present knowledge of the demography in the world is. Portugal figures high on the most aged countries, having a network of post-acute care - the National Network of Integrated Continuous Care (RNCCI) - which assists a large part of that population. The conceptual aspects of functioning according to WHO and operated by the International Classification of Functioning (ICF), have been insufficiently addressed concerning its adequate applicability in our country, hindering the contributions of its operation. In the same way, also the Core Sets of the Classification have not been subjected to validation procedures that include portuguese samples, keeping the unawareness of specificity of the contextual factors in our population. The objectives of the present study were to know the evolution of the functioning of the elderly assisted in the RNCCI in the Algarve region in units of convalescence and average duration, validate the WHO Geriatric Core Set and propose an abridged version of this comprehensive core set in this healthcare context. The sample was composed by 451 elderly people, of which 62.1% were women, they showed favourable levels in functioning in the pre-morbid state, except for Domestic Activities. However, the oldest (≥ 85 years), the individuals with no education, women and widowed/ unmarried showed more unfavourable cases when compared to their peers. In the evolution of functioning we observed significant improvements in all domains assessed, with diferences with respect to age and education. In spite of positive results, the oldest and the individuals with no education showed lower levels of evolution. However, the functioning achieved showed significantly lower results when compared to the those observed in pre-morbidity state. Regression models reveal that Mental Functions, the Perceived Health Status and the Use of the Phone activity, were the variables that better explain the functioning of the outcomes achieved. The validation of the Geriatric Core Set of ICF was possible in most categories, and Body Functions was the component where this process showed greatest weakness. Neuromusculoskeletal and Movement-Related Functions experienced in both evaluation times with higher rates of disability, while in the Activities & Participation component this occurred in the Fine Hand Use activity. The Support and Relationships and Attitudes chapters were considered the Environmental Factors most Facilitators but also with greater impact Barrier. The proposal for the Brief Geriatric Core Set has resulted from the independent categories that explained the regression models of functioning and includes a set of 27 categories, with na important emphasis on Activities & Participation component where we can highlight the areas of Mobility and Self Care domains. The functioning of individuals and populations should be considered as an unavoidable variable of Public Health, of which the assessment should reflect a biopsychosocial approach, based on the International Classification of Functioning. The operationalization of the Classification from the Core Sets requires further research regarding the psychometric characteristics of their qualifiers and their validation procedure.

Mental health care assessed based on structure, process and outcome : a retrospective cohort study

RESUMO: As doenças mentais são comuns, universais e associadas a uma significativa sobrecarga pessoal, familiar, social e económica. Os Serviços de Saúde Mental devem abordar de forma adequada as necessidades dos pacientes e familiares tanto ao nível clínico como também ao nível social. O presente estudo foi realizado num período de grande transformação nos sistemas de saúde primário e de saúde mental em Portugal, num Departamento de Psiquiatria desenvolvido com base nos princípios da OMS. Os objectivos incluem a caracterização: 1) das Unidades Funcionais do Departamento; 2) dos pacientes internados pela primeira vez no internamento de agudos; 3) da utilização dos serviços nas equipas comunitárias após a alta; e 4) da avaliação de alguns dos indicadores de qualidade do departamento, com recurso ao modelo de Donabedian sobre a articulação entre a Estrutura-Processo-Resultados. Metodologia: Foi escolhido um estudo de coorte retrospectivo. Todos os pacientes internados pela primeira vez entre 2008 e 2010 foram incluídos no estudo. Os seus processos clínicos e a base de dados do hospital onde são registados todos os contactos que estes tiveram com os profissionais de saúde mental foram revistos de forma a obter dados sociodemográficos e clínicos, durante o período do estudo e após a alta. Os instrumentos utilizados foram o WHO-ICMHC (Classificação Internacional de Cuidados de Saúde Mental), para caracterizar o Departamento, o AIESMP (Avaliação Inicial de Enfermagem em Saúde Mental e Psiquiatria) para recolha dos dados sociodemográficos, e o VSSS (Escala de Satisfação com os Serviços de Verona) de forma a avaliar a satisfação dos pacientes em relação aos cuidados recebidos. A análise estatística incluiu a análise descritiva, quantitativa e qualitativa dos dados. Resultados: As Unidades Funcionais do Departamento revelaram níveis elevados de articulação e consistência com as necessidades de cuidados psiquiátricos e reabilitação psicossocial dos pacientes. Os 543 pacientes admitidos pela primeira vez eram maioritariamente (56.9%) mulheres, caucasianas (81.2%), com diagnóstico de perturbações do humor (66.3%), internadas voluntariamente (59.7%), e uma idade média de 45.1 anos. Estas eram significativamente mais velhas, mais frequentemente empregadas, casadas/coabitar e tinham uma prevalência mais elevada de perturbações do humor, comparativamente aos homens. O internamento compulsivo era mais significativo nos homens (54.7%). A taxa de abandono no pós-alta (4.2%) e a taxa de reinternamentos (2.9%) na quinzena após a alta revelaram-se inferiores aos padrões na literatura internacional. De forma global, a satisfação dos pacientes com os cuidados de saúde mental foi positiva. Conclusões: Os cuidados prestados mostraram-se eficazes, adaptados e baseados nas necessidades e problemas específicos dos pacientes. A continuidade e a abrangência de cuidados foram difundidos e mantidos ao longo do processo de cuidados. Este Departamento pode ser considerado um exemplo de como proporcionar tratamento digno e eficiente, e uma referência para futuros serviços de psiquiatria.-------------- ABSTRACT: Mental health disorders are common, universal, and associated with heavy personal, family, social and economic burden. Mental health services should be aimed at adequately addressing patients’ and families’ needs at clinical and social level. The current study was carried out at a time of great transformation in the health and mental health systems in Portugal, in a Psychiatric Department developed taking in consideration the WHO principles. The objectives included characterizing: 1) the Psychiatric Department’s different units; 2) the patients admitted for the first time to the inpatient unit; 3) their use of community mental health services after discharge; and 4) assessing some of the department’s quality indicators, with resource to Donabedian’s Structure-Process-Outcome model. Methodology: A retrospective cohort design was chosen. All the firstly admitted patients in the period between 2008 and 2010 were included in the study. Their clinical records and the hospital’s database which registers all of the contacts the patients had with the mental health professionals during the study period, were reviewed to retrieve sociodemographic and clinical data and information on follow-up. The instruments used were the WHO International Classification of Mental Health Care (ICMHC) to characterize the department, the Initial Nurses’ Assessment in Mental Health and Psychiatry (AIESMP) for patients’ sociodemographic data, and the Verona Service Satisfaction Scale (VSSS) to assess patients’ satisfaction with care received. Statistical analysis included descriptive, quantitative and qualitative analysis of the data. Results: The Department’s Functional units revealed high levels of articulation, and were consistent with patients’ needs for psychiatric care and psychosocial rehabilitation. The 543 patients firstly admitted were mainly (56.9%) female, Caucasian (81.2%), diagnosed with mood disorders (66.3%), voluntarily admitted (59.7%), and with a mean age of 45.1 years. Female patients were significantly older, more frequently employed, married/cohabiting and had a higher prevalence of mood disorders when compared to males. Involuntary admission was more significant in males (54.7%). Dropout rates during follow-up (4.2%) and readmission rates (2.9%) in the fortnight following discharge were lower than standards in international literature. Overall patients’ satisfaction with mental health care was positive. Conclusions: The care delivered was effective, adapted and based on the patients’ specific needs and problems. Continuity and comprehensiveness of care was endorsed and maintained throughout the care process. This department may be considered an example of both humane and effective treatment, and a reference for future psychiatric care.

An overview of the higher level classification of Pucciniomycotina based on combined analyses of nuclear large and small subunit rDNA sequences

Mycologia, Vol. 98, nº6

Adherence to health-related behaviors: effectiveness of implementation intentions and posthypnotic suggestion in college students

Resumo: Com base no conceito de implementação de intenções (Gollwitzer, 1993, 1999) e na teoria do contexto de resposta de Kirsch & Lynn (1997), o presente trabalho testou a eficácia de uma intervenção combinada de implementação de intenções com hipnose e sugestão pós-hipnótica na promoção da adesão a uma tarefa simples (avaliação do humor) e uma tarefa difícil (actividade física). Os participantes são estudantes universitários de uma universidade na Nova Jérsia, (N=124, Estudo 1, EUA) e em Lisboa (N=323, Estudo 2, Portugal). Em ambos os estudos os participantes foram seleccionados a partir de uma amostra mais vasta baseado num escrutínio da sua sugestibilidade hipnótica avaliada por meio da Escala de Grupo de Sugestibilidade Hipnótica de Waterloo-Stanford (WSGC): Forma C. O Estudo 1 usou um desenho factorial do tipo 2x2x3 (tipo de intenção formada x hipnose x nível de sugestionabilidade) e o Estudo 2 usou um desenho factorial do tipo 2 x 2x 2 x 4 (tipo de tarefa x tipo de intenção formada x hipnose x nível de sugestionabilidade). No Estudo 1 foi pedido aos participantes que corressem todos os dias e durante três semanas durante 5 minutos, que medissem a sua pulsação antes e depois da actividade física e que mandassem um e-mail ao experimentador, fornecendo assim uma medida comportamental e uma medida de auto-relato. Aos participantes no grupo de intenções de meta foi apenas pedido que corressem todos os dias. Aos participantes no grupo de implementação de intenções foi pedido que especificasses com exactidão quando e onde iriam correr e enviar o e-mail. Para além disso, cerca de metade dos participantes foram hipnotizados e receberam uma sugestão pós-hipnótica em que lhes foi sugerido que o pensamento de correr todos os dias lhes viria à mente sem esforço no momento apropriado. A outra metade dos participantes não recebeu qualquer sugestão hipnótica. No Estudo 2 foi seguido o mesmo procedimento, mas a cerca de metade dos participantes foi atribuída uma tarefa fácil (enviar um Adherence to health-related behaviors ix SMS com a avaliação diária do seu estado de humor naquele momento) e à outra metade da amostra foi atribuída a tarefa de exercício físico atrás descrita (tarefa difícil). Os resultados do estudo 1 mostraram uma interacção significativa entre o nível de sugestionabilidade dos participantes e a sugestão pós-hipnótica (p<.01) indicando que a administração da sugestão pós-hipnótica aumentou a adesão nos participantes muito sugestionáveis, mas baixou a adesão nos participantes pouco sugestionáveis. Não se encontraram diferenças entre os grupos que formaram intenções de meta e os que formaram implementação de intenções. No Estudo 2 os resultados indicaram que os participantes aderiram significativamente mais à tarefa fácil do que à tarefa difícil (p<.001). Os resultados não revelaram diferenças significativas entre as condições implementações de intenções, hipnose e as duas estratégias combinadas, indicando que a implementação de intenções não foi eficaz no aumento da adesão às duas tarefas propostas e não beneficiou da combinação com as sugestões pós-hipnóticas. A utilização da hipnose com sugestão pós-hipnótica significativamente reduziu a adesão a ambas as tarefas. Dado que não existiam instrumentos em Português destinados a avaliar a sugestionabilidade hipnótica, traduziu-se e adaptou-se para Português Escala de Grupo de sugestibilidade hipnótica de Waterloo-Stanford (WSGC): Forma C. A amostra Portuguesa (N=625) apresentou resultados semelhantes aos encontrados nas amostras de referência em termos do formato da distribuição dos padrões da pontuação e do índice de dificuldade dos itens. Contudo, a proporção de estudantes portugueses encontrada que pontuaram na zona superior de sugestionabilidade foi significativamente inferior à proporção de participantes na mesma zona encontrada nas amostras de referência. No sentido de lançar alguma luz sobre as razões para este resultado, inquiriu-se alguns dos participantes acerca das suas atitudes face à hipnose utilizando uma versão portuguesa da Escala de Valência de Atitudes e Crenças face à Hipnose e comparou-se com a opinião de Adherence to health-related behaviors xAbstract: On the basis of Gollwitzer’s (1993, 1999) implementation intentions’ concept, and Kirsch & Lynn’s (1997) response set theory, this dissertation tested the effectiveness of a combined intervention of implementation intentions with hypnosis with posthypnotic suggestions in enhancing adherence to a simple (mood report) and a difficult (physical activity) health-related task. Participants were enrolled in a university in New Jersey (N=124, Study 1, USA) and in two universities in Lisbon (N=323, Study 2, Portugal). In both studies participants were selected from a broader sample based on their suggestibility scores using the Waterloo-Stanford Group C (WSGC) scale of hypnotic susceptibility and then randomly assigned to the experimental groups. Study 1 used a 2x2x3 factorial design (instruction x hypnosis x level of suggestibility) and Study 2 used a 2 x 2x 2 x 4 factorial design (task x instructions x hypnosis x level of suggestibility). In Study 1 participants were asked to run in place for 5 minutes each day for a three-week period, to take their pulse rate before and after the activity, and to send a daily email report to the experimenter, thus providing both a self-report and a behavioral measure of adherence. Participants in the goal intention condition were simply asked to run in place and send the e-mail once a day. Those in the implementation intention condition were further asked to specify the exact place and time they would perform the physical activity and send the e-mail. In addition, half of the participants were given a post-hypnotic suggestion indicating that the thought of running in place would come to mind without effort at the appropriate moment. The other half did not receive a posthypnotic suggestion. Study 2 followed the same procedure, but additionally half of the participants were instructed to send a mood report by SMS (easy task) and half were assigned to the physical activity task described above (difficult task). Adherence to health-related behaviors vii Study 1 result’s showed a significant interaction between participant’s suggestibility level and posthypnotic suggestion (p<.01) indicating that posthypnotic suggestion enhanced adherence among highly suggestible participants, but lowered it among low suggestible individuals. No differences between the goal intention and the implementation intentions groups were found. In Study 2, participants adhered significantly more (p<.001) to the easy task than to the difficult task. Results did not revealed significant differences between the implementation intentions, hypnosis and the two conditions combined, indicating that implementation intentions was not enhanced by hypnosis with posthypnotic suggestion, neither was effective as single intervention in enhancing adherence to any of the tasks. Hypnosis with posthypnotic suggestion alone significantly reduced adherence to both tasks in comparison with participants that did not receive hypnosis. Since there were no instruments in Portuguese language to asses hypnotic suggestibility, the Waterloo-Stanford Group C (WSGC) scale of hypnotic susceptibility was translated and adapted to Portuguese and was used in the screening of a sample of college students from Lisbon (N=625). Results showed that the Portuguese sample has distribution shapes and difficulty patterns of hypnotic suggestibility scores similar to the reference samples, with the exception of the proportion of Portuguese students scoring in the high range of hypnotic suggestibility, that was found lower than the in reference samples. In order to shed some light on the reasons for this finding participant’s attitudes toward hypnosis were inquired using a Portuguese translation and adaptation of the Escala de Valencia de Actitudes y Creencias Hacia la Hipnosis, Versión Cliente, and compared with participants with no prior hypnosis experience (N=444). Significant differences were found between the two groups with participants without hypnosis experience scoring higher in factors indicating misconceptions and negative attitudes about hypnosis.

Unsupervised classification of remote sensing images combining Self Organizing Maps and segmentation techniques

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Risk and return: The international expansion of EDP Renováveis

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

Rehabilitation and reintegration needs of female inmates and promotion mental health in Georgian prison

RESUMO: As mulheres presas encontram-se num sistema essencialmente dirigido por e concebido para homens. As mulheres que entram na prisão geralmente vêm de ambientes marginalizados e desfavorecidos e muitas vezes têm histórias de violência e abuso físico e sexual. As mulheres presas são um grupo particularmente vulnerável, uma vez que dentro do sistema prisional as suas necessidades de saúde e higiene são muitas vezes negligenciadas. O primeiro passo para o desenvolvimento de programas e práticas sensíveis ao género é compreender as características das mulheres delinquentes e definir fatores de vida específicos que contribuem para a formação do comportamento criminoso de mulheres. Em junho de 2012 foi realizada uma investigação na única prisão feminina da Geórgia, para estudar as necessidades mentais e psicossociais das mulheres presas. O objetivo da pesquisa foi o desenvolvimento de programas de apoio pertinentes para a reabilitação, ressocialização e reintegração, e a elaboração de recomendações práticas para a gestão das prisões. Foi desenvolvido um instrumento de pesquisa (inquérito) com uma fundamentação conceptual baseada em quatro principais teorias: Teoria dos Caminhos (Pathways Theory), teoria do desenvolvimento psicológico da mulher (Theory of Women’s Psychological Development), Trauma e Teorias da Dependência (Trauma and Addiction Theories). Foram inquiridas 120 mulheres presas. Os resultados deste estudo mostram que muitas das necessidades das mulheres presas são diferentes das dos homens e requerem estratégias adaptadas às suas características e situações psicossociais específicas. A maioria das mulheres encarceradas é jovem, enérgica, pode trabalhar, tem profissão e família. As presas sofrem de problemas psicológicos e muitas vezes são rejeitadas pelas suas famílias. Uma parte substancial das mulheres presas tem múltiplos problemas de saúde física e mental. A maioria delas tem filhos e sofre com o facto das crianças estarem a crescer longe da mãe. Com base nos resultados desta investigação é possível elaborar um contexto promotor do planeamento e desenvolvimento de serviços com um enfoque de género na prisão. Na perspetiva de longo prazo, o conhecimento das necessidades básicas e a introdução de programas e serviços com necessidades específicas pertinentes irá beneficiar as presas e as suas famílias, e melhorar a eficácia do sistema de justiça criminal.----------ABSTRACT: Female inmates find themselves in a system essentially run by men for men. Women who enter prison usually come from marginalized and disadvantaged backgrounds and are often characterized by histories of violence, physical and sexual abuse. Female prisoners constitute an especially vulnerable group given their specific health and hygienic needs within the system are often neglected. The first step in developing gender-sensitive program and practice is to understand female offenders’ characteristics and the specific life factors that shape women’s patterns of offending. In June 2012 a research was carried out in the Georgian only female prison facility to assess the mental and psychosocial needs of women prisoners, aiming to develop effective support programs for their rehabilitation, re-socialization and reintegration, as well as to elaborate new recommendations concerning prison management. A survey instrument (questionnaire) was developed within a theoretical framework based on four fundamental theories: Pathways Theory, Theory of Women’s Psychological Development and Trauma and Addiction Theories. Sample size was defined to be 120 surveyed persons. The study showed that needs of incarcerated women were different from those of men, thus requiring approaches tailored to their specific psychosocial characteristics and situations. The basic population of imprisoned women consisted of young, energetic, working-age females, most often with a professional qualification. Female prisoners suffered from psychological problems and are were more likely to be rejected by their families. Most of them had children and suffered that the children were growing without mothers. A substantial proportion of women offenders had multiple physical and mental health problems. Based on the study findings a conceptual framework can be elaborated towards planning and developing gender-sensitive services in prison. In the long-term perspective, acknowledgement of baseline needs and introduction of the relevant needs-specific programs and services may benefit women prisoners as well as their families, improving the effectiveness of the criminal justice system.

The World Health Organization Multi-Professional Patient Safety Curriculum : implementation of key modules and its impact on patient safety knowledge, skills, and attitudes of medical students at the University of Algarve

ABSTRACT - Objectives: We attempted to show how the implementation of the key elements of the World Health Organization Patient Safety Curriculum Guide Multi-professional Edition in an undergraduate curriculum affected the knowledge, skills, and attitudes towards patient safety in a graduate entry Portuguese Medical School. Methods: After receiving formal recognition by the WHO as a Complementary Test Site and approval of the organizational ethics committee , the validated pre-course questionnaires measuring the knowledge, skills, and attitudes to patient safety were administered to the 2nd and3rd year students pursuing a four-year course (N = 46). The key modules of the curriculum were implemented over the academic year by employing a variety of learning strategies including expert lecturers, small group problem-based teaching sessions, and Simulation Laboratory sessions. The identical questionnaires were then administered and the impact was measured. The Curriculum Guide was evaluated as a health education tool in this context. Results: A significant number of the respondents, 47 % (n = 22), reported having received some form of prior patient safety training. The effect on Patient Safety Knowledge was assessed by using the percentage of correct pre- and post-course answers to construct 2 × 2 contingency tables and by applying Fishers’ test (two-tailed). No significant differences were detected (p < 0.05). To assess the effect of the intervention on Patient Safety skills and attitudes, the mean and standard deviation were calculated for the pre and post-course responses, and independent samples were subjected to Mann-Whitney’s test. The attitudinal survey indicated a very high baseline incidence of desirable attitudes and skills toward patient safety. Significant changes were detected (p < 0.05) regarding what should happen if an error is made (p = 0.016), the role of healthcare organizations in error reporting (p = 0.006), and the extent of medical error (p = 0.005). Conclusions: The implementation of selected modules of the WHO Patient Safety Curriculum was associated with a number of positive changes regarding patient safety skills and attitudes, with a baseline incidence of highly desirable patient safety attitudes, but no measureable change on the patient safety knowledge, at the University of Algarve Medical School. The significance of these results is discussed along with implications and suggestions for future research.

The role of s-nitrosothiols and rho-kinase 1 in glucose and lipid metabolism

RESUMO: Na sociedade contemporânea a diabetes tipo 2 e a obesidade estão a aumentar exponencialmente, representando um grave problema de saúde pública. De acordo com a IDF “A diabetes e a obesidade são o principal problema de saúde pública do século XXI’. Para além destas duas patologias, a prevalência de esteatose hepática não-alcoólica (NAFLD), entre a população obesa e diabética, é de cerca de 90%. O aumento da obesidade, diabetes e NAFLD tem uma forte correlação com o aumento do consumo de gorduras e açúcares, acompanhado de um decréscimo acentuado da actividade física. A obesidade, diabetes e NAFLD tem sido escrupolosamente investigada mas as terapêuticas disponíveis continuam a ser muito limitadas. Tendo em conta o número crescente e alarmante de obesos e diabéticos o conhecimento detalhado da patofisiologia da obesidade, diabetes e NAFLD, tendo em vista a necessidade extrema de desenvolvimento de novas estratégias terapêuticas, é da mais elevada urgência. O fígado é reconhecido como um orgão primordial no controlo da homeostase. No estado pós-prandial, o fígado converte a glucose em glicogénio e lípidos. Em contraste, no estado de jejum, o fígado promove a produção de glucose. Sistemas neuronais e hormonais, bem como o estado metabólico do fígado, controlam de forma muito precisa a alternância entre os diferentes substratos metabólicos, dependente do estado prandial. A insulina tem um papel central no controlo do metabolismo energético no fígado; se, por um lado, inibe a produção hepática de glucose e corpos cetónicos, por outro, promove a glicólise e a lipogénese. O metabolismo energético no fígado é também regulado por vários factores de transcrição e co-reguladores que, por sua vez, são regulados pela insulina, glucagina e outras hormonas metabólicas. Em conjunto, todos estes factores e reguladores vão controlar de forma muito estreita a gluconeogénese, a β-oxidação e a lipogénese, no fígado. Para além dos já conhecidos reguladores do metabolismo hepático, novas moléculas têm sido estudadas como tendo um papel fundamental na regulação do metabolismo energético no fígado. Qualquer desequilíbrio no metabolismo hepático vai contribuir para a insulino-resistência, NAFLD e diabetes tipo 2. O principal objectivo do trabalho de investigação aqui apresentado é o contributo para o estudo detalhado da patogénese da diabetes e obesidade, num contexto de dietas ricas em açúcares e gorduras, e com a perspectiva de explorar novas estratégias terapêuticas. Os objectivos específicos deste trabalho eram: primeiro, determinar se o tratamento com glutationo (GSH) e óxido nítrico (NO) era suficiente para melhorar a insulino-resistência associada ao elevado consumo de sacarose; segundo, determinar o papel da Rho-kinase 1 (ROCK1) na regulação do metabolismo hepático da glucose e dos lípidos; e terceiro, estudar o efeito do metilsulfonilmetano (MSM) em doenças metabólicas associadas à obesidade. Na primeira parte deste trabalho de investigação foram utilizados ratos Wistar machos sujeitos a uma dieta rica em sacarose (HS). Tal como esperado, estes animais apresentavam insulino-resistência e hiperinsulinémia. A dieta HS levou ao aumento dos níveis hepáticos de NO e ao decréscimo dos níveis de GSH no fígado. Em jejum, a administração intraportal de GSH e NO, a animais saudáveis promoveu um aumento significativo da sensibilidade à insulina. Também nestes animais, a administração intravenosa de S-nitrosotióis, compostos orgânicos que contém um grupo nitroso acoplado a um átomo de enxofre de um tiol, promoveu o aumento significativo da sensibilidade à insulina. Pelo contrário, em animais sujeitos à dieta HS, as doses padrão de GSH + NO e de S-nitrosotióis não conseguiram promover o aumento da sensibilidade à insulina. No entanto, ao aumentar a dose de S-nitrosotióis administrados por via intravenosa, foi possível observar o aumento da sensibilidade à insulina dependente da dose, indicando um possível papel dos S-nitrosotióis como sensibilizadores de insulina. O estudo detalhado do papel dos S-nitrosotióis na via de sinalização da insulina revelou que há um aumento da fosforilação do receptor da insulina (IR) e da proteína cinase B (Akt), sugerindo um efeito dos S-nitrosotióis nesta via de sinalização. Os resultados apresentados nesta primeira parte sugerem que os S-nitrosotióis promovem a correcta acção da insulina, podendo vir a ser importantes alvos terapêuticos. Na segunda parte deste trabalho de investigação utilizámos murganhos, com uma delecção específica da ROCK1 no fígado, e sujeitos a uma dieta rica em lípidos (HFD). Foi possível concluir que a ausência da ROCK1 no fígado previne a obesidade, melhora a sensibilidade à insulina e protege contra a esteatose hepática. A ausência de ROCK1 no fígado levou a um decréscimo significativo da expressão génica de genes associados à lipogénese, com uma diminuição acentuada do fluxo metabólico associado a esta via. Pelo contrário, a sobreexpressão de ROCK1, exclusivamente no fígado, promove a insulino-resistência e a esteatose hepática no contexto de obesidade induzida pela dieta. Para além disto, a delecção da ROCK1 no fígado de animais obesos e diabéticos, os murganhos deficientes em leptina, corroborou os dados obtidos no primeiro modelo animal, com a franca melhoria da hiperglicémia, hiperinsulinémia e esteatose hepática. Os dados que compõem esta parte do trabalho de investigação sugerem que a ROCK1 tem um papel crucial na regulação do metabolismo lipídico. Na terceira e última parte deste trabalho de investigação foi investigado o efeito do composto metilsulfunilmetano (MSM), um composto organosulfúrico naturalmente presente em plantas e utilizado também como suplemento dietético, em murganhos obesos e insulino-resistentes, por exposição a uma dieta rica em lípidos (DIO). O tratamento com MSM melhorou a insulino-resistência e protegeu contra a esteatose hepática. O conteúdo hepático em triglicéridos e colesterol também diminuíu de forma significativa nos animais DIO sujeitos ao tratamento com MSM, bem como a expressão génica associada à lipogénese. Para além disto, o tratamento com MSM levou a uma diminuição da expressão génica associada à inflamação. De realçar que o tratamento com MSM levou a uma melhoria do perfil hematopoiético destes animais, tanto na medula óssea como no sangue. Para comprovar o efeito benéfico do MSM na obesidade e insulino-resistência utilizámos murganhos deficientes no receptor da leptina, e por isso obesos e diabéticos, tendo observado um perfil semelhante ao obtido para murganhos sujeitos a uma dieta rica em lípidos e tratados com MSM. Concluímos, através dos dados recolhidos, que o MSM como suplemento pode ter efeitos benéficos na hiperinsulinémia, insulino-resistência e inflamação que caracterizam a diabetes tipo 2. Em resumo, os dados obtidos neste trabalho de investigação mostram que os S-nitrosotióis podem ter um papel importante como sensibilizadores da insulina, promovendo um aumento da sensibilidade à insulina num contexto de dietas ricas em sacarose. Para além disto, estudos in vitro, sugerem que os S-nitrosotióis regulam, especificamente, a via de sinalização da insulina. Este trabalho teve também como objectivo o estudo da ROCK1 como regulador do metabolismo da glucose e dos lípidos no fígado. Através do estudo de animais com uma delecção ou uma sobreexpressão da ROCK1 no fígado mostrou-se que esta tem um papel crucial na patogénese da obesidade e diabetes tipo 2, especificamente através do controlo da lipogénese de novo. Finalmente, foi também objectivo deste trabalho, explorar o efeito do MSM em animais DIO e deficientes em leptina. O tratamento com MSM protege de forma evidente contra a obesidade e insulino-resistência, com especial enfâse para a capacidade que esta molécula demonstrou ter na protecção contra a inflamação. Em conjunto os vários estudos aqui apresentados mostram que tanto os S-nitrosotióis como a ROCK1 têm um papel na patogénese da obesidade e diabetes tipo 2 e que a utilização de MSM como suplemento às terapêuticas convencionais pode ter um papel no tratamentos de doenças metabólicas.-------------------------------ABSTRACT: In modern western societies type 2 diabetes and obesity are increasing exponentially, representing a somber public concern. According to the International Diabetes Federation (IDF) ‘Diabetes and Obesity are the biggest public health challenges of the 21st century’. Aside from these the prevalence of nonalcoholic fatty liver disease (NAFLD), among the diabetic and obese population, is as high as 90%. It is now well established that the increase in obesity, diabetes and NAFLD strongly correlates with an increase in fat and sugar intake in our diet, alongside physical inactivity. The pathogenesis of obesity, diabetes and NAFLD has been thoroughly studied but the treatment options available are still narrow. Considering the alarming number in the obese and diabetic population the complete understanding of the pathogenesis, keeping in mind that new therapeutic strategies need to be attained, is of the highest urgency. The liver has been well established as a fundamental organ in regulating whole-body homeostasis. In the fed state the liver converts the glucose into glycogen and lipids. Conversely, in the fasted state, glucose will be produced in the liver. Neuronal and hormonal systems, as well as the hepatic metabolic states, tightly control the fast to fed switch in metabolic fuels. Insulin has a central role in controlling hepatic energy metabolism, by suppressing glucose production and ketogenesis, while stimulating glycolysis and lipogenesis. Liver energy metabolism is also regulated by various transcription factors and coregulators that are, in turn, regulated by insulin, glucagon and other metabolic hormones. Together, these regulators will act to control gluconeogenesis, β-oxidation and lipogenesis in the liver. Aside from the well-established regulators of liver energy metabolism new molecules are being studied has having a role in regulating hepatic metabolism. Any imbalance in the liver energy metabolism is a major contributor to insulin resistance, NAFLD and type 2 diabetes. The overall goal of this research work was to contribute to the understanding of the pathogenesis of diabetes and obesity, on a setting of high-sucrose and high-fat diets, and to explore potential therapeutic options. The specific aims were: first, to determine if treatment with glutathione (GSH) and nitric oxide (NO) was sufficient to ameliorate insulin resistance induced by high-sucrose feeding; second, to determine the physiological role of rho-kinase 1 (ROCK1) in regulating hepatic and lipid metabolism; and third, to study the effect of methylsulfonylmethane (MSM) on obesity-linked metabolic disorders. In the first part of this research work we used male Wistar rats fed a high-sucrose (HS) diet. As expected, rats fed a HS diet were insulin resistant and hyperinsulinemic. HS feeding increased hepatic levels of NO, while decreasing GSH. In fasted healthy animals administration of both GSH and NO, to the liver, was able to increase insulin sensitivity. Intravenous administration of S-nitrosothiols, organic compounds containing a nitroso group attached to the sulfur atom of a thiol, in fasted control animals also increased insulin sensitivity. Under HS feeding the standard doses of GSH + NO and S-nitrosothiols were unable to promote an increase in insulin sensitivity. However, the intravenous administration of increasing concentrations of S-nitrosothiols was able to restore insulin sensitivity, suggesting that S-nitrosothiols have an insulin sensitizing effect. Investigation of the effect of S-nitrosothiols on the insulin signaling pathway showed increased phosphorylation of the insulin receptor (IR) and protein kinase B (Akt), suggesting that S-nitrosothiols may have an effect on the insulin signaling pathway. Together, these data showed that S-nitrosothiols promote normal insulin action, suggesting that they may act as potential pharmacological tools. In the second part of this research work we used liver-specific ROCK1 knockout mice fed a high-fat (HF) diet. Liver-specific deletion of ROCK1 prevented obesity, improved insulin sensitivity and protected against hepatic steatosis. Deficiency of ROCK1 in the liver caused a significant decrease in the gene expression of lipogenesis associated gene, ultimately leading to decreased lipogenesis. Contrariwise, ROCK1 overexpression in the liver promoted insulin resistance and hepatic steatosis in diet-induced obesity. Furthermore, liver-specific deletion of ROCK1 in obese and diabetic mice, the leptin-deficient mice, improved the typical hyperglycemia, hyperinsulinemia and liver steatosis. Together, these data identify ROCK1 as a crucial regulator of lipid metabolism. In the third and final part of this research work we investigated the effect of MSM, an organosulfur compound naturally found in plants and used as a dietary supplement, on diet-induced obese (DIO) and insulin resistant mice. MSM treatment ameliorated insulin resistance and protected against hepatosteatosis. Hepatic content in triglycerides and cholesterol was significantly decreased by MSM treatment, as well as lipogenesis associated gene expression. Furthermore, MSM treated mice had decreased inflammation associated gene expression in the liver. Importantly, FACS analysis showed that MSM treatment rescued the inflammatory hematopoietic phenotype of DIO mice in the bone marrow and the peripheral blood. Moreover, MSM treatment of the obese and diabetic mice, the leptin-deficient mice, resulted in similar effects as the ones observed for DIO mice. Collectively, these data suggest that MSM supplementation has a beneficial effect on hyperinsulinemia, insulin resistance and inflammation, which are often found in type 2 diabetes. In conclusion, this research work showed that S-nitrosothiols may play a role as insulin sensitizers, restoring insulin sensitivity in a setting of high-sucrose induced insulin resistance. Furthermore, in vitro studies suggest that S-nitrosothiols specifically regulate the insulin signaling pathway. This research work also investigated the role of hepatic ROCK1 in regulation of glucose and lipid metabolism. Using liver-specific ROCK 1 knockout and ROCK1 overexpressing mice it was shown that ROCK1 plays a role in the pathogenesis of obesity and type 2 diabetes, specifically through regulation of the de novo lipogenesis pathway. Finally, this research work aimed to explore the effect of MSM in DIO and leptin receptor-deficient mice. MSM strongly protects against obesity and insulin resistance, moreover showed a robust ability to decrease inflammation. Together, the individual studies that compose this dissertation showed that S-nitrosothiols and ROCK1 play a role in the pathogenesis of obesity and type 2 diabetes and that MSM supplementation may have a role in the treatment of metabolic disorders.