Conception and first results of a cross-sectional national study on the demography, disease characteristics and socioeconomics status of the Portuguese patients with multiple sclerosis : the PORT-MS study

RESUMO: Introdução e objetivos: Não existia um estudo multicêntrico que descrevesse as características dos doentes com EM, da doença em si, ou do seu tratamento, em Portugal.Métodos: Doentes McDonald 2010 positivos foram sequencialmente recrutados em 7 centros entre Maio e Novembro 2014. Aplicou-se um Caderno de Recolha de Dados incidindo na demografia, doença, educação e emprego (estudo PORT-MS). Resultados: 561 doentes incluídos. Primeiros sintomas aos 30,2±10,5 anos (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnóstico 3,2±5,3 anos depois (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); tempo de doença após diagnóstico 9,4±7,2 anos (semelhante RRMS no diagnóstico e PPMS); idade atual 42,9±12,4 anos (grupo RRMS no diagnóstico 42,0±12,1, PPMS 52,5±11,3, p<0,001); EDSS atual 2,5 (RRMS 2.0, PPMS 6.0); proporção feminino:masculino é 2,5:1 (RRMS semelhante, PPMS 1,1:1, p<0,05); no diagnóstico RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% dos RRMS encontravam-se em SP na inclusão (nomeadamente os com mais idade no diagnóstico e/ou atualidade ou tempo de doença mais prolongado). PPMS mais frequente em doentes diagnosticados mais tardiamente (p<0,001), onde aumenta também ligeiramente a proporção de mulheres na PPMS. Nas últimas décadas: novos casos mostram estabilidade na proporção de géneros e tipos de doença; idade nos primeiros sintomas e no diagnóstico aumentou ligeiramente, tempo entre eles diminuiu ligeiramente. Proporção sob DMT (Maio 2014): global 84,5%; atualmente RRMS 90,4%; SPMS 70,8%; PPMS 36,8%; progressivas agregadas 48%. Tipo de DMT, amostra global: interferões 56,5%, GA 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Global: economicamente ativos 61,5%, desemprego 13,5%, 74,1% dos não activos estão reformados por doença. Gravidezes após diagnóstico em 15% mulheres. Casos com história familiar positiva 7,8%. Discussão e conclusões: Incluída cerca de 10% da população portuguesa. Resultados congruentes com dados internacionais. Elevada proporção sob DMT, mesmo EDSS alto e formas progressivas. Terapêuticas de segunda linha sub representadas. Doentes jovens e com doença ligeira com vida económica ativa; restantes essencialmente reformados por doença.---------------- ABSTRACT : Background/aims: In Portugal, there wasn’t a multicentric study on the general characteristics (demography, disease milestones, DMT, socioeconomic status) of Multiple Sclerosis patients. Methods: Patients fulfilling McDonald 2010 criteria were sequentially recruited from May to November 2014 in 7 centers and data was systematically collected. Results: 561 patients included. First symptoms occurred at 30,2±10,5 years-old (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnosis 3,2±5,3 years later (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); 9,4±7,2 years elapsed since diagnosis (similar for those is RRMS at diagnosis and PPMS); current age 42,9±12,4 years-old (group RRMS at diagnosis 42,0±12,1, PPMS 52,5±11,3, p<0,001); current EDSS 2,5 (RRMS 2.0, PPMS 6.0); females to males 2,5:1 (RRMS similar, PPMS 1,1:1, p<0,05); at diagnosis RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% of RRMS reached SP at inclusion (those older at diagnosis, in actuality, or with longer follow-up). PPMS more frequente in patients diagnosed at older ages (p<0,001), also slight increase in females. Along the last decades: new cases have showed stable proportions of gender and disease types; age at first symptoms and diagnosis slightly increased, time between them slightly decreased. Proportion on DMT (May 2014): 84,5% of all; 90,4% of currently in RRMS; 70,8% of SPMS; 36,8% of PPMS; 48% of progressive forms together. Type of DMT, all patients: interferons 56,5%, Glatiramer Acetate 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Economically active 61,5% of all, unemployment 13,5%, 74,1% of non-active are retired due to disease. Females pregnant after diagnosis 15%. Positive family cases in 7,8%. Discussion/Conclusions: 10% of the national MS population collected. Data generally consistente with international reports. Proportion under DMT relatively high in all disease types, but second line therapies underrepresented. Young patients with mild disease have an active economic life. Those not active are essentially retired due to disease.

Classificação Internacional de Funcionalidade, Incapacidade e Saúde : uma dimensão do neurodesenvolvimento

RESUMO: Objetivo Principal • Determinar a consistência da utilização dos instrumentos de avaliação da capacidade intelectual – escalas de Griffiths e WISC III – no enquadramento dos domínios e dos qualificadores da CIF-CJ, restrita às funções mentais do corpo. Objetivo secundário: • Estudar a efetividade e concordância inter-observador da aplicação da CIF, com base na leitura dos dados obtidos em avaliação efetuada com os instrumentos referidos, por duas observadoras independentes, em contexto de articulação saúde, respetivamente educação e segurança social Métodos • Estudo observacional, descritivo, transversal e prospetivo. • Foi estudada uma amostra de conveniência 355 crianças, num período de três anos (Maio de 2010 a 30 de Abril de 2013), com patologia da área da pediatria do neurodesenvolvimento (total de 4000 consultas) no Centro de Desenvolvimento (CD) do Hospital de Dona Estefânia (HDE), Centro Hospitalar de Lisboa Central, EPE (CHLC, EPE). • Critérios de inclusão: crianças de ambos os sexos, observadas no CD do HDE, CHLC (primeiras consultas e consultas de reavaliação) com idade ≥12 meses e ≤17 anos e incapacidade intelectual definida de acordo com os critérios da DSM-IV-TR, DSM 5 e CID-10. • Critérios de exclusão: crianças com autismo, perturbações específicas da linguagem, hiperatividade, défice de atenção e concentração, défices sensoriais congénitos (baixa visão e ou audição), ou com outros diagnósticos de perturbações de neurodesenvolvimento. • O estudo teve duas fases: na primeira, a investigadora principal colheu ou atualizou a história clínica, observou clinicamente as crianças solicitando os exames complementares considerados necessários e foi efetuada avaliação psicológica com os instrumentos adiante descritos, pela mesma psicóloga clínica, devidamente credenciada, e com larga experiência nas escalas referidas. Com base nos dados colhidos, quer por observação direta, quer através dos resultados das escalas Griffiths e WISC – III, a investigadora aplicou a CIF-CJ, circunscrita aos domínios e funções (variáveis): 1. FUNÇÕESMENTAIS GLOBAIS (b110- Funções da consciência, b114- Funções da orientação no espaço e no tempo, b117 – Funções intelectuais, b122- Funções psicossociais globais, b125- Funções intrapessoais, b126- Funções do temperamento e da personalidade); 2.FUNÇÕES MENTAIS ESPECÌFICAS (b140- funções da atenção, b147- Funções psicomotoras, b152- Funções emocionais, b156- Funções da perceção, b163- Funções cognitivas básicas, b164- Funções cognitivas de nível superior, b167- Funções mentais da linguagem 3. FUNÇÕES DA VOZ E DA FALA (b320- Funções da articulação, b330- Funções da fluência e do ritmo da fala). Numa segunda fase, foi solicitada a colaboração de duas co-investigadoras, com formação específica nas escalas utilizadas e na CIF-CJ, a aplicação da CIF nos mesmos domínios e funções. Estas observadoras não efetuaram observações diretas das crianças envolvidas. • Para efetuar a análise estatística e analisar a relação entre os qualificadores (0 a 4) das variáveis da CIF em estudo (b117, b122, b147, b163, b164, b167, b320 e b330) e os instrumentos psicométricos (escalas de Griffiths e WISC III), que constitui a primeira parte do estudo, recorreu-se à técnica estatística não paramétrica do coeficiente de correlação de Spearman, que quantifica a intensidade e sinal da eventual correlação existente entre as variáveis em estudo. • Para determinar as correlações referentes à segunda parte do estudo, foram utilizados os programas SPSS®, (IBM SPSS Statistics) e Statistica® (StatSoft, Inc., 2011). STATISTICA (data analysis software system, version 10. www.statsoft.com.), tendo-se dado preferência aos gráficos deste último. Resultados 1. Observou-se um predomínio do sexo masculino (relação de 1:1,9); relativamente à idade no momento de avaliação, 242 crianças (68,1%) tinham entre zero e seis anos e, dentro destas, a maioria (189) situava-se entre os três e os seis anos. 2. De acordo com a DSM-IV e DSM-5, 261 (73,4%) crianças apresentavam incapacidade intelectual ligeira. 3. A avaliação da competência intelectual pelas escalas de Ruth Griffiths e WISC III (QI), revelaram correlação negativa predominantemente forte e muito forte (índice de Spearman) com os qualificadores das funções do corpo estudadas (funções mentais, mentais específicas e da voz). Os resultados obtidos pela co-investigadora A foram sobreponíveis aos da investigadora principal. Os resultados obtidos pela co-investigadora B revelaram correlação negativa moderada e forte, correlação inferior à da investigadora principal; Conclusões Os resultados permitem inferir que as escalas de Ruth Griffiths e WISC-III são instrumentos adequados para caracterizar a incapacidade intelectual na CIF-CJ; a concordância inter-observador, moderada, nos qualificadores atribuídos nas funções em análise pela investigadora e co-investigadoras, permite concluir que as escalas de Ruth Griffiths e WISC IIIl são bons instrumentos para caracterizar os qualificadores nos domínios e funções estudados, por diferentes grupos de profissionais ligados à infância. Subsistem dificuldades na diferenciação entre qualificadores, designadamente entre os qualificadores 1 e 2, o que tem necessariamente implicações na elegibilidade das crianças para os apoios preconizados pelo DL 3/2008. ------------------------ ABSTRACT: Main objective • To determine the consistency of the use of assessment tools for intellectual ability - Griffiths and WISC III scales - in the context of domains and qualifiers for the ICF-CY, restricted to the mental functions of the body. Secondary objective • Studying the effectiveness and inter-observer concordance concerning the application of the ICF, based on the data recovered from the assessment made with the mentioned instruments, carried out by two independent observers including their perspective on health, education and social security. Methods • Observational, descriptive, cross-sectional and prospective study. • A convenience sample of 355 children was studied over a period of three years (May 2010 to April 2013), with a pathology in the area of pediatric neurodevelopment – intellectual disability (total of 4000 consultations, including first consultations and revaluations) were observed in the Development Centre (CD) in Hospital de Dona Estefânia (HDE), Centro Hospitalar de Lisboa Central, EPE (CHLC). • Inclusion criteria: children of both sexes aged ≥12 months and years ≤17 and intellectual disability defined according to the criteria in the DSM-IV-TR, DSM 5 and ICD-10. • Exclusion criteria: children with autism; specific language impairment, hyperactivity; attention deficit disorder; severe birth sensory deficits (eg, impaired vision and hearing); amongst other diagnoses for neurodevelopmental disorders. • The study was conducted in two phases: in the first phase the principal investigator collected or updated medical history, clinically observed children requesting additional investigations if she deemed necessary. Psychological evaluation was performed by a single, duly licensed clinical psychologist with extensive experience in the referred scales using the instruments described below. Based on data collected, either by direct observation or through the results of Griffiths scales and WISC - III, the researcher applied the ICF-CY confined to the following fields and functions (variables): 1. GLOBAL MENTAL FUNCTIONS (b110- functions of consciousness, b114- Functions referring to space and time orientation , b117 - intellectual functions, b122- global psychosocial functions, b125- intrapersonal functions, b126- functions related to temperament and personality); 2. SPECIFIC MENTAL FUNCTIONS ( b140- attention functions, b147-psychomotor functions, b152- Emotional functions, b156- perception functions, b163- basic cognitive functions and cognitive functions b164- top level b167- language related mental functions. ) 3. VOICE AND SPEECH FUNCTIONS (b320-articulation functions, b330- fluency and rhythm of speech functions). • In the second phase, two co-investigators, with specific training on the scales used and the ICF-CY have applied the ICF in the domains and functions mentioned above, based on the scales results. These co-investigators did not make any direct observation of the studied children. • To perform the statistical analysis and analyze the relationship between the qualifiers (0-4) of the variables in the ICF study (b117, b122, b147, B163, B164, b167, b320 and B330) and psychometric instruments (Griffiths scale and WISC III), which is the first part of the study, the statistical technique of non-parametric Spearman correlation coefficient was used, which quantifies the strength and sign of the possible correlation between the variables under study. • For submission of correlations related to the second part of the study, SPSS (IBM SPSS) and Statistica (StatSoft, Inc., 2011) programs were used. STATISTICA (data analysis software system, version 10 www.statsoft.com.). Preference was given to graphs computed in Statistica. Results • Male predominated (ratio of 1: 1.9). 242 children (68.1% of the sample) were aged between zero and six years and, among these, the majority (189) was aged largest number between three and six years. • According to the DSM-IV and DSM-5, 261 (73.4%) children had mild intellectual disability. The correlation between the assessment of intellectual competence by Ruth Griffiths scales and WISC III (QI), was predominantly negative strong and very strong correlation with the qualifiers of body functions studied (specific mental functions, mental and voice functions using Spearman index). The levels of correlation obtained by the co-investigatores were in agreeance with the results from the principal investigator. The results obtained by co-investigator B showed moderate to strong negative correlation, levels that were lower to the those registered by the principal investigator; Conclusions These results indicate that Ruth Griffiths and WISC-III scales are adequate tools to characterize intellectual disability in the ICF-CY; moderate inter-observer agreement in the qualifiers assigned the functions under analysis by the researcher and co-researchers, shows that the scales are also good tools to measure CIF qualifyers by diferent technicians with different professional orientations, related to children. However, there are still difficulties in differentiating qualifiers, namely between qualifiers 1/2 and 3/4, which necessarily has implications for the eligibility of children for the state support advocated by the Portuguese Decret Law 3/2008.

Strengthening to seismic action of reinforced columns with rectangular cross-section

The first part of this research work regards the assessment of the mathematical modelling of reinforced concrete columns confined with carbon fibre (CFRP) sheets under axial loading. The purpose was to evaluate existing analytical models, contribute to possible improvements and choose the best model(s) to be part of a new model for the prediction of the behaviour of confined columns under bending and compression. For circular columns, a wide group of authors have proposed several models specific for FRP-confined concrete. The analysis of some of the existing models was carried out by comparing these with several tested columns. Although several models predict fairly the peak load only few can properly estimate the load-strain and dilation behaviour of the columns. Square columns confined with CFRP show a more complex interpretation of their behaviour. Accordingly, the analysis of two experimental programs was carried out to propose new modelling equations for the whole behaviour of columns. The modelling results show that the analytical curves are in general agreement with the presented experimental curves for a wide range of dimensions. An analysis similar to the one done for circular columns was this turn carried out for square columns. Few models can fairly estimate the whole behaviour of the columns and with less accuracy at all levels when compared with circular columns. The second part of this study includes seven experimental tests carried out on reinforced concrete rectangular columns with rounded corners, different damage condition and with confinement and longitudinal strengthening systems. It was concluded that the use of CFRP confinement is viable and of effective performance enhancement alone and combined with other techniques, maintaining a good ductile behaviour for established threshold displacements. As regards the use of external longitudinal strengthening combined with CFRP confinement, this system is effective for the performance enhancement and viable in terms of execution. The load capacity was increased significantly, preserving also in this case a good ductile behaviour for threshold displacements. As to the numerical nonlinear modelling of the tested columns, the results show a variation of the peak load of 1% to 10% compared with tests results. The good results are partly due to the inclusion of the concrete constitutive model by Mander et al. modified by Faustino, Chastre & Paula taking into account the confinement effect. Despite the reasonable approximation to tests results, the modelling results showed higher unloading, which leads to an overestimate dissipated energy and residualdisplacement.

Semantics bias in cross-national comparative analyses : Is it good or bad to have "fair" health?

The Health Behavior in School-aged Children is a cross-national study collecting data on social and health indicators on adolescents in 43 countries. The study provides comparable data on health behaviors and health outcomes through the use of a common protocol, which have been a back bone of the study sine its initiation in 1983. Recent years, researchers within the study have noticed a questionable comparability on the widely used item on self-rated health. One of the four response categories to the item "Would you say your health is….?" showed particular variation, as the response category "Fair" varied from 20 % in Latvia and Moldova to 3-4 % in Bulgaria and Macedonia. A qualitative mini-survey of the back-translations showed that the response category "Fair" had a negative slant in 25 countries, a positive slant in 10 countries and was considered neutral in 9 countries. This finding indicates that there are what may be called semantic issues affecting comparability in international studies, since the same original word (in an English original) is interpreted differently across countries and cultures. The paper test and discuss a few possible explanations to this, however, only leaving to future studies to hold a cautious approach to international comparisons if working with the self-rated health item with four response categories.

Impact of oral health on health-related quality of life : A cross-sectional study

Background: Despite the consensus regarding the existence of a relationship between “impacts on oral health” and “health-related quality of life”, this relationship, considering the latent nature of these variables, is still poorly investigated. Thus, we performed this study in order to determine the magnitude of the impacts of oral health, demographic and symptom/clinical variables on the health-related quality of life in a Brazilian sample of dental patients. Methods: A total of 1,007 adult subjects enrolled in the School of Dentistry of São Paulo State University (UNESP) - Araraquara Campus for dentistry care between September/2012 and April/2013, participated. 72.4 % were female. The mean age was 45.7 (SD = 12.5) years. The Oral Health Impact Profile (OHIP-14) and the Short Form Health Survey (SF-36) were used. The demographic and symptom/clinical variables collected were gender, age, economic status, presence of pain and chronic disease. The impact of studied variables on health-related quality of life were evaluated with a structural equation model, considering the factor “Health” as the central construct. The fit of the model was first analyzed by the evaluation of the goodness of fit indices (χ 2 /df ≤ 2.0, CFI and TLI ≥ 0.90 and RMSEA < 0.10) and the evaluation of the variables’ impact over health-related quality of life was based on the statistical significance of causal paths (β), evaluated by z tests, for a significance level of 5 %. Results: We observed adequate fit of the model to the data (χ 2 /df = 3.55; CFI = 0.95; TLI = 0.94; RMSEA = 0.05). The impacts on oral health explained 28.0 % of the variability of the health-related quality of life construct, while the total variance explained of the model was 39.0 %. For the demographic and symptom/clinical variables, only age, presence of pain and chronic disease showed significant impacts (p < 0.05). Conclusion: The oral health, age, presence of pain and chronic disease of individuals had significant influence on health-related quality of life.

Hepatitis B virus genotypes and mutations in the basal core promoter and pre-core/core in chronically infected patients in southern Brazil: a cross-sectional study of HBV genotypes and mutations in chronic carriers

Introduction In Brazil, little data exist regarding the distribution of genotypes in relation to basal core promoter (BCP) and precore/core mutations among chronic hepatitis B virus (HBV) carriers from different regions of the country. The aim of this study was to identify HBV genotypes and the frequency of mutations at the BCP and precore/core region among the prevalent genotypes in chronic carriers from southern Brazil. Methods Nested-polymerase chain reaction (nested-PCR) products amplified from the S-polymerase gene, BCP and precore/core region from 54 samples were sequenced and analyzed. Results Phylogenetic analysis of the S-polymerase gene sequences showed that 66.7% (36/54) of the patients were infected with genotype D (D1, D2, D3), 25.9% (14/54) with genotype A (A1, A2), 5.6% (3/54) with subgenotype C2, and 2% (1/54) with genotype E. A comparison of virological characteristics showed significant differences between genotypes A, C and D. The comparison between HBeAg status and the G1896A stop codon mutation in patients with genotype D revealed a relationship between HBV G1896A precore mutants and genotype D and hepatitis B e antigen (HBeAg) seroconversion. Genotype D had a higher prevalence of the G1896A mutation and the presence of a thymine at position 1858. Genotype A was associated with a higher prevalence of the G1862T mutation and the presence of a cytosine at position 1858. Conclusions HBV genotype D (D3) is predominant in HBV chronic carriers from southern Brazil. The presence of mutations in the BCP and precore/core region was correlated with the HBV genotype and HBeAg negative status.

The determinants of mutual fund performance: A cross-country study

We use a new data set to study the determinants of the performance of open–end actively managed equity mutual funds in 27 countries. We find that mutual funds underperform the market overall. The results show important differences in the determinants of fund performance in the USA and elsewhere in the world. The US evidence of diminishing returns to scale is not a universal truth as the performance of funds located outside the USA and funds that invest overseas is not negatively affected by scale. Our findings suggest that the adverse scale effects in the USA are related to liquidity constraints faced by funds that, by virtue of their style, have to invest in small and domestic stocks. Country characteristics also explain fund performance. Funds located in countries with liquid stock markets and strong legal institutions display better performance.

Single-tube nested PCR assay with in-house DNA extraction for Mycobacterium tuberculosis detection in blood and urine

Abstract: INTRODUCTION : Molecular analyses are auxiliary tools for detecting Koch's bacilli in clinical specimens from patients with suspected tuberculosis (TB). However, there are still no efficient diagnostic tests that combine high sensitivity and specificity and yield rapid results in the detection of TB. This study evaluated single-tube nested polymerase chain reaction (STNPCR) as a molecular diagnostic test with low risk of cross contamination for detecting Mycobacterium tuberculosis in clinical samples. METHODS: Mycobacterium tuberculosis deoxyribonucleic acid (DNA) was detected in blood and urine samples by STNPCR followed by agarose gel electrophoresis. In this system, reaction tubes were not opened between the two stages of PCR (simple and nested). RESULTS: STNPCR demonstrated good accuracy in clinical samples with no cross contamination between microtubes. Sensitivity in blood and urine, analyzed in parallel, was 35%-62% for pulmonary and 41%-72% for extrapulmonary TB. The specificity of STNPCR was 100% in most analyses, depending on the type of clinical sample (blood or urine) and clinical form of disease (pulmonary or extrapulmonary). CONCLUSIONS: STNPCR was effective in detecting TB, especially the extrapulmonary form for which sensitivity was higher, and had the advantage of less invasive sample collection from patients for whom a spontaneous sputum sample was unavailable. With low risk of cross contamination, the STNPCR can be used as an adjunct to conventional methods for diagnosing TB.

Predictive factors for Leishmania infantum infection in dogs examined at a veterinary teaching hospital in Teresina, State of Piauí, Brazil

Abstract: INTRODUCTION: In Brazil, culling of seropositive dogs is one of the recommended strategies to control visceral leishmaniasis. Since infectiousness is correlated with clinical signs, control measures targeting symptomatic dogs could be more effective. METHODS: A cross-sectional study was carried out among 1,410 dogs, predictive models were developed based on clinical signs and an indirect immunofluorescence antibody test. RESULTS: The validated predictive model showed sensitivity and specificity of 86.5% and 70.0%, respectively. CONCLUSIONS: Predictive models could be used as tools to aid control programs in focusing on a smaller fraction of dogs contributing more to infection dissemination.

Product extension services deployment platform

Due to the progresses made in the branch of embedded technologies, manufacturers are becoming able to pack their shop floor level manufacturing resources with even more complex functionalities. This technological progression is radically changing the way production systems are designed and deployed, as well as, monitored and controlled. The dissemination of smart devices inside production processes confers new visibility on the production system while enabling for a more efficient and effective management of the operations. By turning the current manufacturing resources functionalities into services based on a Service Oriented Architecture (SOA), in order to expose them as a service to the user, the binomial manufacturing resource/service will push the entire manufacturing enterprise visibility to another level while enabling the global optimization of the operations and processes of a production system while, at the same time, supporting its accommodation to the operational spike easily and with reduced impact on production. The present work implements a Cloud Manufacturing infrastructure for achieving the resource/service value-added i.e. to facilitate the creation of services that are the composition of currently available atomic services. In this context, manufacturing resource virtualization (i.e. formalization of resources capabilities into services accessible inside and outside the enterprise) and semantic representation/description are the pillars for achieving resource service composition. In conclusion, the present work aims to act on the manufacturing resource layer where physical resources and shop floor capabilities are going to be provided to the user as a SaaS (Software as a Service) and/or IaaS (Infrastructure as a Service).

Reflux esophagitis and gastroesophageal reflux disease: a cross-sectional study of gastroesophageal reflux disease patients by age group

The purpose of this study was to explore the relationship between the intensity of acid reflux and severity of esophageal tissue damage in a cross-sectional study of patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with were selected in accordance with the strict 24-hour ambulatory esophageal pHmetry (24h-pHM) criteria and distributed into three age groups: Group A: 14 - 24 years of age. Group B: 25 - 54; and Group C: 55 - 64. The 24h-pHM was carried out in accordance with DeMeester standardization, and the Savary-Miller classification for the diagnosis of reflux esophagitis was used. The groups were similar in 24h-pHM parameters (p > 0.05), having above normal values. For the study group as a whole, there was no correlation between age group and intensity of acid reflux, and there was no correlation between intensity of acid reflux and severity of esophageal tissue damage. However, when the same patients were sub-grouped in accordance with the depth of their epithelial injury and then distributed into age groups, there was a significant difference in esophagitis without epithelial discontinuity. Younger patients had less epithelial damage than older patients. Additionally, although there was a significant progression from the least severe to the moderate stages of epithelial damage among the age groups, there was no apparent difference among the age groups in the distribution between the moderate stages and most severe stages. The findings support the conclusion that the protective response of individuals to acid reflux varies widely. Continued aggression by acid reflux appears to lead to the exhaustion of individual mechanisms of epithelial protection in some patients, but not others, regardless of age or duration of the disease. Therefore, the diagnosis and follow-up of GERD should include both measurements of the quantity of refluxed acid and an assessment of the damage to the esophageal epithelium.

Molecular tools in the diagnostic and epidemiology of infections caused by members of Mycobacterium avium Complex

Mycobacterium avium Complex (MAC) comprises microorganisms that affect a wide range of animals including humans. The most relevant are Mycobacterium avium subspecies hominissuis (Mah) with a high impact on public health affecting mainly immunocompromised individuals and Mycobacterium avium subspecies paratuberculosis (Map) causing paratuberculosis in animals with a high economic impact worldwide. In this work, we characterized 28 human and 67 porcine Mah isolates and evaluated the relationship among them by Multiple-Locus Variable number tandem repeat Analysis (MLVA). We concluded that Mah population presented a high genetic diversity and no correlations were inferred based on geographical origin, host or biological sample. For the first time in Portugal Map strains, from asymptomatic bovine faecal samples were isolated highlighting the need of more reliable and rapid diagnostic methods for Map direct detection. Therefore, we developed an IS900 nested real time PCR with high sensitivity and specificity associated with optimized DNA extraction methodologies for faecal and milk samples. We detected 83% of 155 faecal samples from goats, cattle and sheep, and 26% of 98 milk samples from cattle, positive for Map IS900 nested real time PCR. A novel SNPs (single nucleotide polymorphisms) assay to Map characterization based on a Whole Genome Sequencing analysis was developed to elucidate the genetic relationship between strains. Based on sequential detection of 14 SNPs and on a decision tree we were able to differentiate 14 phylogenetic groups with a higher discriminatory power compared to other typing methods. A pigmented Map strain was isolated and characterized evidencing for the first time to our knowledge the existence of pigmented Type C strains. With this work, we intended to improve the ante mortem direct molecular detection of Map, to conscientiously aware for the existence of Map animal infections widespread in Portugal and to contribute to the improvement of Map and Mah epidemiological studies.

A systematic methodology to analyse the performance and design configurations of business interoperability in cooperative industrial networks

This thesis proposes a methodology for modelling business interoperability in a context of cooperative industrial networks. The purpose is to develop a methodology that enables the design of cooperative industrial network platforms that are able to deliver business interoperability and the analysis of its impact on the performance of these platforms. To achieve the proposed objective, two modelling tools have been employed: the Axiomatic Design Theory for the design of interoperable platforms; and Agent-Based Simulation for the analysis of the impact of business interoperability. The sequence of the application of the two modelling tools depends on the scenario under analysis, i.e. whether the cooperative industrial network platform exists or not. If the cooperative industrial network platform does not exist, the methodology suggests first the application of the Axiomatic Design Theory to design different configurations of interoperable cooperative industrial network platforms, and then the use of Agent-Based Simulation to analyse or predict the business interoperability and operational performance of the designed configurations. Otherwise, one should start by analysing the performance of the existing platform and based on the achieved results, decide whether it is necessary to redesign it or not. If the redesign is needed, simulation is once again used to predict the performance of the redesigned platform. To explain how those two modelling tools can be applied in practice, a theoretical modelling framework, a theoretical Axiomatic Design model and a theoretical Agent-Based Simulation model are proposed. To demonstrate the applicability of the proposed methodology and/or to validate the proposed theoretical models, a case study regarding a Portuguese Reverse Logistics cooperative network (Valorpneu network) and a case study regarding a Portuguese construction project (Dam Baixo Sabor network) are presented. The findings of the application of the proposed methodology to these two case studies suggest that indeed the Axiomatic Design Theory can effectively contribute in the design of interoperable cooperative industrial network platforms and that Agent-Based Simulation provides an effective set of tools for analysing the impact of business interoperability on the performance of those platforms. However, these conclusions cannot be generalised as only two case studies have been carried out. In terms of relevance to theory, this is the first time that the network effect is addressed in the analysis of the impact of business interoperability on the performance of networked companies and also the first time that a holistic approach is proposed to design interoperable cooperative industrial network platforms. Regarding the practical implications, the proposed methodology is intended to provide industrial managers a management tool that can guide them easily, and in practical and systematic way, in the design of configurations of interoperable cooperative industrial network platforms and/or in the analysis of the impact of business interoperability on the performance of their companies and the networks where their companies operate.

Development and validation of gold nanoprobes for human SNP detection towards commercial application

Conventional molecular techniques for detection and characterization of relevant nucleic acid (i.e. DNA) sequences are, nowadays, cumbersome, expensive and with reduced portability. The main objective of this dissertation consisted in the optimization and validation of a fast and low-cost colorimetric nanodiagnostic methodology for the detection of single nucleotide polymorphisms (SNPs). This was done considering SNPs associated to obesity of commercial interest for STAB VIDA, and subsequent evaluation of other clinically relevant targets. Also, integration of this methodology into a microfluidic platform envisaging portability and application on points-of-care (POC) was achieved. To warrant success in pursuing these objectives, the experimental work was divided in four sections: i) genetic association of SNPs to obesity in the Portuguese population; ii) optimization and validation of the non-cross-linking approach for complete genotype characterization of these SNPs; iii) incorporation into a microfluidic platform; and iv) translation to other relevant commercial targets. FTO dbSNP rs#:9939609 carriers had higher body mass index (BMI), total body fat mass, waist perimeter and 2.5 times higher risk to obesity. AuNPs functionalized with thiolated oligonucleotides (Au-nanoprobes) were used via the non-cross-linking to validate a diagnostics approach against the gold standard technique - Sanger Sequencing - with high levels of sensitivity (87.50%) and specificity (91.67%). A proof-of-concept POC microfluidic device was assembled towards incorporation of the molecular detection strategy. In conclusion a successful framework was developed and validated for the detection of SNPs with commercial interest for STAB VIDA, towards future translation into a POC device.

Socio-demographic correlates of physical activity of European adults: A cross-sectional study from the European Social Survey

ABSTRACT - Background: From a public health perspective, the study of socio-demographic factors related to physical activity is important in order to identify subgroups for intervention programs. Purpose: This study also aimed to identify the prevalence and the socio-demographic correlates related with the achievement of recommended physical activity levels. Methods: Using data from the European Social Survey round 6, physical activity and socio-demographic characteristics were collected from 39278 European adults (18271 men, 21006 women), aged 18-64 years, from 28 countries in 2012. Meeting physical activity guidelines was assessed using World Health Organization criteria. Results: 64.50% (63.36% men, 66.49% women) attained physical activity recommended levels. The likelihood of attaining physical activity recommendations was higher in age group of 55-64 years (men: OR=1.22, p<0.05; women: OR=1.66, p<0.001), among those who had completed high school (men: OR=1.28, p<0.01; women: OR=1.26, p<0.05), among those who lived in rural areas (men: OR=1.20, p<0.001; women: OR=1.10, p<0.05), and among those who had 3 or more people living at home (men: OR=1.40, p<0.001; women: OR=1.43, p<0.001). On the other hand, attaining physical activity recommendations was negatively associated with being unemployed (men: OR=0.70, p<0.001; women: OR=0.87, p<0.05), being a student (men: OR=0.56, p<0.001; women: OR=0.64, p<0.01), being a retired person (men: OR=0.86, p<0.05) and with having a higher household income (OR=0.80, p<0.001; women: OR=0.81, p<0.01). Conclusion: This research helped clarify that, as the promotion of physical activity is critical to sustain health and prevent disease, socio-demographic factors are important to consider when planning the increase of physical activity.