Indicadores de prognóstico em utentes com disfunção do ombro submetidos a uma intervenção terapêutica direcionada para a estabilidade dinâmica da escápulo-torácica

RESUMO: Introdução/ Objetivo: Segundo a revisão sistemática de Chester e colaboradores (2013b)apenas dois fatores de prognóstico demonstraram uma associação consistente com o resultado que foram a duração dos sintomas e a funcionalidade na avaliação inicial. O objetivo do estudo é identificar indicadores de bom e mau prognóstico em utentes com disfunção do complexo articular do ombro (DCAO), tendo por base, aspetos da avaliação inicial do utente e critérios de alta de abolição da dor, aumento da funcionalidade e da estabilidade dinâmica considerando uma intervenção terapêutica direcionada para o aumento da estabilidade dinâmica da escápulo-torácica. Metodologia: Efetuou-se um estudo de coorte clínico retrospetivo. Para tal, aplicou-se um protocolo de intervenção terapêutica e analisou-se os resultados. A amostra foi constituída por 82 indivíduos com DCAO [53 com síndrome do conflito subacromial (SCSA) e 29 com instabilidade da glenoumeral (IGU)], residentes nos distritos de Lisboa, Setúbal e Santarém com o intuito de iniciar tratamento de fisioterapia. A análise dos dados foi efetuada tendo em consideração dois procedimentos: análise univariada (através do método de Kaplan-Meier para cada CVP) e análise multifatorial (pela análise de regressão de Cox e regressão logística nos grupos de utentes com SCSA, IGU e DCAO). Resultados: O tempo mediano de continuação no tratamento em fisioterapia foi de 7 semanas para os utentes com SCSA e 6 semanas para utentes com IGU. Segundo o teste de Logrank, na análise univariada, existem sete e oito covariáveis preditoras (CVP) com associação estatisticamente significativa (p<0,05) para o subgrupo SCSA e IGU, respectivamente. De acordo com estes resultados, a primeira parte da DASH e a SPADI são as únicas CVP com associação comuns às duas disfunções. Pela análise multifatorial e, em congruência com o teste de Wald, nenhuma das CVP contribui estatisticamente para o modelo preditivo de continuidade do tratamento de fisioterapia em qualquer um dos três modelos estudados: subgrupo SCSA, subgrupo IGU e utentes com DCAO. Conclusão: Por uma análise univariada verificou-se que existem CVP associadas à alta dos tratamentos em fisioterapia e estas não são as mesmas em ambas as DCAO. Contudo, a magnitude do efeito de cada CVP nos modelos multifatoriais definidos para os grupos de utentes com SCSA, IGU e DCAO não demonstraram valor estatisticamente significativo pelo que não foi possível determinar modelos de prognóstico em utentes com DCAO.-------------ABSTRACT: Background/ Purpose: According with the systematic review from Chester and collaborators (2013b) just two prognostic factors demonstrated a consistent association with the outcome: the duration of symptoms and functionality in the initial assessment. The purpose of the study is to identify indicators of good and poor prognosis in patients with shoulder’s dysfunctions, based on aspects of the initial assessment and discharge criteria of absence of pain, increased functionality and dynamic stability considering a therapeutic intervention used to increase the dynamic stability of scapulo-thoracic. Methodology: It was conducted a retrospective study of clinical cohort. For this purpose it was applied a protocol with therapeutic intervention and the results were analyzed. The sample consisted of 82 individuals with shoulder’s dysfunction (53 with subacromial impingement (SIMP) and 29 with shoulder instability (SINS) residing in the districts of Lisbon, Setúbal and Santarém in order to start physiotherapy. Data analysis was performed taking into account two procedures: univariate analysis [using the Kaplan-Meier method for each co-variant predictor variable (CVP)] and multifactorial analysis [analysis by Cox regression and logistic regression on groups of patients with SIMP, SINS and shoulder’s dysfunction (SD)]. Results: The median time of follow-up treatment at physical therapy was 7 weeks for patients with SIMP and 6 weeks for patients with SINS. According to the Logrank test in the univariate analysis, there are seven and eight CVP with a statistically significant association (p<0.05) for the patients with SIMP and SINS, respectively. According to these results, the first part of the DASH and SPADI are the only CVP common to both disorders association. By multifatorial analyses, and in agreement with the Wald test, none of the CVP contributes statistically to the predictive model of continuity of physiotherapy treatment in any of the three studied models: patients with SIMP, patients with SINS and patients with SD. Conclusion: In an univariate analysis, it was verified that there are CVP associated with discharge from treatments of physical therapy and these are not the same in both SD. However, the magnitude of effect of each CVP in multifactorial models for defined patients groups with SIMP, SINS and SD showed no statistically significant. Therefore, it was not possible to determine prognostic models for patients with SD.

Fatores de prognóstico para os resultados de sucesso da fisioterapia multimodal em utentes com dor cervical crónica

RESUMO: Introdução: O conhecimento acerca da influência das características dos indivíduos com dor cervical crónica (DCC) no prognóstico dos resultados alcançados com a Fisioterapia é ainda inconsistente, sendo escassos os estudos desenvolvidos neste âmbito. Objetivo: Este relatório pretende determinar se um modelo baseado em fatores de prognóstico é capaz de prever os resultados de sucesso da Fisioterapia, a curto prazo, em utentes com DCC, ao nível da incapacidade funcional, intensidade da dor e perceção global de melhoria. Metodologia: Trata-se de estudo de coorte prospetivo com 112 participantes. Os utentes foram avaliados na primeira semana de tratamento e sete semanas após o início da intervenção. Os instrumentos utilizados foram o Neck Disability Index–Versão Portuguesa (NDI-PT) e a Escala Numérica da Dor (END) nos dois momentos de avaliação, um Questionário de Caracterização Sociodemográfica e Clínica da Amostra na baseline e a Patient Global Impression Change Scale–Versão Portuguesa (PGIC-PT) no follow-up. As características sociodemográficas e clínicas foram incluídas como potenciais fatores de prognóstico e estes foram definidos com base nas diferenças mínimas clinicamente importantes (DMCI) dos instrumentos NDIPT (DMCI≥6) e END (DMCI≥2) e no critério de pontuação ≥5 na PGIC-PT. A análise dos dados foi realizada através do método de regressão logística (backward conditional procedure) para identificar as associações entre os indicadores e as variáveis de resultado (p<0.05). Resultados: Dos 112 participantes incluídos no estudo, 108 completaram o follow-up (média de idade: 51.76±10.19). No modelo multivariado relativo à incapacidade funcional, os resultados de sucesso encontram-se associados a elevados níveis de incapacidade na baseline (OR=1.123; 95% IC 1.056–1.194) e a duração da dor inferior a 12 meses (OR=2.704; 95% IC 1.138–6.424). Este modelo explica 30.0% da variância da melhoria da funcionalidade e classifica corretamente 74.1% dos utentes (sensibilidade: 75.9%; especificidade: 72.0%). O modelo relativo à intensidade da dor identificou apenas a associação do outcome com níveis elevados de intensidade da dor na baseline (OR=1.321; 95% IC 1.047–1.668), explicando 7.5% da variância da redução da mesma e classificando corretamente 68.2% dos utentes (sensibilidade: 94.4%; especificidade: 16.7%). O modelo final referente à perceção global de melhoria apresentou uma associação com a intensidade da dor na baseline (OR=0.621; 95% IC 0.465–0.829), com a presença de cefaleias e/ou tonturas (OR=2.538; 95% IC 0.987–6.526) e com a duração da dor superior a 12 meses (OR=0.279; 95% IC 0.109–0.719). Este modelo explica 27.5% da variância dos resultados de sucesso para este outcome e classifica corretamente 73.1% dos utentes (sensibilidade: 81.8%; especificidade: 59.5%). Conclusões: Utentes com DCC com elevada incapacidade na baseline e queixas de dor há menos de 12 meses apresentam maior probabilidade de obter melhorias ao nível da incapacidade funcional. Elevados níveis de intensidade da dor na baseline predizem resultados de sucesso na redução da dor após sete semanas de tratamento. Utentes com DCC com baixos níveis de dor na baseline, com cefaleias e/ou tonturas e com queixas de dor há mais de 12 meses apresentam maior probabilidade de obter uma melhor perceção de melhoria.--------------- ABSTRACT:Introduction: The influence of the characteristics of individuals with chronic neck pain (CNP) on the prognosis of physiotherapy outcomes is still inconsistent, there being few studies developed in this context. Aim: This study seeks to determine whether a model based on prognostic factors can predict the short-term physiotherapy successful outcomes in CNP patients, regarding functional disability, pain intensity and perceived recovery. Methodology: This is a prospective cohort study with 112 participants. Patients were assessed during the first week of treatment and seven weeks after the start of the intervention. The instruments used were the Neck Disability Index–Portuguese Version (NDI-PT) and the Numerical Rating Scale (NRS) at both moments of assessment, a Sample Sociodemographic and Clinical Characterization Questionnaire at baseline and Patient Global Impression Change Scale–Portuguese Version (PGIC-PT) at the follow-up. The sociodemographic and clinical characteristics were included as potential predictors of successful outcomes, and these were defined on the basis of minimal clinically important differences (MCID) of NDI-PT (MCID≥6) and END (MCID≥2) and the criteria score ≥5 on the PGIC-PT. Data analysis was performed using logistic regression (backward conditional procedure) to identify associations between predictors and outcomes (p<0.05). Results: Of the 112 participants included in the study, 108 completed the follow-up (mean age: 51.76±10.19). In the multivariate model of functional disability, the successful outcomes are associated with high levels of disability at baseline (OR = 1.123; 95% CI 1.056-1.194), and pain duration shorter than 12 months (OR=2.704; 95% CI 1.138–6.424). This model explains 30.0% of the variance of improved functional capacity and correctly classifies 74.1% of the patients (sensitivity: 75.9%, specificity: 72.0%). The model for pain intensity solely identified an outcome association with high pain intensity at baseline (OR=1.321; 95% CI 1.047-1.668), explaining 7.5% of the variance of pain reduction and correctly classifying 68.2% of the patients (sensitivity: 94.4%, specificity: 16.7%). The final model of perceived recovery showed an association with pain intensity at baseline (OR=0.621; 95% CI 0465-0829), with the presence of headache and/or dizziness (OR=2.538; 95% CI 0.987-6.526) and the duration of pain over 12 months (OR=0.279; 95% CI 0.109-0.719). This model explains 27.5% of the variance of successful outcomes and correctly classifies 73.1% of the patients (sensitivity: 81.8%, specificity: 59.5%). Conclusions: Patients with CNP with high disability at baseline and complaints of pain for less than 12 months are more likely to obtain improvements in functional disability. High levels of pain intensity at baseline predict successful outcomes in pain reduction after seven weeks of treatment. Patients with CNP with low levels of pain at baseline, with headache and/or dizziness and with pain complaints for more than 12 months are more likely to get a better perceived recovery.

Curso clínico da dor lombar crónica após alta da fisioterapia : trajetórias de dor no follow-up aos quatro e seis meses

RESUMO:Introdução: O conhecimento acerca da influência das características dos indivíduos com dor cervical crónica (DCC) no prognóstico dos resultados alcançados com a Fisioterapia é ainda inconsistente, sendo escassos os estudos desenvolvidos neste âmbito. Objetivo: Este relatório pretende determinar se um modelo baseado em fatores de prognóstico é capaz de prever os resultados de sucesso da Fisioterapia, a curto prazo, em utentes com DCC, ao nível da incapacidade funcional, intensidade da dor e perceção global de melhoria. Metodologia: Trata-se de estudo de coorte prospetivo com 112 participantes. Os utentes foram avaliados na primeira semana de tratamento e sete semanas após o início da intervenção. Os instrumentos utilizados foram o Neck Disability Index–Versão Portuguesa (NDI-PT) e a Escala Numérica da Dor (END) nos dois momentos de avaliação, um Questionário de Caracterização Sociodemográfica e Clínica da Amostra na baseline e a Patient Global Impression Change Scale–Versão Portuguesa (PGIC-PT) no follow-up. As características sociodemográficas e clínicas foram incluídas como potenciais fatores de prognóstico e estes foram definidos com base nas diferenças mínimas clinicamente importantes (DMCI) dos instrumentos NDIPT (DMCI≥6) e END (DMCI≥2) e no critério de pontuação ≥5 na PGIC-PT. A análise dos dados foi realizada através do método de regressão logística (backward conditional procedure) para identificar as associações entre os indicadores e as variáveis de resultado (p<0.05). Resultados: Dos 112 participantes incluídos no estudo, 108 completaram o follow-up (média de idade: 51.76±10.19). No modelo multivariado relativo à incapacidade funcional, os resultados de sucesso encontram-se associados a elevados níveis de incapacidade na baseline (OR=1.123; 95% IC 1.056–1.194) e a duração da dor inferior a 12 meses (OR=2.704; 95% IC 1.138–6.424). Este modelo explica 30.0% da variância da melhoria da funcionalidade e classifica corretamente 74.1% dos utentes (sensibilidade: 75.9%; especificidade: 72.0%). O modelo relativo à intensidade da dor identificou apenas a associação do outcome com níveis elevados de intensidade da dor na baseline (OR=1.321; 95% IC 1.047–1.668), explicando 7.5% da variância da redução da mesma e classificando corretamente 68.2% dos utentes (sensibilidade: 94.4%; especificidade: 16.7%). O modelo final referente à perceção global de melhoria apresentou uma associação com a intensidade da dor na baseline (OR=0.621; 95% IC 0.465–0.829), com a presença de cefaleias e/ou tonturas (OR=2.538; 95% IC 0.987–6.526) e com a duração da dor superior a 12 meses (OR=0.279; 95% IC 0.109–0.719). Este modelo explica 27.5% da variância dos resultados de sucesso para este outcome e classifica corretamente 73.1% dos utentes (sensibilidade: 81.8%; especificidade: 59.5%). Conclusões: Utentes com DCC com elevada incapacidade na baseline e queixas de dor há menos de 12 meses apresentam maior probabilidade de obter melhorias ao nível da incapacidade funcional. Elevados níveis de intensidade da dor na baseline predizem resultados de sucesso na redução da dor após sete semanas de tratamento. Utentes com DCC com baixos níveis de dor na baseline, com cefaleias e/ou tonturas e com queixas de dor há mais de 12 meses apresentam maior probabilidade de obter uma melhor perceção de melhoria.-----------ABSTRACT: Introduction: The influence of the characteristics of individuals with chronic neck pain (CNP) on the prognosis of physiotherapy outcomes is still inconsistent, there being few studies developed in this context. Aim: This study seeks to determine whether a model based on prognostic factors can predict the short-term physiotherapy successful outcomes in CNP patients, regarding functional disability, pain intensity and perceived recovery. Methodology: This is a prospective cohort study with 112 participants. Patients were assessed during the first week of treatment and seven weeks after the start of the intervention. The instruments used were the Neck Disability Index–Portuguese Version (NDI-PT) and the Numerical Rating Scale (NRS) at both moments of assessment, a Sample Sociodemographic and Clinical Characterization Questionnaire at baseline and Patient Global Impression Change Scale–Portuguese Version (PGIC-PT) at the follow-up. The sociodemographic and clinical characteristics were included as potential predictors of successful outcomes, and these were defined on the basis of minimal clinically important differences (MCID) of NDI-PT (MCID≥6) and END (MCID≥2) and the criteria score ≥5 on the PGIC-PT. Data analysis was performed using logistic regression (backward conditional procedure) to identify associations between predictors and outcomes (p<0.05). Results: Of the 112 participants included in the study, 108 completed the follow-up (mean age: 51.76±10.19). In the multivariate model of functional disability, the successful outcomes are associated with high levels of disability at baseline (OR = 1.123; 95% CI 1.056-1.194), and pain duration shorter than 12 months (OR=2.704; 95% CI 1.138–6.424). This model explains 30.0% of the variance of improved functional capacity and correctly classifies 74.1% of the patients (sensitivity: 75.9%, specificity: 72.0%). The model for pain intensity solely identified an outcome association with high pain intensity at baseline (OR=1.321; 95% CI 1.047- 1.668), explaining 7.5% of the variance of pain reduction and correctly classifying 68.2% of the patients (sensitivity: 94.4%, specificity: 16.7%). The final model of perceived recovery showed an association with pain intensity at baseline (OR=0.621; 95% CI 0465-0829), with the presence of headache and/or dizziness (OR=2.538; 95% CI 0.987-6.526) and the duration of pain over 12 months (OR=0.279; 95% CI 0.109- 0.719). This model explains 27.5% of the variance of successful outcomes and correctly classifies 73.1% of the patients (sensitivity: 81.8%, specificity: 59.5%). Conclusions: Patients with CNP with high disability at baseline and complaints of pain for less than 12 months are more likely to obtain improvements in functional disability. High levels of pain intensity at baseline predict successful outcomes in pain reduction after seven weeks of treatment. Patients with CNP with low levels of pain at baseline, with headache and/or dizziness and with pain complaints for more than 12 months are more likely to get a better perceived recovery.

Conselho de Resolução de Litígios

The scope of the following study is to present an alternative and preventive dispute resolution method known as Dispute Resolution Board. The Dispute Resolution Board mechanism is included in construction contracts to support project participants in avoiding and resolving disputes. Over the years the construction industry dealt with the resolution of claims and disputes through several methods. One of the most successful and lasting is the Dispute Resolution Board. A Dispute Resolution Board is a board of impartial professionals formed at the start of the project to follow construction progress, prevent arising disputes, and assist in the resolution of disputes during the project. When a dispute arises the Board meets with the parties to settle this dispute. The recommendation of this Board is non-binding for the parties. In Portugal there is no experience with this form of conciliation.

Almirante: Evaluating the board game: Board game, startup, discounted cash flow, venture capital method, real options

This thesis evaluates a start-up company (Jogos Almirante Lda) whose single asset is a board game named Almirante. It aims to conclude whether it makes sense to create a company or just earn copyrights. The thesis analyzes the board game’s market, as part of the general toy’s market, from which some data exists: European countries as well as the USA. In this work it is analyzed the several ways to finance a start-up company and then present an overview of the valuation of the Jogos Almirante based on three different methods: Discounted Cash Flow, Venture Capital Method and Real Options.

How to design and develop There App: A mobile app focused on live video streaming, promoting new social interactions

This work project aims to demonstrate how to design and develop an innovative concept of video streaming app. The project combines technology push and market pull theories into developing a product that is more suitable for the customer needs, with the particularity that there is no other way of seeing any place in the world, live and ondemand. An analysis on the bigger influencers in terms of design-thinking and new product development, as Tim Brown or Paul Trott, lead to a better understanding on how There App should evolve, keeping in mind the customer desires and technical features.

The born global phenomenon- The Portuguese case

The growing significance of companies that conduct international business at or near their funding has been critically challenging previous incremental models of international expansion. This thesis aims to cross-compare, by means of a multiple-case study, eight Portuguese start-ups among themselves and with the theoretical concept of born global firms versus traditional ones. This work project finds that: (1) active entrepreneurs with global vision from inception are essential for the implementation of international strategies; (2) only formal network plays a key role for successful internationalization and (3) inimitable sources of value creation, niche-focused strategies and unique intangible assets are also crucial.

The role of individual ability and structural embeddedness on entrepreneurial success

In the present thesis I analyse the roles of individual ability and structural embeddedness on entrepreneurial success. The results retrieved from a matched employer-employee longitudinal data set show prior worker productivities and environmental embeddedness to have a persistent positive impact on the size and growth rates of new firms. What is more, embeddedness facilitates the impact of ability on start-up performance with outsiders of comparable abilities starting smaller and slower growing firms. Those in higher ability categories are more likely to transfer and also, albeit to a lesser extent, close their ventures, an effect attributed to the higher opportunity costs associated with the group. Firms managed by embedded agents enjoy longer longevities and have better chances of finding a new owner after the departure of the previous one. Finally, higher ability types show evidence of specialisation in serial entrepreneurship.

Monitoring the treatment of sepsis with vancomycin in term newborn infants

A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. Purpose: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique , SBT by the macro-broth dilution method, and MIC by diffusion test in agar . RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20--40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 µg/mL). Only 48% had adequate trough concentrations (5--10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 µg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.

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.

Understanding churn and its reasons: The GuestU case

In the age of computerisation, entrepreneurs around the world aim to revolutionise their field with ground-breaking ICTs. GuestU is one of those offering mobile application development to small and medium-sized tourism enterprises. To assure the young start-ups steady growth this paper aims to identify reasons for the high customer churn risk. Primary data is used to analyse end-user behaviour and particularly the success of acquisition and activation. Results show troubling download quantities as well as retention rates leading to the recommendations for GuestU to incentivise and guide their customers in increasing promotion for the applications.

Princípios de terapêutica antibiótica na doença crítica

RESUMO: A infeção é frequente durante a doença crítica, quer como causa da doença crítica quer como complicação da sua evolução. Paradoxalmente, os avanços da medicina moderna aumentaram eles próprios o risco de infeção, ao permitir a sobrevida até idades avançadas, ao criar um novo grupo de doentes imunodeprimidos, nomeadamente doentes tratados com fármacos que interferem com as suas defesas naturais (corticóides, citostáticos), ao aumentar o tempo de vida de hospedeiros com comorbilidades debilitantes. Os antibióticos são um dos elos essenciais no tratamento da infeção. Contudo o seu uso também promove a seleção e crescimento de bactérias resistentes. Para além disso as doses convencionais de antibióticos foram selecionadas numa altura em que a resistência era um fenómeno raro e podem não ser atualmente as mais adequadas. Existe hoje muita evidência acumulada que os doentes críticos sofrem alterações da sua farmacocinética (PK) que podem facilitar a ocorrência de falência terapêutica ou de toxicidade tanto por sub como por sobredosagem de antibióticos. Essas alterações são complexas e difíceis de estudar. Finalmente, também a farmacodinâmica (PD) dos antibióticos pode estar alterada nesta população, podendo haver necessidade de ajustar os alvos terapêuticos de forma individual. O objetivo deste trabalho foi investigar a relação entre a terapêutica antibiótica, as suas características PK e PD, a carga bacteriana e o prognóstico dos doentes críticos. O plano de investigação incluiu: 1. Dados da epidemiologia portuguesa de doentes críticos com infeção; 2. Avaliação da relação entre a carga bacteriana, o tempo até ao início do tratamento antibiótico e o prognóstico dos doentes críticos; 3. Avaliação da evolução da PK durante o tratamento da infeção; 4. Um estudo multicêntrico para avaliação da eficácia da terapêutica com um β- lactâmico doseado de acordo com a relação PK/PD. Na introdução é descrita a importância dos antibióticos, a sua origem e o problema crescente das resistências bacterianas relacionadas com o seu emprego e abuso. É salientada a importância de racionalizar a posologia, de acordo com os conceitos de PK e de PD. No Capítulo 1 são apresentados dados de epidemiologia portuguesa de infeção em doentes críticos, sobretudo retirados de dois estudos prospetivos, observacionais, os quais incluíram mais de 50% da capacidade de internamento em cuidados intensivos existente em Portugal. No Capítulo 2 são descritos os conceitos de PK e as suas alterações nos doentes críticos. De seguida são revistos os conceitos de PD de antibióticos e a sua aplicação a esta população, em particular durante as infeções graves (Capítulo 3). Nos capítulos seguintes são aprofundadas estas alterações da PK nos doentes críticos e as suas causas, de forma a destacar a importância da monitorização da concentração dos antibióticos. São apresentados os dados duma revisão sistemática de PK de antibóticos nesta população (Capítulo 4), pormenorizadas as alterações da PD que comprometem a eficácia da terapêutica antibiótica, facilitam o desenvolvimento de resistências e podem levar a falência terapêutica (Capítulo 5). Consequentemente a compreensão global destas alterações, da sua relevância clínica e a revisão da evidência disponível facilitou o desenvolvimento do próprio plano global de investigação (Capítulos 6 e 7). No Capítulo 6.1 são descritos os antibióticos tempo-dependente e a importância de aumentar o seu tempo de perfusão. Foi desenhado um estudo multicêntrico para comparar a eficácia e segurança da perfusão contínua da piperacilina tazobactam (um antibiótico β-lactâmico associado a um inibidor de β-lactamases) com a mesma dose do antibiótico, administrado em dose convencional, intermitente. A importância de dosear corretamente os antibióticos concentração-dependente foi também avaliada num estudo a primeira dose dos aminoglicosídeos (Capítulo 6.2). Outras estratégias para melhorar os resultados assistenciais dos doentes infetados são abordadas no Capítulo 7, em particular a importância da terapêutica antibiótica precoce, a avaliação da carga bacteriana e a compreensão da variação da PK ao longo do tratamento da infeção. Foi desenvolvido um algoritmo de abordagem terapêutica que incluiu estas alterações da PK e da PD nos doentes críticos. Finalmente no Capítulo 8 são descritos mecanismos de desenvolvimento das resistências bacterianas bem como estratégias para a sua abordagem. O Capítulo final (Capítulo 9) aponta um plano para futuras áreas de trabalho. O elemento chave identificado neste trabalho de investigação é o reconhecimento da variabilidade significativa da PK dos antibióticos durante a doença crítica, a qual condiciona a sua posologia. Estas alterações estão relacionadas com a própria gravidade da doença e tendem a diminuir ao longo do seu tratamento. No entanto nem a gravidade da doença nem as características individuais as permitem prever de forma aceitável pelo que a utilização duma posologia universal, independente da situação clínica concreta, pode ser inadequada. As estratégias para melhorar os resultados assistenciais dos doentes críticos infetados devem ser baseadas na individualização da posologia antibiótica de acordo com os princípios da PK e da PD, preferencialmente apoiadas em doseamentos da sua concentração. ------------------------------------ ABSTRACT: Infection commonly occurred during critical illness, either as a cause or complicating the course of the disease. Advances in medicine had paradoxically increase the risk of infection, both by improving survival to older ages and by introducing a new group of immunosuppressed patients, those who are treated with drugs that interfere with their natural defenses (corticosteroids, cytostatics) and those who survived longer with aggressive diseases. Antibiotics are of paramount importance for treating infection. However the use of these drugs also promote the selection and growth of resistant bacteria. Furthermore conventional antibiotic doses were calculated for less severe patients during a time when resistance was rare. Nowadays there is increasing evidence that critically ill patients experiment altered pharmacokinetics (PK) that may lead to therapeutic failure and/or drug toxicity. Equally, such PK alterations are complex and challenging to investigate. Finally pharmacodynamics (PD) may also be different in this population and antibiotic targets may need to be tailored to the individual patient. The aim of this research was to investigate the relationship between antibiotic therapy, its PK and PD, bacterial burden and critically ill patients outcomes. The research plan comprised of: 1. Epidemiological portuguese data of critically ill infected patients; 2. Relationship between burden of bacteria, time until the start of antibiotics and patient outcomes; 3. Evaluation of PK during treatment of infection; 4. A multicentre study evaluating PK guided β-lactam therapy. The introductory chapter outlines the importance of antibiotics, its origins, the problem of increasing bacteria resistance, related to its use and overuse and the importance of rational drug dosing using PK and PD concepts. In Chapter 1 portuguese epidemiological data of infections in critically ill patients is presented, mostly coming from two prospective observational studies, encompassing more than 50% of critically ill beds available in Portugal. Chapter 2 describes the concepts of PK and the changes occurring in critically ill patients. This is followed by a review of the concepts of PD of antibiotics and its application to this population, especially during severe infections (Chapter 3). In the following chapter these changes in antibiotics PK in critical illness are and its causes are detailed, to outline the importance of therapeutic drug monitoring. Data on a systematic review of antibiotics PK in those patients is provided (Chapter 4). The following chapter (Chapter 5) elucidates important changes in PD, that compromises antibiotic therapy, facilitate the occurrence of resistance and may lead to therapeutic failure. Thus, an understanding of the clinical problem and available evidence facilitated the development of a comprehensive research plan (Chapter 6 and Chapter 7). Chapter 6.1 describes time-dependent antibiotics and the importance of extending its perfusion time. A multicenter study was designed to compare the continuous infusion of piperacillin tazobactam (a β-lactam antibiotic) with the same daily dose, prescribed in a conventional, intermittent dose. The importance of correct dosing of antibiotics was also assessed through a study addressing aminoglycoside (a concentration-dependent antibiotic) therapy (Chapter 6.2), focusing on its first dose. Strategies to improve severe infected patients outcomes were addressed in Chapter 7, namely the importance of early antibiotic therapy, assessing the burden of bacteria and understanding changes in antibiotic concentration during the course of infection. An algorithm to include all the described changes in both PK and PD of critically ill patients was developed. Finally in Chapter 8 mechanisms of the increasing resistance of bacteria are described and strategies to address that problem are proposed. The closing chapter (Chapter 9) lays a roadmap for future work. The key finding of this research is the significant variability of the antibiotics PK during critical illness, which makes dosing a challenging issue. These changes are related to the severity of the infection itself and improve through the course of the disease. However neither disease severity nor individual characteristics are useful to predict PK changes. Therefore, the use of a universal dose approach, regardless of the individual patient, may not be the best approach. Strategies to improve patients’ outcomes should be based on tailoring antibiotics to the individual patient, according to PK and PD principles, preferentially supported by therapeutic drug monitoring.

Protecção de crianças e jovens em Portugal

The causes of children rights and youth rights have been the focus of our attention. The ideals of freedom and justice accompany us in our daily lives and, as such, this thesis aims to study the questions of major importance in the field of children and youth protection in Portugal which deserve deep and serious reflection. We shall start with a brief theoretical framework of the evolution of the rights of children and youth in Portugal, defining some concepts. This will be followed by an analysis of all relevant Portuguese legislation, which will set out its fields of application, measures, objectives and underlying principles. There are multiple reasons to raise awareness to the importance of the topics that will be treated and to the necessity and urgency of thinking about an effective promotion and protection of children and youth in Portugal. Keywords: children,

Orthogonal models, structure crossing, nesting and inference

We intend to study the algebraic structure of the simple orthogonal models to use them, through binary operations as building blocks in the construction of more complex orthogonal models. We start by presenting some matrix results considering Commutative Jordan Algebras of symmetric matrices, CJAs. Next, we use these results to study the algebraic structure of orthogonal models, obtained by crossing and nesting simpler ones. Then, we study the normal models with OBS, which can also be orthogonal models. We intend to study normal models with OBS (Orthogonal Block Structure), NOBS (Normal Orthogonal Block Structure), obtaining condition for having complete and suffcient statistics, having UMVUE, is unbiased estimators with minimal covariance matrices whatever the variance components. Lastly, see ([Pereira et al. (2014)]), we study the algebraic structure of orthogonal models, mixed models whose variance covariance matrices are all positive semi definite, linear combinations of known orthogonal pairwise orthogonal projection matrices, OPOPM, and whose least square estimators, LSE, of estimable vectors are best linear unbiased estimator, BLUE, whatever the variance components, so they are uniformly BLUE, UBLUE. From the results of the algebraic structure we will get explicit expressions for the LSE of these models.

The perfect paint in modern art conservation: a comparative study of 21st century vinyl emulsions

Contemporary painting places, and will continue to place, several questions about its meaning, its chemical nature, its durability and the best way to preserve it. This research aims at putting together comprehensive data on vinyl based paints, including their components, their properties, their aging behavior and their response to selected cleaning products. In this project degradation mechanisms of vinyl binders and formulations used in the 20th and 21st century were studied. Stability over time of selected vinyl polymers was assessed through natural indoor and artificially aging. The objective was to enhance knowledge and understanding of vinyl emulsion formulations and their performance over time. Overall conservation state of pictorial layers namely, adhesion, cohesion and discoloration of selected case studies from the Portuguese artist Julião Sarmento (b.1948) was correlated with the observed molecular level changes studied in laboratory experiments. Sarmento’s paintings were chosen due to conservation concerns (discoloration) on some of his works from the 90’s. Besides, research was carried out to start increasing the knowledge of what can be expected of PVAc based paints in terms of response to conservation treatments namely, surface cleaning. Artificial aging showed that the most recent formulations which are based on a poly(vinyl acetate), poly(vinyl chloride) and polyethylene terpolymer are less stable when compared to some homopolymer formulations. From the four pigments studied, titanium dioxide rutile and a carbon based black proved to be stabilizers for both types of polymer. The mixture lithopone plus calcium carbonate has showed to have a photocatalytic effect on the binders. The studied paintings showed to be in an overall good state of conservation except for the paintings created in the 90’s with white glue and a mixture of white lithoponeand calcium carbonate. Discoloration of this white paint seems to be irreversible and ongoing and is still a major concern. The disapearance of the plasticizer was the only change detected. The current works created by Sarmento are expected to be more stable as they were painted using the rutile titanium dioxide. Immersion/cleaning tests showed that vinyl based paints can be susceptible to water and organic solvents like ethanol as some evidences point to the removal/diffusion of additives from the paint. The observations made point to the need to further proceed in this research field.