Reduction of spleen size in a child with Hyperreactive Malarious Splenomegaly (HMS) treated outside the Brazilian endemic area of malaria with only one course of quinine

We report the clinical picture, treatment and evolution of a child with hyperreactive malarious splenomegaly treated outside the endemic area of malaria. The patient presented gross splenomegaly, proceeded from an area where malaria is endemic, showed increased immunoglobulins levels, high antimalarial antibody titres and hepatic sinusoidal lymphocytosis. The child did not return to an area where malaria is endemic and showed a favorable response to only one course of quinine. The response of this patient to limited antimalarial therapy suggests the importance of reinfection with malaria in the development and maintenance of this syndrome.

Ultrassonografia torácica : impacto no diagnóstico e estadiamento do cancro do pulmão

RESUMO:RESUMO: Nos últimos anos a ultrassonografia emergiu como um instrumento importante no diagnóstico da patologia torácica. O progresso tecnológico possibilitou a conceção de novos equipamentos como a ecoendoscopia brônquica radial e linear. Verificou-se, igualmente, o aparecimento de indicações para a realização de ecografia transtorácica. Uma das principais doenças impulsionadoras da técnica ultrassonográfica no tórax foi o cancro do pulmão, primeira causa de morte oncológica a nível mundial. A aplicabilidade e conhecimento do papel dos ultrassons no âmbito do diagnóstico e estadiamento do cancro do pulmão não se encontram esgotados, persistindo focos de controvérsia e dúvida científica que se pretendem esclarecer. A presente tese foi organizada em cinco capítulos: o primeiro abordou de forma geral e introdutória o estado da arte referente à ultrassonografia torácica, cancro do pulmão e a sua conjugação; o segundo destacou os principais objetivos; o terceiro sumarizou a metodologia utilizada; o quarto englobou os cinco estudos publicados, descritos subsequentemente, e o quinto incluiu uma discussão concisa, as principais conclusões e perspetivas futuras. O primeiro estudo avaliou a rentabilidade diagnóstica, segurança e curva de aprendizagem num coorte de 179 doentes submetidos a ecoendoscopia brônquica linear. De acordo com as indicações para este procedimento os doentes foram subdivididos em três grupos: (1) diagnóstico, (2) diagnóstico e estadiamento e (3) estadiamento. Para o primeiro, segundo e terceiro grupos a sensibilidade da ecoendoscopia foi 86.1%, 86.7% e 95% respetivamente e a precisão técnica foi 87.5%, 93.1% e 97.7% respetivamente. O treino originou um aumento progressivo do número de locais puncionados por doente, com menor duração e sem complicações, comprovando a eficácia e segurança do método quando realizado na população Portuguesa por broncologistas com experiência. O segundo estudo foi conduzido para averiguar a eficácia e custo da ecoendoscopia brônquica linear realizada através da via aérea e/ou esófago no diagnóstico de lesões sugestivas de neoplasia do pulmão, após ineficácia das técnicas convencionais. Nos doentes incluídos prospetivamente alcançou-se um diagnóstico definitivo em 106 casos (87.6%). A sensibilidade global para o diagnóstico de cancro do pulmão foi 89.8%, a especificidade foi 100%, o valor preditivo positivo foi 100%, o valor preditivo negativo foi 20% e a precisão foi 90.1%. Esta estratégia ultrassonográfica abrangente evitou intervenções cirúrgicas diagnósticas em doentes anteriormente submetidos a broncoscopia flexível ou punção aspirativa transtorácica guiada por tomografia computorizada, proporcionando uma redução significativa dos custos. No terceiro estudo investigou-se a viabilidade e papel da conjugação da ecoendoscopia brônquica linear com técnicas moleculares na avaliação de antigénios tumorais e padrões de metastização ganglionar em doentes com cancro do pulmão de não-pequenas células (CPNPC). Os marcadores citoqueratina 19 (CK-19), antigénio carcinoembrionário (CEA), molécula de adesão celular epitelial (EPCAM), sialyl-Lewis X e CD44 foram determinados nos aspirados ganglionares de 33 doentes com neoplasia e 17 controlos 10 Ultrassonografia através de citometria de fluxo (CF) e reação em cadeia da polimerase em tempo real (RTPCR). Os doentes com CPNPC possuíam um compartimento celular epitelial significativamente aumentado e com marcação superior de CK-19 comparativamente ao grupo de controlo. O compartimento imune foi também analisado nestas amostras e revelou-se alterado no CPNPC com aumento da população de monócitos e diminuição das subpopulações linfocitárias. Os transcriptos de CK-19, CEA e EPCAM estavam elevados nos doentes com cancro do pulmão, identificando-se uma correlação positiva entre estes marcadores e o tamanho da lesão primária. Concluiu-se que a identificação de CK-19, CEA e EPCAM nas amostras obtidas por ecoendoscopia e avaliadas por CF e RTPCR foi viável, podendo auxiliar na deteção de metástases ganglionares no CPNPC. O quarto estudo envolveu a combinação da ecoendoscopia brônquica radial com uma criosonda para o diagnóstico de lesões pulmonares sólidas periféricas. Foi determinada a viabilidade, rentabilidade diagnóstica, tamanho das amostras e segurança do método. Lesões inferiores a 40mm foram localizadas por ultrassonografia sendo os doentes randomizados para a realização de biópsias transbrônquicas com pinça seguidas por criosonda ou vice-versa. Nos 39 casos incluídos a lesão foi visualizada pela minisonda em 31 doentes (79.5%), com 80.6% de prevalência de cancro do pulmão na amostra. A rentabilidade diagnóstica da pinça de biópsia foi 61.3% e da criosonda foi 74.2%. O tamanho do tecido adquirido pelas criobiópsias foi significativamente maior do que o alcançado por pinça (11.17mm2 vs. 4.69mm2, p<0.001). Ocorreu um único caso de hemorragia moderada, controlada através de medidas conservadoras. As biópsias transbrônquicas com criosonda sob orientação de ecoendoscopia radial foram seguras e eficazes na obtenção de amostras histológicas. O quinto estudo determinou o valor diagnóstico da ecografia transtorácica na identificação de malignidade em doentes com derrame pleural de natureza indeterminada. Foram examinados de forma prospetiva 154 doentes. Os resultados clínicos e radiológicos de cada caso foram ocultados ao executante do exame que gerou imagens estáticas e vídeos ultrassonográficos relevantes. Estes foram posteriormente visualizados, sendo as suas características classificadas por revisores independentes e comparadas com o diagnóstico definitivo. Em 66 casos o diagnóstico foi de derrame pleural maligno (68.2% com cancro do pulmão) e em 67 de derrame benigno. A ecografia torácica obteve 80.3% de sensibilidade, 83.6% de especificidade, 81.2% de valor preditivo negativo e 82.8% de valor preditivo positivo na deteção de malignidade. A nodularidade pleural ou diafragmática, espessamento pleural superior a 10mm e sinal de swirling foram significativamente diferentes (p<0.001) sendo sugestivos de derrame maligno. A existência de nodularidade pleural e ausência de broncograma aéreo ecográfico aumentaram a probabilidade de malignidade (OR 29.0 e OR 10.4, respetivamente). A ecografia transtorácica permitiu diferenciar derrame pleural maligno do benigno. A existência de nódulos pleurais constituiu o fator discriminador mais relevante. Em conclusão, os resultados desta tese possibilitam uma melhor compreensão do papel da ecoendoscopia brônquica (linear e radial) e ecografia transtorácica no diagnóstico e estadiamento do cancro do pulmão, com implicações e aplicabilidade na prática clínica.------------- ABSTRACT: In recent years ultrasonography has emerged as an important instrument in the diagnosis of thoracic diseases. Technological progress has enabled the design of new equipment such as radial and linear endobronchial ultrasound. In addition, indications for transthoracic echography were established. One of the main diseases responsible for the progression of chest sonography was lung cancer, the leading cause of cancer mortality worldwide. The applicability and knowledge of the role of ultrasonography in diagnosing and staging lung cancer is not depleted, persisting foci of controversy and scientific doubt that we intend to elucidate. The present thesis was organized into five chapters: the first included a general introduction regarding chest ultrasound, lung cancer and their combination; the second emphasized the main objectives; the third summarized the methodology used; the fourth encompassed the five published studies, subsequently described, and the fifth included a concise discussion, the main findings and future perspectives. The first study evaluated the diagnostic yield, safety and learning curve in a cohort of 179 patients submitted to linear endobronchial ultrasound. According to procedure indications, the patients were divided into three groups: (1) diagnosis, (2) diagnosis and staging, and (3) staging. For the first, second and third groups, endobronchial ultrasound sensitivity was 86.1%, 86.7% and 95% respectively and accuracy was 87.5%, 93.1% and 97.7% respectively. Practise led to an increase number of punctured sites per patient, in a shorter period of time and without complications, proving the safety and efficacy of the method when performed in the Portuguese population by expert echoscopists. The second study was conducted to determine the efficacy and cost of linear endobronchial ultrasound performed through the airway and/or oesophagus for diagnosis of lesions suggestive of lung cancer, after failure of conventional techniques. Of the patients prospectively enrolled a definitive diagnosis was reached in 106 cases (87.6%). The overall sensitivity for the diagnosis of lung cancer was 89.8%, specificity was 100%, positive predictive value was 100%, negative predictive value was 20% and accuracy was 90.1%. In conclusion, this global ultrasonographic strategy avoided diagnostic surgical procedures in patients that had undergone flexible bronchoscopy or computed tomography-guided transthoracic needle aspiration, providing a significant cost reduction. In the third study, the feasibility and role of linear endobronchial ultrasound combined with molecular techniques in the evaluation of tumour antigens and patterns of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) was investigated. Cytokeratin 19 (CK-19), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EPCAM), sialyl Lewis-X and CD44 were determined in lymph node aspirates of 33 lung cancer patients and 17 controls, using flow cytometry (FC) and reverse transcription polymerase chain reaction (RT-PCR). In patients with NSCLC the epithelial cell compartment was significantly increased nd showed brighter CK-19 staining, compared to the control group. In NSCLC patients the immune compartment revealed an increased monocyte population and decreased lymphocyte subsets. The transcripts of CK- 19, CEA and EPCAM were higher in lung cancer patients and a positive correlation between these markers and the size of the primary lesion was also found. We concluded that the identification of CK-19, CEA and EPCAM in endobronchial ultrasound samples, using RT-PCR and FC was feasible and might aid in the detection of NSCLC lymph node metastases. The fourth study involved the combination of the radial endobronchial ultrasound with the cryoprobe for diagnosing solid peripheral lung lesions. We determined the feasibility, diagnostic yield, sample size and safety of the method. Lesions less than 40mm were located by ultrasound and forceps or cryobiopsies were performed in a randomized order. Of the 39 cases included, the lesion could be visualized by the miniprobe in 31 patients (79.5%), and lung cancer prevalence was 80.6%. The diagnostic yield of the biopsy forceps was 61.3% and for the cryobiopsy was 74.2 %. Cryobiopsies were significantly larger than forceps biopsies (11.17mm2 vs. 4.69mm2, p<0.001). There was only one case of moderate bleeding that was controlled by conservative measures. Transbronchial cryobiopsies under radial endobronchial ultrasound guidance were safe and effective in obtaining histological samples. The fifth study determined the diagnostic value of transthoracic sonography in predicting malignancy in patients with an undiagnosed pleural effusion. One hundred and fifty four patients were prospectively scanned. Relevant ultrasound images and videos were generated by an operator blinded to clinical and radiological results. These were subsequently visualized, its characteristics classified by independent reviewers and compared to the final diagnosis. A malignant pleural effusion was diagnosed in 66 cases (68.2 % with lung cancer) and a benign effusion in 67 cases. Thoracic ultrasound had a sensitivity of 80.3 %, specificity of 83.6%, negative predictive value of 81.2 % and positive predictive value of 82.8% to detect malignancy. The presence of pleural or diaphragmatic nodularity, pleural thickening greater than 10mm and swirling signal were significantly different (p<0.001 ), being suggestive of malignant effusion. The existence of pleural nodularity and absence of lung air bronchogram were more likely to indicate malignancy (OR 29.0 and OR 10.4, respectively). Transthoracic ultrasonography permits the distinction between malignant and benign pleural effusions. Pleural nodules were the most relevant feature. In conclusion, the results of this thesis provide a better understanding of the role of endobronchial ultrasound (linear and radial) and transthoracic sonography in lung cancer diagnosis and staging, with direct implications and applicability in clinical practice.

Size-Control Regulation during Regeneration

Functional regeneration of organs upon injury is a key process for animals survival. Contrary to humans, some vertebrates are remarkably competent in regenerating after acute organ or appendage lesions. This advantageous skill allows overcoming limitations in repair even in adult stages, when tissues are fully developed, via a process of epimorphic regeneration. One such organism is the zebrafish, which can regenerate several organs, namely its heart, retina, spinal cord and fins. (...)

The role of deposit insurance and bank’s asset size in the 2008 financial crisis

In this paper we analyze the role of deposit insurance in providing the market with liquidity in times of financial turmoil. To do so, we look at the variation in insured and uninsured deposits between 2005Q3 and 2011Q3, controlling for liquidity, solvency and capital adequacy indicators, and find evidence that deposit insurance does provide some confidence in keeping funds in banks in times of turmoil. Additionally we follow an event study methodology to assess the impact of deposit insurance oriented policies on bank holding companies stock market returns, and find a TBTF effect.

Prospective system analysis of stationary battery systems under the frame of Constructive Technology Assessment

Based on the report for the unit “Project IV” of the PhD programme on Technology Assessment under the supervision of Dr.-Ing. Marcel Weil and Prof. Dr. António Brandão Moniz. The report was presented and discussed at the Doctorate Conference on Technologogy Assessment in July 2013 at the University Nova Lisboa, Caparica campus.

Paradox of choice: The influence of assortment size on customer satisfaction

Recently researchers showed that more choice is not always better. Choosing from large assortments can be overwhelming, raising expectations and decreasing overall level of consumer satisfaction. Author contributes to existing overchoice studies by using real assortment of online stores to find influence of assortment size on customer satisfaction. 90 students participated in the main experiment, where they chose a smartphone case for their friend. Results of the study show that large assortment size leads to higher expectations, higher choice difficulty and higher level of satisfaction. This research does not show overchoice presence and author suggests future studies could focus more on assortment variety and more personal characteristics of consumers, like preference uncertainty.

Size of gastroesophageal varices: its behavior after the surgical treatment of portal hypertension

The size of gastroesophageal varices is one of the most important factors leading to hemorrhage related to portal hypertension. An endoscopic evaluation of the size of gastroesophageal varices before and after different operations for portal hypertension was performed in 73 patients with schistosomiasis, as part of a randomized trial: proximal splenorenal shunt (PSS n=24), distal splenorenal shunt (DSS n=24), and esophagogastric devascularization with splenectomy (EGDS n=25). The endoscopic evaluation was performed before and up to 10 years after the operations. Variceal size was graded according to Palmer's classification: grade 1 -- up to 3 mm, grade 2 -- from 3 to 6 mm, grade 3 -- greater than 6 mm, and were analyzed in four anatomical locations: inferior, middle or superior third of the esophagus, and proximal stomach. The total number of points in the pre-operative grading minus the number of points in the post-operative grading gave a differential grading, allowing statistical comparison among the surgical groups. Good results, in terms of disappearance or decrease of variceal size, were observed more frequently after PSS than after DSS or EGDS - 95.8%, 83.3%, and 72%, respectively. When differential grading was analyzed, a statistically significant difference was observed between PSS and EGDS, but not between proximal and distal splenorenal shunts. In conclusion, shunt surgeries were more efficient than devascularization in diminishing variceal size.

Analysis and Treatment of a male portrait in oil and a study of the size layer with reconstructions from Vibert’s recipe (1892)

This thesis project concentrated on both the study and treatment of an early 20th century male portrait in oil from Colecção Caixa Geral de Depósitos, Lisbon, Portugal. The portrait of Januário Correia de Almeida, exhibits a tear (approximately 4.0 cm by 2.3 cm) associated with paint loss on the right upper side, where it is possible to observe an unusually thick size layer (approximately 50 microns) and an open weave mesh canvas. Size layers made from animal glue remain subject to severe dimensional changes due to changes in relative humidity (RH), thereby affecting the stability of the painting. In this case, the response to moisture of the size layer is minimal and the painting is largely uncracked with very little active flaking. This suggests that the size layer has undergone pre-treatment to render it unresponsive to moisture or water. Reconstructions based on late nineteenth century recipes using historically appropriate materials are used to explore various options for modifying the characteristics of gelatine, some of which may relate to the Portrait’s size layer. The thesis is separated into two parts: Part 1: Describes the history, condition, materials and techniques of the painting. It also details the treatment of Januário Correia de Almeida as well as the choices made and problems encountered during the treatment. Part 2: Discusses the history of commercial gelatine production, the choice of the appropriate animal source to extract the collagen to produce reconstructions of the portrait’s size layer as well as the characterization of selected reconstructions. The execution of a shallow textured infill led to one publication and one presentation: Abstract accepted for presentation and publication, International Meeting on Retouching of Cultural Heritage (RECH3), Francisco Brites, Leslie Carlyle and Raquel Marques, ‘’Hand building a Low Profile Textured Fill for a Large Loss’’.

Analysis and treatment of a nineteenth century portrait, study of Artsorb® and a proposal for a microclimate frame

The present work is divided in two parts: Part 1 is focused on the analysis and treatment of a 19th century portrait of Domingos Affonso, which belongs to the Ecomuseu Municipal do Seixal; and Part 2, which is entitled “The Microclimate Frame Project” is focused on the study of Artsorb® and on the planning of a microclimate frame for the painting. In Part 1, a study of the painting’s materials was performed using complementary analytical techniques and the painting’s condition was carefully evaluated. The painting exhibited signs of mould growth, and a more detailed investigation was made of this topic to understand if the fungal community was active and if it represented a real danger to the painting. A treatment was proposed, appropriate to the painting’s condition. A description of the treatment carried out, comprising the treatment options, is also present in this section. Within the study of the microclimate frame, in Part 2, the study of the potential corrosiveness of Artsorb® was a central subject. Artsorb® sheets are one of the most widely used materials for buffering relative humidity fluctuations in microclimate frames and its reported excellent performance is enhanced by its availability in lightweight sheets that can be easily placed inside microclimate frames. However, concerns have arisen regarding the presence of the corrosive salt lithium chloride in the composition of this buffer. Consequently, the present work also aimed to understand the potential risks of using Artsorb® and the possibility of avoiding exposure of lithium chloride to the artworks through the use of Tyvek®. Results from the preliminary tests seem to indicate that Artsorb® releases lithium chloride into air. This study also showed that a Tyvek® cover over Artsorb® reduces but does not eliminate evidence of chlorine contamination, and it significantly reduces the effectiveness of the buffering material. Considering that Artsorb® appears to be unsuitable due to the release of the corrosive salt, that Tyvek® was not efficient as a barrier for lithium chloride or as a permeable material to enable the proper functioning of Artsorb®, the buffering material proposed for the use in the microclimate frames is silica gel without indicator. Based on the choice of buffering material, as a result of this study, a microclimate frame is proposed.

Experimental analysis of the cyclic response of traditional timber joints and their influence on the seismic capacity of timber frame structures

Timber connections represent the crucial part of a timber structure and a great variability exists in terms of types of connections and mechanisms. Taking as case study the widespread traditional timber frame structures, in particular the Portuguese Pombalino buildings, one of the most common timber connection is the half-lap joint. Connections play a major role in the overall behaviour of a structure, particularly when assessing their seismic response, since damage is concentrated at the connections. For this reason, an experimental campaign was designed and distinct types of tests were carried out on traditional half-lap joints to assess their in-plane response. In particular, pull-out and in-plane cyclic tests were carried out on real scale unreinforced connections. Subsequently, the connections were retrofitted, using strengthening techniques such as self-tapping screws, steel plates and GFRP sheets. The tests chosen were meant to capture the hysteretic behaviour and dissipative capacity of the connections and characterise their response and, therefore, their influence on the seismic response of timber frame walls, particularly concerning their uplifting and rotation capacity, that could lead to rocking in the walls. In this paper, the results of the experimental campaign are presented in terms of hysteretic curves, dissipated energy and equivalent viscous damping ratio. Moreover, recommendations are provided on the most appropriate retrofitting solutions.

Seismic behaviour of traditional timber frame walls: experimental results on unreinforced walls

Timber frame buildings are well known as an efficient seismic resistant structure and they are used worldwide. Moreover, they have been specifically adopted in codes and regulations during the XVIII and XIX centuries in the Mediterranean area. These structures generally consist of exterior masonry walls with timber elements embedded which tie the walls together and internal walls which have a timber frame with masonry infill and act as shearwalls. In order to preserve these structureswhich characterizemany cities in theworld it is important to better understand their behaviour under seismic actions. Furthermore, historic technologies could be used even in modern constructions to build seismic resistant buildings using more natural materials with lesser costs. Generally, different types of infill could be applied to timber frame walls depending on the country, among which brick masonry, rubble masonry, hay and mud. The focus of this paper is to study the seismic behaviour of the walls considering different types of infill, specifically: masonry infill, lath and plaster and timber frame with no infill. Static cyclic tests have been performed on unreinforced timber frame walls in order to study their seismic capacity in terms of strength, stiffness, ductility and energy dissipation. The tests showed how in the unreinforced condition, the infill is able to guarantee a greater stiffness, ductility and ultimate capacity of the wall.

Application of near surface mounted (NSM) strengthening technique to traditional timber frame walls

Timber frame buildings are well known as an efficient seismic resistant structure popular all over the world not only due to their seismic performance, but also to their low cost and the strength they offer. These constructions still exist today and it is important to be able to preserve them, so a better knowledge on their behaviour is sought. Furthermore, historic technologies could be used even in modern constructions to build seismic resistant buildings using more natural materials with lesser costs. A great rehabilitation effort is being carried out on this type of buildings, as their neglect has led to decay or their change in use and alterations to the structure has led to the need to retrofit such buildings; only recently studies on their behaviour have become available and only a few of them address the issue of possible strengthening techniques for this kind of walls. In this scope, an innovative retrofitting technique (near surface mounted steel flat bars) is proposed and validated on traditional timber frame walls based on an extensive experimental program. The results of the static cyclic tests on distinct wall typologies retrofitted with the NSM technique are herein presented and discussed in detail. The main features on deformation, lateral stiffness, lateral resistance and seismic performance indexes are analysed

Traditional timber frame walls: mechanical behavior analysis and retrofitting

Timber frame construction is characteristic of several historic city centres as well as of vernacular architecture in several countries around the world, either motivated by the availability of materials and construction traditions or by the need of reducing the seismic vulnerability of buildings, namely in south European countries, where this construction technique was adopted for seismic-resistance purposes. From past earthquakes, it has been seen that timber frame construction can be viewed as an interesting technology as it has exhibited a very reasonable behaviour when compared to other traditional construction techniques such as masonry walls. This chapter provides an overview of the main insights on the seismic performance of timber frame buildings from the evidences of past earthquakes and provides the main results of recent research focused on the in-plane cyclic behavior of timber frame walls with distinct geometrical configurations. Additionally, the main seismic performance indexes of timber frame walls, both unreinforced and retrofitted, are presented and discussed in detail.

Numerical approaches for the analysis of timber frame walls

A numerical approach to simulate the behaviour of timber shear walls under both static and dynamic loading is proposed. Because the behaviour of timber shear walls hinges on the behaviour of the nail connections, the force-displacement behaviour of sheathing-to-framing nail connections are first determined and then used to define the hysteretic properties of finite elements representing these connections. The model nails are subsequently implemented into model walls. The model walls are verified using experimental results for both monotonic and cyclic loading. It is demonstrated that the complex hysteretic behaviour of timber shear walls can be reasonably represented using model shear walls in which nonlinear material failure is concentrated only at the sheathing-to-framing nail connections.

Local seismic cultures: the use of timber frame structures in the south of Portugal

Given the fact that using timber frame structures has proven to improve the seismic behavior of vernacular architecture, as has been reported in past earthquakes in many countries, its preservation as a traditional earthquake resistant practice is important. This paper firstly intends to evaluate whether the use of timber frames as a traditional seismic resistant technique for vernacular architecture in the South of Portugal, traditionally a seismic region, is still active. Secondly, the city of Vila Real de Santo António was selected as a case study because it also followed a Pombaline development contemporary to the reconstruction of Lisbon. The plan included the provision of timber frame partition walls for some of the buildings and, thus, an overview of the type of constructions originally conceived is provided. Finally, the alterations done in the original constructions and the current state of the city center are described and the effect of these changes on the seismic vulnerability of the city is discussed.