Chagas' disease: an algorithm for donor screening and positive donor counseling

Classical serological screening assays for Chagas' disease are time consuming and subjective. The objective of the present work is to evaluate the enzyme immuno-assay (ELISA) methodology and to propose an algorithm for blood banks to be applied to Chagas' disease. Seven thousand, nine hundred and ninety nine blood donor samples were screened by both reverse passive hemagglutination (RPHA) and indirect immunofluorescence assay (IFA). Samples reactive on RPHA and/or IFA were submitted to supplementary RPHA, IFA and complement fixation (CFA) tests. This strategy allowed us to create a panel of 60 samples to evaluate the ELISA methodology from 3 different manufacturers. The sensitivity of the screening by IFA and the 3 different ELISA's was 100%. The specificity was better on ELISA methodology. For Chagas disease, ELISA seems to be the best test for blood donor screening, because it showed high sensitivity and specificity, it is not subjective and can be automated. Therefore, it was possible to propose an algorithm to screen samples and confirm donor results at the blood bank.

Maintaining the correctness of transactional memory programs

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

Revision based total semantics for extended normal logic programs

Dissertação para obtenção do Grau de Doutor em Matemática - Lógica e Fundamentos da Matemática

Diffusional kurtosis imaging using a fast heuristic constrained linear least squares algorithm: a plugin for OsiriX

Diffusion Kurtosis Imaging (DKI) is a fairly new magnetic resonance imag-ing (MRI) technique that tackles the non-gaussian motion of water in biological tissues by taking into account the restrictions imposed by tissue microstructure, which are not considered in Diffusion Tensor Imaging (DTI), where the water diffusion is considered purely gaussian. As a result DKI provides more accurate information on biological structures and is able to detect important abnormalities which are not visible in standard DTI analysis. This work regards the development of a tool for DKI computation to be implemented as an OsiriX plugin. Thus, as OsiriX runs under Mac OS X, the pro-gram is written in Objective-C and also makes use of Apple’s Cocoa framework. The whole program is developed in the Xcode integrated development environ-ment (IDE). The plugin implements a fast heuristic constrained linear least squares al-gorithm (CLLS-H) for estimating the diffusion and kurtosis tensors, and offers the user the possibility to choose which maps are to be generated for not only standard DTI quantities such as Mean Diffusion (MD), Radial Diffusion (RD), Axial Diffusion (AD) and Fractional Anisotropy (FA), but also DKI metrics, Mean Kurtosis (MK), Radial Kurtosis (RK) and Axial Kurtosis (AK).The plugin was subjected to both a qualitative and a semi-quantitative analysis which yielded convincing results. A more accurate validation pro-cess is still being developed, after which, and with some few minor adjust-ments the plugin shall become a valid option for DKI computation

Impact of using different radiation therapy techniques in breat cancer: contralateral breast dose

RESUMO: O cancro de mama e o mais frequente diagnoticado a indiv duos do sexo feminino. O conhecimento cientifico e a tecnologia tem permitido a cria ção de muitas e diferentes estrat egias para tratar esta patologia. A Radioterapia (RT) est a entre as diretrizes atuais para a maioria dos tratamentos de cancro de mama. No entanto, a radia ção e como uma arma de dois canos: apesar de tratar, pode ser indutora de neoplasias secund arias. A mama contralateral (CLB) e um orgão susceptivel de absorver doses com o tratamento da outra mama, potenciando o risco de desenvolver um tumor secund ario. Nos departamentos de radioterapia tem sido implementadas novas tecnicas relacionadas com a radia ção, com complexas estrat egias de administra ção da dose e resultados promissores. No entanto, algumas questões precisam de ser devidamente colocadas, tais como: E seguro avançar para tecnicas complexas para obter melhores indices de conformidade nos volumes alvo, em radioterapia de mama? O que acontece aos volumes alvo e aos tecidos saudaveis adjacentes? Quão exata e a administração de dose? Quais são as limitações e vantagens das técnicas e algoritmos atualmente usados? A resposta a estas questões e conseguida recorrendo a m etodos de Monte Carlo para modelar com precisão os diferentes componentes do equipamento produtor de radia ção(alvos, ltros, colimadores, etc), a m de obter uma descri cão apropriada dos campos de radia cão usados, bem como uma representa ção geometrica detalhada e a composição dos materiais que constituem os orgãos e os tecidos envolvidos. Este trabalho visa investigar o impacto de tratar cancro de mama esquerda usando diferentes tecnicas de radioterapia f-IMRT (intensidade modulada por planeamento direto), IMRT por planeamento inverso (IMRT2, usando 2 feixes; IMRT5, com 5 feixes) e DCART (arco conformacional dinamico) e os seus impactos em irradia ção da mama e na irradia ção indesejada dos tecidos saud aveis adjacentes. Dois algoritmos do sistema de planeamento iPlan da BrainLAB foram usados: Pencil Beam Convolution (PBC) e Monte Carlo comercial iMC. Foi ainda usado um modelo de Monte Carlo criado para o acelerador usado (Trilogy da VARIAN Medical Systems), no c odigo EGSnrc MC, para determinar as doses depositadas na mama contralateral. Para atingir este objetivo foi necess ario modelar o novo colimador multi-laminas High- De nition que nunca antes havia sido simulado. O modelo desenvolvido est a agora disponí vel no pacote do c odigo EGSnrc MC do National Research Council Canada (NRC). O acelerador simulado foi validado com medidas realizadas em agua e posteriormente com c alculos realizados no sistema de planeamento (TPS).As distribui ções de dose no volume alvo (PTV) e a dose nos orgãos de risco (OAR) foram comparadas atrav es da an alise de histogramas de dose-volume; an alise estati stica complementar foi realizadas usando o software IBM SPSS v20. Para o algoritmo PBC, todas as tecnicas proporcionaram uma cobertura adequada do PTV. No entanto, foram encontradas diferen cas estatisticamente significativas entre as t ecnicas, no PTV, nos OAR e ainda no padrão da distribui ção de dose pelos tecidos sãos. IMRT5 e DCART contribuem para maior dispersão de doses baixas pelos tecidos normais, mama direita, pulmão direito, cora cão e at e pelo pulmão esquerdo, quando comparados com as tecnicas tangenciais (f-IMRT e IMRT2). No entanto, os planos de IMRT5 melhoram a distribuição de dose no PTV apresentando melhor conformidade e homogeneidade no volume alvo e percentagens de dose mais baixas nos orgãos do mesmo lado. A t ecnica de DCART não apresenta vantagens comparativamente com as restantes t ecnicas investigadas. Foram tamb em identi cadas diferen cas entre os algoritmos de c alculos: em geral, o PBC estimou doses mais elevadas para o PTV, pulmão esquerdo e cora ção, do que os algoritmos de MC. Os algoritmos de MC, entre si, apresentaram resultados semelhantes (com dferen cas at e 2%). Considera-se que o PBC não e preciso na determina ção de dose em meios homog eneos e na região de build-up. Nesse sentido, atualmente na cl nica, a equipa da F sica realiza medi ções para adquirir dados para outro algoritmo de c alculo. Apesar de melhor homogeneidade e conformidade no PTV considera-se que h a um aumento de risco de cancro na mama contralateral quando se utilizam t ecnicas não-tangenciais. Os resultados globais dos estudos apresentados confirmam o excelente poder de previsão com precisão na determinação e c alculo das distribui ções de dose nos orgãos e tecidos das tecnicas de simulação de Monte Carlo usados.---------ABSTRACT:Breast cancer is the most frequent in women. Scienti c knowledge and technology have created many and di erent strategies to treat this pathology. Radiotherapy (RT) is in the actual standard guidelines for most of breast cancer treatments. However, radiation is a two-sword weapon: although it may heal cancer, it may also induce secondary cancer. The contralateral breast (CLB) is a susceptible organ to absorb doses with the treatment of the other breast, being at signi cant risk to develop a secondary tumor. New radiation related techniques, with more complex delivery strategies and promising results are being implemented and used in radiotherapy departments. However some questions have to be properly addressed, such as: Is it safe to move to complex techniques to achieve better conformation in the target volumes, in breast radiotherapy? What happens to the target volumes and surrounding healthy tissues? How accurate is dose delivery? What are the shortcomings and limitations of currently used treatment planning systems (TPS)? The answers to these questions largely rely in the use of Monte Carlo (MC) simulations using state-of-the-art computer programs to accurately model the di erent components of the equipment (target, lters, collimators, etc.) and obtain an adequate description of the radiation elds used, as well as the detailed geometric representation and material composition of organs and tissues. This work aims at investigating the impact of treating left breast cancer using di erent radiation therapy (RT) techniques f-IMRT (forwardly-planned intensity-modulated), inversely-planned IMRT (IMRT2, using 2 beams; IMRT5, using 5 beams) and dynamic conformal arc (DCART) RT and their e ects on the whole-breast irradiation and in the undesirable irradiation of the surrounding healthy tissues. Two algorithms of iPlan BrainLAB TPS were used: Pencil Beam Convolution (PBC)and commercial Monte Carlo (iMC). Furthermore, an accurate Monte Carlo (MC) model of the linear accelerator used (a Trilogy R VARIANR) was done with the EGSnrc MC code, to accurately determine the doses that reach the CLB. For this purpose it was necessary to model the new High De nition multileaf collimator that had never before been simulated. The model developed was then included on the EGSnrc MC package of National Research Council Canada (NRC). The linac was benchmarked with water measurements and later on validated against the TPS calculations. The dose distributions in the planning target volume (PTV) and the dose to the organs at risk (OAR) were compared analyzing dose-volume histograms; further statistical analysis was performed using IBM SPSS v20 software. For PBC, all the techniques provided adequate coverage of the PTV. However, statistically significant dose di erences were observed between the techniques, in the PTV, OAR and also in the pattern of dose distribution spreading into normal tissues. IMRT5 and DCART spread low doses into greater volumes of normal tissue, right breast, right lung, heart and even the left lung than tangential techniques (f-IMRT and IMRT2). However,IMRT5 plans improved distributions for the PTV, exhibiting better conformity and homogeneity in target and reduced high dose percentages in ipsilateral OAR. DCART did not present advantages over any of the techniques investigated. Di erences were also found comparing the calculation algorithms: PBC estimated higher doses for the PTV, ipsilateral lung and heart than the MC algorithms predicted. The MC algorithms presented similar results (within 2% di erences). The PBC algorithm was considered not accurate in determining the dose in heterogeneous media and in build-up regions. Therefore, a major e ort is being done at the clinic to acquire data to move from PBC to another calculation algorithm. Despite better PTV homogeneity and conformity there is an increased risk of CLB cancer development, when using non-tangential techniques. The overall results of the studies performed con rm the outstanding predictive power and accuracy in the assessment and calculation of dose distributions in organs and tissues rendered possible by the utilization and implementation of MC simulation techniques in RT TPS.

Extended-spectrum β-lactamase-producing Salmonella enterica serovar Oranienburg (CTX-M-2 group) in a pediatric hospital in Tucumán, Argentina

INTRODUCTION: Salmonella sp infections have been reported over recent years in hospitals in Argentina and other countries due to multiresistant strains. The aim of this study was to characterize the extended-spectrum β-lactamases in third-generation cephalosporin-resistant strains of Salmonella enterica serovar Oranienburg. METHODS: We studied 60 strains isolated from children with gastroenteritis and/or extraintestinal complications. The antibiotic susceptibility patterns of the isolates were analyzed and the β-lactamases were characterized using phenotyping and genotyping methods. RESULTS: All the strains were resistant to ampicillin, cefotaxime, cefepime and aztreonam and partially susceptible to ceftazidime, thus corresponding well with the resistance phenotype conferred by CTX-M-type β-lactamases. An isoelectric point enzyme (pI = 7.9) was detected in all of the strains, and this was confirmed by PCR as a member of the CTX-M-2 group. CONCLUSIONS: This is the first report of Salmonella enterica serovar Oranienburg producing β-lactamases of the CTX-M-2 group in a pediatric hospital in Tucumán, Argentina.

Epidemiology of extended spectrum β-lactamase producing Enterobacter bacteremia in a brazilian hospital

INTRODUCTION: Enterobacter can be included in the group of extended spectrum β-lactamases (EBSL)-producing bacteria, though few studies exist evaluating risk factors associated with this microorganism. A retrospective cohort study was conducted to determine risk factors associated with ESBL-producing-Enterobacter and mortality METHODS: A retrospective cohort study with 58 bacteremia caused by ESBL-producing-Enterobacter (28 cases) and non-ESBL (30 cases) RESULTS: Risk factors associated with ESBL-Enterobacter were trauma, length of hospitalization, admission to the intensive care unit, urinary catheter and elective surgery (p< 0.05). The survival curves were similar for ESBL and non-ESBL CONCLUSIONS: ESBL-producing-Enterobacter bacteremia is prevalent and the survival curve was similar to non-ESBL-producing strains.

Nosocomial infection and characterization of extended-spectrum β-lactamases-producing Enterobacteriaceae in Northeast Brazil

INTRODUCTION: Extended spectrum β-lactamases (ESBLs) are enzymes that degrade β-lactam antibiotics and have been reported to be an important cause of nosocomial infection in worldwide. METHODS: During 2009, 659 enterobacteria strains were isolated from different clinical specimens and tested for ESBL production. The disk approximation test, combined disk method and addition of clavulanic acid were used for phenotypic detection of the ESBL-producing strains and PCR for detection of the blaTEM and blaCTX-M genes. RESULTS: Among the isolates, 125 were ESBL producers. The blaCTX-M and blaTEM genes were detected in 90.4% and 75% of the strains, respectively. Most strains were isolated from urine. Klebsiella pneumoniae was the most prevalent organism. Microorganisms presented high resistance to the antibiotics. CONCLUSIONS: These results support the need for extending ESBL detection methods to different pathogens of the Enterobacteriaceae family because these methods are only currently standardized by the CLSI for Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Proteus mirabilis. Carbapenems were the antibiotic class of choice for the treatment of infections caused by ESBL-producing Enterobacteriaceae.

Towards an integrated technology management across the rail supply chain extended to society: building the case study on high-speed trains

The present paper was prepared for the course “Project III”, with the supervision of Prof. António Moniz, reporting on the author speaking notes at the Winter School on Technology Assessment, 6-7 December 2010, as part of the Doctoral Programme on Technology Assessment at FCT-UNL.

EDP - A new estimation algorithm

The aim of this work project is to analyze the current algorithm used by EDP to estimate their clients’ electrical energy consumptions, create a new algorithm and compare the advantages and disadvantages of both. This new algorithm is different from the current one as it incorporates some effects from temperature variations. The results of the comparison show that this new algorithm with temperature variables performed better than the same algorithm without temperature variables, although there is still potential for further improvements of the current algorithm, if the prediction model is estimated using a sample of daily data, which is the case of the current EDP algorithm.

Distribution of extended-spectrum β-lactamase types in a Brazilian tertiary hospital

INTRODUCTION: Epidemiological data on the prevalence of extended-spectrum β-lactamases (ESBLs) are scarce in Brazil despite the fact that these data are essential for empirical treatment and control measures. The objective of this study was to evaluate the prevalence of different ESBLs by type and distribution in a tertiary hospital in southern Brazil. METHODS: We evaluated 1,827 enterobacterial isolates between August 2003 and March 2008 isolated from patients at a tertiary hospital. Samples were identified using a Vitek automated system and were confirmed by biochemical testing. The identified ESBL strains were characterized by phenotypic methods, polymerase chain reaction (PCR), and sequencing. Genetic similarities were evaluated by pulsed-field gel electrophoresis. RESULTS: It was 390 (21.3%) ESBL-producing strains, which expressed the ESBLs CTX-M (292), SHV (84), CTX and SHV (10), TEM (2), and PER (2). CONCLUSIONS: The prevalence of ESBL-expressing strains was high, especially in Klebsiella pneumoniae and Enterobacter spp. CTX-M was the predominant type of ESBL observed, and its genetic variability indicates a polyclonal distribution.

Phenotypic and molecular characterization of CTX-M extended-spectrum beta-lactamase-producing Escherichia coli isolates in Shiraz, Iran

AbstractINTRODUCTIONThe aim of this study was to detect the prevalence of the extended-spectrum beta-lactamase (ESBL)-encoding CTX-M gene in Escherichia coliisolates.METHODS:Phenotypic screening of 376 E. coli isolates for ESBL was conducted using disk diffusion. ESBL-producing isolates were tested using PCR and specific primers. The blaCTX-M cluster was identified using the RFLP method, and its genotype was sequenced.RESULTS:From 202 ESBL-producing E. coli , 185 (91.5%) possessed CTX-M genes. CTX-M-1 subtypes were found in 98% of the isolates. The blaCTX-M gene was identical to CTX-M-15.CONCLUSIONS:A high prevalence of CTX-M-1-producing E. coli apparently exists in Shiraz, Iran.

Occurrence and sensitivity profile of extended spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary hospital in Southern Brazil

Abstract: INTRODUCTION: Nosocomial infections are closely associated with antimicrobial drug resistance. One of the most important mechanisms of resistance to β-lactam antibiotics is the production of extended spectrum β-lactamases (ESBLs). The objective of the present study was to evaluate the prevalence and antimicrobial susceptibility profile of ESBL-producing strains and to assess the evolution of antimicrobial drug resistance between 2007 and 2013 at the Hospital São Vicente de Paulo, Passo Fundo, State of Rio Grande do Sul, Brazil. METHODS: We conducted a descriptive, observational, cross-sectional study. Bacterial culture was performed from January to December 2013. The antimicrobial susceptibility profile of these cultures was determined using the disk diffusion method. Phenotypic screening for ESBL production was performed using the disk approximation method. RESULTS : We analyzed a total of 19,112 cultures, 11.5% of which were positive for Enterobacteriaceae. Of these, 30.3% of the isolates were positive for ESBL production, and the most prevalent species was Klebsiella sp. (37.5%). Over 95% of these isolates showed reduced susceptibility to all cephalosporins, aztreonam, and amoxicillin/clavulanic acid. The isolates also showed high sensitivity to the following antimicrobials: amikacin, meropenem, and piperacillin/tazobactam. Overall, the resistance rates among ESBL-producing Enterobacteriaceae decreased from 2007 to 2013. CONCLUSIONS : In our hospital, the increased sensitivity to certain antimicrobial agents seems to be directly related to the implementation of improvements in the methods to prevent and control nosocomial infections in addition to the natural development of other resistance mechanisms.