Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial

OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.

Validação de um método de cromatografia de alta eficiência para determinação de conservantes em géneros alimentícios

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Química e Biológica

Validity and reliability of a health care service evaluation instrument for tuberculosis

OBJECTIVE To evaluate the validity and reliability of an instrument that evaluates the structure of primary health care units for the treatment of tuberculosis.METHODS This cross-sectional study used simple random sampling and evaluated 1,037 health care professionals from five Brazilian municipalities (Natal, state of Rio Grande do Norte; Cabedelo, state of Paraíba; Foz do Iguaçu, state of Parana; Sao José do Rio Preto, state of Sao Paulo, and Uberaba, state of Minas Gerais) in 2011. Structural indicators were identified and validated, considering different methods of organization of the health care system in the municipalities of different population sizes. Each structure represented the organization of health care services and contained the resources available for the execution of health care services: physical resources (equipment, consumables, and facilities); human resources (number and qualification); and resources for maintenance of the existing infrastructure and technology (deemed as the organization of health care services). The statistical analyses used in the validation process included reliability analysis, exploratory factor analysis, and confirmatory factor analysis.RESULTS The validation process indicated the retention of five factors, with 85.9% of the total variance explained, internal consistency between 0.6460 and 0.7802, and quality of fit of the confirmatory factor analysis of 0.995 using the goodness-of-fit index. The retained factors comprised five structural indicators: professionals involved in the care of tuberculosis patients, training, access to recording instruments, availability of supplies, and coordination of health care services with other levels of care. Availability of supplies had the best performance and the lowest coefficient of variation among the services evaluated. The indicators of assessment of human resources and coordination with other levels of care had satisfactory performance, but the latter showed the highest coefficient of variation. The performance of the indicators “training” and “access to recording instruments” was inferior to that of other indicators.CONCLUSIONS The instrument showed feasibility of application and potential to assess the structure of primary health care units for the treatment of tuberculosis.

Phage display as a tool for development of novel therapeutics for breast cancer

Phage display technology is a powerful platform for the generation of highly specific human monoclonal antibodies (Abs) with potential use in clinical applications. Moreover, this technique has also proven to be a reliable approach in identifying and validating new cancer-related targets. For scientific or medical applications, different types of Ab libraries can be constructed. The use of Fab Immune libraries allows the production of high quality and affinity antigen-specific Abs. In this work, two immune human phage display IgG Fab libraries were generated from the Ab repertoire of 16 breast cancer patients, in order to obtain a tool for the development of new therapeutic Abs for breast cancer, a condition that has great impact worldwide. The generated libraries are estimated to contain more than 108 independent clones and a diversity over 90%. Libraries validation was pursued by selection against BSA, a foreign and highly immunogenic protein, and HER2, a well established cancer target. Preliminary results suggested that phage pools with affinity for these antigens were selected and enriched. Individual clones were isolated, however, it was not possible to obtain enough data to further characterize them. Selection against the DLL1 protein was also performed, once it is a known ligand of the Notch pathway, whose deregulation is associated to breast cancer, making it an interesting target for the generation of function-blocking Abs. Selection resulted in the isolation of a clone with low affinity and Fab expression levels. The validation process was not completed and further effort will have to be put in this task in the future. Although immune libraries concept implies limited applicability, the library reported here has a wide range of use possibilities, since it was not restrained to a single antigen but instead thought to be used against any breast cancer associated target, thus being a valuable tool.

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.

Desenvolvendo a qualidade em parcerias: a voz de um grupo de educadoras

Tese de Doutoramento em Estudos da Criança (Especialidade de Metodologia e Supervisão em Educação de Infância)

Simulador de conducció enfocat a la investigació

El desenvolupament de sistemes d’assistència a la conducció (ADAS) és, avui dia, una de les àrees de recerca de més interès pel Centre de Visió per Computador. A partir de la informació adquirida per sensors instal·lats en un vehicle, els ADAS assisteixen al conductor per tal d’evitar situacions de perill. La validació d’aquests sistemes però, requereix de l’obtenció "manual" de les dades que defineixen l’entorn de conducció de forma precisa: una tasca costosa i subjecta a l’error humà. Per tal de resoldre aquest problema, en aquest projecte s’ha implementat IOCS, un simulador de conducció creat a partir d’un de robots, capaç de crear entorns realistes de conducció i d’obtenir, simultàniament, les dades sobre l’entorn inferides per un ADAS i les que el descriuen objectivament. Aquesta funcionalitat facilita extremadament el procés de validació actual dels sistemes d’assistència a la conducció.

Validación de la versión española del cuestionario sobre la práctica basada en la evidencia en enfermería

Background: The lack of adequate instruments prevents the possibility of assessing the competence of health care staff in evidence-based decision making and further, the identification of areas for improvement with tailored strategies. The aim of this study is to report about the validation process in the Spanish context of the Evidence-Based Practice Questionnaire (EBPQ) from Upton y Upton. Methods: A multicentre, cross-sectional, descriptive psychometric validation study was carried out. For cultural adaptation, a bidirectional translation was developed, accordingly to usual standards. The measuring model from the questionnaire was undergone to contrast, reproducing the original structure by Exploratory Factorial Analysis (EFA) and Confirmatory Factorial Analysis (CFA), including the reliability of factors. Results: Both EFA (57.545% of total variance explained) and CFA (chi2=2359,9555; gl=252; p<0.0001; RMSEA=0,1844; SRMR=0,1081), detected problems with items 7, 16, 22, 23 and 24, regarding to the original trifactorial version of EBPQ. After deleting some questions, a reduced version containing 19 items obtained an adequate factorial structure (62.29% of total variance explained), but the CFA did not fit well. Nevertheless, it was significantly better than the original version (chi2=673.1261; gl=149; p<0.0001; RMSEA=0.1196; SRMR=0.0648). Conclusions: The trifactorial model obtained good empiric evidence and could be used in our context, but the results invite to advance with further refinements into the factor “attitude”, testing it in more contexts and with more diverse professional profiles.

Estudio y construcción de herramientas de validación HTML

The Final Year Project consists of two essentially different parts, which share acommon theme: HTML code validation. The first of these two parts focuses on the study of the validation process. It supplies a brief introduction to the evolution of HTML and XHTML, the new tags introduced in HTML5 and the most common errors found in today's websites. Already developed HTML validation tools are analyzed and examined in detail in order to compare their features and evaluate their performances. Lastly, a comparison of the parsing process in the most common browsers found nowadays is provided. In the second part of the project the focus of the project is shifted towards the development of a XHTML5 validation tool. The input is a XHTML5 file whose content may or may not comply with the W3C specification, and therefore, may or may not be a valid XHTML5 document. The output provided by this tool will be a fixed XHTML5 document and an error log returned in the form of a XML file. Information as to the course of action pursued to fix the error and its location will also be included.

Tornadoes and waterspouts in Catalonia (1950-2009)

This paper presents a preliminary climatology of tornadoes and waterspouts in Catalonia (NE Iberian Peninsula). A database spanning 60 yr (1950-2009) has been developed on the basis of information collected from various sources such as weather reports, insurance companies, newspapers and damage surveys. This database has been subjected to a rigorous validation process, and the climatology describes its main features: timing, spatial pattern, and trends in the tornado and waterspout distribution. Results show the highest concentration of tornadoes from August to October, the highest density in the heavily populated coastal areas and a growing positive trend that is likely more closely linked to an increase in observation and perception rather than a real climatic trend.

Multidisciplinary consensus on the approach to hospital malnutrition in Spain

Rationale: Disease-related malnutrition constitutes a highly prevalent healthcare problem with high costs associated. In Spain, the prevalence of malnutrition in hospitalized patients has been reported from 30% to 50%. Objectives: Main purposes of this consensus document were to establish recommendations that facilitate decision- making and action to prevent and early-diagnose disease-related hospital malnutrition, on the management of nutritional support methods and actions to evaluate nutritional treatment compliance and efficacy. Methods: A systematic bibliographical search of authors was performed, complemented by updated bibliography by author references up to 2010. From this review, some recommendations were defined, modified and critically evaluated by the representatives of scientific societies in a consensus conference (Dec 2010) following a structured brainstorming technique: the Metaplan® technique. A double validation process was undertaken until final recommendations were obtained. Results: 30 consensus recommendations for the prevention and management of hospital malnutrition are presented in this document. Recommendations cover all clinical care settings as well as prevention, screening, diagnosis, treatment and follow-up of disease-related malnutrition. Conclusions: Nutritional screening is strongly recommended at all clinical settings when nutritional risk factors are identified or there is clinical suspicion of malnutrition. Nutritional assessment should be designed and performed according to centers’ resources, but clearly identified protocols should be available.

Aïllament d'una activitat triacilglicèrid hidrolasa a fetge de nadó de rata

The validation process of an affinity chromatography on heparine-Sepharose method is described.

Aplicación de imágenes radar de satélite a la cartografía de la vegetación en zonas boreales

El presente estudio se enmarca en el proyecto europeo SIBERIA. Trata de explorar el uso de imágenes radar de satélite (ERS y JERS) para la actualización de la cartografía de vegetación de zonas boreales. Se dispone de 8 imágenes de amplitud y coherencia tomadas en 1998, así como de un inventario de vegetación georreferenciado de dos pequeñas zonas. Se proponen tres tipos de clasificaciones supervisadas por el método de máxima verosimilitud. La primera con las imágenes de satélite, la segunda añadiendo algunas imágenes texturales, y la tercera utilizando sólo las imágenes de los componentes principales más significativos. Se siguen los criterios establecidos en el proyecto SIBERIA para la obtención de áreas de entrenamiento. Se propone una doble validación, por una parte vía matrices de confusión a partir de áreas de verdad-terreno obtenidas por el mismo método que las áreas de entrenamiento, y por otra parte contrastando y correlacionando las clasificaciones con los parámetros de inventario disponibles para dos pequeñas áreas de verdad-terreno. Los resultados indican una sensible mejora en la clasificación con la incorporación de imágenes texturales (la precisión aumenta de un 66% a un 75%), y señalan el parámetro biomasa como el mejor correlacionado con las clasificaciones derivadas (coeficiente de correlación r de hasta 0,49). Diferentes fuentes de error permiten augurar un margen de mejora para posteriores estudios.

A Spanish version of the athens insomnia scale

Objectives To develop and validate a Spanish version of the Athens Insomnia Scale (AIS). Methods The AIS is designed to assess sleep difficulty and comprises eight items: the first five refer to the sleep disturbance and the last three to the daytime consequences. Either the full eight-item scale (AIS-8) or the brief form (AIS-5) can be administered. The adaptation used a backtranslation design. The validation process was based on a sample of 323 participants (undergraduates, community sample and psychiatric outpatients), which completed the AIS and other questionnaires: anxiety (BAI), depression (BDI) and psychological well-being (GHQ-12) scales. Results The internal consistency coefficients for both versions were above 0.80. The study of dimensionality revealed a single factor with high loadings and a percentage of explained variance above 50% in both versions. Test-retest reliability was above 0.70 (AIS-5) and over 0.80 (AIS-8) at a one-month interval. The correlation between the AIS and the previously mentioned scales was for both the AIS-5 and the AIS-8 above 0.40 and 0.50, respectively.

Tolerance and Relative Utility: Two Proposed Indices for Comparing Change in Clinical Measurement Noise Between Different Populations (Repeatability) or Measurement Methods (Agreement).

Reaching a consensus in terms of interchangeability and utility (i.e., disease detection/monitoring) of a medical device is the eventual aim of repeatability and agreement studies. The aim of the tolerance and relative utility indices described in this report is to provide a methodology to compare change in clinical measurement noise between different populations (repeatability) or measurement methods (agreement), so as to highlight problematic areas. No longitudinal data are required to calculate these indices. Both indices establish a metric of least to most effected across all parameters to facilitate comparison. If validated, these indices may prove useful tools when combining reports and forming the consensus required in the validation process for software updates and new medical devices.