Estudo da mutação do recetor do fator de crescimento epidérmico, durante 5 anos, numa população de doentes com cancro do pulmão de não pequenas células

ResumoIntroduçãoEm 2006, a Unidade de Pneumologia Oncológica do Serviço de Pneumologia do Centro Hospitalar de Vila Nova de Gaia/Espinho iniciou a sequenciação da mutação do recetor do fator de crescimento epidérmico (EGFR) em doentes com CPNPC selecionados e desde 2010 realiza a sequenciação sistematicamente em todos os doentes, independentemente da histologia, hábitos tabágicos, idade ou sexo. O objetivo deste trabalho foi caracterizar o grupo de doentes que efetuou a sequenciação entre 2006-2010, determinar a frequência da mutação EGFR, avaliar as sobrevidas globais e após uso de inibidores da tirosina quinase (ITK), nos doentes que efetuaram esta terapêutica em 2.a e 3.a linha com conhecimento do estado da mutação do EGFR.MétodosAnálise estatística descritiva dos doentes que efetuaram sequenciação EGFR em 2006-2010 e sobrevida mediana global nos doentes que efetuaefetuaram ITK em 2.a e 3.a linha. Registo do material disponível para análise e demora média de resultado do exame, de acordo com o material enviado.ResultadosA sequenciação foi efetuada em 374 doentes, 71,1% sexo masculino, 67,1% não/ex-fumadores, 32,9% fumadores; 57,8% adenocarcinoma e 23,5% carcinoma epidermoide (CE). A mutação foi detetada em 49 doentes (13,1%). No total dos doentes estudados, a taxa de mutação foi de 9% no sexo masculino e 23% no sexo feminino. A sobrevida mediana global após o uso de erlotinib foi de 14 meses para os doentes com mutação positiva do EGFR versus 6 meses nos doentes não mutados (p = 0,003).ConclusãoO nosso grupo teve uma taxa de mutação global de 13,1%, com predomínio no sexo feminino, não fumadores, histologia adenocarcinoma. Em doentes selecionados (2006/2009), a taxa de mutação foi de 16%; nos doentes não selecionados (2010) foi de 10,4%. Este estudo tem vindo a permitir um melhor conhecimento da taxa de mutação do EGFR na população portuguesa, bem como avaliar os resultados das sobrevidas dos doentes após uso de inibidores da tirosina quinase (ITK), efetuada em 2.a e 3.a linha com conhecimento prévio do estado da mutação do EGFR, tendo sido encontradas diferenças nas sobrevidas nos 2 grupos de doentes (mutados e não mutados) com significado estatístico.A pesquisa mutação do EGFR deve ser efetuada em todos os doentes com CPNPC, dando possibilidade a um número considerável de doentes de poder efetuar um tratamento de 1.a linha com ITK (doentes mutados), bem como de poder usufruir de outros esquemas de quimioterapia, quando progredirem.AbstractIntroductionIn 2006, the Vila Nova de Gaia/Espinho Hospital Centre Pulmonary Oncology Unit started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010, regardless of histology, smoking habits, age or sex. The aim of this study was to characterize the group of patients that carried out the sequencing between 2006-2010, to determine EGFR mutation frequency, to evaluate the overall survival and the survival after the use of tyrosine kinase inhibitors (TKI), in patients who performed this therapy in second and third line, knowing the EGFR mutation status.MethodsDescriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy. Record of the material available for analysis and average delay of exam results, according to the material submitted.ResultsThe sequencing was performed in 374 patients, 71,1% males, 67,1% non/ex-smokers, 32,9% smokers, 57,8% adenocarcinoma and 23,5% squamous cell carcinoma (SCC). The mutation was detected in 49 patients (13,1%). In all studied patients, the mutation rate was 9% in males and 23% in females. Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6 months in not mutated patients (p = 0.003).ConclusionOur group had an overall mutation rate of 13.1% with female, non-smokers, adenocarcinoma histology predominance. In selected patients (2006/2009), the mutation rate was 16%, in not selected patients (2010) the mutation rate was 10.4%. This study has permitted a better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors, in second and third line therapy with previous knowledge of the EGFR mutational status. Statistical significant differences in survival were found in the two patient groups (EGFR mutated and non mutated).The EGFR mutation research should be performed in all patients with NSCLC, giving the possibility to a considerable number of patients to perform a first line treatment with TKI (EGFR mutated patients) and the advantage of performing other chemotherapy schemes, when progression occurs

The use of tools of data mining to decision making in engineering education—A systematic mapping study

In recent years, there has been an increasing amount of theoretical and applied research that has focused on educational data mining. The learning analytics is a discipline that uses techniques, methods, and algorithms that allow the user to discover and extract patterns in stored educational data, with the purpose of improving the teaching‐learning process. However, there are many requirements related to the use of new technologies in teaching‐learning processes that are practically unaddressed from the learning analytics. In an analysis of the literature, the existence of a systematic revision of the application of learning analytics in the field of engineering education is not evident. The study described in this article provides researchers with an overview of the progress made to date and identifies areas in which research is missing. To this end, a systematic mapping study has been carried out, oriented toward the classification of publications that focus on the type of research and the type of contribution. The results show a trend toward case study research that is mainly directed at software and computer science engineering. Furthermore, trends in the application of learning analytics are highlighted in the topics, such as student retention or dropout prediction, analysis of academic student data, student learning assessment and student behavior analysis. Although this systematic mapping study has focused on the application of learning analytics in engineering education, some of the results can also be applied to other educational areas

Circunferência da cintura e circunferência da cintura/estatura entre adolescentes indígenas Kaingáng do Rio Grande do Sul, Brasil

The aim of this study was to describe the distribution of waist circumference (WC) and WC to height (WCTH) values among Kaingáng indigenous adolescents in order to estimate the prevalence of high WCTH values and evaluate the correlation between WC and WCTH and body mass index (BMI)-for-age. A total of 1,803 indigenous adolescents were evaluated using a school-based cross-sectional study. WCTH values > 0.5 were considered high. Higher mean WC and WCTH values were observed for girls in all age categories. WCTH values > 0.5 were observed in 25.68% of the overall sample of adolescents. Mean WC and WCTH values were significantly higher for adolescents with BMI/age z-scores > 2 than for those with normal z-scores. The correlation coefficients of WC and WCTH for BMI/age were r = 0.68 and 0.76, respectively, for boys, and r = 0.79 and 0.80, respectively, for girls. This study highlights elevated mean WC and WCTH values and high prevalence of abdominal obesity among Kaingáng indigenous adolescents

Congenital Hyperinsulinism in Two Siblings with ABCC8 Mutation: Same Genotype, Different Phenotypes

Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected genes. Therapeutic options include diazoxide, somatostatin analogues and surgery, which is curative in focal CHI. We report the case of two siblings (born two years apart) that presented themselves with hypoketotic hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis of diffuse CHI due to an ABCC8 compound mutation (c.3576delG and c.742C>T) was concluded. They did not benefit from diazoxide therapy (or pancreatectomy performed in patient number 1) yet responded to somatostatin analogues. Patient number 1 developed various neurological deficits (including epilepsy), however patient number 2 experienced an entirely normal neurodevelopment. We believe this case shows how previous knowledge of the firstborn sibling's disease contributed to a better and timelier medical care in patient number 2, which could potentially explain her better neurological outcome despite their same genotype.info:eu-repo/semantics/publishedVersio

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (−159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (−159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (−159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult CaucasiansThis study was funded by grants from Sociedad Española de Neumología y Cirugía Torácica, (SEPAR) (121/2012) and Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Fondo de Investigación Sanitaria, FIS; co-financed by European Union ERDF funds) (PI13/02046). JJNF is a recipient of a Xunta de Galicia Fellowship (Co-financed by European Social Fund (ESF))S

Economic Valuation of Health Care Services in Public Health Systems: A Study about Willingness to Pay (WTP) for Nursing Consultations

Background: Identifying the economic value assigned by users to a particular health service is of principal interest in planning the service. The aim of this study was to evaluate the perception of economic value of nursing consultation in primary care (PC) by its users. Methods and Results: Economic study using contingent valuation methodology. A total of 662 users of nursing consultation from 23 health centers were included. Data on demographic and socioeconomic characteristics, health needs, pattern of usage, and satisfaction with provided service were compiled. The validity of the response was evaluated by an explanatory mixed-effects multilevel model in order to assess the factors associated with the response according to the welfare theory. Response reliability was also evaluated. Subjects included in the study indicated an average Willingness to Pay (WTP) of €14.4 (CI 95%: €13.2–15.5; median €10) and an average Willingness to Accept [Compensation] (WTA) of €20.9 (CI 95%: €19.6–22.2; median €20). Average area income, personal income, consultation duration, home visit, and education level correlated with greater WTP. Women and older subjects showed lower WTP. Fixed parameters explained 8.41% of the residual variability, and response clustering in different health centers explained 4–6% of the total variability. The influence of income on WTP was different in each center. The responses for WTP and WTA in a subgroup of subjects were consistent when reassessed after 2 weeks (intraclass correlation coefficients 0.952 and 0.893, respectively). Conclusions: The economic value of nursing services provided within PC in a public health system is clearly perceived by its user. The perception of this value is influenced by socioeconomic and demographic characteristics of the subjects and their environment, and by the unique characteristics of the evaluated service. The method of contingent valuation is useful for making explicit this perception of value of health services

Open and Hidden Charm Production in 920 GeV Proton-Nucleus Collisions

The HERA-B collaboration has studied the production of charmonium and open charm states in collisions of 920 GeV protons with wire targets of different materials. The acceptance of the HERA-B spectrometer covers negative values of xF up to xF=-0.3 and a broad range in transverse momentum from 0.0 to 4.8 GeV/c. The studies presented in this paper include J/psi differential distributions and the suppression of J/psi production in nuclear media. Furthermore, production cross sections and cross section ratios for open charm mesons are discussed.Comment: 5 pages, 9 figures, to be published in the proceedings of the 6th International Conference on Hyperons, Charm & Beauty Hadrons (BEACH04), Chicago, IL, June 27 - July 3, 200

A Novel Method for Y Photons Depth of Interaction Discrimination on Monolithic LYSO Crystals for Brain PET/MRI

The MindView European Project pursues the development of a high efficiency and high resolution brain dedicated PET detector, simultaneously working with a Magnetic Resonance Imaging (MRI) system. Since the PET scanner is based on a small diameter ring and on thick monolithic scintillation crystals to assess high efficiency, the parallax error related to off-center positron annihilation is a critical issue. The Depth of Interaction (DoI) discrimination can reduce the blurring due to this phenomenon. In this work, we propose a novel DoI estimator, based on the ratio of the integral of scintillation light distribution to its maximum (named N/I). In a preliminary way, by means of Monte Carlo simulation, we have validated the correlation between this parameter and the DoI. Furthermore, we have experimentally tested the capability of such DoI estimator on a monolithic 20mm-thick LYSO crystal optically coupled to a 12x12 silicon photomultipliers (SiPMs) array. Thanks to the proposed method, it is possible to select interaction events coming from different depths of the crystal. The DoI discrimination capability has been confirmed by using a collimated slanted pencil-beam: the proposed estimator allows to produce different images coming from events belonging to different depths of the crystal. From the experimental results a DoI discrimination resolution ranging from 4mm to 6mm has been obtained. The proposed method is expected to reduce the parallax error and, consequently, the width of lines of response coming from off- center positron annihilation of about 70% respect to the method without DoI discrimination