875 resultados para Xavier, Rafael
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El objetivo del presente trabajo de investigación es arrojar luz sobre los factores que explican la menor intencionalidad en la población femenina para involucrarse en procesos de creación de empresas. Para ello, se ha desarrollado un modelo de ecuaciones estructurales que identifica un conjunto de variables que permiten explicar la intención de emprender en la población potencialmente emprendedora. La validación del modelo se ha realizado mediante una encuesta realizada a 1222 estudiantes de 12 titulaciones diferentes de la Universidad de Málaga. La aplicación del modelo a las poblaciones masculina y femenina ha permitido apreciar diferencias significativas en los patrones de comportamiento en función del género, identificando un proceso más complejo y necesitado de apoyo externo en la población femenina con respecto a la masculina.
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CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naı¨ve cells, P = 0.0001; CD8+ naı¨ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells.
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Background The prognosis of patients bearing high grade glioma remains dismal. Epidermal Growth Factor Receptor (EGFR) is well validated as a primary contributor of glioma initiation and progression. Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors, in nonclinical and clinical setting. While it has similar activity when compared to other anti-EGFR antibodies, it does not induce skin toxicity or hypomagnesemia. Methods A randomized, double blind, multicentric clinical trial was conducted in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment and placebo groups were well-balanced for the most important prognostic variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy. Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks. The objectives of this study were to assess the comparative overall survival, progression free survival, response rate, immunogenicity and safety. Results The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses. The combination of nimotuzumab and RT was well-tolerated. The most prevalent related adverse reactions included nausea, fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response was detected, confirming the antibody low immunogenicity. The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. Conclusions In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation.
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Sobre esta obra Inocêncio informa que a compilação ocorrida por ordem do Rei D. João I e seu filho D. Duarte esteve a cargo, inicialmente, de João Mendes e, posteriormente, de Rui Fernandes. Entretanto, sua conclusão só ocorreu no reinado de D. Afonso V, a 17 de julho de 1446, acrescida de revisões e aperfeiçoada por uma junta composta pelo mesmo Rui Fernandes, por Lopo Vasques, corregedor de Lisboa, e por Luíz Martins e Fernão Rodrigues, desembargadores do rei. Finalmente concluída , a compilação recebeu a denominação de Código ou Ordenaçoens do Senhor Rey D. Affonso V, que, após ficar por alguns séculos quase desconhecida, foi publicada pela primeira vez em Coimbra, em 1792, por mandado e diligência de D. Francisco Rafael de Castro, então reitor e reformador da universidade. A direção e a responsabilidade pela impressão foram confiadas a Joaquim Correa da Silva, autor do prefácio que aparece no início do Tomo I. A obra reveste-se de grande importância devido à grande utilidade que apresenta para os estudos da jurisprudência, da história de Portugal, da filologia e para o conhecimento do idioma português.
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Galeria dos brasileiros illustres traz retratos copiados do natural e litografados das principais figuras brasileiras da política, ciências e letras, com biografias redigidas por diversos escritos da época, por alguns dos próprios biografados ou por membros de suas famílias. Considerada a mais importante de Sisson, esta obra teve tiragem reduzida e muitos exemplares foram desmanchados por antiquários que emolduravam os retratos, vendendo-os por alto preço. Segundo Borba de Moraes, "é muito difícil encontrar-se hoje em dia um exemplar perfeito e em boas condições" e que "só muito raramente aparece um exemplar à venda."
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[EN] Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high-affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3). Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus (LC) neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 LC neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in LC and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients.
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Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (P-replication=0.042; P-pooled=5.523x10(-03); OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (P-replication=0.039; P-pooled=6.985x10(-5); OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.
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Query-by-Example Spoken Term Detection (QbE STD) aims at retrieving data from a speech data repository given an acoustic query containing the term of interest as input. Nowadays, it has been receiving much interest due to the high volume of information stored in audio or audiovisual format. QbE STD differs from automatic speech recognition (ASR) and keyword spotting (KWS)/spoken term detection (STD) since ASR is interested in all the terms/words that appear in the speech signal and KWS/STD relies on a textual transcription of the search term to retrieve the speech data. This paper presents the systems submitted to the ALBAYZIN 2012 QbE STD evaluation held as a part of ALBAYZIN 2012 evaluation campaign within the context of the IberSPEECH 2012 Conference(a). The evaluation consists of retrieving the speech files that contain the input queries, indicating their start and end timestamps within the appropriate speech file. Evaluation is conducted on a Spanish spontaneous speech database containing a set of talks from MAVIR workshops(b), which amount at about 7 h of speech in total. We present the database metric systems submitted along with all results and some discussion. Four different research groups took part in the evaluation. Evaluation results show the difficulty of this task and the limited performance indicates there is still a lot of room for improvement. The best result is achieved by a dynamic time warping-based search over Gaussian posteriorgrams/posterior phoneme probabilities. This paper also compares the systems aiming at establishing the best technique dealing with that difficult task and looking for defining promising directions for this relatively novel task.
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One of the major concerns in an Intelligent Transportation System (ITS) scenario, such as that which may be found on a long-distance train service, is the provision of efficient communication services, satisfying users' expectations, and fulfilling even highly demanding application requirements, such as safety-oriented services. In an ITS scenario, it is common to have a significant amount of onboard devices that comprise a cluster of nodes (a mobile network) that demand connectivity to the outside networks. This demand has to be satisfied without service disruption. Consequently, the mobility of the mobile network has to be managed. Due to the nature of mobile networks, efficient and lightweight protocols are desired in the ITS context to ensure adequate service performance. However, the security is also a key factor in this scenario. Since the management of the mobility is essential for providing communications, the protocol for managing this mobility has to be protected. Furthermore, there are safety-oriented services in this scenario, so user application data should also be protected. Nevertheless, providing security is expensive in terms of efficiency. Based on this considerations, we have developed a solution for managing the network mobility for ITS scenarios: the NeMHIP protocol. This approach provides a secure management of network mobility in an efficient manner. In this article, we present this protocol and the strategy developed to maintain its security and efficiency in satisfactory levels. We also present the developed analytical models to analyze quantitatively the efficiency of the protocol. More specifically, we have developed models for assessing it in terms of signaling cost, which demonstrates that NeMHIP generates up to 73.47% less signaling compared to other relevant approaches. Therefore, the results obtained demonstrate that NeMHIP is the most efficient and secure solution for providing communications in mobile network scenarios such as in an ITS context.
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Background: Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods: A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was >= 1: 160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results: Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions: This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.
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12 p.
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11 p.
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Monografia (especialização) – Curso de Parlamento e Direito, Câmara dos Deputados, Centro de Formação, Treinamento e Aperfeiçoamento (Cefor), 2015.
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Ao alto do título: Conde das Galveas.