Évaluation prospective de l’état nutritionnel et risque de complications post-opératoires de la cystectomie radicale

La cystectomie radicale est le traitement de référence pour les cancers de la vessie infiltrant le muscle. Cette chirurgie entraine un taux élevé de complications et diminue la qualité de vie des patients à court et à long terme. Une revue de la littérature a d’abord été effectuée afin d’identifier les facteurs de l’état nutritionnel associés au risque de complications et de mortalité après la cystectomie radicale. L’hypoalbuminémie a été identifiée comme un prédicteur potentiel de la mortalité post-opératoire. Une étude de cohorte a ensuite été menée afin d’identifier des facteurs de l’état nutritionnel associés au risque de développer des complications après cette chirurgie. Un indice de masse corporelle élevé, une baisse de l’appétit, une perte de poids, une hypo-albuminémie et une hypo-préalbuminémie avant l’opération sont les facteurs qui ont été associés au développement de complications post-opératoires. Des analyses et des études supplémentaires doivent être menées dans l’optique développer des interventions qui pourraient diminuer le risque de complications après la cystectomie radicale.

Conflit sexuel et polyandrie de la commodité chez une espèce polygynandre: les effets combinés des processus pré- et post- copulatoires sur le succès reproducteur de "Gerris buenoi"

Chez les patineurs, des processus postcopulatoires sont documentés et un conflit sexuel sur le taux d’accouplement est démontré. Cependant, leurs effets combinés sur le succès reproducteur ont rarement été investigués. Cette étude joint une analyse de filiation génétique à des observations comportementales pour évaluer l’effet des processus pré- et post- copulatoires sur le succès reproducteur de Gerris buenoi. Nos résultats montrent la nature antagoniste des combats précopulatoires et un niveau de résistance optimal intermédiaire pour les femelles. Cependant, le taux d’accouplement n’a eu aucune influence sur le succès reproducteur des deux sexes. Un taux d’accouplement élevé permettant à des processus postcopulatoires de se mettre en place ainsi que plusieurs copulations superflues ont vraisemblablement masqué les effets attendus du taux d’accouplement. Notre étude confirme l’idée que des précisions peuvent être apportées sur les forces de sélection sexuelle en jeu lorsque l’on considère tous les épisodes d’un cycle d’accouplement chez les animaux polygynandres.

Contribution to fundamental aspects of biophysics, radiobiology, and modeling of cellular response to low radiation doses

Tese de doutoramento, Engenharia Biomédica e Biofísica, Universidade de Lisboa, Faculdade de Ciências, 2014

Using genomics for drug discovery in medulloblastoma

Tese de doutoramento, Medicina (Neurocirurgia), Universidade de Lisboa, Faculdade de Medicina, 2014

Electroanalytical study of the antidepressant sertraline

Aflowinjection squarewave cathodic stripping voltammetric method has been developed for the determination of sertraline in a pharmaceutical preparation. The method shows linearity between peak current intensity and sertraline concentration for the interval between 0.20×10−6 and 1.20×10−6 mol L−1. Limits of detection and quantification were found to be 1.5×10−7 and 5.0×10−7 mol L−1, respectively. Up to 70 samples per hour can be analysed with a good precision (R.S.D. = 2.5%). The proposed method was successfully applied to the determination of sertraline in a commercial product. In the voltammetric determination of sertraline in flow, a high sample rate is obtained at reduced costs, opening the possibility to compete with the chromatographic methods generally used for this analysis.

Um retrato do Empreendedorismo em Malanje-Angola: análise de negócios criados entre 2008-2012

Dissertação de Mestrado em Empreendedorismo e Internacionalização apresentada ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Empreendedorismo e Internacionalização, sob orientação de Professora Doutora Celsa Maria Carvalho Machado e Mestre Maria Luísa Verdelho Alves

Standard commercial education robotic platform: intermediate solution to teaching robotics

Teaching robotics to students at the beginning of their studies has become a huge challenge. Simulation environments can be an effective solution to that challenge where students can interact with simulated robots and have the first contact with robotic constraints. From our previous experience with simulation environments it was possible to observe that students with lower background knowledge in robotics where able to deal with a limited number of constraints, implement a simulated robotic platform and study several sensors. The question is: after this first phase what should be the best approach? Should the student start developing their own hardware? Hardware development is a very important part of an engineer's education but it can also be a difficult phase that could lead to discouragement and loss of motivation in some students. Considering the previous constraints and first year engineering students’ high abandonment rate it is important to develop teaching strategies to deal with this problem in a feasible way. The solution that we propose is the integration of a low-cost standard robotic platform WowWee Rovio as an intermediate solution between the simulation phase and the stage where the students can develop their own robots. This approach will allow the students to keep working in robotic areas such as: cooperative behaviour, perception, navigation and data fusion. The propose approach proved to be a motivation step not only for the students but also for the teachers. Students and teachers were able to reach an agreement between the level of demand imposed by the teachers and satisfaction/motivation of the students.

the liver endoplasmic reticulum in malaria liver infection

Malaria, a disease caused by Plasmodium, represents a major health problem with a still disconcertingly high mortality rate (655 000 malaria deaths were estimated by the World Health Organization in 2012), mainly in Africa [1]. After a bite by an infected Anopheles mosquito occurs, Plasmodium sporozoites reach their target organ, the liver, within minutes. After traversing several hepatocytes, the parasite invades a final one and establishes a parasitophorous vacuole, where it replicates exponentially generating thousands of infective merozoites, the red blood cell infectious forms that are released in the blood stream. The liver stage is the first obligatory phase of malaria infection and, although no symptoms are associated with it, it is absolutely crucial to the establishment of a successful infection.(...)

Sistemas prisionais europeus

Ao longo dos últimos anos a reforma dos sistemas prisionais e a eficácia da reinserção social têm vindo a integrar as agendas políticas dos governos dos países europeus. Esta reforma deriva de vários problemas e carências com que se debatem os diversos sistemas prisionais, nomeadamente a sobrelotação, o ambiente propício à violência, o consumo de drogas, a inactividade do recluso e o elevado índice de reincidência criminal. Porém, qualquer reforma que se venha a delinear compreende matérias muito complexas que vão desde os direitos humanos aos recursos humanos e financeiros, imperativos legais, bem como a conciliação entre a punição e a ressocialização. Estas matérias não dependem apenas da vontade política, mas igualmente da sociedade, a qual ainda ergue barreiras à reinserção, tratando o ex-recluso como um excluído da sociedade. Neste sentido, os estudos universitários constituem um elemento chave na procura de soluções para esta problemática, na medida em que se servem das várias áreas do saber para de alguma forma contribuir com possíveis soluções, tendo em vista a melhoria de todo o sistema prisional e a eficácia da reinserção social. Esta dissertação tem assim como objectivo apresentar os principais modelos de sistemas prisionais adoptados em países europeus e efectuar uma comparação entre estes. Pretende-se retirar os aspectos mais relevantes de cada sistema e que têm contribuído para a melhoria das condições dos reclusos e do aumento da reinserção destes na sociedade, bem como na diminuição da taxa de reincidência criminal.

A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer.

BACKGROUND: Early detection and treatment of colorectal adenomatous polyps (AP) and colorectal cancer (CRC) is associated with decreased mortality for CRC. However, accurate, non-invasive and compliant tests to screen for AP and early stages of CRC are not yet available. A blood-based screening test is highly attractive due to limited invasiveness and high acceptance rate among patients. AIM: To demonstrate whether gene expression signatures in the peripheral blood mononuclear cells (PBMC) were able to detect the presence of AP and early stages CRC. METHODS: A total of 85 PBMC samples derived from colonoscopy-verified subjects without lesion (controls) (n = 41), with AP (n = 21) or with CRC (n = 23) were used as training sets. A 42-gene panel for CRC and AP discrimination, including genes identified by Digital Gene Expression-tag profiling of PBMC, and genes previously characterised and reported in the literature, was validated on the training set by qPCR. Logistic regression analysis followed by bootstrap validation determined CRC- and AP-specific classifiers, which discriminate patients with CRC and AP from controls. RESULTS: The CRC and AP classifiers were able to detect CRC with a sensitivity of 78% and AP with a sensitivity of 46% respectively. Both classifiers had a specificity of 92% with very low false-positive detection when applied on subjects with inflammatory bowel disease (n = 23) or tumours other than CRC (n = 14). CONCLUSION: This pilot study demonstrates the potential of developing a minimally invasive, accurate test to screen patients at average risk for colorectal cancer, based on gene expression analysis of peripheral blood mononuclear cells obtained from a simple blood sample.

Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.

Candidaemia is the fourth most common cause of bloodstream infection, with a high mortality rate of up to 40%. Identification of host genetic factors that confer susceptibility to candidaemia may aid in designing adjunctive immunotherapeutic strategies. Here we hypothesize that variation in immune genes may predispose to candidaemia. We analyse 118,989 single-nucleotide polymorphisms (SNPs) across 186 loci known to be associated with immune-mediated diseases in the largest candidaemia cohort to date of 217 patients of European ancestry and a group of 11,920 controls. We validate the significant associations by comparison with a disease-matched control group. We observe significant association between candidaemia and SNPs in the CD58 (P = 1.97 × 10(-11); odds ratio (OR) = 4.68), LCE4A-C1orf68 (P = 1.98 × 10(-10); OR = 4.25) and TAGAP (P = 1.84 × 10(-8); OR = 2.96) loci. Individuals carrying two or more risk alleles have an increased risk for candidaemia of 19.4-fold compared with individuals carrying no risk allele. We identify three novel genetic risk factors for candidaemia, which we subsequently validate for their role in antifungal host defence.

Stem cell transplantation in brain tumors: a new field for molecular imaging?

Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.

HIV-1 drug resistance transmission networks in southwest Switzerland.

To determine viral subtypes and resistance mutations to antiretroviral treatment (ART) in untreated HIV-1 acutely infected subjects from Southwest Switzerland. Clinical samples were obtained from the HIV primary infection cohort from Lausanne. Briefly, pol gene was amplified by nested PCR and sequenced to generate a 1?kb sequence spanning protease and reverse transcriptase key protein regions. Nucleotide sequences were used to assess viral genotype and ART resistance mutations. Blood specimens and medical information were obtained from 30 patients. Main viral subtypes corresponded to clade B, CRF02_AG, and F1. Resistant mutations to PIs consisted of L10V and accessory mutations 16E and 60E present in all F1 clades. The NNRTI major resistant mutation 103N was detected in all F1 viruses and in other 2 clades. Additionally, we identified F1 sequences from other 6 HIV infected and untreated individuals from Southwest Switzerland, harboring nucleotide motifs and resistance mutations to ART as observed in the F1 strains from the cohort. These data reveal a high transmission rate (16.6%) for NNRTI resistant mutation 103N in a cohort of HIV acute infection. Three of the 5 resistant strains were F1 clades closely related to other F1 isolates from HIV-1 infection untreated patients also coming from Southwest Switzerland. Overall, we provide strong evidence towards an HIV-1 resistant transmission network in Southwest Switzerland. These findings have relevant implications for the local molecular mapping of HIV-1 and future ART surveillance studies in the region.

Microsatellites can be misleading: an empirical and simulation study.

It has been long recognized that highly polymorphic genetic markers can lead to underestimation of divergence between populations when migration is low. Microsatellite loci, which are characterized by extremely high mutation rates, are particularly likely to be affected. Here, we report genetic differentiation estimates in a contact zone between two chromosome races of the common shrew (Sorex araneus), based on 10 autosomal microsatellites, a newly developed Y-chromosome microsatellite, and mitochondrial DNA. These results are compared to previous data on proteins and karyotypes. Estimates of genetic differentiation based on F- and R-statistics are much lower for autosomal microsatellites than for all other genetic markers. We show by simulations that this discrepancy stems mainly from the high mutation rate of microsatellite markers for F-statistics and from deviations from a single-step mutation model for R-statistics. The sex-linked genetic markers show that all gene exchange between races is mediated by females. The absence of male-mediated gene flow most likely results from male hybrid sterility.

Mentorships and co-op placements as a means of heightening the need for a secondary school diploma to the education of at-risk students.--

Both educators and politicians appear to be quite concerned about a dropout rate in Ontario's public schools of some 30 percent. With the basic understanding that a high dropout rate is costly both in economic terms and in human terms, something quite obviously needs to be done to reduce the dropout rate in Ontario schools and, in doing so, ensuring Ontario and its graduates an active role in a growing global economy. This study is an exploratory pilot study in that it examined mentoring and the role that mentoring can play in assisting a student in staying in school and graduating from secondary school. Also incorporated in this is co-operative education and the role it can play, through mentoring, in making students aware of lifestyle level of employment, and of the skills necessary to obtain gainful, meaningful employment. In order to gain information on student attitudes, needs and expectations of a mentoring situation, a series of three questionnaires was used. Also, a questionnaire was distributed to the various co-operative education employers. The intent of this questionnaire was to probe the attitudes, needs and expectations of a mentoring situation from the perspective of an employer. The findings of this study indicated that co-operative education and mentoring are a very valuable and useful component in education. There exist certain factors in a co-operative education setting that serve to enhance and to augment the traditional or "theoretical" setting of the classroom. In addition, a mentoring situation tends to add a sense of relevance to education that students seem to require. Also, an opportunity is offered that allows a student to practice and further refine the skills that have been taught over the course of the student's academic life. Results from this study suggested that a mentoring situation, occurring through a co-operative education situation, adds relevance and a sense of "application" to the traditional or classroom schooling situation. The whole idea of mentoring bodes well for the future of education and of the student. Many advantages are identified in a mentoring situation. One of the advantages is that the schools are able to work quite closely with the community and business in order to stay current and informed on the needs and expected needs of the business community. Co-operative education has now gone beyond being an "experimental" mode of education. All students can benefit from being involved in the program. Certainly at-risk students are aided with staying in school. Those students who are said to be not at-risk can also benefit from being enrolled in the program by gaining hands-on work experience and some of the necessary skills to ensure a place in a growing world economy.