Dissertations / Theses on the topic 'Factors'

En la presente tesis de aplicación de Factores de Inversión: Value, Volatility, Quality y Momentum en la Bolsa de Valores de Lima (BVL), se utilizó como Benchmark el Índice General de la Bolsa de Valores de Lima (IGBVL), conformada por 39 valores, que mediante filtros de liquidez y tiempo de cotización en la Bolsa quedaron 27, por falta de datos se llegó finalmente a 25 valores. Luego, se definen las variables de cada factor. Para el Factor Value: PER y PBV (Price to Book). Para el Factor Momentum la variable momento de los precios. Para el Factor Quality la variable ROE. Para el Factor Volatility la variable Volatilidad total. Seguidamente, se aplican procedimientos para analizar las variables de los cuatro factores a los datos para escoger aquellos que puedan superar al Benchmark. Finalmente, se demuestra que en los últimos diez años que el portafolio, con valores que tengan un ratio PER (Variable del Factor Value) inferior al promedio de la Bolsa y actualizando la cartera de manera trimestral, tiene un mejor rendimiento que el Benchmark y el portafolio conformado por empresas con ratio PER superior al promedio de la Bolsa. Los resultados han sido enmarcados en un nivel de confianza al 95%.
In this thesis of application of Investment Factors: Value, Volatility, Quality and Momentum in the Lima Stock Exchange (BVL), the General Index of the Lima Stock Exchange (IGBVL) was used as Benchmark, consisting of 39 values, which by means of liquidity filters and time of quotation in the Stock Exchange were 27, due to lack of data, finally 25 values were reached. Then, the variables of each factor are defined. For the Value Factor: PER and the Price to Book. For the Momentum Factor the price momentum variable. For the Quality Factor, the variable ROE. For the Volatility Factor the variable Total Volatility. Next, procedures are applied to analyze the variables of the four factors to the data to choose those that can surpass the Benchmark. Finally, it is shown that in the last ten years that the portfolio, with values that have a PER (Variable Value Factor) ratio lower than the average of the Exchange and updating the portfolio quarterly, has a better performance than the Benchmark and the portfolio made up of companies with a PER ratio higher than the average of the Stock Exchange. The results have been framed at a 95% confidence level.
Trabajo de investigación

La synthèse d’ARN messagers résulte d’une cascade d’évènements temporellement et spatialement orchestrée. Au moment de l’initiation de la transcription, divers facteurs tels que les facteurs généraux de transcription, le complexe Médiateur, des co-activateurs, des facteurs de remodelage de la chromatine ainsi que l’ARN polymérase II sont recrutés au niveau de la région promotrice du gène. Certains facteurs de la voie NER de réparation de l’ADN sont également recrutés. En utilisant des cellules de patients porteurs de mutations dans les gènes MED12 (sous-unité du Médiateur) ou XPC (facteur initiant la voie NER), nous avons pu étudier le rôle de ces protéines dans la transcription. Les patients MED12 sont notamment caractérisés par une lourde déficience intellectuelle et des malformations congénitales. Nous avons montré que MED12 est impliqué dans le contrôle de certains gènes de réponse immédiate comme JUN, qui contribue notamment au développent et à la plasticité cérébrale. L’expression de ce dernier est affectée par les mutations de MED12, mais différemment en fonction de la position de la mutation, apportant une possible indication sur l’origine des variations phénotypiques observées chez les patients. En parallèle, les patients XPC se caractérisent par une forte photosensibilité. Nous avons montré que la protéine XPC, en collaboration avec le facteur E2F1, est impliquée dans le recrutement de l’histone acetyl-transférase GCN5 au niveau du promoteur d’un certain nombre de gènes. Cette dernière permet notamment l’a modification de l’environnement chromatinien, en coopération avec le facteur général de transcription TFIIH et participe ainsi à l’initiation de la transcription. En plus d’approfondir la compréhension des mécanismes régissant la transcription, ces résultats ont permis de mieux comprendre l’étiologie des maladies associées aux mutations
The synthesis of messenger RNA is a highly regulated process. During transcription initiation, a large number of proteins are recruited to gene promoter, including the RNA polymerase II, general transcription factors, co-activators, chromatin remodellers and the Mediator complex. Some DNA repair factors from the NER pathway are also recruited. Using cells derived from patients bearing mutations in either MED12 gene or XPC gene, we studied the roles of such proteins in transcription. MED12 patients are mostly characterised by intellectual disability and developmental delay. We showed that MED12 is implicated in the transcription regulation of immediate early genes like JUN, known for its role in neurological development and neuronal plasticity. JUN expression is markedly altered by MED12 mutations. We also showed that the position of the mutation influences this alteration, bringing possible explanation for inter-patients symptom variability. Meanwhile, XPC patients are mostly characterized by photosensitivity. We showed that XPC protein, which engages one of the NER pathways, is implicated in chromatin post-translational modification. Together with E2F1, it helps the recruitment of GCN5 acetyl-transferase to promoter of a certain set of genes. On the promoter, GCN5 notably cooperates with TFIIH to modify the chromatin environment during transcription initiation. In addition to help the comprehension of the transcription mechanisms, these results bring knew insight into the aetiology of mutations associated diseases

The present study had the objectives of analyzing the prevalence of eating disorders in adolescent women attending school in Metropolitan Lima, identifying the factors related to those disorders and defining the population at risk of developing any of those disorders. A total of 2141 adolescents between 13 and 19 years old in their last three years of high school made up the probabilistic sample. This sample was chosen by clusters in two moments and stratified according to either prívate or public school. The Eating Behavior Inventory (ICA) was administered. Results showed that 16.4% of the cases had one or more eating disorders and 15.1% of the sample was at risk of developing one.
El presente estudio consistió en analizar la prevalencia de los trastornos alimentarios en la población de mujeres adolescentes escolares de Lima Metropolitana y los factores asociados a dichos trastornos. Asimismo, se buscó determinar la población en riesgo de desarrollar alguno de estos trastornos. Se evaluó un total de 2141 adolescentes entre los 13 y los 19 años, de 3° a 5° de secundaria, seleccionadas mediante un muestreo probabilístico bietápico por conglomerados y estratificado según régimen de gestión del colegio (público o privado), y se les aplicó el Inventario de Conductas Alimentarias (ICA) de Zusman (2000). Los resultados mostraron un 16.4% de casos con uno o más trastornos alimentarios y un 15.1% de la población en situación de riesgo.

Mestrado em Ciências Empresariais
O Empreendedorismo na área do turismo constitui um importante campo de estudo particularmente na Região Autónoma da Madeira, devido ao peso que o mesmo representa na economia regional. Temos assistido na região a um aumento da migração, sendo esta responsável por gerar importantes impactos no aumento de alguns empreendedores imigrantes. As novas empresas por eles criadas têm-se revelado um elemento fundamental para o desenvolvimento tecnológico e de equilíbrio do mercado regional, através de novos investimentos, da exploração de novas oportunidades de negócio, no aproveitamento mais eficiente de recursos e na criação de emprego. A partir da observação realizada a três empreendedores imigrantes de diferentes origens, Abdurrahman Can Apo, Roland Bachmeier e Rob Winjntj verificou-se que cada um possuía características próprias que os diferenciava dos restantes. A escolha da Madeira como local para investirem e permanecerem, não foi por acaso. Existiram uma série de factores extrínsecos e intrínsecos determinantes nessa decisão.
Entrepreneurship in the tourism area constitutes an important field of study, particularly in Madeira Island, due to the importance that tourism has in the regional economy. We have assisted to an increase of migration, being it responsible for creating important impacts in the raise of some immigrant entrepreneurs. The new businesses created by these immigrant entrepreneurs have revealed a fundamental element for the technological development and regional market stability, through new investments, exploitation of new business opportunities, in taking advantage of more efficient resources and in the creation of jobs. During the observation applied to the three entrepreneur immigrants, from different origins, Abdurrahman Can Apo, Roland Bachmeier e Rob Winjntje it was verified that each owned distinct characteristics which differentiated them from others. Their preference in choosing Madeira Island to invest and live did not happen by chance. There was a series of extrinsic and intrinsic factors that were determinant for their decision.

The general aim of the thesis was to assess the role of nutritional factors in asthma in the French E3N study. The first objective was to compare principal component (PCA) with confirmatory factor analysis (CFA) to identify dietary patterns. In comparison with PCA patterns, CFA patterns were more relevant in terms of correlations with food groups and socio-economic characteristics, and associations with adult-onset asthma. The second objective was to assess the joint roles of physical activity and obesity on asthma using marginal structural models. Analyses showed that obesity was related causally to current asthma with symptoms independently of physical activity, whereas no association was reported for physical activity. The third objective was to assess the modifying role of overweight in the association between domestic cleaning spray use and current asthma. Analyses showed that among women without anti-inflammatory therapy, the effect of spray use on asthma was higher in overweight women.
L’objectiu general de la tesi fou avaluar el paper dels factors nutricionals en l’asma. El primer objectiu fou comparar l’anàlisi de components principals (PCA) amb l’anàlisi factorial confirmatori (CFA) per identificar patrons de dieta. Comparat amb els patrons obtinguts amb PCA, els patrons obtinguts amb CFA mostraven major correlació amb grups d’aliments i característiques sociodemogràfiques, i aconseguien millor predicció de la incidència d’asma. El segon objectiu fou avaluar l’efecte conjunt de l’activitat física i l’obesitat en l’asma, utilitzant models marginals estructurals. Els resultats mostraren que l’obesitat es relaciona causalment amb els símptomes d’asma independentment de l’activitat física, mentre que no es va trobar cap efecte de l’activitat física. El tercer objectiu fou estudiar el paper modificador del sobrepès en l’associació entre l’ús de pulveritzadors de neteja domèstica i la presència d’asma. Les anàlisis mostraren que l’efecte de l’ús dels pulveritzadors era més gran en dones amb sobrepès i tractament antiinflamatori

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em Enfermagem
Actualmente as doenças cardiovasculares são o principal motivo de morbilidade e mortalidade em Portugal. Os factores de risco, conhecidos como causas que aumentam a probabilidade de ocorrência de um determinado evento, antecedem em vários anos às doenças cardiovasculares, dentro destes distinguem-se os factores de risco modificáveis e os factos de risco não modificáveis. Os factores de risco modificáveis considerados como os possíveis de serem controlados têm forte prevalência na população portuguesa, sendo que o excesso de peso, que consequentemente leva à obesidade provenientes de um estilo de vida cada vez mais sedentário, atinge na actualidade valores consideráveis, sendo vários os estudos que têm revelado que estes valores têm vindo a aumentar ao longo dos anos e o mais preocupante é que na adolescência estes valores percentuais têm cada vez mais incidência. Desta forma, se os nossos jovens têm excesso de peso na adolescência apresentam um elevado risco de se tornarem obesos na idade adulta. Assim sendo, o principal objectivo da presente monografia é saber o “Conhecimento do alunos do ensino secundário sobre os factores de risco para as doenças cardiovasculares”, sendo que optou-se por se efectuar um estudo exploratório, descritivo e transversal com metodologia quantitativa, com o intuito de percepcionar se estes têm o conhecimento de que há factores de risco potencialmente fatais e debilitantes que estão associados a um risco de desenvolver futuramente doenças do foro cardíaco e vascular. O instrumento de colheita de dados usado foi elaborado pela investigadora e a população escolhida para esta investigação foram alunos do ensino secundário (10º,11º e 12º ano) das turmas do curso de Ciências e Tecnologias da Escola António Sérgio em Vila Nova de Gaia, sendo a amostra total de sessenta alunos.
Currently the cardiovascular diseases are the main cause of morbidity and mortality in Portugal. The risk factors, known as causes that increase the likelihood of occurrence of a particular event, preceding several years to cardiovascular diseases, within these are distinguishable the modifiable and non-modifiable risk facts. Modifiable risk factors considered as possible to be controlled have strong prevalence in the portuguese population, being the overweightness, that consequently leads to obesity coming from a lifestyle more and more sedentary, reaches considerable values currently, several studies have revealed that these values have been increasing over the years and the most worrisome is that are in teenagers that these percentage values have increasingly incidence. So if our young people are overweight in adolescence present a high risk of becoming obese in adulthood. So, the main objective of this monograph is knowing the "high school students knowledge about the cardiovascular diseases risk factors", being that we decided to execute an exploratory study, descriptive and transversal with quantitative methodology, in order to perceive if these have the knowledge that there are risk factors potentially fatal and debilitating that are associated with a risk of developing in the future heart and vascular diseases. The data collection instrument used was prepared by researcher and the population chosen for this investigation were high school students (10th, 11th and 12th grade) classes of the area of science and technology in the Escola António Sérgio, Vila Nova de Gaia, with a total sample of sixty students.
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This paper investigates the factors that influence in the drop-out of university students, of the first cycle of distance education belonging to the administration school of the university Lord of Sipán, between 2011-I to 2013-I. It addresses the individual, socio-economic, academic and finally institutional factors.Among the individual factors, the one that most influenced the drop-out was the lack of time dedicated to the study (53% of the total respondents). With regard to socio-economic factors such as: employment status, salaries received, dependents, etc. none of them influenced student dropouts (79.3% of all respondents). Among institutional factors such as: care received, administrative support, virtual environment, etc. did not influence desertion. Finally, academic factors such as: conformity with curriculum, training received, etc., were not relevant in desertion.
En el presente trabajo se investiga los factores que influyen en la deserción de los estudiantes universitarios del primer ciclo de educación a distancia, pertenecientes a la Escuela de Administración de la Universidad Señor de Sipán, entre los semestres 2011-I y 2013-I. Del mismo modo se aborda los factores individuales, socioeconómicos, académicos y finalmente los institucionales.Dentro de los factores individuales, el que más influyó en la deserción fue la falta de tiempo dedicado al estudio (53% del total de encuestados). Respecto a los factores socioeconómicos, como situación laboral, sueldos percibidos, personas a cargo, etc., ninguno de ellos influyó en la deserción de la mayoría de estudiantes (79,3% del total de encuestados). Los factores institucionales como la atención recibida, el apoyo administrativo, el entorno virtual, entre otros, no influyeron en la deserción. Finalmente, los factores académicos, como la conformidad con el plan de estudios, la capacitación recibida, etc., no fueron influyentes para la deserción.
Este trabalho investiga os fatores que influenciam o abandono de estudantes universitários do primeiro ciclo de ensino à distância, pertencentes à escola de administração da universidade Senhor do Sipán, entre 2011-I a 2013-I. Aborda os fatores individuais, socioeconômicos, acadêmicos e, finalmente, institucionais.Entre os fatores individuais, o que mais influenciou o abandono foi a falta de tempo dedicado ao estudo (53% do total de inquiridos). No que diz respeito a fatores socioeconômicos, tais como: status de emprego, salários recebidos, dependentes, etc. nenhum deles influenciou o abandono escolar (79,3% de todos os entrevistados). Fatores institucionais, tais como: cuidados recebidos, suporte administrativo, ambiente virtual, etc. não influenciou a deserção. Finalmente, fatores acadêmicos, tais como: conformidade com currículo, treinamento recebido, etc. não eram relevantes em deserção.

Mestrado em Finanças
O objectivo desta dissertação de mestrado é identificar os factores que têm impacto sobre a decisão de estrutura de capital das empresas francesas, alemãs, irlandesas e portuguesas cotadas em bolsa. Pretendemos também identificar diferenças nesta escolha empresarial causada pela recente crise financeira internacional. Para atingir o objectivo principal desta dissertação, este trabalho apresenta um resumo da pesquisa empírica realizada em torno do tema estrutura de capital, seguida por uma secção onde a metodologia utilizada no estudo é descrita, bem como as principais informações detalhadas sobre os dados recolhidos. Posteriormente, os resultados e as principais conclusões da dissertação serão apresentados nas últimas duas seções. Em geral, os resultados transmitem a ideia de que as empresas, ao decidir como financiar as suas necessidades de financiamento, levam em consideração um grupo de factores específicos de cada empresa e características dos respectivos países. Durante a análise das regressões estimadas, os factores macroeconómicos juntamente com o país de origem mostraram ser estatisticamente significativo. Quanto aos factores específicos das empresas, apenas alguns foram considerados significantes para a decisão relativa à estrutura de capital. De destacar que estas decisões de estrutura de capital são influenciados pelo período temporal que as empresas enfrentam, que responde a uma das principais perguntas desta pesquisa, que foi identificar diferenças antes e depois do início da crise internacional.
The aim of this master thesis is to identify the factors that have an impact on the capital structure decision of French, German, Irish and Portuguese listed companies. We also aim to identify differences in this corporate choice caused by the recent international financial crisis. In order to achieve the main purpose of this dissertation, this thesis presents a summary of the empirical research conducted around the capital structure theme, followed by a section where the methodology used in the study is described as well as the detailed key information about the collected data. Subsequently the results and main conclusions of the dissertation will be presented, in the last two sections. In general the outcomes transmit the idea that companies, when deciding how to finance their funding necessities, take in consideration a group of firm and country factors. Throughout the analysis of the estimated regression, the macroeconomic factors along with the country of origin are shown to be statistically significant. As for firm factors, only a few were considered significant when deciding about capital structure. It is worth highlighting that this capital structure decisions are influenced by the time period companies face, which answers one of the major questions of this research, that was to identify differences before and after the beginning of the international crisis.

The objective of this research was to examine the relationship between academic achievement and home factors in third grade students attending urban and rural schools in Guatemala. The sample consisted of 4,952 students selected at random (52% males and 48% females). Mathematics and reading tests were administered to the students and other associated factors were obtained through a questionnaire. The data was analyzed using two statistical approaches: multiple regression and analysis of multiple correspondence. Results showed that an important percentage of the variance in reading achievement is explained by the variables related to home environment. The rest is probably related to factors associated to the teacher or school per se or by individual characteristics of the students that were not possible to measure.
La presente investigación tuvo como objetivo examinar la relación que existe entre el rendimiento escolar y los factores asociados al hogar de alumnos de tercer grado de primaria que asisten a escuelas primarias localizadas en áreas urbanas y rurales de Guatemala. Se tomó al azar una muestra de 4,952 estudiantes (52% niños y 48% niñas) de tercer grado a nivel nacional. Se aplicaron pruebas de lectura y matemática y se obtuvo información de los factores asociados al rendimiento. Se analizaron los datos mediante dos técnicas estadísticas: análisis de regresión múltiple y análisis de correspondencia múltiple. Los resultados obtenidos muestran que un porcentaje importante de la varianza en el rendimiento, especialmente en lectura, se explica  por ciertas variables relacionadas con el entorno del hogar. El resto, probablemente, se podría explicar por factores relacionados con el docente y con la escuela en sí, o por características individuales de los alumnos, que no pudieron ser medidos.

In the past years Väderstad Verken has been developing rapidly and expanding the sales of its machines in new markets, in particular in Eastern Europe. Due to the growing sales and some risks related to possible increases in the import duties on some agricultural equipment the company is considering the possibility of building a factory in the Eastern Europe to serve that market.

For this reason the company was interested in a pre-study on the important factors for the factory start-up in Eastern Europe, in particular, Russia and Ukraine. Thus the scope of the thesis included the research and identification of the factors important particularly for Väderstad Verken as well as identifying some general steps necessary for the factory start-up. In order to identify and analyse location factors critical for Väderstad Verken, literature on location analysis was analysed in order to identify a list of possible factors as well as tools which could be used to evaluate them.

Center of Gravity and Analytic Hierarchy Process (AHP) have been selected to evaluate the performance of several regions on these factors to identify the suitable location of the factory. Expert Choice software was applied in order to simplify the comparison of various factors following the AHP steps.

A specification for the potential factory has been defined given the desired production capacity and requirements. Two factory layouts have been suggested taking into consideration the possibility of the factory expansion.

In some way this master thesis could be used as a guideline for the selection of suitable manufacturing location as well as factory start-up.

Le retard de croissance intra-utérin (RCIU) reste une complication fréquente de la grossesse et expose non seulement à une mortalité néonatale plus élevée, mais également au risque d'un cortège de pathologies chroniques (cardio-métaboliques) à l'âge adulte. Étant un fardeau important pour la santé publique dans le monde entier, il n'existe pas encore à ce jour de traitement curatif autre qu'une extraction plus. précoce avec éventuellement une prématurité. Une étude récente de notre équipe a montré que l'administration de citrulline pendant la gestation améliore la croissance et la synthèse protéique fœtales dans un modèle de RCIU induit chez la rate par la restriction sévère en protéines. L'objectif de ce travail de thèse était donc d'explorer les mécanismes d'action de la supplémentation en citrulline pendant la période périnatale (gestation et allaitement) dans le même modèle. Notre première partie de ce travail confirme que la citrulline stimule la croissance en nous montrant que la supplémentation anténatale en citrulline agit dès le milieu de la gestation sur des gènes codant pour des facteurs de croissance, d’angiogenèse et de transporteurs d'acides aminés pour aboutir à une efficacité placentaire renforcée jusqu'à la fin de la gestation fœtale. Dans la deuxième partie, nous n'avons pas mis en évidence d'effet bénéfique de cette supplémentation postnatale chez des ratons nés dénutris, puis soumis à un régime déséquilibré riche en fructose, ni en termes de croissance, ni sur le métabolisme glucido-lipidique à l'âge adulte jeune. La vigilance impose davantage d'explorations mécanistiques avant d'envisager une étude translationnelle clinique à ce stade sensible de développement qu'est la période néonatale. En revanche, dans le cas de la période gestationnelle, nos résultats incitent à réfléchir à la mise en place d'essais cliniques pertinents pour cette pathologie de la croissance fœtale
Intra-uterine growth restriction (IUGR) remains a common pregnancy-related complication resulting not only in a significant neonatal mortality, but in an increased risk of chronic cardio-metabolic diseases in adulthood as well. This condition represents a serious burden to public health across the world due to lack of a curative treatment except early cessation of gestation with induced prematurity. Developing alternative strategies aimed towards targeted therapy would thus be highly desirable. In recent studies, we showed that citrulline supplementation during gestation in rats under severe dietary protein restriction enhanced fetal growth and protein synthesis. The objective of this work was to further investigate the mechanisms mediating the effect of citrulline during the perinatal period, i.e. gestation and nursing in the same model. In the first part, we confirmed that citrulline improved fetal growth, and further demonstrated that citrulline activated placental genes coding for growth factors, angiogenesis and amino acid transporters early from mid-gestation, resulting in improved fetal weight. However, in the second part of the current work, we failed to observe any beneficial effect of neonatal citrulline supplementation neither on growth, nor on the prevention of alterations of glucose and lipid metabolism in IUGR rats that were later exposed to an unbalanced, fructose-enriched diet. Therefore, further explorations are needed for a better mechanistic understanding before postnatal citrulline supplementation can be considered in translational trials. Otherwise, the results obtained in the gestational period in this work suggest clinical trails should be envisioned for prenatal citrulline supplementation in targeted populations of patients

Els trastorns genòmics són malalties causades per alteracions en regions inestables del genoma que afecten a gens sensibles a dosi. L’arquitectura genòmica d’aquestes regions es caracteritza per la presència de regions de còpia única flanquejada per low-copy repeats. Els risc de recurrència dels trastorns genòmics es considera negligible en famílies on ambdós progenitors presenten un cariotip normal i no expressen trets fenotípics compatibles amb el trastorn que afecta a la seva descendència. No obstant, aquesta consideració es basa en estudis epidemiològics que presenten limitacions relacionades principalment amb un poder estadístic reduït degut a l’anàlisi de cohorts formades per poques famílies. A més, les aproximacions epidemiològiques no aprofundeixen en l’estudi dels mecanismes moleculars que causen les delecions (recombinació homòloga no al·lèlica, NAHR), ni determinen si existeixen factors genètics que predisposen a la NAHR. En aquesta Tesi Doctoral s’ha utilitzat la síndrome de la deleció 22q11.2 com a model d’estudi, per a identificar si, en progenitors amb descendència afecta per trastorns genòmics originats per deleció, existeixen factors que afecten els mecanismes que originen les delecions i que, per tant, incrementen el risc de recurrència i transmissió. Els resultats obtinguts permeten assegurar que una de cada quatre famílies analitzades presenta un risc de transmissió superior a la mitja poblacional. En concret, en un 4% dels progenitors analitzats vàrem identificar la deleció 22q11.2 en mosaic, fet que incrementa notablement el risc de transmissió en aquests individus. A més, vàrem detectar que un 20% dels pares produeixen més delecions 22q11.2 en espermatozoides, la qual cosa s’ha estimat que incrementa el risc de transmissió entre 3 i 5 vegades respecte al risc basal. Per altra banda, vàrem investigar, en els progenitors transmissors de la deleció, les causes que poguessin incrementar la susceptibilitat al fenomen de NAHR i incrementar la generació de delecions. Els nostres resultats han posat de manifest que ni l’edat paterna ni la inversió en heterozigosi de la regió 22q11.2 són factors de predisposició. No obstant, vàrem identificar variants de gens implicats en el procés de recombinació meiòtica (BRIP1, LIG3, PRDM9, RECQL5, SHOC1, TEX19) que mitjançant anàlisis in silico s’han pogut relacionar amb alteracions que predisposen a la NAHR i generen delecions. En conjunt, l’avaluació dels factors de predisposició a la inestabilitat genòmica de la regió 22q11.2 suggereixen que el risc a la NAHR és complex i atribuïble a la confluència de diferents característiques genètiques. Pel que fa a la projecció clínica dels resultats, les nostres dades indiquen que la valoració del risc de recurrència mitjançant l’anàlisi del grau de mosaïcisme i l’anàlisi de delecions en espermatozoides, aportaria una informació rellevant en l’assessorament genètic reproductiu que reben les famílies amb descendència afecta per trastorns genòmics.
Los trastornos genómicos son enfermedades originadas por alteraciones en regiones inestables del genoma que afectan a genes sensibles a dosis. La arquitectura de estas regiones se caracteriza por la presencia de regiones de copia única flanqueada por low copy repeats. El riesgo de recurrencia de los trastornos genómicos se considera negligible en familias donde ambos progenitores presentan un cariotipo normal y no expresan rasgos fenotípicos compatibles con el trastorno que afecta su descendencia. No obstante, esta consideración se basa en estudios epidemiológicos que presentan limitaciones relacionadas principalmente con un poder estadístico reducido debido al análisis de cohortes formadas por pocas familias. Además, las aproximaciones epidemiológicas no ahondan en el estudio de los mecanismos moleculares que causan las deleciones (recombinación homóloga no alélica; NAHR), ni tampoco determinan si existen factores genéticos predisponentes a la NAHR. En esta Tesis Doctoral se ha utilizado el síndrome de la deleción 22q11.2 como modelo de estudio, para identificar si en progenitores con descendencia afecta por trastornos genómicos originados por deleción, existen factores que afecten los mecanismos que originan las deleciones y que, por ende, incrementen el riesgo de recurrencia y transmisión. Los resultados conseguidos permiten asegurar que una de cada cuatro familias analizadas presenta un riesgo de transmisión superior a la media poblacional. En concreto, en un 4% de los progenitores analizados identificamos la deleción 22q11.2 en mosaico lo cual incrementa notablemente el riesgo de transmisión en estos individuos. Además, hemos identificado que un 20% de los padres producen más deleciones 22q11.2 en espermatozoides lo cual se ha estimado que incrementa el riesgo de transmisión entre 3 y 5 veces respecto al riesgo basal. Por otra parte, hemos investigado en los progenitores transmisores de la deleción las causas que pudieran incrementar la susceptibilidad al fenómeno de NAHR e incrementar la generación de deleciones. Nuestros resultados han puesto de manifiesto que ni la edad paterna, ni la inversión en heterocigosis de la región 22q11.2 son factores de predisposición. No obstante, hemos identificado variantes de genes implicados en el proceso de recombinación meiótica (BRIP1, LIG3, PRDM9, RECQL5, SHOC1, TEX19) que mediante análisis in silico se han podido relacionar con alteraciones que predisponen a la NAHR y generan deleciones. En conjunto, la evaluación de los factores de predisposición a la inestabilidad genómica de la región 22q11.2 sugieren que el riesgo a la NAHR es complejo y atribuible a la confluencia de diferentes características genéticas. En cuanto a la proyección clínica de los resultados, nuestros datos indican que la valoración del riesgo de recurrencia mediante el análisis del grado de mosaicismo, y mediante el análisis de deleciones en espermatozoides, aportaría una información relevante en el asesoramiento genético reproductivo que reciben las familias con descendencia afecta por trastornos genómicos.
Genomic disorders are diseases caused by alterations in unstable regions of the genome that affect dose-sensitive genes. The genomic architecture of these regions is characterized by the presence of single-copy regions flanked by low-copy repeats. The risk of recurrence of genomic disorders is considered negligible in families where both parents present a normal karyotype and do not express phenotypic features compatible with the disorder affecting their offspring. However, this consideration is based on epidemiological studies that present several limitations related to reduced statistical power due to the analysis of cohorts formed by a reduced number of families. In addition, epidemiological approaches do not delve into the study of the molecular mechanisms that cause deletions (nonallelic homologous recombination, NAHR), nor do they determine whether genetic factors predispose to NAHR. In this Doctoral Thesis, the 22q11.2 deletion syndrome has been used as a study model, to identify whether, in parents with offspring affected by genomic disorders caused by deletion, there are factors that affect the mechanisms which give rise to deletions and which therefore increase the risk of recurrence and transmission. The results obtained allow us to ensure that one in four families analyzed has a risk of transmission higher than the population average. Specifically, in 4% of the parents analyzed we identified the 22q11.2 deletion in mosaic, which significantly increases the risk of transmission in these individuals. In addition, we found that 20% of parents produce more 22q11.2 deletions in spermatozoa, which has been estimated to increase the risk of transmission by 3 to 5 times the baseline risk. On the other hand, we investigated, in the parents transmitting the deletion, the causes that could increase the susceptibility to the NAHR phenomenon and increase the generation of deletions. Our results have shown that neither paternal age nor inversion in heterozygosity of the 22q11.2 region are predisposing factors. Nevertheless, we identified variants of genes involved in the meiotic recombination process (BRIP1, LIG3, PRDM9, RECQL5, SHOC1, TEX19) that by in silico analysis could be related to alterations that predispose to NAHR and generate deletions. Taken together, the assessment of predisposing factors for genomic instability in the 22q11.2 region suggests that the risk in NAHR is complex and attributable to the confluence of different genetic traits. Regarding the clinical projection of the results, our data indicate that the assessment of the risk of recurrence by the analysis of the degree of mosaicism and the analysis of sperm deletions would provide relevant information in the reproductive genetic counseling received by families with offspring affected by genomic disorders.
Universitat Autònoma de Barcelona. Programa de Doctorat en Biologia Cel·lular

La present tesi és una aportació a el coneixement de nous factors de risc per al tumor testicular de cèl·lules germinals (TTCG). El TTCG presenta una etiologia multifactorial, atribuïble a un retard en la diferenciació dels gonocitos fetals. El TTCG és més freqüent en homes amb una espermatogènesi alterada, suggerint una possible etiopatogènia comuna. El cromosoma I conté gens essencials per a una correcta espermatogènesi, les regions de l'factor d'azoospèrmia (AZF). La regió AZF més dinàmica és la regió AZFc que presenta punts fràgils que predisposa a reordenaments. El reordenament parcial més rellevant des del punt de vista clínic de la regió AZFc és la deleció gr / gr. S'ha relacionat la delació gr / gr amb un major risc de desenvolupar un TTCG, però la falta d'informació sobre els paràmetres seminals dels pacients no ha permès d'aclarir si l'associació observada està relacionada amb l'espermatogènesi alterada o si és un factor de risc independent. A més, encara queda per establir si altres tipus de delecions i duplicacions de la regió AZFc presenten relació amb el TTCG. La primera part d'aquesta tesi s'enfoca en l'estudi dels reordenaments parcials de la regió AZFc al TTCG. S'han analitzat 497 pacients amb TTCG i 2030 controls sense TTCG. Un 3.8% dels pacients amb TTCG presentaven algun tipus de deleció parcial de la regió AZFc respecte a l'2.5% de el grup control (p = 0.078). La deleció parcial més freqüent va ser la deleció gr / gr, mentre que els altres tipus de delecions parcials de la regió AZFc van resultar ser molt rares. Segons el fenotip seminal, es va observar un major risc de TTCG en pacients normozoospérmicos portadors de delecions parcials de la regió AZFc respecte als controls normozoospérmicos. No hi va haver diferències significatives entre pacients i controls segons les duplicacions parcials de la regió AZFc. Es va mostrar que les alteracions en la dosi de el gen DAZ confereixen un major risc de TTCG. Aquests resultats confirmen que un dèficit de l'contingut gènic de la regió AZFc juga un paper important en la etiopatogènesi de l'TTCG. En particular, la deleció gr / gr confereix un risc significatiu per al desenvolupament de l'TTCG independentment dels paràmetres seminals. Els factors ambientals també estan involucrats en la etiopatogènesi de l'TTCG, especialment si interfereixen en un període específic de el desenvolupament testicular, en el denominat ""masculinization programming window"" (MPW). Un desequilibri hormonal en aquest període compromet a la correcta funció de les cèl·lules fetals de Sertoli i Leydig, originant la síndrome de disgenèsia testicular (SDT). La distància anogenital (DAG) és considerada un biomarcador de l'acció dels andrògens durant el MPW. La DAG més curta ha estat relacionada amb tots els components de l'SDT, excepte amb el TTCG. La segona part d'aquesta tesi valora l'associació entre la DAG i el TTCG. A més avalua el paper de l'polimorfisme CAG de el gen AR en el desenvolupament de l'TTCG i la DAG. Es van analitzar a 156 pacients amb TTCG i 110 controls sans normozoospérmicos. Es va observar una distància anopeneana (DAGap) i una distància anoescrotal (dagues) significativament més curta en els TTCG respecte als controls. Es van definir uns punt de tall (DAGap: 130mm; dagues: 53mm) que indiquen un major risc de TTCG en aquells individus que es trobin per sota d'aquests valors. No s'ha trobat relació entre el polimorfisme CAG i el TTCG o la longitud de la DAG. En conclusió, les dades revelen que els pacients amb una DAG més curta presenten un major risc de TTCG, recolzant la teoria sobre la influència de l'desequilibri androgènic durant el desenvolupament fetal en l'etiopatogènia de l'TTCG.
La presente tesis es una aportación al conocimiento de nuevos factores de riesgo para el tumor testicular de células germinales (TTCG). El TTCG presenta una etiología multifactorial, atribuible a un retraso en la diferenciación de los gonocitos fetales. El TTCG es más frecuente en varones con una espermatogénesis alterada, sugiriendo una posible etiopatogenia común. El cromosoma Y contiene genes esenciales para una correcta espermatogénesis, las regiones del factor de azoospermia (AZF). La región AZF más dinámica es la región AZFc que presenta puntos frágiles que predispone a reordenamientos. El reordenamiento parcial más relevante desde el punto de vista clínico de la región AZFc es la deleción gr/gr. Se ha relacionado la delación gr/gr con un mayor riesgo de desarrollar un TTCG, pero la falta de información sobre los parámetros seminales de los pacientes no ha permitido de clarificar si la asociación observada está relacionada con la espermatogénesis alterada o si es un factor de riesgo independiente. Además, aún queda por establecer si otros tipos de deleciones y duplicaciones de la región AZFc presentan relación con el TTCG. La primera parte de esta tesis se enfoca en el estudio de los reordenamientos parciales de la región AZFc en el TTCG. Se han analizado 497 pacientes con TTCG y 2030 controles sin TTCG. Un 3.8% de los pacientes con TTCG presentaban algún tipo de deleción parcial de la región AZFc respecto al 2.5% del grupo control (p= 0.078). La deleción parcial más frecuente fue la deleción gr/gr, mientras que los otros tipos de deleciones parciales de la región AZFc resultaron ser muy raras. Según el fenotipo seminal, se observó un mayor riesgo de TTCG en pacientes normozoospérmicos portadores de deleciones parciales de la región AZFc respecto a los controles normozoospérmicos. No hubo diferencias significativas entre pacientes y controles según las duplicaciones parciales de la región AZFc. Se mostró que las alteraciones en la dosis del gen DAZ confieren un mayor riesgo de TTCG. Estos resultados confirman que un déficit del contenido génico de la región AZFc juega un papel importante en la etiopatogénesis del TTCG. En particular, la deleción gr/gr confiere un riesgo significativo para el desarrollo del TTCG independientemente de los parámetros seminales. Los factores ambientales también están involucrados en la etiopatogénesis del TTCG, especialmente si interfieren en un periodo específico del desarrollo testicular, en el denominado "masculinization programming window" (MPW). Un desequilibrio hormonal en este periodo compromete la correcta función de las células fetales de Sertoli y Leydig, originando el síndrome de disgenesia testicular (SDT). La distancia anogenital (DAG) es considerada un biomarcador de la acción de los andrógenos durante el MPW. La DAG más corta ha sido relacionada con todos los componentes del SDT, excepto con el TTCG. La segunda parte de esta tesis valora la asociación entre la DAG y el TTCG. Además evalúa el papel del polimorfismo CAG del gen AR en el desarrollo del TTCG y la DAG. Se analizaron a 156 pacientes con TTCG y 110 controles sanos normozoospérmicos. Se observó una distancia anopeneana (DAGap) y una distancia anoescrotal (DAGas) significativamente más corta en los TTCG respecto a los controles. Se definieron unos punto de corte (DAGap: 130mm ;DAGas: 53mm) que indican un mayor riesgo de TTCG en aquellos individuos que se encuentren por debajo de estos valores. No se encontró relación entre el polimorfismo CAG y el TTCG o la longitud de la DAG. En conclusión, los datos revelan que los pacientes con una DAG más corta presentan un mayor riesgo de TTCG, apoyando la teoría sobre la influencia del desequilibrio androgénico durante el desarrollo fetal en la etiopatogenia del TTCG.
This thesis is a contribution to the knowledge of new risk factors for testicular germ cell tumor (TTCG). TTCG has a multifactorial etiology, attributable to a delay in the differentiation of fetal gonocytes. TTCG is more frequent in men with altered spermatogenesis, suggesting a possible common etiopathogenesis. The Y chromosome contains essential genes for correct spermatogenesis, the azoospermia factor (AZF) regions. The most dynamic AZF region is the AZFc region that presents fragile points that predispose to rearrangements. The most clinically relevant partial rearrangement of the AZFc region is the gr / gr deletion. gr / gr cheating has been associated with an increased risk of developing TTCG, but the lack of information on the seminal parameters of the patients has not made it possible to clarify whether the observed association is related to altered spermatogenesis or if it is a factor of independent risk. Furthermore, it remains to be established whether other types of deletions and duplications of the AZFc region are related to TTCG. The first part of this thesis focuses on the study of partial rearrangements of the AZFc region in the TTCG. 497 patients with TTCG and 2030 controls without TTCG have been analyzed. 3.8% of the patients with TTCG presented some type of partial deletion of the AZFc region compared to 2.5% of the control group (p = 0.078). The most frequent partial deletion was the gr / gr deletion, while the other types of partial deletions of the AZFc region were found to be very rare. According to the seminal phenotype, a higher risk of TTCG was observed in normozoospermic patients carrying partial deletions of the AZFc region compared to normozoospermic controls. There were no significant differences between patients and controls according to the partial duplications of the AZFc region. Alterations in the dose of the DAZ gene were shown to confer an increased risk These results confirm that a deficit in the gene content of the AZFc region plays an important role in the etiopathogenesis of TTCG. In particular, the gr / gr deletion confers a significant risk for the development of TTCG regardless of seminal parameters. Environmental factors are also involved in the aetiopathogenesis of TTCG, especially if they interfere in a specific period of testicular development, in the so-called "masculinization programming window" (MPW). A hormonal imbalance in this period compromises the correct function of the fetal Sertoli and Leydig cells, causing the testicular dysgenesis syndrome (TDS). The anogenital distance (DAG) is considered a biomarker of the action of androgens during MPW. The shorter DAG has been related to all components of the SDT, except the TTCG. The second part of this thesis assesses the association between the DAG and the TTCG. It also evaluates the role of the CAG polymorphism of the AR gene in the development of TTCG and DAG. 156 patients with TTCG and 110 healthy normozoospermic controls were analyzed. A significantly shorter anopeneal distance (DAGap) and anoscrotal distance (DAGas) were observed in TTCG compared to controls. Cut-off points were defined (DAGap: 130mm; DAGas: 53mm) that indicate a greater risk of TTCG in those individuals who are below these values. No relationship was found between the CAG polymorphism and the TTCG or the length of the DAG. In conclusion, the data reveal that patients with a shorter DAG have a higher risk of TTCG, supporting the theory about the influence of androgen imbalance during fetal development on the etiopathogenesis of TTCG.

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de licenciado em Criminologia
O presente trabalho tem como título “Famílias com comportamentos transgressores e o impacto no desenvolvimento psico-educativo de um jovem delinquente” e encontra-se dividido em duas grandes partes. Na primeira é apresentada uma pesquisa bibliográfica em que se dá a conhecer o conceito de adolescência, o conceito e perspectivas da Delinquência Juvenil, as teorias explicativas da Delinquência Juvenil, os factores de risco e protecção, a teoria da Vinculação e como a família pode representar um factor de risco potenciador da delinquência juvenil. Na segunda fase deste projecto, que diz respeito ao estudo empírico, é aplicado um questionário a 50 alunos da Escola Secundária Rodrigues de Freitas (de ambos os sexos) com idades compreendidas entre os 12 e os 17 anos, e que se encontram sinalizados pela CPCJ, tribunais ou apresentam comportamento inadequado no contexto escolar e social. Este questionário visa obter dados sócio-demógráficos, de delinquência auto-revelada, da percepção dos jovens acerca da vinculação com os seus progenitores, das dinâmicas familiares, entre outros. Ainda nesta fase, é também aplicado á Psicóloga do Agrupamento de Escolas e aos Técnicos que trabalham com estes alunos e respectivas famílias uma entrevista semi-estruturada, de forma a compreender, de acordo com a opinião dos inquiridos, se realmente existe uma relação entre a ausência de vínculos e a adopção de comportamentos desviantes e comprovar que a existência de antecedentes criminais/comportamentos delinquentes na família pode funcionar como potenciador para o desenvolvimento psico-educativo de um jovem delinquente.
This project is entitled “Families with lawless behavior and the impact on psycho-educational development of a juvenile offender "and is divided into two major parts. In the first one, a bibliographical research is presented, in which the concept of adolescence is shown, as well as the concept and perspectives of Juvenile Delinquency, the risk and protection factors, the Link Theory, and how family may represent an enhancing factor in juvenile delinquency. In the second phase of this project, which concerns the empirical study, it is applied a questionnaire to 50 students (from both genders), from the Rodrigues de Freitas Secondary School, that are signalized by the Children and Youth Protection Commission, by courts or showing inadequate behavior in the social and scholar context. This questionnaire aims to obtain socio demographic data of self-revealed delinquency, from the youth’s perception on the ties with the progenitors, the family dynamics, among others. Still in this phase, it is also applied a semi-structured interview to the Psychologist from the School Group, as well as to the Technicians that work with these students and respective families, in order to understand, according to the respondents’ opinion, if there really is a connection between the absence of ties and the adoption of deviant behaviors, and to prove that the presence of criminal background/delinquent behavior in the family context can work as an enhancer in the psycho-educational development of a juvenile offender.

La presente tesis de investigación busca hallar los factores que explican las exportaciones de la quinua de Perú hacia Estados Unidos durante los años 2007 al 2017; ésta se ha desarrollado en 5 capítulos: El primer capítulo incluye información sobre el producto elegido, un acercamiento al mercado mundial de la quinua, así como el destino específico de Estados Unidos; investigaciones anteriores, bases teóricas y definición de las variables del modelo econométrico a seguir. El segundo capítulo plantea la situación problemática, problemas específicos, hipótesis y objetivos, los cuales serán satisfechos a través de una investigación cuantitativa. El tercer capítulo desarrolla el tipo, alcance y diseño de la investigación, la operacionalización de las variables y los instrumentos metodológicos para el recojo de la investigación. El cuarto capítulo comprende el desarrollo y la aplicación del modelo de regresión lineal planteada en la tesis de Mamani (2015). El quinto capítulo muestra el análisis de los resultados obtenidos, conclusiones y recomendaciones. Según el análisis estadístico realizado, se puede concluir que las exportaciones de la quinua de Perú hacia Estados Unidos durante los años 2007 al 2017, son significativamente afectadas por los factores externos de Producto Bruto Interno de Estados Unidos, el precio internacional y la tarifa arancelaria.
This research thesis seeks to find the factors that explain the exports of quinoa from Peru to the United States during the years from 2007 to 2017; This has been developed in 5 chapters: The first chapter includes information about the chosen product, an approach to the world market of quinoa, as well as the specific destination of the United States; previous investigations, theoretical bases and definition of the variables of the followed econometric model. The second chapter presents the problematic situation, specific problems, hypotheses and objectives, which will be satisfied through a quantitative research. The third chapter develops the type, scope and design of the research, the operationalization of the variables and the methodological instruments for the collection of information. The fourth chapter includes the development and application of the linear regression model proposed in the thesis of Mamani (2015). The fifth chapter shows the analysis of the results obtained, conclusions and recommendations. According to the statistical analysis carried out, it can be concluded that the exports of quinoa from Peru to the United States during the years from 2007 to 2017 are significantly affected by the external factors of the United States Gross Domestic Product, the international price and the tariff rate.
Tesis

La presente tesis tiene como objetivo principal identificar la relación entre la motivación y la productividad en el área administrativa del sector de certificaciones de sistemas de gestión en el Perú en el primer semestre del año 2018. Tiene un enfoque de investigación cuantitativa de diseño no experimental y tipo descriptivo correlacional. Para la recolección de datos en la investigación cuantitativa se usaron dos cuestionarios en los colaboradores, una para medir los factores motivacionales y de higiene de Frederick Herzberg, y otro para medir la eficacia y eficiencia en dicha área, en ambos se tomó en cuenta la escala de Likert, donde se eligieron 5 niveles que iban desde Totalmente en desacuerdo hasta Totalmente de acuerdo. La muestra cuantitativa fue de 51 colaboradores, y para apoyar y validar la información obtenida se realizaron entrevistas a expertos de dicho sector, con la finalidad obtener información complementaria que nos pudiera corroborar los resultados. Luego de la realización del análisis de datos, los resultados revelaron que existen una correlación positiva muy alta entre la motivación y la productividad laboral, con un nivel de coeficiente de correlación de 0.909; por otro lado, el único factor de higiene que no tiene una correlación con la productividad es la relación con los superiores; y para finalizar, el factor de higiene “relaciones interpersonales” tiene una correlación negativa moderada de 0.473 con la productividad. Con ello se demuestra la gran implicancia que tiene la motivación sobre la productividad dentro de una organización.
The main objective of this thesis is to identify the relationship between motivation and productivity in the administrative area of the management system certifications sector in Peru in the first half of the 2018. It has a non-experimental design quantitative research approach and correlational descriptive type. For the collection of data in quantitative research two questionnaires were used in the collaborators, one to measure the motivational and hygiene factors of Frederick Herzberg, and another to measure the effectiveness and efficiency in that area, in both the scale was considered from Likert, where 5 levels were chosen ranging from Totally Disagree to Totally Agree. The quantitative sample consisted of 51 (Fifty-one) collaborators, and to support and validate the information obtained, interviews were conducted with experts in the sector, so that we could obtain information that corroborate the results. After revising the data analysis, the results revealed that employees have a very high positive correlation between motivation and work productivity, with a correlation coefficient level of 0.909; On the other hand, the only factor of hygiene that does not have a correlation with productivity is the relationship with superiors; and finally, the hygiene factor "interpersonal relationships" has a moderate negative correlation of 0.473 with productivity. With this in consideration it demonstrates the great implication that motivation has on productivity within an organization.
Tesis

Although stroke is the third leading cause of death and the leading cause of long-term disability, the cause of stroke is largely viewed as environmentally impacted and modifiable unlike the top two leading causes of death, heart disease and cancer. In order to understand the complexity of stroke and the impact it has on patients and their family members when environmental factors do not provide a full explanation, this thesis seeks to explore the potential genetic factors that contribute to the incidence of stroke. Single-gene disorders, polygenic/genome-wide disorders, and epigenetic influences to the presentation of stroke will be explored and an assessment on how stroke genetics could be applied in clinical practice will be discussed.

La Mauritanie est caractérisée par un climat sec et chaud, Saharien au nord et sahélien au sud. Les vents au nord-est, sont fréquents et favorisent la progression de l'ensablement. La saison des pluies est très hétérogène sur le plan spatio-temporel. Une grande partie du pays reçoit moins de 300 mm / an. Au cours des trente dernières années, trois grandes sécheresses ont été enregistrées au cours desquelles les précipitations ont été inférieures à 35 à 70% de la moyenne. Les principales ressources agro-pastorales du pays sont: l'agriculture, les ressources en terres, l'élevage, les ressources en eau et la population rurale. Au niveau macroéconomique, le secteur rural, en dehors de la pêche artisanale, occupe environ 56% de la population et joue un rôle important dans l'économie nationale : il contribue à plus de 17,5% du PIB, soit environ 68 milliards d'ouguiyas en 2011. De nombreuses contraintes, défis et opportunités peuvent être identifiées:1)En termes de contraintes, on peut inclure: pluies insuffisantes et irrégulières et inondations, faible productivité de la production agricole et pastorale, exode rural. 2)En termes d'opportunités: décentralisation, situation géographique du pays, ressources foncières du pays, une classe d'entrepreneurs ayant des capacités financières et un bon réseau de communication. Cette thèse montre que la Mauritanie dispose d'un potentiel important qui est loin d'être pleinement exploité, en dépit d'importants investissements, notamment dans le secteur irrigué. Bien que les facteurs climatiques ont une responsabilité majeure dans la situation actuelle, cette thèse évalue le poids des aspects techniques, socio-économiques, structurelles, les facteurs organisationnels.

Preferential processing favouring threatening information has received increased attention because cognitive formulations have placed increased emphasis on its role as a key cognitive factor underlying vulnerability to and maintenance of anxiety disorders. The present dissertation comprises four empirical studies within the area of preferential processing. Two different outcome measures were used to index preferential processing of threat-related information: Skin conductance responses (SCRs) were used in Studies I, II, and III. The emotional Stroop task was used in Study IV. The main focus has been on preferential processing of threat-related information that occurs outside awareness, thus preferential preattentive processing. Study I investigated the role of traumatic combat experience with regard to preferential processing among UN soldiers following a presentation of threat-related pictures. Results indicated that soldiers with combat experience consistently reacted with lower SCRs compared to soldiers without combat experience. One issue addressed in the individual studies was the association between preferential preattentive processing and trait anxiety. Studies II, III, and IV showed that elevated levels of trait anxiety promote preferential preattentive processing of negatively valenced information, whereas elevated levels of social desirability generally prevent preferential preattentive processing of negatively valenced information. Study II highlighted the importance of including the social desirability factor when studying effects of trait anxiety on preferential processing. In addition, Studies III and IV explored the relationship between preferential processing and emotional vulnerability. The main findings support the notion of preferential preattentive processing of threat representing an underlying predisposition to heightened emotional vulnerability in response to stressful events.

Journal impact factors play an increasing role in academics as a tool for evaluating faculty, research, and resource allocations. These evaluations may be effective in departments where the subject matter is reasonably unified. However, given the diversity found within the subject matter of psychology, the impact factors of journals may not be comparable across the various areas. This study compares the average impact factors across decile levels of journals from seven areas of psychology. It is found that impact factor scores are not comparable across the seven areas of psychology. This difference is more pronounced when looking at higher decile journals. Further research could be conducted to investigate differences among psychology areas using other bibliographic variables, including some of the newer indices of individual scholar productivity, such as the h-index.

La compréhension des déterminants de l’activité physique (AP) et de l’activité sédentaire (AS) constitue un problème de santé public majeur en vue de promouvoir l’AP et de diminuer l’AS. Les principaux objectifs de cette recherche sont a) décrire les niveaux d'activité physique modérée à vigoureuse (APMV) et les niveaux d’AS d’adolescents des villes de Tarbes (France) et Huesca (Espagne) et b) analyser l'influence de plusieurs facteurs environnementaux, sociaux et psychologiques sur les niveaux de ces mêmes variables. Les cadres théoriques des modèles socio-écologiques et de la théorie de l’autodétermination ont été utilisées comme base à ce travail. Un total de 828 adolescents (14.32±.73 ans), dont 50,5% d'espagnols, a participé au projet. Cette thèse se compose de six études. Les résultats ont montré que les niveaux d’APMV sont plus élevés en Espagne (~ 60 minutes/jour) qu'en France (~ 47 minutes/jour). Ces différences ont été mises en évidence lors de presque tous les moments de la semaine, à l’exception du temps scolaire. Il a été également montré que la pratique de plusieurs comportements sédentaires (SB) semble excessive, aussi bien en Espagne qu’en France (plus de deux heures par jour de temps d'écran). L’analyse des déterminants montre que des températures plus élevées, des niveaux de précipitation plus faibles et l'utilisation du transport actif favorisent des niveaux plus élevés d’APMV dans les deux pays. Il apparaît également qu’une motivation plus autodéterminée, des niveaux plus élevés de satisfaction des besoins psychologiques fondamentaux (compétence et affiliation) ainsi qu’un soutien plus élevé du père conduisent à des niveaux plus élevés d’APMV
Physical activity (PA) and its factors of influence constitute important elements of study. The main objectives of this research are a) to describe the moderate-to-vigorous physical activity (MVPA) levels and sedentary activity levels of a sample of adolescents from cities of Tarbes (France) and Huesca (Spain), and b) to analyse the influence of several environmental, social, and psychological factors on their PA levels. A total of 828 adolescents (14.32±.73 years), of which 50.5% were Spaniards, took part in the project. This dissertation is made up of six studies. Results showed that MVPA levels are higher in Spain (~ 60 minutes) than in France (~ 47 minutes). These differences were found at almost any given time of the week, except during school time. Results also showed that the practice of several sedentary behaviours (SB) seems excessive, both in Spain and France (more than two hours per day of screen time). Considering factors of influence, it can be said that warmer temperatures, lower levels of rainfall and the use of active transport all promote higher MVPA levels in both countries. It is also shown how more self-determined motivation, higher levels of basic psychological needs satisfaction (except the perception of autonomy) and greater support from the father lead to higher MVPA levels. Programmes to promote PA need to be implemented

Els col·lectius animals presenten unes característiques que afavoreixen la transmissió i manteniment de determinats patògens. L’elevada densitat d’animals, la contaminació ambiental, l’estrés, o l’existència de portadors assimptomàtics, són alguns dels factors implicats en l’epidemiologia dels processos infecto-contagiosos. En el cas dels col·lectius felins, els paràsits interns constitueixen un dels problemas més habituals amb important repercussió, tant en salut animal com en salut pública. Estudis epidemiològics realitzats en diferents col·lectius han evidenciat que, sovint, els mecanismes de control establerts no són suficientment efectius. Amb l’objectiu de determinar la prevalença d’infecció de paràsits interns, i poder establir estratègies de control adients, es va dur a terme un estudi epidemiològic en el qual es van avaluar diferents col·lectius felins, incloent centres d’acollida, gateres, colònies felines i criadors. Per això, es van recollir mostres de femta i es van analitzar mitjançant tècniques coprològiques i immunològiques. Algunes mostres, a més a més, es van procesar mitjançant tècniques de biología molecular per a poder identificar els genotips de Giardia spp. i espècies de Cryptosporidium spp. Per a poder establir unes mesures de control adients, es van avaluar aquells factors considerats de risc i que poden ser modificables, com ara factors vinculats a l’ambient o al maneig. Paral·lelament, i tenint en compte que l’estrés pot exercir un rol destacable en la presentació clínica de determinades parasitosis, es va avaluar la resposta d’estrés com un altre indicador a tenir en compte a l’hora de dissenyar unes estratègies de control apropiades. La prevalença total de parasitosis observada en col·lectius felins fou de 53%. Tots els col·lectius mostrejats van mostrar prevalences d’infecció que oscil·laven del 83% al 94%. Els col·lectius que van presentar les prevalences més elevades van ser les colònies felines (70.4%), seguides dels centres d’acollida (58.8%), i les gateres (41.4%). Als criadors, es van observar les prevalences més baixes (20.8%) i, fins i tot, a un dels centres avaluats no es va detectar cap paràsit. No obstant, els paràsits observats van ser diferents en els diversos col·lectius. Així, els gats de colònia, animals que viuen en semi-llibertat i mostren un marcat comportament depredador, van presentar prevalences significativament superiors a helmints, mentre que els centres d’acollida, les gateres i els criadors, constituits per animals que viuen confinats i sense accés, o molt limitat, a l’exterior, van presentar prevalences molt més altes a protozous. En el cas concret dels criadors, no es van detectar helmints. El paràsit més prevalent va ser Giardia spp., identificant-se tant el genotip F, propi dels felins, com l’A considerat potencialment zoonòtic. En el cas de Cryptosporidium spp., C. felis va ser l’única espècie identificada. El nivell de benestar dels animals, es va avaluar a partir de la quantificació de metabòlits de glucocorticoids fecals (FGM), en dos mostrejos diferents. Per això, es va validar bioquímicament un immunoassaig per a l’espècie i la matriu biológica objectes d’estudi. Amb la metodología validada, es va procedir a la quantificació dels FGM, i es van relacionar els valors mitjos obtinguts amb diferents variables d’interés. Els criadors van ser els centres on els valors mitjos de FMG van ser més elevats, fet que es va atribuir a l’estat fisiològic dels animals en reproducció. Els centres d’acollida van mostrar nivells significativament més alts que les gateres i les colònies felines. Els dos primers són ambients on els animals viuen confinats, mentre que les colònies es relacionen amb un estil de vida lliure.
Los colectivos animales presentan unas características que favorecen la transmisión y el mantenimiento de determinados patógenos. Una alta densidad de animales, contaminación ambiental, el estrés, o la existencia de portadores asintomáticos son algunos de los factores implicados en la epidemiología de los procesos infecto-contagiosos. En el caso de los colectivos felinos, los parásitos internos consituyen uno de los problemas más habituales con una importante repercusión, no sólo en sanidad animal sino también en salud pública. Estudios epidemiológicos realizados en distintos colectivos han evidenciado que, a menudo, los mecanismos de control establecidos no son suficientemente efectivos. Con el objetivo de determinar la prevalencia de infección de parásitos internos y poder establecer estrategias de control eficientes, se procedió a un estudio epidemiológico en el que se evaluaron distintos colectivos felinos, que incluían centros de acogida, gateras, criaderos y colonias. Para ello se tomaron muestras de heces que se analizaron mediante técnicas coprológicas e inmunológicas. Algunas de ellas, además, se procesaron mediante técnicas de biología molecular para poder identificar los genotipos de Giardia spp. i especies de Cryptosporidium. Para poder establecer unas medidas de control adecuadas, se evaluaron aquellos factores considerados de riesgo y que podrían ser modificables, como factores vinculados al ambiente o al manejo. Paralelalmente, y teniendo en cuenta que el estrés puede desempeñar un rol destacable en la presentación clínica de determinadas parasitosis, se evaluó la respuesta al estrés como otro indicador que hay que tener en cuenta a la hora de diseñar unas estrategias de control apropiadas. La prevalencia total de parasitosis observada en colectivos felinos fue del 53%. Todos los colectivos evaluados mostraron prevalencias de infección que oscilaron del 8.3% al 94%. Los colectivos que presentaron prevalencias más elevadas fueron las colonias felinas (70.4%), seguido de los centros de acogida (58.8%), y las gateras (41.4%). En los criaderos, se observaron las prevalencias más bajas (20.8%) e, incluso, en uno de los centros evaluados no se detectó infección por parásitos. Además, los parásitos detectados fueron distintos en función al tipo de colectivo. Así, los gatos de colonia, animales que viven en semi-libertad y presentan un marcado comportamiento depredador, presentaban prevalencias significativamente superiores a helmintos, mientras que los centros de acogida, las gateras, y los criadores, constituidos por animales que viven confinados y sin acceso, o muy limitado, al exterior, presentaron prevalencias mucho más altas frente a protozoos. En el caso concreto de los criaderos, no se detectaron helmintos. El parásito más prevalente resultó ser Giardia spp., identificándose tanto el genotipo F, propio de los felinos, como el A, considerado potencialmente zoonótico. En el caso de Cryptosporidium spp., C. felis fue la única especie identificada. El nivel de bienestar de los animales, se evaluó a partir de la cuantificación de los metabolitos de glucocorticoides fecales (FGM), en dos muestreos diferentes. Para ello, se validó bioquímicamente un enzimoinmunoensayos para la especie y la matriz biológica objeto de estudio. Con la metodología validada, se procedió a la cuantificación de los FGM, y se relacionaron los valores medios obtenidos con diferentes variables de interés. Los criaderos fueron los centros donde los valores medios de FGM fueron más elevados, lo que se atribuyó al estado fisiológico de los animales en reproducción. Los centros de acogida mostraron niveles significativamente más altos que las gateras y las colonias felinas. Los dos primeros son ambientes donde los animales viven confinados, mientras que las colonias se relacionan con un estilo de vida libre.
In animal collectivities, infectious diseases are difficult to prevent and control. Several factors such as high animal density, environmental contamination, stress, or the existence of subclinical carriers, may contribute to the spread and maintenance of such diseases. Particularly, in multi-cat environments, endoparasite infections are both of veterinary and public health concern. Epidemiological studies have demonstrated that, frequently, the rutinary measures adopted fail in the control effectiveness of such infections. In order to evaluate the prevalence of endoparasite infections, and to establish efficient control strategies, an epidemiological study was performed in several multi-cat environments, including rescue shelters, catteries, feline colonies and breeding catteries. Fecal samples were collected and analyzed by coprological and immunological techniques. Moreover, a certain amount of samples were analyzed by molecular methods in order to identify Giardia spp. assemblages, and Cryptosporidium sprecies. With the aim to establish such control measures, those risk factors that can be modified, regarding the environment and the management, were evaluated. Furthermore, and taking into account the important role of stress in the clinical presentation of some parasite infections, we evaluated the stress response as an indicator when designing appropriate control stategies. In this study, the overall prevalence of parasite infection was 53%. Infections were noted in 26 out of 27 of the facilities sampled with prevalence ranging from 8.3% to 94%. Feline colonies showed the highest prevalence (70.4%) followed by rescue shelters (58.8%) and catteries (41.4%). Breeding catteries showed the least prevalences (20.8%), and in one of such no parasite infection was detected. In addition, the parasite population was different according to the kind of collectivity. Thus, in feline colonies, free roaming cats which show a markedly predatory behavior were significantly more parasitized by helminths, whereas in cats living in the other collectivities involving confinement and with limited or no contact outdoors, protozoa infections were predominant. It is noteworthy to note that, in breeding catteries no helminth infection was detected. Giardia spp. was the most prevalent intestinal parasite reported, and both the cat specific (assemblage F), and assemblage A, regarded as potentially zoonotic, were identified. Concerning Cryptosporidium spp., only C. felis was detected. Finally, animal welfare was evaluated by quantifying fecal glucocorticoid metabolites (FGM), by two different sampling. Thus, an enzymoimmunoassay was previously validated for the specie and biological matrix of interest. Once validated, FGM were quantified, and the results were statistically analyzed. Breeding catteries showed the highest mean value of FGM, probably because of the physiological alterations during the reproductive process. Rescue shelters showed significantly higher levels than both catteries and feline colonies. The first two involved confinement, whereas feline colonies are related to free-ranging lifestyle.

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de licenciado em Criminologia
A Adolescência é uma idade controversa que se caracteriza essencialmente pela busca de uma identidade, cujo papel do grupo de pares é extremamente importante. No entanto, o papel deste grupo de pares, pode ter uma influência negativa, contribuindo para que o jovem adopte comportamentos desviantes e delinquentes. A delinquência juvenil, é um dos grandes problemas a nível social, pois este incorpora uma variedade de comportamentos, que são influenciados por uma série de factores, os chamados factores de risco e os factores de protecção. O grupo de pares, o consumo de drogas, a impulsividade, e as famílias destruturadas são os principais factores de risco que levam o jovem a delinquir, bem como, a entrar em gangues juvenis. Este trabalho propõe assim, a criação de um Plano de Prevenção a nível escolar, que será realizado junto de alunos sinalizados com problemas de comportamentos de risco e de condutas de pares desviantes, bem como das famílias destes, de forma a fazer com que os jovens se consciencializem dos problemas e consequências que a entrada para um gangue tem para a vida futura, tendo também como objectivo evitar este tipo de situações de diminuir os factores de risco, aumentando os de protecção.
Adolescence is a controversial age characterized by the search of identity, in which the role of peer group is extremely important. However, this role of peer group can have a negative influence, helping the young to adopt deviant and delinquent behavior. Juvenile Delinquency is one of the biggest social problems, as it incorporates a variety of behaviors that are influenced by numerous factors, so called risk factors or protection factors. The peer group, drugs consumption, impulsivity and non-structured families are the main factors that lead a young into delinquency, as well as youth gangs.Thus, this work proposes the creation of a prevention plan on scholar level, which should be conducted among flagged students with risky behaviors and deviant peer behaviors, as well as the families of these in order to make young people become aware of the problems and consequences of the entry into a gang has for their future life, and also aiming to avoid such situations to reduce the risk factors, increasing the protective ones.

Dissertação de Mestrado em Psicologia Comunitária apresentada ao ISPA - Instituto Universitário
Este estudo teve como objectivo identificar possíveis factores potenciadores de stress e de suporte social percepcionados por famílias homoparentais que recorreram à adopção individual. Participaram no estudo dois casais, um de homens gays e outro de mulheres lésbicas. Na recolha de dados foi utilizada a entrevista semi-estruturada, tendo emergido da Análise Temática sete grandes temas: Contexto Familiar, Adopção, Amigos, Comunidade Educativa, Meio Profissional, Comunidade Lésbica, Gay, Bissexual e Transgénero (LGBT) e Quadro Legal. Os principais resultados evidenciam que os factores de stress situam-se, fundamentalmente, ao nível do preconceito e discriminação em relação à homossexualidade, em diferentes contextos relacionais (particularmente Familiar e Meio profissional), reflectindo-se na Adopção devido sobretudo quer à internalização do estigma quer às limitações legais.O suporte da Família de origem e Amigos, foi indicado como capaz de colmatar o impacto do preconceito, contudo, estes contextos relacionais também evidenciaram poder constituir uma fonte de stress. O processo de adopção, e experiências adjacentes, foram percepcionados como factores promotores de stress, devido à orientação sexual e internalização do estigma, o que se deve, em grande parte, ao Quadro legal vigente em Portugal, discriminatório na adopção por casais homoparentais. A Comunidade Educativa é considerada um contexto com características de suporte, apesar de ser explicitamente manifesta a incompreensão da variedade familiar. A Comunidade LGBT foi identificada como estrutura de suporte na partilha de experiências, na aquisição de informação sobre a prática parental e na construção de uma identidade. Estas evidências sugerem a importância de compreender melhor e de forma mais aprofundada, as necessidades, a natureza e as causas da percepção do reduzido suporte social e do stress experienciado pelos casais homossexuais adoptantes, no sentido de serem desenvolvidas e implementadas intervenções adequadas e sustentáveis.
ABSTRACT: This study’s aime was to identify possible stress and social support factors, as perceived by same-sex headed families, who resorted to individual adoption. The participants were two same-sex couples, one male and one female. In the data collection, a semi-structured interview was used, which has emerged from the Thematic Analysis six major themes: Family Context, Friends, Educational Community, Professional Environment, Lesbian, Gay, Bisexual and Transgender (LGBT) Community and Legal Framework. The main results show that the stress factors are related essentially to the level of prejudice and discrimination towards homosexuality in different relational contexts (mostly family and professional environment); this is reflected in the adoption mainly due to the internalization of stigma or legal restrictions. The family and friends support was indicated as able to offset the impact of prejudice, however also showed a possible source of stress. The process of adoption and inherent experiences were perceived as promoters of stress due to sexual orientation and stigma internalization, which is largely dued to the current legal framework in Portugal, which adoption by same-sex couples is discriminatory. The educational community is considered a context with supporting features; despite this is explicitly expressed incomprehension of the family diversity. The LGBT community was identified as a support structure in the sharing of experiences, the acquisition of information on parenting and identity construction. These evidences suggest the importance of better and more deeply understanding, the needs, the nature and causes of perception of reduced social support and of stress, experienced by same-sex couples who adopt, so that new and sustainable interventions could be developed and implemented.

Dissertação de Mestrado em Ciências Empresariais – Gestão de Pequenas e Médias Empresas
Os estudos sobre os critérios fundamentais para a escolha de um banco já são alvo de interesse desde os finais dos anos 60, sendo a maioria da literatura relativa ao comportamento de compra bancário nos EUA e Europa. Pretende-se com este trabalho estudar os factores que influenciam a escolha do banco em Portugal, num segmento bastante estratégico e valorizado na banca: os jovens. Na revisão da literatura surgiram os seguintes factores como explicativos da escolha do banco: qualidade no atendimento, reputação / imagem, influência de terceiros, influência não pessoal, conveniência / localização, serviços electrónicos e preço. Todas as variáveis identificadas neste estudo foram interligadas a um Modelo Conceptual de Investigação. A metodologia de investigação contemplou um inquérito por questionário aplicado a 185 jovens estudantes universitários do Instituto Politécnico de Setúbal, nomeadamente na Escola Superior de Ciências Empresariais. Os resultados da análise através de regressão logística apontam para a reputação / imagem do banco e o género como as variáveis explicativas relevantes na escolha de um banco.
Studies about the key criteria factors for choosing a bank are already the interest of the financial / banking sector since the late '60s. Most of its literature relative to the buying behavior was developed in the U.S. and European market. The objective of this work is to study the factors that influence choosing a bank in Portugal, focusing in a strategic and valued segment towards banking sector: the youngsters. In the literature that was studied, regarding bank choosing, the mainly factors emerged were: quality of service, reputation / image, influence of others, non-personal influence, convenience / location, electronic services and price. All variables identified in this study were linked to a Conceptual Model Research of investigation. The research methodology included a survey applied to 185 university students from the Polytechnic Institute of Setúbal, at the School of Business (ESCE). The logistic regression analysis results indicate that bank reputation / image and gender were the most relevant factors regarding bank choosing.

Introducció: Els carcinomes escamosos de cap i coll (CECC) són tumors que es diagnostiquen freqüentment en una fase localment avançada, fet que condiciona un modest pronòstic. Tot i el maneig multidisciplinari, presenten una supervivència global (SG) menor a 40% als 5 anys, deguda a 50-60% de recurrències locals i 20-30% de metàstasi a distància als 2 anys. Per tot això, hi ha una necessitat de detectar biomarcadors que ens ajudin a seleccionar la millor modalitat terapèutica per a cada pacient i a desenvolupar noves estratègies que reverteixin les resistències als tractaments convencionals. Objectius: Amb la hipòtesi que els nivells d'expressió de gens implicats en les vies de reparació de l'ADN i l'activació de la via de l'transductor de senyal i activador de la transcripció 3 (STAT3) poden jugar un paper pronòstic i predictiu de resposta a diferents tractaments de CECC, avaluem la correlació dels primers amb l'eficàcia a l'quimioradioteràpia (QRT) amb platí i de la segona amb la de la combinació de paclitaxel i cetuximab. Material i mètodes: Per avaluar el primer objectiu, vam determinar els nivells d'expressió d'ARNm dels gens BRCA1, RAP80, proteïna 1 de unió a p53 (53BP1), mediador del punt de control de el dany de l'ADN 1 (MDC1) i RNF8, tots ells relacionats amb la reparació de l'ADN, i els correlacionem amb la resposta i la SG en 72 pacients amb CECC localment avançat (CECC-LA) tractats amb carboplatí setmanal AUC 2 i radioteràpia (RT). Per avaluar el segon objectiu, analitzem retrospectivament les mostres tumorals disponibles de 52 pacients d'una sèrie amb CECC recurrent / metastàsic (CECC R / M) tractats amb paclitaxel i cetuximab entre 2008 i 2017, i vam determinar els nivells transcripcionals de STAT3, l'expressió de STAT3 fosforilat (pSTAT3) i la hipermetilació de promotor del gen de la fosfatasa T de proteïna tirosina de tipus receptor (PTPRT). Resultats: A la primera sèrie, la resposta completa (RC) a la QRT va ser significativament superior en els pacients que tenien tumors amb nivells baixos de 53BP1 en comparació amb aquells amb tumors amb nivells elevats, i s'acompanyava d'una tendència a una millor SG. Per a un petit grup de pacients amb tumors amb baixa expressió de 53BP1 i BRCA1 o RAP80 alt, la taxa de RC encara era superior. A la segona sèrie, 58,82% dels tumors van presentar metilació de promotor de PRPRT i aquesta es va associar significativament amb una menor taxa de resposta (TR) a paclitaxel i cetuximab. La sobreexpressió de la proteïna pSTAT3 es va detectar en el 66,67% dels tumors i també es va correlacionar amb resistència a el tractament, encara que no es van obtenir diferències significatives. Conclusions: En el nostre primer treball vam observar que l'eficàcia de la RT en combinació amb carboplatí en el tractament de CECC-LA es correlaciona amb els nivells d'expressió d'ARNm de 53BP1 i que els nivells d'expressió d'ARNm de BRCA1 i RAP80 semblen reforçar el seu valor predictiu . En el nostre segon treball, l'activació de la via STAT3, valorada per la sobreexpressió de pSTAT3 i regulada per la metilació de l'promotor de PTPRT, prediu resistència a paclitaxel i cetuximab en CECC R/M.
Introducción: Los carcinomas escamosos de cabeza y cuello (CECC) son tumores que se diagnostican frecuentemente en una fase localmente avanzada, hecho que condiciona un modesto pronóstico. A pesar del manejo multidisciplinar, presentan una supervivencia global (SG) menor al 40% a los 5 años, debida a un 50-60 % de recurrencias locales y un 20-30% de metástasis a distancia a los 2 años. Por todo esto, existe una necesidad de detectar biomarcadores que nos ayuden a seleccionar la mejor modalidad terapéutica para cada paciente y a desarrollar nuevas estrategias que reviertan las resistencias a los tratamientos convencionales. Objetivos: Con la hipótesis de que los niveles de expresión de genes implicados en las vías de reparación del ADN y la activación de la vía del transductor de señal y activador de la transcripción 3 (STAT3) pueden jugar un papel pronóstico y predictivo de respuesta a diferentes tratamientos del CECC, evaluamos la correlación de los primeros con la eficacia a la quimiorradioterapia (QRT) con platino y de la segunda con la de la combinación de paclitaxel y cetuximab. Material y métodos: Para evaluar el primer objetivo, determinamos los niveles de expresión de ARNm de los genes BRCA1, RAP80, proteína 1 de unión a p53 (53BP1), mediador del punto de control del daño del ADN 1 (MDC1) y RNF8, todos ellos relacionados con la reparación del ADN, y los correlacionamos con la respuesta y la SG en 72 pacientes con CECC localmente avanzado (CECC-LA) tratados con carboplatino semanal AUC 2 y radioterapia (RT). Para evaluar el segundo objetivo, analizamos retrospectivamente las muestras tumorales disponibles de 52 pacientes de una serie con CECC recurrente/metastásico (CECC R/M) tratados con paclitaxel y cetuximab entre 2008 y 2017, y determinamos los niveles transcripcionales de STAT3, la expresión de STAT3 fosforilado (pSTAT3) y la hipermetilación del promotor del gen de la fosfatasa T de proteína tirosina de tipo receptor (PTPRT). Resultados: En la primera serie, la respuesta completa (RC) a la QRT fue significativamente superior en los pacientes que tenían tumores con niveles bajos de 53BP1 en comparación con aquellos con tumores con niveles elevados, y se acompañaba de una tendencia a una mejor SG. Para un pequeño grupo de pacientes con tumores con baja expresión de 53BP1 y BRCA1 o RAP80 alto, la tasa de RC todavía era superior. En la segunda serie, 58,82% de los tumores presentaron metilación del promotor de PRPRT y ésta se asoció significativamente con una menor tasa de respuesta (TR) a paclitaxel y cetuximab. La sobreexpresión de la proteína pSTAT3 se detectó en el 66,67% de los tumores y también se correlacionó con resistencia al tratamiento, aunque no se obtuvieron diferencias significativas. Conclusiones: En nuestro primer trabajo observamos que la eficacia de la RT en combinación con carboplatino en el tratamiento del CECC-LA se correlaciona con los niveles de expresión de ARNm de 53BP1 y que los niveles de expresión de ARNm de BRCA1 y RAP80 parecen reforzar su valor predictivo. En nuestro segundo trabajo, la activación de la vía STAT3, valorada por la sobrexpresión de pSTAT3 y mediada por la metilación del promotor de PTPRT, predice resistencia a paclitaxel y cetuximab en CECC R/M.
Background: Head and neck squamous cell carcinomas (HNSCC) are tumors that are frequently diagnosed in a locally advanced phase, a fact that determines a bad prognosis. Despite multidisciplinary management, they have a 5-year overall survival (OS) of less than 40%, due to 50-60% local recurrences and 20-30% 2-year distant metastases. For this reason, there is a need to detect biomarkers that help us to select the best therapeutic modality for each patient and develop new strategies to reverse resistance to conventional treatments. Objectives: With the hypothesis that the expression levels of genes involved in DNA repair pathways and the activation of the signal transducer and activator of transcription 3 (STAT3) pathway may play a prognostic and predictive role in response to different HNSCC treatments, we evaluated the correlation of the first ones with the efficacy of chemoradiotherapy (CRT) with platinum and of the second ones with that of the combination of paclitaxel and cetuximab. Material and methods: To evaluate the first endpoint, we determined the mRNA expression levels of the genes BRCA1, RAP80, p53-binding protein 1 (53BP1), mediator of DNA damage checkpoint 1 (MDC1) and RNF8, all of them related to DNA repair and correlated them with response and OS in 72 patients with locally advanced HNSCC (LA-HNSCC) treated with weekly AUC 2 carboplatin and radiotherapy (RT). To evaluate the second endpoint, we retrospectively analyzed the available tumor samples from 52 patients from a series with recurrent / metastatic HNSCC (R / M HNSCC) treated with paclitaxel and cetuximab between 2008 and 2017, and we determined the transcriptional levels of STAT3, the expression of phosphorylated STAT3 (pSTAT3), and the hypermethylation of the receptor-type tyrosine-protein phosphatase T (PTPRT) promoter. Results: In the first series, the complete response (CR) to CRT was significantly higher in patients who had tumors with low levels of 53BP1 compared to those with tumors with elevated levels, and a trend towards better OS. For a small group of patients with tumors with low expression of 53BP1 and high BRCA1 or RAP80 expression, the CR rate was still higher. In the second series, 58.82% of the tumors presented PRPRT promoter methylation and it was significantly associated with a lower response rate to paclitaxel and cetuximab. The overexpression of the pSTAT3 protein was detected in 66.67% of the tumors and was also correlated with resistance to treatment, although no significant differences were reached. Conclusions: In our first work we observe that the efficacy of RT in combination with carboplatin in the treatment of LA-HNSCC is correlated with the levels of expression of 53BP1 mRNA, and that the levels of expression of BRCA1 mRNA and RAP80 seem to reinforce its predictive value. In our second work, the activation of the STAT3 pathway measured by the overexpression of pSTAT3 and mediated by the methylation of the PTPRT promoter predicts resistance to paclitaxel and cetuximab in R / M HNSCC.
Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina

Thirty thousand colonies of a bovine liver cDNA library were screened with a mixture of synthetic oligodeoxyribonucleotides coding for bovine factor X. Five positive colonies were identified, and plasmid DNA was isolated. Cleavage with restriction endonucleases showed that these plasmids (designated pBXl-5) contained inserts of 1530 bp, 770 bp, 700 bp, 1100 bp and 930 bp. DNA sequence analysis of the plasmid with the largest insert (pBXl) confirmed that bovine factor X cDNAs had been cloned. The cDNA sequence predicts that factor X is synthesized as a single chain precursor in which the light and heavy chains of plasma factor X are linked by the dipeptide Arg-Arg. The cDNA sequence also predicts that factor X is synthesized with a preproleader peptide. It is proposed that at least five specific proteolytic events occur during the conversion of preprofactor X to plasma factor Xa. A human liver cDNA library was screened by colony hybridization with a bovine factor X cDNA probe. Three of the positive plasmids contained overlapping DNA that coded for most of human factor X mRNA. A second human liver cDNA library was screened by in situ hybridization with 32P-labeled human factor X cDNA clones obtained from the first screen. Several clones were isolated that contained longer inserts. DNA sequence analysis of these clones allowed the prediction of the amino acid sequence of the precursor form of human plasma factor X. From these studies, it is predicted that human factor X is synthesized as a single polypeptide chain precursor in which the light and heavy chains of plasma factor X are linked by the tripeptide Arg-Lys-Arg. The cDNA sequence also predicts that human factor X is synthesized as a preproprotein having an aminoterminal leader peptide of 40 amino acid residues. A comparison of the amino acid sequences of human and bovine factor X shows high sequence identity around the calcium- binding regions and catalytic regions but low sequence identity around the nonfunctional regions. A human genomic phage library was screened with a human factor X cDNA as a hybridization probe. Thirty-two overlapping phage clones were isolated. Characterization of six of these clones indicates that over 32 Kbp of contiguous sequence is represented. DNA sequence and restriction map analysis shows that the factor X gene is comprised of at least 8 exons and 7 introns. No clones representing the 5' untranslated region and the prepeptide of the leader sequence were identified. Two further genomic phage libraries and two libraries specific for the 5' region of the factor X gene were screened, but no 5' end clones were obtained. Restriction enzyme mapping and Southern blot analysis indicate that thus far, the human factor X gene maps to 24 Kbp of the human genome. Comparison of the factor X gene with other vitamin K-dependent blood coagulation factor genes reveals homologous exon organization. Within the blood coagulation serine proteases factor X, factor IX, factor VII, and protein C form a closely related gene family.
Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate

COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
A partir das equações de Williams e Creager foi desenvolvido um método híbrido, que acopla fotoelasticidade a um método numérico-computacional para determinação a dos fatores de intensificação de tensões (FIT) em placas planas sujeitas aos Modos I e II de abertura, com ou sem arredondamento na raiz do entalhe. Às equações propostas acopla-se um polinômio completo que representa uma tensão não-singular (sigma). Assim feito é possível a determinação dos coeficientes KI, KI e termos de sigma. Três programas de computador foram desenvolvidos para as formulações (Williams ou Creager): O primeiro: a partir da configuração das franjas isocromáticas, obtém-se KI e KII e os termos relativos à tensão não singular. O segundo: o desvio relativo a cada ordem de franja é determinado a partir dos termos acima. O terceiro: a partir dos valores determinados regenera-se as franjas isocromáticas para compara-las com as originais. As formulações foram testadas em modelos de barras com trincas e entalhes (com e sem arredondamento na raiz) e seus resultados comparados com dados disponíveis na literatura. Os fatores de influência na determinação de KI e KII, estudados foram: a quantidade de pontos e o ângulo delimitador da região de coleta de dados, bem como a influência dos termos referentes ao campo não singular e alguns aspectos do método numérico implementado. Como aplicação estudou-se o caso do corpo de prova tipo Charpy, onde, a partir das equações de Creager e dos valores de KI e KII assim determinados, pôde-se obter o valor de Kt para uma dada geometria.
A hybrid method coupling photoelasticity to a numerical-computational method which implements the William s (modes I and II) and Creager s (mode I) equations has been developed to determine the mixed-mode stress intensity factors in sharp notches and blunt cracks. The equations take into account the presence or not of a radius in the tip of the notch. To the proposed equations was added a complete polynomial, which represents the non-singular stress field. Three computational programs were developed for both formulations (William s and Creager): one to determine KI, KII and the non-singular terms, the second to evaluate the error between the actual situation and the results obtained and the third to regenerate the isochromatic fringes. The method has been tested in bars with cracks and notches (taking or not into account the existence of the radius at the depth of the notch) and the results were compared to experimental and analytical data found in the literature. Factors which have influence on the determination of KI, KII, were discussed: the number of data points and sector angle where those points are collected as well as the influence of the number of non-singular terms and some aspects of the numeric method. Two applications were studied: Charpy type test specimen under tension and bending and a beam with deep simetrycal grooves. With the values of KI and KII obtained by the Creager s equations one can determine the valeu of sigma x and sigma y in the analyzed situation, as well as the Kt value.