Programa de competências parentais para prevenção da negligência

Projecto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em CriminologiaNos dias que decorrem os maus-tratos e a negligência por parte dos progenitores aos menores que se encontram à sua responsabilidade têm vindo a crescer de um modo quase exponencial. Contudo este é um tema que não é atual, uma vez que já nos nossos antepassados existiram registos de situações de maus-tratos com crianças e situações de escravidão. Tal como sabemos os efeitos dos maus-tratos não são apenas evidências físicas, tais como pisaduras, mordeduras… Estes podem ainda ser afetivos, sociais, comportamentais ou até mesmo cognitivos. O que pode levar a um défice no desenvolvimento integral do indivíduo. De um modo geral, com os questionários que foram sendo administrados, com as visitas domiciliárias e com as sessões de formação de competências parentais foi notório que os progenitores conseguem identificar quais os tipos e sinais dos maus-tratos assim como os comportamentos que são reconhecidos como uma forma maltratante. Com a implementação do programa de competências parentais verificaram-se melhorias nos estilos parentais dos progenitores envolvidos assim como no ambiente familiar e na organização da habitação.In days to derive the mistreatment and neglect by parents to children who are the responsibility has been growing almost exponentially. This topic is not current, since they already exist in our records ancestors of situations of abuse with children and situations of slavery. As we know the effects of abuse is not just physical evidence such as bruises, bites ... These can still be affective, social, behavioral, or even cognitive. This can take to a deficit in the development of an individual. In general, with questionnaires being administered, with home visits and training sessions of parenting skills was apparent that parents can identify which types and signs of abuse as well as the behaviors that are identified as such. With the implementation of parenting skills program saw improvements in parenting styles of the parents involved as well as the family atmosphere and organization of housing

A model for the nonlinear, time-dependent and strengthening analysis of shear critical frame concrete structures

Nonlinear fibre beam models, due to its intrinsic simplicity and computational efficiency, are often an adequate alternative to the complex nonlinear plane and solid FE models for the assessment of entire frame structures. Nevertheless, simulations of structural concrete members undergoing relevant shear stresses cannot be performed by these models, as nonlinear shear effects and shear-bending interaction are neglected. In turn, the presence of shear stresses in cracked reinforced concrete (RC) elements leads to a rather complex resistant mechanism which numerical modelling is neither straightforward nor clearly established. Within this problematic, the formulation proposed in this thesis is an upgrade version of an existent flexural fibre beam model for the time-dependent analysis of segmentally constructed RC frames by taking into account the shear effects. The model is devised for the analysis of 2D RC and prestressed frame elements under combined axial, bending and shear forces. Shear-bending interaction is taken into account by means of a hybrid kinematic/force-based sectional approach. The key characteristics of the proposed model are: (i) at the material level RC is simulated through a smeared cracked approach with rotating cracks; (ii) at the fibre level an iterative procedure guarantees equilibrium between concrete and transversal reinforcement, allowing to compute the biaxial stress-strain state of each fibre; (iii) at the section level a uniform shear stress flow is assumed in order to estimate the internal shear stress-strain distribution and (iv) at the element level, the Timoshenko beam theory takes into account the deformation due to shear. As a result, the relevant attributes of the proposed formulation can be resumed as: (i) its capability for considering shear effects in both service and ultimate levels; (ii) the time step-by-step solution procedure enables taking into account the time-dependent response due to creep and shrinkage of concrete, temperature variations and relaxation of prestressing steel considering the multiaxial stress-strain state of the fibres and; (iii) the sequential type of analysis allows capturing the strengthening effects, accounting for the state of the structure prior to the intervention. The model is validated through experimental tests available in the literature, as well as through an experimental campaign carried out by the author. Accordingly, the capacity of the model to efficiently reproduce the behaviour of shear critical beams is demonstrated. The importance of including shear-bending interaction in the numerical analysis is underlined by comparing the results with the ones provided by the pure flexural basis model. The influence of transversal stresses on the time-dependent response of shear and bending dominant beams is also studied with the proposed model. Considering shear effects in modelling the time-dependent response of diagonally cracked RC and prestressed beams is found to be relevant. The proposed model is successfully used to predict the experimental results of a shear damaged and subsequently strengthened RC beam, available in the literature. An alternative strengthening solution for the damaged beam based on post-tensioned stirrups is numerically analysed. This technique showed to be effective to avoid brittle shear failure allowing for the development of all the flexural capacity of the repaired beam. The importance of considering previous damage in the numerical assessment of strengthened RC beams is revealed. Finally, the response of a dismantled prestressed concrete bridge, with deficient shear resistance, submitted to full-scale tests is successfully simulated with the proposed model. In addition, different strengthening proposals based on post-tensioning measures are studied for this bridge. In this manner, the capacity of the model to determine the safety of existent structures and to analyse the performance of strengthening measures is demonstrated.Los modelos de vigas, debido a su simplicidad inherente y eficiencia computacional, pueden ser alternativas adecuadas a complejos modelos de elementos finitos planos y sólidos. Sin embargo, el comportamiento de elementos estructurales de hormigón sometidos a fuertes esfuerzos cortantes, no pueden ser correctamente simulado mediante estos modelos, ya que no consideran los efectos no lineales del cortante y la interacción cortante-flexión. A su vez, la presencia del cortante en el hormigón armado fisurado da lugar a un complejo mecanismo resistente cuya modelización no está aún claramente definida. En esta tesis si propone un modelo de vigas que considera la no linealidad y el comportamiento paso-a-paso en el tiempo de estructuras porticadas de hormigón construidas evolutivamente teniendo en cuenta los efectos del cortante. El modelo se basa en una formulación existente de flexión y está concebido para el análisis de estructuras planas porticadas de hormigón armado (HA) y pretensado sometido a la acción combinada del esfuerzo axil, flexión y cortante. La interacción cortante-flexión si consigue mediante una formulación seccional basada en suposiciones mixtas de cinemática y fuerza. Las características clave del modelo son: (i) a nivel del material el HA se simula mediante una aproximación de fisuración distribuida rotacional; (ii) a nivel de la fibra un procedimiento iterativo garantiza el equilibrio entre el hormigón y la armadura transversal, permitiendo calcular el estado biaxial de tensiones y deformaciones en cada fibra; (iii) a nivel de la sección un patrón de tensiones tangenciales constantes estima la distribución interna de tensiones y deformaciones de cortante y (iv) a nivel del elemento se aplicada la formulación del elemento de viga Timoshenko. De este modo, los aspectos relevantes de la formulación propuesta se resumen en: (i) su capacidad para considerar los efectos del cortante en estados de servicio y últimos; (ii) el procedimiento paso-a-paso en el tiempo permite tener en cuenta la respuesta diferida debido a fluencia y retracción del hormigón, variaciones de temperatura y relajación del pretensado considerando el estado multiaxial de tensiones y deformaciones en las fibras y; (iii) el análisis secuencial permite evaluar los efectos del refuerzo teniendo en cuenta el estado de la estructura antes de la intervención El modelo se valida mediante ensayos experimentales disponibles en la literatura, así como, a través de una campaña experimental realizada por la autora, demostrando su capacidad para reproducir la respuesta de vigas críticas a cortante. La importancia de incluir la interacción cortante-flexión en el análisis numérico es destacada por medio de la comparación de los resultados con los proporcionados por el modelo básico de flexión. Con el modelo propuesto se estudia la influencia del cortante en la respuesta diferida de vigas dominadas por cortante y flexión. La consideración de los efectos del cortante es relevante en la modelación de la respuesta diferida de vigas de HA con fisuras diagonales y en vigas pretensadas. El modelo propuesto se compara con éxito con los resultados experimentales de una viga dañada a cortante y posteriormente reforzada mediante un recrecido de hormigón y armadura transversal. Adicionalmente, se analiza numéricamente otra solución alternativa de refuerzo basada en estribos pretensados. La importancia de considerar el daño previo de la viga reforzada queda demostrada en la evaluación numérica. Finalmente, se simula la respuesta de un puente pretensado desmantelado con deficiente resistencia a cortante y sometido a ensayos de carga a larga-escala. Son también estudiadas diferentes propuestas de refuerzo basadas en soluciones de pos-tensado. De este modo, se demuestra la capacidad del modelo para determinar la seguridad de estructuras existentes y analizar la eficiencia de las medidas de refuerzo

The role of glucagon : GCGR axis in pancreatic neuroendocrine

Abstract Cancer metabolism research has studied the relationship between cellular bioenergetics, biosynthesis, and tumour progression. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This thesis delves into the role of glucagon, a key hormone in systemic metabolism, particularly its influence on pancreatic neuroendocrine tumours (pNETs). Glucagon ability to bind to its natural receptor, GCGR, and its regulator, GLP-1R, introduces intricate dynamics to cancer biology. Our research focused on the role of glucagon in the regulation of cancer cell features and the metabolic remodelling in the presence and absence of glucose. To fulfil the experiments pNETs cell lines (BON-1 and QGP-1) and non-malignant pancreatic α-TC1 cell line were used as models. Results showed pNETs cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNETs cells upregulated GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions. Glucagon activated the MAPK/ERK pathway, especially in pNETs cells without glucose and α-TC1 cells with high glucose. Tests revealed that glucagon enhanced metabolic viability, proliferation, and migration in pNETs cells under glucose deprived conditions and hyperglucagonemia. Meanwhile, in α-TC1 cell line, glucagon modulated these features under high-glucose conditions and physiological glucagon levels. The study also explored the effects of blocking GCGR using an inhibitor, LGD-6972. The results varied across cell lines and glucagon conditions. Metabolic analysis using NMR revealed differences in amino acid levels and metabolic processes based on glucose availability between cell lines. Interestingly, QGP-1 and α-TC1 produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1. Furthermore, gene expression analysis showed that glucose conditions largely influenced gene expression patterns in both pNETs and non-malignant α-cells. The increased levels of alanine, and the ability of QGP-1 and α-TC1 cells to produce glucose together with the upregulation of gluconeogenesis related genes it was clear that the synthesis of glucose is a core pathway in α-TC1 cell biology and QGP-1 cells. Hence gluconeogenesis may be beneficial for some pNETs subsets and its open new perspectives to novel metabolism-based strategies to clinically manage pNETs. Furthermore, the production of glucose by α-cells was not described so far and is a step forward in endocrinology and systemic metabolism. Lastly, the study examined the association between GCGR and disease parameters in pNETs cases. Findings revealed a negative correlation between GCGR expression and tumour grading. Additionally, GLP-1R expression was lower in pNETs than in healthy tissue. This underscores the significant, yet not fully understood, role of glucagon signalling in pNETs progression. The complex relationship between glucose conditions, glucagon signalling, and cellular characteristics warrants further exploration for future therapeutic strategies for pNETs and related diseases.Resumo À medida que a investigação sobre o metabolismo em cancro aprofunda a sua compreensão da relação entre bioenergética e biossíntese celular e progressão tumoral, as influências do metabolismo sistémico e da dieta na evolução tumoral permanecem amplamente inexploradas. Esta tese pretende explorar a relevância do glucagon, uma hormona vital no metabolismo sistémico, investigando o seu papel na biologia do cancro e progressão da doença, especificamente em tumores neuroendócrinos pancreáticos (pNETs). A capacidade do glucagon ligar-se tanto ao seu recetor natural, GCGR, como ao recetor do seu controlador GLP-1 (GLP-1R) introduz dinâmicas complexas no contexto da biologia do cancro. O nosso estudo centrou-se no papel do glucagon na regulação das características das células malignas e na remodelação metabólica na presença e ausência de glucose. Para tal, foram usadas como modelo as linhas celulares de pNETs (BON-1 e QGP-1) e a linha celular pancreática não maligna α-TC1. Identificámos uma resposta adaptativa nas linhas celulares de pNETs sob privação de glucose com o aumento da expressão do GCGR. Em contraste, células α-TC1mostraram um aumento da expressão do GCGR em condições de elevados níveis de glucose. O glucagon ativou a via MAPK/ERK, observado pelo aumento dos níveis de pERK, especialmente nas células celulares de pNETs sob privação de glucose e em células α-TC1 em condições ricas em glucose. Foi realizada uma análise intensiva para compreender os efeitos do glucagon nas características celulares como a viabilidade metabólica, a proliferação e a migração celular. Observou-se que, em condições de privação de glucose e hiperglucagonemia, o glucagon aumentou estas atividades nas linhas BON-1 e QGP-1. Entretanto, na linha celular αTC1, o glucagon teve o mesmo efeito, mas sob condições ricas em glucose e níveis fisiológicos de glucagon. O estudo também explorou os efeitos do bloqueio do GCGR usando um inibidor competitivo, LGD-6972. Os resultados variaram entre linhas celulares e condições de glucagon. Ao aplicar a técnica de espetroscopia de ressonância magnética nuclear (RMN), observamos diferenças nos níveis de aminoácidos e remodelação metabólica com base na disponibilidade de glucose entre as linhas celulares. Curiosamente, as linhas celulares QGP-1 e α-TC1 produziram glucose em condições sem glucose, e o glucagon aumentou a produção de glucose nas α-TC1. Além disso, a análise da expressão genética mostrou que as condições de glucose influenciaram amplamente os padrões de expressão genética em ambas as linhas celulares de pNETs e células α não malignas. A capacidade das células QGP-1 e α-TC1 de produzir glucose, juntamente com regulação positiva de genes relacionados com a gluconeogénese, tornou claro que a síntese de glucose é uma via central na biologia celular α-TC1 e nas células QGP-1. Além disso, a produção de glucose por células α não foi descrita até agora e representa um avanço na endocrinologia e no metabolismo sistémico. Por último, o estudo avaliou a associação entre a expressão de GCGR e parâmetros da doença em casos de pNETs. Os resultados revelaram uma correlação negativa entre a expressão de GCGR o grau da doença. Além disso, a expressão de GLP-1R foi menor nos pNETs do que em tecido saudável. Isto sublinha o papel significativo, mas ainda não totalmente compreendido, da sinalização do glucagon na progressão dos pNETs. A relação complexa entre condições de glucose, sinalização de glucagon e características celulares exige mais investigação para futuras estratégias terapêuticas para pNETs e outras patologias relacionadas

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Influence of time-dependent restrained strains in the shear response of RC frames

The final publication is available at Springer via http://dx.doi.org/10.1617/s11527-016-0875-8Time-dependent strains, when restrained, can lead to important tensile forces and damage, affecting, among other aspects, the shear response and ultimate load carrying capacity of shear-critical RC frames. This paper presents a detailed study of this problematic by means of an extension of a shear-sensitive fibre beam model to time dependent behaviour of concrete. The model is firstly validated with experimental tests on diagonally pre-cracked beams under sustained loads. From these analyses, the contributions of shear distortions and bending curvatures to the total long-term deflection of the beams are discerned. Afterwards, the model is applied to study the influence of restraining strains due to long-term creep and shrinkage in the service and ultimate shear response of frames. In contrast with flexural resistant mechanisms, delayed strains may influence the latter shear resistance of integral structures by reducing the concrete contribution to shear resistance and leading to a sooner activation of the transversal reinforcement. These aspects can be relevant in assessing existing structures and this model, due to its relative simplicity, can be advantageous for practical applications.Peer ReviewedPostprint (author's final draft

from bioprocess development to final formulation

Viral products, including viral vaccines and viral vectors, are important tools for disease prevention and therapy. Viral vaccines, such as attenuated or inactivated rabies virus, influenza virus or hepatitis virus vaccines are powerful tools to limit the number of serious viral infections and pandemics. This type of biopharmaceuticals are used to improve human quality of life with vaccination being the most cost-effective method available for preventing economic losses and increasing the lifespan of both people and livestock. On the other hand, adenoviruses, adeno-associated viruses and retroviruses are among the viral vectors currently being developed for delivering genetic material to the target cell in a growing number of gene therapy clinical applications(...

Analysis of FRP shear strengthening solutions for reinforced concrete beams considering debonding failure

In this paper, a fiber beam model previously developed by the authors for the nonlinear analysis of strengthened elements, including the effects of shear, is used to predict the response of reinforced concrete (RC) beams strengthened in shear with fiber reinforced polymers (FRP) sheets. In the previous version of the model, debonding failure of FRP was not included; hence, its application was limited to the simulation of wrapped configurations. The model is now extended to account for debonding failure in order to allow for its application to beams strengthened with U-shaped and side-bonded configurations. Existing experimental tests on RC beams strengthened in shear by FRP sheets in both wrapped and U-shaped configurations were numerically simulated. The model reproduces, with reasonable accuracy, the experimental failure loads, the load-deflection behavior, and the strains in FRP and stirrups with increasing load. The advantages of this proposal are related with the simplicity and straightforwardness of the beam models to be applied in practical engineering problems.Peer ReviewedPostprint (author's final draft