Diante das evidências da existência de um sistema endocanabinóide em humanos, possivelmente disfuncional em transtornos de ansiedade e do crescente interesse terapêutico no uso do canabidiol (CBD), justifica-se um estudo da comparação entre as concentrações plasmáticas do CBD, administrados por via oral na forma de pó e dissolvido em óleo, para que se defina a forma de administração ideal do CBD e sua eficácia terapêutica na dose de 150mg, baseados em estudos cinéticos e dinâmicos (PK/PD). Neste contexto, o estudo investigou 39 voluntários sadios, alocados aleatoriamente em 3 grupos, que receberam 150 mg de CBD, em cápsulas na forma de pó (Grupo 1), dissolvido em óleo de milho (Grupo 2 ) e amido de milho (Grupo placebo). A concentração plasmática do CBD, por cromatografia gasosa acoplada a espectrometria de massas, foi determinada nos tempos: 0, 0,5, 1,0, 1,5, 2,0, 2,5, 3,0, 4,0 h, após a administração do fármaco. Os instrumentos de avaliação de medidas psicológicas foram: escala analógica de humor (VAMS) e a escala de identificação de ansiedade traço estado (IDATE) e nas medidas fisiológicas foram monitoradas a pressão arterial (PA) e a frequência cardíaca (FC). O teste ansiogênico aplicado foi o Teste de Simulação de Falar em Público (TSFP). No reconhecimento de expressões faciais (REF) foi realizada a tarefa Touch, em indicar a emoção apresentada na expressão do indivíduo. Nos resultados das medidas subjetivas (VAMS e IDATE), não se constatou o efeito ansiolítico; houve elevação da PA sistólica e diastólica e da FC; a intensidade da resposta no REF foi de 93% no Grupo 1 (pó) e de 81% no Grupo 2 (óleo). O pico plasmático médio foi de 20,70±1,68 ng/mL em 2,5h (CBD pó) e CBD em óleo de 82,59±9,52 ng/mL em 2h. Desta forma, este estudo PK/PD demonstrou que a forma farmacêutica ideal para a administração do CBD foi a em óleo e no estudo de dose /resposta, 150mg não possui eficácia terapêutico em relação a ansiedade. / In the face of the existence of an endocannabinoid system in humans, possibly dysfunctional in anxiety disorders and the growing interest in the therapeutic use of cannabidiol (CBD), justified a study comparing plasma concentrations of CBD, administered orally in powder form and dissolved in oil, in ordre to define the optimal mode of administration of the CBD and their therapeutic efficacy at a dose of 150mg, based on dynamic and kinetic studies (PK/PD). In this contexto, the study researched 39 healthy volunteers, allocated randomly in 3 groups, receiving 150 mg of CBD, capsules in powder form (Group 1), dissolved in corn oil (Group 2) and corn starch (placebo group). The plasmatic concentration of CBD was determined by gas chromatography coupled to mass spectrometry at the times: 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 h, after administration of the drug. Assessment instruments of psychological measures were: analogical scale mood (VAMS) and scale identification of trait anxiety state (IDATE) and physiological measures were monitored in arterial pressure (PA) and heart rate (HR). The anxiogenic test applied was Simulated Public Speaking (TSFP). In recognition of facial expressions (REF) was performed the task touch, that consists in indicate the emotion shown the facial expression of the individual. The results of subjective measures (VAMS and IDATE) was not found the anxiolytic effect; there was increase of systolic and diastolic pressure and heart frequency; the response intensity in the REF was 93% in group 1 (powder) and 81% in Group 2 (oil). The peak mean plasma was 20.70 ± 1.68 ng / mL (CBD powder) in 2.5 h and 82.59 ± 9.52 ng / mL (CBD in oil) in 2h. Thus, this study PK / PD demonstrated that the ideal pharmaceutical form for administration of the CBD has been in oil and study of dose / response, 150mg has no therapeutic efficacy in relation to anxiety.

Diante das evidências da existência de um sistema endocanabinóide em humanos, possivelmente disfuncional em transtornos de ansiedade e do crescente interesse terapêutico no uso do canabidiol (CBD), justifica-se um estudo da comparação entre as concentrações plasmáticas do CBD, administrados por via oral na forma de pó e dissolvido em óleo, para que se defina a forma de administração ideal do CBD e sua eficácia terapêutica na dose de 150mg, baseados em estudos cinéticos e dinâmicos (PK/PD). Neste contexto, o estudo investigou 39 voluntários sadios, alocados aleatoriamente em 3 grupos, que receberam 150 mg de CBD, em cápsulas na forma de pó (Grupo 1), dissolvido em óleo de milho (Grupo 2 ) e amido de milho (Grupo placebo). A concentração plasmática do CBD, por cromatografia gasosa acoplada a espectrometria de massas, foi determinada nos tempos: 0, 0,5, 1,0, 1,5, 2,0, 2,5, 3,0, 4,0 h, após a administração do fármaco. Os instrumentos de avaliação de medidas psicológicas foram: escala analógica de humor (VAMS) e a escala de identificação de ansiedade traço estado (IDATE) e nas medidas fisiológicas foram monitoradas a pressão arterial (PA) e a frequência cardíaca (FC). O teste ansiogênico aplicado foi o Teste de Simulação de Falar em Público (TSFP). No reconhecimento de expressões faciais (REF) foi realizada a tarefa Touch, em indicar a emoção apresentada na expressão do indivíduo. Nos resultados das medidas subjetivas (VAMS e IDATE), não se constatou o efeito ansiolítico; houve elevação da PA sistólica e diastólica e da FC; a intensidade da resposta no REF foi de 93% no Grupo 1 (pó) e de 81% no Grupo 2 (óleo). O pico plasmático médio foi de 20,70±1,68 ng/mL em 2,5h (CBD pó) e CBD em óleo de 82,59±9,52 ng/mL em 2h. Desta forma, este estudo PK/PD demonstrou que a forma farmacêutica ideal para a administração do CBD foi a em óleo e no estudo de dose /resposta, 150mg não possui eficácia terapêutico em relação a ansiedade. / In the face of the existence of an endocannabinoid system in humans, possibly dysfunctional in anxiety disorders and the growing interest in the therapeutic use of cannabidiol (CBD), justified a study comparing plasma concentrations of CBD, administered orally in powder form and dissolved in oil, in ordre to define the optimal mode of administration of the CBD and their therapeutic efficacy at a dose of 150mg, based on dynamic and kinetic studies (PK/PD). In this contexto, the study researched 39 healthy volunteers, allocated randomly in 3 groups, receiving 150 mg of CBD, capsules in powder form (Group 1), dissolved in corn oil (Group 2) and corn starch (placebo group). The plasmatic concentration of CBD was determined by gas chromatography coupled to mass spectrometry at the times: 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 h, after administration of the drug. Assessment instruments of psychological measures were: analogical scale mood (VAMS) and scale identification of trait anxiety state (IDATE) and physiological measures were monitored in arterial pressure (PA) and heart rate (HR). The anxiogenic test applied was Simulated Public Speaking (TSFP). In recognition of facial expressions (REF) was performed the task touch, that consists in indicate the emotion shown the facial expression of the individual. The results of subjective measures (VAMS and IDATE) was not found the anxiolytic effect; there was increase of systolic and diastolic pressure and heart frequency; the response intensity in the REF was 93% in group 1 (powder) and 81% in Group 2 (oil). The peak mean plasma was 20.70 ± 1.68 ng / mL (CBD powder) in 2.5 h and 82.59 ± 9.52 ng / mL (CBD in oil) in 2h. Thus, this study PK / PD demonstrated that the ideal pharmaceutical form for administration of the CBD has been in oil and study of dose / response, 150mg has no therapeutic efficacy in relation to anxiety.

No description available.

O aumento do consumo e a geração de resíduos e as novas propostas de desenvolvimento de conceitos e práticas de sustentabilidade fizeram com que a sociedade passasse a refletir sobre tais eventos, colocando em discussão o ciclo de vida dos produtos. Neste contexto, o conceito de logística reversa (LR) se desenvolveu, principalmente quanto ao aspecto econômico. Mas, sendo este conceito fundamentado ao da sustentabilidade, torna-se importante acompanhar as práticas, inclusive quanto aos efeitos sociais e ambientais. Atrelado a isso e a dois outros fatores: i) o fato de que alguns trabalhos identificaram que processos de LR nem sempre garantem melhorias econômicas para a empresa, sendo que o efeito econômico estava relacionado aos fatores intrínsecos do processo, e que ii) o Pet é um dos materiais de fácil acesso pela população, ocasionando um grande volume de resíduos de longa decomposição; o objetivo desta pesquisa foi identificar quais decisões sobre os fatores inerentes a um processo produtivo envolvendo LR de Ref Pet são capazes de impactar na sustentabilidade do mesmo. Neste sentido, a proposta volta-se para o desenvolvimento de um modelo que permita analisar os benefícios econômicos, sociais e ambientais, com base em informações do processo, de modo que a empresa possa acompanhar e melhorar o equilíbrio deste tripé em seu processo produtivo, buscando garantir ou identificar necessidades de mudanças para alcançar a sustentabilidade. O desenvolvimento do modelo deu-se por meio da revisão bibliográfica e do estudo exploratório realizado em uma indústria de refrigerantes, permitindo conhecer em detalhes o processo de logística reversa de Ref Pet. Esta etapa foi fundamental para a definição dos inputs, subindicadores e indicadores que formaram os três índices: econômico, social e ambiental. A transformação dos indicadores em índices ocorreu por meio da técnica de análise fatorial, sendo que, depois de finalizado o modelo procedeu-se com análise de sensibilidade, a qual permitiu identificar o fator intrínseco ao processo mais representativo para cada índice. Demonstrou-se que, com este modelo a empresa pode simular cenários de decisão, identificando o impacto que eles trarão para a sustentabilidade do processo produtivo, uma vez que é permitido identificar qual a sensibilidade de cada índice frente aos fatores inerentes ao processo. Assim, a empresa pode tomar decisões visando o equilíbrio econômico, social e ambiental em seu negócio buscando ações para mantê-lo, exercendo papel importante na sociedade. Portanto, o modelo proposto pode auxiliar uma empresa na identificação do impacto de seu processo de logística reversa nos três índices, acompanhando a evolução e tomando medidas para melhorá-los. Ademais, permite analisar a sensibilidade da sustentabilidade do processo quando das variações dos inputs. Finalmente, o estudo traz detalhamentos sobre as especificidades de um processo de logística reversa de Ref PET, capaz de contribuir para a literatura e para os próximos estudos nesta linha. / The increased consumption, and waste generation, and the new proposals of development concepts, and sustainability practices have caused society to reflect about these events, inciting discussions regarding the life cycle of these products. In this context, the reverse logistics concept (RL) was developed referring mainly to the economic aspect. But, considering that the RL concept is based on sustainability, it is important to monitor the practices including those that concern social and environmental effects. Connecting to this and to two other factors: i) the fact that some studies have identified that RL processes does not always guarantee economic improvements for the company, whereas economic effect was related to intrinsic factors in the process, and ii) Pet is easily accessible by the population, resulting in large amounts of long decomposition waste; the objective of this research was to identify which decisions regarding inherent factors in the production process involving RL Returnable PET Bottles can impact sustainability. In this sense, the proposal is aimed to the development of a model to analyze the economic, social and environmental benefits, based on information from the process, so that the company can monitor and improve the balance of this tripod in its production process, seeking to guarantee or identify changing needs to achieve sustainability. The development of the model occurred by means of literature review and exploratory study in a soft drink industry, which allowed knowing in detail the process of Returnable PET Bottles involving RL. This step was fundamental in order to define the inputs, indicators and sub-indicators that formed the three indices: economic, social and environmental. The transformation of the indicators into indices was obtained by applying technique of factor analysis, and, after the finalization of the model, sensitivity analysis was conducted, which allowed identifying the most representative intrinsic factor in the process for each index. Therefore, demonstrating with this model that the company can simulate scenarios for decision, identifying the impact they will bring upon the sustainability of the production process. Since it is possible to identify the sensitivity of each index compared to the inherent factors in the process. Thereby, the company can take decisions seeking economic, social and environmental balance in their business, seeking actions to maintain, performing an important role in society. Thus, the proposed model can assist a company in identifying the impact of their reverse logistics process in the three indices, monitoring the evolution and taking steps to improve them. Furthermore, the model allows analyzing the sensitivity of the sustainability of the process in the case of input variations. Finally, the study brings more details on the specific characteristics of a Reverse Logistics process of Returnable PET Bottles, contributing to the literature and future studies in this research line.

The Self-Regulatory Executive Function (S-REF) model (Wells & Matthew, 2015) states that psychological disorder results from an unhelpful thinking style called the Cognitive Attentional Syndrome (CAS). The CAS incorporates worry/rumination, threat monitoring and unhelpful thought control strategies and is controlled by erroneous metacognitive beliefs. The contribution of the S-REF model to the understating of rumination (paper one) and suicidal ideation (paper two) is evaluated within this thesis. Rumination is one component of the CAS. According to the S-REF model, its execution is guided by metacognitive beliefs. Paper one describes a systematic review and meta-analysis that was undertaken to establish the nature and strength of the relationships between rumination and metacognitive beliefs. Robust relationships, of moderate strength, were observed between rumination and beliefs about its benefits and between rumination and beliefs about its negative consequences. Future research should aim to delineate causality in the observed relationships and consider confounder variables. In paper two it is argued that the S-REF conceptualisation represents a promising new approach to the understanding of suicidal ideation. The importance of considering CAS processes was supported by the study findings. Worry and punishment-related thought control strategies, alongside rumination, predicted suicidal ideation. Distraction, social control and reappraisal strategies negatively predicted suicidal ideation. Some evidence that CAS processes were controlled by erroneous metacognitive beliefs was also obtained. However, this was not conclusive and should be considered again in a larger sample. Paper three describes the development of papers one and two in more detail, highlighting and justifying the important decisions made. Further reflections on methodology are also provided to demonstrate the learning achieved.

Notch signaling is important for development in Caenorhabditis elegans and the REF-1 family pro-teins, a set of the bHLH transcription factors, are the first targets of Notch signaling. Little is known about the molecular mechanisms employed by the REF-1 family to regulate development. In this project, I iden-tified novel targets of three REF-1 family proteins, HLH-25/HLH-28/HLH-29, and determined which target genes are activated and which are repressed by the REF-1 proteins. These targets were identified by gene expression microarray and were functionally categorized by Gene Oncology analysis. A systems biology approach was performed to identify networks associated with those targets. In addition to the mo-lecular genetics studies, I identified and better characterized the range of phenotypes induced by muta-tions in ref-1 family genes.

Th.--Sci. math.--Paris 6, 1978.

O aumento do consumo e a geração de resíduos e as novas propostas de desenvolvimento de conceitos e práticas de sustentabilidade fizeram com que a sociedade passasse a refletir sobre tais eventos, colocando em discussão o ciclo de vida dos produtos. Neste contexto, o conceito de logística reversa (LR) se desenvolveu, principalmente quanto ao aspecto econômico. Mas, sendo este conceito fundamentado ao da sustentabilidade, torna-se importante acompanhar as práticas, inclusive quanto aos efeitos sociais e ambientais. Atrelado a isso e a dois outros fatores: i) o fato de que alguns trabalhos identificaram que processos de LR nem sempre garantem melhorias econômicas para a empresa, sendo que o efeito econômico estava relacionado aos fatores intrínsecos do processo, e que ii) o Pet é um dos materiais de fácil acesso pela população, ocasionando um grande volume de resíduos de longa decomposição; o objetivo desta pesquisa foi identificar quais decisões sobre os fatores inerentes a um processo produtivo envolvendo LR de Ref Pet são capazes de impactar na sustentabilidade do mesmo. Neste sentido, a proposta volta-se para o desenvolvimento de um modelo que permita analisar os benefícios econômicos, sociais e ambientais, com base em informações do processo, de modo que a empresa possa acompanhar e melhorar o equilíbrio deste tripé em seu processo produtivo, buscando garantir ou identificar necessidades de mudanças para alcançar a sustentabilidade. O desenvolvimento do modelo deu-se por meio da revisão bibliográfica e do estudo exploratório realizado em uma indústria de refrigerantes, permitindo conhecer em detalhes o processo de logística reversa de Ref Pet. Esta etapa foi fundamental para a definição dos inputs, subindicadores e indicadores que formaram os três índices: econômico, social e ambiental. A transformação dos indicadores em índices ocorreu por meio da técnica de análise fatorial, sendo que, depois de finalizado o modelo procedeu-se com análise de sensibilidade, a qual permitiu identificar o fator intrínseco ao processo mais representativo para cada índice. Demonstrou-se que, com este modelo a empresa pode simular cenários de decisão, identificando o impacto que eles trarão para a sustentabilidade do processo produtivo, uma vez que é permitido identificar qual a sensibilidade de cada índice frente aos fatores inerentes ao processo. Assim, a empresa pode tomar decisões visando o equilíbrio econômico, social e ambiental em seu negócio buscando ações para mantê-lo, exercendo papel importante na sociedade. Portanto, o modelo proposto pode auxiliar uma empresa na identificação do impacto de seu processo de logística reversa nos três índices, acompanhando a evolução e tomando medidas para melhorá-los. Ademais, permite analisar a sensibilidade da sustentabilidade do processo quando das variações dos inputs. Finalmente, o estudo traz detalhamentos sobre as especificidades de um processo de logística reversa de Ref PET, capaz de contribuir para a literatura e para os próximos estudos nesta linha. / The increased consumption, and waste generation, and the new proposals of development concepts, and sustainability practices have caused society to reflect about these events, inciting discussions regarding the life cycle of these products. In this context, the reverse logistics concept (RL) was developed referring mainly to the economic aspect. But, considering that the RL concept is based on sustainability, it is important to monitor the practices including those that concern social and environmental effects. Connecting to this and to two other factors: i) the fact that some studies have identified that RL processes does not always guarantee economic improvements for the company, whereas economic effect was related to intrinsic factors in the process, and ii) Pet is easily accessible by the population, resulting in large amounts of long decomposition waste; the objective of this research was to identify which decisions regarding inherent factors in the production process involving RL Returnable PET Bottles can impact sustainability. In this sense, the proposal is aimed to the development of a model to analyze the economic, social and environmental benefits, based on information from the process, so that the company can monitor and improve the balance of this tripod in its production process, seeking to guarantee or identify changing needs to achieve sustainability. The development of the model occurred by means of literature review and exploratory study in a soft drink industry, which allowed knowing in detail the process of Returnable PET Bottles involving RL. This step was fundamental in order to define the inputs, indicators and sub-indicators that formed the three indices: economic, social and environmental. The transformation of the indicators into indices was obtained by applying technique of factor analysis, and, after the finalization of the model, sensitivity analysis was conducted, which allowed identifying the most representative intrinsic factor in the process for each index. Therefore, demonstrating with this model that the company can simulate scenarios for decision, identifying the impact they will bring upon the sustainability of the production process. Since it is possible to identify the sensitivity of each index compared to the inherent factors in the process. Thereby, the company can take decisions seeking economic, social and environmental balance in their business, seeking actions to maintain, performing an important role in society. Thus, the proposed model can assist a company in identifying the impact of their reverse logistics process in the three indices, monitoring the evolution and taking steps to improve them. Furthermore, the model allows analyzing the sensitivity of the sustainability of the process in the case of input variations. Finally, the study brings more details on the specific characteristics of a Reverse Logistics process of Returnable PET Bottles, contributing to the literature and future studies in this research line.

This PhD investigated the theoretical and clinical applications of a meta-cognitive model of psychological disorders in social anxiety. The main objective was to identify potential associations between meta-cognitive knowledge (i.e. meta-cognitive beliefs) and social anxiety. These associations could be direct or indirect via information-processing mechanisms, such as anticipatory processing (AP), focus of attention, and post-mortem processing (PM). The current thesis reports six studies (N = 686).Study 1 explored cross-sectionally the potential contribution of meta-cognitive beliefs about general worry to social anxiety. The results showed that positive and uncontrollability beliefs along with AP were individual positive predictors of social anxiety. Furthermore, these beliefs had an indirect effect on social anxiety through anticipatory processing and the post-mortem. These results prompted further exploration of the nature of meta-cognitive beliefs in social anxiety. Study 2 employed semi-structured interviews to elicit meta-cognitive beliefs that could be specific to social anxiety. High and low socially anxious individuals reported beliefs about anticipatory processing, focusing on an observer perspective (OP) self-image, and the post-mortem. The high socially anxious group reported greater engagement in both AP and focusing on the OP, and spending greater time trying to control AP, OP, and the post-mortem. Moreover, the two groups differed in beliefs about these mechanisms, in coping strategies, and in stop signals. The beliefs elicited informed two new questionnaires that were investigated in Study 3. Each questionnaire revealed three subscales of positive and negative beliefs about AP and about the OP self-image, respectively. The subscales showed good reliability and stability. In addition, the new beliefs revealed further associations with social anxiety. Study 4 investigated whether meta-cognitive beliefs could affect attentional bias in social anxiety. High and low socially anxious individuals completed a dot-probe task with emotional, social and physical words matched with neutral words. The results indicated a potential moderation effect of social anxiety and positive meta-cognitive beliefs on attentional bias. Moreover, meta-cognitive beliefs predicted attentional bias in both social anxiety groups. The above results implicated meta-cognitive beliefs in the maintenance of social anxiety. Study 5 explored whether these beliefs could affect state anxiety in high socially anxious individuals that engaged in either AP or a distraction task prior to giving a speech. The results replicated previous findings that AP was associated with more anxiety compared with distraction. Additionally, uncontrollability beliefs were associated with increased state anxiety before the speech, while positive beliefs interfered with distraction and were associated with the maintenance of anxiety after the speech was over. Finally, Study 6 explored whether a meta-cognitive intervention could be effective in the treatment of social anxiety. In a cross-over design, high socially anxious individuals practiced detached mindfulness and thought challenging prior to giving a speech. The results showed that detached mindfulness was associated with greater reductions in negative beliefs, worry, and the OP. In conclusion, the results of a series of studies support the application of the meta-cognitive model to social anxiety.

No / We present an explicit polynomial solution method for surface generation. In this case the surface in question is characterized by some boundary configuration whereby the resulting surface conforms to a fourth order linear elliptic Partial Differential Equation, the Euler–Lagrange equation of a quadratic functional defined by a norm. In particular, the paper deals with surfaces generated as explicit Bézier polynomial solutions for the chosen Partial Differential Equation. To present the explicit solution methodologies adopted here we divide the Partial Differential Equations into two groups namely the orthogonal and the non-orthogonal cases. In order to demonstrate our methodology we discuss a series of examples which utilize the explicit solutions to generate smooth surfaces that interpolate a given boundary configuration. We compare the speed of our explicit solution scheme with the solution arising from directly solving the associated linear system.