Avaliação da bioequivalência entre duas formulações de Trazodona – comprimidos revestidos de 100 mg

Introdução: A trazodona é um antidepressivo atípico derivado da triazolopiridina, indicado para o tratamento da depressão com ou sem episódios de ansiedade, dor associada à neuropatia diabética e outros tipos de dor crônica. Objetivo: Este estudo teve como objetivo avaliar a bioequivalência entre a formulação teste de Trazodona 100 mg (Sanofi Medley Farmacêutica Ltda) e o produto de referência, Donaren (Apsen Farmacêutica S/A) de acordo com a legislação vigente. Método: Foi realizado um estudo cruzado, aberto, randomizado, de dose única com indivíduos saudáveis ​​de ambos os sexos. A fase clínica foi realizada com 48 indivíduos que receberam os medicamentos em condições de alimentação. A fármaco foi quantificado no plasma por cromatografia líquida acoplada a espectrometria de massas (LC-MS/MS). A avaliação da bioequivalência foi baseada em critérios de aceitação pré-definidos de 80,00 – 125,00% para o intervalo de confiança de 90% para a razão dos produtos teste e referência para os dados log-transformados da área sob a curva (ASC) e da concentração plasmática máxima (Cmax), conforme recomendação da Anvisa. Resultados: As razões geométricas médias (intervalos de confiança de 90%) para Cmax e ASC0-t foram 103,22% (96,13 – 110,84) e 99,06% (94,80 – 103,150), respectivamente. Não houve eventos adversos durante o estudo. Conclusão: As formulações teste e de referência foram consideradas estatisticamente bioequivalentes de acordo com os requisitos regulatórios. A formulação do teste tem sido disponibilizada no mercado local, contribuindo para o acesso da população a medicamentos genéricos de qualidade para o tratamento de transtornos depressivos

Transformational Leadership and Job Satisfaction: Assessing the Influence of Organizational Contextual Factors and Individual Characteristics

Purpose – In this study we investigate the influence of organizational contextual factors and individual characteristics on the relationship between transformational leadership and job satisfaction. Design/methodology/approach – Quantitative research, with data collected through electronic questionnaires, answered by 166 individuals from different types of organizations, areas of professional training, and gender, subsequently applying sequential regression analyses. Findings – The results indicate that the relationship between transformational leadership and job satisfaction is moderated by the followers’ gender, being stronger for female followers. The relationship is not affected by the followers’ area of professional training, nor by type of organization (public/private). The study also evidenced the importance of taking into account individual affective states in studies of work attitudes. Originality/value – The research examines boundary conditions for the effect of transformational leaders in modern organizations, expanding the knowledge on organizational contextual factors that strengthen their influence on employee attitudes, while also controlling for individual differences

Thin and Deep Gaussian Processes

Gaussian processes (GPs) can provide a principled approach to uncertainty quantification with easy-to-interpret kernel hyperparameters, such as the lengthscale, which controls the correlation distance of function values. However, selecting an appropriate kernel can be challenging. Deep GPs avoid manual kernel engineering by successively parameterizing kernels with GP layers, allowing them to learn low-dimensional embeddings of the inputs that explain the output data. Following the architecture of deep neural networks, the most common deep GPs warp the input space layer-by-layer but lose all the interpretability of shallow GPs. An alternative construction is to successively parameterize the lengthscale of a kernel, improving the interpretability but ultimately giving away the notion of learning lower-dimensional embeddings. Unfortunately, both methods are susceptible to particular pathologies which may hinder fitting and limit their interpretability. This work proposes a novel synthesis of both previous approaches: Thin and Deep GP (TDGP). Each TDGP layer defines locally linear transformations of the original input data maintaining the concept of latent embeddings while also retaining the interpretation of lengthscales of a kernel. Moreover, unlike the prior solutions, TDGP induces non-pathological manifolds that admit learning lower-dimensional representations. We show with theoretical and experimental results that i) TDGP is, unlike previous models, tailored to specifically discover lower-dimensional manifolds in the input data, ii) TDGP behaves well when increasing the number of layers, and iii) TDGP performs well in standard benchmark datasets.Comment: Accepted at the Conference on Neural Information Processing Systems (NeurIPS) 202

A new desert-dwelling dinosaur (Theropoda, Noasaurinae) from the Cretaceous of south Brazil

Noasaurines form an enigmatic group of small-bodied predatory theropod dinosaurs known from the Late Cretaceous of Gondwana. They are relatively rare, with notable records in Argentina and Madagascar, and possible remains reported for Brazil, India, and continental Africa. In south-central Brazil, the deposits of the Bauru Basin have yielded a rich tetrapod fauna, which is concentrated in the Bauru Group. The mainly aeolian deposits of the Caiuá Group, on the contrary, bear a scarce fossil record composed only of lizards, turtles, and pterosaurs. Here, we describe the first dinosaur of the Caiuá Group, which also represents the best-preserved theropod of the entire Bauru Basin known to date. The recovered skeletal parts (vertebrae, girdles, limbs, and scarce cranial elements) show that the new taxon was just over 1 m long, with a unique anatomy among theropods. The shafts of its metatarsals II and IV are very lateromedially compressed, as are the blade-like ungual phalanges of the respective digits. This implies that the new taxon could have been functionally monodactyl, with a main central weight-bearing digit, flanked by neighbouring elements positioned very close to digit III or even held free of the ground. Such anatomical adaptation is formerly unrecorded among archosaurs, but has been previously inferred from footprints of the same stratigraphic unit that yielded the new dinosaur. A phylogenetic analysis nests the new taxon within the Noasaurinae clade, which is unresolved because of the multiple alternative positions that Noasaurus leali can acquire in the optimal trees. The exclusion of the latter form results in positioning the new dinosaur as the sister-taxon of the Argentinean Velocisaurus unicus.Fil: Langer, Max Cardoso. Universidade de Sao Paulo; BrasilFil: de Oliveira Martins, Neurides. Museu de Paleontologia de Cruzeiro do Oeste; BrasilFil: Manzig, Paulo César. Museu de Paleontologia de Cruzeiro do Oeste; BrasilFil: de Souza Ferreira, Gabriel. Universidade de Sao Paulo; BrasilFil: de Almeida Marsola, Júlio César. Universidade de Sao Paulo; BrasilFil: Fortes, Edison. UNIVERSIDADE ESTADUAL DE MARINGÁ (UEM);Fil: Lima, Rosana. UNIVERSIDADE ESTADUAL DE MARINGÁ (UEM);Fil: Frediani Sant'ana, Lucas Cesar. UNIVERSIDADE ESTADUAL DE MARINGÁ (UEM);Fil: da Silva Vidal, Luciano. Universidade Federal do Rio de Janeiro; BrasilFil: da Silva Lorençato, Rosangela Honório. Universidade Federal do Rio de Janeiro; BrasilFil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin