Objetivos: Descrever o uso e determinar a prevalência de medicamentos potencialmente perigosos e de uso off label e não aprovados em prescrições de unidades de pediatria geral de um hospital universitário no sul do Brasil. Método: Estudo transversal, realizado de novembro de 2007 a janeiro de 2008, envolvendo pacientes até 14 anos de idade, com período de internação superior a 24 horas. Pacientes de unidades de terapia intensiva e oncologia pediátrica foram excluídos. A classificação quanto aos critérios de aprovação da Food and Drug Administration foi realizada pela fonte terciária DrugDex-Micromedex e a classificação dos potencialmente perigosos, pelo Institute for Safe Medication Practices. Resultados e discussão: No período de estudo foram analisadas 342 prescrições de 342 pacientes. O sexo masculino foi o mais freqüente (57%) e mais da metade dos pacientes já apresentavam doenças crônicas à internação. Analgésicos foi a classe terapêutica mais prescrita (26,9%) e entre os off label, os antiespasmódicos (31,5%) foram os mais prevalentes. Das prescrições analisadas, aproximadamente 39% tiveram pelo menos um medicamento de uso off label prescrito, principalmente em relação à indicação terapêutica (38,4%) e à idade (21,9 %), e 11,8% dos pacientes fizeram uso de fármacos não aprovados. Do total de itens (2026), cerca de 6% foram classificados como potencialmente perigosos, destacando-se os analgésicos opióides (35%). Não houve relação de associação entre medicamentos de uso off label e os potencialmente perigosos. Conclusão: As frequências encontradas de medicamentos off label e não aprovados estão de acordo com a literatura e podem ser consideradas elevadas. Os potencialmente perigosos, apesar da baixa prevalência, oferecem risco pelos efeitos prejudiciais que possam vir a causar nos pacientes. Assim, os medicamentos em destaque neste estudo representam uma preocupação constante em hospitais. / Objectives: Describe the use and determine the prevalence of high-alert medications, off label use and unlicensed drugs in prescriptions of general pediatric units of a university hospital in southern Brazil. Method: Cross-sectional study, performed from November 2007 to January 2008, involving patients up to 14 years of age, with admission period over 24 hours. Patients of intensive care and pediatric oncology units were excluded. The classification regarding the Food and Drug Administration approval criteria was performed according to the DrugDex-Micromedex tertiary source and the classification of high-alert medications according to the Institute for Safe Medication Practices. Results e discussion: In the study period, 342 prescriptions were analyzed. Males were more frequent (57%) and over half of the patients already presented chronic diseases for admission. Analgesic drugs were the most frequently prescribed therapeutic class of drugs (26.9%) and among the off-label drugs, antispasmodic drugs (31.5%) were the most prevalent. Around 39% of the analyzed prescriptions had at least one off-label use drug, especially in relation to therapeutic indication (38.4%) and age (21.9%), and 11.8% of the patients received unlicensed drugs. About 6% of the total items (2026) were classified as high-alert medications, such as opioid analgesic drugs (35%). No relation of association was observed between off-label use and high-alert medications. Conclusion: The frequency analyses found of off-label and unlicensed drugs are according to the literature and can be considered as high. The high-alert medications, although of low prevalence, offer risks due to negative effects that can occur in patients. Then, the drugs highlighted in this study constitute a constant concern in hospitals.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / nÃo hà / A Flutamida à um medicamento anti-androgÃnico nÃo esterÃide aprovado para o tratamento do cÃncer de prÃstata. Seu efeito hepatotÃxico foi conhecido desde o inÃcio do perÃodo de comercializaÃÃo, hà mais de 10 anos. Em marÃo e junho de 2002, a Unidade de FarmacovigilÃncia da ANVISA recebeu as primeiras comunicaÃÃes de Ãbitos por hepatite fulminante associados ao uso da substÃncia (medicamento manipulado) em jovens do sexo feminino. A literatura mundial nunca registrara caso semelhante. O objetivo deste trabalho foi revisar e acrescentar informaÃÃes a respeito da seguranÃa da Flutamida quando utilizadas por pacientes do sexo feminino para o tratamento de hirsutismo, acne e alopecia androgenÃtica. Foram realizadas pesquisas para conhecer a indicaÃÃo aprovada em outros paÃses e as notificaÃÃes de reaÃÃes adversas graves em mulheres no banco de dados da OMS. AlÃm disso, por meio de busca ativa, tentou-se identificar outros casos no Brasil; rever as informaÃÃes das bulas de todos os medicamentos comercializados e analisar se as informaÃÃes obrigatÃrias e relevantes para diminuir o risco de reaÃÃes hepÃticas graves estavam presentes. Por fim, foi realizada pesquisa com os prescritores, por meio de questionÃrio eletrÃnico, para conhecer as informaÃÃes de que dispunham sobre a utilizaÃÃo do medicamento em mulheres e comparar estas informaÃÃes com uma revisÃo crÃtica da literatura no que tange à seguranÃa e eficÃcia. Os resultados de todas estas estratÃgias mostraram que a substÃncia tambÃm à utilizada off label em mulheres em outros paÃses, e tambÃm causou reaÃÃes adversas graves, mas nenhum Ãbito no sexo feminino fora relatado. Durante o trabalho, outros casos de Ãbito no Brasil foram identificados. Todas as bulas comercializadas no Brasil mencionavam que a substÃncia nÃo devia ser utilizada por mulheres, assim como mencionavam as reaÃÃes hepÃticas graves. As respostas dos prescritores ao questionÃrio permitem afirmar que a Flutamida se constitui em importante arsenal terapÃutico, e que o risco de seu uso vem sendo subestimado. O trabalho permite concluir que a Flutamida mostra-se eficaz para as condiÃÃes em que vem sendo utilizada em mulheres. Entretanto, os riscos evidenciam uma relaÃÃo benefÃcio/risco inaceitÃvel para as condiÃÃes estÃticas em que vem sendo empregada. / Flutamide is a non steroid anti-androgenic drug used to treat prostate cancer patients. When it became commercialized, more than 10 years ago, the hepatotoxic effect of flutamide was already recognized. In March and July 2002, the first cases of deaths in young females caused by fulminant hepatitis associated to off label use of this substance (magistral drug) was reported to the Pharmacovigilance Office/ANVISA. Up to now, similar cases were not described in the international literature. This work aimed to review and add information about the adequate use of flutamide by female patients to treat hirsutism, acne and androgenetic alopecia. To identify the standard prescriptions and the reported serious reactions in females worldwide, an extensive research through data provided by OMS was conducted. Moreover, using active search we looked for new local cases and review the information from package insert of all commercialized drugs in Brazil to analyze if the required and relevant information warning patients against the serious hepatic risks were provided. Finally, a survey with the prescribers was carried on through the web to identify the available information about the use of this drug in females and to make comparisons with data from the literature about the safety and efficacy of the use of this substance. The results showed that this substance is also used off label by women from other countries, who also presented serious adverse reactions. However, it was not reported any case of female death. Over the study, new cases of obituary occurred in Brazil, despite all analyzed package insert explain that this substance should not be used by females and mention serious hepatic reactions. The answers of the prescribers to the survey indicated that flutamide is an important therapeutic arsenal and that the risk of the use of this substance seem to have been underestimated. We concluded that flutamide is effective for the women treatment which it has been used. However, the threats of this drug point to the unacceptable use of this drug when applied for the esthetic finality.

Submitted by Aline Amarante (1146629@mackenzie.br) on 2018-11-08T21:19:52Z No. of bitstreams: 2 GRACIELA DIAS COELHO JONES.pdf: 1099806 bytes, checksum: 1581ca4d4cf4f822855955bf8ba1b856 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Paola Damato (repositorio@mackenzie.br) on 2018-11-14T13:31:06Z (GMT) No. of bitstreams: 2 GRACIELA DIAS COELHO JONES.pdf: 1099806 bytes, checksum: 1581ca4d4cf4f822855955bf8ba1b856 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-11-14T13:31:06Z (GMT). No. of bitstreams: 2 GRACIELA DIAS COELHO JONES.pdf: 1099806 bytes, checksum: 1581ca4d4cf4f822855955bf8ba1b856 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-05-28 / Universidade Presbiteriana Mackenzie / This paper presents as theme the relation between indebtedness and magnitude, volatility and growth of cash flow throughout time. The objective is to study some approaches on the indebtedness of Brazilian publicly traded companies, analyzing if the magnitude, volatility and the growth of cash flow throughout time have any influence on the indebtedness in Brazil. In addition, a conceptual, theoretical model is presented: the modified Trade-off theory. The Pecking Order theory predicts that there is a negative relation between profitability and indebtedness, and the Trade-off theory predicts that there is a positive relation between profitability and indebtedness. In the modified Trade-off theory discussed herein, the analysis that is being adopted is the relation between indebtedness and cash flow. It is assumed that more profitable companies trend to generate a higher cash amount and this indicates a future cash flow, which as a result increases its indebtedness potential. The dependent variable is the Indebtedness, which adopts the following metrics: Net Debt and Gross Debt, totalizing six tested variables. To measure the cash flow magnitude, the following proxies are used: ROA (Return On Assets), ROIC (Return On Invested Capital) and Market to Book Value, in actual cash values. The cash flow volatility is estimated through the standard deviation of the proxies ROA, ROIC and Market to Book Value. The adopted control variables are the size and tangibility. This paper also tests the interaction between magnitude, volatility and growth of cash flow throughout time. The sample is comprised of the Brazilian publicly traded companies. Data are collected from Economática® and are related to the period from 2008 to 2016, with annual periodicity, of 94 Brazilian publicly traded companies. For data analysis, the Descriptive Statistics, Correlation Analysis and Data Cross Section and Panel are adopted, using the Stata software. The analyses’ results testify the importance of the interaction between growth and magnitude of ROA, ROIC and Market to Book to explain the indebtedness of Brazilian companies as tested in the panels. All of the tested indebtedness types presented herein, except for the net indebtedness, make sense. It was found that the indebtedness of Brazilian companies can be predominantly explained by the magnitude and growth of cash flow rather then volatility. Other important finding is the role of the growth of cash flow as a key determining factor to explain the indebtedness of Brazilian companies. / A presente pesquisa apresenta como tema a relação do endividamento com a magnitude, a volatilidade e o crescimento da geração de caixa ao longo do tempo. O objetivo foi estudar algumas abordagens sobre o endividamento das empresas brasileiras de capital aberto, levantando se a magnitude, a volatilidade e o crescimento da geração do caixa ao longo do tempo influenciam o endividamento no Brasil. Adicionalmente, foi apresentado um modelo teórico conceitual: a teoria do Trade-off modificada. A teoria do Pecking order prevê que existe uma relação negativa entre a rentabilidade e o endividamento, e a teoria do Trade-off prevê que existe uma relação positiva entre a rentabilidade e o endividamento. Na teoria do Trade-off modificada defendida, a análise que está sendo adotada é a relação entre o endividamento e a geração de caixa. Supõe-se que empresas mais rentáveis tendem a gerar um maior montante de caixa, e isso sinaliza uma geração de caixa futura, e consequentemente, aumenta o seu potencial de endividamento. A variável dependente foi o Endividamento que adotou as seguintes métricas: Dívida Líquida e Dívida Bruta. Para mensurar a magnitude da geração de caixa foram usadas as seguintes proxies: ROA (Return on assets), ROIC (Return on invested capital) e Market to Book Value, em valores reais. A volatilidade da geração de caixa foi estimada pelo desvio-padrão das proxies ROA, ROIC e Market to Book Value. As variáveis de controle adotadas foram tamanho e tangibilidade. A pesquisa testou, também a interação entre a magnitude, a volatilidade e o crescimento da geração de caixa ao longo do tempo. A amostra foi composta pelas empresas brasileiras de capital aberto. Os dados foram coletados na Economática® e compreendeu o período de 2008 – 2016, com periodicidade anual, de 94 empresas brasileiras de capital aberto. Para análise dos dados adotou-se Estatística Descritiva, Análise de Correlação, Cros Section e Painel de dados com a utilização do software Stata. Os resultados das análises testificaram a importância da interação entre o crescimento e a magnitude do ROA, do ROIC e do Market to Book Value, para explicar o endividamento das empresas brasileiras, conforme foram testados. Todos os endividamentos testados pela presente pesquisa, com exceção do endividamento líquido, fazeram sentido. Constatou-se que o endividamento das empresas brasileiras pode ser explicado, de forma mais predominante, pela magnitude e pelo crescimento da geração de caixa do que pela volatilidade. Outra importante constatação foi o papel do crescimento da geração de caixa, como um fator-chave determinante para explicar o endividamento das empresas brasileiras.

As decisões relacionadas à configuração da estrutura de capital das empresas impulsionam as pesquisas há mais de cinqüenta anos. Muito embora o assunto seja recorrente e atual no meio acadêmico, ele se mantém bastante controverso. Neste trabalho são exploradas diretamente duas bases teóricas distintas: a Static Trade off Theory (STT), a partir do modelo proposto por Frank e Goyal (2003) e a Pecking Order Theory (POT), a partir do modelo proposto por Shyam-Sunder e Myers (1999). Os resultados destes testes são comparados aos modelos propostos por Qiu e Smith (2007) e Bahng e Jeong (2012) para analisar a estrutura de endividamento das empresas a níveis diferentes de alavancagem. A amostra selecionada consiste de empresas brasileiras de capital aberto, não-financeiras e não-regulamentadas, listadas na Bolsa de Valores Mobiliários de São Paulo (BM&FBovespa) no período entre 2002 e 2011. Utilizou-se como metodologia as técnicas Regressão Múltipla por meio do método dos Mínimos Quadrados Ordinários (MQO) comparativamente à Regressão Quantílica. Como resultados destacou-se uma velocidade de ajuste à estrutura de capital alvo entre 6% e 14% ao ano, nos teste da teoria trade off. Quanto aos testes da teoria pecking order, constatou-se que as empresas brasileiras se orientam conforme esta teoria na tomada de decisão sobre estrutura de capital, financiando-se em grande parte com capital de terceiros. / Decisions related to the configuration of the capital structure of companies drive research for over fifty years. Although it is recurrent and current in academia, it remains quite controversial. This paper explored directly two different theoretical bases: the Static Trade off Theory (STT), from the model proposed by Frank and Goyal (2003) and the Pecking Order Theory (POT), from the model proposed by Shyam-Sunder and Myers (1999). The results of these tests are compared to the models proposed by Qiu and Smith (2007) and Bahng and Jeong (2012) to analyze the debt structure of firms at different levels of leverage. The sample consists of Brazilian companies traded, non-financial and non-regulated, listed on the Securities Exchange of São Paulo (BM & FBovespa) between 2002 and 2011. It was used as a methodology techniques Multiple Regression by the method of Ordinary Least Squares (OLS) compared to Quantile Regression. The results pointed to a speed of adjustment to target capital structure between 6% and 14% per year, the trade off theory test. As for testing the pecking order theory, it was found that Brazilian companies are oriented according to this theory in decision making on capital structure, financing itself largely with debt capital.

Avec la découverte en juillet 2012 par les collaborations CMS et ATLAS d'un nouveau scalaire, aux propriétés similaires à celles d'un boson prédit plus de 50 ans auparavant, la phénoménologie au-delà du modèle standard (SM) a fait un grand pas. En effet, la découverte de cette pièce manquante du puzzle électrofaible a rendu certains modèles impossibles, tout en renforçant la crédibilité du SM. Cependant, on sait que le SM n'est pas le mot de la fin, car certaines de ses prédictions ne s'accordent pas avec les expériences, et ce boson est donc vu comme une porte vers de nouveaux secteurs de la physique. Après une introduction au SM et aux statistiques de la physique des particules, nous présenterons un paramétrage des couplages mesurés au LHC, afin de contraindre, via ces couplages, des modèles de physique au-delà du SM, plus fondamentaux. Ce paramétrage, s'intéressant particulièrement aux couplages à boucles, permettrait de lever une corrélation existant entre les paramètres actuellement utilisés. Nous étudierons ensuite la possibilité d'existence d'un scalaire, plus léger que celui observé, et ayant échappé aux recherches passées, et de sa recherche au LHC à l'aide de ce paramétrage. Nous donnerons des exemples de paramètres faisant apparaître un tel scalaire, dans le 2HDM et le NMSSM. Enfin, nous verrons que le scalaire peut influencer la production d'une paire de bosons de jauge faible, et qu'à l'aide de notre paramétrage, l'analyse de ce processus peut être utilisée de manière cohérente avec les mesures au pic de masse pour contraindre ces couplages. Nous finirons avec quelques limites de cette approche, ainsi que des propositions d'améliorations / With the discovery of a new particle in July 2012 by the CMS and ATLAS experiments, with properties resembling those of a boson predicted about 50 years earlier by theorists, the search for physics outside of the standard model of particle physics (SM) has made a big step. Indeed, the existence of this piece of the electroweak symmetry breaking proved wrong many theories, while giving more credit to the SM. However, because of some observations it fails to match, we know the SM cannot be the final word, and it is hoped that the study of this new particle will be a path to new sectors of physics. After a brief description of the SM and of the statistics of particle physics, we will present a way to parametrise the couplings measured at CERN, in order to constrain, through these couplings, more fundamental models describing physics beyond the standard model. This parametrisation, focusing on loop-induced couplings, would allow to lift a correlation existing between parameters currently used by experimentalists. We will then study the feasibility of a search for another scalar, lighter than the one discovered and which would have escaped previous searches, through the use of the same parametrisation. In two models, the 2HDM and the NSSSM, values of parameters yet unconstrained are shown.Finally, we will see that this scalar can also influence the joint production of two weak gauge bosons. We will show that the analysis of this process can be used in a coherent manner with on-shell Higgs measurements to constrain its couplings through our parametrisation. We will then end with a brief look at some limitation of this approach, before suggesting ways to overcome them

This thesis estimates the treatment effect of inflation targeting adoption on inflation, inflation variability, output, and output variability for 25 explicit inflation targeting countries. I implement the propensity score matching methodology that takes into account the problems of non-experimental nature, such as selection bias or selection on observable, and allows me to effectively mimic properties of randomized experiment and compute unbiased treatment effect estimates. I introduce a variety of propensity score matching methods that were recently developed in the treatment effect literature, including Nearest Neighbor, Radius matching, Kernel matching, and Inverse Probability Weighting. The results indicate that both industrial and developing inflation targeting countries exhibit lower inflation levels and at the same time higher output growth than non-targeting countries. The estimates are however in most cases statistically insignificant. Moreover, it appears that both industrial and developing countries achieve combination of lower inflation variability and output variability compared to non-targeting countries. Nonetheless, majority of the estimates are again statistically insignificant. The results are to a small extent sensitive to the choice of propensity score matching method. Radius matching with tight calipers (r=0.005, r=0.001) tends to provide the most reliable estimates. Balancing properties of the models are reasonable and compared to the previous research the standardised biases are quantitatively better.

Title: Relation between selected off-ice tests and performance in on-ice Illinois Agility test of ice hockey players between 14-17 years old in Czech elite category. Objectives: The main goal of this thesis was to determine whether the somatotype and selected off-ice tests are significant predictors for performance in the on-ice agility test in ice hockey players in the youth elite category. Methods: The research group consisted 28 ice hockey players (8 forwards and 18 defenders) x̅ = 14,88 ± 0,57. Players played highest youth league during the measurement period. The method of Heath and Carter (1990) was used to determine the somatotype. Squat Jump, Countermovement Jump, Free Arm Countermovement Jump, Sit and Reach, pull-ups and off- ice Illinois Agility with a ball were used as off-ice tests. The Aspin-Welch two-samle T-test with Effect size (ES) Hedges' g was used to evaluate the degree of difference in performance between forwards and defenders. Pearson's correlation coefficient with ES coefficient of determination R2 was applied to determine the tightness of relationships between selected variables. Evaluation of the significance of predictors for performance in on- ice agility tests was performed through multiple regression analysis. The significance of the model was assessed according to the...

The diploma thesis deals with force-distance spectroscopy method as a tool for determining pull-off force on graphit/graphene sheets under varied conditions. There is described also a contact angle method which is used to idetify contact angles of water on six investigated samples. Results of both method were discussed with respect to utilization of force-distance spectroscopy in wetting measurements of materials. Finally it was carried out modification of graphen sheet by local anodic oxidation.

The main goal of this diploma thesis is to create a design of an off-road vehicle. The vehicle has become a concept vision of an ecological off-road of the future fueled by hydrogen fuel cells. The secondary goal is: to bring new innovative form elements into conventional design solution of off-road vehicles and to highlight the problem with ecology, environmental protection and limited resources of fossil fuels.

This thesis is oriented to technological and design direction. It is focused on the upgrading of existing machinery from a structural perspective. There is studied the impact of design modifications to the existing production process from a technological point of view. This thesis is specifically concentrated on the technology division of the material, especially on the technology cutting-off in dry condition. There is examined the ability of self-sharpening cutting tools and the quality of the final product under varying input conditions. The job is finished by the carried out techno-economic evaluation, where are compared the costs of the structural adjustments in comparison with mechanical equipment, that could be purchased on the market. The thesis is finished with overall analysis of the optimal efficiency of the production process.