The Amphetamine Years is a history of psychostimulant drugs and their clinical applications in post-World War II American medicine. Comprising such well-known substances as the amphetamines (Benzedrine, Dexedrine), methylphenidate (Ritalin), and phenmetrazine (Preludin), this class of pharmaceuticals has been among the most widely consumed in the past half-century. Their therapeutic uses for a variety of indications such as depression, obesity, and attention-deficit/hyperactivity disorder (ADHD) in children, not to mention their relevance for a number of different medical specialties, reveals that psychostimulants have occupied an important, if underappreciated role in the practice of modern medicine. In this dissertation, I illuminate the various ways in which physicians, particularly psychiatrists, put these drugs to work in clinical practice. In short, I contend that physicians exploited the wide range of physiological and psychological effects of psychostimulants and made a place for them in different therapeutic settings, even ones characterized by competing views and theories about the workings of the human body and mind. My dissertation is distinguished by two prominent themes. First, I emphasize the clinician perspective as a vehicle for understanding the history of the psychostimulants, as well as related developments in psychiatry, pharmacotherapy, and the political economy of drugs, in the second half of the twentieth century. Scholars such Nicolas Rasmussen, David Courtwright, and Ilina Singh have elucidated the history of psychostimulants by emphasizing how pharmaceutical companies positioned their products in the medical marketplace. My dissertation takes a different, yet complimentary approach by studying clinicians, themselves, to further historical comprehension of the place of these pharmaceuticals within postwar medicine, society, and culture. Second, I advance the concept of "therapeutic versatility" to explain their historical trajectories. The complex set of psychological and physical effects these drugs produced made them ideal for a diverse range of therapeutic applications, which explains why they were embraced by many different medical specialties, why they were marketed by manufacturers for a variety of indications, and why they have enjoyed an enduring therapeutic lifespan, in spite of increasing efforts since the mid-1960s to regulate their availability and control their consumption. In addition to these two overarching themes, I advance five specific arguments in my dissertation. First, I contend that pharmaceutical markets were simultaneously created by the drug industry and clinicians. Pharmaceutical firms' efforts to develop markets for their products have been well documented by historians, but in my dissertation, I underscore the role also played by clinicians in discerning drugs' applications. Second, I argue that twentieth-century psychiatry's conception of illness and therapeutics may not be served best by strictly dividing its history along lines of institutional and outpatient treatment. Third, I demonstrate how the use of psychostimulants by analytically oriented psychiatrists during the 1950s complicates historical notions of paradigm shift from a psychodynamic to biological orientation. Psychotherapy and psychopharmacology were not competing paradigms; in practice, doctors often employed both. Fourth, I assert that an appreciation of psychiatrists' empirical and eclectic approaches to the use of drugs is necessary to comprehend the rise of psychiatric pharmacotherapy in the postwar era. Finally, I contend that in order to understand the relationship between medical applications of psychostimulants and their extramedical consumption, it is necessary to conceive of a plurality of distinct "amphetamine cultures," each characterized by a unique set of relationships between physician-prescribers, patient-consumers, pharmaceutical firms, and political authorities.

Dentre os atuais desafios do direito societário brasileiro, a estrutura da propriedade acionária das sociedades por ações de capital aberto e a identificação daqueles que as comandam merecem destaque. O aquecimento das transações realizadas via mercado de capitais e a consolidação dos segmentos especiais de governança corporativa no Brasil resultaram no chamado fenômeno de dispersão acionária, que evidenciou certa ruptura na tradicional estrutura de propriedade acionária exclusivamente concentrada, até então predominante nas companhias brasileiras. Diante desse cenário contrastante, de mudanças no perfil do poder de controle sobre as companhias brasileiras, o presente trabalho apresentará em seu capítulo terceiro, após breve análise das estruturas de capital identificadas em diferentes economias e de retrospectiva sobre a propriedade acionária das companhias brasileiras (a serem apresentadas em seu segundo capítulo), extensa pesquisa empírica realizada com o propósito de identificar a atual estrutura de propriedade acionária predominante entre as companhias brasileiras listadas no segmento especial do Novo Mercado da BMF&BOVESPA (Novo Mercado), e com o objetivo de averiguar a existência do chamado controle societário minoritário entre tais companhias, conforme detalhado nos apêndices desta dissertação. Referida pesquisa empírica representa, ainda, rico processamento da base de dados e informações divulgadas à Comissão de Valores Mobiliários (CVM) pelas companhias listadas no Novo Mercado, e serve de base para a avaliação da necessidade de eventuais mudanças nos conceitos adotados pelo Direito Societário pátrio, tendo em vista entendimento divergente identificado na doutrina e em julgados da CVM no âmbito da possibilidade de existência de um controle societário exercido por acionista ou grupo de acionistas não detentores da maioria do capital social votante, conforme detalhado no quarto capítulo deste estudo. Por fim, serão apresentadas, no quinto e último capítulo, as considerações finais à análise proposta, com destaque para as principais conclusões obtidas na elaboração dos capítulos terceiro e quarto descritos acima, dentre elas a existência do controle societário interno não majoritário (controle minoritário) entre companhias listadas no Novo Mercado, bem como os reflexos dessa constatação no âmbito da prática do Direito Societário. / Among the current challenges of the Brazilian Corporate Law, the structure of the capital ownership of the corporations and the identification of those who exercises control over it remains an important aspect to be taken into consideration when analyzing the main aspects of the Brazilian capital market. The heat up of the transactions carried out through the capital market, and the consolidation of the special corporate governance segments in Brazil resulted in the so called phenomenon of the dispersed ownership, which revealed a rupture from the traditional structure of extremely concentrated ownership, that was prevailing until now among the Brazilian corporations. Given such contrasting scenario of changes in the profile of corporate power over Brazilian corporations, these thesis, after describing, over its first two chapters, the structures of capital ownership existent in different economies and providing a retrospective on the capital ownership of Brazilian corporations, presents, in its third chapter, an extensive empirical research performed with the purposes of identifying the current structure of capital ownership prevailing among the Brazilian companies listed in the Novo Mercado, special segment of the Brazilian Exchange BMF&BOVESPA (the New Market), as well as ascertaining the existence of minority corporate control among such companies, as detailed in the appendixes hereto. The referred empirical research presents, furthermore, detailed data processing in connection with the information disclosed by such companies to the Brazilian Stock Exchange Commission, the Comissão de Valores Mobiliários (CVM), and is also used as basis for reviewing the need of eventual changes in the concepts embodied by the Brazilian Corporate Law, in view of the divergent understanding identified in the Brazilian doctrine and judgments issued by the CVM in connection with the existence of a corporate control exercised by a shareholder or group of shareholders owner of shareholding not representative of the majority of the voting capital stock, as detailed in the fourth chapter of these thesis. Finally, the fifth and last chapter of these study presents the final considerations in connection with the review proposed hereto, highlighting the main conclusions obtained through the elaboration of the third and fourth chapters described above, among them the existence of a not majority internal control (minority control) in companies listed in the New Market, as well as the effects of such conclusion in the light of the practice of corporate law.

Matrizes hidrofílicas de diclofenaco sódico e de cetoprofeno foram preparadas por meio de compressão direta ou granulação úmida seguida de compressão, utilizando-se hipromelose para modular a dissolução do fármaco. Foram também obtidos péletes de liberação prolongada de cetoprofeno, mediante extrusão-esferonização e revestimento, em leito fluidizado, com Kollicoat® EMM 30D. Um planejamento fatorial 22 foi usado para elucidar os efeitos de variáveis de formulação sobre os perfis de liberação do fármaco a partir dos sistemas em estudo, determinados empregando-se os métodos da pá e/ou Bio-Dis. No caso dos comprimidos matriciais, os efeitos do grau de viscosidade e concentração de hipromelose foram investigados. Para os péletes, avaliou-se os efeitos da granulometria e ganho de peso em revestimento. A influência do pH sobre a liberação do fármaco a partir dos sistemas preparados foi também estudada, usando-se meios de dissolução com pH 1,2-7,2. Os métodos ANOVA e teste de Tukey (comparação estatística entre porcentuais de fármaco dissolvido e/ou eficiência de dissolução), f1, f2 e Weibull foram usados para caracterizar e comparar os perfis de dissolução. O grau de viscosidade e concentração de hipromelose influenciaram a liberação de diclofenaco sádico e cetoprofeno a partir das matrizes em estudo, sendo a concentração do polímero o fator principal que governou o processo. A granulação alterou os perfis de dissolução de cetoprofeno em relação às matrizes obtidas por compressão direta, diminuindo a velocidade e modificando o mecanismo de liberação. No caso dos péletes, o ganho de peso em revestimento foi o parâmetro que exerceu maior efeito sobre a liberação do cetoprofeno, enquanto a granulometria apenas influenciou os perfis de dissolução dás formulações com maior ganho de peso em revestimento. A liberação do fármaco a partir dos sistemas em estudo aumentou com a elevação do pH, o que ocorreu devido à solubilidade pH-dependente do cetoprofeno e diclofenaco sódico. / Diclofenac sodium and ketoprofen hydrophilic matrices were prepared by direct compression or wet granulation followed by compression, using hypromellose to modulate the drug dissolution. Sustained release ketoprofen pellets were also obtained by extrusion-spheronization and fluidized bed coating with Kollicoat® EMM 30D. A 22 factorial design has been used to elucidate the effects of formulation variables on the drug release profiles from the systems in study, determined using the paddle method and Bio-Dis. In the case of matrix tablets, the effects of the viscosity grade and concentration of hypromellose were investigated. For the pellets, the effects of granulometry and weight gain were evaluated. The influence of the pH value on the drug release from the prepared systems was also studied, using pH 1,2-7,2 dissolution media. ANOVA and Tukey\'s test (statistical comparison between percentages of drug dissolved and/or dissolution efficiency), f1, f2 and Weibull methods were used to characterize and compare the dissolution profiles. The concentration and viscosity grade of hypromellose influenced the ketoprofen and diclofenac sodium release from the studied matrices, being the polymer concentration the main factor that has governed the process. Granulation has modified the dissolution profiles of ketoprofen in relation to the matrices obtained by direct compression, reducing the rate and modifying the mechanism of drug release. In the pellets case, weight gain was the main factor that has influenced the ketoprofen release, while ganulometry has only influenced the dissolution profiles of the formulation with the highest weight gain. Drug release from the systems under study increased with the increase of the pH value of the medium because of the diclofenac sodium and ketoprofen pH-dependent solubility.

In this essay, the research question: “How can I make teenagers use drugs more responsibly without using a scaremongering approach?” will be explored. The process will include theoretical research on the definition of drugs in relation to a strategy for reducing risks in the lives of adolescents, from a sustainable take. Another question that will be answered is why anti-drug campaigns fail, and my solution to this will be given. The result of this project will be in the form of an interactive online guide for teenagers. The aim of this project will be to provide high school students with a way to find important informa- tion they should know, before trying drugs. The case study is Romania. Here drugs are still a taboo subject and they are not explained nor talked about, in schools or families. Therefore, my guide provides explanations based on several people’s experiences and opinions about the most common drugs here.

Objective: This research aimed at reviewing the information provided by the online drug misuse communities with reference to the available evidence-based literature on the novel psychoactive substances. Methodology: Among hundreds of novel psychoactive substances, four groups (phenethylamines, tryptamines, piperazines and miscellaneous) were selected for the study. Various website drug fora were identified by Google and Yahoo search engines using a set of specific key words. The methods consisted of extracting and analysing qualitative data from the identified website fora. This was also supplemented by critical reviewing the existing evidence-based literature search for each of the selected psychoactive compounds. Results: The combined search results identified 84 unique website fora from which qualitative data were extracted for thirty novel psychoactive substances and organised into technical folders. This data extracted from online communities has thrown some light on factors such as the mode of purchase, subjective experiences, reasons for use, combinations, legislation, mechanisms of action in the CNS, side effects, toxicity and its management. This would enable the clinicians to be obtain full history when assessing and would inform better treatment choices. Conclusions: A range of novel psychoactive substances have been made recently available across the globe. The sale is easily achieved through the Internet. New legislations are made to control some recreational substances whilst newer substances appear. Furthermore, the distributors sell the backlog of products even after controlling of the substance has occured and hence are liable to potentiating criminal investigations. It is here suggested as well that the 'genuinity' of each onlince susbtance is questionable. Evidence-based literature is scant for the vast majority of these substances. Accidental overdoses are common occurences and some of the potential life-threatening clinical situations include sympathomimetic toxidrome and serotonin syndrome. Benzodiazepines appear to help with agitation and neuropsychiatric manifestations. Better levels of international cooperation and rapid share of available information may be needed to tackle the emerging problem of the novel psychoactive substances.

Opérations particulièrement complexes, les offres publiques d'acquisition ne cessent de faire parler d'elles, plus particulièrement lorsqu'elles présentent un caractère hostile pour la société visée. De nombreux efforts législatifs ont été mis en œuvre en vue d'encadrer les OPA et de lutter contre les prises de contrôle rampantes. L'analyse du droit positif permet de mettre en lumière ces différents efforts ainsi que leur mise en œuvre à travers diverses techniques par les sociétés visées. Ces dernières ont par ailleurs développé un certain nombre de mécanismes de défense anti-OPA particulièrement efficaces, mais se révélant le plus souvent insuffisants face à l'ingéniosité dont peut faire preuve l'initiateur. Le droit positif montre ainsi ses limites face à des pratiques qui ne cessent d'évoluer. L'analyse prospective du droit anti-OPA permet d'observer les nouvelles mutations que subit le droit positif au regard des nouveaux enjeux économiques. Elle permet également d'envisager de nouveaux modes d'appréhension des OPA hostiles. Il est ainsi possible d'observer que le gouvernement d'entreprise prend une place considérable dans la vie des sociétés cotées. De même, la montée en puissance de la régulation et l'interventionnisme de l’État sont de plus en plus marqués ; et les salariés s'impliquent de plus en plus dans la gestion de l'entreprise. L'ensemble de ces paramètres marquent un glissement progressif vers une réorganisation du mode de fonctionnement des sociétés, ce qui a amené au développement du soft law, un droit à la frontière du droit positif et des pratiques des sociétés. Le soft law constitue à ce titre une approche inédite des OPA hostiles, dont l'analyse permet de cerner les apports liés à la mutation du droit positif et d'envisager l'émergence de nouveaux moyens de défense. Celui-ci doit toutefois demeurer complémentaire au cadre législatif et réglementaire existant. / No abstract

L'objectif de cette thèse est d'analyser le système juridique français et brésilien concernant les stratégies de défense contre les offres publiques d'acquisition visant à prendre le contrôle des sociétés cotées en bourse. Les offres publiques d'acquisition font l'objet d'un vif débat, plus particulièrement lorsqu'elles présentent un caractère hostile pour la société cible. En France, de nombreux efforts législatifs ont été mis en œuvre en vue d'encadrer les OPA et de lutter contre les prises de contrôle rampantes. L'analyse du droit positif permet de mettre en lumière ces différents efforts ainsi que leur mise en œuvre à travers diverses techniques par les sociétés visées. Grâce à l'analyse juridique des stratégies anti-OPA en France, le système brésilien peut prendre connaissance de cette expérience et trouver la meilleure approche juridique pour les sociétés cotées ayant un capital flottant important. Au Brésil, la récente vague d'IPO a été possible grâce à la réforme dans la bourse BM&FBOVESPA. Dorénavant, la BM&FBOVESPA présente le scénario idéal pour prendre le contrôle des sociétés cotées. Ainsi, l'importance de ce thème est le résultat de la dispersion de l'actionnariat après la première vague d'introduction en bourse dans le marché de capitaux brésilien, et en France, elle se traduit par l'évolution dans environnement légal des défenses anti-OPA face à des pratiques qui ne cessent d'évoluer. / The objective of this thesis is to analyse the French experience and the Brazilian legal environment concerning the defense strategies against hostile corporate takeovers aimed at taking control over public companies. Through the analysis of the French legal system of the anti-takeover strategies, the Brazilian system will be able to acquire this experience and find the best legal approach for Brazilian public companies with dispersed ownership. The importance of this theme is the result of the ownership dispersion following the first IPOs in the current Brazilian securities exchange market, which provides the ideal scenario for taking control of these publicly-traded companies, as well as the changes and the evolution in the French legal environment.