A utilização de substâncias estimulantes tipo-anfetamínicos (ATS) por motoristas com objetivo de aumentar o tempo de vigília é um conhecido problema nacional com consequências sociais e legais. A dietilpropiona (DIE) e o femproporex (FEN) figuram entre os estimulantes do sistema nervoso central (SNC) mais utilizados por condutores no trânsito brasileiro. O metilfenidato (MPH) é um fármaco que apresenta propriedades similares à cocaína e à anfetamina (AMP). Sua utilização como droga de rua e recreacional tem aumentado nos últimos anos e seu uso tem ganhado espaço com a restrição da comercialização de DIE e FEN pela Agência Nacional de Vigilância Sanitária (ANVISA) em 2011. O estudo do trânsito implica necessariamente o conhecimento do perfil dos condutores e da prevalência do uso de substâncias. Para a monitorização do consumo de substâncias no trânsito, é necessário o emprego de métodos analíticos validados para as matrizes biológicas de interesse. Sabe-se ainda que muitos condutores compram medicamentos ATS ilegalmente, em postos de combustível e pela internet. Conhecer o perfil químico e detectar falsificações desses medicamentos é parte essencial no desenvolvimento e aplicação de políticas públicas preventivas do uso de substâncias no trânsito. Objetivos: avaliar dados do trânsito da região sul do Brasil, enfatizando o uso de substâncias, a idade e o sexo dos envolvidos em acidentes; desenvolver e validar métodos cromatográficos acoplados a detector de massas para quantificação simultânea de FEN, DIE e MPH em fluido oral e em plasma; avaliar o perfil de falsificações de medicamentos a base de ATS. Resultados: os dados de acidentes de trânsito com vítimas fatais no Estado de Santa Catarina no período de junho de 2008 a novembro de 2010, revelaram que 11,9 % dos casos apresentaram resultados toxicológicos positivos, sendo canabinóides (42 %) e cocaína (29,4 %) as substâncias mais prevalentes, seguidas de antidepressivos (10,3 %), anfetamínicos (9,5 %), benzodiazepínicos (7,1 %) e barbitúricos (1,6 %). A maioria das vítimas (44 %) era jovem – entre 16 e 30 anos – e do sexo masculino. O desenvolvimento e validação de método de extração e quantificação simultânea de AMP, FEN e DIE em plasma utilizando a técnica de imersão direta em micro-extração em fase sólida (SPME-DI) seguida de análise por cromatografia gasosa acoplada a espectrômetro de massas (GC-MS) compreendeu etapas de desproteinização da matriz e derivatização dos ATS. O método foi linear de 5,0 a 100 ng/ml. Os limites de detecção foram 1,0; 1,5; 2,0 ng/ml para AMP, DIE e FEN respectivamente. A exatidão variou de 85,58 a 108,33 % e a precisão, calculada pelo desvio padrão relativo, não excedeu 15 %. A recuperação esteve entre 46,35 – 84,46 %. Também foi desenvolvida e validada metodologia para análise simultânea de FEN, DIE e MPH em fluido oral por cromatografia líquida acoplada a detector de massas em tandem (LC-MS/MS). As curvas de calibração utilizando o padrão interno propranolol apresentaram linearidade entre 2,5 e 90 ng/ml. O limite inferior de quantificação e o limite de detecção foram de 2,5 ng/ml e 0,5 ng/ml respectivamente, para todos os ATS. Precisão e exatidão intra e inter-dias mantiveram-se dentro dos limites preconizados pelas guias regulatórias. Não foram observados efeito de matriz nem carry-over. Por fim, foram desenvolvidos e aplicados métodos para a análise de apreensões de ATS os quais revelaram a existência de ativo farmacêutico diverso (sibutramina) daquele especificado no rótulo do medicamento (FEN), em concentrações que variaram de 1/3 até 2 vezes a dose diária preconizada. Pela análise estatística dos espectros de infravermelho foi possível diferenciar amostras autênticas e amostras falsas e ainda agrupar falsificações com perfis semelhantes. Conclusões: os objetivos de estudo propostos nesta tese foram satisfatoriamente cumpridos e os resultados alcançados estão dispostos na forma de cinco artigos. Estes manuscritos contemplam temas relacionados ao uso de substâncias no trânsito, ao desenvolvimento e validação de metodologias analíticas e à análise de falsificações de medicamentos a base de ATS, demonstrando assim, a amplitude e multidisciplinariedade envolvidas no estudo dos compostos anfetamínicos. / The use of amphetamine-type stimulants compounds (ATS) for drivers aiming to stay awake is a known national problem, with social and legal implications. Diethylpropion (DIE) and fenproporex (FEN) are among the central nervous system stimulant most used by drivers in Brazil. Methylphenidate (MPH) is a drug that has properties similar to cocaine and amphetamine (AMP). Its use as a recreational and street drug has increased in recent years and its use has achieved space by the restriction of the marketing of DIE and FEN by the National Agency for Sanitary Surveillance (ANVISA) in 2011. The traffic analysis necessarily implies knowledge of the profile of drivers and the prevalence of substance use. To monitor the consumption of substances in transit, validated analytical methods in different biological matrices should be employed and toxicological data interpreted according pharmacokinetics of each substance. It is also known that many motorists buy ATS illegally in gas stations and the Internet. Knowing the chemical profile and detect forgeries of these medications is an essential part in the development and implementation of public policies to prevent the use of ATS in traffic. Objectives: to evaluate the traffic data from southern Brazil, emphasizing the use of substances, age and sex of those involved in traffic accidents; develop and validate chromatographic methods coupled to mass spectrometry for quantification of FEN, DIE and MPH in oral fluid and in plasma; evaluate the profile of counterfeit medications based on ATS. Results: data analysis of traffic accidents with fatalities from June 2008 to November 2010 in the State of Santa Catarina revealed that 11.9 % of cases had positive toxicology results. Cannabinoids (42 %) and cocaine (29.4 %) had the highest prevalence, followed by antidepressants (10.3 %), amphetamines (9.5 %), benzodiazepines (7.1 %) and barbiturates (1.6 %). Most victims (44 %) were aged between 16 and 30 years old and male. A validated method for the simultaneous analysis of AMP, DIE and FEN in plasma samples employing direct immersion-solid phase microextraction (DI-SPME) followed by gas chromatographic/mass spectrometric analyses (GC-MS) was developed. Deproteinization and derivatization of ATS were employed. The method was linear from 5.0 ngml-1 at 100 ngml-1. The detection limits were 1.0, 1.5, 2.0 ngml-1 for AMP, DIE and FEN respectively. The accuracy ranged from 85.58 to 108.33 % and precision, calculated by the relative standard deviation did not exceed 15 %. The recovery was between 46.35 to 84.46 %. Also was developed and validated a new method for simultaneous determination of FEN, DIE and MPH in oral fluid by liquidchromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS). The calibration curves, using an internal standard, demonstrated good linearity throughout the concentration range from 2.5–90 ngml-1 in oral fluid. The lower limit of quantification and the limit of detection were 2.5 and 1.0 ngml-1 respectively for all ATS. Intra- and inter-assay precision and accuracy values were within regulatory limits. Matrix effect and carry-over were not detected. Finally, methods have been developed and applied to analysis of seizures of ATS and the results showed the existence of active pharmaceutical (sibutramine) other than that specified on the label of the drug (FEN). The concentrations founded ranging from 1/3 to 2 times the recommended daily dose. Through the statistical analysis of the infrared spectra was possible to distinguish between authentic samples and counterfeit samples and also cluster the counterfeit ATS by their similar profiles. Conclusions: the proposed objectives of this thesis were satisfactorily completed and the results are arranged in the form of five manuscripts. These articles address issues related to substance use in traffic, development and validation of analytical methodologies and analysis of counterfeit medications based on ATS, highlighting the extent and multidisciplinary in the study of amphetamine compounds.

Suite aux fouilles du second atelier monétaire royal de La Rochelle (17), une grande quantité de matériel a pu être mis au jour. Cette découverte est exceptionnelle par deux aspects puisqu’il s’agit à ce jour de l’unique atelier officiel fouillé en France et que les structures et objets découverts permettent en une première lecture, d’ébaucher une chaîne de production de la monnaie. Ce matériel précurseur complété de céramiques provenant de l’atelier médiéval de Montreuil-Bonnin (86) constitue la base de cette étude archéométrique inédite des techniques monétaires officielles. Cette recherche, par définition multidisciplinaire, s’appuie sur la caractérisation physico-chimique de corpus archéologiques mais également sur une étude des sources historiques : traités monétaires, procès-verbaux, comptes d’atelier... Enfin, les reconstitutions paléométallurgiques participent pour une part importante aux discussions engagées. Elles renseignent sur la complexité des opérations tout en produisant des analogues librement étudiables, comparés aux échantillons anciens. La compilation de toutes les données collectées permet non seulement de proposer une description des techniques du monnayage au marteau telles qu’elles étaient mises en oeuvre dans les fabriques monétaires jusqu’au milieu du XVIIe siècle et de révéler les matières premières utilisées mais également de comprendre le fondement des opérations pratiquées. En tant que fabrication monétaire particulière, les techniques propres au faux-monnayage ont parallèlement été considérées par le biais de l’étude de deux exemples localisés au début de la Période Moderne dans le département de l’Aude (11). En suivant la même démarche expérimentale, il a été possible de mettre en évidence les particularismes de ces activités et de révéler plusieurs analogies avec les techniques officielles. / In the Nineties excavations made in La Rochelle (France) have produced objects of archaeometallurgical evidence with regards to the second royal mint. For the time being, this workshop is still the only one that has been discovered in France. Moreover, the observations of the artefacts seem to allow the reading of the whole money making process. These archaeological samples, complemented with ceramics from the medieval mint of Montreuil-Bonnin (France), have been studied by an archaeometric approach to propose an original research on the official French hammer striking process. This multidisciplinary study is based on the analysis of historical samples but also on a bibliographic compilation: monetary treaties, official reports, mint accounts… The experimental work takes an important part in the study too. Providing more than experimental samples easily studied and compared with the archaeological ones, this pragmatic method allows to point out the complexity of a technique. Finally, the gathering of all data defines the raw materials and the processes used in the French hammer coining until the mid XVIIth century, but also their respective purposes. As a particular coinage, counterfeiting has also been studied through two post-medieval examples that took place in Southern France caves. The experimental study reveals the originalities of these illegal activities besides some links with the official processes.

The developed research sought to achieve an interdisciplinary approach to counterfeiting of the Brazilian Real ballots, identifying its possible innovations and socio-economic impacts, aiming in their considerations propose possible solutions to minimize the possible losses arising from the issue to the Company. The method was characterized by case study applied to Real ballots of the Brazilian currency, using bibliographic and documentary resources complemented by field studies through an interdisciplinary approach involving disciplines such as history, law, economics and Technological Innovation. For elements of history, there was a brief overview of the emergence of money in Brazil and the various denominations modified until the appearance of the second family of the real, still pointing the first counterfeit registration in Brazil, as the law of the aspects was mainly aimed the elements that make up the legal framework protecting the rights related to intellectual property. With regard to the economy was still drawn a macroeconomic analysis of counterfeit depending on income and the number of inhabitants. In aspects of technological innovation were accounted for the various innovations occurring in the manufacture of Real ballots since its existence to the present day. The results showed by basic principles of Applied Statistics that 100 people at least 4 possibly handled a false ballot and to minimize the increasing falsification of ballots, one should invest in technological safety innovations and conscious orientation to society. / A pesquisa desenvolvida buscou realizar uma abordagem interdisciplinar da contrafação das cédulas do Real Brasileiro, identificando suas possíveis inovações e impactos sócio-econômicos, objetivando em suas considerações propor possíveis soluções que minimizem as possíveis perdas ocasionadas pela temática à Sociedade. O método caracterizou-se por Estudo de Caso aplicado às cédulas do Real da moeda brasileira, utilizando-se de recursos bibliográfico-documental complementado por estudo de campo por meio de uma abordagem interdisciplinar envolvendo disciplinas como História, Direito, Economia e Inovação Tecnológica. Para elementos da História, fez-se um breve apanhado do surgimento do dinheiro no Brasil e as diversas denominações modificadas até o surgimento da segunda família do Real, apontando ainda o primeiro registro de contrafação do Brasil; quanto aos aspectos do Direito foram apontados principalmente os elementos que compõem o arcabouço legal que protegem os direitos relacionados à propriedade intelectual. Tratando-se da Economia foi traçado uma análise macroeconômica da contrafação em função da renda e o contingente populacional. Nos aspectos da inovação tecnológica foram contabilizadas as diversas inovações ocorridas no fabrico das cédulas do Real desde sua existência aos dias atuais. Os resultados apontaram, com base nos princípios básicos da Estatística Aplicada, que a cada 100 pessoas, pelo menos 4 possivelmente manusearam uma cédula falsa e que para minimizar o aumento crescente da falsificação de cédulas, deve-se investir em inovações tecnológicas de segurança e orientação consciente para a sociedade.

A utilização de substâncias estimulantes tipo-anfetamínicos (ATS) por motoristas com objetivo de aumentar o tempo de vigília é um conhecido problema nacional com consequências sociais e legais. A dietilpropiona (DIE) e o femproporex (FEN) figuram entre os estimulantes do sistema nervoso central (SNC) mais utilizados por condutores no trânsito brasileiro. O metilfenidato (MPH) é um fármaco que apresenta propriedades similares à cocaína e à anfetamina (AMP). Sua utilização como droga de rua e recreacional tem aumentado nos últimos anos e seu uso tem ganhado espaço com a restrição da comercialização de DIE e FEN pela Agência Nacional de Vigilância Sanitária (ANVISA) em 2011. O estudo do trânsito implica necessariamente o conhecimento do perfil dos condutores e da prevalência do uso de substâncias. Para a monitorização do consumo de substâncias no trânsito, é necessário o emprego de métodos analíticos validados para as matrizes biológicas de interesse. Sabe-se ainda que muitos condutores compram medicamentos ATS ilegalmente, em postos de combustível e pela internet. Conhecer o perfil químico e detectar falsificações desses medicamentos é parte essencial no desenvolvimento e aplicação de políticas públicas preventivas do uso de substâncias no trânsito. Objetivos: avaliar dados do trânsito da região sul do Brasil, enfatizando o uso de substâncias, a idade e o sexo dos envolvidos em acidentes; desenvolver e validar métodos cromatográficos acoplados a detector de massas para quantificação simultânea de FEN, DIE e MPH em fluido oral e em plasma; avaliar o perfil de falsificações de medicamentos a base de ATS. Resultados: os dados de acidentes de trânsito com vítimas fatais no Estado de Santa Catarina no período de junho de 2008 a novembro de 2010, revelaram que 11,9 % dos casos apresentaram resultados toxicológicos positivos, sendo canabinóides (42 %) e cocaína (29,4 %) as substâncias mais prevalentes, seguidas de antidepressivos (10,3 %), anfetamínicos (9,5 %), benzodiazepínicos (7,1 %) e barbitúricos (1,6 %). A maioria das vítimas (44 %) era jovem – entre 16 e 30 anos – e do sexo masculino. O desenvolvimento e validação de método de extração e quantificação simultânea de AMP, FEN e DIE em plasma utilizando a técnica de imersão direta em micro-extração em fase sólida (SPME-DI) seguida de análise por cromatografia gasosa acoplada a espectrômetro de massas (GC-MS) compreendeu etapas de desproteinização da matriz e derivatização dos ATS. O método foi linear de 5,0 a 100 ng/ml. Os limites de detecção foram 1,0; 1,5; 2,0 ng/ml para AMP, DIE e FEN respectivamente. A exatidão variou de 85,58 a 108,33 % e a precisão, calculada pelo desvio padrão relativo, não excedeu 15 %. A recuperação esteve entre 46,35 – 84,46 %. Também foi desenvolvida e validada metodologia para análise simultânea de FEN, DIE e MPH em fluido oral por cromatografia líquida acoplada a detector de massas em tandem (LC-MS/MS). As curvas de calibração utilizando o padrão interno propranolol apresentaram linearidade entre 2,5 e 90 ng/ml. O limite inferior de quantificação e o limite de detecção foram de 2,5 ng/ml e 0,5 ng/ml respectivamente, para todos os ATS. Precisão e exatidão intra e inter-dias mantiveram-se dentro dos limites preconizados pelas guias regulatórias. Não foram observados efeito de matriz nem carry-over. Por fim, foram desenvolvidos e aplicados métodos para a análise de apreensões de ATS os quais revelaram a existência de ativo farmacêutico diverso (sibutramina) daquele especificado no rótulo do medicamento (FEN), em concentrações que variaram de 1/3 até 2 vezes a dose diária preconizada. Pela análise estatística dos espectros de infravermelho foi possível diferenciar amostras autênticas e amostras falsas e ainda agrupar falsificações com perfis semelhantes. Conclusões: os objetivos de estudo propostos nesta tese foram satisfatoriamente cumpridos e os resultados alcançados estão dispostos na forma de cinco artigos. Estes manuscritos contemplam temas relacionados ao uso de substâncias no trânsito, ao desenvolvimento e validação de metodologias analíticas e à análise de falsificações de medicamentos a base de ATS, demonstrando assim, a amplitude e multidisciplinariedade envolvidas no estudo dos compostos anfetamínicos. / The use of amphetamine-type stimulants compounds (ATS) for drivers aiming to stay awake is a known national problem, with social and legal implications. Diethylpropion (DIE) and fenproporex (FEN) are among the central nervous system stimulant most used by drivers in Brazil. Methylphenidate (MPH) is a drug that has properties similar to cocaine and amphetamine (AMP). Its use as a recreational and street drug has increased in recent years and its use has achieved space by the restriction of the marketing of DIE and FEN by the National Agency for Sanitary Surveillance (ANVISA) in 2011. The traffic analysis necessarily implies knowledge of the profile of drivers and the prevalence of substance use. To monitor the consumption of substances in transit, validated analytical methods in different biological matrices should be employed and toxicological data interpreted according pharmacokinetics of each substance. It is also known that many motorists buy ATS illegally in gas stations and the Internet. Knowing the chemical profile and detect forgeries of these medications is an essential part in the development and implementation of public policies to prevent the use of ATS in traffic. Objectives: to evaluate the traffic data from southern Brazil, emphasizing the use of substances, age and sex of those involved in traffic accidents; develop and validate chromatographic methods coupled to mass spectrometry for quantification of FEN, DIE and MPH in oral fluid and in plasma; evaluate the profile of counterfeit medications based on ATS. Results: data analysis of traffic accidents with fatalities from June 2008 to November 2010 in the State of Santa Catarina revealed that 11.9 % of cases had positive toxicology results. Cannabinoids (42 %) and cocaine (29.4 %) had the highest prevalence, followed by antidepressants (10.3 %), amphetamines (9.5 %), benzodiazepines (7.1 %) and barbiturates (1.6 %). Most victims (44 %) were aged between 16 and 30 years old and male. A validated method for the simultaneous analysis of AMP, DIE and FEN in plasma samples employing direct immersion-solid phase microextraction (DI-SPME) followed by gas chromatographic/mass spectrometric analyses (GC-MS) was developed. Deproteinization and derivatization of ATS were employed. The method was linear from 5.0 ngml-1 at 100 ngml-1. The detection limits were 1.0, 1.5, 2.0 ngml-1 for AMP, DIE and FEN respectively. The accuracy ranged from 85.58 to 108.33 % and precision, calculated by the relative standard deviation did not exceed 15 %. The recovery was between 46.35 to 84.46 %. Also was developed and validated a new method for simultaneous determination of FEN, DIE and MPH in oral fluid by liquidchromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS). The calibration curves, using an internal standard, demonstrated good linearity throughout the concentration range from 2.5–90 ngml-1 in oral fluid. The lower limit of quantification and the limit of detection were 2.5 and 1.0 ngml-1 respectively for all ATS. Intra- and inter-assay precision and accuracy values were within regulatory limits. Matrix effect and carry-over were not detected. Finally, methods have been developed and applied to analysis of seizures of ATS and the results showed the existence of active pharmaceutical (sibutramine) other than that specified on the label of the drug (FEN). The concentrations founded ranging from 1/3 to 2 times the recommended daily dose. Through the statistical analysis of the infrared spectra was possible to distinguish between authentic samples and counterfeit samples and also cluster the counterfeit ATS by their similar profiles. Conclusions: the proposed objectives of this thesis were satisfactorily completed and the results are arranged in the form of five manuscripts. These articles address issues related to substance use in traffic, development and validation of analytical methodologies and analysis of counterfeit medications based on ATS, highlighting the extent and multidisciplinary in the study of amphetamine compounds.

A utilização de substâncias estimulantes tipo-anfetamínicos (ATS) por motoristas com objetivo de aumentar o tempo de vigília é um conhecido problema nacional com consequências sociais e legais. A dietilpropiona (DIE) e o femproporex (FEN) figuram entre os estimulantes do sistema nervoso central (SNC) mais utilizados por condutores no trânsito brasileiro. O metilfenidato (MPH) é um fármaco que apresenta propriedades similares à cocaína e à anfetamina (AMP). Sua utilização como droga de rua e recreacional tem aumentado nos últimos anos e seu uso tem ganhado espaço com a restrição da comercialização de DIE e FEN pela Agência Nacional de Vigilância Sanitária (ANVISA) em 2011. O estudo do trânsito implica necessariamente o conhecimento do perfil dos condutores e da prevalência do uso de substâncias. Para a monitorização do consumo de substâncias no trânsito, é necessário o emprego de métodos analíticos validados para as matrizes biológicas de interesse. Sabe-se ainda que muitos condutores compram medicamentos ATS ilegalmente, em postos de combustível e pela internet. Conhecer o perfil químico e detectar falsificações desses medicamentos é parte essencial no desenvolvimento e aplicação de políticas públicas preventivas do uso de substâncias no trânsito. Objetivos: avaliar dados do trânsito da região sul do Brasil, enfatizando o uso de substâncias, a idade e o sexo dos envolvidos em acidentes; desenvolver e validar métodos cromatográficos acoplados a detector de massas para quantificação simultânea de FEN, DIE e MPH em fluido oral e em plasma; avaliar o perfil de falsificações de medicamentos a base de ATS. Resultados: os dados de acidentes de trânsito com vítimas fatais no Estado de Santa Catarina no período de junho de 2008 a novembro de 2010, revelaram que 11,9 % dos casos apresentaram resultados toxicológicos positivos, sendo canabinóides (42 %) e cocaína (29,4 %) as substâncias mais prevalentes, seguidas de antidepressivos (10,3 %), anfetamínicos (9,5 %), benzodiazepínicos (7,1 %) e barbitúricos (1,6 %). A maioria das vítimas (44 %) era jovem – entre 16 e 30 anos – e do sexo masculino. O desenvolvimento e validação de método de extração e quantificação simultânea de AMP, FEN e DIE em plasma utilizando a técnica de imersão direta em micro-extração em fase sólida (SPME-DI) seguida de análise por cromatografia gasosa acoplada a espectrômetro de massas (GC-MS) compreendeu etapas de desproteinização da matriz e derivatização dos ATS. O método foi linear de 5,0 a 100 ng/ml. Os limites de detecção foram 1,0; 1,5; 2,0 ng/ml para AMP, DIE e FEN respectivamente. A exatidão variou de 85,58 a 108,33 % e a precisão, calculada pelo desvio padrão relativo, não excedeu 15 %. A recuperação esteve entre 46,35 – 84,46 %. Também foi desenvolvida e validada metodologia para análise simultânea de FEN, DIE e MPH em fluido oral por cromatografia líquida acoplada a detector de massas em tandem (LC-MS/MS). As curvas de calibração utilizando o padrão interno propranolol apresentaram linearidade entre 2,5 e 90 ng/ml. O limite inferior de quantificação e o limite de detecção foram de 2,5 ng/ml e 0,5 ng/ml respectivamente, para todos os ATS. Precisão e exatidão intra e inter-dias mantiveram-se dentro dos limites preconizados pelas guias regulatórias. Não foram observados efeito de matriz nem carry-over. Por fim, foram desenvolvidos e aplicados métodos para a análise de apreensões de ATS os quais revelaram a existência de ativo farmacêutico diverso (sibutramina) daquele especificado no rótulo do medicamento (FEN), em concentrações que variaram de 1/3 até 2 vezes a dose diária preconizada. Pela análise estatística dos espectros de infravermelho foi possível diferenciar amostras autênticas e amostras falsas e ainda agrupar falsificações com perfis semelhantes. Conclusões: os objetivos de estudo propostos nesta tese foram satisfatoriamente cumpridos e os resultados alcançados estão dispostos na forma de cinco artigos. Estes manuscritos contemplam temas relacionados ao uso de substâncias no trânsito, ao desenvolvimento e validação de metodologias analíticas e à análise de falsificações de medicamentos a base de ATS, demonstrando assim, a amplitude e multidisciplinariedade envolvidas no estudo dos compostos anfetamínicos. / The use of amphetamine-type stimulants compounds (ATS) for drivers aiming to stay awake is a known national problem, with social and legal implications. Diethylpropion (DIE) and fenproporex (FEN) are among the central nervous system stimulant most used by drivers in Brazil. Methylphenidate (MPH) is a drug that has properties similar to cocaine and amphetamine (AMP). Its use as a recreational and street drug has increased in recent years and its use has achieved space by the restriction of the marketing of DIE and FEN by the National Agency for Sanitary Surveillance (ANVISA) in 2011. The traffic analysis necessarily implies knowledge of the profile of drivers and the prevalence of substance use. To monitor the consumption of substances in transit, validated analytical methods in different biological matrices should be employed and toxicological data interpreted according pharmacokinetics of each substance. It is also known that many motorists buy ATS illegally in gas stations and the Internet. Knowing the chemical profile and detect forgeries of these medications is an essential part in the development and implementation of public policies to prevent the use of ATS in traffic. Objectives: to evaluate the traffic data from southern Brazil, emphasizing the use of substances, age and sex of those involved in traffic accidents; develop and validate chromatographic methods coupled to mass spectrometry for quantification of FEN, DIE and MPH in oral fluid and in plasma; evaluate the profile of counterfeit medications based on ATS. Results: data analysis of traffic accidents with fatalities from June 2008 to November 2010 in the State of Santa Catarina revealed that 11.9 % of cases had positive toxicology results. Cannabinoids (42 %) and cocaine (29.4 %) had the highest prevalence, followed by antidepressants (10.3 %), amphetamines (9.5 %), benzodiazepines (7.1 %) and barbiturates (1.6 %). Most victims (44 %) were aged between 16 and 30 years old and male. A validated method for the simultaneous analysis of AMP, DIE and FEN in plasma samples employing direct immersion-solid phase microextraction (DI-SPME) followed by gas chromatographic/mass spectrometric analyses (GC-MS) was developed. Deproteinization and derivatization of ATS were employed. The method was linear from 5.0 ngml-1 at 100 ngml-1. The detection limits were 1.0, 1.5, 2.0 ngml-1 for AMP, DIE and FEN respectively. The accuracy ranged from 85.58 to 108.33 % and precision, calculated by the relative standard deviation did not exceed 15 %. The recovery was between 46.35 to 84.46 %. Also was developed and validated a new method for simultaneous determination of FEN, DIE and MPH in oral fluid by liquidchromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS). The calibration curves, using an internal standard, demonstrated good linearity throughout the concentration range from 2.5–90 ngml-1 in oral fluid. The lower limit of quantification and the limit of detection were 2.5 and 1.0 ngml-1 respectively for all ATS. Intra- and inter-assay precision and accuracy values were within regulatory limits. Matrix effect and carry-over were not detected. Finally, methods have been developed and applied to analysis of seizures of ATS and the results showed the existence of active pharmaceutical (sibutramine) other than that specified on the label of the drug (FEN). The concentrations founded ranging from 1/3 to 2 times the recommended daily dose. Through the statistical analysis of the infrared spectra was possible to distinguish between authentic samples and counterfeit samples and also cluster the counterfeit ATS by their similar profiles. Conclusions: the proposed objectives of this thesis were satisfactorily completed and the results are arranged in the form of five manuscripts. These articles address issues related to substance use in traffic, development and validation of analytical methodologies and analysis of counterfeit medications based on ATS, highlighting the extent and multidisciplinary in the study of amphetamine compounds.

The developed research sought to achieve an interdisciplinary approach to counterfeiting of the Brazilian Real ballots, identifying its possible innovations and socio-economic impacts, aiming in their considerations propose possible solutions to minimize the possible losses arising from the issue to the Company. The method was characterized by case study applied to Real ballots of the Brazilian currency, using bibliographic and documentary resources complemented by field studies through an interdisciplinary approach involving disciplines such as history, law, economics and Technological Innovation. For elements of history, there was a brief overview of the emergence of money in Brazil and the various denominations modified until the appearance of the second family of the real, still pointing the first counterfeit registration in Brazil, as the law of the aspects was mainly aimed the elements that make up the legal framework protecting the rights related to intellectual property. With regard to the economy was still drawn a macroeconomic analysis of counterfeit depending on income and the number of inhabitants. In aspects of technological innovation were accounted for the various innovations occurring in the manufacture of Real ballots since its existence to the present day. The results showed by basic principles of Applied Statistics that 100 people at least 4 possibly handled a false ballot and to minimize the increasing falsification of ballots, one should invest in technological safety innovations and conscious orientation to society. / A pesquisa desenvolvida buscou realizar uma abordagem interdisciplinar da contrafação das cédulas do Real Brasileiro, identificando suas possíveis inovações e impactos sócio-econômicos, objetivando em suas considerações propor possíveis soluções que minimizem as possíveis perdas ocasionadas pela temática à Sociedade. O método caracterizou-se por Estudo de Caso aplicado às cédulas do Real da moeda brasileira, utilizando-se de recursos bibliográfico-documental complementado por estudo de campo por meio de uma abordagem interdisciplinar envolvendo disciplinas como História, Direito, Economia e Inovação Tecnológica. Para elementos da História, fez-se um breve apanhado do surgimento do dinheiro no Brasil e as diversas denominações modificadas até o surgimento da segunda família do Real, apontando ainda o primeiro registro de contrafação do Brasil; quanto aos aspectos do Direito foram apontados principalmente os elementos que compõem o arcabouço legal que protegem os direitos relacionados à propriedade intelectual. Tratando-se da Economia foi traçado uma análise macroeconômica da contrafação em função da renda e o contingente populacional. Nos aspectos da inovação tecnológica foram contabilizadas as diversas inovações ocorridas no fabrico das cédulas do Real desde sua existência aos dias atuais. Os resultados apontaram, com base nos princípios básicos da Estatística Aplicada, que a cada 100 pessoas, pelo menos 4 possivelmente manusearam uma cédula falsa e que para minimizar o aumento crescente da falsificação de cédulas, deve-se investir em inovações tecnológicas de segurança e orientação consciente para a sociedade.

Recently the society has been turning from the use of paper-based technologies to plastic cards in certain spheres of our life. With the emergence and proliferation of high technologies we cannot content with the security provided bypaper only. Therefore the society has chosen plastic to protect its information because it offers far more security based not only on human perception but also on machine-readable elements. The number of plastic cards in circulation in different spheres of our everyday life increases constantly. They replace money, documents and allow easy and safe access to some services. In spite of its security the plastic card however is subjected to fraud. Plastic card fraud results in significant losses for the various industries. Since the first appearance of plastic cards methods of committing fraud have changed dramatically. Now there is a wide range of high technologies at the disposal of criminals as well as card manufacturers. Therefore we have put the great emphasize of this work on the analysis of the most common card technologies in the Plastic Card World, the magnetic stripe and the chip, existing crimes and main means of their committing. And we also have revealed the weak and strong sides of the prevention techniques, which are currently in use.

Face à l’ampleur de la contrefaçon des œuvres sur Internet et à la crise de légitimité du droit de la propriété littéraire et artistique qui l’accompagne, il est permis de s’interroger sur les moyens de lutter. La recherche d’une solution miracle, d’une solution unique à la contrefaçon sur Internet est illusoire, elle n’est d’ailleurs pas souhaitable. À la complexité du phénomène doivent être opposées des réponses multiples destinées à former un maillage pour protéger la propriété littéraire et artistique sur Internet. Une telle réponse plurielle existe aujourd’hui et elle doit être encouragée. C’est en effet de la combinaison de ces outils, de leur pluralité et de leur diversité, dont découlera une meilleure protection. Ainsi la protection résulte aujourd’hui à la fois des acteurs institutionnels, que sont le législateur et le juge, et des acteurs privés. De cette manière, elle devient progressivement l’affaire de tous, ce que nous ne pouvons qu’approuver. La protection imposée par la loi et le juge a dû se réinventer avec Internet, s’adapter à ce phénomène avec plus ou moins de succès. La loi a ainsi multiplié les outils, elle a innové en proposant de nouvelles approches telles que la prévention (notamment à travers la Hadopi) et la responsabilisation des acteurs du numérique (particulièrement avec l’articleL. 336-2 du Code de la propriété intellectuelle). Le juge est, quant à lui, à la recherche d’un équilibre. Il est aujourd’hui réticent à condamner les internautes et davantage enclin à responsabiliser les intermédiaires techniques qu’à les sanctionner. La protection imposée n’est pas parfaite, elle peut être améliorée, corrigée. Elle est aussi complétée par une protection spontanée issue des acteurs privés. Elle se manifeste d’abord à travers le recours aux contrats : la question de la protection du droit de la propriété littéraire et artistique contre la contrefaçon hier absente de ces derniers, y a fait son apparition avec la généralisation d’Internet. Le contrat n’est toutefois pas toujours à la hauteur des attentes placées en lui et souffre de limites qui peuvent être corrigées dans une certaine mesure. Les titulaires de droits et les acteurs du numérique innovent également en ayant recours à des instruments de droit souple comme la charte ou le code de bonne conduite. Certains acteurs du numérique vont même plus loin en proposant, de leur propre initiative, des moyens de protection, plus ou moins efficaces, contre la contrefaçon (déclassement, retrait de mots-clés). L’ensemble de ces outils constitue un maillage qui n’est pas parfait, que nous nous proposons de corriger, mais qui est nécessaire pour l’amélioration de la protection contre la contrefaçon sur Internet. / Considering the amount of counterfeit pieces of work on the Internet, and faced with the resulting legitimacy crisis within the literary and artistic property rights, we may wonder about the strategies for fighting online counterfeiting. It would not be realistic, nor advisable, actually, to be looking for a miracle cure, a unique anti-counterfeiting solution. The complexity of this phenomenon should be addressed with multiple responses. They should be designed to create a network that would protect literary and artistic property on the Internet. It is indeed the combination of these tools, their variety, and their diversity that will lead to a more effective protection. Therefore, today, this protection results from both institutional actors, such as the legislator or the judge, and private actors. Gradually, everybody is concerned by the matter and that is a fact that we can but approve of. With the development of the Internet, the protection dictated by the law and the judge has had to re-shape itself. It has more or less successfully adapted itself to this new phenomenon. The law has produced more tools, and offered new approaches such as prevention, through Hadopi, for example, or making of the actors of the digital industry aware of their responsibilities (especially through the following article L. 336-2 of the Intellectual Property Code). As for the judge, he is seeking a balance. He is now unwilling to sentence the Internet users, and he is more prone to make the technical intermediaries aware of their responsibilities than to punish them. This dictated protection is not perfect, it could be improved and revised. It is supplemented by a voluntary protection which the private actors provide. This protection is first visible through the use of contracts. The protection of literary and artistic property rights against counterfeiting did not use to be included in these contracts before, but it has now appeared in them since the Internet has begun to spread. However, the contract does not always live up to the expectations placed on it. It has limitations that can only be fixed to a certain extent. Rightholders and actors of the digital industry are also innovating: they resort to soft legal instruments such as the code of conduct. Some actors go even further and voluntarily offer more or less effective protection means against counterfeiting (downgrading, keyword removal) .All of these tools form a network, which is not perfect and which we are proposing to revise, but that is a key component to the improvement of the protection against counterfeiting online.

This research explores the international and national (such as Kenya, South Africa, Uganda, Tanzania and the OAPI region) standards of trademark law as well as the international rules promoting free flow of goods and how these two legal systems safeguard the consumers’ right to health. Focuses on the following two specific aspects of trademark law: counterfeiting which includes infringement, and licensing of a trademark in relation to consumers’ protection. / Thesis (LLM (Human Rights and Democratisation in Africa))--University of Pretoria, 2007. / Dissertation submitted to the Faculty of Law University of Pretoria, in partial fulfilment of the requirements for the degree Masters of Law (LLM in Human Rights and Democratisation in Africa). Prepared under the supervision of Dr Atangcho N Akonumbo Senior Lecturer, Catholic University Yaounde, Cameroon. / http://www.chr.up.ac.za/ / Centre for Human Rights / LLM

Binder jetting (BJT) is a powder bed based additive manufacturing (AM) process where the interaction of inkjetted droplets of a binder and particles in the powder bed create 3D geometries in a layerwise fashion. The fabricated green parts are usually thermally post-processed for densification and strengthening. BJT holds distinct advantages over other AM processes as it can fabricate parts with virtually any materials (metals, ceramics, and polymers) in a fast and cost-effective way, while achieving isotropic material properties in the parts. However, broad adoption of this process for production is still lagging, partially due to the lack of repeatable part quality, which largely stems from the limited understanding of the process physics, namely binder-powder (B/P) interaction. To bridge this knowledge gap, it is necessary to understand the implications of B/P interaction on process-structure-property relationships and discover ways to achieve new functionalities for enhanced properties. Thus, this research is broadly focused in establishing understanding in (i) binder-powder interaction and (ii) the impact of binder on part densification. Prior studies have focused on the effects of powder interaction with micro/meso-scale binder droplets, despite commercial BJT systems featuring picoliter-scale droplets. These studies have explored the effects of B/P interaction on printed primitive formation, but it's implication on final part properties have not been studied. In this work, the effects of particle size distribution and droplet size variation on final part properties are explored. Additionally, the effects of B/P interaction on accuracy and the resolution of the printed parts are investigated. Densification of parts is a primary focus of many BJT studies as it dictates the final part properties and is influenced by factors from both the printing process and post-processing treatments. Binder plays an integral role in the shaping of parts and maintaining part integrity until densification through sintering. Prior studies on the effects of binder content on densification are inclusive. In this work, a new approach termed as "shell printing" is introduced to vary the binder content in the parts. The process-structure-properties influenced by this approach are investigated. It was found that binder hinders densification, and through the selective variation of binder content throughout the part volume, this new approach is introduced as a means for enhancing part properties. Finally, the insights from the impact of binder on densification are leveraged to create an anti-counterfeiting tagging strategy by controlling the pores and grain microstructures inside a part. In this novel approach, binder concentration is controlled in a manner that the stochastically formed pores are clustered to create a designed domain that represents a secret 'tag' within the part volume. The created tagging domains, and the feature resolvability of this approach are investigated through metallographic characterization and non-destructively evaluated through micro-computed tomography. / Doctor of Philosophy / Binder jetting (BJT) is an additive manufacturing (AM) process to create 3D geometries from powder particles. Liquid droplets of binder from an inkjet printhead are jetted on a bed of packed powders, binding the particles. The as-printed parts, known as green parts, are generally fragile and require thermal post-processing (through sintering) for densification and strengthening. BJT holds distinct advantages over other AM processes as it can fabricate parts with virtually any powdered materials (metals, ceramics, and polymers) in a fast and cost-effective way. However, broad adoption of this process for production is still lagging, partially due to the lack of repeatable part quality, which largely stems from the limited understanding of the process physics, namely binder-powder (B/P) interaction. In this study the implications of B/P interaction on part quality (e.g., density, strength) and dimensional accuracy are studied. Additionally, the impact of binder on sintering densification is studied. Specifically, the effects of varying amount of binder on sintered part density, strength and internal pore and grain microstructures are empirically investigated. Finally, a novel anti-counterfeiting method for BJT printed parts is introduced based on the insights gained from the study of the impact of binder on densification. Through control over binder placement throughout the part, porous regions can be generated selectively throughout the part volume, which can be detected through x-ray computed tomography. Overall, an improved understanding of BJT processing conditions is achieved through this research, which can guide future designers to fabricate BJT parts with enhanced part properties and functionality.