Otimização e validação de método empregando SPE e LC-APCI-MS/MS para determinação de fármacos em água de supefície e de abastecimento público

O uso mundial dos fármacos classificados como contaminantes emergentes tornouse um novo problema ambiental devido à possível contaminação das águas de superfície e de abastecimento, podendo impactar o meio ambiente e causar danos à saúde pública. Na cidade de Rio Grande, RS, Brasil, o suprimento de água potável é realizado pela CORSAN (Companhia Riograndense de Saneamento), que capta a água do Canal São Gonçalo, o qual estabelece uma ligação entre as lagoas: dos Patos e Mirim. Neste trabalho um método analítico empregando Extração em Fase Sólida (SPE) e Cromatografia Líquida com Fonte de Ionização Química a Pressão Atmosférica acoplada a Espectrometria de Massas (LC-APCI-MS/MS) foi desenvolvido e validado para a determinação dos fármacos atenolol, cafeína, diclofenaco, fluoxetina e sulfametoxazol em amostras de água superficial e de abastecimento público. O método foi validado conforme parâmetros do INMETRO e SANCO. Os limites de detecção do método variaram entre 0,053 – 0,53 µg L -1 , enquanto para os limites de quantificação a variação foi de 0,16 – 1,6 µg L-1 . Todos os compostos apresentaram excelente linearidade, com coeficiente de correlação maior do que 0,99. Os valores de recuperação estiveram na faixa de 70 a 120%, com RSD menores que 20% para todos os compostos. Através do monitoramento de múltiplas reações (MRM), duas transições diferentes (íon precursor – íon produto) foram selecionadas para cada composto, uma para quantificação e outra para confirmação, o que aumentou a seletividade do método. O efeito de matriz foi avaliado, e dois compostos apresentaram supressão de sinal. O efeito de matriz foi compensado com calibração dos padrões na matriz.

Chromatographic analysis and survey studies to evaluate the emerging drugs of synthetic cannabinoids in Scotland and Saudi Arabia

Synthetic cannabinoid receptor agonists or more commonly known as synthetic cannabinoids (SCs) were originally created to obtain the medicinal value of THC but they are an emerging social problem. SCs are mostly produced coated on herbal materials or in powder form and marketed under a variety of brand names, e.g. “Spice”, “K2”. Despite many SCs becoming controlled under drug legislation, many of them remain legal in some countries around the world. In Scotland, SCs are controlled under the Misuse of Drugs Act 1971 and Psychoactive Substances Act 2016 that only cover a few early SCs. In Saudi Arabia, even fewer are controlled. The picture of the SCs-problem in Scotland is vague due to insufficient prevalence data, particularly that using biological samples. Whilst there is evidence of increasing use of SCs throughout the world, in Saudi Arabia, there is currently no data regarding the use of products containing SCs among Saudi people. Several studies indicate that SCs may cause serious toxicity and impairment to health therefore it is important to understand the scale of use within society. A simple and sensitive method was developed for the simultaneous analysis of 10 parent SCs (JWH-018, JWH-073, JWH-250, JWH-200, AM-1248, UR-144, A-796260, AB-FUBINACA, 5F-AKB-48 and 5F-PB-22) in whole blood and 8 corresponding metabolites (JWH-018 4-OH pentyl, JWH-073 3-OH butyl, JWH-250 4-OH pentyl, AM-2201 4-OH pentyl, JWH-122 5-OH pentyl, JWH-210 5-OH pentyl, 5F-AKB-48 (N-4 OH pentyl), 5F-PB-22 3-carboxyindole)in urine using LLE and LC-MS/MS. The method was validated according to the standard practices for method validation in forensic toxicology (SWGTOX, May 2013). All analytes gave acceptable precision, linearity and recovery for analysing blood and urine samples. The method was applied to 1,496 biological samples, a mixture of whole blood and urine. Blood and/or urine samples were analysed from 114 patients presenting at Accident and Emergency in Glasgow Royal Infirmary, in spring 2014 and JuneDecember 2015. 5F-AKB-48, 5F-PB-22 and MDMB-CHMICA were detected in 9, 7 and 9 cases respectively. 904 urine samples from individuals admitted to/liberated from Scottish prisons over November 2013 were tested for the presence of SCs. 5F-AKB-48 (N-4 OH pentyl) was detected in 10 cases and 5F-PB-22 3-carboxyindole in 3 cases. Blood and urine samples from two post-mortem cases in Scotland with suspected ingestion of SCs were analysed. Both cases were confirmed positive for 5F-AKB-48. A total of 463 urine samples were collected from personnel who presented to the Security Forces Hospital in Ryiadh for workplace drug testing as a requirement for their job during July 2014. The results of the analysis found 2 samples to be positive for 5F-PB-22 3carboxyindole. A further study in Saudi Arabia using a questionnaire was carried out among 3 subpopulations: medical professionals, members of the public in and around smoking cafes and known drug users. With regards to general awareness of Spice products, 16%, 11% and 22% of those participants of medical professionals, members of the public in and around smoking cafes and known drug users, respectively, were aware of the existence of SCs or Spice products. The respondents had an overall average of 4.5% who had a friend who used these Spice products. It is clear from the results obtained in both blood and urine testing and surveys that SCs are being used in both Scotland and Saudi Arabia. The extent of their use is not clear and the data presented here is an initial look into their prevalence. Blood and urine findings suggest changing trends in SC use, moving away from JWH and AM SCs to the newer 5F-AKB-48, 5-F-PB-22 and MDMBCHMICA compounds worldwide. In both countries 5F-PB-22 was detected. These findings clarify how the SCs phenomenon is a worldwide problem and how the information of every country regarding what SCs are seized can help and is not specific for that country. The analytes included in the method were selected due to their apparent availability in both countries, however it is possible that some newer analytes have been used and these would not have been detected. For this reason it is important that methods for testing SCs are updated regularly and evolve with the ever-changing availability of these drugs worldwide. In addition, there is little published literature regarding the concentrations of these drugs found in blood and urine samples and this work goes some way towards understanding these.

La déconstruction de l'onto-théologie par Jacques Derrida : détour littéraire et mise en relief de la matrice langagière comme "différance"

Le mouvement derridien de la différance marque la rupture avec l'affirmation de la métaphysique de la présence, avec l'autorité du signifié transcendantal. Dans cet univers mouvant de signifiants qui se renvoient perpétuellement les uns aux autres, la logique d'univocité se disloque. La "présence" n'est que fantomatique, s'esquissant au sein d'une chaîne ininterrompue de signifiants et se laissant toujours creuser par la marque d'un irréductible manque. Face au logocentrisme, corollaire de l'affirmation de la présence, l'écriture se veut siège et articulation de la trace, d'une origine qui ne peut être que raturée, véhicule d'une irrémédiable fêlure. La volet littéraire de la déconstruction a pour but de mettre en évidence le fonctionnement de l'"indécidabilité" du discours, soit une certaine ambivalence dans la signification qui caractérise tout texte. L'objectif principal de la présente recherche est de fournir une compréhension plus approfondie de la déconstruction en insistant sur l'ancrage langagier de tout texte. Le discours philosophique n'échappe ainsi pas au mécanisme différentiel du langage et de la dérive métaphorique. La parenté entre la perspective déconstructiviste derridienne et la conception mallarméenne du langage poétique semble frappante. La mise en oeuvre, par Mallarmé, d'une dislocation de l'espace textuel, son minutieux "creusement" du vers après renoncement à toute quête d'"Idéal", la mise en relief du leurre de l'appropriation langagière, voilà qui trouve un écho particulier dans les thèses derridiennes. La "mimésis" platonicienne se voit au travers du prisme de la "mimique" mallarméenne. La déconstruction poursuit son travail de "luxation" de l'oreille philosophique, insérant les philosophèmes dans la matrice langagière, les livrant ainsi au hasard du cheminement textuel et les confrontant à l'aporie. La philosophie n'a alors d'autre choix que d'abandonner ses prétentions transcendantales. La marche de la "différance" instaure une inexorable distance qui prive le sujet de tout rapport direct avec une origine assurée et lui ôte toute possibilité de maîtrise sur le monde. Au travers de la langue, se profile la question de l'altérité, de la relation dissymétrique qui nous lie à cet "autre", ce "tout-autre" qui nous fonde et nous constitue. L'accueil inconditionnel de cette altérité nous mènera à l'étude de la "religion", la déconstruction se tournant vers le "religieux" tout en effectuant un "retournement" habile de tout credo essentialiste.

The impact of geometric non-linearities on the fatigue analysis of trailing edge bond lines in wind turbine rotor blades

The accurate prediction of stress histories for the fatigue analysis is of utmost importance for the design process of wind turbine rotor blades. As detailed, transient, and geometrically non-linear three-dimensional finite element analyses are computationally weigh too expensive, it is commonly regarded sufficient to calculate the stresses with a geometrically linear analysis and superimpose different stress states in order to obtain the complete stress histories. In order to quantify the error from geometrically linear simulations for the calculation of stress histories and to verify the practical applicability of the superposition principal in fatigue analyses, this paper studies the influence of geometric non-linearity in the example of a trailing edge bond line, as this subcomponent suffers from high strains in span-wise direction. The blade under consideration is that of the IWES IWT-7.5-164 reference wind turbine. From turbine simulations the highest edgewise loading scenario from the fatigue load cases is used as the reference. A 3D finite element model of the blade is created and the bond line fatigue assessment is performed according to the GL certification guidelines in its 2010 edition, and in comparison to the latest DNV GL standard from end of 2015. The results show a significant difference between the geometrically linear and non-linear stress analyses when the bending moments are approximated via a corresponding external loading, especially in case of the 2010 GL certification guidelines. This finding emphasizes the demand to reconsider the application of the superposition principal in fatigue analyses of modern flexible rotor blades, where geometrical nonlinearities become significant. In addition, a new load application methodology is introduced that reduces the geometrically non-linear behaviour of the blade in the finite element analysis.

Estandarización del método para alcoholemias por cromatografía de gases

La ingesta de etanol se ha relacionado a consecuencias lamentables a nivel social, familiar y jurídico; siendo importante el desarrollo de métodos de detección de etanol en sangre, prueba más confiable a nivel cuantitativo. En el presente trabajo se realizó la primera fase de la optimización de un método para el análisis de alcoholemia por cromatografía de gases con inyección directa y detección de ionización de llama (GC-FID). Se realizó la optimización de algunos parámetros cualitativos y cuantitativos, incluyendo tiempos de retención estables, selectividad del método demostrado por la ausencia de sustancias interferentes en el análisis; linealidad a bajos niveles con un coeficiente de determinación de R2 = 0.996. La aplicabilidad del método en un pool de 33 muestras con distintas concentraciones de etanol tomadas cómo puntos de referencia de baja, media y alta concentración. La cuantificación se realizó por estandarización interna mediante el uso de un estándar interno (n-butanol) y la estandarización externa mediante la curva de calibración a 4 niveles.

Validation d’un procédé automatisé d’extraction sur phase solide de glandes digestives de moules pour l’identification et la quantification des dinophysistoxines en LC/ESI/SM2 par piégeage d’ions quadripolaire

This report presents a new extraction method of the dinophysistoxins (DTXs), confirmed by quantification using high-performance liquid chromatography coupled to mass spectrometry with an ion trap and electro spray interface (HPLC/ESI/MS2). The method originality consists on the adaptation of DTXs basic extraction procedure (liquid/ liquid) to a solid phase extraction (SPE) via a robotic station: ASPEC XLi The parameters of the automatization procedure were optimized to obtain the best DTXs recovery rate. These improvements were loaded with digestive gland mussel homogenat realized on a silica cartridge SPE, activated in hexane/chloroform (50:50), washed with hexane/chloroform (50:50) and extracted by an elution gradient (chloroform methanol (65:35) and methanol (100%)). This method was validated according to two normative referentials (linearity, detection quantification limits and accuracy…) : - The Guide of the Pharmacy industry: Analytical Validation, report of the commission SFSTP 1992 (French Corporation of the Sciences and Technical Pharmaceutical), - - The Procedure of validation of an alternative method in compare to a reference method. (AFNOR, 1998. NF V 03-110). Comparison with the classical liquid/liquid extraction and the automated method present clear advantages. In an analytical method the extraction is generally considered to be the most labor-intensive and error-prone step. This new procedure allowed us to increase throughput, to improve the reproducibility and to reduce the error risks due to the individual manual treatments.

Modelação e previsão de um índice financeiro (FTSE 100)

A presente dissertação visa uma aplicação de séries temporais, na modelação do índice financeiro FTSE100. Com base na série de retornos, foram estudadas a estacionaridade através do teste Phillips-Perron, a normalidade pelo Teste Jarque-Bera, a independência analisada pela função de autocorrelação e pelo teste de Ljung-Box, e utilizados modelos GARCH, com a finalidade de modelar e prever a variância condicional (volatilidade) da série financeira em estudo. As séries temporais financeiras apresentam características peculiares, revelando períodos mais voláteis do que outros. Esses períodos encontram-se distribuídos em clusters, sugerindo um grau de dependência no tempo. Atendendo à presença de tais grupos de volatilidade (não linearidade), torna-se necessário o recurso a modelos heterocedásticos condicionais, isto é, modelos que consideram que a variância condicional de uma série temporal não é constante e dependente do tempo. Face à grande variabilidade das séries temporais financeiras ao longo do tempo, os modelos ARCH (Engle, 1982) e a sua generalização GARCH (Bollerslev, 1986) revelam-se os mais adequados para o estudo da volatilidade. Em particular, estes modelos não lineares apresentam uma variância condicional aleatória, sendo possível, através do seu estudo, estimar e prever a volatilidade futura da série. Por fim, é apresentado o estudo empírico que se baseia numa proposta de modelação e previsão de um conjunto de dados reais do índice financeiro FTSE100.

Influência da adição de cálcio nas propriedades de pastas geopoliméricas destinadas a cimentação de poços de petróleo

Nowadays, the search for new technologies that are able to follow the upcoming challenges in oil industry is a constant. Always trying properties improvements of the used materials, looking for the best performance and greater life time. Besides the search for technologies that show an improvement of performance, the search for materials environmentally correct along the whole production process. In Oil well cementing, this search for new technologies passes through the development of slurry systems that support these requests and that are also environmentally friendly. In this context, the use of geopolymer slurries is a great alternative route to cementing oil wells. Besides having good properties, comparable to Portland cement slurries, this alternative material releases much less CO2 gas in the production of their root materials when compared the production of Portland cement, which releases tons of CO2. In order to improve the properties of geopolymer slurries has been added Calcium Oxide, as observed in other studies that slurries where the Calcium is present the values of compressive strength is greater. The addition has been realized based in the CaO/SiO2 molar ratio of 0.05, 0.10 and 0.15. Have been performed compressive strength tests, thickening time, rheology and fliud loss control test of the slurries, following NBR 9831, as well as the physical chemical characterization of XRD, SEM and TG. Has been observed in most of the tests the slurries follow a tendency until the ratio of 0.10, which inverses in the ratio 0.15. This behavior can be explained by two phenomena that occur simultaneously, the first one is the break of the polymer chains and a consequent increase in molucules mobility, which prevails until the ratio of 0.1, and the second is possible approach of the chains due to the capacity of the calcium ions stabilize the charges of two different aluminum. There is only one linearity in the mechanical behavior that can be attributed to the appereance of the C-S-H phase. Based on this, it is concluded that the phenomenon of breaking the polymer chains predominates until the ratio of 0.1, causing an increase of the filtrate volume, lower rheological parameters and increasing thickening time. From the ratio of 0.15 the approach of the chains predominates, and the behavior is reversed

Hyperlinks in e-books : expanding the functionality of end-notes

With its powerful search engines and billions of published pages, the Worldwide Web has become the ultimate tool to explore the human experience. But, despite the advent of the digital revolution, e-books, at their core, have remained remarkably similar to their printed siblings. This has resulted in a clear dichotomy between two ways of reading: on one side, the multi-dimensional world of the Web; on the other, the linearity of books and e-books. My investigation of the literature indicates that the focus of attempts to merge these two modes of production, and hence of reading, has been the insertion of interactivity into fiction. As I will show in the Literature Review, a clear thrust of research since the early 1990s, and in my opinion the most significant, has concentrated on presenting the reader with choices that affect the plot. This has resulted in interactive stories in which the structure of the narrative can be altered by the reader of experimental fiction. The interest in this area of research is not surprising, as the interaction of readers with the fabric of the narrative provides a fertile ground for exploring, analysing, and discussing issues of plot consistency and continuity. I found in the literature several papers concerned with the effects of hyperlinking on literature, but none about how hyperlinked material and narrative could be integrated without compromising the narrative flow as designed by the author. It led me to think that the researchers had accepted hypertextuality and the linear organisation of fiction as being antithetical, thereby ignoring the possibility of exploiting the first while preserving the second. All the works I consulted were focussed on exploring the possibilities provided to authors (and readers) by hypertext or how hypertext literature affects literary criticism. This was true in earlier works by Landow and Harpold and remained true in later works by Bolter and Grusin. To quote another example, in his book Hypertext 3.0, Landow states: “Most who have speculated on the relation between hypertextuality and fiction concentrate [...] on the effects it will have on linear narrative”, and “hypertext opens major questions about story and plot by apparently doing away with linear organization” (Landow, 2006, pp. 220, 221). In other words, the authors have added narrative elements to Web pages, effectively placing their stories in a subordinate role. By focussing on “opening up” the plots, the researchers have missed the opportunity to maintain the integrity of their stories and use hyperlinked information to provide interactive access to backstory and factual bases. This would represent a missing link between the traditional way of reading, in which the readers have no influence on the path the author has laid out for them, and interactive narrative, in which the readers choose their way across alternatives, thereby, at least to a certain extent, creating their own path. It would be, to continue the metaphor, as if the readers could follow the main path created by the author while being able to get “sidetracked” into exploring hyperlinked material. In Hypertext 3.0, Landow refers to an “Axial structure [of hypertext] characteristic of electronic books and scholarly books with foot-and endnotes” versus a “Network structure of hypertext” (Landow, 2006, p. 70). My research aims at generalising the axial structure and extending it to fiction without losing the linearity at its core. In creative nonfiction, the introduction of places, scenes, and settings, together with characterisation, brings to life the facts without altering them; while much fiction draws on facts to provide a foundation, or narrative elements, for the work. But how can the reader distinguish between facts and representations? For example, to what extent do dialogues and perceptions present what was actually said and thought? Some authors of creative nonfiction use end-notes to provide comments and citations while minimising disruption the flow of the main text, but they are limited in scope and constrained in space. Each reader should be able to enjoy the narrative as if it were a novel but also to explore the facts at the level of detail s/he needs. For this to be possible, end-notes should provide a Web-like way of exploring in more detail what the author has already researched. My research aims to develop ways of integrating narrative prose and hyperlinked documents into a Hyperbook. Its goal is to create a new writing paradigm in which a story incorporates a gateway to detailed information. While creative nonfiction uses the techniques of fictional writing to provide reportage of actual events and fact-based fiction illuminates the affectual dimensions of what happened (e.g., Kate Grenville’s The Secret River and Hilary Mantel’s Wolf Hall), Hyperbooks go one step further and link narrative prose to the details of the events on which the narrative is based or, more in general, to information the reader might find of interest. My dissertation introduces and utilises Hyperbooks to engage in two parallel types of investigation Build knowledge about Italian WWII POWs held in Australia and present it as part of a novella in Hyperbook format. Develop a new piece of technology capable of extending the writing and reading process.

Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C

International audience

Desenvolvimento e validação de metodologias para quantificação de 3,4 metilenodioximetanfetamina (MDMA) em comprimidos de ecstasy por cromatografia gasosa e ressonância magnética nuclear

Dissertação (mestrado)—Universidade de Brasília, Instituto de Química, 2016.

Algoritmos construtivos para treino de redes neuronais b-spline

Dissertação de mest. em Engenharia de Sistemas e Computação - Área de Sistemas de Controlo, Faculdade de Ciências e Tecnologia, Univ.do Algarve, 2001

Novos Meisho

Dissertação para obtenção do grau de Mestre em Arquitectura, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

Quality evaluation of cortex berberidis from different geographical origins by simultaneous high performance liquid chromatography combined with statistical methods

Purpose: To develop an effective method for evaluating the quality of Cortex berberidis from different geographical origins. Methods: A simple, precise and accurate high performance liquid chromatography (HPLC) method was first developed for simultaneous quantification of four active alkaloids (magnoflorine, jatrorrhizine, palmatine, and berberine) in Cortex berberidis obtained from Qinghai, Tibet and Sichuan Provinces of China. Method validation was performed in terms of precision, repeatability, stability, accuracy, and linearity. Besides, partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA) were applied to study the quality variations of Cortex berberidis from various geographical origins. Results: The proposed HPLC method showed good linearity, precision, repeatability, and accuracy. The four alkaloids were detected in all samples of Cortex berberidis. Among them, magnoflorine (36.46 - 87.30 mg/g) consistently showed the highest amounts in all the samples, followed by berberine (16.00 - 37.50 mg/g). The content varied in the range of 0.66 - 4.57 mg/g for palmatine and 1.53 - 16.26 mg/g for jatrorrhizine, respectively. The total content of the four alkaloids ranged from 67.62 to 114.79 mg/g. Moreover, the results obtained by the PLS-DA and ANOVA showed that magnoflorine level and the total content of these four alkaloids in Qinghai and Tibet samples were significantly higher (p < 0.01) than those in Sichuan samples. Conclusion: Quantification of multi-ingredients by HPLC combined with statistical methods provide an effective approach for achieving origin discrimination and quality evaluation of Cortex berberidis. The quality of Cortex berberidis closely correlates to the geographical origin of the samples, with Cortex berberidis samples from Qinghai and Tibet exhibiting superior qualities to those from Sichuan.

Production et articulation des appartenances au mouvement Slow Fashion sur Twitter

Ce mémoire explore les productions et les articulations des appartenances au mouvement Slow Fashion sur Twitter. En réaction au modèle actuel prédominant du Fast Fashion, basé sur une surproduction et une surconsommation des vêtements, le Slow Fashion sensibilise les différents acteurs du secteur de la mode à avoir une vision plus consciente des impacts de leurs pratiques sur les travailleurs, les communautés et les écosystèmes (Fletcher, 2007) et propose une décélération des cycles de production et de consommation des vêtements. L’enjeu de cette recherche est de montrer que le Slow Fashion se dessine notamment à travers les relations entres les différents acteurs sur Twitter et que l'ensemble de ces interactions prend la forme d'un rhizome, c’est-à-dire d’un système dans lequel les éléments qui le composent ne suivent aucune arborescence, aucune hiérarchie et n’émanent pas d’un seul point d’origine. (Deleuze & Guattari, 1976) Sur Twitter, les appartenances au Slow Fashion font surface, se connectent les unes aux autres par des liens de nature différente. Consommateurs, designers, entreprises, journalistes, etc., ces parties prenantes construisent collectivement le Slow Fashion comme mouvement alternatif à la mode mainstream actuelle. Mon cadre théorique s’est construit grâce à une analyse de la littérature des concepts de mode, d’identité et d’appartenance afin de mieux appréhender le contexte dans lequel le mouvement a émergé. Puis, j’ai également réalisé une étude exploratoire netnographique sur Twitter au cours de laquelle j’ai observé, tout en y participant, les interactions sur la plateforme abordant le Slow Fashion et/ou la mode éthique. Publiée sur ce blogue (http://belongingtoslowfashion.blogspot.ca), cette « creative presentation of research » (Chapman & Sawchuk, 2012) ne constitue pas une histoire présentant les prétendues origines de ce mouvement mais plutôt une photographie partielle à un certain moment du Slow Fashion. Construite tel un rhizome, elle n’a ni début, ni fin, ni hiérarchie. J’invite alors les lectrices/lecteurs à choisir n’importe quelle entrée et à délaisser toute logique linéaire et déductive. Cette exploration sera guidée par des liens hypertextes ou des annotations qui tisseront des connexions avec d’autres parties ou feront émerger d’autres questionnements. Il s’agit d’offrir une introduction aux enjeux que pose le Slow Fashion, d’ouvrir la voie à d’autres recherches et d’autres réflexions, ou encore de sensibiliser sur ce sujet.