915 resultados para Performance evaluation. Competencies. Pharmaceutical industry. Strategy. Drug sellers propagandists


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This study considers a dual-hop cognitive inter-vehicular relay-assisted communication system where all
communication links are non-line of sight ones and their fading is modelled by the double Rayleigh fading distribution.
Road-side relays (or access points) implementing the decode-and-forward relaying protocol are employed and one of
them is selected according to a predetermined policy to enable communication between vehicles. The performance of
the considered cognitive cooperative system is investigated for Kth best partial and full relay selection (RS) as well as
for two distinct fading scenarios. In the first scenario, all channels are double Rayleigh distributed. In the second
scenario, only the secondary source to relay and relay to destination channels are considered to be subject to double
Rayleigh fading whereas, channels between the secondary transmitters and the primary user are modelled by the
Rayleigh distribution. Exact and approximate expressions for the outage probability performance for all considered RS
policies and fading scenarios are presented. In addition to the analytical results, complementary computer simulated
performance evaluation results have been obtained by means of Monte Carlo simulations. The perfect match between
these two sets of results has verified the accuracy of the proposed mathematical analysis.

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The present thesis describes the development of heterogeneous catalytic methodologies using metal−organic frameworks (MOFs) as porous matrices for supporting transition metal catalysts. A wide spectrum of chemical reactions is covered. Following the introductory section (Chapter 1), the results are divided between one descriptive part (Chapter 2) and four experimental parts (Chapters 3–6). Chapter 2 provides a detailed account of MOFs and their role in heterogeneous catalysis. Specific synthesis methods and characterization techniques that may be unfamiliar to organic chemists are illustrated based on examples from this work. Pd-catalyzed heterogeneous C−C coupling and C−H functionalization reactions are studied in Chapter 3, with focus on their practical utility. A vast functional group tolerance is reported, allowing access to substrates of relevance for the pharmaceutical industry. Issues concerning the recyclability of MOF-supported catalysts, leaching and operation under continuous flow are discussed in detail. The following chapter explores puzzling questions regarding the nature of the catalytically active species and the pathways of deactivation for Pd@MOF catalysts. These questions are addressed through detailed mechanistic investigations which include in situ XRD and XAS data acquisition. For this purpose a custom reaction cell is also described in Chapter 4. The scope of Pd@MOF-catalyzed reactions is expanded in Chapter 5. A strategy for boosting the thermal and chemical robustness of MOF crystals is presented. Pd@MOF catalysts are coated with a protecting SiO2 layer, which improves their mechanical properties without impeding diffusion. The resulting nanocomposite is better suited to withstand the harsh conditions of aerobic oxidation reactions. In this chapter, the influence of the nanoparticles’ geometry over the catalyst’s selectivity is also investigated. While Chapters 3–5 dealt with Pd-catalyzed processes, Chapter 6 introduces hybrid materials based on first-row transition metals. Their reactivity is explored towards light-driven water splitting. The heterogenization process leads to stabilized active sites, facilitating the spectroscopic probing of intermediates in the catalytic cycle.

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We evaluate the impact of the Eurozone sovereign debt crisis on the performance and performance persistence of a survivorship bias-free sample of bond funds from a small market, identified as one of the most affected by this event, during the 2001–2012 period. Besides avoiding data mining, we also introduce a methodological innovation in assessing bond fund performance persistence. Our results show that bond funds underperform significantly both during crisis and non-crisis periods. Besides, we find strong evidence of performance persistence, for both short- and longer-term horizons, during non-crisis periods but not during the debt crisis. In this way, the persistence phenomenon in small markets seems to occur only during non-crisis periods and this is valuable information for bond fund investors to exploit.

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This paper provides the first investigation about bond mutual fund performance during recession and expansion periods separately. Based on multi-factor performance evaluation models, results show that bond funds significantly underperform the market during both phases of the business cycle. Nevertheless, unlike equity funds, bond funds exhibit considerably higher alphas during good economic states than during market downturns. These results, however, seem entirely driven by the global financial crisis subperiod. In contrast, during the recession associated to the Euro sovereign debt crisis, bond funds are able to accomplish neutral performance. This improved performance throughout the debt crisis seems to be related to more conservative investment strategies, which reflect an increase in managers’ risk aversion.

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Segundo o paradigma económico vigente, os intangíveis são hoje os principais factores de produção que criam riqueza no meio empresarial, devendo ser entendidos pelos gestores como factores críticos de sucesso. O conjunto de intangíveis que criam valor organizacional e sustentam a vantagem competitiva constituem o capital intelectual. Se no meio académico, o capital intelectual é visto como um motor do desenvolvimento económico, no âmbito da sociedade do conhecimento, já no meio empresarial apesar do reconhecimento da sua importância estratégica, poucos conseguem defini-lo e identificá-lo, não sabendo mesmo como tirar proveito dele. Acresce ainda o facto de o principal entrave poder estar relacionado na dificuldade em medir e representar o valor gerado por este recurso intangível. A generalidade dos autores que se dedica ao estudo do capital intelectual sustenta a existência de uma relação entre este e o desempenho organizacional, numa óptica de criação e manutenção de vantagens competitivas sustentáveis. Este trabalho apresenta um estudo exploratório realizado no âmbito da indústria farmacêutica portuguesa, com o objectivo de investigar, por um lado, a presença dos três elementos do capital intelectual: capital humano, capital estrutural e capital relacional e, por outro, o seu inter-relacionamento dentro do contexto farmacêutico português. Por fim, pretende-se investigar até que ponto o capital intelectual contribui para o sucesso das organizações analisadas. / According to the prevailing economic paradigm, intangibles are now the main factors of production that are creating wealth in the business world and they should be seen by managers as crucial factors of success. The intangible assets that create organisational value and sustain a competitive edge constitute intellectual capital. In academia intellectual capital is viewed as a driving force for economic development, in the context of the knowledge society, but in the corporate world, although recognised for its strategic importance few people can define it and identify it, or even know how to exploit it. The chief obstacle may be related to the difficulty in measuring and representing the value engendered by this intangible resource. Most authors involved in studying intellectual capital believe that it is related to organisational performance in terms of creating and retaining sustainable competitive advantages. This work is an exploratory study of the Portuguese pharmaceutical industry and it set out, first, to inquire into the presence of the three elements of intellectual capital, human capital, structural capital and relational capital, and also to examine their interrelations within the Portuguese pharmaceutical context. A final objective was to ascertain the part played by intellectual capital in the success of the organizations studied.

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Le byssus est un amas de fibres que les moules produisent afin de s’ancrer aux surfaces immergées sous l’eau. Ces fibres sont pourvues de propriétés mécaniques impressionnantes combinant rigidité, élasticité et ténacité élevées. De plus, elles possèdent un comportement d’auto-guérison de leurs propriétés mécaniques en fonction du temps lorsque la contrainte initialement appliquée est retirée. Les propriétés mécaniques de ces fibres sont le résultat de l’agencement hiérarchique de protéines de type copolymère blocs riches en collagène et de la présence de métaux formant des liens sacrificiels réversibles avec certains acides aminés comme les DOPA et les histidines. Bien que cette fibre soit très intéressante pour la production de matériaux grâce à son contenu élevé en collagène potentiellement biocompatible, cette ressource naturelle est traitée comme un déchet par les mytiliculteurs. L’objectif de cette thèse était de valoriser cette fibre en extrayant les protéines pour générer une nouvelle classe de matériaux biomimétiques. Un hydrolysat de protéines de byssus (BPH) riche en acides aminés chargés, i.e. ~30 % mol, et permettant de former des films a pu être généré. Lorsque solubilisé à pH 10.5, le BPH forme un hydrogel contenant des structures en triple hélice de collagène et des feuillets β anti-parallèles intra- et inter-moléculaires. Suite à l’évaporation de l’eau, le film de BPH résultant est insoluble en milieu aqueux à cause des structures secondaires très stables agissant comme points de réticulation effectifs. Les propriétés mécaniques des films de BPH sont modulables en fonction du pH. Au point isoélectrique (pI = 4.5), les interactions électrostatiques entre les charges opposées agissent comme points de réticulation et augmentent la rigidité des films et leur contrainte à la rupture sans affecter la déformation à la rupture. À pH plus élevé ou plus bas que le pI, les performances mécaniques des films sont plus faibles à cause de la répulsion entre les groupements fonctionnels de même charge qui interagissent plutôt avec les molécules d’eau et causent le gonflement de la matrice protéique des films. Le BPH contenant un nombre élevé d’acides aminés chargés et réactifs, nous avons pu réticuler les films de manière covalente à l’aide d’EDC ou de glutaraldéhyde. Les propriétés mécaniques des films sont modulables en fonction de la concentration d’EDC utilisée lors de la réticulation ou en employant du glutaraldéhyde comme agent réticulant. Les films sont à la fois plus rigides et plus forts avec un degré de réticulation élevé, mais perdent leur extensibilité à mesure que les segments libres de s’étirer lors d’une traction deviennent entravés par les points de réticulation. La réticulation augmente également la résistance à la dégradation enzymatique par la collagénase, les films les plus fortement réticulés lui étant pratiquement insensibles. La spectroscopie infrarouge montre enfin que la réticulation entraîne une transition de feuillets β anti-parallèles inter-moléculaires vers des structures de type hélices de collagène/PPII hydratées. Des liens sacrificiels ont été formés dans les films de BPH par traitement au pI et/ou avec différents métaux, i.e. Na+, Ca2+, Fe3+, afin de moduler les propriétés mécaniques statiques et d’évaluer le rôle de ces traitements sur le comportement d’auto-guérison lors de tests mécaniques cycliques avec différents temps de repos. Plus la valence des ions métalliques ajoutés augmente, plus les propriétés mécaniques statiques affichent un module, une contrainte à la rupture et une ténacité élevés sans toutefois affecter la déformation à la rupture, confirmant la formation de liens sacrificiels. Les tests mécaniques cycliques montrent que les traitements au pI ou avec Ca2+ créent des liens sacrificiels ioniques réversibles qui mènent à un processus d’auto-guérison des performances mécaniques dépendant du pH. L’ajout de Fe3+ à différentes concentrations module les performances mécaniques sur un plus large intervalle et la nature plus covalente de son interaction avec les acides aminés permet d’atteindre des valeurs nettement plus élevées que les autres traitements étudiés. Le Fe3+ permet aussi la formation de liens sacrificiels réversibles menant à l’auto-guérison des propriétés mécaniques. Les spectroscopies Raman et infrarouge confirment que le fer crée des liaisons avec plusieurs acides aminés, dont les histidines et les DOPA. Les résultats dans leur ensemble démontrent que les films de BPH sont des hydrogels biomimétiques du byssus qui peuvent être traités ou réticulés de différentes façons afin de moduler leurs performances mécaniques. Ils pourraient ainsi servir de matrices pour des applications potentielles dans le domaine pharmaceutique ou en ingénierie tissulaire.

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Aditivos químicos têm como principal objetivo melhorar os produtos industrializados, como fármacos, conferindo-lhes cor, aroma, textura, conservação, entre outros. Os aditivos utilizados na indústria farmacêutica são denominados excipientes, completando a massa ou o volume especificado no medicamento. São considerados substâncias inativas, uma vez que não apresentam propriedades curativas ou preventivas de doenças ou dos seus sintomas. No âmbito deste trabalho, foi realizado uma revisão bibliográfica sobre os excipientes naturais e sintéticos mais usados na indústria farmacêutica, agrupando-os mediante a sua função específica. Assim, foi feita uma breve descrição sobre alguns dos excipientes mais utilizados nas formulações farmacêuticas, nomeadamente os antioxidantes, os corantes, os edulcorantes e os conservantes, que visam garantir a conservação do produto em condições viáveis. Uma vez que os excipientes são considerados substâncias inativas, são vistos como inofensivos para a saúde. No entanto, é cada vez mais evidente que os excipientes não são sempre inertes e podem apresentar riscos para o desenvolvimento de reações alérgicas, podendo promover alterações mais prejudiciais. As reações alérgicas associadas aos excipientes são consideradas raras, visto que são incorporadas baixas concentrações destes em formulações farmacêuticas, tendo surgido, no entanto, diversos casos associados aos diferentes excipientes anteriormente referidos. Dependendo do excipiente e da sensibilidade do indivíduo, as alergias podem originar dermatites de contacto, prurido, urticária, edema, reações anafiláticas, entre outros. É importante salientar que o excesso de aditivos pode originar problemas de saúde, normalmente em indivíduos suscetíveis e na população pediátrica, sendo necessário aplicar cuidados adicionais que promovam uma maior vigilância e orientação no uso de medicamentos.

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Succinate is a naturally occurring metabolite in organism’s cell and is industrially important chemical with various applications in food and pharmaceutical industry. It is also widely used to produce bio-degradable plastics, surfactants, detergents etc. In last decades, emphasis has been given to bio-based chemical production using industrial biotechnology route rather than fossil-based production considering sustainability and environment friendly economy. In this thesis I am presenting a computational model for silico metabolic engineering of Saccharomyces cerevisiae for large scale production of succinate. For metabolic modelling, I have used OptKnock and OptGene optimization algorithms to identify the reactions to delete from the genome-scale metabolic model of S. cerevisiae to overproduce succinate by coupling with organism’s growth. Both OptKnock and OptGene proposed numerous straightforward and non-intuitive deletion strategies when number of constraints including growth constraint to the model were applied. The most interesting strategy identified by both algorithms was deletion combination of pyruvate decarboxylase and Ubiquinol:ferricytochrome c reductase(respiratory enzyme) reactions thereby also suggesting anaerobic fermentation of the organism in glucose medium. Such strategy was never reported earlier for growth-coupled succinate production in S.cerevisiae.

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Mestrado em Controlo da Gestão e dos Negócios

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New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.

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In this thesis, tool support is addressed for the combined disciplines of Model-based testing and performance testing. Model-based testing (MBT) utilizes abstract behavioral models to automate test generation, thus decreasing time and cost of test creation. MBT is a functional testing technique, thereby focusing on output, behavior, and functionality. Performance testing, however, is non-functional and is concerned with responsiveness and stability under various load conditions. MBPeT (Model-Based Performance evaluation Tool) is one such tool which utilizes probabilistic models, representing dynamic real-world user behavior patterns, to generate synthetic workload against a System Under Test and in turn carry out performance analysis based on key performance indicators (KPI). Developed at Åbo Akademi University, the MBPeT tool is currently comprised of a downloadable command-line based tool as well as a graphical user interface. The goal of this thesis project is two-fold: 1) to extend the existing MBPeT tool by deploying it as a web-based application, thereby removing the requirement of local installation, and 2) to design a user interface for this web application which will add new user interaction paradigms to the existing feature set of the tool. All phases of the MBPeT process will be realized via this single web deployment location including probabilistic model creation, test configurations, test session execution against a SUT with real-time monitoring of user configurable metric, and final test report generation and display. This web application (MBPeT Dashboard) is implemented with the Java programming language on top of the Vaadin framework for rich internet application development. The Vaadin framework handles the complicated web communications processes and front-end technologies, freeing developers to implement the business logic as well as the user interface in pure Java. A number of experiments are run in a case study environment to validate the functionality of the newly developed Dashboard application as well as the scalability of the solution implemented in handling multiple concurrent users. The results support a successful solution with regards to the functional and performance criteria defined, while improvements and optimizations are suggested to increase both of these factors.

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Protection of innovation in the pharmaceutical industry has traditionally been realised through protection of inventions via patents. However, in the European Union regulatory exclusivities restricting market entry of generic products confer tailored, industry specific protection for final, marketable products. This paper retraces the protection conferred by the different forms of exclusivity and assesses them in the light of recent transparency policies of the European Medicines Agency. The purpose of the paper is to argue for rethinking the role of regulatory data as a key tool of innovation policy and for refocusing the attention from patents to the existing regulatory framework. After detailed assessment of the exclusivity regime, the paper identifies key areas of improvement calling for reassessment so as to promote better functioning of the regime as an incentive for accelerated innovation. While economic and public health analysis necessarily provide final answers as to necessity of reform, this paper provides a legal perspective to the issue, appraising the current regulatory framework and identifying areas for further analysis.

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International audience

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Com o aumento constante de procura de recursos naturais por parte dos vários setores da sociedade é urgente encontrar soluções para reduzir o seu consumo sem se travar a expansão demográfica que se tem vindo a sentir nos grandes centros urbanos. É através da implementação de medidas de sustentabilidade e pelo aumento da eficiência de utilização desses recursos que se tem vindo a combater esta tendência cada vez maior de consumismo global, sendo isto apenas possível com a implementação de ferramentas tecnológicas avançadas que permitem estabelecer limites ao considerado eficiente e premiando, em termos financeiros e de imagem de marketing, as entidades que o alcancem. O LEED é um sistema de certificação de sustentabilidade voluntário de edifícios residenciais e comerciais que estabelece métricas de comparação de parâmetros indicadores de consumos energéticos, hídricos e de materiais em todo o ciclo de vida do edifício e que tem vindo a ganhar destaque em crescendo a nível mundial. Esta dissertação teve como objetivo comparar a performance de consumo energético no âmbito do sistema LEED com a do sistema de certificação energética de edifícios nacional (SCE) de um grande edifício de serviços, estabelecendo um paralelismo de semelhanças e diferenças entre os dois e de avaliar os efeitos de potenciais medidas de eficiência energética e seus efeitos nas classificações de mérito obtidas em cada sistema. Os resultados obtidos na simulação que permitiu avaliar a performance foi muito satisfatório, tendo sido aproveitado pela empresa para efeitos de certificação LEED do edifício em estudo.