The specialised nature of the stratum corneum makes it an efficient barrier to foreign substances, including drug molecules. Therefore, cutaneous drug absorption is a slow and complex process of which stratum corneum penetration is the rate limiting step. The rate and extent of stratum corneum penetration by a drug compound depends greatly on the presence of penetration enhancing/retarding excipients and therefore the clinical outcomes of a product rely greatly on the components and quality of the formulation. Hence, establishing bioequivalence between topical products is crucial to ensure that patients receiving multisource drug products are assured of the same efficacy and safety as the brand product. Since locally acting topical formulations do not target the systemic circulation, conventional methods of assessing bioequivalence using plasma levels are not appropriate. Consequently, the current regulatory guidelines require comparative clinical trials to be carried out to show bioequivalence between topical products. As these studies are very expensive and time consuming, the development of a more direct and relatively rapid and inexpensive method for determining bioequivalence between topical products is required. Clotrimazole is an anti-fungal agent where the target site of action is in the stratum corneum. In this work, tape stripping, which involves the sampling of stratum corneum, was investigated as a tool for the determination of bioequivalence between topical clotrimazole products. The tape stripping method involved the analysis of each tape strip individually and standardization of stratum corneum thickness between subjects was carried out using TEWL measurements. This approach provided detailed information regarding the amount of clotrimazole present in the stratum corneum as well as the extent of drug penetration. Prior to the tape stripping studies an HPLC method was developed for the quantitative analysis of clotrimazole from the tape strip samples. This method was shown to be accurate and reproducible across the required range. It was also shown to be selective for clotrimazole in the presence of possible interfering substances such as those present in the tape adhesive and also skin components. The bioequivalence studies were conducted using a single “uptake” time point. In order to determine an appropriate dose duration for these studies a novel approach was employed, involving a preliminary dose duration study. For the bioequivalence investigations, Canesten® Topical cream was used as both test and reference products to determine if the method was capable of showing bioequivalence. Subsequently, Canesten® Topical cream was also compared to a 1% gel formulation to determine if the method could detect formulation differences. The conventional BE limits of 0.8 – 1.25 were used for the assessment of BE, however, the clinical relevance of using these limits for dermal studies is debatable since they are derived from oral pharmacokinetic studies. Therefore, the data from the tape stripping investigations were also assessed using more realistic limits of 0.75 – 1.33 and even 0.7 – 1.44. In addition to the tape stripping studies a novel method of determining the amount of drug present in the stratum corneum, the “Residual Method”, was investigated. This method involved assaying the amount of clotrimazole found in the residual formulation after a specified dose duration had elapsed and subtracting that amount from the amount of clotrimazole initially applied. The results of tape stripping investigations showed that, if the study is sufficiently powered, tape stripping may be used to determine bioequivalence according to the conventional limits, as well as possibly detect formulation differences between different clotrimazole products. Bioequivalence assessment using the widened intervals showed that fewer subjects were required to achieve a sufficient statistical power. The variability associated with this method was acceptable and tape stripping may therefore have the potential to be used as a BE tool in a regulatory setting for clotrimazole or other antifungal topical formulations. The “Residual Method” also showed promising results as a bioequivalence tool, but further investigation and extensive validation of this method is required before it can be suggested as a regulatory method. The results of these studies have clearly indicated that tape stripping has the potential to be used as an alternative to comparative clinical trails for the assessment of bioequivalence between clotrimazole formulations and also to assess bioequivalence between other antifungal products.

Microbes usually live in large communities, where they interact with other organisms and species. These interactions include cooperation, when individuals facilitate each others growth and reproduction. Such cooperation has been for instance observed within pathogens in the process of infection. Therefore, given the number and the frequency of infectious diseases, understanding the nature and the dynamics of microbial cooperation may be a crucial step in modern medicine. Microbes often secrete costly enzymes which extracellularly metabolise resources available in the environment. This external metabolism is a form of ’public good cooperation’, in which individuals invest their energy in producing ’public goods’, available to other organisms. To study this phenomenon we deploy mathematical models which are based on biologically relevant assumptions. Our models not only aim to capture the dynamics of studied microbial communities, but also to remove the natural complexity arising in the empirical studies and thus to provide a mechanistic understanding of their results. We first recover and explain the recent empirical finding, about mixed strain infections, showing that an addition of a low virulent strain which does not produce public goods (termed ’cheat’) may counter-intuitively enhance the total population virulence. What drives this result turns out to be an interaction of two different cooperative traits and the presence of spatial structure. Next we study the competition between the strains that do and do not produce public goods. Our results depend on environmental conditions, such as resource concentration and population density, but they are also determined by the degree of spatial structure - the ecological trait which so far has been treated only as a binary variable. Finally, we identify some environmental threats for the external metabolism feeding strategy, and we examine its competitiveness in comparison to ’internal metabolism’, in which the costly enzymes are private.

O fenômeno de sândi vocálico externo apresenta três realizações possíveis: a elisão, a degeminação e a ditongação. Este trabalho tem como proposta analisar o fenômeno de ditongação como processo de resolução de hiato em fronteira de palavras (camisa usada ~ cami[zaw]sada), baseado na amostra da cidade de Lages, em Santa Catarina, incluída no banco de dados do projeto VARSUL (Variação linguística na região sul do Brasil). O embasamento teórico se apoia em Bisol (1996, 2002 e 2005) para a descrição do processo; em Labov (2008) para fundamentos de teoria da variação; além de teorias fonológicas, como Fonologia Prosódica e Fonologia Lexical. Os objetivos específicos são os que seguem: a) identificar, em nossa amostra, fatores linguísticos que possam favorecer ou bloquear a aplicação da ditongação como processo de sândi externo; b) a partir dos resultados obtidos, corroborar ou não resultados de pesquisas já realizadas a respeito deste processo; c) ampliar a compreensão do fenômeno e oferecer subsídios para uma descrição geral do processo do sândi externo e do português falado no sul do Brasil. As hipóteses que procuramos confirmar são as seguintes: a) quanto à tonicidade, o contexto ideal para a aplicação da ditongação é o de atonicidade máxima (casa escura ~ ca[zaj]scura) (conforme Bisol, 1996; Bisol, 2002); b) o contexto interno à frase fonológica é mais favorecedor na aplicação do fenômeno (velho exemplo ~ velh[we]zemplo) (conforme Bisol, 1996). A análise estatística dos dados foi realizada pelo pacote de programas VARBRUL/GoldvarbX. A amostra, constituída de 16 informantes, mostrou, dentre outros fatores, que a ditongação crescente e a ditongação decrescente têm diferentes contextos favorecedores em relação ao acento e à categoria das vogais e têm contextos favorecedores semelhantes em outras variáveis em comum. Para a ditongação, confirmamos nossas hipóteses: a atonicidade máxima e o contexto interior à frase fonológica se mostraram favorecedores. A seleção das variáveis relevantes não foi idêntica para as duas realizações. / The external vowel sandhi phenomenon presents three possible ways of realization: the elision, the degemination and the diphthongization. This work analyzes the diphthongization phenomenon as a gap resolution process in words boundary (camisa usada ~ cami[zaw]sada) based on the sample of the city of Lages, Santa Catarina, included in the project database VARSUL (linguistic variation in southern Brazil). The theoretical basis is Bisol (1996, 2002 and 2005) for the description of the process; Labov (2008) for the variation theory fundamentals; and Brescancini (2005) for variational research methodology. The specific objectives are the following: a) to identify, in our sample, linguistic factors that may favor or block the application of external vowel sandhi processes; b) from the results obtained, to prove or disprove results of previous studies regarding this process; c) to increase the understanding of the phenomenon and provide support for a general description of the process of external sandhi and Portuguese spoken in southern Brazil. The hypotheses we intend to confirm are the following: a) the ideal context for the three external sandhi processes is an unstressed vowel + an unstressed vowel (casa escura ~ ca[zaj]scura) (as Bisol, 1996; Bisol, 2002; Ludwig-Gayer, 2008; Vianna, 2009); b) the internal context to phonological phrase is more favorable to the application of the phenomenon (velho exemplo ~ velh[we]zemplo) (as Bisol, 1996). Statistical analysis of data was performed by VARBRUL / GoldvarbX software. The sample consisted of 16 informants showed that rising diphthongization and decreased diphthongization have different favorable contexts related to stress and vowel category, and they have similar favorable contexts in same variables. Related to diphthongization, we confirmed our hypotheses: the sequence of unstressed vowels and the phonological phrase are favorable to the process. The selection of the variable was not exactly the same for both processes.

Federal downsizing and reduced appropriations within the USDA Forest Service (USFS) have resulted in increased use of partnerships to deliver visitor services. Partnerships are the relationships in which two or more parties combine resources (e.g., funds, labor, information, skills) to accomplish a shared objective. Examples of USFS recreation partners include individual volunteers, professional contractors, and concessionaires. Partnerships provide a variety of services that may be otherwise neglected with fiscal constraints; for example, campground hosts, trail maintenance crews, and specialized recreation outfitters and guides provide visitor services the public desires. Although previous studies and USFS Accomplishment Reports indicate that partners are being used to deliver recreation services, there is a lack of understanding concerning the structure and function of these relationships. This thesis presents data from the second phase of a multi-phase study exploring the role of recreation partnerships on national forests. Using grounded theory, Phase I gathered and analyzed semi-structured interview data with key informants (n = 21). From these interviews, a conceptual framework of USFS recreation partnerships evolved, and internal commitment to partnerships and the external environment of forests emerged as indicators of agency capacity to partner. Internal commitment was defined by the presence, or lack of, a partnership coordinator on the forest. External environment was characterized by geographical location with urban forests, rural forests and amenity forests typifying various levels of partnership access for forest personnel. Phase II investigated these themes of commitment and environment using a multiple-case study methodology. Interviews with USFS personnel (n = 45) on six national forests representing a variety of internal commitment and external environment scenarios enabled the refinement of the partnership conceptual framework and indicators of agency capacity to administer partnerships. Specifically, this study illustrated that personnel motivations also influence agency capacity to partner. Fifteen distinct motivations emerged from informant interviews, which were classified within three categories of motivations: interpersonal, intrapersonal, and institutional. Together these themes of agency capacity--commitment, environment, and motivation--describe six unique cases of partnership involvement. These findings enable an increased awareness of agency capacity to partner and may enhance the leadership support, agency-partner interactions, and personnel motivations necessary to sustain USFS partnerships.

No description available.

No description available.

Within team sports, coaches aim to improve physical preparation by optimising the training process specific to competition. Unfortunately, at the elite level of wheelchair rugby (WCR) evidence-based information to guide this process is currently lacking. The present thesis investigates measures of external load during elite competition and explores whether this can be translated to inform current training practices. The first study established the suitability of a radio frequency-based, indoor tracking system (ITS) for the collection of movements specific to WCR. Minimal relative distance errors (< 0.2%) were seen across different sampling frequencies. Peak speed displayed the greatest relative error in 4 Hz tags (2%), with significantly lower errors observed in higher frequency tags (< 1%). The ITS was therefore deemed an acceptable tool for quantifying external load specific to WCR using a sampling frequency of 8 or 16 Hz. The external demands of elite competition were determined in Chapters 4 and 5. Notable differences in the volume of activity were displayed across the International Wheelchair Rugby Federation (IWRF) classification groups. However, the specific positional requirements of low-point (LP) and high-point players (HP) appeared to influence the intensity of external load (Chapter 4). Chapter 5 extended this work and established that peak speed and the ability to perform at high-intensities were best associated with successful mobility performance in WCR, as defined by team rank. This was further shown to be roledependent, whereby high-ranked HP players achieved greater peak speeds and performed more high-intensity activities (HIA) than respective lower-ranked players. Comparisons between the current external demands of training were then compared to that of competition (Chapter 6). Conditioning drills were shown to exceed the demands of competition, irrespective of classification. Notable differences in skill-based and game related drills were displayed across player classifications, whereby both were shown to be roledependent. Although game-simulation drills provided the best representation of competition, the duration appeared important since this factor influenced the results (Chapter 6). When the format of these drills were further modified (Chapter 7), drills containing fewer players increased the volume and intensity of training, specifically in HP. Whilst a 30-second shotclock elicited no changes in external load, differences were revealed when the shot-clock was further reduced to 15-s. Coaches can therefore modify the external training response by making subtle changes to the format of game-simulation drills. This thesis revealed that functional classification and positional-role are key factors during competition, and training should therefore be structured with this in mind. Conditioning drills can be used to elicit a progressive overload in the external responses, whilst game-simulation drills can provide the best representation of competition. Given the importance of gamesimulation drills, the combination of different formats throughout training sessions are critical in order to maximise the preparation of elite WCR players.

Made available in DSpace on 2014-06-11T19:24:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-08-17Bitstream added on 2014-06-13T18:52:05Z : No. of bitstreams: 1 mendes_smf_me_arafcl.pdf: 324785 bytes, checksum: a944d87285a748dffda18169f9d24b65 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O comércio internacional do setor têxtil-vestuário foi caracterizado pela existência de acordos comerciais, os quais estipulavam cotas às exportações dos países fornecedores, até dezembro de 2004. Janeiro de 2005 foi marcado pelo fim do Acordo de Têxteis e Vestuário (ATV), com a eliminação das restrições quantitativas e a integração do comércio de produtos têxteis e confeccionados às regras da Organização Mundial do Comércio (OMC). Esta dissertação tem como objetivo geral analisar os impactos do fim do sistema de cotas sobre o comércio realizado entre os principais mercados consumidores (Estados Unidos e União Européia) e os países em desenvolvimento no período 2005-2006. Em particular, são identificados os principais impactos sobre o setor têxtil-vestuário brasileiro. As conclusões mostram que os países desenvolvidos continuam a buscar novas formas de proteger suas indústrias domésticas, o que prejudica interesses comerciais e os ganhos esperados por alguns países em desenvolvimento. No breve período pós-ATV, o que se observou foi a redução das exportações dos países próximos a EUA e UE e o aumento das exportações de países geograficamente mais distantes, em especial, países menos desenvolvidos. Além disso, a China tem apresentado um significativo aumento de suas exportações de artigos têxteis e confeccionados no total das exportações mundiais. No Brasil, os impactos do fim do ATV foram pouco sentidos pela ótica das exportações. Uma pesquisa realizada a partir de cinco grandes empresas brasileiras do setor mostrou que iniciativas efetivas em direção à expansão para o mercado externo ainda são pontuais. Entretanto, as importações brasileiras de produtos oriundos principalmente da China têm aumentado e a estratégia adotada pelo governo brasileiro tem sido de caráter defensivo, via aumento das barreiras tarifárias. / The international trade of the textile and clothing sector was characterized by the existence of trade agreements, which stipulated quotas to the exports of the suppling countries, until December 2004. January 2005 was marked by the end of the Agreement on Textiles and Clothing (ATC), together with the elimination of the quantitative restrictions and the trade integration of the textiles and apparel products into the World Trade Organization (WTO) rules. The general objetive of this dissertation is to analyse the impacts of the end of the quota system on the trade between the main consumer markets (United States and European Union) and the developing countries during the period 2005-2006. Particularly, the prime impacts on the Brazilian textile and clothing sector are identified. The conclusions show that the developed countries continue to look for new forms of industrial protection, which is harmful to the comercial interests and expected gains of some developing countries. In the brief period post-ATC, it was noted the reduction of the exports from countries near US and EU and the elevation of the exports from countries geographicaly distants, specially the least developed countries. Besides this, China has been strongly increasing its textile and clothing exports in the total world-wide exports. In Brazil, the impacts of the end of ATC have been small on the export side. A research carried through five great Brazilian entreprises of the sector showed that effective initiatives towards the expansion to the external market are still prompt. However, the Brazilian imports of products coming specially from China have been increasing and the strategy adopted by the Brazilian government have been defensive, by way of raising the tariff barriers.

AbstractTitleEntry mode decision for Swedish business-to-business firms internationalizing to India. AuthorsJesper Mårtensson, Joep van den BrinkSubjectMaster Thesis in International Marketing KeywordsInternationalization, Entry Mode, BRIC-markets, Internal &amp; External Factors, Effectuation &amp; Causation. Question(s)How do internal and external factors influence the entry mode decision for Swedish business-to-businessfirms internationalizing to India?How can the entry mode decision process be characterized for Swedish business-to-businessfirms when internationalizing to India?How does the entry mode, used by Swedish business-to-business firms in India, follows the Transaction Cost Approach to entry modes and the Resource Based Approach to entry modes?PurposeThe purpose of this study is to get a deeper understanding of how internal and external factors influence the entry mode decision forSwedish business-to-business firms that internationalize to India. Furthermore, the study aims at bringing in a process-based view of the entry mode decision literature.The study also aims to investigate entry modes used in India to see how it followsthe recommendations of the transaction cost and the Resource Based explanation to entry mode choice. MethodQualitative multiple case study consisting of three cases. The data was collected through personal interviews. The cases have been analyzed using a within-case analysis and a cross-case analysis.ConclusionThe findings of our study show that firms evaluate just a few internal and external factors when internationalizing to India. As can be derived from our study, the product has an importantinfluence on the entry mode decision for the investigated firms. The more standardized a product is, the easier it is to penetrate the Indian market using low-control entry modes. The higher the complexity of the product, the more knowledge is required from the firm and thus, the higher the likelihood for a firm to internationalize to the Indian market using high-control entry modes. It is also shown that firms tend to rely on earlier experiences when internationalizing to India, whereas this could limit the firms for choosing the right entry mode. Furthermore, the specific market barriers for the Indian market have an influence on the entry mode decision as well. It is also found that firms that have a causational approach to foreign entry mode will not allow for a rapid switch in the level of foreign involvement before they have reliable information as a base for the decision. The firms with an effectual approach made their entry mode decision based on selecting an entry mode with low resource commitment, seeing their achieved turnovers in India as a bonus. / Master in International Marketing

Resumo: Na indústria metal-mecânica um dos geradores de riqueza mais importantes da atualidade, o uso do fluido de corte, por exemplo, indispensável nas operações de usinagem e um poluente em potencial, tem sido constantemente estudado para que seja substituído, utilizado na mínima quantidade possível ou mesmo abolido do processo, visando diminuir ou zerar o impacto ambiental, sem afetar a qualidade e o volume de produção de tais operações. Dentre as alternativas, destacam-se a usinagem a seco e a utilização a mínima quantidade de lubrificante (MQL). Este último, que é a pulverização de uma quantidade mínima (10 a 100 ml/h) de óleo integral em um fluxo de ar comprimido, também pode ser utilizado, em alguns casos, com o lubrificante misturado em água (MQL/Água) e pulverizado na mesma quantidade (10 a 100 ml/h) no fluxo de ar comprimido, diminuindo ainda mais o volume de óleo aplicado. Este estudo tem por objetivo analisar o comportamento da técnica de mínima quantidade de lubrificante (MQL) com três proporções de água/óleo (1:1; 1:3 e 1:5) no processo de retificação cilíndrica externa de mergulho, em cerâmicas, com rebolo diamantado e compará-lo ao comportamento das técnicas da MQL tradicional e lubri-refrigeração convencional. O estudo foi feito através da análise e avaliação das variáveis de saída do processo de retificação de mergulho: rugosidade, desvio de circularidade, desgaste diametral do rebolo e microscopia eletrônica de varredura (MEV). Diante da análise dos resultados alcançados pode-se afirmar que, no geral, para os valores obtidos das variáveis de saída, nas condições citadas, os de MQL/Água são satisfatórios em relação às demais condições ensaiadas. A média dos valores de rugosidade do MQL/Água (1:1) foi cerca de 35% maior que a convencional e 20% menor que a MQL tradicional. / Abstract: In the metalworking industry, one of the most important generators of wealth today, the use of cutting fluid, for example, essential in machining operations and a potential pollutant, has been constantly studied to be replaced, used in minimum amount possible or even abolushied from the process, aiming to reduce the environmental impact or zero it, without affecting the quality and production volume of such transactions. Among the alternatives, we highlight the use of dry machining and minimum quantly of lubricant (MQL). The latter, which is the spraying of a minimum amount (10 to 100 ml/h) full of oil in stream of compressed air, can also be used in some cases, the lubricant mixed with water (MQL/Water) and sprayed in the same amount (10 to 100 ml/h) in the flow of compressed air, further reducing the volume of oil applied. This study aims to analyze the behavior of the technique of minimal amount of lubrificant (MQL) with three ratios of oil/water (1:1, 1:3 and 1:5) in the process of cylindrical grinding diving in ceramics, with diamond wheel and compare it to be behavior of the techniques of traditional and MQL conventional lubridification and cooling. The study was done by examining and evaluating the output variables of the grinding process outside of diving: roughness, roundness deviation, diametral wear of the grinding wheel and scanning electron microscopy (SEM). Before the analysis of results, can be stated that, in general, for values of output variables, in the mentioned conditions, the MQL/Water are safisfactory in relation to the other conditions tested. The average roughness values of the MQL/water (1:1) was about 35% higher than the conventional and 20% less than the Traditional MQL. / Orientador: Eduardo Carlos Bianchi / Coorientador: Anselmo Eduardo Diniz / Banca: Carlos Alberto Fortulan / Banca: Gilberto de Magalh B. Gonçalves / Mestre