This Master’s thesis evaluates the survey that mapped using management tools in contemporary practice. Respondents were senior and middle management of companies from the Czech Republic. They had to answer what they expect from the tools and what they think about the various claims concerning the parameters of the attractiveness of the market and competition. The survey was focused on portfolio analysis.

The diploma thesis aims at analyzing Miss Claire Ltd., a distributor of perfumes and cosmetic goods. The situation of external and internal environment is described based on Porter Value Chain, indicators of financial analysis, PESTE and SWOT matrix. GE model and BCG matrix serve as complementary tools. All suggested strategies fulfill SMART criteria as well as strategic goal of Miss Claire Ltd, which is achievement of profitability and stabilization of market position.

The diploma thesis "Marketing strategy of a company“which is divided into theoretical, analytical and design. The main objective of this thesis is to design a marketing strategy of the manufacturing company, focusing on key products and strengthen its position in the chosen market segment. The chosen strategy is built on identifying key product (the product or at least profitable product, which is losing market position), its detailed analysis and recommendations for appropriate development activities, including its location on the selected market. These outputs are also the basis for the formulation and determination of optimal strategic objectives and action steps to comply with this proposed strategy.

Bladder cancer is a potentially curable malignancy; however in regards to the state of current therapy regimens, a plateau has been reached in both the non-muscle and muscle invasive types. To obtain effective treatment, and consequently a decreased mortality, it has become imperative to test and understand aspects affecting therapy response. The aim of this thesis is to illustrate a better understanding of clinical factors affecting therapy response using new drug combinations and new tumor markers alongside established risk criteria. In Paper I we reported the 5 year follow up from a multicenter, prospectively randomized study and we evaluated the 5-year outcomes of BCG alone compared to a combination of epirubicin and interferon-a2b in the treatment of patients with T1 bladder cancer. Treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant Cis was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection. In Paper II &III we investigated the validity of emmprin, survivin and CCTα proteins as biomarkers for response and survival before neoadjuvant cisplatin chemotherapy. Bladder tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry (IHC). Patients in the chemotherapy cohort with negative emmprin and CCTα expression had significantly better overall survival (OS) than those with positive expression. In Paper IV primary end point was examining STMN1 as prognostic factor in bladder cancer.  Analysis was performed on three bladder cancer patient cohorts using IHC, western blot and a bladder cancer cell line. High levels of STMN1, expression correlated to shorter disease-specific survival and the growth and migration of the cells were significantly reduced when transfecting the cells with STMN1 siRNA. Conclusion Risk assessment and predictors of outcomes could help in individualized treatment and follow up.  Biomarkers will become more important for treatment choices in bladder cancer management.

Thesis (MScMedSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection without showing signs of illness. Steroid hormones such as glucocorticoids (GCs) however can lead to reactivation of TB. Currently two different injectable contraceptives are available in South Africa, medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET). MPA is able to bind to and activate the glucocorticoid receptor (GR) and possesses selective GC activity, a pharmacological characteristic absent in NET. The aim of this study was to investigate the immune modulatory effects of the two contraceptives MPA and NET on immune responses to mycobacteria in vitro and in vivo. Human peripheral blood mononuclear cells (PBMCs) were infected with BCG (M. bovis Bacille Calmette-Guérin) and treated with MPA, NET, progesterone or cortisol and cytokine expression was measured in order to determine whether the synthetic progestins mimic endogenous progesterone or the GC cortisol. MPA, but not NET suppressed the expression of IFN-γ, IL-1α, IL-1β, IL-2, IL-12p40 and IL-13 similarly to cortisol. Furthermore expression of miRNAs, small double stranded RNA molecules that bind to complementary sequences in mRNAs of target genes and cause their degradation, was determined under the different experimental conditions. The expression of several miRNAs including miR-30c, miR-222, miR-454 and miR-331-3p were differentially influenced by MPA, cortisol and/or NET in PBMCs stimulated with BCG. For example, BCG induced the expression of miR-454 (p=0.003) which was then inhibited to basal levels by cortisol (p=0.008), MPA (p=0.002) and NET (p=0.002). These results demonstrate that steroid hormones including the contraceptives MPA and NET can modulate immune responses to mycobacteria at the miRNA level. To determine the effect of MPA and NET on BCG-induced expression of miRNAs in vivo a mouse model was used. C57BL/6 mice were injected weekly with either MPA or NET using a dose equivalent to humans and then infected with BCG. Mice treated with MPA had a higher spleen bacterial load 21 days after infection compared to both NET treated and control mice (p=0.023). In whole blood, MPA and NET treatment suppressed the BCG-induced production of miR-100 and miR-509-3p to basal levels. In contrast to NET, MPA induced expression of miR-99a expression independent of BCG infection. In the lung, the site of disease, a total number of 22 out of 377 miRNAs tested were differentially expressed 21 days after infection. The results of this study indicate that both synthetic progestins altered the immune response to BCG at the level of cytokine expression as well as the miRNA level. MPA was found to mimic cortisol by inhibiting secretion of inflammatory cytokines whereas NET appeared to have more progestogenic properties. Each of the steroid hormones was observed to induce a characteristic miRNA expression profile, both in vitro as well as in vivo, although not identical. These results highlight that the two contraceptives – although used interchangeably by women in developing countries - are pharmacologically unique and differentially modulate immune responses to mycobacteria. These data support the urgent need for further research into the link between hormonal contraceptives and susceptibility to infectious diseases. / AFRIKAANSE OPSOMMING: Individue wat latent met Mycobacterium tuberculosis ( M.tb ) geïnfekteer is, onderdruk die infeksie en wys geen simptome van die siekte nie. Steroïed hormone soos glukokortikoïede (GKe) kan egter tot die heraktivering van TB lei. Daar is tans twee verskillende inspuitbare voorbehoedmiddels beskikbaar in Suid-Afrika, medroksiprogesteroon-asetaat (MPA) en noretisteroon enantaat (NET). MPA is staat om aan die glukokortikoïed reseptor (GR) te bind en dit te aktiveer. MPA beskik ook selektiewe GK aktiwiteit, 'n farmakologiese eienskap wat afwesig is in NET. Die doel van hierdie studie was om die immuun-regulerende effekte van die twee voorbehoedmiddels, MPA en NET, op immuunresponse teen mikobakterieë in vitro en in vivo te ondersoek. Menslike perifêre bloed mononukleêre selle (PBMSe) is met BCG geïnfekteer en met MPA, NET, progesteroon of kortisol behandel. Sitokien uitdrukking was gemeet om vas te stel of die sintetiese progestiene, endogene progesteroon of die GK kortisol naboots. MPA, maar nie NET, onderdruk die produksie van IFN-γ, IL- 1α, IL- 1β, IL- 2, IL- 12p40 en IL- 13 soortgelyk aan kortisol. Verder is uitdrukking van miRNAs, klein dubbelstring RNS molekules wat aan komplimentêre volgorde in mRNAs van teiken gene bind en wat hul degradering veroorsaak, bepaal in elk van die verskillende eksperimentele toestande. Die uitdrukking van verskeie miRNAs insluitende miR-30c, miR-222, miR-454 en miR-331-3p is differensieël beïnvloed deur MPA, kortisol en/of NET in PBMSe wat met BCG gestimuleer is. Byvoorbeeld, BCG veroorsaak die uitdrukking van miR-454 wat dan geïnhibeer word tot agtergrondvlakke deur kortisol, MPA en NET. Hierdie resultate toon dat steroïed hormone, insluitend die voorbehoedmiddels MPA en NET, die immuunrespons teen mikobakterieë op miRNA-vlak affekteer. Om die effek van MPA en NET op BCG-geïnduseerde uitdrukking van miRNAs in vivo te bepaal, is ʼn muismodel gebruik. C57BL/6 muise is weekliks met 'n dosis van MPA of NET, ekwivalent aan dosisse gebruik in die mens, ingespuit en met BCG geïnfekteer. Muise wat met MPA behandel is, het 'n hoër bakteriële lading in die milt 21 dae na infeksie in vergelyking met NET-behandelde muise en kontrole muise. In hul bloed, onderdruk MPA en NET behandeling die BCG-geïnduseerde produksie van miR-100 en miR-509-3p tot basale vlakke. In teenstelling met NET, induseer MPA die uitdrukking van miR-99a onafhanklik van BCG infeksie. In die long is 'n totaal van 23 miRNAs differensieël uitgedruk 21 dae na die infeksie. Die resultate van hierdie studie dui daarop dat beide sintetiese progestien die immuunrespons teen BCG verander op sitokien sowel as miRNA vlak. MPA boots hoofsaaklik kortisol na deur inhibering van sitokien-produksie terwyl NET meer progesterone eienskappe het. Op miRNA vlak veroorsaak elk van die steroïed hormone 'n kenmerkende miRNA uitdrukkingsprofiel, beide in vitro asook in vivo. Hierdie resultate beklemtoon dat die twee voorbehoedmiddels - alhoewel hulle afwisselend gebruik word deur vroue in ontwikkelende lande - farmakologies uniek is en differensieël die immuunrespons reguleer teen Mycobacterium. Hierdie data ondersteun die dringende behoefte aan verdere navorsing in verband met hormonale voorbehoedmiddels en vatbaarheid vir aansteeklike siektes.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

本文主要的研究目的，在於分析與探討自1994至2001年，製造業各產業發展的動態策略。利用各年版《中國統計年鑑》所提供的中國大陸自1993年至2001年期間，製造業28個產業別的實質工業增加值官方統計資料，再利用BCG矩陣做為分析架構。本文主要的研究發現為，在1994至2001年期間，菸草加工業、交通運輸設備製造業、電氣機械及器材製造業、電子及通信設備製造業為本文研究期間的明星型產業，也是帶動此一時期經濟高度增長的主要產業。機電、石化、交通等重點產業的高度發展，符合「八五」與「九五」計畫中產業政策的預期成效。然而，在產業政策中，希望能提升傳統能源、冶金、輕紡、一般加工業等骨幹企業的產業素質及技術，似乎仍有待加強。

電子高科技產業的全球市場變化快速，產業位移的趨勢已然成形，電子產業已進入成長動力趨緩的階段，且現今台灣電子產業面臨中國經濟趨緩、紅色供應鏈的威脅，使得台灣一直賴以為生的電子產業重挫，大家熟悉的電子產業已經不再亮眼。加上全球人口老化已成趨勢，醫療保健逐漸受到重視，生技醫療產業是目前最具投資價值的產業，由電子產業跨領域至生技，進而建立與醫管服務跨領域互補互利的合作機制，有機會發揮雙向連動國際行銷的效益。 生技產業是一個和電子產業完全不同的產業，電子產業為尋求快速獲利，商業模式就是降低生產成本，生技產業講究的是價值，並非以「量」取勝，價值經營遠大於成本控制。電子產業進入門檻低，產品變化快，電子產品生命週期往往都不到一年，而醫療產品剛好相反，進入門檻高，需要經過很多年的認證，但產品生命週期也很長。生技產業是一個資金、技術、專業相當密集的產業。 轉投資行為是企業在業務拓展或轉型的重要策略之一，轉投資與本業相關或非相關產業，分散經營風險並提升企業競爭力。本研究個案公司所處產業為印刷電路板產業，該產業在電子業中已是成熟產業，且外部環境深受中國紅色供應鏈的進逼，其供應鏈影響層面，不僅僅是台灣與中國大陸之間的問題，全球市場都有被中國大陸取代的威脅。公司在如此嚴峻的經營環境下，雖依然維持獲利，但營收卻無法突破成長，在財務資金方面，因本業成長趨緩，使得資金應用上保守穩健。本研究從產業的經營環境，再透過公司現況SWOT、財務狀況及公司各事業部門成長能力分析後，選擇轉投資電子非相關產業—生技產業。轉投資除了善用財務資源外，也藉由透過進入不同的產業領域，建立新的事業版圖尋求成長機會，使企業績效成長、永續經營下去。

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2015-05-06T18:11:47Z No. of bitstreams: 1 Luciana Trindade.pdf: 3487418 bytes, checksum: 8534f7bbe6d652914e76771ea1fd0451 (MD5) / Made available in DSpace on 2015-05-06T18:11:48Z (GMT). No. of bitstreams: 1 Luciana Trindade.pdf: 3487418 bytes, checksum: 8534f7bbe6d652914e76771ea1fd0451 (MD5) Previous issue date: 2015-02-23 / Leprosy remains a public health problem in Brazil. Despite the improvement in epidemiological indicators, case detection rate remains high in the country. Studies show that household contacts of leprosy patients are the group with the highest risk of developing the disease and the monitoring of contacts is among the priority actions for early diagnosis and control of disease in the country. General Objective: To evaluate the occurrence of leprosy among household contacts of patients diagnosed in 2012 in João Pessoa / PB. Method and sample: Observational study, crosssectional, whose population were household contacts of new leprosy cases diagnosed in 2012 in João Pessoa / PB. Research assistants conducted household interviews - using a pre-tested form containing the variables of interest - and they did physical examination of contacts, to search for lesions suggestive of leprosy and BCG scar. A descriptive analysis of all variables was made; the association between two qualitative variables was verified by the chi-square test; logistic regression models were applied to investigate possible risk factors; we adopted the 0.05 significance level. All ethical aspects were respected. Results: One hundred and ninety contacts related to 72 index cases were interviewed. The prevalence rate of leprosy cases among contacts was 9/191 people (4.7%). In the socioeconomic and demographic data, there was a female predominance (61.1%); the median age was 33 years; most were single (59.5%); nearly 85% had some degree of education; the most common race was white (52.6%); family income was between one and five minimum wages in almost 95% of households; the most common occupation was student (33.7%). In assessing contacts diagnosed with leprosy, leprosy borderline predominated (62.5%), multibacillary (87.5%) and the disability grade one (50.0%) were most common. On four occasions, the operational form was equal to the case and the contact. In the other, the contact showed a multibacillary, while the index case was paucibacillary. Sixty-three percent of the contacts mentioned were invited to attend the health unit, 52.1% attended and 52.4% were instructed to receive the BCG. The majority had some vaccination scar, and 73.1% had only one. Half of contacts who developed the disease had a BCG scar and the other half did not have any. Together, the factors associated with the risk of developing leprosy were the absence of vaccination with BCG and the chronic use of medications. Discussion and Conclusions: The incidence of leprosy among contacts was high and it was similar to that found by other authors. Failures were noted in the surveillance activities by health facilities. The control measures of contacts established by the Ministry of Health and the compatible strategies with local endemic variations and education of the population may bring an adequate coverage of contacts, improving detection and preventing disability and reducing the stigma related to diagnosis lateonset disease. / A hanseníase permanece como um problema de saúde pública no Brasil e, apesar da melhoria nos indicadores epidemiológicos, a detecção mantém-se alta no país. Estudos comprovam que os contatos intradomiciliares dos doentes constituem o grupo de maior risco de desenvolver a doença e a vigilância dos contatos está entre as ações prioritárias para o diagnóstico precoce e o controle da endemia no país. Objetivo geral: Avaliar a ocorrência de casos de hanseníase entre os contatos intradomiciliares dos pacientes diagnosticados em 2012, em João Pessoa/PB. Método e casuística: Estudo observacional, transversal, cuja população foram os contatos intradomiciliares dos casos novos de hanseníase diagnosticados no ano de 2012, em João Pessoa/PB. Assistentes de pesquisa realizaram entrevistas domiciliares - utilizando um formulário pré-testado, contendo as variáveis de interesse - e o exame físico dos contatos, buscando lesões sugestivas de hanseníase e cicatriz de BCG. Foi feita a análise descritiva de todas as variáveis; verificou-se a associação entre duas variáveis qualitativas pelo teste do quiquadrado; aplicaram-se modelos de regressão logística para averiguar possíveis fatores de risco; foi adotado o nível de significância de 0,05. Todos os aspectos éticos foram respeitados. Resultados: Entrevistaram-se 190 contatos relacionados a 72 casos índices. A prevalência de casos de hanseníase entre os contatos foi de 9/191 pessoas (4,7%). No perfil socioeconômico e demográfico, houve predomínio do sexo feminino (61,1%); a idade mediana foi de 33 anos; a maioria era solteira (59,5%); quase 85% apresentava algum grau de escolaridade; a raça mais comum foi a branca (52,6%); a renda familiar foi de um a cinco salários-mínimos em quase 95% das famílias; a profissão mais comum foi a de estudante (33,7%). Na avaliação dos contatos diagnosticados com hanseníase, predominou a forma clínica dimorfa (62,5%), a operacional multibacilar (87,5%) e o grau um de incapacidade física (50,0%). Em quatro situações, a forma operacional foi igual para o caso e o contato. Nas demais, o contato apresentou uma forma multibacilar, enquanto o caso índice era paucibacilar. Sessenta e três por cento dos contatos referiram que foram convidados a comparecer à unidade de saúde, 52,1% compareceram e 52,4% foram orientados a receber a BCG. A maioria apresentava alguma cicatriz vacinal, sendo que 73,1% apresentavam apenas uma. Metade dos contatos que desenvolveu a doença tinha uma cicatriz vacinal e a outra metade não apresentava nenhuma. Os fatores que, em conjunto, associaram-se ao risco de desenvolver a hanseníase foram a ausência da vacinação BCG e o uso crônico de medicações. Discussão e Conclusões: A ocorrência de hanseníase entre os contatos do estudo foi elevada e semelhante à encontrada por outros autores. Foram percebidas falhas nas ações de vigilância desenvolvidas nas unidades de saúde. As medidas de controle dos contatos estabelecidas pelo Ministério da Saúde, além de estratégias compatíveis com as variações locais de endemicidade e de escolaridade da população, poderão trazer uma cobertura adequada dos contatos, melhorando a detecção e prevenindo incapacidades e diminuindo o estigma relacionado ao diagnóstico tardio da doença.

Mycobacterium tuberculosis (Mtb), one of the major pathogens of mankind, kills approximately 2 million people each year. Mtb induces inflammation at the site of infection, leading to leakage of serum proteins, which in turn, are likely to come in contact with the pathogen, thus modulate the pathogenesis of tuberculosis. We studied some of these proteins such as surfactant protein D (SP-D), complement protein C1q and fibronectin, which are either produced locally or they leak-out from serum during inflammation, for their interaction with M.smegmatis and BCG. These non-pathogenic mycobacteria were used as model for Mtb. In this study, the recombinant form of truncated human surfactant protein D (rhSP-D) and three globular heads of human C1q (ghA, ghB, and ghC) were expressed in E.coli. The interaction of each of these proteins with mycobacteria and human monocytic cell line THP-1, was examined via ELISA. We demonstrated that rhSP-D, C1q, three globular heads of C1q and fibronectin bind with both mycobacteria and THP-1 cells. Moreover, using rhSP-D and globular heads of C1q, the binding of SP-D and C1q was localised to C-terminal globular regions. The direct effect for each of these proteins on mycobacterial growth, their effect on the uptake and intracellular fate of mycobacteria inside THP-1 cells were also investigated. Direct interaction of rhSP-D and C1q inhibited mycobacterial growth, whereas fibronectin interaction with the mycobacteria increased their growth. RhSP-D inhibited the uptake and growth of mycobacteria inside THP-1 cells, whereas C1q and each individual globular heads of C1q enhanced the uptake of mycobacteria by THP-1 cells. However, C1q protein inhibited BCG growth but enhanced M.smegmatis growth inside these cells and the later activity was localised to ghA. Fibronectin increased the uptake and growth of mycobacteria inside THP-1 cells. Examining the gene expression of inducible nitric oxide synthase, pro-inflammatory and anti-inflammatory cytokines produced by THP-1 cells infected with the proteins treated and untreated mycobacteria, along with cytokine neutralization experiments, suggest that the nitric oxide components and cytokines could be responsible for mycobacterial growth control inside THP-1 cells. These novel and interesting functions of SP-D, C1q, and fibronectin on mycobacteria provide an insight into the modulatory function of these proteins on Mtb infection, and, therefore, in the pathogenesis of tuberculosis.