No description available.

Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease characterized by autoantibody production and an activated type I interferon system. Cardiovascular disease (CVD) is as a major cause of morbidity and mortality. The aim of this thesis was to identify genetic risk factors for CVD in SLE. The role of T cells in regulation of the interferon-α (IFNα) production by plasmacytoid dendritic cells (pDCs) was also investigated.    In paper I, a thicker intima, thinner media and increased intima/media ratio was found in young premenopausal women with SLE compared to healthy controls indicating increased cardiovascular risk. As traditional ultrasound assessment of the common carotid intima-media thickness (CCA-IMT) in SLE has given conflicting results separate measurement of the intima and media can be a useful tool to identify SLE patients at increased risk of CVD.    In paper II, an association was demonstrated in SLE between a STAT4 risk allele and ischemic cerebrovascular disease and presence of anti-phospholipid antibodies (aPL). The association remained after adjustment for traditional CVD risk factors. A possible mechanism for this association is that the risk allele leads to increased production of aPL, which promotes thromboembolism.    In paper III, a genetic locus in IRF8 was identified to be associated to coronary heart disease (CHD) in SLE. The association remained after adjustment of other CHD risk factors.  Patients with the IRF8 risk variant had increased CCA-IMT, more carotid plaques and reduced frequency of circulating B cells. Weaker binding of nuclear protein to the risk allele was demonstrated, suggesting a regulatory function of the IRF8 risk variant.    In paper IV, activated T cells were found to strongly enhance the IFNα production by pDC stimulated with RNA-containing immune complexes via GM-CSF and IL-3. Activated SLE T cells enhanced the IFNα production to the same extent as T cells from healthy controls. This finding together with previous observations in SLE of increased levels of GM-CSF and IL-3 suggests that T cells contribute to the activated type I interferon system in SLE.    In conclusion, this thesis demonstrates that genetic predisposition is important for CVD in SLE and describes a new role for T cells in the pathogenesis of SLE.

Dendritic cells (DC) are antigen-presenting cells that are critical for the initiation and regulation of the immune response. Several DC subtypes within mouse spleen have previously been characterised and these include the plasmacytoid (pDC), and conventional DC (cDC) of the CD8+ and CD8- subtypes. Each subtype appears to have a specialised role in the various arms of immunity and tolerance. Less clear is the process by which these DC develop from haematopoietic precursors, of the precursor stages and branch points from bone marrow (BM) stem cells to each of the peripheral DC subtypes. The research described herein had the aim of identifying and isolating some of the intermediate precursors of DC, downstream of stem cells, and determining whether these differed in the steady-state versus inflammation. Particular was given to DC of the spleen. Experiments that sought the identity of such precursors involved both i) transfer of cell fractions that contained DC precursors into steady-state or inflamed recipient mice to assess their in vivo development at later times, and ii) analysis of an in vitro culture system to question whether it reflected development of the steady-state DC subtypes.

Information system projects are gaining immense popularity among the manufacturing organisations across the globe. Due to the challenges associated with the information system project management with the manufacturing organisation, organisations have started focusing on technology-oriented solutions such as Information system (IS) projects. However, the success or failure of these projects is ultimately dependent on a range of critical success factors. The purpose of the research was to investigate the Critical Success Factors (CSF) in an Information System (IS) project using the case of Wartsila, a manufacturing organisation operating in marine and energy sector. For this purpose, a qualitative research method was adopted with semi-structured interviews carried out with the IT manager, the Integration Manager (Int. M), and the project teams involved in the project. Thematic analysis, which was chosen as the appropriate data analysis method, assisted in the identification of several codes that were categorized and finally guided to the extraction of seven (7) key themes. A conceptual framework was drawn from the secondary literature review containing CSF within the two major categories such as subjective and objective CSFs. The set of subjective CSFs included project management and team member, commitment and management support, training, change management perceptions, communication, and project planning and management. On the other side, the set of objective CSFs included the process of redesigning, technological difficulties in system design, costs, time engineering, and quality.   These literature-based factors were simultaneously analysed by the responses of the interviewees, ultimately ending up in the development of a modified and comprehensive framework for the manufacturing organisation. The findings revealed the significance of subjective factor in shaping the accomplishment of objective factors, drive the project towards the success. These findings have further recommended the need for culturally sensitive ‘training’ and integration of formal and informal ‘communication’ methods for the success of the projects in the manufacturing organisations.

An Enterprise Resource Planning (ERP) system implementation is a massive undertaking for any organization, and we have all heard about success and failure stories. This research study has identified the Critical Success Factors (CSF) after a successful ERP system upgrade at a pharmaceutical distribution company. The company of interest stores and distributes pharmaceuticals to pharmacies in Finland and Sweden. The company used an old version of the ERP system from 1999 that had been heavily modified over the years to cater for new regulations, business and customer requirements. The upgrade was a complete success, and the new version of the ERP system has been running without major issues ever since go-live in autumn 2016. The qualitative interpretive research was conducted by using two data collection methods, semi-structured interviews and card sorting to gather data from the participants. The participants were selected from the three (3) central roles in the project team to capture the perceived CSFs from several perspectives. The data was a subject for a thematic analysis process to generate codes, themes, and concepts within the extensive data set. The findings revealed that the reasons for the upgrade were the end of support for the ERP system, need for new features and to reduce platform dependency. The participants regarded a stable system after go-live with minimal impact on business and harm to customers as the primary definition of success. The ten (10) identified CSFs were; (1) Top management commitment and support, (2) Software analysis, testing and acceptance control, (3) Project team leadership, empowered decision makers, (4) Project management and (5) Strategy planning, scope and vision, (6) Involvement of end-users and stakeholders, (7) Data conversion and integrity, (8) Consultant selection and relationship, (9) Balanced team and (10) Project team: the best and brightest. Even though the ERP upgrade at the pharmaceutical distribution company was considered a success, there were several areas identified for improvements. The lessons learned was for example related to data quality and test data. The need to introduce new resources by learning from key resources before and during the ERP project. The project model and project organization were other areas that were identified for improvements to reduce administrative work and to obtain a better fit towards the company organization. Several similar ERP system upgrades and new implementations are planned the coming years, and the outcome of this thesis provides valuable guidelines and recommendations to the company. The research thesis will also contribute to the field of CSF analysis and ERP systems and offer suggestions for further research.

Finding an indicator that can point to a high risk group for suicide has long been a desirable aid for the prevention of completed suicides. The studies reviewed in this essay presume that a biological aspect can point out the high risk individual. The focus of the studies lies on the serotonin 5-hydroxytryptamine (5-HT) monoamine neurotransmitter and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) which is the principal metabolite of 5-HT in depression. The studies on 5-HT metabolites have led to the belief that these may play a key role in the neurochemistry of suicidal behaviour. It is suggested that the core behavioural effect of low CSF 5-HIAA concentration might result in an increase in impulsive and violent behaviour to self and others. The predictability is based on the fact that patients with low CSF 5-HIAA are more prone to reattempt and complete suicide by violent means. A number of well-designed studies concerning suicidal individuals and control subjects have however not shown any difference in concentration of CSF 5-HIAA in suicide attempters compared to non-suicide attempters which could be explained by methodological flaws. Low CSF 5-HIAA does seem to characterize the high risk individual, but it is not yet determined what role it plays in actual suicidality.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-07T13:12:44Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Fatores Críticos de Sucesso na Aderência de Processos de Negócio de ERP às Organizações do Setor Público - Julliane Mágero.pdf: 2612858 bytes, checksum: ac5ae5d0b64ccb5859bf1434a201a7f7 (MD5) / Made available in DSpace on 2016-04-07T13:12:44Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Fatores Críticos de Sucesso na Aderência de Processos de Negócio de ERP às Organizações do Setor Público - Julliane Mágero.pdf: 2612858 bytes, checksum: ac5ae5d0b64ccb5859bf1434a201a7f7 (MD5) Previous issue date: 2015-08-20 / A implantação de sistemas integrados de gestão (ERP) juntamente com a Gestão de Processos de Negócio (BPM) têm se tornado uma expressiva abordagem para aumentar a eficiência e eficácia dos serviços prestados pelas organizações, especialmente as instituições públicas. Contudo, a implantação de sistemas ERP é um processo complexo e de alto risco para as empresas, as quais tem o BPM como ferramenta essencial de apoio para identificar a aderência dos requisitos de negócios específicos da instituição em relação aos requisitos funcionais do ERP. Sendo assim, o objetivo dessa pesquisa é analisar os desafios envolvidos na aderência dos processos de negócio de um ERP administrativo no setor público, com a proposta de identificar os fatores que são críticos para o seu sucesso, sob a ótica dos patrocinadores, líderes, analistas de negócio e usuários. Para compreender este problema a partir de uma perspectiva prática, foi realizado um estudo de caso exploratório em uma instituição pública de ensino superior que está implantando um sistema ERP. Foram realizadas entrevistas, observações e análise documental para coletar os dados, que foram analisados posteriormente. O estudo de caso exploratório propiciou a identificação dos fatores críticos de sucesso que influenciam, como facilitadores ou barreiras, na implantação dos sistemas integrados de gestão. Assim, a realização desse estudo e os resultados encontrados colaboraram para o aumento do conhecimento sobre quais os fatores influenciam na fase de aderência durante a implantação de um ERP, possibilitando a mitigação dos possíveis impactos negativos. / The implementation of integrated management systems (ERP) together with the Business Process Management (BPM) has become an expressive approach to increase the efficiency and effectiveness of services provided by organizations, especially public institutions. However, the implementation of ERP systems is a complex and risky process for companies, which have the BPM as an essential support tool to identify adherence to the specific business requirements of the institution in relation to functional ERP requirements. Thus, the objective of this research is to analyze the challenges involved in adherence of the business processes of an administrative ERP in the public sector, with the purpose of identifying the factors that are critical to its success, from the perspective of sponsors, leaders, business analysts and users. To understand this issue from a practical perspective, an exploratory case study was conducted in a public institution of higher education that is implementing an ERP system. Interviews were conducted, as well as observations and documental analysis for data collection, which were analyzed later. The exploratory case study led to the identification of critical success factors that influence as facilitators or barriers in the implementation of integrated management systems. Thus, the realization of this study and the results obtained contributed to increase the knowledge about which factors influence the adherence phase when deploying an ERP, enabling the mitigation of possible negative impacts.

Desenvolveram-se métodos bioanalíticos para determinação de anfotericina B e fluconazol em apenas 200 L de plasma e líquor (LCR) através da cromatografia líquida de alta eficiência (CLAE UV-VIS). A anfotericina B foi determinada através de CLAE-VIS utilizando p-nitrofenol como padrão interno, após purificação das matrizes biológicas com acetonitrila, seguida da análise em coluna Nova Pak C18 (150 x 3,9mm, 4 micron) e fase móvel constituída por tampão acetato 0,1M pH 5,0 e acetonitrila (50:50,v/v) 0,5mL/min em 385nm; o tempo de corrida foi 15 min. Através da validação o método mostrou-se robusto com 0,2-25,0 µg/mL(linearidade, r2 0,9999), LD 0,1 µg/mL, precisão (5,4% e 6,9%), exatidão expressa através do erro sistemático (3,3% e 2,2%): intra e interdias). Os estudos de estabilidade evidenciaram 1,0% para o erro sistemático e 3% de precisão na bandeja (tempo e condição de análise por 24 h), e os ciclos de congelamento evidenciaram boa estabilidade uma vez que todos os ensaios foram realizados em Laboratório de luz amarela. O fluconazol foi determinado através de CLAE-UV utilizando carbamazepina como padrão interno, após purificação das matrizes biológicas pela extração líquido-líquido com diclorometano em meio alcalino, seguido da análise em coluna Nova Pak C18 (150 x 3,9mm, 4 micron) e fase móvel constituída por água UP e acetonitrila (70:30,v/v) 0,5mL/min em 210nm; o tempo de corrida foi 15 min. O método mostrou-se robusto com 0,2-250 µg/mL(linearidade, r2 0,9998), LD 0,1µg/mL, com boa recuperação absoluta (98%) e relativa (100%), precisão 0,5%/1,3%, exatidão expressa através do erro sistemático (1,2%). Evidenciou-se ótima estabilidade para os extratos em bandeja (tempo e condição de análise por 24 h), na longa duração (20° C, 9 meses) e através dos ciclos de congelamento. Investigaram-se 21 pacientes adultos de ambos os sexos portadores de meningite criptocócica com AIDS após internação emergencial em terapia de alta dose com anfotericina B (1mg/Kg) e fluonazol (400 mg, 12/12 horas) durante 12 semanas. O monitoramento das concentrações de anfotericina B e fluconazol no plasma e no LCR forneceram as razões que permitiram estimar a penetração dos antifúngicos no SNC. Obtiveram-se concentrações de anfotericina B, médias (IC95%): 2,30 (0,02-5,08) µg/mL no plasma e 0,30 (0,19-0,36) µg/mL no LCR. As concentrações do fluconazol, médias (IC95%) foram: 31,7 (20,1-43,3) µg/mL no plasma e 19,4 (11,1-27,7) µg/mL no LCR. Com base nos resultados obtidos conclui-se que a penetração da anfotericina B foi insuficiente (10-27%), enquanto que a do fluconazol mostrou-se adequada com valores médios (IC95%) de 67 (47-87) %. / Analytical methods were developed to determine amphotericin B and fluconazole in only 200 L of plasma and in cerebrospinal fluid (CSF) by liquid chromatography (HPLC UVVIS). Amphotericin B was determined by HPLC - VIS using p-nitrophenol as internal standard, after the purification of biological matrices using acetonitrile, followed by chromatographic analysis in a Nova Pak C18 column (150 x 3.9mm, 4 micron) and mobile phase consisting of acetate buffer 0.1M pH 5.0 plus acetonitrile (50:50,v/v) 0.5mL/min at 385nm; the run time required was 15 min. Bioanalytical method validated showed robustness, 0.2-25,0µg/mL (linearity, r2 0.9999), DL 0.1µg/mL, precision (5.4%/6.0%), accuracy expressed as systematic error (3.3%/2.2%). The stability was investigated, error systematic was 1% for the vials on the rack (time and conditions of drug analysis, 24h). Thawing cycles showed good stability after three freezing-thawing cycles. All procedures were performed under yellow light at room temperature. Fluconazole was determined by HPLC - UV using carbamazepine as internal standard, after the purification of biological matrices using liquid-liquid extraction in alkaline medium, followed by chromatographic analysis in a Nova Pak C18 column (150 x 3.9mm, 4 micron) and mobile phase consisting of purified water plus acetonitrile (70:30,v/v) 0.5mL/min at 210nm; the run time required was 15 min. Bioanalytical method validated showed robustness, 0.2-250 µg/mL(linearity, r2 0.9998), DL 0.1µg/mL. Absolute recovery was 98% and relative recovery was 100%, intra/interday precision were 0,5/-1,3%; accuracy expressed as systematic error were 1.2%/1.2%.and relative recovery was 100%. Good stability for the vials on the rack (time and conditions of drug analysis, 24h) and long term stability (at 20o C for 9 months) were demonstrated. Also thawing cycles showed good stability after three freezing-thawing cycles. Twenty one adult patients of both sex were investigated. Inpatients with meningitis by Cryptococcus neoformans with AIDS were under high dose therapy with amphotericin B 1mg/Kg plus fluonazole 400 mg, every 12h during 12 weeks. Therapeutic monitoring of amphotericin B and fluconazole in plasma and in CSF showed ratios that indicate the penetration of antifungal drugs into CNS. Mean (CI95%) data were for amphotericin B 2.30 (0.02-5.08 ) µg/mL in plasma and 0.30 (0.19-0.36) µg/mL in CSF. Fluconazole showed 31.7 (20.1-43.3) µg/mL in plasma and 19.4 (11.1-27.7) µg/mL in CSF. Based on data obtained we conclude that the penetration of amphotericin B was poor (10-27%) while fluconazole was adequate 67% (47-87%), mean (CI95%).

A hidrocefalia é uma doença ocasionada pelo distúrbio na formação, circulação ou absorção do líquido cefalorraquidiano (líquor) que acarreta na elevação da pressão intracraniana. O tratamento mais usual para a disfunção é a derivação ventrículo-peritoneal (DVP) responsável pela drenagem do líquor do ventrículo até o abdômen do paciente, através do implante de um cateter ventricular, uma válvula neurológica e um cateter peritoneal. Desse modo, o presente estudo apresenta o conceito de uma nova válvula neurológica com um mecanismo inovador para alteração da pressão de funcionamento, com um menor custo produtivo e de possível aceitação pelo Sistema Único de Saúde (SUS). A norma ISO 7197 forneceu as diretrizes atendidas no desenvolvimento da válvula neurológica ajustável e as informações para a construção das bancadas de testes, utilizadas para a realização dos ensaios hidrodinâmicos no protótipo do dispositivo valvular. Foram pesquisados os biomateriais empregados na fabricação de válvulas neurológicas comerciais, para a proposição dos materiais necessários para a construção da válvula ajustável por acionamento mecânico proposta. O aparato utilizado nos testes hidrodinâmicos apresentou incertezas experimentais, que não comprometem os resultados e a avaliação do desempenho in vitro do dispositivo testado. O protótipo da válvula resistiu aos testes de vazamento e de refluxo de fluido. As pressões de abertura e de fechamento apresentaram-se adequadas para o início e a interrupção do escoamento na DVP. Também foi obtido o comportamento do diferencial de pressão, em função da vazão, para as quatro classes de funcionamento disponíveis no protótipo testado. A avaliação hidrodinâmica do protótipo da válvula ajustável por acionamento mecânico apresenta resultados satisfatórios no controle da drenagem de líquor, frente a todos os ensaios hidrodinâmicos realizados. / Hydrocephalus is a disease caused by disturbance in formation, circulation or absorption of cerebrospinal fluid (CSF) which causes high intracranial pressure. The most common treatment for the dysfunction is the ventricle-peritoneal shunt responsible for drainage of cerebrospinal fluid from the patient\'s ventricle to the abdomen, through the implant of a ventricular catheter, a neurological valve and a peritoneal catheter. Thus, the present study introduces the concept of a new valve with an innovative mechanism to change the working pressure, with a lower cost of production and possible acceptance by the Brazilian Health System. ISO 7197 provided the guidelines met in the development of adjustable neurological valve and the information for the construction of testing rigs, used for hydrodynamic testing on the valve device prototype. Biomaterials used in manufacturing commercial neurological valves have been researched for proposition of materials needed for the proposed adjustable neurological valve by mechanical drive. The apparatus used in hydrodynamic tests presented experimental uncertainties, which do not compromise the results and evaluation of in vitro performance of the device tested. The prototype of the valve withstood the leak and the fluid backflow testing. The opening and closing pressures were suitable for the beginning and the interruption of the flow in the ventricle-peritoneal shunt. It was also obtained the behavior of the pressure differential, due to the flow, for the four classes of operation available in the prototype tested. Hydrodynamic evaluation of the prototype of the adjustable valve by mechanical drive shows satisfactory results in the control of CSF drain, dealing with all hydrodynamic tests carried out.

I denna studie jämfördes två olika metoder för att analysera cerbrospinalvätska (CSF); spinal-protein och spinal-albumin. Syftet med studien var att undersöka om spinal-albumin som baseras på turbidimetri skulle kunna ersätta spinal-protein som baseras på spektrofotometri. Denna används idag som rutinanalys på laboratoriet för klinisk kemi på S Södra Älvsborgs sjukhus (SÄS). 35 prover analyserades, tagna från det CSF -prover som ankom till SÄS. Varje prov kördes två gånger med respektive metod. Studien visade en god korrelation mellan metoderna, dock visade Bland-Altman diagram mindre spridning av värdena som erhölls med albumin-metoden. Resultaten för albumin jämfördes mot Sahlgrenska universitetssjukhus (SU) resultat, då albumin-metoden ingår i deras rutiner.   Studien visade också att de dagliga kontrollerna som kördes ej var lämpade för albumin metoden, då både innehåll och koncentration inte var anpassad till spinalprover. Kontrollerna kommer att bytas ut mot andra mer lämpade kontroller. Metoden för spinal-albumin kommer att kunna ersätta total-protein som rutinanalys av CFS.