972 resultados para Integrated biomarker response


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Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Electrotécnica e Computadores

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The excessive use of pesticides and fertilisers in agriculture has generated a decrease in groundwater and surface water quality in many regions of the EU, constituting a hazard for human health and the environment. Besides, on-site sewage disposal is an important source of groundwater contamination in urban and peri-urban areas. The assessment of groundwater vulnerability to contamination is an important tool to fulfil the demands of EU Directives. The purpose of this study is to assess the groundwater vulnerability to contamination related mainly to agricultural activities in a peri-urban area (Vila do Conde, NW Portugal). The hydrogeological framework is characterised mainly by fissured granitic basement and sedimentary cover. Water samples were collected and analysed for temperature, pH, electrical conductivity, chloride, phosphate, nitrate and nitrite. An evaluation of groundwater vulnerability to contamination was applied (GOD-S, Pesticide DRASTIC-Fm, SINTACS and SI) and the potential nitrate contamination risk was assessed, both on a hydrogeological GIS-based mapping. A principal component analysis was performed to characterised patterns of relationship among groundwater contamination, vulnerability, and the hydrogeological setting assessed. Levels of nitrate above legislation limits were detected in 75 % of the samples analysed. Alluvia units showed the highest nitrate concentrations and also the highest vulnerability and risk. Nitrate contamination is a serious problem affecting groundwater, particularly shallow aquifers, especially due to agriculture activities, livestock and cesspools. GIS-based cartography provided an accurate way to improve knowledge on water circulation models and global functioning of local aquifer systems. Finally, this study highlights the adequacy of an integrated approach, combining hydrogeochemical data, vulnerability assessments and multivariate analysis, to understand groundwater processes in peri-urban areas.

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BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

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Bartonellosis (Carrion's Disease) during pregnancy is associated with high rates of maternal and perinatal mortality. We report the immunological patterns in two cases of human bartonellosis during pregnancy. One patient had an uncomplicated course while the second patient developed life threatening anasarca and cardiac tamponade. The patient with a complicated course had a Th1 response with a higher elevation of IL-10. This elevation has been associated with poor outcome pregnancies during bacterial infections.

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Smart Grids (SGs) have emerged as the new paradigm for power system operation and management, being designed to include large amounts of distributed energy resources. This new paradigm requires new Energy Resource Management (ERM) methodologies considering different operation strategies and the existence of new management players such as several types of aggregators. This paper proposes a methodology to facilitate the coalition between distributed generation units originating Virtual Power Players (VPP) considering a game theory approach. The proposed approach consists in the analysis of the classifications that were attributed by each VPP to the distributed generation units, as well as in the analysis of the previous established contracts by each player. The proposed classification model is based in fourteen parameters including technical, economical and behavioural ones. Depending of the VPP strategies, size and goals, each parameter has different importance. VPP can also manage other type of energy resources, like storage units, electric vehicles, demand response programs or even parts of the MV and LV distribution network. A case study with twelve VPPs with different characteristics and one hundred and fifty real distributed generation units is included in the paper.

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Further improvements in demand response programs implementation are needed in order to take full advantage of this resource, namely for the participation in energy and reserve market products, requiring adequate aggregation and remuneration of small size resources. The present paper focuses on SPIDER, a demand response simulation that has been improved in order to simulate demand response, including realistic power system simulation. For illustration of the simulator’s capabilities, the present paper is proposes a methodology focusing on the aggregation of consumers and generators, providing adequate tolls for the demand response program’s adoption by evolved players. The methodology proposed in the present paper focuses on a Virtual Power Player that manages and aggregates the available demand response and distributed generation resources in order to satisfy the required electrical energy demand and reserve. The aggregation of resources is addressed by the use of clustering algorithms, and operation costs for the VPP are minimized. The presented case study is based on a set of 32 consumers and 66 distributed generation units, running on 180 distinct operation scenarios.

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In this paper, we formulate the electricity retailers’ short-term decision-making problem in a liberalized retail market as a multi-objective optimization model. Retailers with light physical assets, such as generation and storage units in the distribution network, are considered. Following advances in smart grid technologies, electricity retailers are becoming able to employ incentive-based demand response (DR) programs in addition to their physical assets to effectively manage the risks of market price and load variations. In this model, the DR scheduling is performed simultaneously with the dispatch of generation and storage units. The ultimate goal is to find the optimal values of the hourly financial incentives offered to the end-users. The proposed model considers the capacity obligations imposed on retailers by the grid operator. The profit seeking retailer also has the objective to minimize the peak demand to avoid the high capacity charges in form of grid tariffs or penalties. The non-dominated sorting genetic algorithm II (NSGA-II) is used to solve the multi-objective problem. It is a fast and elitist multi-objective evolutionary algorithm. A case study is solved to illustrate the efficient performance of the proposed methodology. Simulation results show the effectiveness of the model for designing the incentive-based DR programs and indicate the efficiency of NSGA-II in solving the retailers’ multi-objective problem.

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This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.

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The painting activity is one of the most complex and important activities in automobile manufacturing. The inherent complexity of the painting activity and the frequent need for repainting usually turn the painting process into a bottleneck in automobile assembly plants, which is reflected in higher operating costs and longer overall cycle times. One possible approach for optimizing the performance of the paint shop is to improve the efficiency of the color planning. This can be accomplished by evaluating the relative merits of a set of vehicle painting plans. Since this problem has a multicriteria nature, we resort to the multicriteria decision analysis (MCDA) methodology to tackle it. A recent trend in the MCDA field is the development of hybrid approaches that are used to achieve operational synergies between different methods. Here we apply, for the first time, an integrated approach that combines the strengths of the analytic hierarchy process (AHP) and the Preference Ranking Organization METHod for Enrichment Evaluations (PROMETHEE), aided by Geometrical Analysis for Interactive Aid (GAIA), to the problem of assessing alternative vehicle painting plans. The management of the assembly plant found the results of value and is currently using them in order to schedule the painting activities such that an enhancement of the operational efficiency of the paint shop is obtained. This efficiency gain has allowed the management to bid for a new automobile model to be assembled at this specific plant.

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CD30+ cutaneous lymphoproliferative disorders (CLPDs) are usually characterized by a benign clinical course. The prognostic value of cytotoxic markers in these lymphomas has not been evaluated in large series. We describe a case of borderline CD30+ CLPD with cytotoxic phenotype, presenting in a 22-year-old male patient as an ulcer on the forearm. He reported having had similar ulcers on the buttock and thigh that spontaneously regressed over the course of 1 year. The lesion resolved with a single course of clarithromycin; a subsequent lesion, too, responded to clarithromycin, and no recurrences or systemic involvement have been documented in the 9-month follow-up. A conservative approach in the management of CD30+ CLPD is recommended. We believe that the anti-inflammatory and apoptotic effects of clarithromycin on T cells may have hastened the remission process.

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The complex interaction between hepatitis C virus infection, iron homeostasis and the response to antiviral treatment remains controversial. The aim of this study was to evaluate the influence of hepatic iron concentration (HIC) on the sustained virological response (SVR) to antiviral therapy in patients with chronic hepatitis C. A total of 50 patients who underwent pretreatment liver biopsy with assessment of HIC by graphite furnace atomic absorption spectroscopy and were subsequently submitted to antiviral treatment with interferon/peginterferon and ribavirin were included in the study. Patients with alcoholism, history of multiple blood transfusion, chronic kidney disease, hemolytic anemia and parenteral iron therapy were excluded. The iron related markers and HIC were compared between those who achieved an SVR and non-responders (NR) patients. The mean age was 45.7 years and the proportion of patients' gender was not different between SVR and NR patients. The median serum iron was 138 and 134 µg/dL (p = 0.9), the median serum ferritin was 152.5 and 179.5 ng/mL (p = 0.87) and the median HIC was 9.9 and 8.2 µmol/g dry tissue (p = 0.51), for SVR and NR patients, respectively. Thus, hepatic iron concentration, determined by a reliable quantitative method, was not a negative predictive factor of SVR in patients with chronic hepatitis C presenting mild to moderate hepatic iron accumulation.

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Resumo: Os mecanismos que regulam a homeostase da glucose no pós-prandial são distintos dos mecanismos desencadeados em situações de jejum. Desta forma o fígado parece desempenhar um papel fundamental na acção periférica da insulina após a refeição através de um mecanismo que envolve os nervos parassimpáticos hepáticos e o óxido nítrico (NO). Esta dissertação procura evidenciar a importância de ambos na fi siologia de manutenção da glicémia pós-prandial e na fi siopatologia da resistência à insulina. Dos resultados obtidos observou-se que após a administração de uma refeição mista o perfi l glicémico foi distinto em animais com ou sem ablação dos nervos parassimpáticos hepáticos. A desnervação parassimpática hepática aumentou as excursões de glucose imediatamente após a refeição. Estas diferenças nas excursões de glucose dependentes do parassimpático ocorreram devido a uma diminuição da clearance de glucose, sem que fosse afectada a taxa de aparecimento de glucose no sangue, a produção endógena de glucose e secreção de insulina ou péptido-C. Este aumento das excursões de glucose revelou-se ser devida à diminuição da clearance de glucose pós-prandial exclusivamente no músculo-esquelético, coração e o rim. Concluiu-se que o fígado teria uma função endócrina nestes três órgãos. Surgiu assim a hipótese dos S-nitrosotiois (RSNOs) poderem mimetizar essa resposta endócrina. Testou-se o seu efeito in vivo na sensibilidade à insulina. Para níveis baixos de sensibilidade à insulina, como jejum, desnervação no estado pós-prandial e resistência à insulina os RSNOs potenciaram a sensibilidade à insulina para valores semelhantes ao pós-prandial indicando-os como potenciais fármacos no tratamento da resistência à insulina. O NO e seus derivados ganharam assim uma evidência cada vez maior na acção periférica da insulina e portanto fez-se uma caracterização dos seus níveis desde a fi siologia à fi siopatologia. Os resultados obtidos nesta dissertação permitiram correlacionar a sintetase de óxido nítrico (NOS), enzima responsável pela síntese de NO como um possível marcador da resistência à insulina. Os resultados obtidos contribuíram substancialmente para compreender os mecanismos fi siológicos e fi siopatológicos de manutenção da glicémia após a refeição, colocando o fígado como órgão primordial na regulação periférica (extra-hepática) da captação de glucose.-------- ABSTRACT: The mechanisms responsible for the postprandial response are different from the ones in the fasted state. Therefore the liver seems to play a fundamental role in postprandial insulin action through a mechanism that evolves the hepatic parasympathetic nerves (HPN) and nitric oxide (NO). This work focused on the importance of both, HPN and NO, on postprandial glycemic control and on the pathophysiology of insulin resistance. We observed that after administration of a mixed meal the glycemic profi les with or without the parasympathetic nerves were distinct, increasing glucose excursions after ablation of HPN.This increase in glucose excursions was due to a decrease on the rate of glucose disappearance in extra-hepatic tissues. Glucose appearance rate, endogenous glucose production and insulin secretion were not related to this mechanism. The increase on glucose excursions after the ablation of hepatic parasympathetic system was due to a decrease on glucose clearance on extra-hepatic tissues, namely skeletal-muscle, heart and kidney. We concluded that the liver has an endocrine function on those tissues increasing their glucose uptake.This mechanism led to propose the hypothesis that S-nitrosothiols (RSNOs) could mimic this mechanism. Therefore RSNOs effects on insulin sensitivity were tested. For low insulin sensitivity levels, i.e. fasted state, ablation of the HPN or insulin resistance state induced by a high sucrose diet RSNOs increased insulin sensitivity to levels normally observed in the postprandial state. These results indicated these drugs as potential pharmacological tools in the treatment of insulin resistance. NO and their derivates emerged as fundamental parts of insulin action. A characterization of nitric oxide and nitric oxide synthase (NOS), the enzyme responsible for NO synthesis was part of the work performed. We concluded that NO could be used as a biomarker for insulin resistance states. This work contributed for understanding the mechanism underlying postprandial glycemic control indicating the liver as a key organ in the regulation of peripheral (extra-hepatic) insulin action.

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In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

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OBJECTIVE: To empirically test, based on a large multicenter, multinational database, whether a modified PIRO (predisposition, insult, response, and organ dysfunction) concept could be applied to predict mortality in patients with infection and sepsis. DESIGN: Substudy of a multicenter multinational cohort study (SAPS 3). PATIENTS: A total of 2,628 patients with signs of infection or sepsis who stayed in the ICU for >48 h. Three boxes of variables were defined, according to the PIRO concept. Box 1 (Predisposition) contained information about the patient's condition before ICU admission. Box 2 (Injury) contained information about the infection at ICU admission. Box 3 (Response) was defined as the response to the infection, expressed as a Sequential Organ Failure Assessment score after 48 h. INTERVENTIONS: None. MAIN MEASUREMENTS AND RESULTS: Most of the infections were community acquired (59.6%); 32.5% were hospital acquired. The median age of the patients was 65 (50-75) years, and 41.1% were female. About 22% (n=576) of the patients presented with infection only, 36.3% (n=953) with signs of sepsis, 23.6% (n=619) with severe sepsis, and 18.3% (n=480) with septic shock. Hospital mortality was 40.6% overall, greater in those with septic shock (52.5%) than in those with infection (34.7%). Several factors related to predisposition, infection and response were associated with hospital mortality. CONCLUSION: The proposed three-level system, by using objectively defined criteria for risk of mortality in sepsis, could be used by physicians to stratify patients at ICU admission or shortly thereafter, contributing to a better selection of management according to the risk of death.

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A liberalização dos mercados de energia elétrica e a crescente integração dos recursos energéticos distribuídos nas redes de distribuição, nomeadamente as unidades de produção distribuída, os sistemas de controlo de cargas através dos programas de demand response, os sistemas de armazenamento e os veículos elétricos, representaram uma evolução no paradigma de operação e gestão dos sistemas elétricos. Este novo paradigma de operação impõe o desenvolvimento de novas metodologias de gestão e controlo que permitam a integração de todas as novas tecnologias de forma eficiente e sustentável. O principal contributo deste trabalho reside no desenvolvimento de metodologias para a gestão de recursos energéticos no contexto de redes inteligentes, que contemplam três horizontes temporais distintos (24 horas, 1 hora e 5 minutos). As metodologias consideram os escalonamentos anteriores assim como as previsões atualizadas de forma a melhorar o desempenho total do sistema e consequentemente aumentar a rentabilidade dos agentes agregadores. As metodologias propostas foram integradas numa ferramenta de simulação, que servirá de apoio à decisão de uma entidade agregadora designada por virtual power player. Ao nível das metodologias desenvolvidas são propostos três algoritmos de gestão distintos, nomeadamente para a segunda (1 hora) e terceira fase (5 minutos) da ferramenta de gestão, diferenciados pela influência que os períodos antecedentes e seguintes têm no período em escalonamento. Outro aspeto relevante apresentado neste documento é o teste e a validação dos modelos propostos numa plataforma de simulação comercial. Para além das metodologias propostas, a aplicação permitiu validar os modelos dos equipamentos considerados, nomeadamente, ao nível das redes de distribuição e dos recursos energéticos distribuidos. Nesta dissertação são apresentados três casos de estudos, cada um com diferentes cenários referentes a cenários de operação futuros. Estes casos de estudos são importantes para verificar a viabilidade da implementação das metodologias e algoritmos propostos. Adicionalmente são apresentadas comparações das metodologias propostas relativamente aos resultados obtidos, complexidade de gestão em ambiente de simulação para as diferentes fases da ferramenta proposta e os benefícios e inconvenientes no uso da ferramenta proposta.