964 resultados para Survival analysis (Biometry) Mathematical models


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Dissertação de mestrado em Engenharia Industrial

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El objeto de estudio de este proyecto son los sistemas de calentamiento de agua mediante energía solar que funcionan termosifónicamente. En particular se tratará con dos diseños particulares generados por fabricantes de la Provincia de Córdoba y que han solicitado el asesoramiento del Grupo de Energía Solar (GES) para el mejoramiento de la performance térmica de dichos equipos. Se trata de dos sistemas que tienen materiales no tradicionales y se diferencian además por tener una distinta disposición del tanque de almacenamiento: uno es en forma vertical y el otro en forma horizontal. Basados en los resultados de un ensayo bajo norma internacional, donde se detectaron algunas puntos factibles de mejora, se propone en este proyecto el análisis en detalle de los equipos, para lo cual se les debe desarmar completos, para realizar un estudio analítico y experimental de los mismos con el objeto de hacer un planteo teórico-analítico del comportamiento de los mismos, con la implementación de propuestas de mejora y chequeo de los resultados. Se propone entonces como objetivo lograr un mejoramiento de la performance térmica de los citados equipos a partir de un estudio experimental y analítico. Asumiendo esta posibilidad de mejora, se plantea la hipótesis de que es posible representar el funcionamiento de estos equipos mediante modelos físico-matemáticos desarrollados a partir de ecuaciones y correlaciones conocidas y procesos a interpretar mediante resoluciones numéricas y softwares específicos de simulación. De esta manera, se plantea el despieze completo de los equipos para estudiar en detalle su estructura y conexiones internas y a partir de la geometría, dimensiones y propiedades termofísicas de materiales constructivos y fluidos de trabajo, realizar modelos físico-matemáticos que permitan realizar variaciones de propiedades y geometría y así buscar las mejores combinaciones que produzcan equipos más eficientes térmicamente. Los modelos físico-matemáticos serán codificados en lenguajes de alto nivel para poder luego de una validación de los modelos, correr simulaciones en un software de reconocimiento internacional que permite sumar dichos modelos mediante un protocolo de comunicación, haciendo que las poderosas prestaciones del software se puedan aplicar a nuestros modelos. Se complementará el estudio con un análisis exergético para identificar los puntos críticos en que se producen las pérdidas de oportunidad de aprovechar la energía disponible, para así analizar cómo solucionar los problemas en dichos puntos. Los materiales a utilizar serán los propios equipos provistos por los fabricantes, que serán modificados convenientemente para operarlos como prototipos Se espera obtener un conocimiento acabado de los procesos y principios de funcionamiento de los equipos, que permita plantear las mejoras, las cuales se implementarán en los prototipos, realizándose una medición mediante norma igual a la inicial para ver en que magnitud se logran las mejoras esperadas. Se pretende además que las mejoras a implementar, en la etapa de transferencia a las empresas involucradas, redunden no sólo en un beneficio técnico, sino que también los sea desde el punto de vista económico. Para ello se trabajará también sobre los procesos y métodos de fabricación para que los equipos mejorados no sean mas caros que los originales y de ser posible sean aún más económicos, todo esto apuntando a la difusión de la energía solar térmica y poner al alcance de todos estos equipos tan convenientes para la propagación de las energías limpias. El proyecto redundará también en un importante beneficio para el conocimiento de la comunidad científica en general, con el aporte de nuevos resultados en diseños novedosos y con nuevos materiales. Además, la institución se beneficiará con la formación que obtendrán los integrantes del proyecto, muchos de ellos en etapa de realización de sus estudios de posgrado y en una etapa importante de su vida como investigadores. The main goal of this project is the improvement of two thermosyphonic solar water heating systems, made of non conventional materials and with different arrangement of their storage tanks: one is vertical and the other one horizontal. The thermosyphonic systems are provided by manufacturers of the Córdoba Province, who came to the Solar Energy Group (GES) of the National University of Río Cuarto looking for help for the design of their products. In an agreement with these manufacturers, it was proposed this project in order to work analytically and experimentally in order to obtain physical-mathematical models of these two systems, which allow for changes to look by means of simulations the best changes to implement on the equipments for the improvement of their thermal performance. Then, the materials to be used are the proper systems provided by the manufacturers, which will be disarmed to be studied in detail. After the analytical study the proposals of improvement will be implemented in a high level language of programming to perform simulations in the environment of a well-known software for energy simulations (TRNSYS). After the simulations, the best modifications will be physically implemented in the prototypes to perform finally the same normalized test of the beginning and check the magnitude of the implemented improvements. The importance of this project is based on the offer of better systems the companies would make, which would benefit the deployment of the thermal solar energy. Another relevant point is to make the new equipments at the same cost of the previous ones or cheaper, in order to achieve a good deployment of the solar water heating systems; then, the manufacture processes and methods must be studied to obtain not only good technical solutions, but also economical equipments. In addition, this project will contribute to the increasing of the knowledge in the area of thermosyphonic solar systems and the training of postgraduate students.

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The purpose of the research is the creation of mathematical models in MATLAB based on the double exponential model of the photovoltaic cell. The developed model allows for different physical and environmental parameters. An equivalent circuit of the model includes a photocurrent source, two diodes, and a series and parallel resistance. The paper presents the simulation results for each parameter. The simulation data are displayed graphically and numerical results are saved in a file.

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Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by (13)C nuclear magnetic resonance (NMR) spectroscopy upon infusion of (13)C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-(13)C]glucose and (13)C enrichment in the brain metabolites was measured by (13)C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining (13)C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (V(TCA)) and neurotransmission rate (V(NT)) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial V(TCA) was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (V(PC)) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.

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BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03). CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

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This paper discuses current strategies for the development of AIDS vaccines wich allow immunzation to disturb the natural course of HIV at different detailed stages of its life cycle. Mathematical models describing the main biological phenomena (i.e. virus and vaccine induced T4 cell growth; virus and vaccine induced activation latently infected T4 cells; incremental changes immune response as infection progress; antibody dependent enhancement and neutralization of infection) and allowing for different vaccination strategies serve as a backgroud for computer simulations. The mathematical models reproduce updated information on the behavior of immune cells, antibody concentrations and free viruses. The results point to some controversial outcomes of an AIDS vaccine such as an early increase in virus concentration among vaccinated when compared to nonvaccinated individuals.

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Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

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AIM OF THE STUDY: To analyse the course of upper limb edema in patients with an arteriovenous fistula used for dialysis and to analyse the available therapeutic options. STUDY DESIGN: Retrospective study of patients with this type of edema, who were treated in our institution from 1992 to 1996. PATIENTS AND METHODS: Seven consecutive patients with an arterioveinous fistula treated for edema of the upper extremity, were reviewed. The fistula was created at the elbow in 6 patients and at the forearm in 1. The edema appeared immediately after operation in 4 patients and after a delay in 3 patients. Stenosis (3 patients) or occlusion (2 patients) of the subclavian vein was documented in 5 patients who were investigated by angiography. RESULTS: The edema regressed spontaneously in 4 patients because collaterals developed in 3 patients, and the fistula thrombosed in 1 patient. Surgical intervention allowed regression of the edema in the other 3 patients: excessive output of the fistula was reduced in 2 patients and an axillojugular bypass was performed in 1 patient. The fistula remained effective in 6 patients. Another fistula was performed on the contralateral arm in 1 patient. CONCLUSION: Non-operative management is recommended in patients who develop edema immediately after creation of the fistula, because spontaneous regression is likely. Measures aimed at reducing the output of the fistula or enhancing the venous capacities of the arm are required when edema appears at a later stage. The fistula can be saved in the majority of cases.

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BACKGROUND: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. METHODS: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. RESULTS: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. CONCLUSIONS: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it represents a marker of much higher risk than previously considered. KRAS mutation status does not seem to represent a strong prognostic variable.

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AIMS OF THE STUDY: Analysis of indications and results of paediatric renal transplantation in a single centre, before and after the introduction of cyclosporine A (CSA). METHODS: Historical retrospective study. RESULTS: 19 transplantations were performed in 14 patients (5 second grafts) between 1971 and 1987 (group I). 13 patients were transplanted between 1988 and 1998 (no second transplant) (group II). In group II, all the patients had immunosuppression with CSA, but none in group I. Group II, with CSA, showed better renal survival than patients without CSA. In group I, obstructive uropathies (posterior urethral valves, pyelo-ureteral junction stenosis, vesico-ureteral reflux) represent a common cause (35%) of terminal chronic renal failure (TCRF), whereas in group II they represent only 15% of the causes and chronic glomerulonephritis is the most common cause (69%) of TCRF. Acute and chronic graft rejections were the cause of 9 and 1 graft losses in group I and II respectively. Living related donors account for 14% of all renal transplantations in group I and 46% in group II. CONCLUSIONS: The incidence of paediatric patients referred to Lausanne for TCRF is stable. We have observed a constant and steady decrease in obstructive uropathies leading to TCRF and renal transplantations, whereas glomerulonephritis are increasingly frequent. Graft survival has much improved since the introduction of cyclosporine A, without an increase in morbidity. In carefully selected cases, intrafamilial renal transplantation provides good results and helps to shorten the time spent on dialysis.

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Anaplastic astrocytoma is an uncommon disease in the adult population. Prognosis is influenced by age, symptom duration, mental status and Karnofsky performance status. A truly complete resection, which is a recognized independent prognostic factor, is not possible and recurrence in the surgical cavity is common. Based on randomized data available, chemotherapy has consistently failed to improve the outcome of patients with anaplastic astrocytoma, while a meta-analysis showed a small, but significant improvement in survival favouring the use of chemotherapy. Outside a clinical trial, postoperative radiotherapy (30 x 2 Gy) remains the standard adjuvant therapy for most patients. For elderly patients, the application of treatment is usually based on performance status and neurological function. In recurrent disease, chemotherapy with temozolomide has been proven to be active and well-tolerated in phase II trials, but no comparative phase III trials of other cytotoxic drugs have been conducted.

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AIM: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated prospectively and compared with other known risk factors of relapse in early stage melanoma. METHODS: Surgery was guided by lymphoscintigraphy, blue dye and gamma probe detection. SLN were analysed by haematoxylin eosin (HE) histochemistry and multimarker immunohistochemistry (IHC). Disease free survival (DFS) was evaluated with Kaplan-Meier plots according to different parameters and Cox analyses of variance. RESULTS: From 210 patients a total of 381 SLN were excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow-up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for early relapse (p < 0.0005) were SLN positivity and a high Breslow index. CONCLUSION: SLN tumour positivity is an independent factor of high risk for early relapse with a higher power of discrimination than the Breslow index.

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OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).