89 resultados para Prognostic Models


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We study effective models of chiral fields and Polyakov loop expected to describe the dynamics responsible for the phase structure of two-flavor QCD at finite temperature and density. We consider chiral sector described either using linear sigma model or Nambu-Jona-Lasinio model and study the phase diagram and determine the location of the critical point as a function of the explicit chiral symmetry breaking (i.e. the bare quark mass $m_q$). We also discuss the possible emergence of the quarkyonic phase in this model.

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Acute heart failure (AHF) is a complex syndrome associated with exceptionally high mortality. Still, characteristics and prognostic factors of contemporary AHF patients have been inadequately studied. Kidney function has emerged as a very powerful prognostic risk factor in cardiovascular disease. This is believed to be the consequence of an interaction between the heart and kidneys, also termed the cardiorenal syndrome, the mechanisms of which are not fully understood. Renal insufficiency is common in heart failure and of particular interest for predicting outcome in AHF. Cystatin C (CysC) is a marker of glomerular filtration rate with properties making it a prospective alternative to the currently used measure creatinine for assessment of renal function. The aim of this thesis is to characterize a representative cohort of patients hospitalized for AHF and to identify risk factors for poor outcome in AHF. In particular, the role of CysC as a marker of renal function is evaluated, including examination of the value of CysC as a predictor of mortality in AHF. The FINN-AKVA (Finnish Acute Heart Failure) study is a national prospective multicenter study conducted to investigate the clinical presentation, aetiology and treatment of, as well as concomitant diseases and outcome in, AHF. Patients hospitalized for AHF were enrolled in the FINN-AKVA study, and mortality was followed for 12 months. The mean age of patients with AHF is 75 years and they frequently have both cardiovascular and non-cardiovascular co-morbidities. The mortality after hospitalization for AHF is high, rising to 27% by 12 months. The present study shows that renal dysfunction is very common in AHF. CysC detects impaired renal function in forty percent of patients. Renal function, measured by CysC, is one of the strongest predictors of mortality independently of other prognostic risk markers, such as age, gender, co-morbidities and systolic blood pressure on admission. Moreover, in patients with normal creatinine values, elevated CysC is associated with a marked increase in mortality. Acute kidney injury, defined as an increase in CysC within 48 hours of hospital admission, occurs in a significant proportion of patients and is associated with increased short- and mid-term mortality. The results suggest that CysC can be used for risk stratification in AHF. Markers of inflammation are elevated both in heart failure and in chronic kidney disease, and inflammation is one of the mechanisms thought to mediate heart-kidney interactions in the cardiorenal syndrome. Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) correlate very differently to markers of cardiac stress and renal function. In particular, TNF-α showed a robust correlation to CysC, but was not associated with levels of NT-proBNP, a marker of hemodynamic cardiac stress. Compared to CysC, the inflammatory markers were not strongly related to mortality in AHF. In conclusion, patients with AHF are elderly with multiple co-morbidities, and renal dysfunction is very common. CysC demonstrates good diagnostic properties both in identifying impaired renal function and acute kidney injury in patients with AHF. CysC, as a measure of renal function, is also a powerful prognostic marker in AHF. CysC shows promise as a marker for assessment of kidney function and risk stratification in patients hospitalized for AHF.

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The question at issue in this dissertation is the epistemic role played by ecological generalizations and models. I investigate and analyze such properties of generalizations as lawlikeness, invariance, and stability, and I ask which of these properties are relevant in the context of scientific explanations. I will claim that there are generalizable and reliable causal explanations in ecology by generalizations, which are invariant and stable. An invariant generalization continues to hold or be valid under a special change called an intervention that changes the value of its variables. Whether a generalization remains invariant during its interventions is the criterion that determines whether it is explanatory. A generalization can be invariant and explanatory regardless of its lawlike status. Stability deals with a generality that has to do with holding of a generalization in possible background conditions. The more stable a generalization, the less dependent it is on background conditions to remain true. Although it is invariance rather than stability of generalizations that furnishes us with explanatory generalizations, there is an important function that stability has in this context of explanations, namely, stability furnishes us with extrapolability and reliability of scientific explanations. I also discuss non-empirical investigations of models that I call robustness and sensitivity analyses. I call sensitivity analyses investigations in which one model is studied with regard to its stability conditions by making changes and variations to the values of the model s parameters. As a general definition of robustness analyses I propose investigations of variations in modeling assumptions of different models of the same phenomenon in which the focus is on whether they produce similar or convergent results or not. Robustness and sensitivity analyses are powerful tools for studying the conditions and assumptions where models break down and they are especially powerful in pointing out reasons as to why they do this. They show which conditions or assumptions the results of models depend on. Key words: ecology, generalizations, invariance, lawlikeness, philosophy of science, robustness, explanation, models, stability

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Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma. It is an indolent and clinically heterogeneous disease, which is generally considered incurable. Currently, immunochemotherapy has significantly improved the outcome of FL patients. This is based on the combination of rituximab, a monoclonal anti-CD20 antibody, with chemotherapy, and is used at present as a standard first-line therapy in FL. Thus far, however, patients have been selected for treatment based on clinical risk factors and indices that were developed before the rituximab era. Therefore, there is a growing need to understand the molecular mechanisms underlying the disease, which would not only provide information to predict survival in the rituximab era, but also enable the design of more targeted therapeutic strategies. In this study, our aim was to identify genes predicting the outcome in FL patients treated with immunochemotherapy. Thus, we performed a cDNA microarray with 24 FL patients. When gene expression differences from diagnostic tumour samples were related to the clinical outcome, we identified novel genes with a prognostic impact on survival. The expression of selected genes was further characterized with quantitative PCR and immunohistochemistry (IHC). Interestingly, the prognostic influence of these genes was often associated with their expression in non-malignant cells instead of tumour cells. Based on the observed gene expression patterns, we analyzed the abundance and prognostic value of non-malignant immune cells in 95-98 FL patients treated with immunochemotherapy. We observed that a high content of tumour-associated macrophages was a marker of a favourable prognosis. In contrast, the accumulation of mast cells correlated with a poor outcome and was further associated with tumour vascularity. Increased microvessel density also correlated with an inferior outcome. In addition, we used the same microarray data with a systems biology approach to identify signalling pathways or groups of genes capable of separating patients with favourable or adverse outcomes. Among the transcripts, there were many genes associated with signal transducers and activators of the transcription (STAT5a) pathway. When IHC was used as validation, STAT5a expression was mostly observed in T-cells and follicular dendritic cells, and expression was found to predict a favourable outcome. In cell cultures, rituximab was observed to induce the expression of STAT5a-associated interleukins in human lymphoma cell lines, which might provide a possible link for the cross-talk between rituximab-induced FL cells and their microenvironment. In conclusion, we have demonstrated that the microenvironment has a prognostic role in FL patients treated with immunochemotherapy. The results also address the importance of re-evaluating the prognostic markers in the rituximab era of lymphoma therapies.

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Yhteenveto: Talvivirtaamien redukointi vesistömallien avulla

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In the thesis we consider inference for cointegration in vector autoregressive (VAR) models. The thesis consists of an introduction and four papers. The first paper proposes a new test for cointegration in VAR models that is directly based on the eigenvalues of the least squares (LS) estimate of the autoregressive matrix. In the second paper we compare a small sample correction for the likelihood ratio (LR) test of cointegrating rank and the bootstrap. The simulation experiments show that the bootstrap works very well in practice and dominates the correction factor. The tests are applied to international stock prices data, and the .nite sample performance of the tests are investigated by simulating the data. The third paper studies the demand for money in Sweden 1970—2000 using the I(2) model. In the fourth paper we re-examine the evidence of cointegration between international stock prices. The paper shows that some of the previous empirical results can be explained by the small-sample bias and size distortion of Johansen’s LR tests for cointegration. In all papers we work with two data sets. The first data set is a Swedish money demand data set with observations on the money stock, the consumer price index, gross domestic product (GDP), the short-term interest rate and the long-term interest rate. The data are quarterly and the sample period is 1970(1)—2000(1). The second data set consists of month-end stock market index observations for Finland, France, Germany, Sweden, the United Kingdom and the United States from 1980(1) to 1997(2). Both data sets are typical of the sample sizes encountered in economic data, and the applications illustrate the usefulness of the models and tests discussed in the thesis.

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This study examined the effects of the Greeks of the options and the trading results of delta hedging strategies, with three different time units or option-pricing models. These time units were calendar time, trading time and continuous time using discrete approximation (CTDA) time. The CTDA time model is a pricing model, that among others accounts for intraday and weekend, patterns in volatility. For the CTDA time model some additional theta measures, which were believed to be usable in trading, were developed. The study appears to verify that there were differences in the Greeks with different time units. It also revealed that these differences influence the delta hedging of options or portfolios. Although it is difficult to say anything about which is the most usable of the different time models, as this much depends on the traders view of the passing of time, different market conditions and different portfolios, the CTDA time model can be viewed as an attractive alternative.

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This paper examines how volatility in financial markets can preferable be modeled. The examination investigates how good the models for the volatility, both linear and nonlinear, are in absorbing skewness and kurtosis. The examination is done on the Nordic stock markets, including Finland, Sweden, Norway and Denmark. Different linear and nonlinear models are applied, and the results indicates that a linear model can almost always be used for modeling the series under investigation, even though nonlinear models performs slightly better in some cases. These results indicate that the markets under study are exposed to asymmetric patterns only to a certain degree. Negative shocks generally have a more prominent effect on the markets, but these effects are not really strong. However, in terms of absorbing skewness and kurtosis, nonlinear models outperform linear ones.

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This study evaluates three different time units in option pricing: trading time, calendar time and continuous time using discrete approximations (CTDA). The CTDA-time model partitions the trading day into 30-minute intervals, where each interval is given a weight corresponding to the historical volatility in the respective interval. Furthermore, the non-trading volatility, both overnight and weekend volatility, is included in the first interval of the trading day in the CTDA model. The three models are tested on market prices. The results indicate that the trading-time model gives the best fit to market prices in line with the results of previous studies, but contrary to expectations under non-arbitrage option pricing. Under non-arbitrage pricing, the option premium should reflect the cost of hedging the expected volatility during the option’s remaining life. The study concludes that the historical patterns in volatility are not fully accounted for by the market, rather the market prices options closer to trading time.

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Yhteenveto: Järvien ainetasemallien kehittäminen.

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Yhteenveto: Lumimallit vesistöjen ennustemalleissa

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Cosmopolitan ideals have been on the philosophical agenda for several millennia but the end of the Cold War started a new discussion on state sovereignty, global democracy, the role of international law and global institutions. The Westphalian state system in practice since the 17th century is transforming and the democracy deficit needs new solutions. An impetus has been the fact that in the present world, an international body representing global citizens does not exist. In this Master’s thesis, the possibility of establishing a world parliament is examined. In a case analysis, 17 models on world parliament from two journals, a volume of essays and two other publications are discussed. Based on general observations, the models are divided into four thematic groups. The models are analyzed with an emphasis on feasible and probable elements. Further, a new scenario with a time frame of thirty years is proposed based on the methodology of normative futures studies, taking special interest in causal relationships and actions leading to change. The scenario presents three gradual steps that each need to be realized before a sustainable world parliament is established. The theoretical framework is based on social constructivism, and changes in international and multi-level governance are examined with the concepts of globalization, democracy and sovereignty. A feasible, desirable and credible world parliament is constituted gradually by implying electoral, democratic and legal measures for members initially from exclusively democratic states, parliamentarians, non-governmental organizations and other groups. The parliament should be located outside the United Nations context, since a new body avoids the problem of inefficiency currently prevailing in the UN. The main objectives of the world parliament are to safeguard peace and international law and to offer legal advice in cases when international law has been violated. A feasible world parliament is advisory in the beginning but it is granted legislative powers in the future. The number of members in the world parliament could also be extended following the example of the EU enlargement process.