Tonsillar cancer (TC) presents an important part of head and neck cancers and its incidence is rising in the Czech Republic. Cigarette smoking and alcohol abuse are risk factors responsible for approximately two thirds of all head and neck cancers. Furthermore, a role of human papillomavirus (HPV) as an independent risk factor has been demonstrated recently. The aims of the present study were to find demographical differences between the group of HPV-positive and negative patients, to determine the prevalence of HPV in TC of Czech patients and also to find out whether the virus in HPV DNA positive tumors is transcriptionally active. Another aim was to test different markers of HPV infection for a precise selection of patients with HPV associated disease and to determine the prognostic role of these markers. A set of 109 patients with primary TC was examined for HPV DNA presence in tumor tissue and for the presence of HPV specific antibodies in serum. Data regarding risk factors were obtained by questionnaires. Forty-five samples were available for E6 and E2 mRNA analysis and for immunohistochemical analysis of p16 and p53 expression. The overall prevalence of HPV DNA in TC was 65%. In 93% of HPV16 DNA positive samples the virus was transcriptionally active. The E2 expression status has shown that in...

The Pilsen region suffers the highest incidence of kidney tumours worldwide. Approximately 240 new cases diagnosed as C64 (malignant renal tumours outside the pelvis) were recorded in this region of about 580,000 inhabitants in 2015. Clear renal cell carcinoma has long held first place as the most common tumour, with papillary renal cell carcinoma (pRCC) being the second most frequently operated kidney tumour at the Urology Department of the University Hospital in Pilsen. The 2016 WHO classification of kidney tumours recognizes officially only the stratification of pRCC to type 1 (pRCC1) and type 2 (pRCC2). Unfortunately, the current division does not correspond with knowledge derived from everyday practice. Most clinical trials involving pRCC do not differentiate between the subtypes, adhering only to the official type 1 and 2 divisions and the atypical papillary forms being excluded from their studies. We therefore have to face the question of whether the histological pRCC subtype affects the risk of recurrence, or death, in surgically treated patients. The aim of this dissertation work is to take into consideration also all other papillary types which differ from characterization of pRCC1 and pRCC2. The analyses of a group of patients with surgically treated and histologically verified pRCC at...

This theoretical-empirical thesis focuses on anticipation in simultaneous interpreting from German into Czech. The theoretical part presents an overview of commonly used interpreting strategies and subsequently concentrates on anticipation, its types, and findings of previous studies on this topic. The theoretical part also describes the main syntactic attributes of German that are likely to lead an interpreter to use anticipation. The aim of the empirical part is to find out if students of interpreting use this strategy. If so, the question is how often anticipation occurs and which type of anticipation is used. The empirical part includes an experiment on two groups of interpreting students, one group having one year worth of experience more with simultaneous interpreting than the other. Their interpretations are subsequently analyzed and compared. Keywords simultaneous interpreting, interpreting strategies, anticipation, probability prognosis

Le carcinome à cellules claires du rein (ccRCC) est une tumeur très hétérogène. Le taux de métastase est de l’ordre de 50% et les métastases des ccRCC sont peu fréquemment opérées. L’objectif de la thèse est d’une part d’analyser les facteurs prédictifs de métastases dans la tumeur primitive, et d’autre part de comparer le phénotype des tumeurs primitives et de leurs métastases dans le ccRCC par différentes approches histopathologiques et génomiques. Parmi les facteurs prédictifs de métastases, la nouvelle classification OMS/ISUP remplace l’ancienne classification de Fuhrman. L’intérêt pronostique de la nécrose tumorale est également mis en évidence. Une tumeur avec un grade donné associée à la présence de nécrose a un pronostic qui se rapproche d’une tumeur de grade plus élevé sans nécrose. Le pourcentage des cellules de grade 4 pourrait également contribuer à la stratification pronostique des patients. Une différence de survie avec un pronostic défavorable est observée pour les tumeurs dont le pourcentage des cellules de grade 4 est plus élevé (>50% vs. <10%). Au niveau moléculaire le statut du gène VHL, gène suppresseur de tumeur inactivé par un « double hit », est impliqué dans le pronostic des patients. Les ccRCC sans aucune altération de VHL sont des tumeurs plus agressives, qu’il convient d’isoler. Il existe une similarité morphologique et immunohistochimique entre les métastases et la composante de plus haut grade des tumeurs primitives correspondantes. Le profil chromosomique des métastases n’est pas totalement superposable à celui des tumeurs primitives. Il existe anomalies cytogénétiques récurrentes dans des métastases de ccRCC à des sites différents (+2p, +3q, +5, +8q, +12, +20). L’hétérogénéité tumorale retrouvée au niveau des tumeurs primitives est également retrouvée au niveau des métastases sous forme d’hétérogénéité inter- et intra-métastatique. L’analyse combinée des profils génomiques et transcriptomiques de 14 échantillons prélevés au sein d’un ccRCC primitif et de ses métastases ont permis d’identifier trois classes de clones tumoraux distincts, ne suivant aucune logique géographique. Enfin il semble exister un phénomène de multi-colonisation, qui implique non pas un, mais plusieurs clones tumoraux qui pourraient agir conjointement dans le processus métastatique. / Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor. The metastatic rate is 50% and metastases are only rarely surgically excised. The objective of this thesis was to analyze the predictive factors of metastasis in the primary tumor on one hand; and to compare primary and metastatic phenotypes on the other hand. We combined different histopathological and genomic approaches. Considering prognostic factors, the new WHO/ISUP classification replaces the previous Fuhrman grade. The interest of tumor necrosis is also highlighted. A tumor of a certain grade with necrosis has a prognosis that is close to a tumor of higher grade without necrosis. The percentage of grade 4 cells could additionally help in stratifying patients. A significant difference in survival is observed between tumors with more than 50% grade 4 cells and tumors with less than 10%. At a molecular level, the VHL gene status (tumor suppressor gene inactivated by a double hit) could be implicated in the prognosis of patients. ccRCCs with no alteration of the gene are more aggressive tumors that need to be identified. There exists a morphological and immunohistochemical similarity between metastases and the high-grade component in corresponding primary tumors. Moreover, the chromosomal profile of metastases differs from those of the corresponding primary tumors. Recurrent cytogenetic events are observed in different metastatic sites (+2p, +3q, +5, +8q, +12, +20). The tumor heterogeneity phenomenon in primary tumors is also observed in metastases with inter- and intra- metastatic heterogeneity. The combined analysis of transcriptomic and genomic analyses of 14 specimens extracted from a single ccRCC and its metastases divided samples into three classes of sub-clones with no spatial link. We observe a multi-colonization process that implies not only one but several tumor clones that could cooperate in the metastatic process.

The development, use, and understanding of severity of illness scoring systems has advanced rapidly in the last decade; their weaknesses and limitations have also become apparent. This work follows some of this development and explores some of these aspects. It was undertaken in three stages and in two countries. The first study investigated three severity of illness scoring systems in a general Intensive Care Unit (ICU) in Cape Town, namely the Acute Physiology and Chronic Health Evaluation (APACHE II) score, the Therapeutic Intervention Scoring System (TISS), and a locally developed organ failure score. All of these showed a good relationship with mortality, with the organ failure score the best predictor of outcome. The TISS score was felt to be more likely to be representative of intensiveness of medical and nursing management than severity of illness. The APACHE II score was already becoming widely used world-wide and although it performed less well in some diagnostic categories (for example Adult Respiratory Distress Syndrome) than had been hoped, it clearly warranted further investigation. Some of the diagnosis-specific problems were eliminated in the next study which concentrated on the application of the APACHE II score in a cardiothoracic surgical ICU in London. Although group predictive ability was statistically impressive, the predictive ability of APACHE II in the individual patient was limited as only very high APACHE II scores confidently predicted death and then only in a small number of patients. However, there were no deaths associated with an APACHE II score of less than 5 and the mortality was less than 1 % when the APACHE II score was less than 10. Finally, having recognised the inadequacies in mortality prediction of the APACHE II score in this scenario, a study was undertaken to evaluate a novel concept: a combination of preoperative, intraoperative, and postoperative (including APACHE II and III) variables in cardiac surgery patients admitted to the same ICU. The aim was to develop a more precise method of predicting length of stay, incidence of complications, and ICU and hospital outcome for these patients. There were 1008 patients entered into the study. There was a statistically significant relationship between increasing Parsonnet (a cardiac surgery risk prediction score), APACHE II, and APACHE III scores and mortality. By forward stepwise logistic regression a model was developed for the probability of hospital death. This model included bypass time, need for inotropes, mean arterial pressure, urea, and Glasgow Coma Scale. Predictive performance was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. The derived model had an area under the ROC curve 0.87, while the Parsonnet score had an area of 0.82 and the APACHE II risk of dying 0.84. It was concluded that a combination of intraoperative and postoperative variables can improve predictive ability.

This report studies how a non-linear autoregressive neural network algorithm for stock market value prognoses is affected by unforeseen events. The study attempts to find out the recovery period for said algorithms after an event, and whether the magnitude of the event affects the recovery period. Tests of 1-day prognoses' deviations from the observed value are carried out on five real stock events and four created simulation sets which exclude the noisy data of the stock market and isolates different kinds of events. The study concludes that the magnitude has no discernible impact on recovery, and that a sudden event will allow recovery within days regardless of magnitude or change in price development rate. However, less sudden events will cause the recovery period to extend. Noise such as surrounding micro-events, aftershocks, or lingering instability of stock prices will affect accuracy and recovery time significantly. / Denna studie undersöker hur ett icke-linjärt autoregressivt neuronnät för aktiemarknadsprognoser påverkas av oväntade händelser. Studien ämnar finna återhämtningsperioden för nätverket efter en händelse, och ta reda på om den initiala påverkan av händelsen påverkar återhämtningen. Tester av endagsprognosers avvikelse från det verkliga värdet genomförs på fem verkliga aktier och fyra skapade dataset som exkluderar den omgivande variationen från aktiemarknaden. Dessa simulerade set isolerar därmed specifika typer av händelser. Studien drar slutsatsen att storleken av händelsen har försumbar betydelse på återhämtningstiden och att plötsliga händelser tillåter återhämtning på några dagar oavsett händelsens ursprungliga storlek eller förändring av prisutvecklingshastighet. Däremot förlänger utdragna händelser återhämtningstiden. Likaså påverkar efterskalv eller kvarvarande instabilitet i prisutvecklingen tillförlitlighet och återhämtningstid avsevärt.

Tonsillar cancer (TC) presents an important part of head and neck cancers and its incidence is rising in the Czech Republic. Cigarette smoking and alcohol abuse are risk factors responsible for approximately two thirds of all head and neck cancers. Furthermore, a role of human papillomavirus (HPV) as an independent risk factor has been demonstrated recently. The aims of the present study were to find demographical differences between the group of HPV-positive and negative patients, to determine the prevalence of HPV in TC of Czech patients and also to find out whether the virus in HPV DNA positive tumors is transcriptionally active. Another aim was to test different markers of HPV infection for a precise selection of patients with HPV associated disease and to determine the prognostic role of these markers. A set of 109 patients with primary TC was examined for HPV DNA presence in tumor tissue and for the presence of HPV specific antibodies in serum. Data regarding risk factors were obtained by questionnaires. Forty-five samples were available for E6 and E2 mRNA analysis and for immunohistochemical analysis of p16 and p53 expression. The overall prevalence of HPV DNA in TC was 65%. In 93% of HPV16 DNA positive samples the virus was transcriptionally active. The E2 expression status has shown that in...

Despite advances in the understanding of cancer biology, most patients with acute myeloid leukemia (AML) still die of their disease. Improving risk-stratification and identifying new targets are important steps towards personalized medicine and outcome improvement. MicroRNAs, short non-coding RNAs that hybridize to their target messenger RNAs (mRNAs) and repress the expression of the encoded proteins, are known to be involved in physiological processes like cellular differentiation, proliferation and cell survival but also play an essential role in cancer, including AML. In this thesis we demonstrated that higher expression of a single microRNA miR-181a was associated with clinical outcome in cytogenetically normal AML (CN AML) patients. In multivariable models, higher expression of miR-181a was associated with achievement of complete remission (CR), with longer disease-free (DFS) and overall survival (OS) even in consideration of other validated prognostic clinical and molecular variables. Measurement of pretreatment levels of this microRNA may improve risk-stratification for AML patients. A genome-wide gene-expression signature gave biological insights into miR-181a associated AML, and provides a basis for further functional studies. Furthermore, as higher miR-181a expression associated with improved treatment response, increasing miR-181a levels by delivering synthetic miR-181a or by agents increasing endogenous levels of this microRNA in AML blasts may represent a novel and personalized therapeutic approach in AML.:Bibliografische Beschreibung 1 Vorbemerkung / Preliminary Remarks 2 Referat / Abstract 3 Einführung / Introduction 4 Publication 13 Zusammenfassung / Conclusion 31 Ausgewählte Publikation / Selected Publication 38 Komplette Publikationsliste / Complete List of Publications 39 Lebenslauf / Curriculum Vitae 46 Erklärung über die eigenständige Abfassung der Arbeit 50 Danksagung / Acknowledgements 51

The prevailing utility, and indeed necessity, of clinical staging models applied in considerations of neuropsychiatric disease progressions is discussed from the perspectives of schizophrenia spectrum disorders and affective disorders, cannabis in schizopsychotic disorder, incidences of affect and psychosis, staging disorders in aging and the indices and prevalence of apathy. There would appear to be a strong current consensus that the pursuit of clinical staging of these and other brain disease states has contributed a systematic conceptual instrument to facilitate the better understanding, diagnosis, prognosis and treatment as derived from a multitude of genetic predispositions, symptoms and syndromes, early-onset and prodromal phases, recurrences and relapses, that have complicated the situation of the patient. Through a staging determination of the disorder, elements of diagnosis will describe the progression of symptoms/syndromes through pre-onset, prodromal, first-episode, recurrences and relapses, and treatment resistance thereby facilitating the eventual prognosis, intervention alternatives and treatment. This approach varies from observations of individuals at early stages of development (infancy, childhood, adolescece) to early middle age, in the case of diseases expressed through the aging processes. Essentially, the major contribution of the staging model may lie in the early identification, diagnosis, and treatments of disorders that afflict the brain and central nervous system.

A minority of patients with end-stage disease are referred to palliative medicine for consultation in advanced heart failure. Educating stakeholders, including primary care, cardiology, and critical care of the benefits of hospice and palliative medicine for patients with poor prognosis, may increase appropriately timed referrals and improve quality of life for these patients. This article reviews multiple tools useful in prognostication in the setting of advanced heart failure.