The thesis focuses on the activism of youth political organizations in the Czech Republic. The aim of this work is to monitor their activities between 2013 and 2017 due to activism in general but also to political parties. A protest event analysis based on document analysis was created to monitor activities. The second type of research data was interviews with representatives of youth organizations. This type develops results from protest event analysis. Research has shown differences in attitude to activism between left-wing and right-wing organizations. The left-wing focused on protest more than right-wing organization and also often cooperated with non-profit organizations. While right-wing organizations are quite active, they prefer institutional channel and orderly decency before protest arena. Youth organizations have little to do with events before elections. Though they also support political parties or protest against them, they have realized most of the events because of their own agendas. Most organizations appreciate mutual cooperation in protests, with one exception when cooperation is rejected from both sides.

Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan-Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, 95% CI [1.03 - 2.11], White = 1.511, 95% CI [1.18 - 1.94], and American Indian/Hawaiian = 1.424, 95% CI [1.12 -1.81] showing positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors.

Spezialprävention – im Sinne der Verminderung von Rückfällen durch Resozialisierung, Abschreckung und Sicherung – gilt als eine der wichtigsten Aufgaben des Strafrechts. Dem entgegengesetzt schreibt der Etikettierungsansatz der Bestrafung einen negativen Effekt auf die Legalbewährung zu. Was die deutsche Strafrechtspraxis in dieser Hinsicht bewirkt, ist allerdings weithin unbekannt. Kriminologische Untersuchungen auf dem Gebiet der Wirkungs- und Behandlungsforschung zeigen keine eindeutigen empirischen Befunde. Zudem sind sie meist zeitlich und räumlich eng begrenzt. In der hier vorgestellten Arbeit soll der Frage nachgegangen werden, ob sich der spezialpräventive Erfolg des Strafrechts mit Hilfe von Bundeszentralregisterdaten empirisch prüfen lässt. Die Arbeit stützt sich auf Daten und Auswertungen, die im Rahmen der Legalbewährungsuntersuchungen 1994-1998 und 2004-2007 erstellt wurden. Diese dort präsentierten deskriptiven Auswertungen werden kritisch analysiert; die Datenanalyse wird durch den Einsatz quasi-experimenteller und multifaktorieller Methoden dort verfeinert, wo es notwendig und sinnvoll erscheint. Mit Hilfe dieser Methoden soll der Frage der – positiven oder negativen – Wirkung der Strafen nachgegangen werden, indem Effekte von personen- und tatbezogenen Prädiktoren kontrolliert werden, um den Effekt der Strafe auf die Wiederverurteilung zu isolieren. Darüber hinaus wird eine deskriptive Analyse der Legalbewährungsdauer, nach unterschiedlichen Sanktionsformen vorgestellt und mit Hilfe von Ereignisanalysen differenziert. Die Ergebnisse zeigen, dass auch unter Berücksichtigung anderer Prädiktoren eine schwächere, aber eigenständige Sanktionswirkung zu beobachten ist. In der Mehrzahl der Fälle zeigen sich geringere (monatliche) Rückfallraten nach weniger eingriffsintensive ambulante Sanktionen als nach schwereren Sanktionen. Hier von negativen Sanktionswirkungen zu sprechen ist dennoch voreilig. Weitere differenzierte Analysen für homogenere Tätergruppen und regionale Vergleiche erscheinen notwendig. Möglichkeiten und Chancen für weiterführende Auswertungen werden sich auch durch die Fortführung der Rückfalluntersuchungen ergeben.

Males and age group 1 to 5 years show a much higher risk for childhood acute lymphoblastic leukemia (ALL). We performed a case-only genome-wide association study (GWAS), using the Illumina Infinium HumanCoreExome Chip, to unmask gender- and age-specific risk variants in 240 non-Hispanic white children with ALL recruited at Texas Children’s Cancer Center, Houston, Texas. Besides statistically most significant results, we also considered results that yielded the highest effect sizes. Existing experimental data and bioinformatic predictions were used to complement results, and to examine the biological significance of statistical results. Our study identified novel risk variants for childhood ALL. The SNP, rs4813720 (RASSF2), showed the statistically most significant gender-specific associations (P < 2 x 10-6). Likewise, rs10505918 (SOX5) yielded the lowest P value (P < 1 x 10-5) for age-specific associations, and also showed the statistically most significant association with age-at-onset (P < 1 x 10-4). Two SNPs, rs12722042 and 12722039, from the HLA-DQA1 region yielded the highest effect sizes (odds ratio (OR) = 15.7; P = 0.002) for gender-specific results, and the SNP, rs17109582 (OR = 12.5; P = 0.006), showed the highest effect size for age-specific results. Sex chromosome variants did not appear to be involved in gender-specific associations. The HLA-DQA1 SNPs belong to DQA1*01:07and confirmed previously reported male-specific association with DQA1*01:07. Twenty one of the SNPs identified as risk markers for gender- or age-specific associations were located in the transcription factor binding sites and 56 SNPs were non-synonymous variants, likely to alter protein function. Although bioinformatic analysis did not implicate a particular mechanism for gender- and age-specific associations, RASSF2 has an estrogen receptor-alpha binding site in its promoter. The unknown mechanisms may be due to lack of interest in gender- and age-specificity in associations. These results provide a foundation for further studies to examine the gender- and age-differential in childhood ALL risk. Following replication and mechanistic studies, risk factors for one gender or age group may have a potential to be used as biomarkers for targeted intervention for prevention and maybe also for treatment.

Diploma thesis "Marihuana: drug or medicine?" deals with recent change of a medicine law and with process enabling treatment by marihuana. It identifies stakeholders and advocacy coalitions involved in the law and public policy enforcement and explains what is the motivation for these coalitions and on which values is the motivation based. Using event analysis this thesis shows timeline of events moving towards the change of the law and reveals the stakeholders who are significant for the change. Their public speeches are analyzed and stakeholders are divided into advocacy coalitions on the basis of the analysis. The conclusion of the qualitative content analysis is verified by half structured interviews with stakeholders representing the coalitions. Three coalitions were identified in cannabis subsystem. First of them is liberal and tries to get the legalization trough, the second one tries to enable a treatment by marihuana for patients and the third coalition is skeptic to cannabis treatment. The thesis explains a participation of these coalitions on the change and their relations to each other.

<p>Hourly archived rainfall records are separated into individual rainfall events with</p> <p>an Inter-Event Time Denition. Individual storms are characterized by their depth,</p> <p>duration, and peak intensity. Severe events are selected from among the events for</p> <p>a given station. A lower limit, or threshold depth is used to make this selection,</p> <p>and an upper duration limit is established. A small number of events per year are</p> <p>left, which have relatively high depth and average intensity appropriate to small</p> <p>to medium catchment responses. The Generalized Pareto Distributions are tted</p> <p>to the storm depth data, and a bounded probability distribution is tted to storm</p> <p>duration. Peak storm intensity is bounded by continuity imposed by storm depth</p> <p>and duration. These physical limits are used to develop an index measure of peak</p> <p>storm intensity, called intensity peak factor, bounded on (0; 1), and tted to the Beta</p> <p>distribution. The joint probability relationship among storm variables is established,</p> <p>combining increasing storm depth, increasing intensity peak factor, with decreasing</p> <p>storm duration as being the best description of increasing rainstorm severity. The</p> <p>joint probability of all three variables can be modelled with a bivariate copula of</p> <p>the marginal distributions of duration and intensity peak factor, combined simply</p> <p>with the marginal distribution of storm depth. The parameters of the marginal</p> <p>distributions of storm variables, and the frequency of occurrence of threshold-excess</p> <p>events are used to assess possible shifts in their values as a function of time and</p> <p>temperature, in order to evaluate potential climate change eects for several stations.</p> <p>Example applications of the joint probability of storm variables are provided that</p> <p>illustrate the need to apply the methods developed.</p> <p>The overall contributions of this research combine applications of existing probabilistic</p> <p>tools, with unique characterizations of rainstorm variables. Relationships</p> <p>between these variables are examined to produce a new description of storm severity,</p> <p>and to begin the assessment of the eects of climate change upon severe rainstorm</p> <p>events.</p> <p>i</p> / Doctor of Philosophy (PhD)

This thesis surveys the method of extending Cox proportional hazard models (1972) and the general class of semiparametric model (2004) in the upgrades or downgrades of credit ratings by S&P. The two kinds of models can be used to modify the relationship of covariates to a recurrent event data of upgrades or downgrades. The benchmark credit-scoring model with a quintet of financial ratios which is inspired by the Z-Score model is employed. These financial ratios include measures of short-term liquidity, leverage, sales efficiency, historical profitability and productivity. The evidences of empirical results show that the financial ratios of historical profitability, leverage, and sales efficiency are significant factors on the rating transitions of upgrades. For the downgrades data setting, the financial ratios of short-term liquidity, productivity, and leverage are significant factors in the extending Cox models, whereas only the historical profitability is significant in the general class of semiparametric model. The empirical analysis of S&P credit ratings provide evidence supporting that the transitions of credit ratings are related to some determined financial ratios under these new econometrics methods.

In Sweden, there has been an long term effort to allow as heavy traffic as possible, provided thatthe road network can handle it. This is because heavy traffic offers a competitive advantage withsocio-economic gains. In July 2018, the Swedish Transport Administration made 12 percent ofthe Swedish road network avaliable for the new maximum vehicle weight of 74 tonnes, basedon a legislative change from 2017. It is known that heavy traffic has a negative effect on thedegradation of the road, but it prevails divided opinions on whether 74 tonnes have a greaterimpact on the degradation rate compared to previous maximum gross weights of 64 tonnes.The 74 tonne vehicles have the same allowed axle load, which means more axles per vehicle. Some argue that an increased total load and more axles affect the degradation associated withtime-dependent material properties, while others argue that 74 tonnes mean fewer heavy vehiclesoverall, and thus should have a positive impact on the road’s lifespan. The construction companySkanska therefore requests a statistical analysis that enables to nuance the effects that heavytraffic has on the Swedish state road network. Since there is very limited data on the effect of 74 tonne traffic, this Master thesis instead focuseson modeling heavy traffic in general in order to be able to draw conclusions on which variablesare significant for a road’s lifetime. The method used is survival analysis where the lifetimeof the road is defined as the time between two maintenance treatments. The model selectedis the semi-parametric ’Cox Proportional Hazard Model’. The model is fitted with data froman open source database called LTPP (Long Term Pavement Performance) which is providedby the National Road and Transport Research Institute (VTI). The result of the modeling ispresented with hazard ratios, which is the relative risk that a road will require maintance atthe next time stamp compared to a reference category. The covariates that turned out to besignificant for a road’s lifetime and thus are included in the model are; lane width, undergroundtype, speed limit, asphalt layer thickness, bearing layer thickness and proportion of heavy traffic. Survival curves estimated by the model are also presented. In addition, a sensitivity analysis ismade by exploring survival curves estimated for different scenarios, with different combinationsof covariate levels.The results is then compared with previous studies on the subject. The most interesting finding isa case study from Finland since Finland allow 76 tonne vehicles since 2013. In the comparison,the model’s significant variables are confirmed, but the significance of precipitation and thenumber of axes for a roads lifetime is also highlighted

Die Beurteilung der Wirkung von Cariporide auf dieEreignis-Wahrscheinlichkeit eines Herzinfarktes oder des Todes imRahmen einer Bypass-Operation ist Gegenstand der Arbeit. DasNHE-Austauschersystem in der Herzmuskelzelle induziert den unterIschämie durch den intrazellulären Protonenüberschusshervorgerufenen Na(+)- und Ca(2+)-Einstrom. Cariporide ist einNHE-Inhibitor, der den unter Ischämie durch die Ca(2+)-Überladunginduzierten Herzmuskelzelltod verzögern soll. In einer kombinierten Phase-II/III-Studie (GUARDIAN, n=11590) war derEinfluss verschiedener intravenöser Dosen von Cariporide auf dieHäufigkeit von Herzinfarkt oder Tod in ACS/NQMI, PTCA undCABG-Patientenkollektiven untersucht worden. Nur die höchstdosierteCABG-Gruppe zeigte eine signifikante Reduktion der Ereignisrate um24,7% (p=0,027) gegenüber Placebo. Diese schwacheDosis-Wirkungs-Beziehung konnte durch eine pharmakokinetische undpharmakodynamische Populationsanalyse in eineKonzentrations-Wirkungs-Beziehung überführt werden. Zur Entwicklungdes Populationsmodells waren verschiedene Submodelle notwendig: 1. Modell für den Zeitverlauf der Ereignisrate: Durch Kombination zweier Weibull-Verteilungen ist es möglich, die beobachteten Daten als Überlebenszeitfunktion nach CABG zu beschreiben. Ein akutes, unmittelbar auf die CABG-Operation zurückzuführendes Risiko wird hier von einem chronischen Risiko unterschieden. 2. Pharmakokinetisches Modell: Ein multiexponentielles populationspharmakokinetisches Modell ist notwendig zur Beschreibung der PK nach iv-Applikation von Cariporide bei Probanden und Patienten. 3. Pharmakodynamisches Modell: Über ein empirisches logistisches Modell wird die Reduktion des akuten Risikos mit der mittleren Cariporide Plasmakonzentration unter der Bypass-Operation verknüpft. In einer Substudie der GUARDIAN-Hauptstudie konnte daspopulationspharmakokinetische Modell aus der früherenPhase-I-Entwicklung mit Probanden für die Patienten validiert werden.Die mit Hilfe der individüllen Dosierung, der demographischen Datenund dem Populationsmodell für die Periode mit dem höchsten Risikowährend der CABG-Operation vorhergesagten mittlerenPlasmakonzentrationen flossen in die Analyse derKonzentrations-Zeit-Abhängigkeit der Ereignis-Wahrscheinlichkeit ein. Eine untere Schwellenkonzentration (0,5mg/l), unterhalb der mitkeinem Effekt zu rechnen ist, wurde bestimmt. Die Daten erlaubten dieSchätzung des maximalen Effekts nur unzureichend. Die maximaleRisikoreduktion von 60% wurde mit einem Konfidenzintervall von29% bis 100% geschätzt. Unter Einsatz einer linearen Näherungdes Hill-Modells wurde eine obere Schwellenkonzentration bei 0,9mg/lbestimmt. Nur 37% aller Patienten der 80mg-Dosisgruppe erreichtenmittlere Konzentrationen oberhalb der unteren Schwellenkonzentration,in der 120mg-Dosisgruppe waren es immerhin schon 75% allerPatienten. Die Infusion von 120mg Cariporide über eine Stunde gefolgt voneiner Erhaltungsdosis von 20mg/h für weitere 47 Stunden sollte bei95% der Patienten während der CABG-Operation zu mittlerenKonzentrationen über der minimal effektiven Konzentration von0,5mg/l führen. Eine auf diese Weise mittels Simulationenoptimierte Dosierungsregel sollte während der CABG-Operation zu einemerhöhten Schutz der Patienten gegen die Folgen ischämischerEreignisse führen. Eine weitere Erhöhung der Erhaltungsdosis aufbis zu 40mg/h mit einer entsprechenden Anpassung der Initialdosissollte 95% der Patienten sogar über die bisher nur unsicher zubestimmende obere Grenzkonzentration von 0,9mg/l bringen. Solltenkeine dosislimitierenden Nebenwirkungen auftreten, kann dieseErhöhung sowohl der Initialdosis als auch der Erhaltungsdosis zueiner weiteren Verbesserung während der Risikoperiode führen undeinen weiteren potentiellen klinischen Vorteil für Cariporideerbringen. / Subject of this analysis is the assessment of the effect of cariporideon the event probability of a myocardial infarction (MI) or death inthe scope of a coronary artery bypass graft. Thesodium-hydrogen-exchange system (NHE) in the myocardial cell inducesthe sodium and calcium influx caused by an ischaemia induced hydrogenoverload. Cariporide is a NHE-inhibitor which is seen to be delayingthe necrosis of myocardial cells caused by the ischaemia inducedcalcium influx. The influence of different intravenous doses of cariporide on thefrequency of MI and death in ACS/NQMI, PTCA, and CABG patients hadbeen investigated in a combined phase II/III trial (GUARDIAN,n=11590). Only the highest dosed CABG-subgroup showed a significantreduction of the event-rate compared to placebo of 24.7% (p=0.027).This weak dose-effect-relationship could be translated into aconcentration-effect relationship by using a populationpharmacokinetic/pharmacodynamic (PK/PD) analysis. To develop thispopulation model a series of sub-models were established: 1) Model for the time-to-event progression: using a combination of two Weibull-distributions, it was possible to describe the observed data following the CABG procedure by means of a survival-function. An acute risk, likely to be related to the CABG-procedure could be discriminated from a chronic risk. 2) Pharmacokinetic model: a multi-exponential population PK model was necessary to describe the PK after iv-application of cariporide in volunteers as well patients. 3) Pharmacodynamic model: using an empirical logistic model the reduction of the acute risk was linked to the cariporide plasma-concentrations. In a sub-study of the GUARDIAN-main study, the population PK model ofthe phase I development in volunteers had been be validated. Usingthe individual dosing, the individual demographic information and thepopulation PK model mean concentrations were calculated for the periodof the highest risk during the CABG procedure. Those concentrationswere then introduced into the analysis of the concentration timedependency of the event probability. A lower threshold concentration (0.5mg/l) was estimated beneath thatno effect would be expected. The data permitted the estimation of themaximum effect only insufficiently. A maximum risk reduction of 60%was estimated with a confidence interval from 29% to 100%. Using thelinear approximation of the Hill-model an upper thresholdconcentration of 0.9mg/l could be determined. Mean concentrationsunder risk were reached above the lower threshold concentration inonly 37% of all patients in the 80mg dose group, whereas in the 120mgdose-group already 75% of the patients exceeded the lower thresholdconcentration. The infusion of 120mg cariporide for an hour followed by a maintenancedose of 20mg/h for further 47 hours should maintain in 95% of thepatients during the CABG-procedure mean concentrations above theminimal effective concentration of 0.5mg/l. A dose regimen optimisedin this sense by means of simulations should lead to an increasedprotection against ischemic events during and after theCABG-operation. A further increase of the maintenance dose up to40mg/h with a corresponding adaptation of the initial dose shouldshift at least 95% of the patients above the so far impreciseestimated upper threshold concentration of 0.9mg. If no dose limitingside-effects occur, this increase of both the initial dose and themaintenance dose may lead to a further improvement during the riskperiod and may result in a further potential clinical advantage forcariporide.

The thesis focuses on a chosen public policy issue, as a part of cultural policy, namely on an implementation of a project of new building of National library of Czech Republic in Prague, arisen from an international architecture competition. This thesis has a form of a case study paper and investigates all relevant events and circumstances of the case, as well as interested stakeholders. They were characterised to disclose their possible role in implementation deficit, which occurred in the case. The aim of this thesis is to provide complex insight into the case, to find the point of implementation deficit in the process and to identify the values and hidden motivations of stakeholders. The thesis is divided into three chapters. In the first chapter, there is a summary of theoretical knowledge about public policy and implementation process and its analysis. The author describes three possible approaches to implementation analysis. Second chapter focuses on culture and its specifics, in the forming of culture policy. The third chapter is a complete analysis of the case, including event analysis and stakeholder analysis. In the conclusion, the author sums up the identified causes of implementation deficit and gives recommendations for possible future implementation of a similar cultural project.