The thesis aims at change-point estimation in gradual change models. Methods avail- able in literature are reviewed and modified for point-of-stabilisation (PoSt) context, present e.g. in drug continuous manufacturing. We describe in detail the estimation in the linear PoSt model and we extend the methods to quadratic and Emax model. We describe construction of confidence intervals for the change-point, discuss their interpre- tation and show how they can be used in practice. We also address the situation when the assumption of homoscedasticity is not fulfilled. Next, we run simulations to calculate the coverage of confidence intervals for the change-point in discussed models using asymp- totic results and bootstrap with different parameter combinations. We also inspect the simulated distribution of derived estimators with finite sample. In the last chapter, we discuss the situation when the model for the data is incorrectly specified and we calculate the coverage of confidence intervals using simulations. 1

Homeownership and suburbanisation are two sides of the same coin in the context of Australia. This thesis explores the housing system that facilitates homeownership under a framework of institutional path dependence and how that has facilitated spatial patterns of suburbanization in contemporary Melbourne. Australia has been considered a homeowner society for the larger part of the 20th century. Living and owning a house on a ‘quarter acre block’ in one of its major cities is said to have been a virtue even before homeownership was in reach for the majority of the Australian population. The years after WWII enabled up to 70 per cent of the population to access homeownership tenure. In that, this thesis analyses the institutional, societal and economic configurations that enabled increased homeownership provision, but also the historical processes that further facilitated a system around a dominant tenure. Path dependency theory, developed in the field of historical institutionalism, offers an analytical toolbox to examine long-term processes. In a broad sense, path dependency refers to the continuous reproduction of institutional systems in place. The second part of this thesis examines urbanisation processes in Melbourne, under a framework of institutional and spatial change. Cities are changing environments that, although, they inhabit determinist and reinforcing spatial patterns and institutions, transition over time. By looking at historical and contemporary institutional processes, this thesis examines metropolitan strategies to consolidate the outward growth in the city of Melbourne. Under the aspect of change, current challenges to the built environment are presented. A third analysis connects the macro discussion with a case study of a local housing provider in Melbourne, that in some regards may be viewed as antithesis to the contemporary building regime in the Australian and Melbourne context. As the first in-depth path dependency analysis in the Australian context, this thesis can be viewed as a contribution to the growing body of path dependency literature with a housing focus that also combines the spatial nature of urban environments.

O presente estudo tem por objetivo analisar a política pública sobre drogas brasileira. Verificase que a política de drogas do Brasil respondeu positivamente ao proibicionismo que caracteriza o regime internacional de controle do trânsito de drogas, que na América Latina viu-se produzido sob forte pressão estadunidense. O trabalho descreve um histórico de produção da política brasileira sobre drogas dividida por duas dimensões: uma delas do campo da saúde, e a outra da justiça e segurança. A seguir, entendendo que a política sobre drogas no Brasil encontra-se em processo de mudança, iniciado há duas décadas e com origem, principalmente, em iniciativas do campo da saúde serão aplicados os modelos de múltiplos fluxos de Kingdon e o de mudança institucional gradual de Mahoney e Thelen a fim de esboçar algumas interpretações sobre a dinâmica desta mudança. / The present study aims to analyze Brazilian public policy on drugs. It is verified that the drug policy of Brazil responded positively to the prohibitionism that characterizes the international regime of control of the traffic of drugs, that in Latin America has been produced under strong American pressure. The paper describes a history of the production of Brazilian drug policy divided into two dimensions: one from the health field and the other from justice and security. Following, understanding that drug policy in Brazil is in a process of changing, initiated two decades ago and mainly originated in initiatives from the field of health will be applied the models of multiple streams of Kingdon and the theory of gradual institutional change from Mahoney and Thelen in order to sketch some interpretations about the dynamics of this change.

O presente estudo tem por objetivo analisar a política pública sobre drogas brasileira. Verificase que a política de drogas do Brasil respondeu positivamente ao proibicionismo que caracteriza o regime internacional de controle do trânsito de drogas, que na América Latina viu-se produzido sob forte pressão estadunidense. O trabalho descreve um histórico de produção da política brasileira sobre drogas dividida por duas dimensões: uma delas do campo da saúde, e a outra da justiça e segurança. A seguir, entendendo que a política sobre drogas no Brasil encontra-se em processo de mudança, iniciado há duas décadas e com origem, principalmente, em iniciativas do campo da saúde serão aplicados os modelos de múltiplos fluxos de Kingdon e o de mudança institucional gradual de Mahoney e Thelen a fim de esboçar algumas interpretações sobre a dinâmica desta mudança. / The present study aims to analyze Brazilian public policy on drugs. It is verified that the drug policy of Brazil responded positively to the prohibitionism that characterizes the international regime of control of the traffic of drugs, that in Latin America has been produced under strong American pressure. The paper describes a history of the production of Brazilian drug policy divided into two dimensions: one from the health field and the other from justice and security. Following, understanding that drug policy in Brazil is in a process of changing, initiated two decades ago and mainly originated in initiatives from the field of health will be applied the models of multiple streams of Kingdon and the theory of gradual institutional change from Mahoney and Thelen in order to sketch some interpretations about the dynamics of this change.

The goal of this diploma thesis is to evaluate the total cost ratio in relation to corporate efficiency. The theoretical part of the thesis deals with basic terms of cost, financial and managerial concept of costs and different approaches to classification of costs. In this part the principle of corporate efficiency is explained and the difference methods of measuring of efficiency are mentioned. The practical part of this thesis is oriented primarily to describing development of costs in company and determination of most important cost items. This part also focuses on the calculation of profitability indicators and pyramidal decomposition of ROE. After this, the influence of sub-indicators to top-indicator was evaluated by using the gradual change method. The ROE was changed between years 2015 and 2016 by -0,1050 CZK. By using the gradual change method, it was determined, that this change was mostly caused by total cost ratio of production con-sumption, because it is the most important cost item in company. The influence of production consump-tion was -0,1078 CZK. Therefore, if the company plans to improve its efficiency and increase profits, the total cost ratio of the production consumption must be better manage.

O presente estudo tem por objetivo analisar a política pública sobre drogas brasileira. Verificase que a política de drogas do Brasil respondeu positivamente ao proibicionismo que caracteriza o regime internacional de controle do trânsito de drogas, que na América Latina viu-se produzido sob forte pressão estadunidense. O trabalho descreve um histórico de produção da política brasileira sobre drogas dividida por duas dimensões: uma delas do campo da saúde, e a outra da justiça e segurança. A seguir, entendendo que a política sobre drogas no Brasil encontra-se em processo de mudança, iniciado há duas décadas e com origem, principalmente, em iniciativas do campo da saúde serão aplicados os modelos de múltiplos fluxos de Kingdon e o de mudança institucional gradual de Mahoney e Thelen a fim de esboçar algumas interpretações sobre a dinâmica desta mudança. / The present study aims to analyze Brazilian public policy on drugs. It is verified that the drug policy of Brazil responded positively to the prohibitionism that characterizes the international regime of control of the traffic of drugs, that in Latin America has been produced under strong American pressure. The paper describes a history of the production of Brazilian drug policy divided into two dimensions: one from the health field and the other from justice and security. Following, understanding that drug policy in Brazil is in a process of changing, initiated two decades ago and mainly originated in initiatives from the field of health will be applied the models of multiple streams of Kingdon and the theory of gradual institutional change from Mahoney and Thelen in order to sketch some interpretations about the dynamics of this change.

Modeling of quantile curves is a common problem across various fields in today's practice. The topic of this thesis is estimating quantile curves in case of two-sample gradual change. That is, when a relationship between two continuous variables in two samples is of interest, where the relationship is the same for both samples until a certain value of the explanatory variable. From that point on the relationship can differ. The result of this thesis is a procedure for estimating quantile curves, which fulfill this concept. 1

Title: Dose-response curves Author: Martin Hezoučký Department: Department of Probability and Mathematical Statistics Supervisor: doc. RNDr. Zdeněk Hlávka, Ph.D., Department of Probability and Mathematical Statistics Abstract: In this thesis, we deal with the process of research and development of new medical substances with a focus on statistical methods used to determine appropriate doses. For this purpose, we examine the dose-response relationship. First, we describe a typical procedure for the development of a new drug. Second, we focus in detail on the MCP-Mod method. Third, we propose a new method based on the theory of gradual change models. This approach tests whether the administration of the drug has a significant effect. If so, the dose with desired effect is estimated using an appropriate model. Specifically, we provide an esti- mate using linear, quadratic and Emax gradual change models. We also describe a construction of a confidence interval for the point of change and also for the dose with the desired effect. The advantage of the proposed method over the MCP-Mod is the determination of the confidence intervals. Finally, we apply the above mentioned methods to data from the U.S. Tox21 research program and compare the results based on several tested substances and clearly demonstrate the...

Testing Structural Changes Using Ratio Type Statistics Barbora Peštová Charles University in Prague, Faculty of Mathematics and Physics, Department of Probability and Mathematical Statistics, Czech Republic Abstract of the doctoral thesis We deal with sequences of observations that are naturally ordered in time and assume various underlying stochastic models. These models are parametric and some of the parameters are possibly subject to change at some unknown time point. The main goal of this thesis is to test whether such an unknown change has occurred or not. The core of the change point methods presented here is in ratio type statistics based on maxima of cumulative sums. Firstly, an overview of thesis' starting points is given. Then we focus on methods for detecting a gradual change in mean. Consequently, procedures for detection of an abrupt change in mean are generalized by considering a score function. We explore the possibility of applying the bootstrap methods for obtaining critical values, while disturbances of the change point model are considered as weakly dependent. Procedures for detection of changes in parameters of linear regression models are shown as well and a permutation version of the test is derived. Then, a related problem of testing a change in autoregression parameter is studied....