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Abstract There is evidence that the process leading to type 1 diabetes may start in early infancy or even in utero, with a prodrome of variable duration preceding clinical manifestation. The purpose of the present work was to learn more about the occurrence and significance of humoral beta-cell autoimmunity during pregnancy and in infancy, to search for possible signs of prenatal or early postnatal induction of beta-cell autoimmunity and to explore the role of enterovirus infections as potential triggers of such autoimmunity. The population comprised mothers and their newborn infants from families with type 1 diabetes who had entered the first (n=20) or the second pilot study (n=208) of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Almost 40% of the mothers with type 1 diabetes had antibodies to islet cells (ICA), 55% to glutamic acid decarboxylase (GADA) and 54% to the IA-2 protein (IA-2A) in the two samples taken during pregnancy, where the frequencies for the unaffected mothers were 5%, 5% and 3%, respectively. All autoantibody specificities were detected in the cord blood largely at the same frequencies as in the maternal circulation. In addition, ICA was found in 2.7%, GADA in 0.6%, IA-2A in 0.3% and insulin autoantibodies (IAA) in 0.1% out of a series of 1002 cord blood samples from infants representing the normal population. None of the infants of the autoantibody-negative mothers in these series had autoantibodies detectable in their cord blood. The rate of decline of transplacentally transferred autoantibodies during the first months of life was observed to be similar to that reported for the disappearance of maternally acquired IgG antibodies, the estimated mean elimination time ranging from 3.1-4.5 months. The higher the initial autoantibody level, the longer was the elimination time, and transplacentally transferred autoantibodies were occasionally detected up to the age of 9-12 months, and even at 15 months in a very few cases. The peak incidence of enterovirus RNA in serum was observed at the age of 6-12 months, while that of infections, based on changes in antibody titres, was seen at the age of 18 months. The frequency of enterovirus infections in the autoantibody-positive infants during the 6 months before the appearance of the first autoantibodies was almost three times higher than in age-matched infants testing negative for autoantibodies. These observations suggest that pregnancy does not have any strong modulating effect on the prevalence and titres of diabetes-associated autoantibodies. If such autoantibodies are present in the mother, most of them are transferred to the foetal circulation and are detectable in the cord blood. No signs of foetal induction of beta-cell autoimmunity were observed, indicating that such a phenomenon is extremely rare. Most of the transplacentally transferred autoantibodies disappear within the first 3-6 months of postnatal life, but they may persist even up to the age of 15 months in exceptional cases, suggesting that the optimal age for the initiation of large-scale screening in the general population is 18-24 months. The temporal association between enterovirus infections and the first signs of beta-cell autoimmunity supports the hypothesis that enteroviruses may induce a primary beta-cell insult.

CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Kahounová Supervizor: Doc. PharmDr. Marie Vopršálová, Ph.D. Ing. Jaroslav Procházka Title of diploma thesis: ELIMINATION OF ALKOHOL IN BLOOD OF PATIENTS TREATED WITH COUMARIN DRUGS Coumarin preparations are the most commonly used oral anticoagulants. The main representative is Warfarin. The most important function of warfarin is to reduce the formation of K-dependent coagulation factors in the liver. Alcohol is the oldest and most widely used addictive substance. Alcohol is the oldest and most commonly used substance. Society is tolerated and regular use of small doses of alcohol is considered "beneficial to health". The aim of my thesis was to find out how the concomitant use of coumarin drugs and alcohol interacts. There were tested 62 people (33 men and 29 women), of whom 27 people (14 men and 13 women) were treated with coumarin drugs, 35 people (19 men and 16 women) formed the control group of individuals without treatment with coumarin drugs. All people were given a standard dose of alcohol. The blood alcohol level (COBAS INTEGRA 400 plus) and INR (SYSMEX CA 1500) were measured in the time-0 (before administration), 1½ and 3 hours (after administration). The data obtained was...

Based on the geometric analysis of Gaussian elimination (GE) found in Neal and Poole (Linear Algebra Appl. 173 (1992) 239-264) and Poole and Neal (Linear Algebra Appl. 149 (1991) 249-272; 162-164 (1992) 309-324), a new pivoting strategy, Rook's pivoting (RP), was introduced in Neal and Poole (Linear Algebra Appl. 173 (1992) 239-264) which encourages stability in the back-substitution phase of GE while controlling the growth of round-off error during the sweep-out. In fact, Foster (J. Comput. Appl. Math. 86 (1997) 177-194) has previously shown that RP, as with complete pivoting, cannot have exponential growth error. Empirical evidence presented in Neal and Poole (Linear Algebra Appl. 173 (1992) 239-264) showed that RP produces computed solutions with consistently greater accuracy than partial pivoting. That is, Rook's pivoting is, on average, more accurate than partial pivoting, with comparable costs. Moreover, the overhead to implement Rook's pivoting in a scalar or serial environment is only about three times the overhead to implement partial pivoting. The theoretical proof establishing this fact is presented here, and is empirically confirmed in this paper and supported in Foster (J. Comput. Appl. Math. 86 (1997) 177-194).

A common approach to the treatment of instrumental problem behavior is the introduction of an acceptable alternative source of reinforcement. However, when alternative reinforcement is removed or reduced, the target behavior tends to relapse. The relapse of a target response following the removal of alternative reinforcement has been termed resurgence. Shahan and Sweeney developed a quantitative model of resurgence based on behavioral momentum theory that captures both the disruptive and strengthening effects of alternative reinforcement on the target response. The quantitative model suggests that although higher rates of alternative reinforcement result in faster response elimination, lower rates of alternative reinforcement result in less relapse when removed. The present study was designed to examine the possibility that good target response suppression and less relapse could be achieved by beginning with a higher (rich) rate of alternative reinforcement and gradually thinning it such that a lower (lean) rate of alternative reinforcement is ultimately removed. Furthermore, the data obtained were generated to provide insight into how thinning rates of alternative reinforcement might be incorporated into the quantitative model of resurgence. Results suggest that rich rates of alternative reinforcement were more effective than lean or thinning rates of alternative reinforcement at response suppression during treatment, but when alternative reinforcement was discontinued, the group that experienced rich rates exhibited a substantial increase. Although lean and thinning rates of alternative reinforcement were not as effective at response suppression during treatment as rich rates, they still resulted in substantial decreases in the target response. Furthermore, removal of lean rates of alternative reinforcement did not result in substantial increase in the target response. Advantages and disadvantages of rich, lean, and thinning alternative reinforcement rates are discussed with respect to target response suppression and sensitivity to the end of treatment, and an alternative response rate is discussed. Although a small modification to the quantitative model was able to similarly account for data produced by rich, lean, and thinning alternative reinforcement, as it currently stands the model is unable to account for the finding that alternative reinforcement may not always serve as a disruptor relative to a no alternative reinforcement control.

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Cette thèse est une contribution à la théorie des modèles des corps valués. Les principaux résultats de ce texte sont des résultats d’éliminations des quantificateurs et des imaginaires. Le premier chapitre contient une étude des imaginaires dans les extensions finies de Qp. On y démontre que ces corps ainsi que leurs ultraproduits éliminent les imaginaires dans le langage géométrique. On en déduit un résultat de rationalité uniforme pour les fonctions zêta associées aux familles de relations d’équivalences définissables dans les extensions finies de Qp. La motivation première du deuxième chapitre est l’étude de W(F_p^alg) en tant que corps valué analytique de différence. Plus généralement, on démontre un théorème d’élimination des quantificateurs de corps dans le langage RV pour les corps valués analytiques -Henséliens de caractéristique nulle. On donne aussi une axiomatisation de la théorie de W(F_p^alg) ainsi qu’une preuve qu’elle est NIP. Dans le troisième chapitre, on prouve la densité des types définissables dans certains enrichissements d’ACVF. On en déduit un critère pour l’élimination des imaginaires et la propriété d’extension invariante. Ce chapitre contient aussi des résultats abstraits sur les ensembles extérieurement définissables dans les théories NIP. Dans le dernier chapitre, les résultats du chapitre précédent sont appliqués à VDF, la modèle complétion des corps valués munis d’une dérivation qui préserve la valuation, pour obtenir l’élimination des imaginaires dans le langage géométrique ainsi que la densité des types définissables et la propriété d’extension invariante. Ce chapitre contient aussi des considérations sur les fonctions définissables, les types et les groupes définissables dans VDF. / This thesis is about the model theory of valued fields. The main results in this text are eliminationsof quantifiers and imaginaries. The first chapter is concerned with imaginaries in finite extensions of Qp. I show that these fields and their ultraproducts eliminate imaginaries in the geometric language. As a corollary, I obtain the uniform rationality of zeta functions associated to families of equivalence relations that aredefinable in finite extensions of Qp.The motivation for the second chapter is to study W(F_p^alg) as an analytic difference valued field. More generally, I show a field quantifier elimination theorem in the RV-language for -Henselian characteristic zero valued fields with an analytic structure. I also axiomatise the theory of W(F_p^alg) and I show that this theory is NIP.In the third chapter, I prove the density of definable types in certain enrichments of ACVF. From this result, I deduce a criterion for the elimination of imaginaries and the invariant property. This chapter also contains abstract results on externally definable sets in NIP theories. In the last chapter, the previous chapter is applied to VDF, the model completion of valued fields with a valuation preserving derivation, to obtain the elimination of imaginaries in the geometric language, as well as the density of definable types and the invariant extension property. This chapter also contains considerations about definable functions, types and definable groupes in VDF.

In Chapter 1 I study the iterative strategy elimination mechanisms for normal form games. The literature is mostly clustered around the order of elimination. The conventional elimination also requires more strict knowledge assumptions if the elimination is iterative. I define an elimination process which requires weaker rationality. I establish some preliminary results suggesting that my mechanism is order independent whenever iterative elimination of weakly dominated strategies (IEWDS) is so. I also specify conditions under which the \undercutting problem" occurs. Comparison of other elimination mechanisms in the literature (Iterated Weak Strategy Elimination, Iterated Strict Strategy Elimination, Generalized Strategy Eliminability Criterion, RBEU, Dekel-Fudenberg Procedure, Asheim- Dufwenberg Procedure) and mine is also studied to some extent. In Chapter 2 I study the axiomatic characterization of a well-known bankruptcy rule: Proportional Division (PROP). The rule allocates shares proportional to agents' claims and hence, is intuitive according to many authors. I give supporting evidence to this opinion by first defining a new type of consistency requirement, i.e. union-consistency and showing that PROP is the only rule that satisfies anonymity, continuity and union-consistency. Note that anonymity and continuity are very general requirements and satisfied by almost all the rules that have been studied in this literature. Thus, I prove that we can choose a unique rule among them by only requiring union-consistency. Then, I define a bankruptcy operator and give some intuition on it. A bankruptcy operator is a mapping from the set of bankruptcy operators to itself. I prove that any rule will converge to PROP under this operator as the claims increase. I show nice characteristics of the operator some of which are related to PROP. I also give a definition for continuity of an operator. In Chapter 3 investigate risk-averse investors' behaviour towards a risky firm. In order to find Pareto Optimal allocations regarding a joint venture, I employ a 2-stage game, first stage of which involves a social-planner committing to an ex-post bankruptcy rule. A bankruptcy rule is a set of suggestions for solving each possible bankruptcy problem. A bankruptcy problem occurs when there is not enough endowment to allocate to the agents each of whom has a claim on it. I devise the game-theoretic approach posed in K1br1s and K1br1s (2013) and extend it further. In fact, that paper considers a comparison among 4 renowned bankruptcy rules whereas mine do not restrict attention to any particular rule but rather aim to find a Pareto Optimal(PO) one. I start with 2 agent case in order to give some insight to the reader and then, generalise the results to an arbitrary number of investors. I find socially desirable (PO) allocations and show that the same can be achieved through financial markets by the help of some well-known results.