published_or_final_version / Social Work / Master / Master of Social Work

Aus pharmakokinetischer Sicht sind neben Parametern wie der oralen Bioverfügbarkeit und der systemischen Clearance, für die Effektivität und Sicherheit eines inhalativ angewendeten Wirkstoffes unter anderem das Ausmaß der pulmonalen Deposition und seine pulmonale Umverteilungskinetik entscheidend. Wird eine topische Wirkung des Arzneistoffes angestrebt, so trägt eine lange Verweilzeit des Arzneistoffes im Zielgewebe, verbunden mit einer langsamen Umverteilung in den systemischen Kreislauf zu einer Wirkungsoptimierung mit gleichzeitiger Minimierung systemischer Nebenwirkungen bei. In-vitro- und ex-vivo-Modelle eignen sich hervorragend zur isolierten Untersuchung solcher pharmakokinetischer Vorgänge ohne den Einfluss verschiedener in-vivo-Faktoren, wie der Verteilung in andere Gewebe, Metabolisierungs- oder Eliminationsprozessen. Das Ziel der vorliegenden Arbeit war es daher, Modelle der humanen Lunge zu etablieren bzw. weiterzuentwickeln, die möglichst realitätsnah die Untersuchung der Pharmakokinetik pulmonal applizierter Wirkstoffe ermöglichen. / From a pharmacokinetic point of view, the extent of pulmonary deposition and the pulmonary redistribution are crucial for an inhaled drug’s effectiveness and safety besides parameters such as oral bioavailability and systemic clearance. Aiming at a local effect, a long residence time in the target tissue combined with a slow redistribution into systemic circulation contribute to a drug’s optimal potency while simultaneously minimizing systemic adverse effects. In-vitro and ex-vivo models are particularly suitable for examining single pharmacokinetic aspects without the influences occurring in-vivo such as distribution into other tissues and processes of metabolism or elimination. Therefore, the aim of the present thesis was to establish, respectively enhance models of the human lung, which were able to describe the pharmacokinetics of pulmonary applied drugs close to reality.

This thesis addresses the use of machine learning techniques to develop clinical diagnostic tools for breast cancer using molecular data. These tools are designed to assist physicians in their evaluation of the clinical outcome of breast cancer (referred to as prognosis). The traditional approach to evaluating breast cancer prognosis is based on the assessment of clinico-pathologic factors known to be associated with breast cancer survival. These factors are used to make recommendations about whether further treatment is required after the removal of a tumor by surgery. Treatment such as chemotherapy depends on the estimation of patients' risk of relapse. Although current approaches do provide good prognostic assessment of breast cancer survival, clinicians are aware that there is still room for improvement in the accuracy of their prognostic estimations. In the late nineties, new high throughput technologies such as the gene expression profiling through microarray technology emerged. Microarrays allowed scientists to analyze for the first time the expression of the whole human genome ("transcriptome"). It was hoped that the analysis of genome-wide molecular data would bring new insights into the critical, underlying biological mechanisms involved in breast cancer progression, as well as significantly improve prognostic prediction. However, the analysis of microarray data is a difficult task due to their intrinsic characteristics: (i) thousands of gene expressions are measured for only few samples; (ii) the measurements are usually "noisy"; and (iii) they are highly correlated due to gene co-expressions. Since traditional statistical methods were not adapted to these settings, machine learning methods were picked up as good candidates to overcome these difficulties. However, applying machine learning methods for microarray analysis involves numerous steps, and the results are prone to overfitting. Several authors have highlighted the major pitfalls of this process in the early publications, shedding new light on the promising but overoptimistic results. Since 2002, large comparative studies have been conducted in order to identify the key characteristics of successful methods for class discovery and classification. Yet methods able to identify robust molecular signatures that can predict breast cancer prognosis have been lacking. To fill this important gap, this thesis presents an original methodology dealing specifically with the analysis of microarray and survival data in order to build prognostic models and provide an honest estimation of their performance. The approach used for signature extraction consists of a set of original methods for feature transformation, feature selection and prediction model building. A novel statistical framework is presented for performance assessment and comparison of risk prediction models. In terms of applications, we show that these methods, used in combination with a priori biological knowledge of breast cancer and numerous public microarray datasets, have resulted in some important discoveries. In particular, the research presented here develops (i) a robust model for the identification of breast molecular subtypes and (ii) a new prognostic model that takes into account the molecular heterogeneity of breast cancers observed previously, in order to improve traditional clinical guidelines and state-of-the-art gene signatures./Cette thèse concerne le développement de techniques d'apprentissage (machine learning) afin de mettre au point de nouveaux outils cliniques basés sur des données moleculaires. Nous avons focalisé notre recherche sur le cancer du sein, un des cancers les plus fréquemment diagnostiqués. Ces outils sont développés dans le but d'aider les médecins dans leur évaluation du devenir clinique des patients cancéreux (cf. le pronostique). Les approches traditionnelles d'évaluation du pronostique d'un patient cancéreux se base sur des critères clinico-pathologiques connus pour être prédictifs de la survie. Cette évaluation permet aux médecins de décider si un traitement est nécessaire après l'extraction de la tumeur. Bien que les outils d'évaluation traditionnels sont d'une aide importante, les cliniciens sont conscients de la nécessité d'améliorer de tels outils. Dans les années 90, de nouvelles technologies à haut-débit, telles que le profilage de l'expression génique par biopuces à ADN (microarrays), ont été mises au point afin de permettre aux scientifiques d'analyser l'expression de l'entièreté du génôme de cellules cancéreuses. Ce nouveau type de données moléculaires porte l'espoir d'améliorer les outils pronostiques traditionnels et d'approfondir nos connaissances concernant la génèse du cancer du sein. Cependant ces données sont extrêmement difficiles à analyser à cause (i) de leur haute dimensionalité (plusieurs dizaines de milliers de gènes pour seulement quelques centaines d'expériences); (ii) du bruit important dans les mesures; (iii) de la collinéarité entre les mesures dûe à la co-expression des gènes. Depuis 2002, des études comparatives à grande échelle ont permis d'identifier les méthodes performantes pour l'analyse de groupements et la classification de données microarray, négligeant l'analyse de survie pertinente pour le pronostique dans le cancer du sein. Pour pallier ce manque, cette thèse présente une méthodologie originale adaptée à l'analyse de données microarray et de survie afin de construire des modèles pronostiques performants et robustes. En termes d'applications, nous montrons que cette méthodologie, utilisée en combinaison avec des connaissances biologiques a priori et de nombreux ensembles de données publiques, a permis d'importantes découvertes. En particulier, il résulte de la recherche presentée dans cette thèse, le développement d'un modèle robuste d'identification des sous-types moléculaires du cancer du sein et de plusieurs signatures géniques améliorant significativement l'état de l'art au niveau pronostique.

This is a study of the ex-dividend day. The study covers six years (2007-2012) and studies the shares included in the OMXS30 on the Stockholm stock exchange. OMXS30 is a share index of the 30 most actively traded stocks on the exchange. The study comprised a total of 145 observations. The purpose of this study is to investigate if the stock price on the ex-dividend day unfolds as the efficient market hypothesis teach or if there exists room for speculation, and thus earn a return higher than the market.The ex-dividend day effect has been studied previously, both on the Swedish market but also abroad. The results of previous researchers are different but they all have one thing in common, namely that there is a certain ex-dividend day effect.When calculating the ex-dividend day effect, the stock prices had to be adjusted for the normal return that occurs during the ex-dividend day. The normal return is not something that is universally known, but must be estimated by the author. In this study, it was estimated using the OMXS30 index movements relative to each company's beta. After that price drop ratio is calculated. The authors found that the share price on average fell by about 90 % of the dividend amount, with the possibility of an excess return of approximately 0.37 %. This was according to statistical tests significantly different from one, indicating that the ex-dividend day effect exists. By studying each year the authors found significant discrepancies between the years that cannot be explained, the authors themselves could conclude that the price drop ratio exists in symbiosis with the current economic situation.

Using Canadian data we estimate the effects of monetary policy shocks on various real and nominal variables using a fully recursive VAR model. We decompose the nominal interest rate into an ex-ante real interest rate and inflationary expectations using the Blanchard-Quah structural VAR model with the identifying restriction that ex-ante real interest rate shocks have but a temporary impact on the nominal interest rate. The inflationary expectations are then employed to estimate a policy reaction function that identifies monetary policy shocks. We find that a positive shock introduced by raising the monetary aggregates raises inflationary expectations and temporarily lowers the ex-ante real interest rate. As well, it depreciates the Canadian dollar and generates other macro effects consistent with conventional monetary theory although these effects are not statistically significant. Using the overnight target rate as the monetary policy instrument we find that a contractionary monetary policy shock lowers inflationary expectations and raises the ex-ante real interest. Such a contractionary monetary policy shock also appreciates the Canadian currency, decreases industrial output and increases the unemployment rate. We obtain qualitatively better results using the overnight target rate rather than a monetary aggregate as the monetary policy instrument. Our estimated results are robust to various modifications of the basic VAR model and do not encounter empirical anomalies such as the liquidity and exchange rate puzzles found in some previous VAR studies of the effects of monetary policy shocks in an open economy.

Using Canadian data we estimate the effects of monetary policy shocks on various real and nominal variables using a fully recursive VAR model. We decompose the nominal interest rate into an ex-ante real interest rate and inflationary expectations using the Blanchard-Quah structural VAR model with the identifying restriction that ex-ante real interest rate shocks have but a temporary impact on the nominal interest rate. The inflationary expectations are then employed to estimate a policy reaction function that identifies monetary policy shocks. We find that a positive shock introduced by raising the monetary aggregates raises inflationary expectations and temporarily lowers the ex-ante real interest rate. As well, it depreciates the Canadian dollar and generates other macro effects consistent with conventional monetary theory although these effects are not statistically significant. Using the overnight target rate as the monetary policy instrument we find that a contractionary monetary policy shock lowers inflationary expectations and raises the ex-ante real interest. Such a contractionary monetary policy shock also appreciates the Canadian currency, decreases industrial output and increases the unemployment rate. We obtain qualitatively better results using the overnight target rate rather than a monetary aggregate as the monetary policy instrument. Our estimated results are robust to various modifications of the basic VAR model and do not encounter empirical anomalies such as the liquidity and exchange rate puzzles found in some previous VAR studies of the effects of monetary policy shocks in an open economy.

La mirada per acostar-se al tema és sociològica. Com a recerca de sociologia vol trobar el context social de les accions i pensaments del grup de sacerdots que van deixar el ministeri i es van allunyar, al voltant dels anys seixanta, del clergat diocesà. El fet es coneix familiarment com "les plegades". Aclarir la complexitat de causes, raons i motius que van tenir per plegar és un dels objectius centrals del treball. Un segon centre d'interès d'aquesta recerca ha estat la identitat dels ex. Cada part del treball aborda aspectes diferents del món social que es vol comprendre i explicar. Cada capítol es podria llegir per separat, com una mirada diferent, com una aproximació diferent al tema. Tanmateix, no són diferents històries, perquè la història que s'explica és sempre la mateixa, destacant -o retallant- ara uns aspectes, ara uns altres. La primera part, "Capellans secularitzats", explica en quin context van decidir fer-se sacerdots (capítol 1) -i per què (capítol 2)- les persones que més tard es van allunyar del ministeri sacerdotal. Es centra en l'ideal que els va moure i en com aquest ideal es va anar transformant (capítol 3). S'apunten algunes de les conseqüències que va tenir la transformació "ideològica". Per tancar aquesta part, es mira d'aclarir quantes són aquestes persones que podem denominar "capellans secularitzats" (excursus).La segona part, "Del Seminari al món real", destaca els contextos institucionals i socials de les trajectòries dels sacerdots secularitzats. El capítol 4 se centra en l'experiència del Seminari com a punt de partida cap al que s'anomena, per contrast, món real. El capítol 5 analitza les característiques que per molts sacerdots va tenir l'experiència del món real i en què va consistir la "realitat" del món. Un cop en el món real, veurem (capítol 6) que desencantament, contradiccions, dubtes i patiment van ser algunes singularitats de l'itinerari de sortida. La tercera part, "Les plegades", ressalta aquells aspectes del context social que podríem considerar, per una banda, camins de sortida i, per altra, causes de les secularitzacions. El capítol 7 analitza algunes de les circumstàncies sociobiogràfiques que van dur als carrerons de la sortida. Formular i classificar les causes, i els motius implícits i explícits dels processos de secularització (o d'allunyament), ocupa bona part del capítol 8. El capítol 9 ofereix una explicació sociològica de les trajectòries vitals dels sacerdots que han estat analitzades. També es dóna veu a altres protagonistes de la història, per exemple, les dones que es van casar amb sacerdots. La quarta part, "La identitat dels ex", aborda el tema de la condició social d'exsacerdot, del canvi d'identitat. En el capítol 10 es tracta de la condició d'ex i es defineixen aquelles dimensions que millor la caracteritzen. En el capítol 11, s'ofereixen alguns models dels processos vitals d'aquestes transformacions que es delimiten entre la maduració i la ruptura. Per acabar, el capítol 12 tracta de respondre què ha estat de la fe professada i de la condició sacerdotal dels excapellans. Les conclusions destaquen tres aspectes del fet d'haver arribat a la fi. En primer lloc, si s'ha arribat al final, no vol dir que sigui l'únic final possible i que l'itinerari escollit no hagués pogut ser diferent. Al llarg del camí han sorgit moltes qüestions que no estaven previstes i d'altres que han quedat pendents. En segon lloc, es fa una mirada enrera per recordar algunes de les brúixoles que han orientat la recerca. Finalment, i en tercer lloc, es volen recollir algunes de les moltes "lliçons" que s'han après. / The perspective for approaching the subject is sociological. As sociological research it wants to find the social context of the actions and thoughts of the group of priests left the ministry and were bent, about the sixties, of the diocesan clergy. The fact is known as Les Plegades. To clarify the complexity of causes, reasons and motives that they had for leaving the priesthood is one of the central goals of the work. A second centre of interest of this research has been the identity of these former priests.Each part of the work approaches different aspects of the social world that the author wants to understand and to explain. Each chapter can be read separately, like a different look, like an different approach to the subject. However, the stories are not different, because the history that is explained is always the same, highlighting -or hiding- sometimes some aspects, at others others.The first part, "Secularized priests", explains in which context they decided to become priests (chapter 1) -and why (chapter 2)- the persons who later left the priesthood. It focuses on the ideal that moved them and on how this ideal kept transforming (chapter 3). Some of the consequences of the "ideological" transformation are highlighted. Finally, an attempt is made to clarify how many of these persons, that we can call "secularized priests" (excursus), there are.The second part, "From the Seminar to the real world", highlights the institutional and social contexts of the trajectories of the secularized priests. Chapter 4 focuses on the experience of the Seminar as a starting point towards the one that is called real world, by contrast. Chapter 5 analyzes the characteristics of the experience of the real world that many priests had and what the "reality" of the world amounted to. Once in the real world, we will see (chapter 6) that disenchantment, contradictions, doubts and suffering were some of the singularities of the exit itinerary.The third part, "Les plegades", underlines out those aspects of the social context that, we could consider, on the one hand, ways out and, on another other hand, causes of the secularization. Chapter 7 analyzes some of the sociobiographical circumstances that bore them towards the way out. Formulating and classifying the causes, and the implicit and explicit motives of the processes of secularization (or of drifting away), occupies the better part of chapter 8. Chapter 9 offers a sociological explanation of the life stories of the priests that have been analyzed. Voice is also given to other protagonists of the story, such as the women who married priests. The fourth part, "The identity of the former priests", approaches the subject of the former priest's social condition and his change of identity. Chapter 10 is about the condition of the former priest and about those dimensions that best characterize them. In chapter 11, some models are offered of the life processes of these transformations are delimited between the maturation and the break. To finish, chapter 12 tries to see what has become of the professed faith and of the priestly condition of these ex-priests.The conclusions highlight three aspects of the fact of having reached the end. In the first place, if the end has been reached, it does not mean that it is the only possible end and that the itinerary chosen might not have been different. Along the way many unforeseen questions emerged, as did others that have remained unanswered. In the second place, a look back is made to remember some of the guidelines that gave direction to the research. Finally, and in the third place, some of the many "lessons" that have been learned are brought together.

Denna studie har undersökt huruvida det är möjligt att på Nasdaq OMX Stockholm generera systematiska överavkastningar i samband med att aktier börjar handlas exklusive rätt till utdelningar. Samtliga utdelningstillfällen har undersökts under perioden 2007-2011 vilket givit en total observationsmängd på 699 stycken tillfällen. Genom att ha tagit hänsyn till eventuella marknadsfluktueringar och vikta dessa med bolagets unika risk, i form av betatal, har resultaten även justerats för normalavkastningar under den undersökta dagen. Resultaten från Large Cap, Mid Cap samt Small Cap har sedan jämförts. Resultaten visar att överavkastningar är möjliga under dagen då aktien slutar handlas inklusive utdelning, samt att effekten är större för de mindre bolagen. / This study, has examined the possibility of achieving abnormal returns in the Swedish stock market on the day when stocks no longer trade with its dividend rights. All stocks on Nasdaq OMX Stockholm had been analyzed during 2007-2011, a total of 699 observations. By also including market fluctuations and weight of these fluctuations with the stock’s unique risk, the results have been adjusted for the normal return during the observed day. The results from Large Cap, Mid Cap and Small Cap have then been compared to one another. The overall result shows that abnormal returns are possible on the day stocks no longer trade with the rights of dividends. The result also shows larger, abnormal returns for smaller companies.

Abstract The primary objective of this study was to determine the isotopic variation of the sedimentary organic carbon (£_13Corg) in the sediment samples of the gravity core 17950-2. The core was retrieved from the northern South China Sea during ¡§Monitoring Monsoon¡¨ cruise onboard R/V Sonne in 1994. The £_13Corg data were further compared with other proxies, such as foraminiferal £_18O and £_13C, TOC wt%, and CaCO3 wt% to decipher the late Quaternary evolution of climate change from the South China Sea for the last 200 ky. Prior to 65 ka, the £_13Corg, calibrated TOC wt% (TOC ex wt%), and Terrestrial wt% fluctuated synchronously. The increased TOC ex wt% and Terrestrial wt% were consistent with the enriched £_13Corg, implying the enhanced productivity due to the increased terrestrial input. The enhanced glacial productivity could have been caused by the increase in terrestrial input and mixed layer by wind-driven upwelling. The South China Sea, however, is a nitrogen-limited basin. The enhanced nitrogen fixation induced by increased dust input can also be a potential candidate that is responsible for the elevated productivity during glacials. Theoretically, the £_13Corg is utilized as a powerful tool to determine the carbon ratio between marine and terrestrial origin in the shelf area and reconstruct the pCO2 history of the low-productivity open ocean. According to TOC ex wt%, the productivity of the northern South China Sea were significantly higher in glacials than interglacials. Therefore, the variation of pCO2 of the northern South China Sea can not be reconstructed properly based on £_13Corg record solely .

The recruit and the selection is the foundation of all the Human Resource Management. Quality Human Resource can increase the total benefits of the enterprise. However, the risk exists in all the selections of the employees. The enterprise must bear some losses if they hire an unsuitable new employee. Therefore, rehire become one of the recruit channels. This channel is worthwhile for many enterprises to adopt. It is not only save recruit cost, but also the during time of new employee adapt company culture and training cost. The other hand, the enterprise can avoid the resignation of new employee because of adapt not very well. It avoid the risk and cost of recruit again. This research collected the relevant information about the ex-employees to be employed again in different industries. The total samples are 231 pieces from 27 enterprises. The research probes: (1) Compared with the 1st employment have rehire employees get higher salaries and position, and work for their company longer ? (2) Will the working experience in the period of leaving of the rehire have higher salaries and positions ? (3) Will the different reason of reemployee of the rehire have different salary and position ? The result shows that the rehire¡¦s salary and position are higher than their 1st employment, and work their company longer than their 1st employment. If the rehire working during their leaving period, their salary are better than their 1st employment. The longer the leaving period is, the higher the salary and position are on their rehire. If the company reemployee the rehire initatively, their salary and position will higher than 1st employment. Finally, this research makes a concise and brief explanation to the research limitation, the future research direction and the suggestion to enterprises. Key words: rehire of ex-employee, recruit channel, performance and salary.