Yes / Purpose: The aim of this research therefore is to explore the causes of drug shortages within the pharmaceutical supply chain and assess the adopted mitigation strategies. Research Approach: The study is carried out from an inductive perspective where we seek to understand the phenomenon by a detailed review of extant literature followed by a series of semi-structured interviews with first tier consumers within a case study framework. The respondents were chosen using purposive sampling as those best to comment on the phenomenon under scrutiny. Data was analysed using thematic analysis, where a dual focus was adopted; 1) the preliminary focus was on the identification of system themes (where the system was impacted and the responds e.g. complexity, disruptions and product alternatives) and 2) the secondary focus was the impact on the patient as system recipient and product user (where themes such as stress, anxiety, and adverse drug reactions emerged). Findings and Originality: The analysis show that drug shortages within the pharmaceutical supply chain in the UK occur as a result of stringent regulatory frameworks, faults in the manufacturing processes, lack of Active Pharmaceutical Ingredients, monopolistic wholesaler markets; lack of information dissemination, offshore trading and price manipulations for profit. The impact on the consumers is reported to be extensive and can endure long after the disruptive event occurs. The findings indicate that existing recovery strategies are however cumbersome, add complexity to the supply chain and in extreme cases facilitate the infiltration of counterfeits. The study is innovative as it explores disruptive events and associated recovery strategies which have not been adequately addressed in supply chain management studies to date. Research Impact: This research contributes to existing literature by extending discussions on supply chain disruptions within a dynamic supply chain whilst focusing on product service supply chain recovery strategies and mechanisms. Practical Impact: This study provides Operations/Supply Chain Managers and Pharmaceutical companies and professionals with strategies that can be adopted can adopt in reducing and recovering in a more resilient manner to disruptive events. This thus presents the bedrock for resilient practice and systems design and development, thus reducing system vulnerability and ultimately leading to improved product availability and patient care.

Introduction: Research shows that the lifespan of large companies gets shorter and shorter, the average age of companies on the list of fortune 500 is 33 years, the average age is expected to decline to 12 years by 2027 (Anthony et al., 2018). Innovations that are driven by social, environmental or sustainability issues are defined as sustainability-driven innovations (Metz, 2016). Not much is known when it comes to what sources can trigger a disruptive sustainability-driven innovation.    Problem background: There has been many troubling studies about the damage we as humans bring upon our blue planet, these studies are apocalyptic (Osborn 1948; Carson 1962; Meadows et al 1972; Cole et al 1973). To be able to meet the aspirations of millions rising from poverty, we need transformation and change throughout society, and disruptive innovations is the key to unlock this transformation (Sterman, 2015). The disruption literature is well developed when it comes to what sources can trigger a disruptive innovation. There does not exist literature on what sources that can trigger sustainability-driven innovations.   Purpose: The purpose of this thesis is to create a conceptual model that show possible sources of disruption for sustainability-driven innovations. The knowledge created by the conceptual model will be used at a later stage to develop a monitoring tool for TOMRA. To fulfill the purpose of this master thesis we have developed the following research question: what sources can trigger a disruptive sustainability-driven innovation?   Methodology: To answer the research question, this thesis used an exploratory research design, inductive research approach and the single case study with participants from four companies that acts in three different industries and five interviews with experts in the field of sustainability-driven innovations as the chosen research method. The primary data has been collected from 13 interviews from new entrants, incumbents, experts and governmental agencies. Secondary data were collected to support the analysis.   Findings: The key findings of this thesis are eight new sources of disruption; established technology, public value, public opinion, political decisions, political goals, legislations, subsidizations and demo-pilots    Conclusion: Our study showed that there was a gap in the disruption literature, especially when it comes to the source of disruption. Because the study found other sources that might trigger a disruption rather than only new technology and new BMs. Realizing that, the sources of disruption were expanded to have three subcategories that influence each other, technology and BM, citizen awareness and policy.

Les disruptions du plasma sont des phénomènes se produisant dans les tokamaks et qui entraînent une perte totale du confinement du plasma et la fin de la décharge. Ces disruptions sont des phénomènes rapides et violents et peuvent endommager les murs du tokamak ainsi que sa structure si elles ne sont pas contrôlées. Un système de mitigation des disruptions est donc indispensable pour ITER afin de réduire les forces électromagnétiques, mitiger les charges thermiques et éviter les électrons runaways générés par les disruptions du plasma. Remplir tous ces objectifs fait du design de ce système une tâche difficile, pour laquelle un apport conséquent de l’expérience et de la modélisation est nécessaire. Nous présentons dans cette thèse des résultats de modélisation sur l’amortissement des disruptions par injection massive de gaz, qui est une des méthodes principales envisagées sur ITER pour le système de mitigation. Premièrement, un modèle issu des premiers principes pour décrire le transport des neutres dans un plasma est donné et est appliqué à l’étude de l’interaction entre l’injection massive de gaz et le plasma. Les principaux mécanismes en jeu sont décrits et étudiés. L’échange de charge entre les neutres et les ions du plasma est isolée comme jouant un rôle majeur dans cette dynamique. Ensuite, le code 3D de Magnétohydrodynamique non linéaire JOREK est appliqué à l’étude des disruptions déclenchées par injection massive de gaz. Un intérêt particulier est porté sur la phase de quench thermique et les phénomènes MHD qui le déclenchent. Les résultats obtenus avec ce code sont comparés avec les expériences effectuées sur le tokamak JET. / Plasma disruptions are events occuring in tokamaks which result in the total loss of the plasma confinement and the end of the discharge. These disruptions are rapid and violent events and they can damage the tokamak walls and its structure if they are not controlled. A Disruption Mitigation System (DMS) is thus mandatory in ITER in order to reduce electromagnetic forces, mitigate heat loads and avoid Runaway Electrons (RE) generated by plasma disruptions. These combined objectives make the design of the DMS a complex and challenging task, for which substantial input from both experiments and modeling is needed. We present here modeling results on disruption mitigation by Massive Gas Injection (MGI), which is one of the main methods considered for the DMS of ITER. First, a model which stems from first principles is given for the tranport of neutrals in a plasma and applied to the study of the interaction of the MGI with the plasma. Main mechanisms responsible for the penetration of the neutral gas are described and studied. Charge-exchange processes between the neutrals and the ions of the plasma is found to play a major role. Then, the 3D non linear MHD code JOREK is applied to the study of MGI-triggered disruptions with a particular focus on the thermal quench phase and the MHD events which are responsible for it. The simulation results are compared to experiments done on the JET tokamak.

Self-injurious behavior (SIB) is a complex phenotype that occurs with an increasing prevalence of about 7-34% in humans and 10-12% in non-human primates (NHPs). This study evaluated the efficacy of probiotic Lactobacillus reuteri as a treatment for self-injurious behavior (SIB) and sleep disruption in rhesus macaques. The treatment was proposed to alleviate mild self-biting, sleep disruption, and reduce chronically elevated hypothalamic-pituitary-adrenocortical (HPA) axis activity, all hallmark features of monkeys with this condition. The probiotic preparation included two strains of L. reuteri (L. reuteri ATCC PTA 6475 & L. reuteri DSM 17938) containing on average 200 million colony forming units per chewable tablet. The study was conducted on 14 rhesus macaque monkeys (9 males) housed at the University of Massachusetts Amherst. To our knowledge this is the first time that a Lactobacillus strain has been used as a treatment for SIB in rhesus macaques. This study utilizes motion-activated infrared camera technology, modified enzyme-immunosorbent-assays (EIAs) techniques to measure hair cortisol concentrations, and daily behavioral observations to provide an overall assessment of the behavioral, physiological, and sleep associated implications of probiotic treatment on SIB and control non-human primates (NHPs). Administration of L reuteri modestly decreased biting behavior in monkeys with SIB (F(2,12) = 5.64, p= 0.02) and showed overall decrease in nighttime activity across all subjects but did not normalize SIB to nonSIB values. Hair cortisol values are pending. These findings and the findings of previous work further strengthen the argument for probiotics as an efficacious treatment for SIB behavior.

This paper discusses the conditional factors indicating market susceptibility toward disruptive innovation. There is a need to separate the different forms of disruptive innovation into segments targeting; technology, product or business model disruption. The concepts are fundamentally different and the literature to date is very one sided toward disruptive technology/product innovation. A shortage of studies on disruptive business model innovation has been discovered. This study therefore presents a framework for evaluating the market susceptibility toward disruptive business model innovation. This paper is a case study looking at two historical cases in the Swedish telecom industry. One case was a highly successful disruptive business model whilst the other has not reached the potential success it could have. The cases are investigated through interviews from persons with strategic positions in the telecom industry during the launch of the business models presented in the cases. This is backed with survey results and statistics from market research conducted by the Swedish post and telecom authority. Conditional factors applied to disruptive technology/product innovations, found in previous studies and theory, are applied to the business model disruption cases. The conditional factors are tested in order to establish to what extent they can be applied on business model disruption. This study also aims to find new conditional factors not covered in previous theory. This study is concluded by presenting 10 conditional factors important for evaluating susceptibility toward disruptive business model innovation. This paper analyses 11 conditional factors from previous theory applied on disruptive technology/product innovation. Out of these, 7 conditional factors can be transferred from disruptive technology/product innovation to disruptive business model innovation theory, whilst 4 conditional factors are dismissed entirely. In addition, 3 conditional factors are added from the empirical findings. The study found that the “change of actors in the value chain” and “high entrance barriers” did not seem to be as important for business model disruption. Market susceptibility in these cases seemed to be more dependent on cost, end customer focus, high margins and scalability. There were however also many conditional factors which have importance both for disruptive business model innovation and disruptive technology/product innovation. These conditional factors concerned the market distribution, the current product, the profitability of the market and the current value chain. Differences between disruptive business model innovation and disruptive technology/product innovation are discovered. The differences are proven crucial when evaluating the market susceptibility toward disruptive innovation. Mainly differences being that business models; are more agile, are not seen as big threats, and seem to be more pull than push oriented. / Den här studien behandlar de faktorer som indikerar en marknads känslighet för disruptiva innovationer. Dessa disruptiva innovationer kan delas upp i tre olika former; produktdisruption, teknologidisruption och affärsmodellsdisruption. Det finns idag en brist på litteratur som behandlar disruption ur ett affärsmodellsperspektiv. Befintlig litteratur för disruptiva innovationer är baserade på fall kring teknologi- och produktdisruptioner. Denna studie presenterar ett ramverk för att utvärdera känsligheten för affärsmodellsdisruption i en viss marknad. I den här artikeln görs en fallstudie kring två historiska händelser då nya affärsmodeller lanserats på den svenska telekommarknaden. En utav dessa var en väldigt framgångsrik affärsmodellsdisruption, medan den andra inte nått samma framgång. Händelserna är undersökta genom intervjuer av personer som hade strategiska positioner inom telekomindustrin under dessa två händelser. Slutsatser som dras är sedan styrkta av enkätresultat och statistik från marknadsundersökningar gjorda av den svenska post- och telestyrelsen. Marknadsfaktorer som är tillämpade på teknologi- och produktdisruptioner från tidigare teori appliceras på dessa affärsmodellshändelser. Faktorerna testas för att se i vilken utsträckning de kan föras över till teori för disruptiv innovation av affärsmodeller. Studien strävar också efter att hitta nya marknadsfaktorer som inte tidigare inkluderats i teorin. Denna artikel avslutas genom att presentera 10 omkringliggande faktorer som är viktiga för att utvärdera känsligheten för disruptiv affärsmodellsinnovation i en marknad. Artikeln utgår från 11 marknadsfaktorer, främst baserade på tidigare teorier om produkt- eller teknologidisruption. 7 av dessa faktorer kan överföras till affärsmodellsdisruption, vilket innebär att 4 faktorer avfärdas i sin helhet. Dessutom visade empirin att ytterligare 3 faktorer var viktiga för affärsmodellsdisruption. Studien fann att ”ändring av aktörer i värdekedjan” samt ”höga inträdesbarriärer” inte verkade vara så viktiga faktorer för affärmodellsdisruption. De marknadsfaktorer som var viktigast för marknadens känslighet för affärsmodellsdisruption var kopplade till kostnads- och slutkundsberoende, höga marginaler och skalbarhet. Det fanns dock flera faktorer som var viktiga för både affärsmodells- och teknologi/produktdisruption. Dessa marknadsfaktorer berörde marknadsfördelningen, den aktuella produkten, lönsamheten, och den aktuella värdekedjan. Skillnader mellan affärsmodellsdisruption och produkt- eller teknologidisruption utreds i denna studie. Skillnaderna visar sig vara viktiga när man undersöker marknadens känslighet för disruptiva innovationer. De stora skillnaderna som upptäcktes var att affärsmodeller är mer agila, är inte sedda som ett lika stort hot, och är mer ”pull”- än ”push”-baserade.

The modern supply chain is long, complex, interconnected and global, and plays a fundamental role in business competitiveness. These conditions, along with various supply chain management trends in recent years have increased risks in supply chains which threaten supply chain performance. Greater impact, especially on cost, from an increased threat of supply disruptions is one area of particular concern. Companies today are struggling to find effective means to manage this increased risk and avoid adverse financial impacts. An approach to managing supply disruption risk in supply chains based on the minimization of the total cost of ownership (TCO) of the supply chain is explored in this thesis. Insights are provided into an appropriate view of supply chain risk and a general four step risk management process to guide the design and evaluation of a new risk management tool based on such an approach. A prototype of the new total cost-based, modeling and simulation tool was created in partnership with ProModel Corporation and a government contractor that requested to remain anonymous. A preliminary assessment of the effectiveness of this tool in minimizing TCO and providing an interface useable by non-modelers is provided. This study also reviews and compares a sample set of current supply chain risk management methods and tools and compares them with the new tool for relevance in aiding users in managing supply disruption risk. Based on literature findings and preliminary feedback from pilot contextual demonstrations of the tool, the total cost approach to risk modeling appears promising, although the execution needs to be improved with further enhancements made to the prototype tool. In this preliminary study and evaluation, sufficient evidence is not available to determine that the new prototype tool is any more effective than other currently available risk management tools to provide necessary information to make supply chain risk management decisions that minimize TCO of a supply chain. Suggestions for further development of the tool, especially for improvement of the total cost approach, are provided as well as a preliminary evaluation procedure and survey instruments for a more robust evaluation of the new tool.

Die subklinische Klauenrehe oder claw horn disruption (CHD) ist von großer wirtschaftlicher Bedeutung für die Rinderhaltung, da sie zu Lahmheiten, Beeinträchtigungen des Allgemeinbefindens sowie einer eingeschränkten Leistungsfähigkeit der Tiere führt. Trotz zahlreicher Untersuchungen sind die pathophysiologischen Grundlagen der CHD noch immer nicht vollständig geklärt. Die derzeitigen Hypothesen weisen auf eine Ischämie in den noch lebensfähigen Epidermisschichten infolge einer veränderten dermalen Mikrozirkulation. Diese hat pathophysiologische Veränderungen zur Folge, die eine Störung der epidermalen Zellproliferation, eine Schädigung der dermo-epidermalen Verbindung sowie eine veränderte Keratinisierung und Hornproduktion umfassen. Von Bedeutung sind daher In-vitro-Ischämiemodelle, um die epidermale Reaktionsmechanismen auf die pathologischen Veränderungen der Dermis zu untersuchen. Ziel in der vorliegenden Arbeit war die Etablierung eines In-vitro-Ischämiemodells auf der Grundlage boviner Keratinozyten aus der Klauenepidermis. Mithilfe dieses Modells sollten die zellulären Pathomechanismen infolge einer Ischämie, einer Hypoxie sowie eines Glukoseentzugs untersucht werden. Des Weiteren stand die Analyse des Differenzierungsverhaltens der Keratinozyten infolge ischämischer, hypoxischer und hypoglykämischer Konditionen im Mittelpunkt. Für die Etablierung des In-vitro-Ischämiemodells diente als Grundlage das oxygen glucose deprivation (OGD)-Modell, das die Untersuchung eines gleichzeitigen Sauerstoff- und Glukosemangels sowie lediglich einer Hypoxie und eines Glukoseentzugs bei bovinen Keratinozyten ermöglichte. Die Versuche wurden in eine Kurzzeitanalyse über 96 Stunden sowie eine Langzeitanalyse über drei Wochen geteilt. Nach erfolgter Exposition wurde die Zellviabilität mittels LDH(Lactatdehydrogenase)- und MTT(3-(4,5-Dimethylhiazol-2-yl)-2,5-diphenyltetrazoliumbromid)-Assay untersucht. Des Weiteren wurde das veränderte Differenzierungsverhalten der Keratinozyten infolge der veränderten Kultivierungsbedingungen mittels Western Blot-Analyse anhand der Involukrin- und Lorikrin-Expression untersucht. Die Keratinozyten zeigten infolge einer OGD nach kurzer Expositionsdauer die höchsten zytotoxischen Effekte, die von einer zeitabhängigen Abnahme der Zellviabilität sowie massiven morphologischen Veränderungen gefolgt wurde. Hypoxische Bedingungen bewirkten eine zeitabhängige Abnahme der Zellviabilität, die erst nach zweiwöchiger Inkubation die größte Zytotoxizität aufwies, sowie eine geringgradig veränderte Zellmorphologie bei Erhaltung des Zellverbands. Der Glukoseentzug bewirkte eine stark verminderte Zellviabilität sowie starke morphologische Zellveränderungen. In der Western Blot-Analyse konnte eine gesteigerte Involukrin- und Lorikrin-Expression infolge einer OGD, einer Hypoxie und eines Glukoseentzugs nachgewiesen werden. In der vorliegenden Arbeit konnte erstmalig ein auf bovinen Keratinozyten basierendes In-vitro-Ischämiemodell etabliert werden, das die Untersuchung zellulärer Mechanismen der Epidermis ermöglichte. Die OGD zeigte den stärksten Einfluss auf die Zellviabilität sowie eine veränderte Zelldifferenzierung der Keratinozyten, was die pathophysiologischen Veränderungen im Rahmen der CHD reflektiert. Die ebenfalls starken Zellveränderungen infolge eines Glukoseentzugs verdeutlichen die Rolle der Glukose im Zellmetabolismus der Keratinozyten. Solch ein epidermaler Glukosemangel ist in Verbindung mit der negativen Energiebilanz der Rinder im peripartalen Zeitraum denkbar. Die Ergebnisse infolge einer Hypoxie verweisen auf vielfältige Adaptationsmechanismen der Keratinozyten an hypoxische Bedingungen, denen sie in der Epidermis in vivo während der Zelldifferenzierung ausgesetzt werden. Damit besitzt das In-vitro-Ischämiemodell ein großes Potenzial für den Einsatz in der Klauenreheforschung, um einerseits die mit einer Ischämie einhergehenden pathologischen Veränderungen der CHD untersuchen zu können. Andererseits liefert das Modell wertvolle Informationen zu den physiologischen Grundlagenmechanismen der Epidermis, die mit der Zelldifferenzierung einhergehen. / The subclinical laminitis or claw horn disruption (CHD) is of great economic importance in the dairy industry as it causes lameness, poor general condition and reduced performance. Despite extensive research efforts, the pathomechanism of CHD remains widely unclear. The current hypotheses on CHD pathogenesis include ischemic alterations of the epidermal keratinocytes resulting from an impaired blood supply. This causes an alteration of cell proliferation, a dermo-epidermal separation and an impaired keratinization and horn production. Therefore, in vitro ischemia models are of critical importance in clarification of the epidermal responses to an altered microcirculation. The aim of this study was the establishment of an in vitro ischemia model based on bovine claw keratinocytes. This in vitro model should enable the investigation of cellular pathomechanisms following exposure to ischemia, hypoxia and glucose deprivation. An additional aim was the analysis of the differentiation pattern of keratinocytes under ischemic, hypoxic and hypoglycaemic conditions. To establish the in vitro ischemia model, the keratinocytes were exposed to oxygen-glucose deprivation (OGD). In addition, this model allowed the parallel examination of hypoxic and hypoglycaemic conditions on bovine claw keratinocytes. The experiments were divided into a short-term analysis over 96h and a long-term analysis over three weeks. Measurement of cell viability was performed by LDH(lactatedehydrogenase) and MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra- zolium bromide) assays. Furthermore, the differentiation pattern of the keratinocytes after exposure to ischemia, hypoxia and glucose deprivation was detected by western blot analysis of the focus on expression of involucrin and loricrin. The highest cytotoxic effect was measured after short exposure to OGD followed by a time-dependent decrease of cell viability and extensive morphological changes of the keratinocytes. Hypoxic conditions lead to a time-dependent decrease of cell viability with the highest cytotoxicity after two weeks. The keratinocytes showed slight changes in cell morphology while maintaining a confluent cell layer. Exposure of keratinocytes to glucose deprivation showed a high decrease of cell viability and strong morphological changes. Furthermore, western blot analysis showed an altered expression pattern with increased involucrin and loricrin levels after exposure to OGD, hypoxia and glucose deprivation. The present study established for the first time an in vitro ischemia model based on bovine claw keratinocytes to study the cellular mechanisms of the epidermis. After exposure to OGD, keratinocytes showed the highest loss in cell viability and an altered cell differentiation. This reflects the pathophysiological changes following epidermal ischemia occurring during the pathogenesis of CHD. The massive cellular alterations after glucose deprivation provide good evidence for the importance of glucose in the cellular metabolism of keratinocytes. An epidermal glucose deficiency may occur in combination with a negative energy balance during peripartal period in cattle. The results of hypoxia show the different adaptive mechanisms of keratinocytes to hypoxic conditions which are present in the epidermis during cell differentiation. Thus, the in vitro ischemia model has a great potential for use in research into CHD pathogenesis and pathomechanisms associated with ischemia. On one side, it is possible to investigate the pathological changes following ischemia during CHD. On the other side, the model offers useful information on physiological response mechanisms of the epidermis that correlate with cell differentiation.

Die vorliegende Arbeit befasst sich mit der Erweiterung des etablierten Stu-dienmodells Xenopus laevis zur Untersuchung der Wirkung von endocrine disruptors auf die Reproduktionsbiologie von Amphibien. Um einen Einblick in die grundlegenden Mechanismen der sexuellen Differenzierung von Amphibien zu gewinnen, wurden die Konzentrationen bestimmt, mit denen androgene und estrogene Sexualsteroide während der larvalen Entwicklung in verschiedenen Stadien von Xenopus vorliegen. Parallel wurde das Auftreten der korrespondierenden Rezeptoren im Verlauf der Entwicklung untersucht, über welche die hormonelle Wirkung vermittelt wird. Auf der Basis der gewonnenen Erkenntnisse konnte eine neue Hypothese zur sexuellen Differenzierung von Amphibien entwickelt und vorgestellt werden. Sie stellt das Enzym 5alpha-Reduktase, das die Umwandlung von Testosteron in das potentere und nicht weiter aromatisierbare Androgen Dihydrotestosteron (DHT) bewerkstelligt, in den Mittelpunkt des Prozesses der Geschlechtsdifferenzierung. Abhängig von der genetisch bedingten Expression dieses Enzyms kommt es zu einem höheren oder niedrigeren Auftreten des DHT und damit zu Unterschieden im Verhältnis von DHT zu Estradiol (E2). Der Charakter dieses Verhältnisses scheint der entscheidende Auslöser für die Entwicklung eines weiblichen oder männlichen Phänotyps zu sein. In einem zweiten, anwendungsorientierten Teil wurde untersucht, in wie weit die bislang auf Laboruntersuchungen beschränkte Arbeit mit X. laevis auf Feldstudien erweiterbar ist und ob sich auf diese Weise gewonnene Daten auf die Situation heimischer Amphibien übertragen lassen. Parallele Expositionen des Krallenfrosches einerseits und des Grasfrosches (Rana temporaria) andererseits gegenüber realen Medien unter Freilandbedingungen bestätigten die hervorragende Eignung des Studienmodells X.laevis zur Beurteilung endokriner Belastungssituationen. Darüber hinaus konnte gezeigt werden, dass sich durch die Verwendung von Festphasenextrakten die endokrinen Wirkungen komplexer Matrizes unter standardisierten Laborbedingungen charakterisieren lassen. Rezeptorbindungsstudien sowie Untersuchungen zur Genexpression spezifischer Marker, histologische Betrachtungen von Gonadengewebe und die Bestimmung von Geschlechterverhältnissen ermöglichten Aussagen auf vielfältigen Nachweisebenen. Auf diese Weise konnte das Potenzial, mit dem Proben jeder Art, sowohl durch kurz- als auch durch langfristige Exposition, adverse Effekte auf das amphibische Hormonsystem hervorrufen können, umfassend und differenziert analysiert werden. / The presented work aims to contribute to the various opportunities of studying the effects of endocrine disruption on sexual differentiation in amphibians provided by the well established model Xenopus laevis. In order to gain insight into the basic mechanisms underlying the sexual differentiation in amphibians, the concentrations of androgen and estrogen sexual steroids during several stages of the larval development of Xenopus were determined. In parallel, the ocurrence of the corresponding receptors, which mediate the effects of the respective hormones, was observed. Based on the results of the studies described, a new hypothesis regarding sexual differentiation in amphibians is presented, which assignes the enzyme 5alpha-reductase as the central element of sexual development. This enzyme converts the androgen testosterone into dihydrotestosterone, which can not be aromatized into estradiol. Depending on the genetic sex of the indivual, genexpression of 5a-reductase may differ and therefore lead to a characteristic ratio of androgens and estrogens. We suggest, that this ratio might be the essential trigger for amphibians to develop into a male or a female. A second part aimed to enlarge the Xenopus model to the use in field studies and to proof the transferability of such data to the situation of endemic amphibians. Exposure in parallel of Xenopus on one hand and the green frog Rana temporaria on the other to the effluent of a bavarian wastewater treatment plant revealed the exceeding suitability of the model to asess the endocrine charge of the environment. Furthermore, the use of solid phase extracts derived from natural samples allowed the characterization of the respective endocrine potential under standardized laboratory conditions. Rezeptor binding studies, detection of genexpression of specific biomarkers, histological examination of gonadal tissue and the determination of sex ratios provided the evaluation of effects on several levels of investigation. By this means the Xenopus model offers the opportunity to assess the ability of any kind of sample to cause endocrine impacts on amphibians after short time as well as after long time exposure in a broad and at the same time differentiated way.

The essential tenet of the behavioral momentum model (BMM) is that relative response rate decreases less in the face of disruption when maintained by a higher reinforcer density. Empirical support exists based on both response-dependent and response-independent reinforcement. In the present study the BMM was tested with college students in 4 multi-element experiments, each using 2 reinforcement schedules and a disrupter. Participants performed a categorical sort (by orientation) of triangles on a computer monitor. Sorting response rates were disrupted by a concurrent task, pressing the keyboard “T” key whenever 2 displayed changing numbers were equal. Initial training established fast (under VR 4) and slow (under DRL 5-s) sorting rates, and provided practice with the disrupting task. In Experiment 1 DRL 5-s provided higher reinforcer density, while in Experiment 2 VR 4 did. In Experiment 3 the higher total reinforcer density was achieved by adding VT 6-s to DRL 5-s while in Experiment 4 it was achieved by adding VT 12-s to VR 4. In all 4 experiments, sorting rate decreased with introduction of the disrupter. In Experiments 1 and 3, relative sorting rate decreased less under DRL based schedule (greater reinforcer density), supporting the BMM. However, in Experiments 2 and 4, relative sorting also decreased less under DRL (lower reinforcer density), contrary to the BMM prediction. Taken together, these data show greater relative resistance to change under DRL (versus VR), independent of reinforcer density. Thus, contrary to the BMM, the nature of the reinforcement schedule seemed to be the principal factor determining behavioral momentum. / May 2009

The essential tenet of the behavioral momentum model (BMM) is that relative response rate decreases less in the face of disruption when maintained by a higher reinforcer density. Empirical support exists based on both response-dependent and response-independent reinforcement. In the present study the BMM was tested with college students in 4 multi-element experiments, each using 2 reinforcement schedules and a disrupter. Participants performed a categorical sort (by orientation) of triangles on a computer monitor. Sorting response rates were disrupted by a concurrent task, pressing the keyboard “T” key whenever 2 displayed changing numbers were equal. Initial training established fast (under VR 4) and slow (under DRL 5-s) sorting rates, and provided practice with the disrupting task. In Experiment 1 DRL 5-s provided higher reinforcer density, while in Experiment 2 VR 4 did. In Experiment 3 the higher total reinforcer density was achieved by adding VT 6-s to DRL 5-s while in Experiment 4 it was achieved by adding VT 12-s to VR 4. In all 4 experiments, sorting rate decreased with introduction of the disrupter. In Experiments 1 and 3, relative sorting rate decreased less under DRL based schedule (greater reinforcer density), supporting the BMM. However, in Experiments 2 and 4, relative sorting also decreased less under DRL (lower reinforcer density), contrary to the BMM prediction. Taken together, these data show greater relative resistance to change under DRL (versus VR), independent of reinforcer density. Thus, contrary to the BMM, the nature of the reinforcement schedule seemed to be the principal factor determining behavioral momentum.