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Climate risk has become a major concern for financial institutions and financial markets. Yet, climate policy is still in its infancy and contributes to increased uncertainty. For example, the lack of a sufficiently high carbon price and the variety of definitions for green activities lower the value of existing and new capital, and complicate risk management. This column argues that it would be welfare-enhancing if policy changes were to follow a predictable longer-term path. Accordingly, the authors suggest a role for financial regulation in the transition.

Using granular supervisory data from Germany, we investigate the impact of unconventional monetary policies via central banks’ purchase of corporate bonds. While this policy results in a loosening of credit market conditions as intended by policy makers, we document two unintended side effects. First, banks that are more exposed to borrowers benefiting from the bond purchases now lend more to high-risk firms with no access to bond markets. Since more loan write-offs arise from these firms and banks are not compensated for this risk by higher interest rates, we document a drop in bank profitability. Second, the policy impacts the allocation of loans among industries. Affected banks reallocate loans from investment grade firms active on bond markets to mainly real estate firms without investment grade rating. Overall, our findings suggest that central banks’ quantitative easing via the corporate bond markets has the potential to contribute to both banking sector instability and real estate bubbles.

Trafikverkets IP-nät består idag av 26345 nätverkskomponenter och växer allt mer på grund av samhällets tekniska framsteg. Det är därför viktigt att överväga kostnaderna för tillväxten årligen för att sätta rätt budgetar. Telekominfrastruktur saknar idag en modell för beräkning av livscykelkostnader, vilket gör det svårt att särskilja de olika investeringsalternativen då framtida kostnader inte ingår. Enligt svensk lag ska upphandlingar ske efter minsta möjliga investeringskostnad, som inte tar hänsyn till kostnader som drift och underhåll. Det kan i sin tur leda till att oväntade dyra kostnader dyker upp, vilket leder till att skattebetalarnas pengar inte används effektivt. Studiens resultat presenteras som en beräkningsmodell vars livscykelkostnad för enskilda produkter kan beräknas, vilket kan läggas till grund för framtida investeringar. Sammanfattningsvis har detta arbete uppnått sitt mål och syfte trots osäkerheten kring skattning av indata.

Supplemental material, sj-docx-1-bcb-10.1177_11782234221086992 for First-Line Treatment of HER2-Positive Metastatic Breast Cancer With Dual Blockade Including Biosimilar Trastuzumab (SB3): Population-Based Real-World Data From the DBCG by Alan Celik, Tobias Berg, Lise Birk Nielsen, Maj-Britt Jensen, Bent Ejlertsen, Ann Knoop and Michael Andersson in Breast Cancer: Basic and Clinical Research

INTRODUCTION: Ovarian cancer has the highest mortality rate among gynaecological cancers and is the tenth most frequent cancer among women. 80% of patients with advanced stage disease will experience a progression either during or after treatment.METHODS: This was a retrospective, observational study of all women referred to adjuvant or neoadjuvant treatment for ovarian cancer between 1 June 2013 and 31 May 2014 at two university hospitals in Denmark.RESULTS: We included 142 women diagnosed with ovarian cancer. The median overall survival from diagnosis was 48.5 months (95% confidence interval (CI): 36.6-57.9 months). Median survival after the first, second, third, fourth and fifth progression was 19.3 (95% CI: 13.9-27-3), 11.4 (95% CI: 7.7-18.8), 9.5 (95% CI: 6.3-12.7), 8.3 (95% CI: 7.6-11.5) and 5.6 (95% CI: 2.9-not assessed) months, respectively. Median progression-free survival from diagnosis was 15.6 months (95% CI: 14.3-18.4 months). Median progression-free survival after first, second, third, fourth and fifth progression was 9.2 (95% CI: 7.7-10.6), 6.0 (95% CI: 3.5-7.7), 3.3 (95% CI: 2.6-4.6), 4.9 (95% CI: 3.6-8.3) and 3.0 (95% CI: 2.4-5.7) months, respectively. The most frequently used treatment at first progression was carboplatin and pegylated liposomal doxorubicin (n = 37). The most used non-platinum containing treatment at progression was pegylated liposomal doxorubicin (n = 26) followed by paclitaxel (n = 23).CONCLUSIONS: Ovarian cancer remains a highly aggressive disease with most patients diagnosed in advanced stages. Treatment has not changed much in the past 15 years and the same is evident for the overall survival.FUNDING: Tobias Berg received an unrestricted research grant from the Danish Cancer Society.TRIAL REGISTRATION: not relevant.

In branching diffusions with immigration (BDI), particles travel on independent diffusion paths in $\mathbb{R}^d$, branch at position-dependent rates and leave offspring -- randomly scattered around the parent's death position -- according to position-dependent laws. We specify a set of conditions which grants ergodicity such that the invariant occupation measure is of finite total mass and admits a continuous Lebesgue density. Under discrete-time observation, BDI configurations being recorded at discrete times $i\Delta$ only, $i\in\mathbb{N}_0$, we lose information about particle identities between successive observation times. We present a reconstruction algorithm which in a high-frequency setting (asymptotics $\Delta\downarrow 0$) allows to reconstruct correctly a sufficiently large proportion of particle identities, and thus allows to recover $\Delta$-increments of unobserved diffusion paths on which particles are travelling. Picking some few well-chosen observations we fill regression schemes which, on cubes $A$ where the invariant occupation density is strictly positive, allow to estimate the diffusion coefficient of the one-particle motion at nonparametric rates., Comment: 60 Pages

Jordbruket har i de siste årene vært utsatt for flere utfordringer, bl.a. sentralisering og effektivisering. I den forbindelse er håndtering og effektiv utnyttelse av husdyrgjødsel en viktig del av norsk matproduksjon. Husdyrgjødsel er en viktig ressurs i alle husdyrhold, men kan også være en kilde til forurensning. Det er ønskelig å begrense tapet av næringsstoffer fra husdyrgjødsla, bl.a. gjennom fordamping og avrenning. Effektivisering av landbruket har stimulert til investeringer i større maskinkapasitet, men dette gir også større utfordringer i forhold til ivaretakelse av jordstruktur. På bakgrunn av utfordringene som finnes ved utnyttelse av husdyrgjødsel har vi i denne oppgaven lyst til å bidra med en ny teknisk løsning som bedrer effektiviteten i arbeidet og som også ivaretar utnyttelsen av næringsstoffene i husdyrgjødsla. Basert på egne erfaringer og det tekniske utstyret som finnes på markedet i dag ønsker vi å finne ei løsning for å oppnå 100% spredeeffektivitet på gjødselvogn med sentrifugalpumpe. Løsningen skal gi bedre forutsetning for jevn spredning, mindre kjøring og mindre pakking av jord. Eksisterende utstyr på markedet i dag la grunnlaget for fire alternative prinsippskisser som kunne løse problemstillingen vår. Gjennom en screeningprosess og detaljutforming har vi kommet fram til en endelig løsning. Den endelige løsninga består av ei mekanisk drevet sentrifugalpumpe og ei hydraulisk drevet matepumpe med et gjødselkammer og en sluseventil. Løsningen er tegnet i 3D for å vise spredeprinsippet tydelig. Vi mener at den endelige løsningen innfrir målene vi har satt for oppgaven. Løsningen gir tilnærmet 100% spredeeffektivitet, og med noen endringer kan man oppnå fullstendig spredning. Løsningen legger til rette for mindre kjøring på jordet, noe som vil føre til mindre pakking av jord og ødeleggelse av jordstruktur. Den endelige løsningen er ikke fullprosjektert. English summary: Agriculture has faced several challenges in recent years, among other things like centralization and efficiency improvement. Handling and efficient utilization of manure has become an important part of Norwegian food production. Livestock manure is an important resource in all animal husbandry but can also be a source of pollution. It is desirable to limit the loss of nutrients from the livestock manure, among other things through evaporation and runoff. Efficiency improvements in agriculture has stimulated to investments in bigger machine capacity, but this also presents greater challenges in relation to safeguarding soil structure. Based on existing challenges when utilizing livestock manure, we want to contribute with a new technical solution that improves the efficiency of the work and which safeguards the utilization of nutrients in livestock manure. Based on our own experience and the technical equipment available on the market today, we want to find a solution to achieve 100% spreading efficiency on a slurry tanker with a centrifugal pump. The solution should provide better conditions for even spreading, less driving and less packing of soil. Existing equipment on the market today laid the foundation for four alternative principle sketches that could solve our problem. Through screening and detail design we have come up with a final solution. The final solution consists of a mechanically driven centrifugal pump and a hydraulically driven feeding pump with a manure chamber and a gate valve. The solution is drawn in 3D to show the spreading principle clearly. We believe that the final solution meets the goals we have set ourselves. The solution provides almost 100% spreading efficiency, and with some changes, complete spreading efficiency can be achieved. The solution allows for less driving on the fields, which will lead to less packing of soil and damaging of soil structure. The final solution is not fully projected.

Diese Projektarbeit beschäftigt sich mit einer zukunftsorientierten Anwendung im Bereich Energiemanagement. Hauptausrichtung ist der Aufbau von Microgrids (Mikro-Strom-Netzen) mit Blockchain-Steuerung, welche vom Stromnetz abkoppelbar sind und autark betrieben werden können. Hierzu wird zuerst der allgemeine Stand der Technik zu Microgrids vorgestellt. Grundlegende Fragestellungen zum Speicher- und Netzbedarf, der Netzanbindung und zur Dimensionierung eines Microgrid werden bearbeitet, um Kriterien für Einsatzgebiete festzulegen. Im Anschluss wird die auf Datenbanken basierende IT-Technologie Blockchain vorgestellt und ihre Relevanz für die Energiebranche erörtert. Hauptziel der Projektarbeit ist es, den technischen Stand beider Technologien darzulegen und dem Betrachter das Potenzial einer Symbiose beider Technologien für die Energiebranche aufzuzeigen. Abschließend wird eine Kombination beider Technologien an bisherigen Pilotprojekten gegeben.

Vor dem Hintergrund der immer noch anhaltenden Flächeninanspruchnahme haben Bund, Länder und Kommunen in den letzten Jahren ihre Bemühungen verstärkt, die gesetzlichen und gesellschaftspolitischen Rahmenbedingungen zu ändern, um diese Entwicklungen zu stoppen bzw. zu verlangsamen. Auch in der Stadt Solingen wurden und werden unterschiedliche Ansätze verfolgt, in denen die Reduzierung der Flächeninanspruchnahme und die Flächenkreislaufwirtschaft wichtige Aspekte darstellen. Bereits seit mehreren Jahren arbeitet die Stadt Solingen mit Flächeninformations- und Monitoringsystemen, deren Sachstand und Perspektiven nachfolgend dargestellt werden. Zudem wird herausgestellt, welcher Nutzen für die Kommune in der Teilnahme an dem ExWoSt-Forschungsfeld "Aktivierung von Innenentwicklungspotenzialen" liegt.

Using a lender cut-off rule that generates plausibly exogenous variation in credit supply, I analyze real effects of loan rejections in a sample of small and medium-sized enterprises. I find that loan rejections reduce asset growth, investments, and employment, and these effects are concentrated among low liquidity firms. Precautionary savings motives aggravate real effects: firms whose loan applications got rejected increase cash holdings and cut non-cash assets in excess of the requested loan amount. These results point to the amplifying effect of precautionary savings motives in the transmission of credit supply shocks.

More than 80% of US syndicated loans contain at least one fee type and contracts typically specify a menu of spread and different types of fees. We test the predictions of existing theories about the main purposes of fees and provide supporting evidence that: (1) fees are used to Price options embedded in loan contracts such as the draw-down option for credit lines and the cancellation option in term loans; and (2) fees are used to screen borrowers about the likelihood of exercising these options. We also propose a new total-cost-of-borrowing measure that includes various fees charged by lenders.

We analyze differences in the pricing of syndicated loans between U.S. and European loans. For credit lines, U.S. borrowers pay significantly higher spreads, but also lower fees, resulting in similar total costs of borrowing in both markets. For term loans, U.S. firms pay significantly higher spreads. While European firms across the rating spectrum issue terms loans, only low quality U.S. firms rely on term loans. U.S. issuers perform worse after loan origination compared to European issuers, which explains 30% of the spread differential. Increasing loan supply by institutional lenders in the U.S. since 2003 eventually fully removed the term loan pricing gap.

More than 80% of US syndicated loans contain at least one fee type and contracts typically specify a menu of spread and different types of fees. We test the predictions of existing theories about the main purposes of fees and provide supporting evidence that: (1) fees are used to Price options embedded in loan contracts such as the draw-down option for credit lines and the cancellation option in term loans; and (2) fees are used to screen borrowers about the likelihood of exercising these options. We also propose a new total-cost-of-borrowing measure that includes various fees charged by lenders.

More than 80% of US syndicated loans contain at least one fee type and contracts typically specify a menu of spread and different types of fees. We test the predictions of existing theories about the main purposes of fees and provide supporting evidence that: (1) fees are used to Price options embedded in loan contracts such as the draw-down option for credit lines and the cancellation option in term loans; and (2) fees are used to screen borrowers about the likelihood of exercising these options. We also propose a new total-cost-of-borrowing measure that includes various fees charged by lenders.

In this paper, we analyze the effect of the conversion price of CoCo bonds on equity holders' incentives. First, we use an option-pricing context to show that CoCo bonds can magnify equity holders' incentives to increase the riskiness of assets and decrease incentives to raise new equity in a crisis in cases in which conversion transfers wealth from CoCo bond holders to equity holders. Second, we present a clinical study of the CoCo bonds issued so far. We show that i) almost all existing CoCo bonds are designed in a way that implies a wealth transfer from CoCo bond holders to equity holders at conversion and ii) this contractual design is reflected in traded prices of CoCo bonds. In particular, CoCo bonds are short volatility with a magnitude five times greater than that which can be observed for straight bonds. These results are robust and economically significant. We conclude that the CoCo bonds issued so far can create perverse incentives for banks' equity holders.

Vielfalt der Informatik : ein Beitrag zu Selbstverständnis und Aussenwirkung / Anja Zeising ...; Bremen : [Univ.] 107-123 (2014). doi:10.18154/RWTH-2015-00877, Published by [Univ.], Bremen

Die Tagungsreihe zur Hochschuldidaktik der Informatik HDI wird vom Fachbereich Informatik und Ausbildung / Didaktik der Informatik (IAD) in der Gesellschaft für Informatik e. V. (GI) organisiert. Sie dient den Lehrenden der Informatik in Studiengängen an Hochschulen als Forum der Information und des Austauschs über neue didaktische Ansätze und bildungspolitische Themen im Bereich der Hochschulausbildung aus der fachlichen Perspektive der Informatik. Diese fünfte HDI 2012 wurde an der Universität Hamburg organisiert. Für sie wurde das spezielle Motto „Informatik für eine nachhaltige Zukunft“ gewählt, um insbesondere Fragen der Bildungsrelevanz informatischer Inhalte, der Kompetenzen für Studierende informatisch geprägter Studiengänge und der Rolle der Informatik in der Hochschulentwicklung zu diskutieren.

Es wird ein vierstufiges Förderkonzept für die Studieneingangsphase im Fach Informatik beschrieben, das derzeit im Rahmen des Projekts IGaDtools4MINT an der RWTH Aachen auf der Basis einer Literaturanalyse und eines daraus abgeleiteten Indikatorenkatalogs entwickelt wird.

Journal Netzwerk Frauen- und Geschlechterforschung NRW, vol. 2013, no. 33, p. 30

We argue that contingent convertible capital (CoCo-Bonds) might have perverse risk-taking incentives for banks (asset substitution problem) and discourage them from investing in positive NPV projects and issuing new equity in times of crisis (debt overhang problem). Whenever the conversion price is set too high - as in the case of the Lloyds CoCo-Bond issuance in November 2009 - a wealth transfer will take place at the time of conversion. This will exacerbate both the asset substitution problem and the debt overhang problem. We propose a new type of contingent convertible capital for banks - which we label Convert-to-Surrender Bonds (CoSu-Bonds) - which eliminates both the asset substitution and the debt overhang problem. CoSu-Bond convert into equity once the equity ratio falls below a certain threshold and CoSu-Bond holders take over the bank while equity holders are totally wiped out. This instrument makes equity holders naturally risk averse and gives incentives to equity holders to raise new equity and to invest also in slightly negative NPV projects in times of financial distress. Our instrument has a unique price if it is augmented by a simple option for old equity holders to issue equity if the trigger is hit, thereby circumventing the problem of multiple equilibria. We develop a tractable model to analyze risk-taking incentives in the banking sector and present a detailled analysis of the Lloyds CoCo-Bond issuance. We finally discuss several policy issues associated with this new instrument including robustness and unique equilibria.

This study calibrates the term structure of risk premia before and during the 2007/2008 financial crisis using a new calibration approach based on credit default swaps. The risk premium term structure was flat before the crisis and downward sloping during the crisis. The instantaneous risk premium increased significantly during the crisis, whereas the long-run mean of the risk premium process was of the same magnitude before and during the crisis. These findings suggest that (marginal) investors have become more risk averse during the crisis. Investors were, however, well aware that risk premia will revert back to normal levels in the long run.

This thesis analyzes risk premia on credit and equity markets. While current research usually looks at risk premia on credit and equity markets separately, we develop a model which allows for an integrated view. After the theoretical analysis an empirical study based on credit default swaps (CDS) from 2003-2007 for the U.S., Europe and Asia is conducted. This results in equity premia of 6.50% (U.S.), 5.44% (Europe) and 6.21% (Asia). An expansion to 2008 shows, that the risk premium term structure was flat before the 2007/2008 financials crisis and became inverse during the crisis. This indicates that investors have become more risk averse during the crisis but were well aware, that risk premia will revert back to normal levels in the long run. Diese Arbeit beschäftigt sich mit der Bestimmung von Risikoprämien auf Fremd- und Eigenkapitalmärkten. Während die bisherige Forschung diese Märkte i. d. R. separat betrachtet, wird hier ein Modell entwickelt, das einen Vergleich von Risikoprämien auf Fremd- und Eigenkapitalmärkten ermöglicht. Nach der theoretischen Analyse erfolgt eine empirische Anwendung auf Basis von Credit Default Swap (CDS) Spreads aus den USA, Europa und Asien von 2003-2007. Die dabei geschätzten Marktriskoprämien liegen bei 6.50% (USA), 5.44% (Europa) und 6.21% (Asien). Eine Erweiterung auf den Zeitraum bis 2008 zeigt, dass die Risikoprämienstrukturkurve vor der Finanzkrise flach verlaufen ist, allerdings während der Finanzkrise einen inversen Verlauf ausweist. Dies deutet darauf hin, dass Investoren während der Finanzkrise risikoaverser geworden sind, sich aber bewusst waren, dass Risikoprämien langfristig wieder zu den ursprünglichen Niveaus zurückkehren werden.

The purpose of this paper is to analyze the influence of uncertainty on the value of real options while allowing for a possible change in the value of the underlying asset. We show that the proposition of a strictly positive influence of uncertainty does not hold, if the value of the underlying asset changes due to a Variation of the Standard deviation. Only if the underlying risk is unsystematic or the binding relation between risk and return is neglected, the strictly positive effect of uncertainty can be retained. In all other cases, the influence becomes ambiguous. In addition, we discuss the consequences of our results on a more economic level to convey an understanding of when the procedure dealt with would be indicated.

Although the equity premium is - both from a conceptual and empirical perspective - a widely researched topic in finance, there is still no consensus in the academic literature about its magnitude. In this paper, we propose a different estimation method which is based on credit valuations. The main idea is straigtforward: We use structural models to link equity valuations to credit valuations. Based on a simple Merton model, we derive an estimator for the market Sharpe ratio. This estimator has several advantages. First, it offers a new line of thought for estimating the equity premium which is not directly linked to current methods. Second, it is only based on observable parameters. We do neither have to calibrate dividend or earnings growth - which is usually necessary in dividend/earnings discount models - nor do we have to calibrate asset values or default barriers - which is usually necessary in traditional applications of structural models. Third, it is robust to model changes. We examine the model of Duffie/Lando (2001) - which is one of the most sophisticated structural models currently discussed in the literature - to show this robustness. In an empirical analysis we have used CDS spreads of the 125 most liquid CDS in the U.S. from 2003 to 2007 to estimate the equity premium. We derive an average implicit market Sharpe ratio of appr. 40%. Adjusting for taxes and other parts of the credit spread not attributable to credit risk yields an average market Sharpe ratio below 30%. This confirms research on the equity premium, which indicates that the historically observed Sharpe ratio of 40-50% - corresponding to an equity premium of 7-9% and a volatility of 15-20% - was partly due to one-time effects. In addition, our research can be used to explain empirical findings about credit risk premia, which are usually measured as the ratio of risk-neutral to actual default probabilities. We show that the behavior of these ratios can be directly inferred from a simple Merton model and that this behavior is robust to model changes.

Although the equity premium is - both from a conceptual and empirical perspective - a widely researched topic in finance, there is still no consensus in the academic literature about its magnitude. In this paper, we propose a different estimation method which is based on credit valuations. The main idea is straigtforward: We use structural models to link equity valuations to credit valuations. Based on a simple Merton model, we derive an estimator for the market Sharpe ratio. This estimator has several advantages. First, it offers a new line of thought for estimating the equity premium which is not directly linked to current methods. Second, it is only based on observable parameters. We do neither have to calibrate dividend or earnings growth - which is usually necessary in dividend/earnings discount models - nor do we have to calibrate asset values or default barriers - which is usually necessary in traditional applications of structural models. Third, it is robust to model changes. We examine the model of Duffie/Lando (2001) - which is one of the most sophisticated structural models currently discussed in the literature - to show this robustness. In an empirical analysis we have used CDS spreads of the 125 most liquid CDS in the U.S. from 2003 to 2007 to estimate the equity premium. We derive an average implicit market Sharpe ratio of appr. 40%. Adjusting for taxes and other parts of the credit spread not attributable to credit risk yields an average market Sharpe ratio below 30%. This confirms research on the equity premium, which indicates that the historically observed Sharpe ratio of 40-50% - corresponding to an equity premium of 7-9% and a volatility of 15-20% - was partly due to one-time effects. In addition, our research can be used to explain empirical findings about credit risk premia, which are usually measured as the ratio of risk-neutral to actual default probabilities. We show that the behavior of these ratios can be directly inferred from a simple Merton model and that this behavior is robust to model changes.

Background: In Sweden approximately 37 000 individuals are affected by myocardial infarction every year. It is important after an infarction to investigate and make preventive changes of lifestyle to prevent another event. Patients have different conditions on how to manage a myocardial infarction and the new life situation they are put in. Through Kim’s domains men’s experiences after a myocardial infarction are separated. Aim: The aim for this study was to elucidate men’s experiences after a myocardial infarction. Methods: Systematic literature review Result: Some men pointed out physical symptoms while others brought out psychological. Many experienced lifestyle changes as difficult. Numerous men felt support from their surrounding; nevertheless they felt that it affected their daily life by being overprotective. Multiple men where dissatisfied with the information from their care givers. Discussion: It is important to see the individual and the person’s life situation. What is the reason for patients’ dissatisfaction regarding information? How would it be possible to facilitate for the patients´ in their situation with an overprotective family and how would it be possible to find those patients´ that are considered as patients at risk without support from their surrounding? Conclusion: The individual behind the sickness is never to be overlooked witch could give negative consequences regarding nursing. For some reason there is a lack of information. This ought to be investigated so that the quality of the information to patients´ could be better. Overprotective family should be more involved in the care.

Purpose; Purpose of this thesis is to review the implementation process of SOX in one company to be able to estimate which factors that are significant for individuals when it comes to accepting SOX as a tool to improving processes. Method: Our approach in attacking the reality has been the golden middle-way, which means we have went into the reality with already constructed theories but along as the study went on we have refined theories, thus shifting between inductive and deductive approach. Results/conclusions; Important obstacles that prevented adoption of the innovation had to do the characteristic of the innovation and the size and complexity of the organization; however we believed that the most significant blockade against change was the non-existing communication between the three different parties, namely consultants, managers and end-users.

In today’s society, strategy becomes more important because of the ever fast changing environment. Companies all around the world set strategies, in order to grow and earn a profit, and wish for them to be implemented the way they were intended to be. Therefore, we believe it is important to investigate individuals’ perceptions of firm strategy. The purpose of this thesis is therefore to investigate individuals’ perception and understanding of firm strategy, and to see how these perceptions show similarities and differences. Our aim is also to see how cognitive mapping in relation to a strategic model can be helpful both for practitioners and researchers. Collection of primary data was done by interviewing five employees on different hierarchical levels in Company X that is active in multiple different business areas both in Sweden and abroad. The interviews were later analysed with the help of theories such as cognitive structures and maps, and Whittington’s (2001) generic perspective of strategy. This model recognizes four approaches to strategizing, namely Classical, Evolutionary, Systemic and Processual. The two former ones have a Profit-maximizing outcome, while the latter two are Pluralistic in outcome. During the analysis we found some similarities and differences. It was found that not all employees, individually or together, could be categorised under one specific approach. It is hypothesized that this could be because of the fact that they are at different levels and positions in the company, but they had similar perception on long-term planning as a firm strategy. The interviewees in Company X have shown different perceptions when relating to strategy. We come to the conclusion that it is important for managers and strategic decision makers that they understand and take the differences and similarities under consideration when delegating and injecting new strategies into a company. We think this could then help them to enhance an understanding of their own strategic organisation. Although case studies tend to be subjective, this is pointed out as the main limitation of the methodology. The researchers’ interpretation of the interviews lay as the foundation of the analysis and conclusion, and in order to make the study as objective as possible, clear and relevant selection of theories and literature was used to support the claims made in the thesis.

Acute myeloid leukemia (AML) is an aggressive cancer of the blood and bone marrow, affecting 1,100 Canadians annually. Older patients make up 75% of cases yet have the lowest survival rates due to the lack of tolerable treatments. Recently, the combination of Venetoclax and Azacitidine (Ven/Aza) has shown great therapeutic promise, however, chemoresistance has become a growing concern. Current evidence points towards a chemoprotective role from the bone marrow (BM) microenvironment, specifically by BM-derived mesenchymal stromal cells (BMSCs) and adipocytes. AML cells can manipulate BMSCs and adipocytes to create a niche that supports its own growth and evades chemotherapy. However, the role of the microenvironment in Ven/Aza chemoresistance has yet to be studied. Our objective was to study the ability of the microenvironment cells to induce AML chemoresistance to Ven/Aza. We employed a 2-dimensional direct contact co-culture system between MOLM-13 AML cells and BMSCs or adipocytes in both the absence and presence of Ven/Aza to determine the effects on the AML cells. In the absence of Ven/Aza, adipocyte co-cultured AML cells showed a 47% reduction in proliferation, 10% reduction in viability, yet a 1.7-fold increase in Maximal respiration when compared to the monocultured cells. In the presence of Ven/Aza, adipocyte co-cultured AML cells showed a significant increase in both proliferation and viability. Preliminary work investigating the mechanism of action of this support points toward an anti-apoptotic mechanism mediated by the upregulation of MCL-1 upon co-culture with adipocytes. Combination of Venetoclax and Tapotoclax, an MCL-1 inhibitor, abrogated the chemoprotection provided by BMSCs and adipocytes. Overall, our data suggests a dual role of adipocytes, where their inhibition or support of AML is context dependent. Therapeutic targeting of mechanisms for adipocyte chemoprotection such as MCL-1 upregulation may re-sensitize AML cells to Ven/Aza, thereby improving patient outcomes. Thesis Master of Science (MSc) Acute myeloid leukemia (AML) is an aggressive cancer of the blood and bone marrow, affecting 1,100 Canadians annually. Older patients make up 75% of cases yet have the lowest survival rates due to the lack of tolerable treatments. A novel combination of Venetoclax and Azacitidine (Ven/Aza) has shown great therapeutic promise, however, chemoresistance remains an important concern. Previous studies have implicated fat cells, or adipocytes, in AML chemoresistance, however, their role in Ven/Aza treatment has yet to be studied. Here, we show that adipocytes reduce growth of AML cells, yet enhance their metabolism. In the presence of Ven/Aza, adipocytes induce chemoresistance. We show preliminary data that this chemoprotection may be mediated by the upregulation of mitochondrial MCL-1 protein as inhibition of this protein neutralized the protection. By understanding the relationship between adipocytes and AML chemoresistance, we can target this and re-sensitize AML to Ven/Aza, thereby improving older patient outcomes.