Published Article / Service-learning is a relatively new teaching and learning method which has been implemented with success at national and international tertiary institutions. The identification and elucidation of the terms and processes that delineate the dynamic character of service-earning satisfactorily pose a particular challenge to researchers within the service-learning environment. Since a degree of confusion still exists amongst researchers and decision-makers regarding the distinguishing characteristics of service-learning as opposed to other forms of experiential learning, it is essential to indicate the specific position of service-learning within this environment.

<p>This dissertation consists of three essays on asymmetric correlations in financial markets. In the first essay, I have two main contributions. First, I show that dividend growth rates have symmetric correlations. Second, I show that asymmetric correlations are different than correlations being counter-cyclical. The correlation asymmetry I study in this dissertation should not be confused with correlations being counter-cyclical, i.e. being higher during recessions than during booms. I show that while counter-cyclical correlations can simply be explained by counter-cyclical aggregate market volatility, the correlation asymmetry with respect to joint upside and downside movements of returns are not just due to the heightened market volatility during those times. </p><p>In the second essay I present a model in order to explain the correlation asymmetry observed in the data. This is the first paper to offer an explanation for observed correlation asymmetry. I formalize the explanation using an equilibrium model. The model is useful to understand both the cross-section and time-series of correlation asymmetry. By the means of my model, we can answer questions about why some stocks have higher correlation asymmetry, and why the correlation asymmetry was higher during 1990s? In the model asset prices respond the realization of dividends and news about the future. However, price responses to news are asymmetric and this asymmetry is endogenous. Price responses are endogenously stronger conditional on bad news than conditional on good news. This asymmetry also generates the observed correlation asymmetry. The price responses are asymmetric due to the ambiguity about the news quality. Information about the quality of the signal is incomplete in the sense that the exact precision of the signal is unknown; it is only known to be in an interval, which makes the representative agent treat news as ambiguous. To model ambiguity aversion, I use Gilboa and Schmeidler (1989)'s max-min expected utility representation. The agent has a set of beliefs about the quality of signals, and the ambiguity-averse agent behaves as if she maximizes expected utility under a worst-case scenario. This incomplete information about the news quality, together with ambiguity-averse agents, generates an asymmetric response to news. Endogenous worst-case scenarios differ depending on the realization of news. When observing ``bad" news, the worst-case scenario is that the news is reliable and the prices of trees decrease strongly. On the other hand, when ``good news" is observed, under the worst-case scenario the news is evaluated as less reliable, and thus the price increases are mild. Therefore, price responses are stronger conditional on a negative signal and this asymmetry creates a higher correlation conditional on a negative signal than conditional on a positive signal. I also show that the results are robust to the smooth ambiguity aversion representation.</p><p>Motivated by the model, I uncover a new empirical regularity that is unknown in the literature. I show that correlation asymmetry is related to idiosyncratic volatility: the higher the idiosyncratic volatility, the higher the correlation asymmetry. This novel empirical finding is also useful to understand the time-series and cross-sectional variation in correlation asymmetry. Stocks with smaller market capitalizations have greater correlation asymmetry compared to stocks with higher market capitalization. However, an explanation for this finding has been lacking. According to the explanation offered in this paper, smaller size stocks have greater correlation asymmetry compared to bigger size stocks because small size stocks tend to have higher idiosyncratic volatilities compared to bigger size stocks. In the time-series, correlation asymmetry shows quite significant variation as well. The average correlation asymmetry is especially high for the 1990s and decreases significantly at the beginning of the 2000s. This pattern in times-series can also be explained in terms of the time-series behavior of idiosyncratic volatilities. Several papers including Brandt et al. (2010), document higher idiosyncratic volatilities during 1990s while the aggregate volatility stays fairly stable. Basically, the high idiosyncratic volatilities during the 1990s also caused greater correlation asymmetry. </p><p>In the third essay, I study the correlation of returns in government bond markets. Similar to the findings in equity markets, I show that there is some evidence for asymmetric correlations in government bond markets. First, I show that the maturity structure matters for correlation asymmetry in bonds markets: Unlike long-maturity bonds, shorter-maturity bonds tend to have asymmetric correlations. Second, I show that the correlation asymmetry observed in European bond markets disappears with the formation of a common currency area. Lastly, I study the correlation between equity and bond returns in different countries. For long-maturity bonds, correlations with the domestic equity returns are asymmetric for half of the countries in the sample, including the U.S. These findings show that results on asymmetric correlations from equity markets can generalize, at least to some extent, to other financial markets.</p> / Dissertation

The mechanisms of idiosyncratic drug reactions (IDRs) are unknown; however, most appear to be immune-mediated. Their idiosyncratic nature and the paucity of animal models make mechanistic studies very difficult. One of the few animal models is penicillamine-induced autoimmunity in Brown Norway rats. The major focus of this thesis was the use of this model to study the interaction between penicillamine and macrophages, the involvement of Th17 cells, and extension of this model to idiosyncratic drug-induced liver injury. One of the costimulatory signals leading to T cell activation appears to be reversible Schiff-base formation between an amine on T cells and an aldehyde on macrophages. We hypothesized that penicillamine binds to these aldehydes leading to macrophage activation and autoimmunity. By using biotinylated aldehyde-reactive agents such as ARP, we demonstrated the existence of aldehydes on the surface of macrophages. We synthesized biotinylated-penicillamine and it also binds to macrophages. Several proteins to which ARP binds were identified providing clues to the signal transduction pathways leading to macrophage activation. Biological consequences of this binding were investigated with a microarray study. ARP binding was also observed in the macrophage cell line, RAW264.7, and incubation with penicillamine stimulated the production of TNF-α, IL-6, and IL-23. Hydralazine and isoniazid, which are known to cause a lupus-like syndrome in humans and irreversibly bind to aldehyde groups, were also found to activate RAW264.7 cells. Th17 cells are prominent in autoimmune syndromes and Th17-associated cytokines such as IL-17 were elevated in the penicillamine-treated animals that developed autoimmunity. We have hypothesized that some drug-induced liver injury has an autoimmune component. A pilot study quantified serum concentrations of 26 cytokines/chemokines in patients with various forms of acute liver failure (ALF): idiosyncratic drug-induced ALF, acetaminophen-induced ALF, and viral hepatitis. IL-17 was elevated in 60% of patients with idiosyncratic drug-induced ALF, which supports an autoimmune component in these patients; however, it was also elevated in many cases of acetaminophen-induced ALF, presumably released by the innate immune system. These studies provide important insights into the mechanism of penicillamine-, hydralazine-, and isoniazid-induced autoimmunity and also provide clues to other IDRs that may have an autoimmune component.

An animal model of nevirapine (NVP)-induced skin rash was used to test the hypothesis that sulfonation of 12-OH NVP, a metabolite of NVP proven essential for rash development, is the link between 12-OH NVP and the skin rash. Female Brown Norway (BN) rats were co-treated with NVP or 12-OH NVP and sulfation inhibitors dehydroepiandrosterone (DHEA) and salicylamide. Co-treatment with salicylamide markedly decreased formation of the sulfate conjugate but did not prevent development of the rash suggesting that the sulfate is not involved. However, it is not known whether the sulfate formation in the skin was affected. Co-treatments with DHEA decreased the sulfate formation and prevented the rash but also had other effects on NVP metabolism. This implies that the sulfate metabolite is responsible for the rash. Additional studies will be required to resolve these conflicting results.

An animal model of nevirapine (NVP)-induced skin rash was used to test the hypothesis that sulfonation of 12-OH NVP, a metabolite of NVP proven essential for rash development, is the link between 12-OH NVP and the skin rash. Female Brown Norway (BN) rats were co-treated with NVP or 12-OH NVP and sulfation inhibitors dehydroepiandrosterone (DHEA) and salicylamide. Co-treatment with salicylamide markedly decreased formation of the sulfate conjugate but did not prevent development of the rash suggesting that the sulfate is not involved. However, it is not known whether the sulfate formation in the skin was affected. Co-treatments with DHEA decreased the sulfate formation and prevented the rash but also had other effects on NVP metabolism. This implies that the sulfate metabolite is responsible for the rash. Additional studies will be required to resolve these conflicting results.

Many previous studies find that family firms are prevalent among the U.S. firms. In particular, more than 35 percent of the S&P 500 firms consist of family firms in which families control about 18 percent of their firms’ shares. According to agency theory, the characteristics of a firm’s ownership, governance, and control play a critical role in the firm’s risk-taking activities and information flow to the market. Our study aims to investigate two controversies in the family business literature: whether family firms undertake fewer or more risks than non-family firms do, and whether family firms exhibit higher or lower information flow, reflected in their stock price informativeness and earnings informativeness, to the market. Using a sample of the S&P 500 companies as of 2003 for the period 2003-2007, we find that compared with non-family firms, the stock prices of family firms have more firm specific information impounded and the accounting earnings of family firms are more informative and thereby have more explanatory power for stock returns. These results are robust to different model specifications and variable proxies. In terms of risk-taking levels in corporate investment, our results indicate that family firms, on average, undertake fewer risks than non-family firms do. In particular, we find that although G-index is negatively associated with corporate risk-taking in non-family firms as previous studies (e.g. John et al., 2008) find for general firms, governance provisions do not have any influence on corporate risk-taking decisions in family firms. Numerous additional sensitivity tests using different corporate risk-taking proxies confirm the robustness of the findings.

The mechanisms of idiosyncratic drug reactions (IDRs) are unknown; however, most appear to be immune-mediated. Their idiosyncratic nature and the paucity of animal models make mechanistic studies very difficult. One of the few animal models is penicillamine-induced autoimmunity in Brown Norway rats. The major focus of this thesis was the use of this model to study the interaction between penicillamine and macrophages, the involvement of Th17 cells, and extension of this model to idiosyncratic drug-induced liver injury. One of the costimulatory signals leading to T cell activation appears to be reversible Schiff-base formation between an amine on T cells and an aldehyde on macrophages. We hypothesized that penicillamine binds to these aldehydes leading to macrophage activation and autoimmunity. By using biotinylated aldehyde-reactive agents such as ARP, we demonstrated the existence of aldehydes on the surface of macrophages. We synthesized biotinylated-penicillamine and it also binds to macrophages. Several proteins to which ARP binds were identified providing clues to the signal transduction pathways leading to macrophage activation. Biological consequences of this binding were investigated with a microarray study. ARP binding was also observed in the macrophage cell line, RAW264.7, and incubation with penicillamine stimulated the production of TNF-α, IL-6, and IL-23. Hydralazine and isoniazid, which are known to cause a lupus-like syndrome in humans and irreversibly bind to aldehyde groups, were also found to activate RAW264.7 cells. Th17 cells are prominent in autoimmune syndromes and Th17-associated cytokines such as IL-17 were elevated in the penicillamine-treated animals that developed autoimmunity. We have hypothesized that some drug-induced liver injury has an autoimmune component. A pilot study quantified serum concentrations of 26 cytokines/chemokines in patients with various forms of acute liver failure (ALF): idiosyncratic drug-induced ALF, acetaminophen-induced ALF, and viral hepatitis. IL-17 was elevated in 60% of patients with idiosyncratic drug-induced ALF, which supports an autoimmune component in these patients; however, it was also elevated in many cases of acetaminophen-induced ALF, presumably released by the innate immune system. These studies provide important insights into the mechanism of penicillamine-, hydralazine-, and isoniazid-induced autoimmunity and also provide clues to other IDRs that may have an autoimmune component.

The Modern Portfolio Theory (MPT) argues that all unsystematic risk can be diversified away thus there should be no relationship between idiosyncratic risk and return. Ooi, Wang and Webb (2009) employ the Fama-French (1993) three-factor model (FF3) to estimate the level of nonsystematic return volatility in REITs as a proxy for idiosyncratic risk. They find a significant positive relationship between expected returns and conditionally estimated idiosyncratic risk contrary to the MPT. In this research, I examine other potential sources of systematic risk in REITs which may explain the seeming violation of the MPT found by Ooi et al (2009). I re-examine the proportion of idiosyncratic risk in REITs with Carhart’s (1997) momentum factor, which is largely applied on the FF3 to control for the persistency of stock returns as supplemental risk in the finance literature. Next, I conduct cross-sectional regression and test the significance of the relationship between idiosyncratic risk and expected returns. I further analyze the role of property sector on idiosyncratic risk as well as on its relationship with expected returns. I argue three conclusions. First, momentum has a relatively minor effect on the idiosyncratic risk consistent with the financial literature. Second, the effect of momentum is not strong enough to cause a significant change in the relationship between idiosyncratic risk and expected returns. Third, a REIT portfolio diversified across property sectors neutralizes the relationship between idiosyncratic risk and expected returns, though the contribution of each property sector is not statistically significant.

Idiosyncratic drug reactions (IDRs) are unpredictable adverse drug reactions. Their exact mechanisms are unknown but most appear to be immune-mediated. Mechanistic studies require valid animal models, but there are very few available and none for the study of drug-induced agranulocytosis. Thus, the first part of my thesis has focused on the development of an animal model of agranulocytosis. We pursued many attempts to develop one in rabbits, guinea pigs, and rats by treatment with aminopyrine, amodiaquine, and clozapine and manipulating the factors hypothesized to be involved in the mechanism of IDRs such as reactive metabolite formation/detoxication and immune stimulation. Clozapine-induced agranulocytosis is not associated with immune memory, which suggests that it may not be immune-mediated. Therefore, other factors, specifically selenium and vitamin C deficiencies, were assessed as possible risk factors for clozapine-induced agranulocytosis. Despite many attempts, we were not able to develop an animal model of idiosyncratic drug-induced agranulocytosis. The second part of this thesis was focused on investigating the effects of clozapine on neutrophils. It is known that the reactive metabolite of clozapine increases neutrophil apoptosis in vitro; however, it was not clear that the conditions of these experiments reflect in vivo conditions. Therefore, the effect of clozapine on neutrophil kinetics in vivo was examined. We found that clozapine treatment decreased the half-life of circulating neutrophils and increased the rate of release of neutrophils in rabbits. Thus, even though these animals did not develop agranulocytosis clozapine did appear to cause neutrophil damage that was compensated for by an increased production of neutrophils. Failure of the bone marrow to keep up with the increased rate of neutrophil destruction in certain individuals could result in agranulocytosis. Alternatively, damage to neutrophils could lead to an immune response in some patients that results in agranulocytosis. The failure to develop an animal model of drug-induced agranulocytosis despite many attempts using interventions based on the current mechanistic hypotheses suggests that these hypotheses are wrong. However, it is also possible that we are just unable to overcome the default response of immune tolerance; future studies will examine this possibility and the mechanism of clozapine-induced neutrophil damage.

Idiosyncratic drug reactions (IDRs) are unpredictable adverse drug reactions. Their exact mechanisms are unknown but most appear to be immune-mediated. Mechanistic studies require valid animal models, but there are very few available and none for the study of drug-induced agranulocytosis. Thus, the first part of my thesis has focused on the development of an animal model of agranulocytosis. We pursued many attempts to develop one in rabbits, guinea pigs, and rats by treatment with aminopyrine, amodiaquine, and clozapine and manipulating the factors hypothesized to be involved in the mechanism of IDRs such as reactive metabolite formation/detoxication and immune stimulation. Clozapine-induced agranulocytosis is not associated with immune memory, which suggests that it may not be immune-mediated. Therefore, other factors, specifically selenium and vitamin C deficiencies, were assessed as possible risk factors for clozapine-induced agranulocytosis. Despite many attempts, we were not able to develop an animal model of idiosyncratic drug-induced agranulocytosis. The second part of this thesis was focused on investigating the effects of clozapine on neutrophils. It is known that the reactive metabolite of clozapine increases neutrophil apoptosis in vitro; however, it was not clear that the conditions of these experiments reflect in vivo conditions. Therefore, the effect of clozapine on neutrophil kinetics in vivo was examined. We found that clozapine treatment decreased the half-life of circulating neutrophils and increased the rate of release of neutrophils in rabbits. Thus, even though these animals did not develop agranulocytosis clozapine did appear to cause neutrophil damage that was compensated for by an increased production of neutrophils. Failure of the bone marrow to keep up with the increased rate of neutrophil destruction in certain individuals could result in agranulocytosis. Alternatively, damage to neutrophils could lead to an immune response in some patients that results in agranulocytosis. The failure to develop an animal model of drug-induced agranulocytosis despite many attempts using interventions based on the current mechanistic hypotheses suggests that these hypotheses are wrong. However, it is also possible that we are just unable to overcome the default response of immune tolerance; future studies will examine this possibility and the mechanism of clozapine-induced neutrophil damage.