Barrett's Esophagus and Associated Adenocarcinoma : studies on pathogenesis, clinical staging and cost-utility of cancer treatment

Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is rapidly increasing disease with a pathophysiology connected to oxidative stress. Exact pre-treatment clinical staging is essential for optimal care of this lethal malignancy. The cost-effectiviness of treatment is increasingly important. We measured oxidative metabolism in the distal and proximal esophagus by myeloperoxidase activity (MPA), glutathione content (GSH), and superoxide dismutase (SOD) in 20 patients operated on with Nissen fundoplication and 9 controls during a 4-year follow-up. Further, we assessed the oxidative damage of DNA by 8-hydroxydeoxyguanosine (8-OHdG) in esophageal samples of subjects (13 Barrett s metaplasia, 6 Barrett s esophagus with high-grade dysplasia, 18 adenocarcinoma of the distal esophagus/GEJ, and 14 normal controls). We estimated the accuracy (42 patients) and preoperative prognostic value (55 patients) of PET compared with computed tomography (CT) and endoscopic ultrasound (EUS) in patients with adenocarcinoma of the esophagus/GEJ. Finally, we clarified the specialty-related costs and the utility of either radical (30 patients) or palliative (23 patients) treatment of esophageal/GEJ carcinoma by the 15 D health-related quality-of-life (HRQoL) questionnaire and the survival rate. The cost-utility of radical treatment of esophageal/GEJ carcinoma was investigated using a decision tree analysis model comparing radical, palliative, and hypothetical new treatment. We found elevated oxidative stress ( measured by MPA) and decreased antioxidant defense (measured by GSH) after antireflux surgery. This indicates that antireflux surgery is not a perfect solution for oxidative stress of the esophageal mucosa. Elevated oxidative stress in turn may partly explain why adenocarcinoma of the distal esophagus is found even after successful fundoplication. In GERD patients, proximal esophageal mucosal anti-oxidative defense seems to be defective before and even years after successful antireflux surgery. In addition, antireflux surgery apparently does not change the level of oxidative stress in the proximal esophagus, suggesting that defective mucosal anti-oxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD. In the malignant transformation of Barrett s esophagus an important component appears to be oxidative stress. DNA damage may be mediated by 8-OHdG, which we found to be increased in Barrett s epithelium and in high-grade dysplasia as well as in adenocarcinoma of the esophagus/GEJ compared with controls. The entire esophagus of Barrett s patients suffers from increased oxidative stress ( measured by 8-OhdG). PET is a useful tool in the staging and prognostication of adenocarcinoma of the esophagus/GEJ detecting organ metastases better than CT, although its accuracy in staging of paratumoral and distant lymph nodes is limited. Radical surgery for esophageal/GEJ carcinoma provides the greatest benefit in terms of survival, and its cost-utility appears to be the best of currently available treatments.

Sustainability and Mission Drift in Microfinance

Microfinance institutions (MFIs) are constrained by double bottom-lines: meeting social obligations (the first bottom-line) and obtaining financial self-sufficiency (the second bottom-line). The proponents of the first bottom-line, however, are increasingly concerned that there is a trade-off between these two bottom-lines—i.e., getting hold of financial self-sufficiency may lead MFIs to drift away from their original social mission of serving the very poor, commonly known as mission drift in microfinance which is still a controversial issue. This study aims at addressing the concerns for mission drift in microfinance in a performance analysis framework. Chapter 1 deals with theoretical background, motivation and objectives of the topic. Then the study explores the validity of three major and related present-day concerns. Chapter 2 explores the impact of profitability on outreach-quality in MFIs, commonly known as mission drift, using a unique panel database that contains 4-9 years’ observations from 253 MFIs in 69 countries. Chapter 3 introduces factor analysis, a multivariate tool, in the process of analysing mission drift in microfinance and the exercise in this chapter demonstrates how the statistical tool of factor analysis can be utilised to examine this conjecture. In order to explore why some microfinance institutions (MFIs) perform better than others, Chapter 4 looks at factors which have an impact on several performance indicators of MFIs—profitability or sustainability, repayment status and cost indicators—based on quality-data on 353 institutions in 77 countries. The study also demonstrates whether such mission drift can be avoided while having self-sustainability. In Chapter 5 we examine the impact of capital and financing structure on the performance of microfinance institutions where estimations with instruments have been performed using a panel dataset of 782 MFIs in 92 countries for the period 2000-2007. Finally, Chapter 6 concludes the study by summarising the results from the previous chapters and suggesting some directions for future studies.

Essays on the Determinants of International Portfolio Investments

Investors significantly overweight domestic assets in their portfolios. This behavior which is commonly called “home bias” contradicts the prescriptions of portfolio theory. This thesis explores potential reasons for the “home bias” by examining the characteristics of the investing and the target countries and features of the interaction between them. A common theme of the four essays is a focus on the importance of information about foreign markets in explaining the share of these markets in investors’ portfolios. The results indicate that the size of the equity ownership in another country strongly relates to the distance to the financial capital of that country, and to trade in goods with and direct investments (FDI) to that country. The first essay empirically investigates the relationship between trade in real goods and portfolio investments. Overall, the evidence indicates a substantial role for trade in reducing the information cost relating to portfolio investments. The second essay examines the implications of the launch of the European Monetary Union (EMU) on international portfolio investments. The evidence on the allocation of Finnish international portfolio investments is more consistent with an information-based than a diversification motive explanation. The third essay employs new data for a large number of countries and further explores the role of trade on international portfolio investments. The results indicate that trade provides important information especially on firms in countries in which the corporate governance structure and the information environment of firms generate less reliable information. The fourth essay examines the relationship between direct investments (FDI) and portfolio investments. In contrast to the predications of portfolio theory, it provides evidence that FDI is a complement rather than a substitute for portfolio investments.

Trade Liberalization, Heterogeneous Firms and Industrial Dynamics

This master thesis studies how trade liberalization affects the firm-level productivity and industrial evolution. To do so, I built a dynamic model that considers firm-level productivity as endogenous to investigate the influence of trade on firm’s productivity and the market structure. In the framework, heterogeneous firms in the same industry operate differently in equilibrium. Specifically, firms are ex ante identical but heterogeneity arises as an equilibrium outcome. Under the setting of monopolistic competition, this type of model yields an industry that is represented not by a steady-state outcome, but by an evolution that rely on the decisions made by individual firms. I prove that trade liberalization has a general positive impact on technological adoption rates and hence increases the firm-level productivity. Besides, this endogenous technology adoption model also captures the stylized facts: exporting firms are larger and more productive than their non-exporting counterparts in the same sector. I assume that the number of firms is endogenous, since, according to the empirical literature, the industrial evolution shows considerably different patterns across countries; some industries experience large scale of firms’ exit in the period of contracting market shares, while some industries display relative stable number of firms or gradually increase quantities. The special word “shakeout” is used to describe the dramatic decrease in the number of firms. In order to explain the causes of shakeout, I construct a model where forward-looking firms decide to enter and exit the market on the basis of their state of technology. In equilibrium, firms choose different dates to adopt innovation which generate a gradual diffusion process. It is exactly this gradual diffusion process that generates the rapid, large-scale exit phenomenon. Specifically, it demonstrates that there is a positive feedback between firm’s exit and adoption, the reduction in the number of firms increases the incentives for remaining firms to adopt innovation. Therefore, in the setting of complete information, this model not only generates a shakeout but also captures the stability of an industry. However, the solely national view of industrial evolution neglects the importance of international trade in determining the shape of market structure. In particular, I show that the higher trade barriers lead to more fragile markets, encouraging the over-entry in the initial stage of industry life cycle and raising the probability of a shakeout. Therefore, more liberalized trade generates more stable market structure from both national and international viewpoints. The main references are Ederington and McCalman(2008,2009).

International Portfolio Investments and The Informational Value of Trade

A large volume of literature suggests that information asymmetry resulting from the spatial separation between investors and investments have a significant impact on the composition of investors’ domestic and international portfolios. I show that institutional factors affecting trading in tangible goods help explain a substantial portion of investors’ spatial bias. More importantly, I demonstrate that an information flow medium with breadth and richness directly linked to the bilateral commitment of resources between countries, that I measure by their trading intensity in tangible goods, is consistent with the prevailing country allocation in investors’ international portfolios.

Evaluating the regional and distributional impacts of forestry cost-share payments.

XVIII IUFRO World Congress, Ljubljana 1986.

Cost and effectiveness of legal mandates for the practice of forestry on private land.

XVIII IUFRO World Congress, Ljubljana 1986.