Computational framework to support integration of biomolecular and clinical data within a translational approach

Background The use of the knowledge produced by sciences to promote human health is the main goal of translational medicine. To make it feasible we need computational methods to handle the large amount of information that arises from bench to bedside and to deal with its heterogeneity. A computational challenge that must be faced is to promote the integration of clinical, socio-demographic and biological data. In this effort, ontologies play an essential role as a powerful artifact for knowledge representation. Chado is a modular ontology-oriented database model that gained popularity due to its robustness and flexibility as a generic platform to store biological data; however it lacks supporting representation of clinical and socio-demographic information. Results We have implemented an extension of Chado – the Clinical Module - to allow the representation of this kind of information. Our approach consists of a framework for data integration through the use of a common reference ontology. The design of this framework has four levels: data level, to store the data; semantic level, to integrate and standardize the data by the use of ontologies; application level, to manage clinical databases, ontologies and data integration process; and web interface level, to allow interaction between the user and the system. The clinical module was built based on the Entity-Attribute-Value (EAV) model. We also proposed a methodology to migrate data from legacy clinical databases to the integrative framework. A Chado instance was initialized using a relational database management system. The Clinical Module was implemented and the framework was loaded using data from a factual clinical research database. Clinical and demographic data as well as biomaterial data were obtained from patients with tumors of head and neck. We implemented the IPTrans tool that is a complete environment for data migration, which comprises: the construction of a model to describe the legacy clinical data, based on an ontology; the Extraction, Transformation and Load (ETL) process to extract the data from the source clinical database and load it in the Clinical Module of Chado; the development of a web tool and a Bridge Layer to adapt the web tool to Chado, as well as other applications. Conclusions Open-source computational solutions currently available for translational science does not have a model to represent biomolecular information and also are not integrated with the existing bioinformatics tools. On the other hand, existing genomic data models do not represent clinical patient data. A framework was developed to support translational research by integrating biomolecular information coming from different “omics” technologies with patient’s clinical and socio-demographic data. This framework should present some features: flexibility, compression and robustness. The experiments accomplished from a use case demonstrated that the proposed system meets requirements of flexibility and robustness, leading to the desired integration. The Clinical Module can be accessed in http://dcm.ffclrp.usp.br/caib/pg=iptrans webcite.

Discretionary-based disclosure: evidence from the Brazilian market

The primary objective of this paper is to identify the factors that explain Brazilian companies level of voluntary disclosure. Underpinning this work is the Discretionary-based Disclosure theory. The sample is composed of the top 100 largest non-financial companies listed in the Bolsa de Valores de São Paulo (Brazilian Securities, Commodities, and Futures exchange - BOVESPA). Information was gathered from Financial Statements for the years ending in 2006, 2007, and 2008, with the use of content analysis. A disclosure framework based on 27 studies from these years was created, with a total of 92 voluntary items divided into two dimensions: economic (43) and socio-environmental (49). Based on the existing literature, a total of 12 hypotheses were elaborated and tested using a panel data approach. Results evidence that: (a) Sector and Origin of Control are statistically significant in all three models tested: economic, socio-environmental, and total; (b) Profitability is relevant in the economic model and in the total model; (c) Tobin s Q is relevant in the socio-environmental model and in the total disclosure model; (d) Leverage and Auditing Firm are only relevant in the economic disclosure model; (e) Size, Governance, Stock Issuing, Growth Opportunities and Concentration of Control are not statistically significant in any of the three models.

The Libor Market Model: from theory to calibration

This thesis is focused on the financial model for interest rates called the LIBOR Market Model. In the appendixes, we provide the necessary mathematical theory. In the inner chapters, firstly, we define the main interest rates and financial instruments concerning with the interest rate models, then, we set the LIBOR market model, demonstrate its existence, derive the dynamics of forward LIBOR rates and justify the pricing of caps according to the Black’s formula. Then, we also present the Swap Market Model, which models the forward swap rates instead of the LIBOR ones. Even this model is justified by a theoretical demonstration and the resulting formula to price the swaptions coincides with the Black’s one. However, the two models are not compatible from a theoretical point. Therefore, we derive various analytical approximating formulae to price the swaptions in the LIBOR market model and we explain how to perform a Monte Carlo simulation. Finally, we present the calibration of the LIBOR market model to the markets of both caps and swaptions, together with various examples of application to the historical correlation matrix and the cascade calibration of the forward volatilities to the matrix of implied swaption volatilities provided by the market.

Le strategie di internazionalizzazione delle imprese distrettuali: un'analisi comparata di tre diversi sistemi locali di produzione in Emilia Romagna

Since the Nineties, the process of globalization has caused a sharp increase in the real and financial integration of the worldwide economy, reducing the obstacles to international trade and minimizing the cost of transaction. The entrance of foreign firms in the domestic market has deeply modified the competitive situation of Italian enterprises, which have been forced to change their strategies in order to cope with those of the new competitors. In this scenario, internationalization is no longer one of the different strategic options available for the firm, but it becomes a forced choice to maintain or acquire a competitive advantage sustainable over time. Internationalization strategies of SMEs, however, are hindered by the shortage of financial resources and entrepreneurial skills, therefore this kind of firms tends toward light forms of foreign expansion, like export and subcontracting. Despite this, many studies have demonstrated that the district localisation increases the firms’ productivity and innovative capacity, so their competiveness both at a domestic and international level. The majority of these empirical contributions has focused mainly on the analysis of commercial flows, confirming that district enterprises reach a superior international performance compared to their external competitors. On the contrary, only few works have tried to evaluate the existence of a district effect on the firms’ ability to invest abroad, but the obtained results are not straightforward. One of the reason of these conclusions is that the phenomena has been analysed without taking into account the differences existing between districts in terms of enterprises’ dimension, diffusion of industrial groups and, above all, the sector of productive specialization, because the technological content of production could improve the innovativeness of district firms, allowing them to adopt advanced forms of internationalisation as foreign direct investments (FDI). The aim of the thesis is to further investigate the district effect on internationalisation, trough an econometric analysis of the international strategies carried out by firms localised in three different local system of production characterised by different technological specialization.

Econometric models of financial risks

The goal of this dissertation is to use statistical tools to analyze specific financial risks that have played dominant roles in the US financial crisis of 2008-2009. The first risk relates to the level of aggregate stress in the financial markets. I estimate the impact of financial stress on economic activity and monetary policy using structural VAR analysis. The second set of risks concerns the US housing market. There are in fact two prominent risks associated with a US mortgage, as borrowers can both prepay or default on a mortgage. I test the existence of unobservable heterogeneity in the borrower's decision to default or prepay on his mortgage by estimating a multinomial logit model with borrower-specific random coefficients.

The informal market of education in Egypt: Private tutoring and its implications /// Arbeitspapiere / Institut für Ethnologie und Afrikastudien ; 88

Education is generally perceived as a public good which should be provided by the state. In Egypt, free and equal access to education has been guaranteed to all citizens since President Nasser’s socialist reforms in the 1950s. However, due to high population growth rates and a lack of financial resources, the public education system has been struggling to accommodate rapidly increasing numbers of students. While enrolment rates have risen steadily, the quality of state-provided services has deteriorated. Teachers and students have to cope with high class densities, insufficient facilities, a rigid syllabus and a centralized examination system. Today, teaching is among the lowest-paying occupations in the public sector. One strategy to cope with this situation is the widespread practice of private tutoring, which usually takes place at students’ homes or in commercial tutoring centers. Based on research carried out in Cairo in 2004/05 and 2006, I use an actor-centered approach to analyze the motivations of Egyptian teachers and students for participating in private tutoring and the impact that this practice has on the relationship between teachers and students. Students of all socio-economic backgrounds resort to tutoring in order to succeed in a highly competitive and exam-oriented education system. However, the form and quality of tutoring that can be accessed depends on the financial means of the family. For teachers, tutoring provides a good opportunity not only to supplement their income, but also, in the case of renowned “star teachers”, to improve their professional status and autonomy. On the informal “market of education” that has developed in Egypt during the last decades, the educational responsibilities of the state are increasingly being taken over by private actors, i.e. the process of teaching and learning is dissociated from the direct control of the state and from school as an institution. At the same time, education is turned into a marketable commodity. Despite the government’s efforts to provide free education to all citizens, the quality of social services that can be accessed in Egypt, thus, depends mainly on the financial means of the individual or the family.

Topics in financial econometrics

In the first chapter, we consider the joint estimation of objective and risk-neutral parameters for SV option pricing models. We propose a strategy which exploits the information contained in large heterogeneous panels of options, and we apply it to S&P 500 index and index call options data. Our approach breaks the stochastic singularity between contemporaneous option prices by assuming that every observation is affected by measurement error. We evaluate the likelihood function by using a MC-IS strategy combined with a Particle Filter algorithm. The second chapter examines the impact of different categories of traders on market transactions. We estimate a model which takes into account traders’ identities at the transaction level, and we find that the stock prices follow the direction of institutional trading. These results are carried out with data from an anonymous market. To explain our estimates, we examine the informativeness of a wide set of market variables and we find that most of them are unambiguously significant to infer the identity of traders. The third chapter investigates the relationship between the categories of market traders and three definitions of financial durations. We consider trade, price and volume durations, and we adopt a Log-ACD model where we include information on traders at the transaction level. As to trade durations, we observe an increase of the trading frequency when informed traders and the liquidity provider intensify their presence in the market. For price and volume durations, we find the same effect to depend on the state of the market activity. The fourth chapter proposes a strategy to express order aggressiveness in quantitative terms. We consider a simultaneous equation model to examine price and volume aggressiveness at Euronext Paris, and we analyse the impact of a wide set of order book variables on the price-quantity decision.

Gold and the Stock Market: 3 Essays on Gold Investments

This thesis gives an overview of the history of gold per se, of gold as an investment good and offers some institutional details about gold and other precious metal markets. The goal of this study is to investigate the role of gold as a store of value and hedge against negative market movements in turbulent times. I investigate gold’s ability to act as a safe haven during periods of financial stress by employing instrumental variable techniques that allow for time varying conditional covariance. I find broad evidence supporting the view that gold acts as an anchor of stability during market downturns. During periods of high uncertainty and low stock market returns, gold tends to have higher than average excess returns. The effectiveness of gold as a safe haven is enhanced during periods of extreme crises: the largest peaks are observed during the global financial crises of 2007-2009 and, in particular, during the Lehman default (October 2008). A further goal of this thesis is to investigate whether gold provides protection from tail risk. I address the issue of asymmetric precious metal behavior conditioned to stock market performance and provide empirical evidence about the contribution of gold to a portfolio’s systematic skewness and kurtosis. I find that gold has positive coskewness with the market portfolio when the market is skewed to the left. Moreover, gold shows low cokurtosis with the market returns during volatile periods. I therefore show that gold is a desirable investment good to risk averse investors, since it tends to decrease the probability of experiencing extreme bad outcomes, and the magnitude of losses in case such events occur. Gold thus bears very important and under-researched characteristics as an asset class per se, which this thesis contributed to address and unveil.

Financial Development and Economic Growth: Time Series Evidence from Albania

The main objective of this thesis is to explore the short and long run causality patterns in the finance – growth nexus and finance-growth-trade nexus before and after the global financial crisis, in the case of Albania. To this end we use quarterly data on real GDP, 13 proxy measures for financial development and the trade openness indicator for the period 1998Q1 – 2013Q2 and 1998Q1-2008Q3. Causality patterns will be explored in a VAR-VECM framework. For this purpose we will proceed as follows: (i) testing for the integration order of the variables; (ii) cointegration analysis and (iii) performing Granger causality tests in a VAR-VECM framework. In the finance-growth nexus, empirical evidence suggests for a positive long run relationship between finance and economic growth, with causality running from financial development to economic growth. The global financial crisis seems to have not affected the causality direction in the finance and growth nexus, thus supporting the finance led growth hypothesis in the long run in the case of Albania. In the finance-growth-trade openness nexus, we found evidence for a positive long run relationship the variables, with causality direction depending on the proxy used for financial development. When the pre-crisis sample is considered, we find evidence for causality running from financial development and trade openness to economic growth. The global financial crisis seems to have affected somewhat the causality direction in the finance-growth-trade nexus, which has become sensible to the proxy used for financial development. On the short run, empirical evidence suggests for a clear unidirectional relationship between finance and growth, with causality mostly running from economic growth to financial development. When we consider the per-crisis sub sample results are mixed, depending on the proxy used for financial development. The same results are confirmed when trade openness is taken into account.

Shareholder protection and stock market development

The dissertation contains five parts: An introduction, three major chapters, and a short conclusion. The First Chapter starts from a survey and discussion of the studies on corporate law and financial development literature. The commonly used methods in these cross-sectional analyses are biased as legal origins are no longer valid instruments. Hence, the model uncertainty becomes a salient problem. The Bayesian Model Averaging algorithm is applied to test the robustness of empirical results in Djankov et al. (2008). The analysis finds that their constructed legal index is not robustly correlated with most of the various stock market outcome variables. The second Chapter looks into the effects of minority shareholders protection in corporate governance regime on entrepreneurs' ex ante incentives to undertake IPO. Most of the current literature focuses on the beneficial part of minority shareholder protection on valuation, while overlooks its private costs on entrepreneur's control. As a result, the entrepreneur trade-offs the costs of monitoring with the benefits of cheap sources of finance when minority shareholder protection improves. The theoretical predictions are empirically tested using panel data and GMM-sys estimator. The third Chapter investigates the corporate law and corporate governance reform in China. The corporate law in China regards shareholder control as the means to the ends of pursuing the interests of stakeholders, which is inefficient. The Chapter combines the recent development of theories of the firm, i.e., the team production theory and the property rights theory, to solve such problem. The enlightened shareholder value, which emphasizes on the long term valuation of the firm, should be adopted as objectives of listed firms. In addition, a move from the mandatory division of power between shareholder meeting and board meeting to the default regime, is proposed.

The market manipulation regime in the European Union

Market manipulation is an illegal practice that enables a person can profit from practices that artificially raise or lower the prices of an instrument in the financial markets. Its prohibition is based on the 2003 Market Abuse Directive in the EU. The current market manipulation regime was broadly considered as a big success except for enforcement and supervisory inconsistencies in the Member States at the initial. A review of the market manipulation regime began at the end of 2007, which became quickly incorporated into the wider EU crisis-era reform program. A number of weaknesses of current regime have been identified, which include regulatory gaps caused by the development of trading venues and financial products, regulatory gaps concerning cross-border and cross-markets manipulation (particular commodity markets), legal uncertainty as a result of various implementation, and inefficient supervision and enforcement. On 12 June 2014, a new regulatory package of market abuse, Market Abuse Regulation and Directive on criminal sanctions for market abuse, has been adopted. And several changes will be made concerning the EU market manipulation regime. A wider scope of the regime and a new prohibition of attempted market manipulation will ensure the prevention of market manipulation at large. The AMPs will be subject to strict scrutiny of ESMA to reduce divergences in implementation. In order to enhance efficiency of supervision and enforcement, powers of national competent authorities will be strengthened, ESMA is imposed more power to settle disagreement between national regulators, and the administrative and criminal sanctioning regimes are both further harmonized. In addition, the protection of fundamental rights is stressed by the new market manipulation regime, and some measures are provided to guarantee its realization. Further, the success EU market manipulation regime could be of significant reference to China, helping China to refine its immature regime.

Credit-Default-Swaps and the 2008 Financial Crisis: An Inquiry into the Underlying Legal Origins and the European Union’s Regulatory Reforms

After the 2008 financial crisis, the financial innovation product Credit-Default-Swap (CDS) was widely blamed as the main cause of this crisis. CDS is one type of over-the-counter (OTC) traded derivatives. Before the crisis, the trading of CDS was very popular among the financial institutions. But meanwhile, excessive speculative CDSs transactions in a legal environment of scant regulation accumulated huge risks in the financial system. This dissertation is divided into three parts. In Part I, we discussed the primers of the CDSs and its market development, then we analyzed in detail the roles CDSs had played in this crisis based on economic studies. It is advanced that CDSs not just promoted the eruption of the crisis in 2007 but also exacerbated it in 2008. In part II, we asked ourselves what are the legal origins of this crisis in relation with CDSs, as we believe that financial instruments could only function, positive or negative, under certain legal institutional environment. After an in-depth inquiry, we observed that at least three traditional legal doctrines were eroded or circumvented by OTC derivatives. It is argued that the malfunction of these doctrines, on the one hand, facilitated the proliferation of speculative CDSs transactions; on the other hand, eroded the original risk-control legal mechanism. Therefore, the 2008 crisis could escalate rapidly into a global financial tsunami, which was out of control of the regulators. In Part III, we focused on the European Union’s regulatory reform towards the OTC derivatives market. In specific, EU introduced mandatory central counterparty clearing obligation for qualified OTC derivatives, and requires that all OTC derivatives shall be reported to a trade repository. It is observable that EU’s approach in re-regulating the derivatives market is different with the traditional administrative regulation, but aiming at constructing a new market infrastructure for OTC derivatives.

The Pre-1980 Roots of Neoliberal Financial Deregulation

U.S. financial deregulation is often popularly presented as a fundamental attack on financial regulation that began with neoliberalism's Big Bang in 1980. This paper argues this position is wrong in two ways. First, it is a process that stretches back decades before 1980. Textbook mentions of 1970s precursor "financial innovations" fall far short of presenting the breadth and duration of the pre-1980 attack on the system of regulation. Second, it has not been an across-the-board attack on financial regulation in the name of market efficiency as required by its ideology and claimed by its advocates, but rather a focused attack on only one of the five pillars of the system of regulation. This paper develops both of these assertions through a presentation of the five central pillars of the pre-1980 system of financial regulation, and the four major attacks on the three different aspects of the restrictions on financial competition.

The Dual Ownership Structure: a Model to Connect the Cooperative Model With Financial Markets

In business literature, the conflicts among workers, shareholders and the management have been studied mostly in the frame of stakeholder theory. The stakeholder theory recognizes this issue as an agency problem, and tries to solve the problem by establishing a contractual relationship between the agent and principals. However, as Marcoux pointed out, the appropriateness of the contract as a medium to reduce the agency problem should be questioned. As an alternative, the cooperative model minimizes the agency costs by integrating the concept of workers, owners and management. Mondragon Corporation is a successful example of the cooperative model which grew into the sixth largest corporation in Spain. However, the cooperative model has long been ignored in discussions of corporate governance, mainly because the success of the cooperative model is extremely difficult to duplicate in reality. This thesis hopes to revitalize the scholarly examination of cooperatives by developing a new model that overcomes the fundamental problem in the cooperative model: the limited access to capital markets. By dividing the ownership interest into financial and control interest, the dual ownership structure allows cooperatives to issue stock in the capital market by making a financial product out of financial interest.

Talents in Migration Processes in the Conditions of the Czech Republic of the Nineties

The transformation of the 1990s has had a bearing on the academic and scientific world, as is becoming increasingly obvious with the changing numbers of foreign students wishing to study in the Czech Republic and of Czech students wishing to study abroad, the virtual collapse of doctoral studies, and the rapidly increasing age of Czech academics (placed at 48 by official sources and at rather more by this research). At the same time there is an apparent lack of interest in analysing and understanding these trends, which Mr. Cermak terms an ostrich policy, although his research showed that academics are in fact both aware and concerned about them. The mid-1990s migration of talent to and from R+D in the Czech Republic is also reflected in the number of talented Czech students studying abroad, who represent the largest and most interesting group of actual and potential migrants. Mr. Cermak's study took the form of a Delphi enquiry participated in by 44 specialists, including experts in the problems of higher education and science policy from the Presidium of the Higher Education Council (n = 23), members of the Council's Science and Research Commission (n = 14), former and current managers of higher education authorities (n = 4) and selected participants of the longitudinal talent research (n = 3). Questions considered included the influence of continuing talent migration from domestic R+D on the efficiency of domestic higher education, the diversification of forms of the brain drain and their impact on other processes in society, the possibility of positive influence on the brain drain processes to minimise the risks it presents, and the use of the knowledge obtained about the brain drain. The study revealed a clear drop of interest in brain drain problems in higher education in the mid-1990s, which is probably related to the collapsed of Czech R+D in the field of talent education. The effects on this segment of the labour market appeared earlier, with a major migration wave in 1991-1993 which significantly "cleared" the area of scientific talent. In addition, prospective talents from the ranks of younger students have not been integrated into domestic R+D, leading to the increasing average age of those working in this field. "Talent scouting" tended to be oriented towards much younger individuals, even in some cases towards undergraduate students. The R+D institutions deprived of human resources considered as basic in a functional R+D system have lost much of their dynamism and so no longer attract not only domestic talent but also talent from other regions. As a result the public, including the mass media and political structures, have stopped regarding the support of domestic science as a priority. This is clear both among the young people who are important for the future development of R+D (support for the education of talented children has dropped), from the drop in the prestige of this area as a profession among university students, and from the lack of explicit support for R+D by any of the political parties. On the basis of his findings Mr. Cermak concludes that there is no basis for the belief that the brain drain will represent a positive force in stimulating the development of the open society. Migration data shows that the outflow of talent from the Czech Republic far exceeds the inflow, and that the latter is largely short-term. Not only has the number of returning Czech professors dropped to half of its level at the beginning of the 1990s, but they also tend to take up only short-term contracts and retain their foreign positions. Recruitment of scientific talent from other countries, including the Slovak Republic, is limited. Furthermore internal contacts between those already involved in R+D have been badly hit by economic pressures and institutional co-operation has dropped to a minimum. There have been few moves to counteract this situation, the only notable one being the Program 250, launched in 1996 with government support to try and attract younger (i.e. under 40) talent into R+D. Its resources are however limited and its effects have not so far been evaluated. The deficit of academic and scientific talent in the Czech Republic is increasing and two major directions of academic work are emerging. Classic higher education science based on the teaching process is declining, largely due to economic factors, while there is an increasing emphasis on special; ad hoc projects which cannot be related directly to teaching but are often interesting to specialists outside the Czech Republic. This is shown clearly by the increase in publishing and in participation in domestic and foreign grant projects, which often serve to supplement the otherwise low salaries in the higher education sector. This tend was also accelerated by the collapse of applied R+D in individual sectors of the national economy and by substantial cutbacks in the Czech Academy of Sciences, which formerly fostered such research. Some part of the output of this research can be used in the education system and its financial contribution does significantly affect the stability of the present staff, but Mr. Cermak sees it as generally unfavourable for the development of talent education. In addition, it has led to a certain resignation on the question of integration into international structures, due to the emphasis on short-term targets, commercial advantages and individualism rather than team work. At the same time, he admits that these developments reflect those in other areas of the transformation in the Czech Republic.