Complexity of N-Myc transcriptional function in childhood neuroblastoma

Myc is a transcription factor that can activate transcription of several hundreds genes by direct binding to their promoters at specific DNA sequences (E-box). However, recent studies have also shown that it can exert its biological role by repressing transcription. Such studies collectively support a model in which c-Myc-mediated repression occurs through interactions with transcription factors bound to promoter DNA regions but not through direct recognition of typical E-box sequences. Here, we investigated whether N-Myc can also repress gene transcription, and how this is mechanistically achieved. We used human neuroblastoma cells as a model system in that N-MYC amplification/over-expression represents a key prognostic marker of this tumour. By means of transcription profile analyses we could identify at least 5 genes (TRKA, p75NTR, ABCC3, TG2, p21) that are specifically repressed by N-Myc. Through a dual-step-ChIP assay and genetic dissection of gene promoters, we found that N-Myc is physically associated with gene promoters in vivo, in proximity of the transcription start site. N-Myc association with promoters requires interaction with other proteins, such as Sp1 and Miz1 transcription factors. Furthermore, we found that N-Myc may repress gene expression by interfering directly with Sp1 and/or with Miz1 activity (i.e. TRKA, p75NTR, ABCC3, p21) or by recruiting Histone Deacetylase 1 (Hdac1) (i.e. TG2). In vitro analyses show that distinct N-Myc domains can interact with Sp1, Miz1 and Hdac1, supporting the idea that Myc may participate in distinct repression complexes by interacting specifically with diverse proteins. Finally, results show that N-Myc, through repressed genes, affects important cellular functions, such as apoptosis, growth, differentiation and motility. Overall, our results support a model in which N-Myc, like c-Myc, can repress gene transcription by direct interaction with Sp1 and/or Miz1, and provide further lines of evidence on the importance of transcriptional repression by Myc factors in tumour biology.

Essays in behavioral economics

In this work we conduct an experimental analysis on different behavioral models of economic choice. In particular, we analyze the role of overconfidence in shaping the beliefs of economics agents about the future path of their consumption or investment. We discuss the relevance of this bias in expectation formation both from a static and from a dynamic point of view and we analyze the effect of possible interventions aimed to achieve some policy goals. The methodology we follow is both theoretical and empirical. In particular, we make large use of controlled economic field experiments in order to test the predictions of the theoretical models we propose. In the second part of the thesis we discuss the role of cognition and personality in affecting economic preferences and choices. In this way we make a bridge between established psychological research and novel findings in economics. Finally, we conduct a field study on the role of incentives on education. We design different incentive schemes and we test, on randomized groups of students, their effectiveness in improving academic performance.

Quantifying the Economics of Medical Malpractice - A View from a Civil Law Perspective

Life is full of uncertainties. Legal rules should have a clear intention, motivation and purpose in order to diminish daily uncertainties. However, practice shows that their consequences are complex and hard to predict. For instance, tort law has the general objectives of deterring future negligent behavior and compensating the victims of someone else's negligence. Achieving these goals are particularly difficult in medical malpractice cases. To start with, when patients search for medical care they are typically sick in the first place. In case harm materializes during the treatment, it might be very hard to assess if it was due to substandard medical care or to the patient's poor health conditions. Moreover, the practice of medicine has a positive externality on the society, meaning that the design of legal rules is crucial: for instance, it should not result in physicians avoiding practicing their activity just because they are afraid of being sued even when they acted according to the standard level of care. The empirical literature on medical malpractice has been developing substantially in the past two decades, with the American case being the most studied one. Evidence from civil law tradition countries is more difficult to find. The aim of this thesis is to contribute to the empirical literature on medical malpractice, using two civil law countries as a case-study: Spain and Italy. The goal of this thesis is to investigate, in the first place, some of the consequences of having two separate sub-systems (administrative and civil) coexisting within the same legal system, which is common in civil law tradition countries with a public national health system (such as Spain, France and Portugal). When this holds, different procedures might apply depending on the type of hospital where the injury took place (essentially whether it is a public hospital or a private hospital). Therefore, a patient injured in a public hospital should file a claim in administrative courts while a patient suffering an identical medical accident should file a claim in civil courts. A natural question that the reader might pose is why should both administrative and civil courts decide medical malpractice cases? Moreover, can this specialization of courts influence how judges decide medical malpractice cases? In the past few years, there was a general concern with patient safety, which is currently on the agenda of several national governments. Some initiatives have been taken at the international level, with the aim of preventing harm to patients during treatment and care. A negligently injured patient might present a claim against the health care provider with the aim of being compensated for the economic loss and for pain and suffering. In several European countries, health care is mainly provided by a public national health system, which means that if a patient harmed in a public hospital succeeds in a claim against the hospital, public expenditures increase because the State takes part in the litigation process. This poses a problem in a context of increasing national health expenditures and public debt. In Italy, with the aim of increasing patient safety, some regions implemented a monitoring system on medical malpractice claims. However, if properly implemented, this reform shall also allow for a reduction in medical malpractice insurance costs. This thesis is organized as follows. Chapter 1 provides a review of the empirical literature on medical malpractice, where studies on outcomes and merit of claims, costs and defensive medicine are presented. Chapter 2 presents an empirical analysis of medical malpractice claims arriving to the Spanish Supreme Court. The focus is on reversal rates for civil and administrative decisions. Administrative decisions appealed by the plaintiff have the highest reversal rates. The results show a bias in lower administrative courts, which tend to focus on the State side. We provide a detailed explanation for these results, which can rely on the organization of administrative judges career. Chapter 3 assesses predictors of compensation in medical malpractice cases appealed to the Spanish Supreme Court and investigates the amount of damages attributed to patients. The results show horizontal equity between administrative and civil decisions (controlling for observable case characteristics) and vertical inequity (patients suffering more severe injuries tend to receive higher payouts). In order to execute these analyses, a database of medical malpractice decisions appealed to the Administrative and Civil Chambers of the Spanish Supreme Court from 2006 until 2009 (designated by the Spanish Supreme Court Medical Malpractice Dataset (SSCMMD)) has been created. A description of how the SSCMMD was built and of the Spanish legal system is presented as well. Chapter 4 includes an empirical investigation of the effect of a monitoring system for medical malpractice claims on insurance premiums. In Italy, some regions adopted this policy in different years, while others did not. The study uses data on insurance premiums from Italian public hospitals for the years 2001-2008. This is a significant difference as most of the studies use the insurance company as unit of analysis. Although insurance premiums have risen from 2001 to 2008, the increase was lower for regions adopting a monitoring system for medical claims. Possible implications of this system are also provided. Finally, Chapter 5 discusses the main findings, describes possible future research and concludes.

The Effectiveness of the Clean Development Mechanism – A law and economics analysis

Climate change has been acknowledged as a threat to humanity. Most scholars agree that to avert dangerous climate change and to transform economies into low-carbon societies, deep global emission reductions are required by the year 2050. Under the framework of the Kyoto Protocol, the Clean Development Mechanism (CDM) is the only market-based instrument that encourages industrialised countries to pursue emission reductions in developing countries. The CDM aims to pay the incremental finance necessary to operationalize emission reduction projects which are otherwise not financially viable. According to the objectives of the Kyoto Protocol, the CDM should finance projects that are additional to those which would have happened anyway, contribute to sustainable development in the countries hosting the projects, and be cost-effective. To enable the identification of such projects, an institutional framework has been established by the Kyoto Protocol which lays out responsibilities for public and private actors. This thesis examines whether the CDM has achieved these objectives in practice and can thus be considered an effective tool to reduce emissions. To complete this investigation, the book applies economic theory and analyses the CDM from two perspectives. The first perspective is the supply-dimension which answers the question of how, in practice, the CDM system identified additional, cost-effective, sustainable projects and, generated emission reductions. The main contribution of this book is the second perspective, the compliance-dimension, which answers the question of whether industrialised countries effectively used the CDM for compliance with their Kyoto targets. The application of the CDM in the European Union Emissions Trading Scheme (EU ETS) is used as a case-study. Where the analysis identifies inefficiencies within the supply or the compliance dimension, potential improvements of the legal framework are proposed and discussed.

Three Essays in Spatial Economics

This work contributes to the field of spatial economics by embracing three distinct modelling approaches, belonging to different strands of the theoretical literature. In the first chapter I present a theoretical model in which the changes in urban system’s degree of functional specialisation are linked to (i) firms’ organisational choices and firms’ location decisions. The interplay between firms’ internal communication/managing costs (between headquarters and production plants) and the cost of communicating with distant business services providers leads the transition process from an “integrated” urban system where each city hosts every different functions to a “functionally specialised” urban system where each city is either a primary business center (hosting advanced business services providers, a secondary business center or a pure manufacturing city and all this city-types coexist in equilibrium.The second chapter investigates the impact of free trade on welfare in a two-country world modelled as an international Hotelling duopoly with quadratic transport costs and asymmetric countries, where a negative environmental externality is associated with the consumption of the good produced in the smaller country. Countries’ relative sizes as well as the intensity of negative environmental externality affect potential welfare gains of trade liberalisation. The third chapter focuses on the paradox, by which, contrary to theoretical predictions, empirical evidence shows that a decrease in international transport costs causes an increase in foreign direct investments (FDIs). Here we propose an explanation to this apparent puzzle by exploiting an approach which delivers a continuum of Bertrand- Nash equilibria ranging above marginal cost pricing. In our setting, two Bertrand firms, supplying a homogeneous good with a convex cost function, enter the market of a foreign country. We show that allowing for a softer price competition may indeed more than offset the standard effect generated by a decrease in trade costs, thereby restoring FDI incentives.

Essays in Household and Demographic Economics

This dissertation consists of three empirical studies that are believed to provide new contributions to the literature exploring the determinants of children/adolescents achievement test scores (Chapter 2), adolescent health risk behaviors (Chapter 3), and children time use patterns (Chapter 4). The second and third studies look at the separate roles of fathers and of mothers in influencing outcomes, wherein parental time is the resource input of interest quantitatively measured and directly derived from time diaries. The last chapter looks at the time allocation of children and how it varies according to child and household characteristics.

Essays in Behavioral Personnel Economics

The thesis contemplates 4 papers and its main goal is to provide evidence on the prominent impact that behavioral analysis can play into the personnel economics domain.The research tool prevalently used in the thesis is the experimental analysis.The first paper provide laboratory evidence on how the standard screening model–based on the assumption that the pecuniary dimension represents the main workers’choice variable–fails when intrinsic motivation is introduced into the analysis.The second paper explores workers’ behavioral reactions when dealing with supervisors that may incur in errors in the assessment of their job performance.In particular,deserving agents that have exerted high effort may not be rewarded(Type-I errors)and undeserving agents that have exerted low effort may be rewarded(Type-II errors).Although a standard neoclassical model predicts both errors to be equally detrimental for effort provision,this prediction fails when tested through a laboratory experiment.Findings from this study suggest how failing to reward deserving agents is significantly more detrimental than rewarding undeserving agents.The third paper investigates the performance of two antithetic non-monetary incentive schemes on schooling achievement.The study is conducted through a field experiment.Students randomized to the main treatments have been incentivized to cooperate or to compete in order to earn additional exam points.Consistently with the theoretical model proposed in the paper,the level of effort in the competitive scheme proved to be higher than in the cooperative setting.Interestingly however,this result is characterized by a strong gender effect.The fourth paper exploits a natural experiment setting generated by the credit crunch occurred in the UK in the2007.The economic turmoil has negatively influenced the private sector,while public sector employees have not been directly hit by the crisis.This shock–through the rise of the unemployment rate and the increasing labor market uncertainty–has generated an exogenous variation in the opportunity cost of maternity leave in private sector labor force.This paper identifies the different responses.

Essays in Environmental Economics

This dissertation comprises four essays on the topic of environmental economics and industrial organization. In the first essay, we develop a two-country world differential game model with a polluting firm in each country to investigate the equilibrium of the game between firms when they decide to trade or not and to see under which conditions social welfare coincides with the market equilibrium. In the second essay, we built a model where firms strategically choose whether to participate in an auction/lottery to attain pollution permits, or instead invest in green R&D, to show that, somewhat counterintuitively, a desirable side effect of the auction is in fact that of fostering environmental R&D in an admissible range of the model parameters. The third essay investigates a second-best trade agreement between two countries when pollution spillovers are asymmetric to examine the strategic behavior of governments in using pollution taxes and tariffs under trade liberalization. The fouth essay studies the profitability of exogenous output constraint in a differential game model with price dynamics under the feedback strategies.

Patent Strategies and R&D in Complex Product Industries

The study aims at providing a framework conceptualizing patenting activities under the condition of intellectual property rights fragmentation. Such a framework has to deal with the interrelated problems of technological complexity in the modern patent landscape. In that respect, ex-post licensing agreements have been incorporated into the analysis. More precisely, by consolidating the right to use patents required for commercialization of a product, private market solutions, such as cross-licensing agreements and patent pools help firms to overcome problems triggered by the intellectual property rights fragmentation. Thereby, private bargaining between parties as such cannot be isolated from the legal framework. A result of this analysis is that policies ignoring market solutions and only focusing on static gains can mitigate the dynamic efficiency gains as induced by the patent system. The evidence found in this thesis supports the opinion that legal reforms that aim to decrease the degree of patent protection or to lift it all together can hamper the functioning of the current system.

Crisi economiche, sostenibilità ambientale e politiche pubbliche: il ruolo del legislatore e della pubblica amministrazione

Il presente lavoro analizza il ruolo ricoperto dal legislatore e dalla pubblica amministrazione rispettivamente nel delineare e attuare politiche pubbliche volte alla promozione di modelli di sviluppo economico caratterizzati da un elevato tasso di sostenibilità ambientale. A tal fine, il lavoro è suddiviso in quattro capitoli. Nel primo capitolo vengono presi in considerazione i principali elementi della teoria generale che costituiscono i piani di lettura del tema trattato. Questa prima fase della ricerca è incentrata, da un lato, sull’analisi (storico-evolutiva) del concetto di ambiente alla luce della prevalente elaborazione giuridica e, dall’altro, sulla formazione del concetto di sviluppo sostenibile, con particolare riguardo alla sua declinazione in chiave ambientale. Nella parte centrale del lavoro, costituita dal secondo e dal terzo capitolo, l’analisi è rivolta a tre settori d’indagine determinanti per l’inquadramento sistematico delle politiche pubbliche del settore: il sistema di rapporti che esiste tra i molteplici soggetti (internazionali, nazionali e locali) coinvolti nella ricerca di soluzioni alla crisi sistemica ambientale; l’individuazione e la definizione dell’insieme dei principi sostanziali che governano il sistema di tutela ambientale e che indirizzano le scelte di policy nel settore; i principali strumenti (giuridici ed economici) di protezione attualmente in vigore. Il quarto ed ultimo capitolo prende in considerazione le politiche relative alle procedure di autorizzazione alla costruzione e all’esercizio degli impianti per la produzione di energia alimentati da fonti energetiche rinnovabili, analizzate quale caso specifico che può essere assunto a paradigma del ruolo ricoperto dal legislatore e dalla pubblica amministrazione nel settore delle politiche di sviluppo sostenibile. L’analisi condotta mostra un elevato tasso di complessità del sistema istituzionale e organizzativo, a cui si aggiungono evidenti limiti di efficienza per quanto riguarda il regime amministrativo delle autorizzazioni introdotto dal legislatore nazionale.

Implicit computational complexity and probabilistic classes

The thesis applies the ICC tecniques to the probabilistic polinomial complexity classes in order to get an implicit characterization of them. The main contribution lays on the implicit characterization of PP (which stands for Probabilistic Polynomial Time) class, showing a syntactical characterisation of PP and a static complexity analyser able to recognise if an imperative program computes in Probabilistic Polynomial Time. The thesis is divided in two parts. The first part focuses on solving the problem by creating a prototype of functional language (a probabilistic variation of lambda calculus with bounded recursion) that is sound and complete respect to Probabilistic Prolynomial Time. The second part, instead, reverses the problem and develops a feasible way to verify if a program, written with a prototype of imperative programming language, is running in Probabilistic polynomial time or not. This thesis would characterise itself as one of the first step for Implicit Computational Complexity over probabilistic classes. There are still open hard problem to investigate and try to solve. There are a lot of theoretical aspects strongly connected with these topics and I expect that in the future there will be wide attention to ICC and probabilistic classes.

The Law and Economics of Eco-labels

Eco-labels and certification are one of the many environmental policy tools that have been under scrutiny in recent years. This is because the damages of environmental degradation are becoming more apparent over time. Hence there is a pressure to come up with tools that help solve even small parts of the problem. Eco-labels have been around for over 30 years. However the market, the environment and eco-labels have changed drastically during this period. Moreover, in the last 5 years there has been a sudden increase in eco-labels making them more visible in the market and to the average consumer. All this has made evident that little is known about the effectiveness of eco-labels as environmental policy tools. Hence, there is a call to find answers regarding the actual effects of eco-labels on the market and on the environment. While this work cannot address whether eco-labels have an environmental impact it addresses the effects of eco-labels on the markets. Moreover, this work aimed to find the role of law in eco-labelling. In addition, it aims to find a legal solution that would improve the performance of eco-labelling and certification.