Role of gender in transthyretin-related amyloidosis: an international perspective based on the Transthyretin Amyloid Outcomes Survey (THAOS)

Background. Transthyretin amyloidosis (ATTR) is an underdiagnosed disease caused by destabilization of transthyretin (TTR) due to pathogenic mutations (ATTRm) or aging (ATTRwt). We explored the role of gender in determining clinical picture using the largest available database on ATTR, the ongoing Transthyretin Amyloid Outcomes Survey (THAOS) international registry. Methods. Data through 1st April 2019 were explored. Symptomatic ATTRm (n=3737), asymptomatic ATTRm (n=644) and ATTRwt (n=874) patients were studied. Results. Male prevalence was 61% in the entire registry, 53% in ATTRm and 95% in ATTRwt. In the overall cohort, cardiac phenotype was more frequent in males (30.7% vs 10.5%, p<0.001). Among ATTRm, 72.3% of patients with amyloidotic cardiomyopathy (ATTR-CM) were males (p<0.001) but echocardiographic features showed no substantial gender differences. Sensory abnormalities (70.1% vs 64.1%, p<0.001), autonomic abnormalities (60% vs 48.5%, p<0.001) and walking disabilities were more frequent among ATTRm males. Carpal tunnel syndrome was more frequent in ATTRm males (18.6% vs 15.5%, p=0.014). In ATTRwt cohort, females had a more pronounced (but anyhow mild) walking disability. Male-to-female ratio varied within genotype, from 0.61 in Val30Met to 11.11 in ATTRwt; furthermore, males’ imbalance was more evident among symptomatic patients rather than in asymptomatic ones. Male gender, age at presentation and specific genotype were independently associated with the presence of ATTR-CM. Conclusions. In ATTR, cardiac involvement is more frequent in men, supporting the hypothesis that some biologic characteristics may “protect” from myocardial amyloid infiltration in women. Further investigations are needed to identify possible underlying protective mechanism and orient the research for innovative, gender-tailored therapeutic approaches.

La riforma dell'ordinamento portuale

Il presente elaborato si prefigge l’obiettivo di verificare la reale e concreta applicazione delle disposizioni derivanti dall’ordinamento comunitario, all’interno della realtà portuale italiana, che, consapevole del fatto che i porti costituiscono forti infrastrutture nonché fonte di ricchezza per il paese, avverte l’esigenza di modificare fermamente il regime amministrativo dei propri porti. Le profonde innovazioni introdotte nel sistema portuale italiano a seguito della riforma del 1994, attraverso l’introduzione di assetti istituzionali ed organizzativi, hanno favorito la crescita dei traffici marittimi del paese. In ragione dei significativi mutamenti che hanno segnato la realtà economica mondiale negli ultimi anni, in cui si è assistito, al fenomeno della c.d. globalizzazione economica, che spinge verso la delocalizzazione produttiva e verso l’apertura di nuovi mercati di consumo, particolare attenzione è stata posta alle esigenze nascenti all’interno del sistema portuale, di apportare delle significative modifiche alla Legge 84/1994, per affrontare le nuove sfide poste dalla competizione comunitaria ed internazionale, e migliorare l’efficienza delle attività produttive ed uniformare l’impianto normativo. Nello specifico è stato esaminato il testo unificato della recente proposta di legge di riforma del settore portuale, le cui novità maggiormente rilevanti si sviluppano essenzialmente su tre livelli: la governance dei porti, la programmazione e la pianificazione delle aree, le attività economiche ed i servizi portuali. In maniera precisa e dettagliata, si è proceduto all’analisi dei servizi portuali tecnico-nautici, prestando attenzione alle prospettive di liberalizzazione del settore ed al principio di uniformità in materia tariffaria, al fine di rendere detti servizi funzionali e trasparenti. Infine, l’attenzione è stata posta alla realtà portuale a livello comunitario, esaminando le recenti disposizioni emanate dalle istituzioni comunitarie, al fine di verificare il miglior funzionamento dei porti marittimi e lo sviluppo della rete transeuropea di trasporto.

Patrimoni storici e fondi speciali nelle biblioteche d'ateneo. Valutazione e impatto dell'Università

Quali benefici possono apportare alla società le biblioteche degli atenei che conservano patrimoni storici e fondi speciali? Per rispondere a questa domanda occorre indagare l’impatto delle loro attività, cioè il cambiamento che il contatto coi servizi della biblioteca determina in un individuo o in un gruppo, secondo la definizione della ISO 16439:2014. Scopo della ricerca è proporre una metodologia per valutare l’impatto delle iniziative di valorizzazione di tali patrimoni attuate dalle biblioteche degli atenei. Il campo d’indagine coincide con il contesto universitario pubblico italiano, osservato criticamente in una prospettiva internazionale grazie all’analisi di esperienze non italiane. Dopo un inquadramento storico della biblioteca di università e della sua apertura alla società, il lavoro si sofferma sull’interpretazione del concetto angloamericano di «special collections» ed esamina le più diffuse modalità di valorizzazione adottate dalle biblioteche di ateneo. Per disporre di un quadro sulla gestione dei patrimoni storici e dei fondi speciali nelle biblioteche degli atenei italiani, il lavoro ha previsto una ricerca sui sistemi bibliotecari degli atenei pubblici del nostro Paese. Le attività di valorizzazione svolte dalle biblioteche di ateneo possono contribuire allo sviluppo culturale del contesto in cui sono radicate, nell’ottica della Terza Missione dell’Università. Alle sollecitazioni della Terza Missione si aggiunge che i benefici della valorizzazione possono legarsi al concetto di «cultural welfare» e promuovere altresì il valore della biodiversità culturale, fattore concorrente alla realizzazione della società auspicata dall’Agenda 2030 delle Nazioni Unite. La tesi propone una metodologia per valutare la risposta delle biblioteche di ateneo che svolgono attività di valorizzazione dei patrimoni storici e dei fondi speciali rispetto alle cornici strategiche di Terza Missione e di Agenda 2030. A completamento della parte teorica, si presentano due casi studio posti a confronto, l’uno riferito alla Biblioteca Històrica della Universitat de València (Spagna) e l’altro alla Biblioteca Universitaria di Bologna.

Reconciling the Irreconcilable? Sovereign Debt Restructuring and the Principles of International Law. A Law and Economics Perspective

This Thesis focuses on the principles of international law relevant to the resolution of legal disputes arising from sovereign insolvency conflicts. It attempts to contribute to the “incremental” approach literature by identifying principles, justifying their application in litigation and assessing whether they may help to reconcile the trade-offs prevalent in that context. For that purpose, this Thesis distinguishes between two different types of principles. First, it investigates the “Principles of Public International Law” (henceforth, “PIL principles”). Said category refers to norms of the law of nations which can be considered functionally and structurally similar to domestic constitutional principles (i.e., that can be regarded as “optimization” or “prima facie” requirements). This Thesis underscores the PIL principles protecting the interests of the creditors and citizens as well as the “public interest”, arguing that decision makers face a trade-off between these principles in the context of restructurings. Secondly, this Thesis inquires into the “general principles of domestic law” (henceforth, “GPDs”) which can be applied in sovereign debt restructuring. Two GPDs are identified: a “stay” on litigation and a “cram down” on dissenting creditors’ claims. Although both principles have been identified by the prior literature, this work advances a small but significant “twist” in the methodology used for that purpose: it relies exclusively on functional and comparative analysis. Moreover, this work justifies the application of said GPDs for two jurisdictions: New York and Germany. Finally, it posits that those GPDs can help to mitigate the trade-offs between PIL principles, thus reconciling the interests at stake.

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 United Nations 'quasi-prosecutorial' investigative mechanisms: assessing a new institutional model in the international criminal justice landscape

This work aims to provide a theoretical examination of three recently created bodies of the United Nations mandated to investigate the alleged international crimes committed in Syria (IIIM), Iraq (UNITAD) and Myanmar (IIMM). Established as a compromise solution in the paralysis of international criminal jurisdictions, these essentially overlapping entities have been depicted as a ‘new generation’ of UN investigative mechanisms. While non-judicial in nature, they depart indeed from traditional commissions of inquiry in several respects due to their increased criminal or ‘quasi-prosecutorial’ character. After clarifying their legal basis and different mandating authorities, a comparative institutional analysis is thus carried out in order to ascertain whether these ‘mechanisms’ can be said to effectively represent a new institutional model. Through an in-depth assessment of their mandates, the thesis is also intended to outline both the strengths and the criticalities of these organs. Given their aim to facilitate criminal proceedings by sharing information and case files, it is suggested that more attention shall be paid to the position of the person under investigation. To this end, some proposals are made in order to enhance the mechanisms’ frameworks, especially from the angle of procedural safeguards. As a third aspect, the cooperation with judicial authorities is explored, in order to shed light on the actors involved, the relevant legal instruments and the possible obstacles, in particular from a human rights perspective. Ultimately, drawing from the detected issues, the thesis seeks to identify some lessons learned which could be taken into account in case of creation of new ad hoc investigative mechanisms or of a permanent institution of this kind.

The Financial Services Regime in International Economic Law: on the Difficult Relationship between Trade Liberalization and Prudential Measures

The PhD thesis analyses the financial services regime in international economic law from the perspective of the difficult relationship between trade liberalisation and prudential measures. Financial stability plays a fundamental role for the well-being and well-functioning of the global economy, but, it is at the same time a complex sector to regulate and supervise and, especially after the 2007-08 economic crisis, States have tightened up their regulation of financial services, introducing more severe and protectionist prudential measures. However, in an increasingly interconnected global economy, the harmonization of prudential regulation at the international level is an essential step to guarantee integrity, fairness and stability of financial markets and trade. The research analyses the tools at disposition to achieve this aim, the related problematic issues and the perspectives and possible solutions for the future, starting from the World Trade Organization (WTO) legal framework and its General Agreement on Trade in Services (GATS), devoted to discipline trade in services among the WTO Members. Then, the research moves to a second legal instrument, the Free Trade Agreements (FTAs), which has witnessed a remarkable spread in the last decades. Finally, the research addresses the international standards, developed by supranational entities and implemented by an increasing number of States, as they offer rules and guidelines adequate to update the international financial scenario. Nevertheless, the international standards alone cannot be the solution because, first, they are not mandatory, as governments decide voluntarily to apply them and, second, their decision-making process do not respect the requirements of transparency and representative membership. In light of this analysis, the thesis aims at providing an answer to its research question: how to give more certainty to States and economic operators in the planning of the domestic disciplines and business activities in order to provide a sound and stable international financial system.

Ex ante contracts to arbitrate tort claims - A law and economics perspective

This research addresses the use of ex ante contracts to arbitrate tort claims in domestic settings using law and economics research methodologies. Potential economic benefits from using arbitration, particularly between informed and knowledgeable parties and in international business transactions, are not guaranteed in domestic disputes. Arbitration can potentially be used to manipulate the adjudication process. This research has several findings. There is a lack of information available concerning the use of arbitration to adjudicate tort claims. Proxy measurements concerning the demand for third party adjudication and other legal indicators are a poor substitute for the information hidden behind the veil of arbitration. There is the potential for the strategic use of ex ante contracts to arbitrate tort claims by repeat player tortfeasors to domestic tort claims, both individually and in concert with other repeat player firms. These strategic efforts aim to: manipulate enforcement errors for tort claims, avoid procedural rules which have the effect of lowering enforcement errors, enable a unique type of domestic forum arbitrage, shirk from taking due care, capture the economic benefit of using arbitration, manipulate the stock of precedents and production of public goods from courts, collude in these underlying efforts, restrain competition, indirectly fix prices, and other aims which increase the repeat player tortfeasor’s or their industries economic gains related to their underlying contracts and tort disputes. This research also demonstrates how this subject is appropriate for further academic research and why states should be cautious of giving carte blanche to arbitrate all domestic tort claims.