Biomarkers in chronic obstructive pulmonary diseases. Clinical and functional correlations.

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct lung diseases with distinctive clinical and inflammatory features. A proportion of asthmatic patients experience a fixed airflow obstruction that persists despite optimal pharmacologic treatment for reasons that are still largely unknown. We found that patients with asthma and COPD sharing a similar fixed airflow obstruction have an increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function is associated with specific features of the underlying inflammation. Airway inflammation increases during asthma exacerbation and disease severity. Less is known about the correlations between symptoms and airway inflammation in COPD patients. We found that there is no correlation between symptoms and lung function in COPD patients. Nevertheless symptoms changes are associated with specific inflammatory changes: cough is associated with an increase of sputum neutrophils in COPD, dyspnoea is associated with an increase of eosinophils. The mechanisms of this correlation remain unknown. Neutrophils inflammation is associated with bacterial colonization in stable COPD. Is not known whether inhaled corticosteroids might facilitate bacterial colonization in COPD patients. We found that the use of inhaled corticosteroids in COPD patients is associated with an increase of airway bacterial load and with an increase of airway pathogen detection. Bacterial and viral infections are the main causes of COPD and asthma exacerbations. Impaired innate immune responses to rhinovirus infections have been described in adult patients with atopic asthma. Whether this impaired immune condition is present early in life and whether is modulated by a concomitant atopic condition is currently unknown. We found that deficient innate immune responses to rhinovirus infection are already present early in life in atopic patients without asthma and in asthmatic subjects. These findings generalize the scenario of increased susceptibility to viral infections to other Th2 oriented conditions.

Stratigraphy and Palaeontology of the Late Cretaceous Wapiti Formation, west-central Alberta, Canada

A complete stratigraphic assessment and revision of the middle Campanian to upper Maastrichtian Wapiti Formation in north-western Alberta and north-eastern British Columbia is the main aim of this research project. The study area encompasses an area of approximately 200X180 km in the Grande Prairie County (west-central Alberta) and easternmost British Columbia, Canada. Results presented here indicate that the 1300m thick succession currently reported in the literature as “undifferentiated lithostratigraphic unit”, consists of five lithostratigraphic units and four unconformity-bounded depositional sequences; their study and description have been documented integrating several geological disciplines, including sequence stratigraphic methods, well-log signatures, facies analysis, and fossil associations. On the whole, particular attention has been given to 1) age and nature of both basal and upper contacts of the Wapiti Formation, 2) effective mappability of lithostratigraphic units and depositional sequences in western Alberta, and 3) the identification of previously undetermined maximum flooding surface of the Bearpaw seaway and Drumheller Marine Tongue, which are reference marine unit in central and southern Alberta. A second, but not less important, guideline for the project has been the rich paleontological record of the Wapiti deposits. Detailed paleoenvironmental and taxonomical information on old and new finds have been the base for correlation with well known associations of Alaska, southern Alberta, and Montana. Newly discovered rich fossil localities documented an extraordinarily diverse fauna during the latest Cretaceous, including dinosaurs, squamates, and fresh-water fishes and reptiles. Lastly, in order to better characterize the Wapiti Formation, major marker beds were described: these include several bentonites (altered volcanic ash deposits) which have been documented over an area of almost 30.000 km2, as well as four major coal zones, characterized by tabular coal seams with an overall thickness of 2 meters. Such marker beds represent a formidable tool for high-resolution chronology and regional correlations within the Late Cretaceous Alberta foreland basin.

Micro and Macro essays in Applied Fiscal Policy

This thesis analysis micro and macro aspect of applied fiscal policy issues. The first chapter investigates the extent to which local budget spending composition reacts to fiscal rules variations. I consider the budget of Italian municipalities and exploit specific changes in the Domestic Stability Pact’s rules, to perform a difference-in-discontinuities analysis. The results show that imposing a cap on the total amount of consumption and investment is not as binding as two caps, one for consumption and a different one for investment. More specifically, consumption is triggered by changes in wages and services spending, while investment relies on infrastructure movements. In addition, there is evidence that when an increase in investment is achieved, there is also a higher budget deficit level. The second chapter intends to analyze the extent to which fiscal policy shocks are able to affect macrovariables during business cycle fluctuations, differentiating among three intervention channels: public taxation, consumption and investment. The econometric methodology implemented is a Panel Vector Autoregressive model with a structural characterization. The results show that fiscal shocks have different multipliers in relation to expansion or contraction periods: output does not react during good times while there are significant effects in bad ones. The third chapter evaluates the effects of fiscal policy announcements by the Italian government on the long-term sovereign bond spread of Italy relative to Germany. After collecting data on relevant fiscal policy announcements, we perform an econometric comparative analysis between the three cabinets that followed one another during the period 2009-2013. The results suggest that only fiscal policy announcements made by members of Monti’s cabinet have been effective in influencing significantly the Italian spread in the expected direction, revealing a remarkable credibility gap between Berlusconi’s and Letta’s governments with respect to Monti’s administration.

An analysis of the regulatory chill hypothesis: environmental protection in international investment law

The goal of this thesis has been to find out whether ISDS and international investment law exert a chilling effect on more stringent environmental standards at the domestic level. Due to the lack of consistent empirical and statistical evidence uncovered during the analysis, this thesis largely dismisses the regulatory chill hypothesis. However, two exceptions are identified: first, there is evidence of the efforts made by domestic industrial groups and trade unions to prevent the implementation of stricter environmental standards; second, it has become apparent that unfounded beliefs, e.g. about ISDS, held by lawmakers and regulators can play an important role in chilling stricter environmental standards. For these reasons, a new and narrower definition of the regulatory chill phenomenon has been proposed, one that only encompasses those instances in which lawmakers, governments and government agencies refrain from adopting the laws and regulations that they deem the most appropriate because they believe that doing so would lead to adverse consequences at the international trade and investment level, despite a lack of consistent and robust evidence supporting their concerns. The second part of this thesis focusses on what could be done in international economic law to promote environmentally friendly FDI, while preventing the few instances in which regulatory chill may take place due to ill-founded beliefs held by lawmakers and regulators. Following an analysis that highlights the paramount role played by public participation and responsive institutions to achieve an appropriate level of environmental protection, this study ends with a proposal that recommends the adoption of a clause within IIAs that makes pre-investment environmental screening mandatory and free from ISDS oversight.