Efficacia e sicurezza della profilassi anti-citomegalovirus rispetto alla strategia pre-sintomatica con valganciclovir in pazienti con trapianto di cuore trattati con everolimus o micofenolato

Il CMV è l’agente patogeno più frequente dopo trapianto (Tx) di cuore determinando sia sindromi cliniche organo specifiche sia un danno immunomediato che può determinare rigetto acuto o malattia coronarica cronica (CAV). I farmaci antivirali in profilassi appaiono superiori all’approccio pre-sintomatico nel ridurre gli eventi da CMV, ma l’effetto anti-CMV dell’everolimus (EVE) in aggiunta alla profilassi antivirale non è stato ancora analizzato. SCOPO DELLO STUDIO: analizzare l’interazione tra le strategie di profilassi antivirale e l’uso di EVE o MMF nell’incidenza di eventi CMV correlati (infezione, necessità di trattamento, malattia/sindrome) nel Tx cardiaco. MATERIALI E METODI: sono stati inclusi pazienti sottoposti a Tx cardiaco e trattati con EVE o MMF e trattamento antivirale di profilassi o pre-sintomatico. L’infezione da CMV è stata monitorata con antigenemia pp65 e PCR DNA. La malattia/sindrome da CMV è stato considerato l’endpoint principale. RISULTATI: 193 pazienti (di cui 10% D+/R-) sono stati inclusi nello studio (42 in EVE e 149 in MMF). Nel complesso, l’infezione da CMV (45% vs. 79%), la necessità di trattamento antivirale (20% vs. 53%), e la malattia/sindrome da CMV (2% vs. 15%) sono risultati significativamente più bassi nel gruppo EVE che nel gruppo MMF (tutte le P<0.01). La profilassi è più efficace nel prevenire tutti gli outcomes rispetto alla strategia pre-sintomatica nei pazienti in MMF (P 0.03), ma non nei pazienti in EVE. In particolare, i pazienti in EVE e strategia pre-sintomatica hanno meno infezioni da CMV (48 vs 70%; P=0.05), e meno malattia/sindrome da CMV (0 vs. 8%; P=0.05) rispetto ai pazienti in MMF e profilassi. CONCLUSIONI: EVE riduce significamene gli eventi correlati al CMV rispetto al MMF. Il beneficio della profilassi risulta conservato solo nei pazienti trattati con MMF mentre l’EVE sembra fornire un ulteriore protezione nel ridurre gli eventi da CMV senza necessità di un estensivo trattamento antivirale.

The Legacy of Frankenstein’s Creature: Monstrosity and Female Grotesque in Mary Shelley, Angela Carter and Jeanette Winterson

This English Literature thesis (European PhD EDGES – Women’s and Gender Studies – 34th cycle) is an investigation into the representation of the monstrous body according to the British writers Mary Shelley, Angela Carter and Jeanette Winterson. The main objective is to observe how the representation of the categories of monstrous, abject and grotesque in Western cultural imagination have been influenced across time and literary genres. In the novels of Shelley, Carter and Winterson, the monstrous subject is configured as an alternative to the anthropocentric ideal embodied by the normative subject, of which Victor Frankenstein is the paradigmatic exponent. Plus, there are places considered anti-topoi within which the monster acquires a situatedness and claims a voice, generating an opposed counter-narrative to the imaginary conveyed by the normative subject. Monstrosity outlined by Shelley in the novels Frankenstein and The Last Man constitutes the starting point of my research, aiming to observe how the discourse of the normative body vs. the anti-normative body intersects with the discourse of the spaces of the centre vs. the spaces of the margin. In Carter's novels The Passion of New Eve and Nights at the Circus, the monstrous female constitutes the embodiment of wills, desires and claims challenging the heteronormative system. The space of otherness in which Carter's monster-woman is confined becomes a possibility of reshaping identity for the Subject, deconstructing the logic of power that moulded her within society. Finally, Winterson creates two monstrous women in Sexing the Cherry and The Passion who move through urban spaces, going from the centre to the margins and testifying to the arbitrariness of the system and its weaknesses. Similarly, in Frankissstein, Winterson recovers Shelley's original novel and transforms it into a parodic and intertextual speculation on the fluidity of identity and the limits of transhumanism.

Landslide activity in contrasting land-cover settings constrained by multi-temporal inventorying

This doctoral thesis focuses on the study of historical shallow landslide activity over time in response to anthropogenic forcing on land use, through the compilation of multi-temporal landslide inventories. The study areas, located in contrasting settings and characterized by different history of land-cover changes, include the Sillaro River basin (Italy) and the Tsitika and Eve River basins (coastal British Columbia). The Sillaro River basin belongs to clay-dominated settings, characterized by extensive badland development, and dominated by earth slides and earthflows. Here, forest removal began in the Roman period and has been followed by agricultural land abandonment and natural revegetation in recent time. By contrast, the Tsitika-Eve River basins are characterized by granitic and basaltic lithologies, and dominated by debris slides, debris flows and debris avalanches. In this setting, anthropogenic impacts started in 1960’s and have involved logging operation. The thesis begins with an introductory chapter, followed by a methodological section, where a multi-temporal mapping approach is proposed and tested at four landslide sites of the Sillaro River basin. Results, in terms of inventory completeness in time and space, are compared against the existing region-wide Emilia-Romagna inventory. This approach is then applied at the Sillaro River basin scale, where the multi-temporal inventory obtained is used to investigate the landslide activity in relation to historical land cover changes across geologic domains and in relation to hydro-meteorological forcing. Then, the impact of timber harvesting and road construction on landslide activity and sediment transfer in the Tsitika-Eve River basins is investigated, with a focus on the controls that interactions between landscape morphometry and cutblock location may have on landslide size-frequency relations. The thesis ends with a summary of the main findings and discusses advantages and limitations associated with the compilation of multi-temporal inventories in the two settings during different periods of human-driven, land-cover dynamics.