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HPV circulating tumor DNA as a marker to monitor response to pembrolizumab and vorinostat combination in patients with advanced HPV-related squamous cell carcinoma
No full textPurpose: Limited data are available on the role of circulating tumor DNA of Human Papillomavirus (HPV-ctDNA) as a pharmacodynamic marker to monitor response to treatment in the recurrent/metastatic (R/M) setting. Our study aimed to investigate the sensitivity and pharmacodynamic value of HPV-ctDNA levels during treatment in patients with R/M HPV-related squamous cell carcinoma (SCC) treated with pembrolizumab in combination with vorinostat. Experimental Design: Plasma samples were prospectively collected from HPV-related SCC patients before treatment initiation and every six weeks until disease progression. HPV-ctDNA was quantified using droplet digital PCR (ddPCR). The levels before treatment were analyzed according to patients and tumor characteristics. Landmark analyses were performed to study the association between HPV-ctDNA level variation and both progression-free survival and overall survival. Results: HPV-ctDNA was detected before treatment in all 57 patients with an HPV-related SCC. HPV-ctDNA levels correlated with the number of HPV copy in tumor tissues (p<0.001). Higher levels of HPV-ctDNA in plasma samples were observed in anal cancer in comparison with other tumor types (p<0.0001), and in patients with distant metastases with or without locoregional recurrence as compared with patients with locoregional recurrence alone (p=0.02). The increase of HPV-ctDNA levels during treatment was associated with a lower overall response rate (p=0.01), as well as shorter progression-free survival and overall survival (both, p=0.01). Conclusions: Dynamic HPV-ctDNA variation levels during treatment have a pharmacodynamic value and may help monitoring treatment response in patients with advanced HPV-related SCC of different locations
Patient data sharing for the improvement of healthcare and medical research: towards a moral duty of patients to share health-related data?
No full textThe project answers to the following central research question: ‘How would a moral duty of patients to transfer (health) data for the benefit of health care improvement, research, and public health in the eHealth sector sit within the existing confidentiality, privacy, and data protection legislations?’. The improvement of healthcare services, research, and public health relies on patient data, which is why one might raise the question concerning a potential moral responsibility of patients to transfer data concerning health. Such a responsibility logically would have subsequent consequences for care providers concerning the further transferring of health data with other healthcare providers or researchers and other organisations (who also possibly transfer the data further with others and other organisations). Otherwise, the purpose of the patients’ moral duty, i.e. to improve the care system and research, would be undermined. Albeit the arguments that may exist in favour of a moral responsibility of patients to share health-related data, there are also some moral hurdles that come with such a moral responsibility. Furthermore, the existing European and national confidentiality, privacy and data protection legislations appear to hamper such a possible moral duty, and they may need to be reconsidered to unlock the full use of data for healthcare and research
The genetic prehistory of Northern Calabria. Archeogenomic investigation of the human remains from Grotta di Pietra Sant’Angelo and Grotta della Monaca.
No full textGiven its strategic position at the center of the Mediterranean Basin, and its unique history of contacts and migrations, Calabria is an ideal region to decipher the genetic traces of at least some of the numerous demographic prehistoric events in Southern Italy. This thesis focuses on the genetic and social changes of ancient inhabitants of Calabria, covering a timeline of approximately 7000 to 3300 years ago, ranging from the Middle Neolithic to the Middle Bronze Age. We generated the first genome-wide data from Calabria, by focusing on the single inhumation of “Grotta di Pietra Sant’Angelo” (San Lorenzo Bellizzi, Cosenza) and on the vast community found buried in “Grotta della Monaca” (Sant’Agata di Esaro, Cosenza). Supported by archaeological evidence, the primary objective of this research was to employ paleogenomic evidence to decipher funerary customs, social organization, family ties, and demographic shifts in Southern Italy over a period extending beyond three millennia. The possibility of gender-related burial practices and kinship ties among the deceased was also explored. Subsequently, the biogeographical origin and ancestry of prehistoric people of Calabria was contextualized within the broad landscape of existing data on Mediterranean populations. By generating the first genomic evidence from prehistoric Calabria, unresolved questions were addressed, related to the appearance and persistence of distinct genomic components, such as the Iran-related and the Steppe-related ancestry, whose impact on ancient Southern Italian genomes remains uncharted
A corpus-assisted approach to apology-like expressions in Japanese computer-mediated discourse
No full textThis thesis provides a corpus-assisted pragmatic investigation of three Japanese expressions commonly signalled as apologetic, namely gomen, su(m)imasen and mōshiwake arimasen,
which can be roughly translated in English with ‘(I’m) sorry’. The analysis is based on a web
corpus of 306,670 tokens collected from the Q&A website Yahoo! Chiebukuro, which is examined combining quantitative (statistical) and qualitative (traditional close reading)
methods. By adopting a form-to-function approach, the aim of the study is to shed light on
three main topics of interest: the pragmatic functions of apology-like expressions, the discursive strategies they co-occur with, and the behaviours that warrant them.
The overall findings reveal that apology-like expressions are multifunctional devices whose meanings extend well beyond ‘apology’ alone. These meanings are affected by a number of
discursive strategies that can either increase or decrease the perceived (im)politeness level of
the speech act to serve interactants’ face needs and communicative goals. The study also
identifies a variety of behaviours that people frame as violations, not necessarily because they
are actually face-threatening to the receiver, but because doing so is functional to the projection
of the apologiser as a moral persona. An additional finding that emerged from the analysis is the pervasiveness of reflexive usages of apology-like expressions, which are often employed
metadiscursively to convey, negotiate and challenge opinions on how language should be used.
To conclude, the study provides a unique insight into the use of three expressions whose pragmatic meanings are more varied than anticipated. The findings reflect the use of
(im)politeness in an online and non-Western context and, hopefully, represent a step towards a more inclusive notion of ‘apologies’ and related speech acts
Compression of left main coronary artery in patients with pulmonary arterial hypertension asymptomatic for angina
No full textLa dilatazione dell’Arteria Polmonare (AP) è frequente in pazienti con ipertensione arteriosa polmonare (IAP) e può favorire l’insorgenza di complicanze meccaniche, come la stenosi del Tronco Comune della coronaria sinistra (TCCS). Una stenosi ab estrinseco del TCCS nei pazienti con IAP può determinare aritmie fatali e morte improvvisa. Sebbene siano disponibili alcuni dati in letteratura sui pazienti che presentano angina, poco è noto negli asintomatici. L’obiettivo principale di questo studio è di definire la prevalenza della stenosi critica ab estrinseco del TCCS nei pazienti con IAP asintomatici. Tra gli obiettivi secondari abbiamo voluto definire il cutoff del diametro dell’AP che determina un incremento del rischio di compressione del TCCS, i fattori che correlano con la dilatazione dell’AP e con la sua crescita nel tempo, la correlazione tra la mortalità totale e il diametro dell’AP o la sua crescita nel tempo e la correlazione tra l’endpoint composito di morte improvvisa e/o compressione del TCCS e il diametro dell’AP o la sua crescita nel tempo. È stata svolta un’analisi retrospettiva di tutti i pazienti con IAP riferiti al Centro di ipertensione polmonare di Bologna. Sono stati inclusi nello studio 958 pazienti con IAP, di cui 180 con sintomi e 778 asintomatici. La compressione è stata confermata in 65 pazienti e di questi, 50 avevano avuto sintomi (28% dei pazienti sintomatici) e 15 erano asintomatici (1.9% dei pazienti asintomatici). Il miglior predittore di stenosi critica del TCCS all’angiografia coronarica in pazienti con IAP è risultato un diametro dell’AP ≥ 40 nei pazienti sintomatici e ≥ 42 mm nei pazienti asintomatici. La crescita annuale del diametro dell’AP è risultata essere predittrice di morte per ogni causa in pazienti con IAP. Il diametro dell’AP e la crescita annua del diametro dell’AP sono risultati correlati all’endpoint composito di morte improvvisa e/o compressione del TCCS.A dilation of the pulmonary artery (PA) is frequent in patients with pulmonary arterial hypertension (PAH) and can lead to mechanical complications, such as the compression of the left main coronary artery (LMCA). A compression of the LMCA in PAH patients can induce fatal arrhythmias and sudden death. Even though there is some available data concerning patients symptomatic for angina, little is known in asymptomatic patients. The main goal of this study is to define the prevalence of ab estrinseco LMCA compression in asymptomatic PAH patients. As secondary endpoints we tried to define a cutoff of the PA diameter beyond which the risk of compression is increased, the factors that correlate with the diameter of the PA and its growth over time, the correlation between total mortality and the diameter of the PA and its growth over time and the correlation between the composite endpoint of sudden death and/or compression of the LMCA and the diameter of the PA and its growth over time. We performed a retrospective analysis of all the patients with PAH that were referred to our centre. Overall, 958 patients were included in the analysis; 180 of them were symptomatic and 778 were not. The compression of the LMCA was confirmed in 65 patients of whom 50 were symptomatic (28%) and 15 were asymptomatic (15%). The best predictor the LMCA compression was a diameter of the PA ≥ 40 mm in symptomatic patients and ≥ 42 mm in asymptomatic patients. The annual growth rate of the PA was found to be a predictor of death for any cause. The diameter of the PA and its annual growth rate were related to the composite endpoint of sudden death and/or compression of the LMCA
Rethinking the block. The 1970s European discourses on the city and the IBA Berlin 1979-87
No full textThe dissertation explores the relationship between projects for urban blocks and the discourses on the city between the late 1960s and the 1980s, with a particular focus on the blocks of the Internationale Bauausstellung (IBA) Berlin 1979-87. The main research questions center on whether and how the block changed in connection with the emerging ideas of the city during this period and whether these changes had, in turn, effects on the whole city. Thus far, despite extensive research on the theories and the ideas of the city between the 1960s and 1980s, there is a lack of studies that interweave this research with insights into the block. To fill this gap, this dissertation examines how the block was thematized in the 1970s discourses on the city. It highlights projects for blocks designed between the late 1960s and the 70s in various European cities, particularly West Berlin. Then, it focuses on the blocks of the IBA Berlin 1979-87, examining them through theory, history, and drawings. The study of the examples reveals three distinctive aspects of all blocks considered in the dissertation: the overcoming of small private plots, the individualization of the buildings, and the accessibility of the courtyards from public streets. These aspects reflect the changing understandings of the city and of the urban spaces in the 1970s and 1980s, which resulted in new compositional logics of the block. When examined with critical distance, the blocks of the 1970s and 80s offer a lesson in architectural and urban composition which is still current.
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The author has made every effort to contact the owners of the copyrights of the material in the dissertation. The author is available to the right holders with whom it was not possible to communicate as well as for any omissions or inaccuracies in quoting the sources
The sale of consumer goods: a study on the basis of Directive 2019/771 of 20 May 2019
No full textLa presente tesis doctoral tiene como objeto el análisis de la transposición española de la Directiva UE 2019/771 de 20 de mayo, relativa a determinados aspectos de los contratos de compraventa de bienes, que ha venido a derogar la Directiva 1999/44/CE y a modificar el Reglamento CE núm. 2017/2394 y la Directiva 2009/22/CE.
Para ello realiza un repaso del régimen de garantías y servicios postventa aplicable a las compraventas de bienes de consumo, poniendo de manifiesto los cambios producidos, así como las diferencias regulatorias con otros países de nuestro entorno. Puesto que, si bien se trataba de una Directiva de máximos, algunos aspectos no han sido objeto de armonización plena y, por ejemplo, existen considerables diferencias en Estados como Italia, e incluso en otros territorios como Cataluña que, desde hace un tiempo, sigue la senda de construir un derecho civil propio.
Asimismo, el trabajo hace un esfuerzo por incluir los diferentes pronunciamientos del Tribunal Supremo Español y el Tribunal de Justicia de la Unión Europea que sobre la materia ha habido en las últimas décadas, para aglutinar todo el acervo jurídico que hasta el momento nos sirve para interpretar esta normativa.
Por último, el cuarto capítulo finaliza con las distintas propuestas doctrinales y legislativas que a día de hoy se han planteado en orden a mejorar el régimen de garantías y servicios postventa desde una perspectiva de una economía sostenible de acuerdo con la agenda marcada por la Unión Europea.The purpose of this doctoral thesis is to analyse the Spanish transposition of EU Directive 2019/771 of 20 May, on certain aspects of contracts for the sale of goods, which repeals Directive 1999/44/EC and amends EC Regulation No. 2017/2394 and Directive 2009/22/EC.
To this end, it reviews the system of guarantees and after-sales services applicable to the sale of consumer goods, as well as the regulatory differences with other countries in our environment. Although this was a maximum Directive, some aspects have not been fully harmonised and, for example, there are considerable differences in States such as Italy, and even in other territories such as Catalonia, which, for some time now, has been following the path of building its own civil law.
Likewise, the work makes an effort to include the different pronouncements of the Spanish Supreme Court and the Court of Justice of the European Union on the subject in recent decades, in order to bring together the entire legal acquis that has served to date to interpret this legislation.
It also attempts to carry out a doctrinal delimitation of the seller's non-compliance regime in the sale of consumer goods, with the aim of studying in depth the assumptions of his liability and the remedies available to the buyer in the event of non-compliance with the obligations of the seller which, ultimately, would result in the delivery of the consumer good and that the consumer good once delivered is in conformity, in accordance with the parameters of conformity set out in consumer protection legislation.
Finally, the fourth chapter ends with the different doctrinal and legislative proposals that have been put forward to improve the system of guarantees and after-sales services from the perspective of a sustainable economy in accordance with the agenda set by the European Union
Antitrust enforcement through private law remedies
No full textLa ricerca indaga due distinti temi: 1) la reale attitudine delle previsioni della Direttiva 2014/104/EU in punto di azioni risarcitorie antitrust a raggiungere gli scopi espressamente assegnati dal legislatore all’istituto; 2) la sorte dei contratti attuativi di un abuso escludente ovvero di abuso di sfruttamento, tenuto conto della funzione regolatoria che il diritto di matrice europea assegna al contratto. Il lavoro si propone, pertanto, di ricostruire i rapporti tra il diritto generale dei contratti e quello speciale antitrust, al fine di vagliare l’eventuale intersezione tra tutela risarcitoria e specifica.
Nell’analisi delle tematiche sopra individuate si sono scelti due canoni ermeneutici ritenuti gli unici idonei ad assicurare che nel processo interpretativo si tenessero in considerazione le peculiarità della disciplina dettata in materia antitrust. L’uno rappresentato dallo scopo della norma violata, l’altro rappresentato dal principio di effettività. Si tratta di due criteri ermeneutici di cui si serve non poco il legislatore europeo e la CGUE.
Sennonché prima ancora di vagliare le singole fattispecie individuate, si tenta di intraprendere una ricognizione dei presupposti e dei paradigmi, impliciti, che sottendono detti canoni ermeneutici, affinché questi effettivamente potranno “far luce” all’interprete allorquando questi si trova nella zona di “intersezione” del diritto speciale e quello generale. In primo luogo, viene ripercorsa la nozione di concorrenza: essa non è autoevidente perché è frutto di valutazioni di politica economica e di diritto. Altro canone ermeneutico individuato è rappresentato dal principio di effettività. Si è approfondito il ruolo che questo ha svolto nell’ordinamento interno e la ben diversa connotazione che assume nel diritto europeo.The research investigates two distinct issues: 1) the real aptitude of the provisions of Directive 2014/104/EU in terms of antitrust damages actions to achieve the purposes expressly assigned by the legislator to the institution and to reconstruct, in the case of gaps, adequate rules for the pursuit of such stated purposes and consistent with the European framework of values on civil liability; 2) the fate of contracts implementing an exclusionary or exploitative abuse, taking into account the regulatory function that European law assigns to the contract, and to reconstruct the relationship between general law and the civil liability; 2) the fate of contracts implementing an exclusionary abuse or exploitative abuse, taking into account the regulatory function that European law assigns to the contract. With regard to the second topic, the essay opens up the problem of the consequences of nullity on the principal relationship.
The antitrust damage development reflects the internal dynamism via which the effectiveness of EU law is affirmed. The doctrinal task is to reconstruct the characteristics of torts, both in reference to the rules established at European level, and for the unregulated aspects, which is recognized in the general logic of non-contractual liability as configured by the European system.
Studying the effectiveness and efficiency of European private antitrust enforcement requires understanding the competitive market’s general protection mechanism. For this reason, this work begins with a description of evolutions in European competition law, in order to show that antitrust experience is built on principles according to which markets need to be protected not only from public power, but also from private power abuse, which has the effect of reducing and defending private autonomy
Psychological load related to training and competitions in athletes: validity and reliability of new differential RPE scales
No full textThe purpose of this PhD thesis was to begin the validation process of two RPE-based scales that separate the psychological load of a training session from the physical one. Five different studies were conducted with more than two hundred semi-professional and élite athletes. The two new differential RPE scales, the perceived mental exertion rating scale (M-RPE) and the perceived physical exertion sclae (P-RPE), results valid compared to the criterion measure, able to discriminate different mental and physical training loads in field and in laboratory environment, and very reliable with athletes on the field. Finally, the ecological validity of the two scales was tested in a pilot study in which 4 professional and semi-professional teams were monitored differentiating the perceived effort experienced by athletes during training and competitions. The results of this multiple research studies support the use of differential RPE scales in the daily practice of monitoring the training loads of individual and team sports athletes. Finally we provided reliable and ecologically valid measures of physical and mental loads in different types of training and competition
Multimodality as a resource in dialogue interpreting: a study of simulated interpreter-mediated interactions in an educational context
No full textNotre étude questionne les compétences interactionnelles multimodales dans la formation des interprètes. Des recherches antérieures ont mis en exergue la contribution des ressources sémiotiques non verbales dans les interactions médiées par interprète. La co-construction de la coordination et la position centrale de l'interprète requièrent, outre des compétences de traduction, des compétences interactionnelles spécifiques qui incluent l'utilisation de la multimodalité. Cependant, cette ressource est rarement prise en compte dans la formation des interprètes et nous nous demandons si, et comment, les étudiants acquièrent ces compétences. Ainsi, nous avons mené une étude qualitative auprès d'un groupe de dix étudiants-interprètes de l'Université de Bologne. Leurs performances lors des sessions de jeux de rôle en contexte d'apprentissage ont été filmées et analysées afin de répondre aux questions suivantes : quelles sont les ressources sémiotiques non verbales mises en œuvre par les étudiants pendant les simulations? À quoi servent-elles ? Comment varient-elles ? Suite à la transcription, avec le logiciel ELAN , des données vidéo, une analyse descriptive a été réalisée sur l'utilisation des ressources multimodales par les étudiants. Nous avons ensuite sélectionné dix-huit extraits à analyser en suivant la méthode d'analyse conversationnelle multimodale. Cette analyse a permis de mettre en lumière la façon dont la multimodalité reflète le caractère situé des interactions et contribue à la qualité de ces dernières. Globalement, les résultats montrent un recours relativement faible à la multimodalité comme ressource. Cependant, l'analyse met en évidence de nombreuses différences individuelles. Elle permet, en outre, d'identifier les questions qui devraient être prises en compte pour optimiser les activités de jeu de rôle dans la formation des interprètes de dialogue et l'inclusion de la multimodalité en tant que ressource.This study focuses on multimodal interactional competences in dialogue interpreters’ education. Previous research has shown that non-verbal semiotic resources play an important role in communication outcome during interpreter-mediated interactions. The co-construction of coordinating actions and the central position of the interpreter require, in addition to translation skills, specific interactional skills which include the use of multimodality as a resource. However, this resource is rarely taken into account in interpreter training. Consequently, we question if and how student interpreters acquire these skills. To this end, a qualitative study was carried out with a group of ten students at the University of Bologna. Their performances during the role play sessions in a learning context were filmed and analysed in order to answer the following questions: what nonverbal semiotic resources are found in student interpreters when simulating interpreter-mediated interactions? What purpose do they serve? How do they vary? After transcription with ELAN software, a descriptive analysis was carried out on students’ use of multimodal resources. This allowed a selection of excerpts to be analysed following a Multimodal Conversation Analysis Method. This fine-grained analysis shed light on a series of salient situations and the different ways in which the embodied and situated actions impact their outcome. In addition, the students took part in semi-directed self-reflection interviews which were also recorded. These were designed to give us access to the students’ criteria and level of multimodal interactional awareness. The overall results show relatively little usage of multimodality as a resource. However, the analysis highlights numerous individual differences and allows identification of issues that should be considered in order to optimise role play activities in dialogue interpreter training, with the inclusion of multimodality as a resource