Re-evaluating the greek foreign policy system in a transforming world politics

The present thesis evaluates the responses of the contemporary Greek foreign policy structures and processes, conceptualised as the Greek foreign policy system, in the face of the transformation of world politics. This transformation, precipitated by the concurrent complex processes of globalisation and regionalisation, pose empirical and analytical challenges to the national management of foreign policy. Consequently, government departments and agencies assigned with responsibility for the conduct of what has been traditionally termed foreign policy, namely the national foreign policy machinery with the foreign ministry and the diplomatic network at its core, find themselves challenged as roles and responsibilities are relocated. Such change underpins the machinery s institutional responses and the need to rethink its role and structure. The thesis synthesises several literatures, primarily those identified with international relations, transformational foreign policy analysis, and new approaches to diplomatic studies informed by insights from institutionalist approaches. This is combined with extensive fieldwork within the Greek bureaucracy and the diplomatic network, and seeks to cast light on a relatively understudied area: namely the organisation and nature of the Greek foreign policy system in an era of considerable change. The thesis draws a dual image of the contemporary Greek foreign policy system which displays elements of both continuity and change. According to the first image, the Greek foreign policy machinery embraces contemporary foreign policy developments, and is enmeshed in a process of change and adaptation as a response to its changing operational environment. The second image depicts the foreign policy system as traditionalist conforming to geopolitical approaches, which are linked to compartmentalisation in the organisation of foreign policy. This image is supported by evidence which suggests that the Greek foreign policy machinery is infused with elements of hierarchy, centralisation and verticality in its organisation, which prevent the adoption of integrated and horizontal models prescribed by globalist approaches to the management of foreign policy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Βελτίωση της ακτινοθεραπευτικής πράξης μέσω υπολογιστικών μοντέλων διαχείρισης ανθρωπίνων παραγόντων

Τα τελευταία χρόνια, νέες και προηγμένες τεχνολογίες έχουν αλλάξει ριζικά τον προγραμματισμό και την εκτέλεση της ακτινοθεραπευτικής πράξης. Με την ανάπτυξη των πολύφυλλων κατευθυντήρων (MLC), η διαμορφούμενης έντασης ακτινοθεραπεία (IMRT) και η ακτινοθεραπεία καθοδηγούμενη από εικόνα (IGRT), παρέχει ένα πιο αυστηρά καθορισμένο όγκο στόχο ενώ παράλληλα ελαχιστοποιούνται οι δόσεις στα κρίσιμα όργανα. Ωστόσο, η διαδικασία θεραπείας έχει γίνει πιο περίπλοκη και για τη βελτίωση της ασφάλειας των ασθενών και της ποιότητας της θεραπείας, η βιομηχανία της ακτινοθεραπείας έχει επικεντρωθεί σε μεγάλο βαθμό στη δημιουργία νέων συσκευών παράδοσης ακτινοβολίας και νέων συστημάτων πληροφορικής. Ενώ αυτές οι νέες τεχνολογίες βελτιώνουν την ποιότητα της ακτινοθεραπείας και μειώνουν τα σφάλματα κατά την ακτινοβόληση, δημιούργησαν νέες πηγές σφαλμάτων. Τα συστήματα καταγραφής και επαλήθευσης (R & V) που αναπτύχθηκαν πρόσφατα για να διασφαλίσουν την ακρίβεια στην παροχή θεραπευτικών σχεδίων συχνά συνδέεται με ζητήματα χρηστικότητας που μπορούν να οδηγήσουν σε σφάλματα. Αυτό καταδεικνύει τη μεγάλη ανάγκη βελτίωσης της αλληλεπίδρασης μεταξύ χρηστών και τεχνολογιών. Ωστόσο, οι περισσότερες αξιολογήσεις τεχνολογιών επικεντρώθηκαν στην βελτίωση των τεχνικών και των τεχνολογιών ενώ περιορισμένες μελέτες εξέτασαν το ρόλο που παίζει ο ανθρώπινος παράγοντας στην ασφάλεια του ασθενή. Ως εκ τούτου, η μελέτη αυτή στοχεύει στην εφαρμογή των μηχανισμών ανθρώπινων παραγόντων προκειμένου να εντοπίσει τις μη ασφαλής παραμέτρους ενός συστήματος ακτινοθεραπείας και να παρέχει συστάσεις σχετικά με τα ζητήματα που προκύπτουν από τα σφάλματα αυτά. Πιο συγκεκριμένα, χωρίζεται σε τέσσερις φάσεις: • Ανασκόπηση των συμβάντων στην ακτινοθεραπεία. • Ανάλυση ροής εργασιών. Unified Modeling Language (UML) διαγράμματα δραστηριοτήτων • Ανάλυση παραγόντων ποσοτικής έρευνα • Ευρετική Αξιολόγηση. Συστηματική επιθεώρηση διεπαφών χρήστη με βάση ένα σύνολο αρχών ευχρηστίας και συστάσειςIn recent years, new and advanced technologies have radically changed the programming and implementation of radiotherapy. With the development of multi-leaf collimator (MLC), intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) provides a more strictly defined target volume while minimising doses to critical organs. However, the treatment process has become more complex and in order to improve patient safety and the quality of treatment, the radiotherapy industry has largely focused on the creation of new radiation delivery devices and new IT systems. While these new technologies improve the quality of radiotherapy and reduce errors in irradiation, they have created new sources of errors. Recently developed recording and verification systems (R & V) to ensure accuracy in the delivery of therapeutic plans are often associated with usability issues that can lead to errors. This demonstrates the great need to improve interaction between users and technologies. However, most technology assessments focused on improving techniques and technologies and limited studies looked at the role the human factor plays in patient safety. Therefore, this study aims to implement human factor mechanisms to identify the unsafe parameters of an radiotherapy system and to provide recommendations on the issues arising from these errors. More specifically, it is divided into four phases: • Review of events in radiotherapy. • Workflow analysis. Unified Modeling Language (UML) activity diagrams • Analysis of quantitative research factors • Heuristic evaluation. Systematic inspection of user interfaces based on a set of user principles and recommendation

Ethical issues invoked by Industry 4.0

Industry 4.0 is universally referred to as the fourth industrial revolution. It is a current trend of automation and data exchange in manufacturing technologies. The computerisation of manufacturing includes, amongst other, cyber-physical systems, the Internet of Things (IoT), cloud computing and cognitive computing. There are many challenges in the realisation of Industry 4.0. In order to adopt a "smart factory" and improved (software) processes many ethical considerations need to be identified and considered if a company is to obtain an ethical development and deployment of Industry 4.0. The purpose of normative ethics is to scrutinise standards about the rightness and wrongness of actions, the ultimate goal being the identification of the true human good. A rational appeal can be made to normative defensible ethical rules in order to arrive at a judicious, ethically justifiable judgement. In this position and constructive design research paper our steps are: First we report on the findings of a broad literature review of related research, which refers to the current challenges in the realisation of Industry 4.0. Second, we identify and list some basic generic Deontological and Teleological ethical principles and theories that can serve as normative guidelines for addressing the challenges identified in the initial step. Third, we prescribe a set of ethical rights and duties that must be exercised and fulfilled by protagonists/stakeholders in Industry 4.0 implementation in order for them to exhibit ethical behaviour. Each of these suggested actions are substantiated via an appeal to one, or a number of the normative guidelines, identified in the second step. By identifying and recommending a set of defensible ethical obligations that must be fulfilled in the development and deployment of smart factories, protagonists such as: employers, project managers, technology suppliers, trade unions, (on a microscopic level) and chambers of commerce, local and national government (on a macroscopic level) and other can fulfil their ethical duties. Thus, a deployed Industry 4.0 solution can result in technological change, social change and changes in the business paradigm, which are all ethically justifiable. Ultimately all the improvement processes of Industry 4.0 implementation must be underpinned with ethical consideration

Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation

Pancreatic β-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Defects in β-cell function lead to hyperglycemia and diabetes mellitus. Here, we show that CNOT3, a CCR4-NOT deadenylase complex subunit, is dysregulated in islets in diabetic db/db mice, and that it is essential for murine β cell maturation and identity. Mice with β cell-specific Cnot3 deletion (Cnot3βKO) exhibit impaired glucose tolerance, decreased β cell mass, and they gradually develop diabetes. Cnot3βKO islets display decreased expression of key regulators of β cell maturation and function. Moreover, they show an increase of progenitor cell markers, β cell-disallowed genes, and genes relevant to altered β cell function. Cnot3βKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increased expression of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously unsuspected post-transcriptional mechanisms essential for β cell identity

A cross-sectional study of explainable machine learning in Alzheimer’s disease: diagnostic classification using MR radiomic features

IntroductionAlzheimer’s disease (AD) even nowadays remains a complex neurodegenerative disease and its diagnosis relies mainly on cognitive tests which have many limitations. On the other hand, qualitative imaging will not provide an early diagnosis because the radiologist will perceive brain atrophy on a late disease stage. Therefore, the main objective of this study is to investigate the necessity of quantitative imaging in the assessment of AD by using machine learning (ML) methods. Nowadays, ML methods are used to address high dimensional data, integrate data from different sources, model the etiological and clinical heterogeneity, and discover new biomarkers in the assessment of AD.MethodsIn this study radiomic features from both entorhinal cortex and hippocampus were extracted from 194 normal controls (NC), 284 mild cognitive impairment (MCI) and 130 AD subjects. Texture analysis evaluates statistical properties of the image intensities which might represent changes in MRI image pixel intensity due to the pathophysiology of a disease. Therefore, this quantitative method could detect smaller-scale changes of neurodegeneration. Then the radiomics signatures extracted by texture analysis and baseline neuropsychological scales, were used to build an XGBoost integrated model which has been trained and integrated.ResultsThe model was explained by using the Shapley values produced by the SHAP (SHapley Additive exPlanations) method. XGBoost produced a f1-score of 0.949, 0.818, and 0.810 between NC vs. AD, MC vs. MCI, and MCI vs. AD, respectively.DiscussionThese directions have the potential to help to the earlier diagnosis and to a better manage of the disease progression and therefore, develop novel treatment strategies. This study clearly showed the importance of explainable ML approach in the assessment of AD

Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity

Aims/hypothesis: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected ‘hub’ cells, important for the propagation of intercellular Ca2+ waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes. At present, the molecular mechanisms through which beta cell hierarchy is established are poorly understood. Changes at the level of the epigenome provide one such possibility, which we explore here by focusing on the imprinted gene Nnat (encoding neuronatin [NNAT]), which is required for normal insulin synthesis and secretion. Methods: Single-cell RNA-seq datasets were examined using Seurat 4.0 and ClusterProfiler running under R. Transgenic mice expressing enhanced GFP under the control of the Nnat enhancer/promoter regions were generated for FACS of beta cells and downstream analysis of CpG methylation by bisulphite sequencing and RNA-seq, respectively. Animals deleted for the de novo methyltransferase DNA methyltransferase 3 alpha (DNMT3A) from the pancreatic progenitor stage were used to explore control of promoter methylation. Proteomics was performed using affinity purification mass spectrometry and Ca2+ dynamics explored by rapid confocal imaging of Cal-520 AM and Cal-590 AM. Insulin secretion was measured using homogeneous time-resolved fluorescence imaging. Results: Nnat mRNA was differentially expressed in a discrete beta cell population in a developmental stage- and DNA methylation (DNMT3A)-dependent manner. Thus, pseudo-time analysis of embryonic datasets demonstrated the early establishment of Nnat-positive and -negative subpopulations during embryogenesis. NNAT expression is also restricted to a subset of beta cells across the human islet that is maintained throughout adult life. NNAT+ beta cells also displayed a discrete transcriptome at adult stages, representing a subpopulation specialised for insulin production, and were diminished in db/db mice. ‘Hub’ cells were less abundant in the NNAT+ population, consistent with epigenetic control of this functional specialisation. Conclusions/interpretation: These findings demonstrate that differential DNA methylation at Nnat represents a novel means through which beta cell heterogeneity is established during development. We therefore hypothesise that changes in methylation at this locus may contribute to a loss of beta cell hierarchy and connectivity, potentially contributing to defective insulin secretion in some forms of diabetes. Data availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD048465. Graphical Abstract