Tetralogy of Fallot with absent pulmonary valve syndrome : an imaging challenge

Congenital absence of pulmonary valve syndrome (APV) represents a fascinating and unique variant of congenital heart disease. It was Chever in 1847 who first described this unique structural heart defect. The anatomic features consist of an incompletely formed, rudimentary pulmonary valve that is both stenotic and regurgitant, massively dilated pulmonary arteries and a large malaligned outlet ventricular septal defect. There is an association of this defect with Tetralogy of Fallot (ToF) due to which this condition is often referred to as Tetralogy of Fallot/absent pulmonary valve syndrome. Another characteristic feature is that there is virtually always absence of a patent ductus arteriosus. That has been hypothesized as being responsible for the pathogenesis of pulmonary artery dysplasia.peer-reviewe

Πως αλλάζει η αντιμετώπιση των πανδημιών στη διάρκεια των χρόνων και τι αποτελέσματα προκύπτουν

Η πανδημία που ξέσπασε στην Κίνα το 2019 αποτέλεσε μια από τις μεγαλύτερες υγειονομικές κρίσεις του τελευταίου αιώνα και την αφορμή για τη εκπόνηση της παρούσας διπλωματικής εργασίας. Αρχικά στο γενικό μέρος αναφερόμαστε στις σημαντικότερες πανδημίες που στιγμάτισαν την ανθρωπότητα: την ισπανική γρίπη του 1918, την ασιατική γρίπη του 1957, την γρίπη του Χονγκ Κονγκ του 1968 , την γρίπη των χοίρων του 2009 και τέλος την πανδημία του SARS-CoV2 του2019. Εν συνεχεία, στο ειδικό μέρος συγκρίνουμε μεταξύ τους τις προαναφερθείσες κρίσεις ως προς τον αριθμό των κρουσμάτων , ως προς τις ανθρώπινες απώλειες, ως προς τα μέτρα που λήφθηκαν για την αντιμετώπισή τους και ως προς τις συνέπειες που επέφεραν στην κοινωνία με το πέρας τους. Τέλος, καθίσταται σαφές ότι η καταγραφή και μελέτη των δεδομένων σχετικών με την πορεία και την αντιμετώπιση της κρίσης που επιφέρει μια πανδημία είναι ουσιώδους σημασίας για την πρόληψη και καταστολή ακόλουθων κρίσεων.The pandemic that broke out in China in 2019 was one of the biggest health crises of the last century and the reason for drafting this diploma thesis. Initially, in the General Part we refer to the most important pandemics that stigmatized humanity: the Spanish flu of 1918, the Asian flu of 1957, the Hong Kong flu of 1968, the Swine flu of 2009 and finally the SARS-CoV2 pandemic of 2019. Then, in the Special Part we compare the aforementioned crisis with each other in terms of the number of cases, in terms of human losses, in terms of the measures taken to deal with them and in terms of the consequences they brought to society at their end. Finally, it becomes clear that the documentation and study of data related to the course and response to the crisis brought about by a pandemic is essential for the prevention and suppression of subsequent crises

Left ventricular hypertrophy induced by weight excess in children and adolescents

Background: Obesity is associated with left ventricular hypertrophy, an independent risk factor of  cardiovascular morbidity. The aim of the present study was to evaluate obesity-induced left ventricular hypertrophy in overweight/obese children and adolescents and demonstrate possible early echocardiographic abnormalities in overweight children compared to obese children.Methods: The study included 55 children and adolescents (24 overweight and 31 with  obesity) and 55 normal weight children. Standard M-mode echocardiography was performed in all participants. Parameters associated with left ventricular structure and function were recorded and statistically analysed.Results: Left ventricular hypertrophy (LVmass/height3>95th percentile) was diagnosed in 33% of overweight children and 66.5% of children with obesity (p=0.01). Mean left ventricular mass/height3 and left ventricular mass/height2.7 were significantly higher in children with obesity compared to overweight children, as well as compared to the normal weight children. On the contrary, mean values of the index left ventricular mass/body surface area did not differ significantly among study groups. Furthermore, mean left ventricular end-diastolic diameter, interventricular septal thickness and left atrial diameter, presented significant differences among the 3 studied groups, even between overweight andnormal weight children. Both systolic and diastolic function of left ventricular function were normal in our study groups.  Conclusions: Overweight children demonstrate significant early changes in left ventricular wall dimensions compared to normal weight children, while children with obesity additionally present a significant increase in left ventricular  mass. Future studies are needed to explore the effect of dietary programs and other interventions on cardiac function parameters in these children

Κίνδυνος Τσουνάμι και Ολοκληρωμένη Διαχείριση Παράκτιας Ζώνης στο Νότιο Αιγαίο

Στη μελέτη αυτή γίνεται προσπάθεια σύνδεσης της έννοιας της ολοκληρωμένης διαχείρισης Παράκτιας Ζώνης, με την επικινδυνότητα εκδήλωσης τσουνάμι στην περιοχή των νοτίων Κυκλάδων. Αρχικά παρουσιάζεται αναλυτικά η έννοια και οι στόχοι της Ολοκληρωμένης Διαχείρισης Παράκτιας Ζώνης, το νομοθετικό πλαίσιο εφαρμογής της σε Ελλάδα και Ευρώπη και οι φυσικοί κίνδυνοι που αντιμετωπίζουν οι παράκτιες περιοχές καταλήγοντας στο φυσικό κίνδυνο που καλείται τσουνάμι. Παρουσιάζονται τα βασικά χαρακτηριστικά ενός τσουνάμι, πως δημιουργείται, πως αυτό συμπεριφέρεται φτάνοντας στην παράκτια ζώνη και οι περιοχές οι οποίες θεωρούνται ως πιθανοί χώροι εκδήλωσης ενός τέτοιου φαινομένου στην Ελλάδα. Στην συνέχεια δίνεται η γεωμορφολογική και γεωλογική περιγραφή της περιοχής μελέτης, όπου αποτελείται από τα νησιά Φολέγανδρος, Σίκινος, Ηρακλειά, Σχοινούσα, Κουφονήσια, Κέρος, Αμοργός, Αστυπάλαια, Ανάφη, Σαντορίνη και φυσικά την θαλάσσια περιοχή που τα περιβάλει. Μια περιγραφή, από την οποία εξακριβώνεται οι επικινδυνότητα δημιουργίας τσουνάμι στην περιοχή, κυρίως προερχόμενη από υποθαλάσσια κατολίσθηση. Η Μεθοδολογία που ακολουθείται για να μπορέσουν να αναδειχτούν οι επιπτώσεις που θα μπορούσε να έχει ένα τσουνάμι στις νότιες Κυκλάδες σήμερα, ξεκινάει με μια συγκέντρωση γεγονότων από όλο τον κόσμο, με περιστατικά εκδήλωσης τσουνάμι προερχόμενα από τις τρεις βασικές κατηγορίες γενεσιουργίας (σεισμός, ηφαίστειο, κατολίσθηση), συμπεριλαμβανομένου δυο γεγονότων που συνέβησαν στην περιοχή μελέτης, καθώς και το μετρούμενο max run up που έδωσε το κάθε ένα από αυτά τα γεγονότα. Από την συγκέντρωση αυτών των πληροφοριών, εξάγονται 7 ζώνες με εύροι τιμών πιθανών run up που θα μπορούσε να παρατηρηθούν στις ακτές του νησιωτικού συμπλέγματος που μελετάμε. Παράλληλα με αυτό τον τρόπο, οριοθετείται η παράκτια ζώνη σε όλα τα νησιά. Εισάγοντας τα δεδομένα στο πρόγραμμα ArcGIS, ζωνοποιείται η παράκτια ζώνη και με αυτό τον τρόπο απεικονίζεται η επικινδυνότητα βαθμιαία, για κάθε νησί. Η ζωνοποίηση της επικινδυνότητας παρουσιάζεται, σε συνδυασμό με τις τιμές run up 6 που είχαν καταγραφεί στο τελευταίο τσουνάμι στην περιοχή, αυτό της Αμοργού, το 1956. Ακολουθεί η ανάδειξη των επιπτώσεων η οποία ξεκινά με μια αναδρομή στις επιπτώσεις που καταγράφτηκαν το 1956 στην ευρύτερη περιοχή του νοτίου Αιγαίου. Στην συνέχεια η ζωνοποίηση εφαρμόζεται πάνω στις σημερινές χρήσεις γης των νησιών αλλά και σε δορυφορικές εικόνες του τώρα, αναδεικνύοντας με αυτό τον τρόπο τι θα συμβεί, εάν ένα τσουνάμι πλήξει την περιοχή των νοτίων Κυκλάδων στις μέρες μας σε κατοικημένες, τουριστικές, βιομηχανικές και γεωργικές περιοχές αντίστοιχα. Μετά την ανάδειξη των επιπτώσεων, προτείνονται μέτρα πρόληψης, τα οποία ήδη είναι εφαρμόσιμα σε χώρες που αντιμετωπίζουν το φαινόμενο τσουνάμι και τα οποία θα μπορούσαν να εφαρμοστούν και στην χώρα μας. Γίνεται σύνδεση της λήψης μέτρων με την έννοια της Ολοκληρωμένης Διαχείρισης Παράκτιας Ζώνης, τονίζοντας ότι η λήψη μέτρων στο φαινόμενο τσουνάμι αλληλοεξαρτάται με τις αρχές της βιώσιμης ανάπτυξης. Η μελέτη ολοκληρώνεται με την εξαγωγή συμπερασμάτων με βασικότερο αυτό της ανάγκης να συμπεριληφθεί η πρόληψη του κινδύνου τσουνάμι σε κάθε στρατηγική Ολοκληρωμένης Διαχείρισης Παράκτιας Ζώνης για τις νότιες Κυκλάδες.The focus of this present research (thesis) lies on associating the concept of integrated coastal zone management with the potential risk of tsunamis in the Cyclades. At the beginning of the thesis the meaning and the objectives of integrated coastal zone management are presented as well as the legislative framework in Greece and Europe respectively. Furthermore, the natural risks that coastal areas face leading to tsunami are examined together with the basic features of this phenomenon, its behavior when it hits a coastal zone and the potential areas of a tsunami outbreak in Greece. After that, the focus turns on the geological and geomorphological description of the area under discussion which mainly consists of the following islands and the sea that surrounds them: Folegandros, Sikinos, Iraklia, Schoinousa, Koufonisia, Keros, Amrogos, Astypalaia, Anafi and Santorini. This particular description verifies the danger of a tsunami creation in the area mainly caused by underwater landslide. As far as the methodology is concerned, in order to highlight the consequences a tsunami could have on Southern Cyclades at present time, a certain pattern is followed concentrating events from all over the world which include certain tsunami incidents caused by the three categories: earthquake, volcano, and landslide. Furthermore, we take into consideration two particular events that took place in the specific area as well as the rate of max run up which each of two events gave and as well of all world events. After carefully examining this information, we can conclude to 7 zones with a range of, which can be observed on the coasts of the island complex. At the same time, by following this pattern, the coastal zone of each island is designated. By inserting the data collected in the ArcGIS, the coastal area is divided into zones; hence the potential risk for every island is illustrated. This zoning of risk is presented together with the run up rates which have been documented in the latest tsunami on the island of Amorgos in 1956. In the next chapter, the effects of tsunami are highlighted starting with a brief history of the tsunami that took place in the wider area of the Southern Aegean Sea. 8 Next, the idea of zoning is applied to the current uses of land on the islands paired with pictures taken from satellites. In this way it is underlined what is going to happen in case a tsunami hits the area of norther Cyclades and the potential impact it will have on the residential, tourist, industrial and agricultural areas accordingly. After stressing the effects, preventive measures are recommended, which are already applicable to countries which face the phenomenon of tsunamis, while, they could be implemented in our country as well. An attempt is being made to associate the measures that have to be taken with the idea of integrated coastal zone putting emphasis on the fact that taking measures heavily rests on the principles of sustainable development. The research is completed reaching to conclusions, most basic one being the one of the necessity to include the prevention of the risk of a tsunami in every strategy of the integrated coastal zone management for south Cyclades

Drug repurposing for rare: progress and opportunities for the rare disease community

Repurposing is one of the key opportunities to address the unmet rare diseases therapeutic need. Based on cases of drug repurposing in small population conditions, and previous work in drug repurposing, we analyzed the most important lessons learned, such as the sharing of clinical observations, reaching out to regulatory scientific advice at an early stage, and public-private collaboration. In addition, current upcoming trends in the field of drug repurposing in rare diseases were analyzed, including the role these trends could play in the rare diseases’ ecosystem. Specifically, we cover the opportunities of innovation platforms, the use of real-world data, the use of artificial intelligence, regulatory initiatives in repurposing, and patient engagement throughout the repurposing project. The outcomes from these emerging activities will help progress the field of drug repurposing for the benefit of patients, public health and medicines development

DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification

AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons, and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement, and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology which resolved 17/22 and 15/21 respectively where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological, and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach

Mediterranean circulation perturbations over the last five centuries : relevance to past Eastern Mediterranean Transient-type events

Unidad de excelencia María de Maeztu MdM-2015-0552The Eastern Mediterranean Transient (EMT) occurred in the Aegean Sea from 1988 to 1995 and is the most significant intermediate-to-deep Mediterranean overturning perturbation reported by instrumental records. The EMT was likely caused by accumulation of high salinity waters in the Levantine and enhanced heat loss in the Aegean Sea, coupled with surface water freshening in the Sicily Channel. It is still unknown whether similar transients occurred in the past and, if so, what their forcing processes were. In this study, sediments from the Sicily Channel document surface water freshening (SCFR) at 1910 ± 12, 1812 ± 18, 1725 ± 25 and 1580 ± 30 CE. A regional ocean hindcast links SCFR to enhanced deep-water production and in turn to strengthened Mediterranean thermohaline circulation. Independent evidence collected in the Aegean Sea supports this reconstruction, showing that enhanced bottom water ventilation in the Eastern Mediterranean was associated with each SCFR event. Comparison between the records and multi-decadal atmospheric circulation patterns and climatic external forcings indicates that Mediterranean circulation destabilisation occurs during positive North Atlantic Oscillation (NAO) and negative Atlantic Multidecadal Oscillation (AMO) phases, reduced solar activity and strong tropical volcanic eruptions. They may have recurrently produced favourable deep-water formation conditions, both increasing salinity and reducing temperature on multi-decadal time scales

Physical forcing and physical/biochemical variability of the Mediterranean Sea: a review of unresolved issues and directions for future research

This paper is the outcome of a workshop held in Rome in November 2011 on the occasion of the 25th anniversary of the POEM (Physical Oceanography of the Eastern Mediterranean) program. In the workshop discussions, a number of unresolved issues were identified for the physical and biogeochemical properties of the Mediterranean Sea as a whole, i.e., comprising the Western and Eastern sub-basins. Over the successive two years, the related ideas were discussed among the group of scientists who participated in the workshop and who have contributed to the writing of this paper. Three major topics were identified, each of them being the object of a section divided into a number of different sub-sections, each addressing a specific physical, chemical or biological issue: 1. Assessment of basin-wide physical/biochemical properties, of their variability and interactions. 2. Relative importance of external forcing functions (wind stress, heat/moisture fluxes, forcing through straits) vs. internal variability. 3. Shelf/deep sea interactions and exchanges of physical/biogeochemical properties and how they affect the sub-basin circulation and property distribution. Furthermore, a number of unresolved scientific/methodological issues were also identified and are reported in each sub-section after a short discussion of the present knowledge. They represent the collegial consensus of the scientists contributing to the paper. Naturally, the unresolved issues presented here constitute the choice of the authors and therefore they may not be exhaustive and/or complete. The overall goal is to stimulate a broader interdisciplinary discussion among the scientists of the Mediterranean oceanographic community, leading to enhanced collaborative efforts and exciting future discoveries

Realising consilience: How better communication between archaeologists, historians and natural scientists can transform the study of past climate change in the Mediterranean

This paper reviews the methodological and practical issues relevant to the ways in which natural scientists, historians and archaeologists may collaborate in the study of past climatic changes in the Mediterranean basin. We begin by discussing the methodologies of these three disciplines in the context of the consilience debate, that is, attempts to unify different research methodologies that address similar problems. We demonstrate that there are a number of similarities in the fundamental methodology between history, archaeology, and the natural sciences that deal with the past (“palaeoenvironmental sciences”), due to their common interest in studying societal and environmental phenomena that no longer exist. The three research traditions, for instance, employ specific narrative structures as a means of communicating research results. We thus present and compare the narratives characteristic of each discipline; in order to engage in fruitful interdisciplinary exchange, we must first understand how each deals with the societal impacts of climatic change. In the second part of the paper, we focus our discussion on the four major practical issues that hinder communication between the three disciplines. These include terminological misunderstandings, problems relevant to project design, divergences in publication cultures, and differing views on the impact of research. Among other recommendations, we suggest that scholars from the three disciplines should aim to create a joint publication culture, which should also appeal to a wider public, both inside and outside of academia.This paper emerged as a result of a workshop at Costa Navarino and the Navarino Environmental Observatory (NEO), Greece in April 2014, which addressed Mediterranean Holocene climate and human societies. The workshop was co-sponsored by IGBP/PAGES, NEO, the MISTRALS/PaleoMex program, the Labex OT-Med, the Bolin Centre for Climate Research at Stockholm University, and the Institute of Oceanography at the Hellenic Centre for Marine Research. We also acknowledge funding from the National Science Centre, Poland, within the scheme of the Centre's postdoctoral fellowships (DEC-2012/04/S/HS3/00226 (A.I)); the Swedish Research Council (grant numbers 421-2014-1181 (E.W.) and 621-2012-4344 (K.H.)); CSIC-Ramón y Cajal post-doctoral program RYC-2013-14073 and Clare Hall College, Cambridge, Shackleton Fellowship (B.M.); the EU/FP7 Project ‘Sea for Society’ (Science and Society - 2011-1, 289066)

Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study

Background: Bayesian networks (BNs) are machine-learning-based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients.Methods and findings: Within the European Network for Individualized Treatment of Endometrial Cancer (ENI-TEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58-71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59-74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60-73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76-0.88) for LNM and 0.82 (95% CI 0.77-0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78-0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with Conclusions: In this study, we illustrated how BNs can be used for individualizing clinical decision-making in oncology by incorporating easily accessible and multimodal biomarkers. The network shows the complex interactions underlying the carcinogenetic process of endometrial cancer by its graphical representation. A prospective feasibility study will be needed prior to implementation in the clinic.</div