30 research outputs found

    Developing Learning Scenarios for Educational Web Radio:a Learning Design Approach

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    Identifying Customer Satisfaction Patterns Via Data Mining: The Case Of Greek E-Shops

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    In an online marketplace reality in which customer satisfaction emerges as a key success factor for e- retailers, it becomes crucial to better understand whether the shoppers are satisfied and what factors affect their satisfaction experience. As we are in the Big Data era, Business Analytic techniques could assist us to better understand our customers and their respective satisfaction. To this end, this paper presents a data mining based approach to identify different satisfaction patterns/profiles from satisfaction survey responses. This approach was applied on data from over 120 Greek e-shops across 18 industries. Apart from its theoretical contribution, the proposed approach extracts hidden satisfaction patterns with a view to better understand the specific needs and preferences of customers. These insights may be used to support several decisions, ranging from marketing actions per customer satisfaction profile, to actionable decision making and customer-oriented strategie

    Evaluation of Human Papilloma Virus Diagnostic Testing in Oropharyngeal Squamous Cell Carcinoma: Sensitivity, Specificity, and Prognostic Discrimination

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    Abstract Purpose: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing. Experimental Design: Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above. Results: HPV16-positive OPSCC presented in younger patients (mean 7.5 years younger, P = 0.003) who smoked less than HPV-negative patients (P = 0.007). The proportion of HPV16-positive cases increased from 15% to 57% (P = 0.001) between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable sensitivity (97%) and specificity (94%) compared with the RNA qPCR “gold standard”, as well as being the best discriminator of favorable outcome (overall survival P = 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (P = 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific to recommend in clinical trials when used in isolation. Conclusions: Caution must be exercised in applying HPV16 diagnostic tests because of significant disparities in accuracy and prognostic value in previously published techniques. Clin Cancer Res; 17(19); 6262–71. ©2011 AACR.</jats:p

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Clarification of the role of HIF in lipid metabolism and inflammation

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    Hypoxia inducible factors (HIFs) mediate the survival of normal cells at low oxygen concentrations and cancer cells in the hypoxic tumor microenvironment. HIFs bind to the promoters of their target genes and regulate cellular functions, such as angiogenesis, erythropoiesis, proliferation and apoptosis. Particularly important is the role of HIF in the modification of carbohydrate metabolism by the activation of anaerobic glycolysis. Recent studies have shown that hypoxia and HIFs also affect lipid metabolism by inducing the expression of genes associated with increased storage, uptake and de novo fatty acid synthesis. Hypoxia and HIF appear to be involved in the development of hepatic disorders associated with the development of chronic inflammation, fibrosis and hepatocarcinoma, such as fatty liver disease, which is characterized by hepatic triglyceride accumulation. The purpose of this PhD thesis is the study of the effect of hypoxia and HIF-1α on the expression of target genes related to lipid synthesis, lipid storage and hepatocellular inflammation in cancer cell lines. Study of the effect of hypoxia and HIF-1α on the expression of genes involved in the triglyceride biosynthesis pathway has shown that 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT2) is induced under hypoxic conditions or in the presence of DMOG in Huh7 and HeLa cancer cell lines. Knock-down of HIF-1α using specific siRNA significantly inhibits induction of AGPAT2 expression under hypoxia. In addition, a sequence of the AGPAT2 gene promoter containing 6 possible HREs activates transcription of a reporter gene under hypoxic conditions or after overexpression of HIF-1α in normoxia. Silencing AGPAT2 with specific siRNA leads to reduced lipid droplet accumulation, reduced cell survival, and increased cell sensitivity to the etoposide chemotherapeutic drug under hypoxia. These findings indicate that AGPAT2 is a direct transcriptional target of HIF-1, suggesting that induction of lipid synthesis via HIF-1 contributes to the adaptation and survival of cancer cells under hypoxic conditions. The role of hypoxia and inflammation mediators (TNFα or LPS) in the development of EMT and fibrosis was investigated in Huh7 hepatoma cells. It was observed that hypoxia induces the expression of genes coding for mediators of fibrosis (TGF-β, PDGFC and PAI-1), EMT markers (E-cadherin, FSP-1) and fibrosis markers (LOX, P4HB and P4HA1), and that this induction is not significantly affected by the presence of TNFα or LPS. Silencing of HIF-1α reduces the hypoxic induction of PDGFC, E-cadherin, LOX and P4HA1 genes, indicating that these genes are potential HIF-1 targets. Finally, incubation of cells with SB431542, a specific inhibitor of the TGF-β ALK 5 receptor, reduces HIF-1α expression and affects the expression of TGF-β, LOX, P4HB, P4HA1 and E-cadherin genes in hypoxic conditions. In conclusion, hypoxia and HIF-1 mediating the induction of genes related to fibrosis and EMT are shown to be important regulators of the progression of hepatocyte inflammatory diseases.Οι επαγόμενοι από την υποξία παράγοντες HIF μεσολαβούν την επιβίωση φυσιολογικών κυττάρων σε χαμηλές συγκεντρώσεις οξυγόνου και καρκινικών κυττάρων στο υποξικό μικροπεριβάλλον του όγκου. Οι HIF προσδένονται στους υποκινητές των γονιδίων στόχων τους και ρυθμίζουν κυτταρικές λειτουργίες, όπως η αγγειογένεση, η ερυθροποίηση, ο πολλαπλασιασμός και η απόπτωση. Ιδιαίτερα σημαντικός είναι ο ρόλος των HIF στην τροποποίηση του μεταβολισμού των υδατανθράκων, μέσω της ενεργοποίησης της αναερόβιας γλυκόλυσης. Πρόσφατες μελέτες δείχνουν ότι η υποξία και οι HIFs επηρεάζουν και το μεταβολισμό των λιπιδίων μέσω της επαγωγής γονιδίων που σχετίζονται με αυξημένη αποθήκευση, πρόσληψη και de novo σύνθεση λιπαρών οξέων. H υποξία και οι HIF φαίνεται να εμπλέκονται στην εμφάνιση ηπατικών διαταραχών που συνδέονται με την ανάπτυξη χρόνιας φλεγμονής, ίνωσης και ηπατοκαρκινώματος, όπως η νόσος του λιπώδους ήπατος, που χαρακτηρίζεται από συσσώρευση τριγλυκεριδίων στα ηπατοκύτταρα. Σκοπός της παρούσας διδακτορικής διατριβής είναι η μελέτη της επίδρασης της υποξίας και του HIF-1α στην έκφραση γονιδίων στόχων που σχετίζονται με τη σύνθεση και αποθήκευση λιπιδίων και την ηπατοκυτταρική φλεγμονή σε καρκινικές κυτταρικές σειρές. Μελέτη της επίδρασης της υποξίας και του HIF-1α στην έκφραση γονιδίων που συμμετέχουν στο μονοπάτι βιοσύνθεσης των τριγλυκεριδίων, υποδεικνύει ότι η ακυλομεταφοράση του φωσφατιδικού οξέος AGPAT2, επάγεται σε συνθήκες υποξίας ή παρουσία DMOG σε καρκινικές κυττταρικές σειρές Huh7 και HeLa. Η αποσιώπηση του HIF-1α με ειδικό siRNA αναστέλλει σε σημαντικό βαθμό την επαγωγή της έκφρασης της AGPAT2 στην υποξία. Επιπλέον, αλληλουχία του υποκινητή του γονιδίου της AGPAT2, που περιέχει 6 πιθανές θέσεις HREs ενεργοποιεί τη μεταγραφή ενός γονιδίου αναφοράς σε συνθήκες υποξίας ή κατόπιν υπερέκφρασης του HIF-1α σε νορμοξία. Η αποσιώπηση της AGPAT2 με ειδικό siRNA οδηγεί σε μειωμένη συσσώρευση λιποσταγονιδίων, μειωμένη κυτταρική επιβίωση και αύξηση της ευαισθησίας των κυττάρων στο χημειοθεραπευτικό φάρμακο ετοποσίδιο, σε υποξία. Τα παραπάνω ευρήματα υποστηρίζουν ότι η AGPAT2 αποτελεί άμεσο μεταγραφικό στόχο του HIF-1, επιβεβαιώνοντας ότι η επαγωγή της σύνθεσης λιπιδίων μέσω του HIF-1 συνεισφέρει στην προσαρμογή και την επιβίωση των καρκινικών κυττάρων σε συνθήκες υποξίας. Ο ρόλος της υποξίας και των φλεγμονωδών παραγόντων (ΤΝΡα ή LPS) στην ανάπτυξη EMT και ίνωσης διερευνήθηκε σε κύτταρα ηπατοκαρκινώματος Huh7. Παρατηρήθηκε ότι η υποξία οδηγεί σε επαγωγή έκφρασης γονιδίων μεσολαβητών της ίνωσης (TGF-β, PDGFC και PAI-1), δεικτών ΕΜΤ (E-cadherin, FSP-1) και δεικτών ίνωσης (LOX, P4HB και P4HA1), η οποία δεν επηρεάζεται σημαντικά από φλεγμονώδεις παράγοντες. Αποσιώπηση του HIF-1α προκαλεί μείωση της επαγωγής των γονιδίων PDGFC, E-cadherin, LOX και P4HA1 από την υποξία, καθιστώντας αυτά τα γονίδια πιθανούς στόχους του HIF-1α. Τέλος, επώαση των κυττάρων με τον SB431542, ειδικό αναστολέα του υποδοχέα του TGF-β ALK 5, μειώνει την έκφραση του HIF-1α και επηρεάζει την έκφραση των γονιδίων TGF-β, LOX, P4HB, P4HA1 και E-cadherin σε συνθήκες υποξίας. Συμπερασματικά, η υποξία και ο HIF-1 μεσολαβώντας στην επαγωγή γονιδίων που σχετίζονται με την ίνωση και την EMT, αναδεικνύονται σημαντικοί ρυθμιστές της εξέλιξης φλεγμονωδών παθήσεων των ηπατοκυττάρων

    Καταγραφή της μακροχρόνιας παρακολούθησης παιδιών που γεννήθηκαν μετά από επιβεβαιωμένη οξεία και πιθανώς οξεία τοξοπλάσμωση στην κύηση

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    Στη γέννηση οι περισσότερες περιπτώσεις συγγενούς τοξοπλάσμωσης είναι ασυμπτωματικές. Τα νεογνά υψηλού κινδύνου πρέπει να εξετάζονται ενδελεχώς, ενώ η θεραπεία μειώνει τη συχνότητα επιπλοκών. Ο σκοπός αυτής της αναδρομικής μελέτης κοορτής είναι να καταγραφεί η μακροχρόνια παρακολούθηση παιδιών γεννημένων μετά από επιβεβαιωμένη οξεία και πιθανώς οξεία τοξοπλάσμωση στην κύηση. Η συλλογή δείγματος έγινε από δύο ιατρεία λοιμώξεων (Αττική, 2006-2019). Οι γυναίκες ρωτήθηκαν τηλεφωνικώς για το παιδί τους-τελευταία μέτρηση IgG ανοσοσφαιρίνης και πιο πρόσφατη οφθαλμολογική εξέταση. Συνολικά 75/95 γυναίκες απάντησαν και 76 παιδιά καταγράφηκαν. Όλες οι μητέρες έλαβαν αγωγή και 59 υπεβλήθησαν σε αμνιοπαρακέντηση. Θετική PCR στο αμνιακό είχαν 7 μητέρες, χωρίς όμως επιβεβαίωση με καλλιέργεια πειραματοζώων. Όλα τα παιδιά ελέγχθηκαν ως νεογνά για τοξοπλάσμωση, 9 συνολικά έλαβαν θεραπεία (διάμεση διάρκεια 5 μήνες), ενώ 2 έλαβαν για 12. Τα περισσότερα παιδιά (74/76) βρέθηκαν αρνητικά για παρουσία IgG αντισωμάτων και όλα είχαν φυσιολογική βυθοσκόπηση. Η ΘΠΑ (PPV) της PCR στο αμνιακό υγρό υπολογίστηκε σε 28,6%. Από τις 37 γυναίκες με πιθανά οξεία τοξοπλάσμωση, καμία δεν είχε θετική PCR αμνιακού και κανένα από τα 39 παιδιά δεν είχε ΣΤ. Εφόσον τα περισσότερα παιδιά της έρευνας δεν είχαν IgG, εικάζεται ότι το αποτέλεσμα της PCR αμνιακoύ υγρού ήταν ψευδώς θετικό. Είναι εμφανής η ανάγκη για παραπομπή σε κέντρα αναφοράς, ώστε να εξασφαλιστεί η σωστή παρακολούθηση.Most cases of congenital toxoplasmosis are asymptomatic at birth. High-risk neonates should be tested thoroughly, while treatment administration decreases the incidence of complications. The aim of this retrospective cohort study was to collect medical data on the long-term follow-up of children born after documented primary, and possibly acute toxoplasma infection during gestation. Data was collected from two outpatient clinics on gestational infections (Attica, 2006-2019). Women were interviewed by phone and asked about their offspring-most recent toxoplasma immunoglobulin G (IgG) test results and results from the latest ocular examination. Overall, 75/95 women responded and 76 children were enrolled. All mothers received treatment and 59 underwent amniocentesis. Although 7 amniocenteses were positive by PCR none was confirmed by culture. All 76 children were tested as neonates for toxoplasmosis, 9 received treatment for a median of 5 months, two babies were treated for 12 months. Most children (74/76) were tested negative for toxo-IgG antibodies and all had normal fundoscopy. The PPV of PCR on amniotic fluid was 28,6%. Among the 37 women with possibly acute toxoplasmosis, none had positive PCR results on amniotic fluid and no child out of 39 in total was diagnosed with CT. Since most children lost transplacentally transferred maternal antibodies, one may postulate that toxoplasma DNA detection by PCR in amniotic fluid was false positive. The need for referral to specialized clinics to ensure treatment and follow up is evident

    Endoscopic ultrasonography for gastric submucosal lesions

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    Gastric submucosal tumors (SMTs) are a rather frequent finding, occurring in about 0.36% of routine upper GI-endoscopies. EUS has emerged as a reliable investigative procedure for evaluation of these lesions. Diagnostic Endoscopic ultrasonography (EUS) has the ability to differentiate intramural tumors from extraluminal compressions and can also show the layer of origin of gastric SMTs. Tumors can be further characterized by their layer of origin, echo pattern and margin. EUS-risk criteria of their malignant potential are presented, although the emergence of EUS-guided fne needle aspiration (EUS-FNA) has opened new indications for transmural tissue diagnosis and expanded the possibilities of EUS in SMTs of the stomach. Tissue diagnosis should address whether the SMT is a Gastrointestinal stromal tumour (GIST) or another tumor type and evaluate the malignant potential of a given GIST. However, there seems to be a lack of data on the optimal strategy in SMTs suspected to be GISTs with a negative EUS-FNA tissue diagnosis. The current management strategies, as well as open questions regarding their treatment are also presented

    A Systematic Review of Peripheral and Central Nervous System Involvement of Rheumatoid Arthritis, Systemic Lupus Erythematosus, Primary Sjögren&apos;s Syndrome, and Associated Immunological Profiles

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    Both central (CNS) and peripheral nervous system (PNS) complications are frequent and varied in connective tissue diseases. A systematic review was conducted between 1989 and 2014 in the databases Medline, Scopus, and Cochrane Library using the search terms, peripheral and central nervous complications and immunological profiles, to identify studies in specific connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren&apos;s syndrome. A total of 675 references were identified, of which 118 were selected for detailed analysis and 22 were included in the final review with a total of 2338 participants. Our search focused only on studies upon connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren&apos;s syndrome associated with seroimmunological data. The reported prevalence of CNS involvement ranges from 9 to 92% across the reported studies. However, the association between CNS and PNS manifestations and seroimmunological profiles remains controversial. Τo date, no laboratory test has been shown as pathognomonic neither for CNS nor for PNS involvement
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