Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non–Small-Cell Lung Cancer

IntroductionThere is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non–small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed.MethodsIn this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non–small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64–68 Gy over days 1–45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate.ResultsFrom June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5–60.0%); PC: 58.4% (95% CI, 42.6–71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0–64.8%); PC: 55.8% (95% CI, 38.0–70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0–12.6 months); PC: 13.1 months (95% CI, 8.3–not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9–NE); PC: 27.0 (95% CI, 23.2–NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy.ConclusionsBecause of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated

Long‐term issues and supportive care needs of adolescent and young adult childhood brain tumour survivors and their caregivers: A systematic review

Objective: Long‐term issues following diagnosis and treatment of a childhood brain tumour often become apparent as the survivor enters adolescence and young adulthood. Their caregivers may additionally face long‐term impacts on their emotional and psychological functioning. This review synthesised evidence on the issues and supportive care needs of adolescent and young adult (AYA) survivors of a brain tumour diagnosed in childhood and their caregivers. Methods: Electronic databases were searched up until September 2017. All studies reporting on issues or needs of childhood brain tumour survivors (aged 14‐39) and their caregivers were included. Narrative synthesis methods were used to summarise, integrate, and interpret findings. Results: Fifty‐six articles (49 studies) met the inclusion criteria. Social issues (ie, isolation and impaired daily functioning) were most commonly reported by survivors, followed by cognitive (ie, impaired memory and attention) and physical issues (ie, endocrine dysfunctions and fatigue). Survivors experienced poorer social functioning and sexual functioning and were less likely to be employed or have children, when compared with other AYA cancer survivors. Caregivers experienced reduced support as the survivor moved into young adulthood. Caregivers reported uncertainty, increased responsibilities, and problems maintaining their own self–well‐being and family relationships. Few studies reported on supportive care needs. Survivors expressed a need for better educational support and age‐specific psychosocial services. Conclusions: Surviving a childhood brain tumour can be particularly challenging for AYA survivors and their caregivers. Robust structured research is needed to identify specific support needs of both survivors and their caregivers and how these can be optimally addressed

Νεότερες-στοχευμένες από του στόματος θεραπείες για τις Ιδιοπαθείς Φλεγμονώδεις Νόσους του Εντέρου και μελλοντικές προοπτικές

Τα Ιδιοπαθή φλεγμονώδη νοσήματα του εντέρου (ΙΦΝΕ) περιλαμβάνουν τη νόσο Crohn (NC) και την ελκώδη κολίτιδα (ΕΚ) και αποτελούν μια χρόνια - αυτοάνοση διαταραχή της γαστρεντερικής οδούς με ποικίλης βαρύτητας κλινικές εκδηλώσεις. Παλιότερα, η θεραπεία τους βασιζόταν αποκλειστικά στη χορήγηση αμινοσαλικυλικών, κορτικοστεροειδών και ανοσοτροποποιητικών φαρμάκων. Τις τελευταίες δύο δεκαετίες με την εφαρμογή των βιολογικών παραγόντων, έχει επιτευχθεί η τροποποίηση της φυσικής πορείας της νόσου σε ασθενείς με βαριά εκδήλωση αυτής. Ωστόσο, μεγάλο ποσοστό των ασθενών δεν ανταποκρίνονται σε αυτές τις θεραπείες και σε συνδυασμό με το υψηλό κόστος και πιθανές ανεπιθύμητες ενέργειες τους, ιδιαίτερο ενδιαφέρον υπάρχει για την ανάπτυξη μικρών, στοχευμένων και αποτελεσματικών από του στόματος μοριακών φαρμάκων. Σκοπός της παρούσας ανασκόπησης είναι η παράθεση διαφορετικών μοριακών μονοπατιών μέσω του οποίου δρουν αυτά τα φάρμακα και των σημαντικότερων ευρημάτων από τις κλινικές μελέτες τους φάσης ΙΙ και ΙΙΙ. Από αυτά σε πιο προχωρημένο στάδιο ανάπτυξης είναι οι αναστολείς Janus kinase (JAK) υποδοχέων και οι τροποποιητές του υποδοχέα σφιγγοσίνης (S1P). Το tofacitinib (αναστολέας JAK) πήρε πρόσφατα έγκριση για θεραπεία μέτριας-βαριάς ΕΚ και άλλοι JAK αναστολείς (filgotinib, upadacitinib) έχουν δείξει ικανοποιητικά αποτελέσματα από μελέτες φάσης ΙΙ. Αντίστοιχα, δεδομένα ασφάλειας και αποτελεσματικότητας έχουν προκύψει για το ozanimod και etrasimod (τροποποιητές S1P υποδοχέα), το AJM-300 (ανταγωνιστή υποδοχέα ιντεγκρινών), το LT-02 (τροποποιημένης αποδέσμευσης φωσφατιδυλοχολίνη) και το Morgensen (αναστολέας πρωτεΐνης SMAD7) με ορισμένα από αυτά να ελέγχονται σε κλινικές μελέτες φάσης ΙΙΙ. Παράλληλα, αρκετοί ακόμα από του στόματος παράγοντες βρίσκονται σε φάση ανάπτυξης και κλινικών δοκιμών. Επομένως, αναμένεται σύντομα να εμπλουτιστεί η θεραπευτική φαρέτρα των ΙΦΝΕ με νεότερες, στοχευμένες, από του στόματος μοριακές θεραπείες, πέραν των παρεντερικώς χορηγούμενων βιολογικών θεραπειών, με απώτερο σκοπό την ύφεση της νόσου και τη βελτίωση της ποιότητας ζωής των ασθενών.Inflammatory bowel disease (IBD), including Crohn's disease (NC) and Ulcerative colitis (UC), is a chronic autoimmune disorder of the gastrointestinal tract with varying degrees of clinical manifestations. In the past, their treatment was based solely on the administration of aminosalicylates, corticosteroids and immunomodulatory drugs. In the last two decades, with the application of biological agents, it has been achieved the modification of the natural history of the disease. However, a large proportion of patients do not respond to these therapies and in combination with their high cost and potential side effects, there is particular interest in developing small, targeted and effective oral molecular drugs. The purpose of this review is to list the different molecular pathways through which these drugs act and the most important findings from Phase II and III clinical trials. Among these, Janus kinase inhibitors (JAK) and sphingosine receptor modulators (S1P) are at a more advanced stage of development. Tofacitinib (JAK inhibitor) has recently been approved for the treatment of moderate to severe UC and other JAK inhibitors (filgotinib, upadacitinib) have shown satisfactory results from phase II studies. Furthermore, safety and efficacy data have been obtained for ozanimod and etrasimod (S1P receptor modulators), AJM-300 (integrin receptor antagonist), LT-02 (modified release phosphatidylcholine) and Morgensen (SMAD7 inhibitor) with some of them being tested in phase III clinical trials. At the same time, several other oral agents are still in development. Therefore, it is expected that the therapeutic choices for IBD will soon be enriched with targeted, oral molecular therapies, in addition to parenterally administered biological therapies, with the ultimate goal being the remission of the disease and the improvement of patients’ quality of life

Αντιδραστήρας θειοαναγωγικών βακτηρίων για την επεξεργασία υγρών βιομηχανικών αποβλήτων που περιέχουν μέταλλα

98 σ.Μεταπτυχιακή Εργασία -- Εθνικό Μετσόβιο Πολυτεχνείο. Διεπιστημονικό - Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) "Περιβάλλον και Ανάπτυξη"Στην παρούσα εργασία μελετήθηκε η λειτουργία ενός βιολογικού αντιδραστήρα θειοαναγωγικών βακτηρίων, εργαστηριακής κλίμακας σταθερής κλίνης και ανοδικής ροής, προκειμένου να αξιολογηθεί συγκριτικά το θρεπτικό υπόστρωμα μεταξύ δύο πηγών άνθρακα: γαλακτικού και αιθανόλης. Ο αντιδραστήρας λειτούργησε σε κλειστούς διαδοχικούς κύκλους τροφοδοσίας έπειτα από τον εμβολιασμό με μικτή καλλιέργεια θειοαναγωγικών βακτηρίων. Τέθηκε αρχικά σε λειτουργία με διάλυμα που περιείχε γαλακτικό νάτριο, θειικά ιόντα και σίδηρο (100 mg/l). Ακολούθησε η σταδιακή αντικατάσταση του γαλακτικού από αιθανόλη σε διάστημα 30 ημερών. Έπειτα προστέθηκαν τα μέταλλα: Zn, Cu, Ni σε συγκέντρωση 100 mg/l και έγινε η παρακολούθηση της απόδοσης του αντιδραστήρα ως προς την αναγωγή των θειικών ιόντων και την καταβύθιση των μετάλλων Fe, Zn, Cu και Ni. Στη συνέχεια η αιθανόλη ελαττώθηκε στη στοιχειομετρικά απαιτούμενη συγκέντρωση για την αναγωγή των θειικών ιόντων. Μέσω της παρακολούθησης των παραμέτρων του pH, της συγκέντρωσης των θειικών ιόντων, των ιόντων του δισθενούς θείου, του συνολικού οργανικού άνθρακα και των διαλυτών μετάλλων (παράμετροι λειτουργίας του βιοαντιδραστήρα) διαπιστώθηκε η επιτυχής λειτουργία του αντιδραστήρα και η ανοχή του βακτηριακού πληθυσμού στις μεταβολές της σύστασης του διαλύματος τροφοδοσίας. Κύρια συμπεράσματα είναι ότι ο αντιδραστήρας λειτούργησε επιτυχώς καθ’ όλη τη διάρκεια των διαδοχικών κύκλων όπως φαίνεται από την παραγωγή αλκαλικότητας, την αναγωγή των θειικών ιόντων, την οξείδωση του οργανικού υποστρώματος και την ποσοτική καταβύθιση των μετάλλων. Τέλος μελετήθηκε η μεταβολή των παραμέτρων λειτουργίας σε συνάρτηση με το χρόνο ξεκινώντας από καθορισμένες αρχικές συνθήκες (πειράματα κινητικής).In the present study, the operation of a laboratory-scale sulphate-reducing reactor, operating in upflow mode, is described under two different carbon sources/electron donors: lactate and ethanol. The bioreactor was operating continuously for 115 days at room temperature. A mixed culture of sulphate-reducing bacteria was added in the bioreactor along with a variation of Postgate’s medium, containing lactate, sulphates and iron (Fe, 100 mg/l). Lactate feed was replaced stepwise with ethanol over 30 days. After the replacement of lactate by ethanol, ethanol was inserted in excess to sulphate with iron (Fe, 100 mg/l). In the following days three more heavy metals were inserted in the bioreactor (Zn, Cu and Ni). Finally, ethanol was added stoichiometrically to sulphate. Samples were taken systematically and apart from pH measurement the concentration of sulphates, sulphide, organic matter and soluble metals (operational parameters of the bioreactor) was determined. Out of these measurements it was concluded that the bioreactor was successfully adjusted to the changing medium. In specific as a result of the alkalinity generated during the SRB metabolism, pH reached a value of 7.5-8.5, sulphates were reduced, the organic substrate was oxidized and all metals were quantitatively precipitated. Apart from the experiments on the different carbon source, batch kinetic experiments were also conducted in the bioreactor starting with different conditions each time.Βασιλική Π. Κουστέν

Executive function deficits in pediatric cerebellar tumor survivors

Development Psychopathology in context: clinical setting

Arabidopsis FHY3 specifically gates phytochrome signaling to the circadian clock

Circadian gating of light signaling limits the timing of maximum responsiveness to light to specific times of day. The fhy3 (for far-red elongated hypocotyl3) mutant of Arabidopsis thaliana is involved in independently gating signaling from a group of photoreceptors to an individual response. fhy3 shows an enhanced response to red light during seedling deetiolation. Analysis of two independent fhy3 alleles links enhanced inhibition of hypocotyl elongation in response to red light with an arrhythmic pattern of hypocotyl elongation. Both alleles also show disrupted rhythmicity of central-clock and clock-output gene expression in constant red light. fhy3 exhibits aberrant phase advances under red light pulses during the subjective day. Release-from-light experiments demonstrate clock disruption in fhy3 during the early part of the subjective day in constant red light, suggesting that FHY3 is important in gating red light signaling for clock resetting. The FHY3 gating function appears crucial in the early part of the day for the maintenance of rhythmicity under these conditions. However, unlike previously described Arabidopsis gating mutants that gate all light signaling, gating of direct red light–induced gene expression in fhy3 is unaffected. FHY3 appears to be a novel gating factor, specifically in gating red light signaling to the clock during daytime

Increasing childhood vaccination coverage of the refugee and migrant population in greece through the european programme philos, april 2017 to april 2018

After the 2016 Balkan route border closures, vaccination of refugee children in Greece was mainly performed by non-governmental organisations. Activities varied between camps, resulting in heterogeneity of vaccination coverage (VC). In April 2017, the European programme ‘PHILOS - Emergency health response to refugee crisis’ took over vaccination coordination. Interventions were planned for the first time for refugee children in the community and unaccompanied minors at safe zones. From April 2017-April 2018, 57,615 vaccinations were performed against measlesmumps- rubella (MMR) (21,031), diphtheria-tetanuspertussis (7,341), poliomyelitis (7,652), pneumococcal disease (5,938), Haemophilus influenzae type b (7,179) and hepatitis B (8,474). In April 2018, the vaccination status of children at camps (reception and identification centres and community facilities such as hostels/ hotels were excluded) was recorded and VC for each disease, stratified by dose, nationality and camp size, was calculated. More than 80% of the children received the first MMR dose, with VC dropping to 45% for the second dose. For all other vaccines, VC was < 50% for the first dose in children aged 0-4 years and < 25% for the second dose. Despite challenges, PHILOS improved planning and monitoring of vaccination activities; however, further efforts towards improving VC in refugee children are needed. © 2019, European Centre for Disease Prevention and Control (ECDC). All rights reserved