11 research outputs found

    Decision-making processes in shipping acquisitions and shipbuilding

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    Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Ocean Engineering, 2004.Includes bibliographical references (leaf 132).The purpose of this thesis is to expand and analyze the decisions that are constantly being made by shipping companies concerning acquisition of newbuildings, the construction of newbuildings, operational aspects as well as financial issues concerning a shipping company. The issues that shall be analyzed and discussed have been deduced after extended discussions with technical directors of some of the major Greek Shipping Companies. Once all issues at hand have been deduced, this thesis shall provide a general introduction, and consequently an analysis of each and every major event at hand, indicating Shipping Company's various options. The next step shall be to analyze the results of all the interviews, and then finally give further comments and suggestions concerning each and every major event at hand shall be indicated.by Vasileios Maroulis.S.M

    Abundance and regulatory roles of tRNA-derived fragments: a computational exploration using Next- Generation Sequencing data

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    Η πρωταρχική και πιο καλά μελετημένη λειτουργία των μεταφορικών RNA (tRNAs) είναι η συμμετοχή τους στην μετάφραση των πρωτεϊνών, όπου μεταφέρουν αμινοξέα στα ριβοσώματα και συμμετέχουν στη βασισμένη στα κωδικόνια διαδοχική επιμήκυνση της νεοσυντιθέμενης πολυπεπτιδικής αλυσίδας. Πρόσφατα δείχθηκε ότι τα tRNAs αποτελούν τη δεξαμενή για τη βιογένεση πολυάριθμων RNAs μικρού μήκους με ρυθμιστικές δυνατότητες. Τα παραγόμενα από tRNA θραύσματα (tRFs) ποικίλουν ως προς το μέγεθος τους και προέρχονται από διαφορετικά σημεία του μορίου του tRNA, το οποίο έχει σχήμα τριφυλλιού. Τα κύρια είδη των tRFs είναι τα «μισά» των tRNAs (tRHs) με μέγεθος ~34 νουκλεοτίδια και τα μικρότερα (18-22 νουκλεοτίδια) 3’ και 5’ tRFs. Ένας αυξανόμενος όγκος δεδομένων υποδεικνύει ότι μικρά tRFs φορτώνονται σε πρωτεΐνες της οικογένειας AGO και καθοδηγούν την εξαρτώμενη από το σύμπλοκο RISC μετα-μεταγραφική καταστολή της γονιδιακής έκφρασης, με τον ίδιο τρόπο με οποίο δρουν τα microRNAs. Σε αυτή τη διπλωματική εργασία έγινε ποσοτικοποίηση των διαφορετικών ειδών tRFs από ανθρώπινα δεδομένα αλληλούχησης μικρών RNA (sRNA-Seq) με τη χρήση του εργαλείου Manatee. To Manatee συνδυάζει πληροφορίες από συστάδες μοναδικά χαρτογραφημένων διαβασμάτων και τον ήδη γνωστό σχολιασμό των μεταγραφικών χαρακτηριστικών για να καθοδηγήσει την αποτελεσματική τοποθέτηση των διαβασμάτων που χαρτογραφούνται σε πολλαπλές γενωμικές θέσεις. Τα tRFs με την μεγαλύτερη αφθονία που ταυτοποιήθηκαν χρησιμοποιήθηκαν στη συνέχεια για να καθοδηγήσουν την ανάλυση δημόσια διαθέσιμων πειραμάτων αλληλούχησης διασταυρούμενης σύνδεσης και ανοσοκαθίζησης πρωτεϊνών AGO (AGO-Cross-Linking Immunoprecipitation, AGO-CLIP) σε αντίστοιχες ανθρώπινες κυτταρικές σειρές, με τη χρήση του εργαλείου microCLIP. Απευθείας αλληλεπιδράσεις μεταξύ των tRFs και mRNAs που ταυτοποιήθηκαν, διερευνήθηκαν λειτουργικά με στατιστική ανάλυση εμπλουτισμού μονοπατιών (pathway enrichment analysis). Τα αποτελέσματα επιδεικνύουν τη χρήση για πρώτη φορά του εργαλείου Manatee στην ποσοτικοποίηση των tRFs, τους περιορισμούς μιας τέτοιας προσέγγισης και τον επακόλουθο χαρακτηρισμό της εμπλοκής των tRFs στη ρύθμιση της γονιδιακής έκφρασης.The primary and most well-studied function of transfer RNAs (tRNAs) is their involvement in protein translation, where they carry amino acid residues into the ribosomes and participate in the codon-based sequential elongation of the nascent peptide chain. Recently, tRNAs were shown to act as a pool for the biogenesis of numerous short RNAs of regulatory potential. tRNA-derived fragments (tRFs) vary in their size and originate from different parts of the tRNA cloverleaf-shaped molecule. The main tRF species are ~34nt 5' and 3' halves of tRNAs (tRHs) and the smaller (18-22nt) 5' and 3' tRFs. Increasing evidence indicates that small tRFs are loaded into AGO proteins and guide RISC-dependent post-transcriptional repression, in the same manner that microRNAs do. In this thesis, tRF species were quantified from human small RNA-Seq (sRNA-Seq) datasets using Manatee tool. Manatee combines information on uniquely aligned read clusters and known annotation of transcriptomic features to guide the efficient placement of multi-mapping reads. The highly abundant tRFs that were identified were subsequently utilized to guide the analysis of publicly available AGO-Cross-Linking Immunoprecipitation (AGO-CLIP) sequencing experiments in relevant cell-lines using microCLIP tool. Directly identified tRF-mRNA interactions were functionally interrogated using pathway enrichment statistics. The results demonstrate the use of Manatee for the quantification of tRFs for the first time and the limitations of such an approach, and the subsequent characterization of tRF implication in gene expression regulation

    Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

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    : The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

    PlasmiR: A Manual Collection of Circulating microRNAs of Prognostic and Diagnostic Value

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    Simple Summary Only recently have the important biomarker capacities of microRNAs (miRNAs) in blood samples during disease been revealed. miRNAs are abundantly detected in circulation, and are less prone to degradation than longer RNA. Details regarding potential discriminatory miRNAs against numerous pathologic conditions are dispersed across articles, while existing resources that catalogue miRNA abundance in blood samples are not tailored to biomarker research. This study presents the meticulous manual curation of more than 200 articles that specifically interrogate the biomarker potential of miRNAs in whole blood, serum, or plasma. This annotation effort resulted in the creation of plasmiR, a database that systematically provides experimental evidence for the diagnostic and prognostic potential of circulating miRNAs against human diseases. plasmiR features 1021 entries, accompanied by rich study-specific meta-information, and an intuitive interface that enables the formation of complex queries and visualizations. Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene expression. Extensive studies in cancer and other disease landscapes investigate the protective/pathogenic functions of dysregulated miRNAs, as well as their biomarker potential. A specialized resource amassing experimentally verified, circulating miRNA biomarkers does not exist. We queried the existing literature to identify articles assessing diagnostic/prognostic roles of miRNAs in blood, serum, or plasma samples. Articles were scrutinized in order to exclude instances lacking sufficient experimental documentation or employing no biomarker assessment methods. We incorporated information from more than 200 biomedical articles, annotating crucial meta-information including cohort sizes, inclusion-exclusion criteria, disease/healthy confirmation methods and quantification details. miRNAs and diseases were systematically characterized using reference resources. Our circulating miRNA biomarker collection is provided as an online database, plasmiR. It consists of 1021 entries regarding 251 miRNAs and 112 diseases. More than half of plasmiR’s entries refer to cancerous and neoplastic conditions, 183 of them (32%) describing prognostic associations. plasmiR facilitates smart queries, emphasizing visualization and exploratory modes for all researchers

    Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

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    © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit
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