Simply Lean Simulations: bridging dynamic discrete-event simulation and Lean Six-Sigma process improvement techniques

Techniques part of the Lean manufacturing philosophy have been widely adopted as a method of improving flow, while at the same time reducing waste within most type of business processes. The financially driven approach of the Six Sigma has not always combined easily with the flow-based principles within lean manufacturing philosophy, but the combination of these two techniques has been proven in the past to be possible with the evolution of the Lean Six Sigma philosophy. That approach can actually improve value to the customer as well as reduce the variation and waste within the critical processes of an organisation in order to deliver real financial benefits to the supply chain. In the past lean practitioners have been wary to whatever had to do with the computer based simulations both due to the time that is needed to be spent in finalising the current and the future state maps and also due to the fact that lean practitioners seem to favour a more hands-on communication with the process itself, rather than a remote analysis like the simulation. Recognition of the “static” drag and drop value stream mapping software, gives an indication that lean practitioners are beginning to accept more the computer-based solutions in order to support collaboration and communication of value stream mapping. BRM3 Ltd, the sponsoring company for this project, have developed a discovery learning simulation exercise called "Simply Lean", which is designed to take its participants from a basic to a full understanding of how to apply the most complex techniques which underpin Lean Six Sigma. The purpose of the project is to investigate the extent to which a library of Lean Templates can be built in Simprocess, so that the enhancement of the learning experience as well as to demonstrate the validity of the simulation as a lean process improvement tool. The investigation in this project is covering the following tasks; Firstly, the successful build of simulation models in Simprocess for each of the two key stages of the simulation exercise. The first model will replicate the Push processing technique used by many small companies the second a Mixed Pull system. Both the models were built with more successful to be the Push model, and the Mixed Pull to be partially incomplete. Secondly, the creation of a “Template Library” consisting of drag and drop V.S.M Icons in Simprocess, in order that simulations models can mimic the accepted appearance of a value stream maps. This was done in full very successfully and in conjunction with the previously mentioned simulation models, the third and last objective was achieved which is the evaluation of the effectiveness of Simprocess within a “Simply Lean” workshop, which was proved as successful since both the models are able to be used as training tools as well as an implementation aid within lean six sigma projects.MRes in Innovative Manufacturin

The causative agents in infective endocarditis: a systematic review comprising 33,214 cases.

Infective endocarditis (IE) incidence remains high with considerable fatality rates; guidelines for prophylaxis against IE are currently under review in some settings which highlights the importance of maintaining up-to-date epidemiological estimates about the most common microbial causes. The objective of this systematic review, following PRISMA guidelines, was to identify the most common microbial causes of IE in recent years. Medline was searched from January 1, 2003 to March 31, 2013 for all articles containing the term "infective endocarditis". All relevant studies reporting diagnostic results were included. Special patient subpopulations were assessed separately. A total of 105 studies were included, from 36 countries, with available data on a total of 33,214 cases. Staphylococcus aureus was found to be the most common microorganism, being the most frequent in 54.3 % of studies (N = 57) (and in 55.4 % of studies using Duke's criteria for diagnosis [N = 51]). Viridans group streptococci (VGS), coagulase-negative staphylococci (CoNS), Enterococcus spp and Streptococcus bovis were among the most common causes. S. aureus was the most common pathogen in almost all population subgroups; however, this was not the case in patients with implantable devices, prosthetic valves, or immunocompromised non-HIV, as well as in the sub-group from Asia, emphasizing that a global one-size-fits-all approach to the management of suspected IE is not appropriate. This review provides an evidence-based map of the most common causative agents of IE, highlighting S. aureus as the leading cause in the 21st century. The changing epidemiology of IE in some patient sub-groups in the last decade and the very high number of microbiologically undiagnosed cases (26.6 %) suggest the need to revisit IE prophylaxis and diagnostic strategies

Η μετα-μεταγραφική επεξεργασία του RNA στη ρευματοειδή αρθρίτιδα

Η μετα-μεταγραφική επεξεργασία του RNA (RNA editing), με πιο συχνή μορφή τη μετατροπή της αδενοσίνης σε ινοσίνη (adenosine-to-inosine RNA editing), είναι μια βασική βιολογική διεργασία η οποία λαμβάνει χώρα κυρίως στις Alu περιοχές του μεταγραφώματος και διαμεσολαβείται από τα ένζυμα ADAR1 και ADAR2. Το ADAR1 έχει 2 ισομορφές, μια πιο μακριά (ADAR1p150) και μια βραχεία (ADAR1p110). Η σημασία του μηχανισμού αυτού τονίζεται από τον ενδομήτριο θάνατο των ποντικιών τα οποία στερούνται της ενζυματικής δράσης του ADAR1. Στην παρούσα μελέτη εξετάσαμε τη συμμετοχή του RNA editing στη Ρευματοειδή Αρθρίτιδα (ΡΑ), μια χρόνια φλεγμονώδη (αυτοάνοση) νόσο που επηρεάζει περίπου το 1% του πληθυσμού. Πιο συγκεκριμένα εξετάσαμε το ρόλο του RNA editing στη ρύθμιση των επιπέδων φλεγμονωδών μορίων. Για το σκοπό αυτό αναλύσαμε ένα RNA sequencing dataset που περιλάμβανε συνολικά 202 βιοψίες αρθρικού υμένα [28 υγιείς, 22 ασθενείς με οστεοαρθρίτιδα, 57 ασθενείς με πρώιμη ΡΑ (διάρκεια νόσου<1 έτος) και 95 ασθενείς με εγκατεστημένη ΡΑ]. Επίσης, συλλέξαμε αίμα από ασθενείς με ενεργό ΡΑ πριν- και 3 μήνες μετά την έναρξη νέας θεραπείας και απομονώσαμε λεμφομονοπύρηνα κύτταρα (PBMCs). Οι τεχνικές που χρησιμοποιήθηκαν ήταν ποσοτική αλυσιδωτή αντίδραση πολυμεράσης (qPCR) και Sanger sequencing. Τα αποτελέσματα της μελέτης ανέδειξαν σημαντική αύξηση της ισομορφής ADAR1p150 τόσο στον αρθρικό υμένα όσο και στο αίμα των ασθενών, ενώ τα επίπεδα της ισομορφής ADAR1p110 καθώς και του ενζύμου ADAR2 δε διέφεραν μεταξύ ασθενών και υγιών. Στη συνέχεια, εξετάσαμε το RNA editing της cathepsin S, ενός μορίου που εμπλέκεται ενεργά στην αντιγονοπαρουσίαση και στην διάσπαση εξωκυττάριας ουσίας και που έχει προταθεί ως σημαντικό κομμάτι της παθοφυσιολογίας της ΡΑ ή ακόμη και ως θεραπευτικός στόχος. Παρατηρήσαμε ότι το RNA editing στο στοιχείο AluSx+ της cathepsin S ήταν σημαντικά αυξημένο στα λεμφομονοπύρηνα κύτταρα ασθενών με ενεργό ΡΑ. Με ιδιαίτερο ενδιαφέρον παρατηρήσαμε πως τόσο η έκφραση του μορίου ADAR1p150 όσο και το RNA editing του AluSx+ της cathepsin S μειώθηκαν σημαντικά μετά τη θεραπεία στους ασθενείς που είχαν καλή ανταπόκριση στη φαρμακευτική αγωγή (κριτήρια EULAR), ενώ παρέμειναν αμετάβλητα στους ασθενείς με μέτρια ή καθόλου ανταπόκριση. Τέλος, η έκφραση της cathepsin S, που ήταν αυξημένη τόσο στον αρθρικό υμένα όσο και στα λεμφομονοπύρηνα κύτταρα των ασθενών, συσχετιζόταν ισχυρά τόσο με το ADAR1p150 όσο και με τα επίπεδα του RNA editing. Συμπερασματικά, προτείνουμε πως το RNA editing μπορεί να δρα ως ένα επιπρόσθετο, μετα-μεταγραφικό επίπεδο ρύθμισης της γονιδιακής έκφρασης στη ΡΑ.Adenosine-to-inosine (A-to-I) RNA editing of Alu retroelements is a primate-specific mechanism mediated by adenosine deaminases acting on RNA (ADARs) that diversifies transcriptome by modifying selected nucleotides in RNA molecules. Herein, we tested the hypothesis that A-to-I RNA editing is altered in rheumatoid arthritis (RA). Synovial expression of ADAR1 and its isoforms, ADAR1p110 and ADAR1p150, was analysed in 152 RA patients and 50 controls. Peripheral blood mononuclear cells (PBMCs) derived from 14 healthy subjects and 19 patients with active RA at baseline and after 12-week treatment were examined for ADAR1p150 and ADAR1p110 isoform expression by RT-qPCR. RNA editing activity was analysed by AluSx+ Sanger-sequencing of cathepsin S, an extracellular matrix degradation enzyme also involved in antigen presentation. ADAR1 was significantly over-expressed in RA synovium regardless of disease duration. Similarly, ADAR1p150 isoform expression was significantly increased in the synovium and blood of active RA patients, while ADAR1p110 levels were similar between patients and controls. Individual nucleotide analysis revealed that A-to-I RNA editing rate in cathepsin S AluSx+ was also significantly increased in RA patients. Both baseline ADAR1p150 expression and individual adenosine RNA editing rates in cathepsin S AluSx+ decreased after treatment only in those patients with good clinical response. Upregulation of the expression and/or activity of the RNA editing machinery was associated with a higher expression of edited Alu-enriched genes including cathepsin S and TNF receptor-associated factors 1,2,3 and 5. In conclusion, herein we describe a previously unrecognized regulation and role of ADAR1p150-mediated A-to-I RNA editing in post-transcriptional control of gene expression in RA, which underpins therapeutic response and fuels inflammatory gene expression, thus representing an interesting therapeutic target

APPLICATION OF ADJOINT CMAQ CHEMICAL TRANSPORT MODEL IN THE ATHENS GREATER AREA: SENSITIVITIES STUDY ON OZONE CONCENTRATIONS

An operational meteorology and air quality forecasting system is currently under development by the Environmental Research Laboratory of NCSR “Demokritos”. The system is based on the meteorological model MM5, the in-house EMISLAB emissions processing system and the chemical transport model CMAQ. It is configured to apply on the Greater Athens Area with a 4-domains nested configuration focusing on a high spatial resolution (1x1 km2) inner domain. The system produces meteorological and air quality predictions for a 72-hours time horizon with 1 hour time step. This paper uses the output of the operational system to apply the CMAQ adjoint for ozone sensitivity calculations, focusing for the two days of 18 and 19 July 2005. In the current study, the calculated ground level ozone concentrations at certain defined locations and times are considered as the “response functional”. Sensitivities of the response functional with respect to the state variables (species concentrations on the grid points and species emissions, e.g., NOX, CO, VOCs) are calculated by running the adjoint model backwards in time (reverse mode). The distribution of the sensitivities in the computational domain, obtained for different times, provides essential information for the analysis: isosurfaces of sensitivities delineate influence regions, i.e., areas where perturbations in some concentrations will result in significant changes in the ozone concentrations in the area of interest at the final time

Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage

Objectives: Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI. Methods: We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T‐tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome. Results: Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2 months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055‐1.680. P = .016]. Conclusion: Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI