A multi-compartment lumped-parameter model for assessing the role of haematocrit in foetal circulation

Foetal circulation, being different from neonatal and adult circulation, is an intricate system. Current knowledge of its haemodynamics is limited 1, while the role of haematocrit at different gestational ages has not yet been examined extensively. This work aims to investigate the effect of haematocrit variations using a multi-compartment lumped parameter model (LPM) of the foetal circulation. The LPM model is developed in Simulink® and includes19 elastic arterial segments and 12 peripheral vascular beds, represented, respectively, by electrical circuits and a 3-element Windkessel model 2,3. Previous data1,2and allometric laws 4 were used to calculate the inflow and boundary conditions for a 33-week gestational age and foetus weight. Two validation studies were completed, one comparing results with adult flow waveforms and another examining the foetal Isthmic Flow Index. Different values of haematocrit (Hct), ranging from 10% to 80% Hct, were investigated, representing a range of anaemic, healthy, and polycythaemic conditions. Results from the validation studies were in good agreement with literature. The foetal LPM enabled calculations of blood flow waveforms at various arterial positions. Computations with 10%, 45%, and 80% Hct were further performed to demonstrate the effect of haematocrit on the foetal arterial flow. A clear difference between the 45% and 80%Hctmodels at the position of the ascending aorta was evident, whereas no apparent difference was detected between the models for 10% and 45% Hct. Similarly, this effect was manifested at the positions of the aortic isthmus, the thoracic aorta, and the umbilical artery. However, at the position of the ductus arteriosus there was no difference between the three models. Finally, the calculations revealed an almost exponential relationship between mean resistance and Hematocrit. Investigating haematocrit variations revealed an important effect on the foetal circulation, resulting insignificant changes in vascular resistances and the pulsatility indices of the flow rate waveforms. Further investigation is required aiming at the improvement of the accuracy of the inflow and boundary conditions

Investigating the role of haematocrit in foetal circulation : a multi-compartment lumped parameter model

Foetal circulation is a complex system that differs from the corresponding neonatal and adult system. Current understanding of the foetal haemodynamics is limited1, while the role of haematocrit at different gestational ages has not yet been investigated extensively. Computational models can aid elucidate circulation haemodynamics2. To this end, this contribution proposes a multi-compartment lumped parameter model of the foetal circulatory system to investigate the effect of haematocrit variations on the systemic arterial flow

From tumour perfusion to drug delivery and clinical translation of in silico cancer models

In silico cancer models have demonstrated great potential as a tool to improve drug design, optimise the delivery of drugs to target sites in the host tissue and, hence, improve therapeutic efficacy and patient outcome. However, there are significant barriers to the successful translation of in silico technology from bench to bedside. More precisely, the specification of unknown model parameters, the necessity for models to adequately reflect in vivo conditions, and the limited amount of pertinent validation data to evaluate models' accuracy and assess their reliability, pose major obstacles in the path towards their clinical translation. This review aims to capture the state-of-the-art in in silico cancer modelling of vascularised solid tumour growth, and identify the important advances and barriers to success of these models in clinical oncology. Particular emphasis has been put on continuum-based models of cancer since they - amongst the class of mechanistic spatio-temporal modelling approaches - are well-established in simulating transport phenomena and the biomechanics of tissues, and have demonstrated potential for clinical translation. Three important avenues in in silico modelling are considered in this contribution: first, since systemic therapy is a major cancer treatment approach, we start with an overview of the tumour perfusion and angiogenesis in silico models. Next, we present the state-of-the-art in silico work encompassing the delivery of chemotherapeutic agents to cancer nanomedicines through the bloodstream, and then review continuum-based modelling approaches that demonstrate great promise for successful clinical translation. We conclude with a discussion of what we view to be the key challenges and opportunities for in silico modelling in personalised and precision medicine

Recipes for calibration and validation of agent-based models in cancer biomedicine

Computational models and simulations are not just appealing because of their intrinsic characteristics across spatiotemporal scales, scalability, and predictive power, but also because the set of problems in cancer biomedicine that can be addressed computationally exceeds the set of those amenable to analytical solutions. Agent-based models and simulations are especially interesting candidates among computational modelling strategies in cancer research due to their capabilities to replicate realistic local and global interaction dynamics at a convenient and relevant scale. Yet, the absence of methods to validate the consistency of the results across scales can hinder adoption by turning fine-tuned models into black boxes. This review compiles relevant literature to explore strategies to leverage high-fidelity simulations of multi-scale, or multi-level, cancer models with a focus on validation approached as simulation calibration. We argue that simulation calibration goes beyond parameter optimization by embedding informative priors to generate plausible parameter configurations across multiple dimensions

Maritime education in EU : strengths and challenges

In a global competitive world, the education progress from school to University and the continuous professional training is the key to enhance productivity, employability and social stability. Continuous education is a key issue for the evolution of human being, not only in the professional sector of life but also in the personal life, enhancing important elements of the character and personality for each individual. Furthermore, new technologies, regulations and policies in maritime industry reveal the necessity for additional educational schemes that will cover the market needs. Considering the growing challenges of port, shipping and logistics, TrainMoS II and On The MoS Way Network (OTMW-N) European projects aimed to the development of students and professionals skills and laid the foundations for a cross-European maritime educational system. TrainMoS II was the evolution of the TrainMoS project, improving the tools developed during the first phase and covering a whole new range of technical and operational topics, including alternative fuels and technologies, logistic issues (including Single Window Directive 65/2010), damage control (incl. IMO ‘Safe Return to Port’ concept) and evacuation/crisis management operations. TrainMoS II focused on the provision of professional training and vocational education activities to undergraduates and professionals who belong to different sectors in the multimodal transport chain. Individual Modules were open to attendance from students to require a Continuous Professional Development (CPD) certification. At the same time, OTMW-N covered the training needs in the use of alternative fuels in marine industry, such as LNG. OTMW-N was also offering professional training and vocational education through a series of activities in which students obtain the opportunity to enhance their academic background and to implement it in simulation programmes. The present paper presents the results and the contribution of these projects to the maritime community. Stakeholder needs from different sectors of maritime industry are examined and the outcomes of the aforementioned projects are presented and discussed

An overview of low back pain

Στόχος αυτής της μελέτης είναι η κατανόηση του οσφυοϊερού άλγους, το οποίο αναμένεται να επηρεάσει περίπου το 80% του πληθυσμού κάποια στιγμή κατά τη διάρκεια της ζωής του, έχοντας μεγάλο αντίκτυπο στις καθημερινές δραστηριότητες και την ποιότητα ζωής του ασθενούς. Το οσφυοϊερό άλγος είναι ένα σύμπτωμα, και όχι μια ασθένεια, που συνήθως ακολουθεί μια αυτοπεριοριζόμενη πορεία. Παρ 'όλα αυτά, πολλοί ασθενείς που θα παρουσιάσουν ένα μονήρες επεισόδιο, θα έχουν σνήθως περαιτέρω υποτροπιάζοντα επεισόδια στο μέλλον. Οι παράγοντες κινδύνου που συνήθως εμπλέκονται με την ανάπτυξη χρόνιου οσφυοϊερού άλγους περιλαμβάνουν την ηλικία, την παχυσαρκία, το επάγγελμα και άλλους ψυχοκοινωνικούς παράγοντες. Το οσφυοϊερό άλγος διαφοροποιείται ανάλογα με το αίτιο σε πόνο μηχανικής φύσεως, συνηθέστερος, ή φλεγμονώδους φύσεως, συσχετιζόμενο συνήθως με κάποια ρευματική νόσο. Η διάκριση γίνεται με τον προσδιορισμό συγκεκριμένων σημείων και συμπτωμάτων μέσω του ιατρικού ιστορικού και της κλινικής εξέτασης. Η χρήση τεχνικών απεικόνισης, με τη μαγνητική τομογραφία να αποτελεί συνήθως την εξέταση εκλογής, ενδείκνυται σε ασθενείς με μακρόχρονο πόνο ή με ανησυχητικά σημεία και συμπτωμάτα. Για τη διαχείριση του οσφυοϊερού άλγους, η σωστή εκπαίδευση, η τροποποίηση των καθημερινών δραστηριοτήτων, η γνωσιακή-συμπεριφορική θεραπεία, και η ψυχοκοινωνική υποστήριξη, θεωρούνται σημαντικές. Η φαρμακευτική αγωγή και η φυσιοθεραπεία έχουν ως στόχο να ανακουφίσουν τον ασθενή και να τον βοηθήσουν να ανταπεξέλθει στην καθημερηνότητά του και στις υποχρεώσεις του. Οι επεμβατικές τεχνικές προορίζονται για ασθενείς μη ανταποκρινόμενους στη συντηρητική θεραπεία ή με σημαντική έκπτωση στην ποιότητα ζωής.The aim of this study is to understand the very serious medical condition of low back pain, affecting approximately 80% of the population sometime in their lifetime, which can have a great impact on everyday activities of the affected individual, thus deteriorating the quality of human life. Low back pain is considered a symptom, rather than a disease, usually running a self-limited course. Despite that, many patients presenting with an episode of low back pain will go on having recurrent episodes. Risk factors usually implicated in the development of chronic low back pain include age, obesity, occupation and other psychosocial factors. The exact etiopathogenic mechanism behind the clinical presentation of low back pain is differentiated as being either mechanical, most commonly, or inflammatory, usually associated with a systemic rheumatic disease. To distinguish between these two entities, the presence of specific signs and symptoms should be identified through the medical history and clinical evaluation. The use of imaging techniques, with MRI being the study of choice, is indicated either in incapacitated patients with long-lasting low back pain or when serious signs and symptoms are identified. For the management of low back pain, proper education, daily activity modification, and, sometimes, cognitive-behavioral therapy and psychosocial support, are considered important. Active treatment with medication and physical therapy, although not always needed, is usually applied, aiming to relieve the patient from the pain and help him cope with his daily routine and responsibilities. More invasive treatment options are reserved for patients not responding to conservative treatment or with significant impairment in life quality

A finite element method for non-linear hyperelasticity applied for the simulation of octopus ARM motions

An implicit non-linear finite element (FE) numerical procedure for the simulation of biological muscular tissues is presented. The method has been developed for studying the motion of muscular hydrostats, such as squid and octopus arms and its general framework is applicable to other muscular tissues. The FE framework considered is suitable for the dynamic numerical simulations of three-dimensional non-linear nearly incompressible hyperelastic materials that undergo large displacements and deformations. Human and animal muscles, consisting of fibers and connective tissues, belong to this class of materials. The stress distribution inside the muscular FE model is considered as the superposition of stresses along the muscular fibers and the connective tissues. The stresses along the fibers are modeled as the sum of active and passive stresses, according to the muscular model of Van Leeuwen and Kier (1997) Philos. Trans. R. Soc. London, 352: 551-571. Passive stress distribution is an experimentally-defined function of fibers’ deformation; while active stress distribution is the product of an activation level time function, a force-stretch function and a force-stretch ratio function. The mechanical behavior of the surrounding tissues is determined adopting a Mooney-Rivlin constitutive model. The incompressibility criterion is met by enforcing large bulk modulus and by introducing modified deformation measures. Due to the non-linear nature of the problem, approximate determination of the Jacobian matrix is performed, in order to utilize the full Newton-Raphson iterative procedure within each time-step. In addition, time discretization is performed via the implicit Newmark method. We developed an open-source finite element code that is capable of simulating large deflection maneuvers of muscular hydrostats. The proposed methodology is validated by comparing the numerical results with existing measurements for the squid arm extension. The efficiency and robustness of the proposed numerical method is demonstrated through a series of octopus arm maneuvers, such as extension, compression and bending

Η διαδικασία της ειδικής διαχείρισης (Ν.4307/2014) στη θεωρία και στη νομολογία: πλεονεκτήματα και νομοτεχνικά προβλήματα

Η διαδικασία της ειδικής διαχείρισης (άρθρα 68-77 ν. 4307/2014) έχει θεσπισθεί στα πρότυπα της κατηργημένης ειδικής εκκαθάρισης του άρθρου 106ια ΠτΚ. Πρόκειται για μία προπτωχευτική συλλογική διαδικασία αφερεγγυότητας, εκκαθαριστικής φύσης, αναγκαστική για τον αφερέγγυο οφειλέτη. Σκοπός της είναι η εκποίηση της αφερέγγυας επιχείρησης ως σύνολο ενεργητικού ή κατά κλάδους σε νέο επενδυτικό φορέα, ενώ αυτή παραμένει σε λειτουργία, μέσω δημόσιου πλειοδοτικού διαγωνισμού, προς βέλτιστη ικανοποίηση των πιστωτών. Βέβαια, πραγματικός σκοπός του νομοθέτη αποδεικνύεται η εξυγίανση των τραπεζών από τα μη αυτοεξυπηρετούμενα «κόκκινα» δάνεια των επιχειρήσεων και η ανάκαμψη της οικονομίας. Η βιαστική και πρόχειρη ενσωμάτωσή στον ν. 4307/2014 είναι ο λόγος που οι διατάξεις της διαδικασίας δεν χαρακτηρίζονται από την δέουσα νομοτεχνική αρτιότητα δυσκολεύοντας τον ερμηνευτή και εφαρμοστή του δικαίου σε αρκετές των περιπτώσεων. Ωστόσο, χάριν κυρίως στη συμβολή της νομολογίας η διαδικασία διαγράφει πλήρως επιτυχημένη πορεία, πετυχαίνοντας το σκοπό για τον οποίο θεσπίστηκε. Η ειδική διαχείριση λειτουργεί προς όφελος της οικονομίας, του τραπεζικού συστήματος και της αγοράς στο σύνολό της, έμμεσα δε έχει θετικό κοινωνικό αντίκτυπο, ενώ καταδεικνύει με χαρακτηριστικό τρόπο τη σημασία της ταχύτητας και της αποτελεσματικότητας στις συλλογικές διαδικασίες αφερεγγυότητας.The procedure “specialized management” (articles 68-77 L. 4307/2014) is legislated by the standards of abolished “special liquidation” of article 106ia Bankruptcy Code. It is a pre-bankruptcy collective insolvency procedure, of a liquidation nature, compulsory for the insolvent debtor. Its purpose is the sale of the insolvent enterprise as a whole of assets or by sectors to a new investment body, while it remains in operation, through a public tender, for optimal satisfaction of the creditors. The real purpose of the legislator proves to be the consolidation of the banks from the non-self-serviced loans and the recovery of the economy. The hasty and rough incorporation in Law 4307/2014 is why the provisions of the procedure are not characterized by the appropriate legal and technical perfection, making it difficult for the interpreter and implementer of the law in several cases. However, mainly thanks to the contribution of the case law, the process has a completely successful course, achieving the purpose for which it was adopted. Specialized management works for the benefit of the economy, the banking system and the market as a whole, and has a positive social impact, while demonstrating in a characteristic way the importance of speed and efficiency in collective insolvency proceedings

Multiscale Mechano-Biological Finite Element Modelling of Oncoplastic Breast Surgery-Numerical Study towards Surgical Planning and Cosmetic Outcome Prediction

Surgical treatment for early-stage breast carcinoma primarily necessitates breast conserving therapy (BCT), where the tumour is removed while preserving the breast shape. To date, there have been very few attempts to develop accurate and efficient computational tools that could be used in the clinical environment for pre-operative planning and oncoplastic breast surgery assessment. Moreover, from the breast cancer research perspective, there has been very little effort to model complex mechano-biological processes involved in wound healing. We address this by providing an integrated numerical framework that can simulate the therapeutic effects of BCT over the extended period of treatment and recovery. A validated, three-dimensional, multiscale finite element procedure that simulates breast tissue deformations and physiological wound healing is presented. In the proposed methodology, a partitioned, continuum-based mathematical model for tissue recovery and angiogenesis, and breast tissue deformation is considered. The effectiveness and accuracy of the proposed numerical scheme is illustrated through patient-specific representative examples. Wound repair and contraction numerical analyses of real MRI-derived breast geometries are investigated, and the final predictions of the breast shape are validated against post-operative follow-up optical surface scans from four patients. Mean (standard deviation) breast surface distance errors in millimetres of 3.1 (±3.1), 3.2 (±2.4), 2.8 (±2.7) and 4.1 (±3.3) were obtained, demonstrating the ability of the surgical simulation tool to predict, pre-operatively, the outcome of BCT to clinically useful accuracy