Ροή αέρα και εναπόθεση σωματιδίων σε εισπνευστήρα ξηράς σκόνης: προσέγγιση υπολογιστικής ρευετοδυναμικής και μεταφοράς σωματιδίων

Dry Powder Inhalers, DPIs, are common asthma treatments and a principle means of delivering pharmaceuticals, due to their ease of use and cost-effectiveness. The main function of a DPI device is the adequate dispersion and delivery of particles initially in the form of a loose powder. The air flow inside the DPI is developed by the pressure difference on the mouthpiece that is imposed by the user. Under the action of airflow the pharmaceutical powder is broken up and released in the form of aggregates and particles. The effective release and dispersion of powder inside the inhaler depends on the characteristic properties of the powders and the material of the DPI walls (e.g. cohesion and adhesion forces, density, particle size distribution) and from the dynamic flow field that develops during inhalation. The main problems of DPIs are drug losses due to deposition in the device, the incomplete development of flow due to the inability of the user to apply the necessary pressure difference, and insufficient breakup into fine particles.The outflow from the DPI mouthpiece is highly important. The characteristics of the outflow stream determines the dispersion and flow behaviour of the particles directed to the oral cavity and consequently influences particle losses in the orolaryngeal region as well as the amount of fine particles that reach the upper respiratory tract. The air and particle flow fields emitting from the DPI mouthpiece, the total number of emitted particles (and therefore drug) and the Fine Particle Fraction (FPF) are the main characteristics of the outflow from the DPI mouthpiece. In most commercial DPI devices, complex and transient flow structures have been observed from laminar to turbulent. However the computational study of the flow fields in DPIs conducted so far have been insufficient and the transport of particles has hardly been studied at all. Furthermore, no computational results on total drug losses due to particle deposition on the DPI walls nor the FPF have been reported. In this thesis the operation of a commercial DPI device, (i.e., Turbuhaler) under conditions of steady and dynamic flow is described in detail using a multi-level computational model based on Computational Fluid Dynamics, CFD. For the first time the total losses of particles (drug) and the FPF are computed for a wide range of operating conditions. The DPI geometry is constructed in a CAD/CAM environment (i.e., CATIA v5) and is then imported into GAMBIT where it is discretized into a computational grid. The Navier-Stokes equations are solved using a commercial CFD software (i.e., FLUENT v6.3). Particle motion and deposition are described using an Eulerian-fluid/ Lagrangian-particle approach. Particle collisions with the DPI walls lead to rebound or deposition according to a particle/wall interaction model. Powder dispersion was assumed to occur instantaneously based on a simple release model. For dynamic simulations, the flow and particle motions equations are solved simultaneously and the pressure difference in the outflow changed with time. This thesis examines the air flow and particle deposition in a wide range of mouthpiece pressure drops (e.g. 800-8800Pa) which correspond to the volumetric flow rates developed in practice (e.g. 20-70L/min). Also, the main features of the outflow are determined, e.g., the dynamic and total fraction of fine particles, and the emitted air and particle flow fields. Finally, the spatial distribution of deposited and emitted particles are determined.It should be noted that this is the first time that such results are reported in the open literature. The computational results were considered highly satisfactory in comparison with literature data considering the dispersion of the available experimental data and the complexity of the problem. It is noteworthy that the comparison was performed without any adjustment of model parameters.Οι εισπνευστήρες ξηράς σκόνης (Dry Powder Inhalers, DPIs), αποτελούν τον κύριο τρόπο χορήγησης φαρμακευτικών ουσιών, όπως για παράδειγμα στη θεραπεία άσθματος, λόγω της ευκολίας χρήσης τους και του χαμηλού κόστους. Η κύρια λειτουργία του εισπνευστήρα είναι η επαρκής διασπορά της φαρμακευτικής σκόνης υπό την μορφή σωματιδίων. Η ροή αέρα μέσα στον εισπνευστήρα αναπτύσσεται από την διαφορά πίεσης στο στόμιο που επιβάλλεται από τον χρήστη. Η ανάπτυξη της ροής στο DPI έχει ως αποτέλεσμα την διάσπαση της φαρμακευτικής σκόνης σε συσσωματώματα και σωματίδια. Η αποτελεσματική διάσπαση και διασπορά της σκόνης μέσα στον εισπνευστήρα εξαρτάται από τις χαρακτηριστικές ιδιότητες της σκόνης και των τοιχωμάτων της συσκευής (όπως π.χ. οι δυνάμεις συνοχής και προσκόλλησης, η πυκνότητα, η κατανομή μεγέθους σωματιδίων) και από το δυναμικό πεδίο ροής του αέρα που αναπτύσσεται κατά την εισπνοή. Κύρια προβλήματα των εισπνευστήρων ξηράς σκόνης είναι η απώλεια φαρμάκου λόγω της επικάθισης στα τοιχώματα, η ελλιπής ανάπτυξη ροής λόγω αδυναμίας επιβολής της απαιτούμενης διαφοράς πίεσης από τον χρήστη, και η ανεπαρκής διάσπαση της σκόνης σε σωματίδια. Η εκροή από το επιστόμιο της συσκευής DPI είναι μεγάλης σημασίας. Τα χαρακτηριστικά του ρεύματος εκροής καθορίζουν την διασπορά και την ροϊκή συμπεριφορά των σωματιδίων που κατευθύνονται προς τη στοματική κοιλότητα, και κατά συνέπεια επηρεάζουν τις απώλειες σωματιδίων στην στοματο-φαρυγγική περιοχή όπως και την ποσότητα των λεπτών σωματιδίων που φτάνουν στο ανώτερο αναπνευστικό σύστημα. Τα πεδία εκροής του αέρα και των σωματιδίων από την επιφάνεια εκροής του εισπνευστήρα, η συνολική ποσότητα σωματιδίων (άρα και φαρμάκου) που εκρέουν και το κλάσμα λεπτών σωματιδίων (Fine Particle Fraction, FPF) είναι τα κύρια χαρακτηριστικά. Στις περισσότερες εμπορικές συσκευές DPI έχουν παρατηρηθεί πολύπλοκα πεδία ροής και δυναμικές δομές ροής από στρωτή έως τυρβώδης. Ωστόσο η υπολογιστή μελέτη των πεδίων ροής μέχρι σήμερα δεν ήταν επαρκής και η μεταφορά σωματιδίων δεν έχει μελετηθεί σχεδόν καθόλου. Επίσης δεν έχουν αναφερθεί ποτέ αποτελέσματα υπολογιστικών προσομοιώσεων που να δίνουν τις συνολικές απώλειες φαρμάκου λόγω επικάθισης σωματιδίων στα τοιχώματα ούτε και η εκροή λεπτών σωματιδίων (FPF). Σε αυτήν την διατριβή, περιγράφεται λεπτομερώς η λειτουργία ενός εμπορικού εισπνευστήρα (Τurbuhaler) υπό συνθήκες σταθερής και δυναμικής ροής με ένα σύνθετο υπολογιστικό μοντέλο βασισμένο στην υπολογιστική ρευστοδυναμική (Computational Fluid Dynamics, CFD). Υπολογίζονται για πρώτη φορά οι συνολικές απώλειες σωματιδίων (φαρμάκου) και το κλάσμα λεπτών σωματιδίων για ένα μεγάλο εύρος συνθηκών. Η γεωμετρία της συσκευής DPI κατασκευάστηκε σε πρόγραμμα CAD/CAM (CATIA v5) και στη συνέχεια εισάχθηκε στην GAMBIT όπου διακριτοποιήθηκε σε ένα υπολογιστικό πλέγμα. Οι εξισώσεις Navier-Stokes λύνονται με τη χρήση των εμπορικού λογισμικού CFD (FLUENT v6.3). Η κίνηση και εναπόθεση των σωματιδίων περιγράφονται με την μέθοδο Eulerian-Fluid/ Lagrangian-Particle. Οι συγκρούσεις των σωματιδίων με τα τοιχώματα της συσκευής οδηγούν σε αναπήδηση ή προσκόλληση με βάση ένα μοντέλο αλληλεπίδρασης σωματιδίων/συσκευής. Η διασπορά της φαρμακευτικής σκόνης θεωρήθηκε ότι γίνεται ακαριαία με βάση ένα απλό μοντέλο διασποράς. Για δυναμικές προσομοιώσεις οι εξισώσεις ροής και σωματιδίων λύνονται ταυτόχρονα και η επιβαλλόμενη διαφορά πίεσης στην επιφάνεια εκροής αλλάζει δυναμικά με το χρόνο. Η διατριβή αυτή εξετάζει την ροή αέρα και την εναπόθεση των σωματιδίων σε ευρύ φάσμα των πιέσεων του στομίου (π.χ. 800 - 8800Pa) που αντιστοιχούν στις ογκομετρικές ροές που αναπτύσσονται στην πράξη (π.χ. 20-70 L/min), Επίσης προσδιορίζονται τα κύρια χαρακτηριστικά της εκροής όπως το δυναμικό και συνολικό κλάσμα λεπτών σωματιδίων, και το πεδίο εκροής αέρα και σωματιδίων. Τέλος περιγράφεται εικονικά οι χωρική κατανομή των σωματιδίων που έχουν εναποτεθεί στα τοιχώματα της συσκευής καθώς και των σωματιδίων που έχουν εξέλθει από την συσκευή. Είναι η πρώτη φορά που αναφέρονται τέτοια αποτελέσματα στην διεθνή βιβλιογραφία. Τα υπολογιστικά αποτελέσματα κρίθηκαν άκρως ικανοποιητικά σε σύγκριση με δεδομένα της βιβλιογραφίας δεδομένου της διασποράς των πειραματικών δεδομένων και της περιπλοκότητας του προβλήματος. Είναι αξιοσημείωτο ότι η σύγκριση έγινε χωρίς να τροποποιηθούν οι παράμετροι του προβλήματος

Assessment of maternal knowledge of infant movement and nutrition guidelines in Canada: The PREVENT survey study (Physical activity, Rest, Exercise and nutrition Values for Education of New moms with Type 2 diabetes/gestational diabetes)

Infants born to mothers with type 2 diabetes (T2D) and gestational diabetes (GDM) are at an increased risk of being overweight/obese. Modifiable lifestyle factors play a role in prevention of overweight and obesity. In 2017, the Canadian 24 h Movement Guidelines for the Early Years (CMG) were released. Alongside physical activity recommendations, sweetened beverage consumption (SBC) recommendations were also released by the American Academy of Pediatrics in 2017. The objective of this study was to determine the knowledge pregnant women with T2D and GDM have on the CMG and SBC recommendations, and to determine what factors affect this. A survey with questions regarding demographics, socioeconomic variables and the CMG and SBC recommendations was administered to pregnant women at Diabetes in Pregnancy clinics in Calgary, Alberta from July 2019 to January 2020. Surveys were analyzed utilizing the non-parametric Kruskall-Wallis Rank-Sum test, chi-square test and linear regression. A total of 79 respondents with T2D and GDM were collected. Respondents had the highest knowledge of SBC recommendations and the lowest knowledge of CMG recommendations. A bachelor’s or higher degree was associated with significantly higher knowledge scores than a high-school education or less. In conclusion, pregnant women with T2D and GDM in this study had overall poor knowledge of the CMG and SBC recommendations, with less knowledge regarding the CMG. Level of education was found to be associated with knowledge regarding these recommendations. Future programs to improve education around infant and toddler physical activity and SBC recommendations may be beneficial for this patient population

Predictive Maintenance Platform Based on Integrated Strategies for Increased Operating Life of Factories

Process output and profitability of the operations are mainly determined by how the equipment is being used. The production planning, operations and machine maintenance influence the overall equipment effectiveness (OEE) of the machinery, resulting in more 'good parts' at the end of the day. The target of the predictive maintenance approaches in this respect is to increase efficiency and effectiveness by optimizing the way machines are being used and to decrease the costs of unplanned interventions for the customer. To this end, development of ad-hoc strategies and their seamless integration into predictive maintenance systems is envisaged to bring substantial advantages in terms of productivity and competitiveness enhancement for manufacturing systems, representing a leap towards the real implementation of the Industry 4.0 vision. Inspired by this challenge, the study provides an approach to develop a novel predictive maintenance platform capable of preventing unexpected-breakdowns based on integrated strategies for extending the operating life span of production systems. The approach and result in this article are based on the development and implementation in a large collaborative EU-funded H2020 research project entitled Z-Bre4k, i.e. Strategies and predictive maintenance models wrapped around physical systems for zero-unexpected-breakdowns and increased operating life of factories

Predictive Maintenance Platform Based on Integrated Strategies for Increased Operating Life of Factories

Part 5: Industry 4.0 - Digital TwinInternational audienceProcess output and profitability of the operations are mainly determined by how the equipment is being used. The production planning, operations and machine maintenance influence the overall equipment effectiveness (OEE) of the machinery, resulting in more ‘good parts’ at the end of the day. The target of the predictive maintenance approaches in this respect is to increase efficiency and effectiveness by optimizing the way machines are being used and to decrease the costs of unplanned interventions for the customer. To this end, development of ad-hoc strategies and their seamless integration into predictive maintenance systems is envisaged to bring substantial advantages in terms of productivity and competitiveness enhancement for manufacturing systems, representing a leap towards the real implementation of the Industry 4.0 vision. Inspired by this challenge, the study provides an approach to develop a novel predictive maintenance platform capable of preventing unexpected-breakdowns based on integrated strategies for extending the operating life span of production systems. The approach and result in this article are based on the development and implementation in a large collaborative EU-funded H2020 research project entitled Z-Bre4k, i.e. Strategies and predictive maintenance models wrapped around physical systems for zero-unexpected-breakdowns and increased operating life of factories

Interoperable Information Flow as Enabler for Efficient Predictive Maintenance

Industry 4.0 enables the modernisation of machines and opens up the digitalisation of processes in the manufacturing industry. As a result, these machines are ready for predictive maintenance as part of Industry 4.0 services. The benefit of predictive maintenance is that it can significantly extend the life of machines. The integration of predictive maintenance into existing production environments faces challenges in terms of data understanding and data preparation for machines and legacy systems. Current AI frameworks lack adequate support for the ongoing task of data integration. In this context, adequate support means that the data analyst does not need to know the technical background of the pilot’s data sources in terms of data formats and schemas. It should be possible to perform data analyses without knowing the characteristics of the pilot’s specific data sources. The aim is to achieve a seamless integration of data as information for predictive maintenance. For this purpose, the developed data-sharing infrastructure enables automatic data acquisition and data integration for AI frameworks using interoperability methods. The evaluation, based on two pilot projects, shows that the step of data understanding and data preparation for predictive maintenance is simplified and that the solution is applicable for new pilot projects

The Antioxidant Supplementation with Filipendula ulmaria Extract Attenuates the Systemic Adverse Effects of Nanosized Calcium Phosphates in Rats

The aim of this study was to investigate and compare the systemic toxicity of three nanosized calcium phosphates (CaPs): hydroxyapatite (HA), tricalcium phosphate (TCP), and amorphous calcium phosphate (ACP) in rats. Since those metallic compounds are widely used as bone replacement materials, including their use in oral surgery, CaPs were applied (per os) equimollary (17.8 mg/kg, 11 mg/kg, and 9.65 mg/kg b.w., respectively) for 30 days in order to mimic the previously described release rate from dental composites. Also, we employed antioxidant supplementation with Filipendula ulmaria (FU) extract. All the applied CaPs significantly increased serum calcium, triglycerides, LDL, and LDH, while serum levels of testosterone and LH declined, with no alterations in the liver enzymes. The evaluation of oxidative stress markers (in the liver, kidney, and testicle) showed an increase in TBARS values, while SOD and CAT activities and GSH levels were significantly reduced. The relative gene expression of Bax and Bcl-2 was shifted to proapoptotic action, accompanied by intense characteristic histological changes in architecture in all investigated organs. The toxic effects were most prominent in groups treated by ACP. FU administration attenuated the majority of nanosized CaP-induced adverse effects, thus recommending this therapeutic approach to minimize nano-CaP systemic toxicities