In silico assessment of mouth-throat effects on regional deposition in the upper tracheobronchial airways

Regional deposition of inhaled medicines is a valuable metric of effectiveness in drug delivery applications to the lung. In silico methods are now emerging as a valuable tool for the detailed description of localized deposition in the respiratory airways. In this context, there is a need to minimize the computational cost of high-fidelity numerical approaches. Motivated by this need, the present study is designed to assess the role of the extrathoracic airways in determining regional deposition in the upper bronchial airways. Three mouth-throat geometries, with significantly different geometric and filtering characteristics, are merged onto the same tracheobronchial tree that extends to generation 8, and Large Eddy Simulations are carried out at steady inhalation flowrates of 30 and View the MathML source. At both flowrates, large flow field differences in the extrathoracic airways across the three geometries largely die out below the main bifurcation. Importantly, localized deposition fractions are found to remain practically identical for particles with aerodynamic diameters of up to View the MathML source and View the MathML source at 30 and View the MathML source, respectively. For larger particles, differences in the localized deposition fractions are shown to be mainly due to variations in the mouth-throat filtering rather than upstream flow effects or differences in the local flow field. Deposition efficiencies in the individual airway segments exhibit strong correlations across the three geometries, for all particle sizes. The results suggest that accurate predictions of regional deposition in the tracheobronchial airways can therefore be obtained if the particle size distribution that escapes filtering in the mouth-throat (ex-cast dose) of a particular patient is known or can be estimated. These findings open the prospect for significant reductions in the computational expense, especially in the context of in silico population studies, where the aerosol size distribution and precomputed flow field from standardized mouth-throat models could be used with large numbers of tracheobronchial trees available in chest-CT databases

The effect of mouth-throat geometry on regional deposition in the tracheobronchial tree

In silico methods offer a valuable approach to predict localized deposition in the tracheobronchial tree, important in the topical treatment of respiratory diseases and the systemic administration of drugs with limited lung bioavailability. In this study, we examine the effect of extrathoracic airway variation on regional deposition in order to assess whether standard mouth-throat models can be adopted for more efficient predictions. Despite large qualitative differences in the extrathoracic airways, deposition patterns and efficiencies in the tracheobronchial region remain largely unaffected for particles smaller than 6 microns. The findings suggest that for drug delivery applications, standard mouth-throat models could be adopted to predict deposition in the central airways

Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge:Effects of inlet velocity profile, inhalation flowrate and electrostatic charge

AbstractUnderstanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200kg/m3). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects of inlet flow conditions, particle size, electrostatic charge, and flowrate. While most computer simulations assume a uniform velocity at the mouth inlet, we found that using a more realistic inlet profile based on Laser Doppler Anemometry measurements resulted in enhanced deposition, mostly on the tongue. Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected. Nevertheless, at the higher flowrates turbulent intensities persisted further downstream in the main bronchi. For dp>2.5μm, the overall Deposition Fractions (DF) increased with flowrate due to greater inertial impaction in the oropharynx. Below dp=1.0μm, the DF was largely independent of particle size; it also increased with flowrate, but remained significantly lower. Electrostatic charge increased the overall DF of smaller particles by as much as sevenfold, with most of the increase located in the mouth–throat. Moreover, significant enhancement in deposition was found in the left and right lung sub-regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp<2.5μm, impaction prevailed over electrostatic deposition for larger particles as the flowrate was increased. Overall, we report a significant interplay between particle size, electrostatic charge, and flowrate. Our results suggest that in silico models should be customized for specific applications, ensuring all relevant physical effects are accounted for in a self-consistent fashion

Still too little evidence: the role of diet in colorectal cancer survivorship - a systematic review

\ua9 2024 The Author(s). Published with license by Taylor &amp; Francis Group, LLC. Colorectal cancer incidence (CRC) is influenced by dietary factors, yet the impact of diet on CRC-specific mortality and recurrence-free survival (RFS) remains unclear. This review provides a narrative summary of existing research on dietary factors affecting CRC-specific mortality, RFS, and disease-free survival (DFS). This study searched electronic databases to identify cross-sectional/prospective research investigating dietary intake on CRC-specific mortality, RFS, or DFS. Twenty-eight studies were included in the corpus. Because of high study heterogeneity, we performed a narrative synthesis of studies. Limited, but suggestive evidence indicates beneficial effects of adhering to the American Cancer Society (ACS) guidelines and a plant rich low-carbohydrate diet on risk of CRC-specific mortality, potentially driven by fiber from cereals, vegetables, and wholegrains, but not fruit. For RFS and DFS, a Western dietary pattern, high intake of refined grains, and sugar sweetened beverages correlated with increased risk of CRC recurrence and development of disease/death. Conversely, greater adherence to the ACS dietary and alcohol guidelines, higher ω-3 polyunsaturated fatty acids, and dark fish consumption reduced risk. Our findings underscore the need for (i) standardized investigations into diet’s role in CRC survivorship, including endpoints, and (ii) comprehensive analyses to isolate specific effects within correlated lifestyle components

Regional aerosol deposition in the human airways: the SimInhale benchmark case and a critical assessment of in silico methods

Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15 years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future

Effect of upper airway on tracheobronchial fluid dynamics

The upper airways play a significant role in the tracheal flow dynamics. Despite many previous studies, however, the effect of the upper airways on the ventilation distribution in distal airways has remained a challenge. The aim of this study is to experimentally and computationally investigate the dynamic behaviour in the intratracheal flow induced by the upper respiratory tract and to assess its influence on the subsequent tributaries. Patient-specific images from 2 different modalities (magnetic resonance imaging of the upper airways and computed tomography of the lower airways) were segmented and combined. An experimental phantom of patient-specific airways (including the oral cavity, larynx, trachea, down to generations 6-8) was generated using 3D printing. The flow velocities in this phantom model were measured by the flow-sensitised phase contrast magnetic resonance imaging technique and compared with the computational fluid dynamics simulations. Both experimental and computational results show a good agreement in the time-averaged velocity fields as well as fluctuating velocity. The flows in the proximal trachea were complex and unsteady under both lower- and higher-flow rate conditions. Computational fluid dynamics simulations were also performed with an airways model without the upper airways. Although the flow near the carina remained unstable only when the inflow rate was high, the influence of the upper airways caused notable changes in distal flow distributions when the 2 airways models were compared with and without the upper airways. The results suggest that the influence of the upper airways should be included in the respiratory flow assessment as the upper airways extensively affect the flows in distal airways and consequent ventilation distribution in the lungs

Environmental and economic impact assessment of innovative concrete recycling systems

Over the last few years, the construction sector has experienced increasing demand for raw materials due to the rapid growth of the urban population. At the same time, most of the post-war buildings in Europe have reached the end of their service life. As a consequence, a period of intense demolition activities withsignificant waste generation is expected in the upcoming years. Both situations are eventually translated into significant environmental pressure. Concrete is the main component in construction and demolition waste (C&amp;DW). Due to the high environmental footprint of this material, it is crucial to eliminate its consumptionthrough recycling and re-use. Currently, concrete rubbles are crushed with regular crushers and used mainly for low-grade applications (down-cycling) such as road foundations. Despite the environmental and financial benefits, this practice is still not at a sustainable level since raw materials are still needed for new structures, while the demand for low-quality secondary materials in the construction sector has already declined.Two innovative recycling technologies called C2CA and Smart crushing (SC) developed recently in the Netherlands, aiming to close the material loop in the construction sector. These technologies recover most of the original concrete materials at high-quality, which can be use in the production of new concrete athigher rates than traditionally. This research focuses on the environmental and financial implications of the novel C2CA and SC recycling systems as alternative solutions to the Traditional crushing (TC) method. The evaluation was conducted based on an integrated LCA&amp;LCC analysis framework in which the monetisedenvironmental impacts (shadow costs) were internalised in the actual costs occurred within the supply chain of recycled concrete (production of primary materials, recycling, transports). On this basis, the recycling systems were compared from two different perspectives. First, the recycled materials produced were used for concrete production according to the current European standards. In this case, the traditional recycled coarse aggregates (TRCAs) were used to replace 50% of the primary gravel, while the innovative coarse (IRCAs) and fine (IRFAs) aggregates from the innovative systems replaced 100% of primary gravel and 60% of primary sand respectively. The maximum potentials of the innovative systems were investigated in a second scenario in which IRCAs and IRFAs completely replaced the primary concrete aggregates. In addition to that, the produced recycled concrete powder (RCP) was used as supplementary cementitious material (SCM) to replace 20% of the primary cement. In this study, the innovative recycling systems were considered mobile units located at the demolition site. In contrast, the TC recycling was executed off-site at a stationary plant to secure the sufficient quality of TRCAs. The results of the integrated LCA&amp;LCC study revealed that both C2CA and SC systems were financially better options than the traditional recycling route. Especially when the SC system was used to replace higher quantities of primary materials, the total cost was reduced by up to 19% relative to the TC method. On the other hand, the C2CA technology showed better performance when following the current standards, where about an 8% cost reduction was achieved. However, environmental improvements were reported only for maximum utilisation of the SC products, resulting in about 17% lower shadow cost than the traditional method. In the case of the C2CA system, the environmental impact was found 5% increase for both scenarios. Both innovative systems displayed overall benefits over the TC method regarding social cost (internalised environmental impacts), with the SC system exhibiting the best overall performance for maximum use of its products. In this case, the overall benefits reached almost 19%, while the rest scenarios were not higher than 5%.The sensitivity analysis emerged that the innovative recycling systems presented benefits only when they were located close to the demolition site due to increased transportation of EoL concrete. For the same locations and up to 23 km away from the demolition site, only the SC2 scenario (maximum use of SC products) was more efficient than the traditional recycling route. The rest scenarios became more effective as the traditional plant was placed away from the demolition site. On the other hand, changes in the recycling phase, such as energy consumption and equipment operating costs, had a negligible impact on the results. Even if renewable energy sources would power the recycling plants, the environmental and cost benefits throughout the supply chain were not higher than 5% and 2.5%, respectivelyCivil Engineering | Building Engineering - Structural Desig

The continuous adjoint method in flow control with jets - Application in a three dimensional rotating compressor cascade

103 σ.Σκοπός της παρούσας διπλωματικής εργασίας είναι η εφαρμογή της συνεχούς συζυγούς μεθόδου (continuous adjoint method) για τον ενεργητικό έλεγχο της ροής (active flow control) ασυμπίεστου ρευστού σε τριδιάστατη περιστρεφόμενη πτερύγωση αξονικού συμπιεστή χωρίς διάκενο (shrouded rotor) έτσι ώστε να έχουμε μείωση των απωλειών σχετικής ολικής πίεσης διαμέσου της πτερύγωσης στη λειτουργία της εκτός του σημείου σχεδιασμού. Οι συζυγείς μεθόδοι χρησιμοποιούνται για την εύρεση της κλίσης της αντικειμενικής συνάρτησης, η οποία εκφράζει τις απώλειες σχετικής ολικής πίεσης μεταξύ εισόδου και εξόδου του χωρίου ροής ως προς τις μεταβλητές σχεδιασμού. Οι μεταβλητές σχεδιασμού σε ένα πρόβλημα ενεργητικού ελέγχου της ροής είναι εικονικές ταχύτητες στα στερεά όρια όπως είναι το πτερύγιο (blade), το κέλυφος κεφαλής (shroud) ή/και ποδός (hub). Οι συνεχείς συζυγείς εξισώσεις, οι οριακές συνθήκες και οι παραγώγοι ευαισθησίας προκύπτουν από την παραγώγιση της συνάρτησης κόστους επαυξημένης με το ολοκλήρωμα, σε όλο το πεδίο, του γινομένου των εξισώσεων κατάστασης (εξισώσεις Navier Stokes) και των συζυγών μεταβλητών. Στην παρούσα εφαρμογή, κατά την πιο πάνω διαδικασία έγινε η υπόθεση της παγωμένης τυρβώδους συνεκτικότητας, δηλαδή οι εξισώσεις του μοντέλου τύρβης δεν συμμετείχαν στην παραγώγιση και η τυρβώδης συνεκτικότητα θεωρήθηκε ανεξάρτητη των μεταβλητών σχεδιασμού. Οι εξισώσεις του συζυγούς προβλήματος διακριτοποιούνται και επιλύονται με τις αντίστοιχες οριακές συνθήκες και έτσι προσδιορίζεται το πεδίο των συζυγών μεταβλητών. Στη συνέχεια, υπολογίζεται ο χάρτης παραγώγων ευαισθησίας που θα υποδείξει τις καταλληλότερες θέσεις τοποθέτησης δεσμών ρευστού για τη μείωση των απωλειών. Γενικά, ο ενεργητικός έλεγχος της ροής με τη χρήση δεσμών ρευστού χρησιμοποιείται γιατί είναι ικανός να αυξήσει σημαντικά την άνωση και να μειώσει την οπισθέλκουσα σε αεροτομές, καθώς επίσης και να μειώσει τις απώλειες ολικής πίεσης σε αγωγούς με την αναρρόφηση ή την έγχυση μικρής ποσότητας ρευστού. Αυτό γίνεται γιατί ελέγχεται κατάλληλα η ανάπτυξη του οριακού στρώματος, η οποία παίζει πολύ σημαντικό ρόλο στην αποτροπή ή στην καθυστέρηση της αποκόλλησης της ροής. Στην εργασία αυτή, μετά την εύρεση των καταλληλότερων, σύμφωνα με το χάρτη παραγώγων ευαισθησίας, θέσεων τοποθέτησης δεσμών ρευστού και του είδους της δέσμης (αναρρόφησης ή έγχυσης ρευστού) με σκοπό την ελαχιστοποίηση των απωλειών σχετικής ολικής πίεσης διαμέσου της περιστρεφόμενης πτερύγωσης, γίνονται διάφορες παραμετρικές διερευνήσεις. Από τα αποτελέσματα της διερεύνησης επιβεβαιώνεται η εύρεση της καταλληλότερης (μεταξύ των εξεταζόμενων) θέσης τοποθέτησης δέσμης όπως προέκυψε από την εφαρμογή της συνεχούς συζυγούς μεθόδου και εξάγονται συμπεράσματα σχετικά με την παροχή και την κατανομή ταχύτητας της δέσμης. Πέρα από την εφαρμογή της συνεχούς συζυγούς μεθόδου για τον ενεργητικό έλεγχο της ροής σε τριδιάστατη περιστρεφόμενη πτερύγωση αξονικού συμπιεστή, γίνεται και σύγκριση των αποτελεσμάτων του ευθέος προβλήματος όταν σε αυτό χρησιμοποιούνται διαφορετικά μοντέλα τύρβης καθώς και διαφορετικό λογισμικό επίλυσης. Συγκεκριμένα γίνεται σύγκριση των αποτελεσμάτων μεταξύ των μοντέλων τύρβης Spalart-Allmaras (μιας διαφορικής εξίσωσης) και k-ε, k-ω SST (δύο διαφορικών εξισώσεων) καθώς και των αποτελεσμάτων του ανοικτού λογισμικού OpenFOAM με το οικείο λογισμικό, το οποίο χρησιμοποιήθηκε για την επίλυση των εξισώσεων της ροής σε άλλη, παράλληλα εξελισσόμενη, διπλωματική εργασία. Το ανοικτό λογισμικό χρησιμοποιεί τον αλγόριθμο SIMPLE (Semi-Implicit Method for Pressure Linked Equations) και κεντροκυψελική διατύπωση πεπερασμένων όγκων για την επίλυση των εξισώσεων Navier - Stokes και τρέχει σε παράλληλους επεξεργαστές (CPUs), ενώ το οικείο λογισμικό χρησιμοποιεί τη μέθοδο της τεχνητής συμπιεστότητας (Artificial Compressibility) με κεντροκομβική διατύπωση πεπερασμένων όγκων και τρέχει σε κάρτες γραφικών (GPUs).The aim of this diploma thesis is the adaptation and use of continuous adjoint methods for the active flow control of incompressible fluids, in a three dimensional rotating axial compressor cascade (shrouded rotor cascade). The purpose of active flow control is the minimization of relative total pressure losses between the inlet and outlet of the domain in an off-design point operation of the engine. The adjoint method is used to compute the derivatives of the objective function which, in the application of the current thesis, is expressed by the relative total pressure losses between the inlet and outlet of the domain, with respect to the design variables. The design variables in an active flow control problem are virtual velocities at wall boundaries (in a rotor cascade wall boundaries are the blade, the hub and the shroud). To do so, the objective function, augmented with the integral, across the field, of the product of the state equations (which in this case are the Navier-Stokes equations), is used in order to find the adjoint equations, the corresponding boundary conditions and the sensitivity derivatives. In the present thesis, the usual assumption of frozen turbulence is used. According to this assumption, the turbulence model quantities are not affected by the control variables. The partial differential equations of the adjoint problem are discretized and solved to determine the field of the adjoint variables and, through them, their sensitivity derivatives with respect to the design variables of the problem.Then, the sensitivity derivatives map is produced and indicates the best locations for placement of active flow control devices (steady suction or blowing jets). Generally, active control of the flow with the use of steady jets is used because it provides significant increase in airfoil lift and reduction in the total pressure losses in channels with the injection or suction of small quantities of fluid. This results to an adequate development of the boundary layer and leads to reduction or even prevention of flow separation. In the present thesis, after finding the most promising locations for placement and the type (suction or blowing) of jets according to the sensitivity derivatives map, a parametricic study is carried out. The results of this parametric study confirm that the continuous adjoint method locates the best, between the examined, position for placement of jets. Also, conclusions according jet`s mass flow rate and velocity profile are exported. Beside the use of continuous adjoint methods for the active flow control in a three dimensional rotating axial compressor cascade, comparisons are carried out between the results of primal problem when different turbulence models and different softwares are used. Specifically, the different turbulence models used here are the one equation Spalart-Allmaras and the two equations k - ε and k - ω SST. The different softwares are the open source OpenFOAM and an in-house developed software. The in-house software is used to numerically solve Navier - Stokes equation in a parrallel evolving diploma thesis. The open source software runs on parallel CPU units, uses the SIMPLE algorithm(Semi-Implicit Method for Pressure Linked Equations) to numerically solve Navier - Stokes equation and the cell-centered finite volume formulation, while the in-house software runs on a GPU unit, uses the artificial compressibility method and the vertex-centered finite volume formulation.Παντελής Γ. Κουλλαπή