Needle-shaped crystals are a common occurrence in many pharmaceutical and fine chemicals processes. Even if the particle size distribution (PSD) obtained in a crystallization step can be controlled by the crystal growth kinetics and hydrodynamic conditions, further fluid-solid separation steps such as filtration, filter washing, drying, and subsequent solids handling can often lead to uncontrolled changes in the PSD due to breakage. In this contribution we present a combined computational and experimental methodology for determining the breakage kernel and the daughter distribution functions of needle-shaped crystals, and for population balance modeling of their breakage. A discrete element model (DEM) of needle-shaped particle breakage was first used in order to find out the appropriate types of the breakage kernel and the daughter distribution functions. A population balance model of breakage was then formulated and used in conjunction with experimental data in order to determine the material-specific parameters appearing in the breakage functions. Quantitative agreement between simulation and experiment has been obtained.

• MeSH
• Models, Chemical MeSH
• Filtration MeSH
• Hydrodynamics MeSH
• Crystallization MeSH
• Pharmaceutical Preparations chemistry   MeSH
• Computer Simulation MeSH
• Particle Size MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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 15years 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.

• MeSH
• Respiratory Tract Absorption MeSH
• Aerosols chemistry   MeSH
• Administration, Inhalation MeSH
• Benchmarking methods   MeSH
• Models, Biological MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Hydrodynamics MeSH
• Laryngeal Masks * MeSH
• Drug Delivery Systems methods   MeSH
• Humans MeSH
• Nebulizers and Vaporizers MeSH
• Permeability MeSH
• Lung drug effects   MeSH
• Computer Simulation * MeSH
• Powders chemistry   MeSH
• Rheology MeSH
• Particle Size MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Recent developments in the prediction of local aerosol deposition in human lungs are driven by the fast development of computational simulations. Although such simulations provide results in unbeatable resolution, significant differences among distinct methods of calculation emphasize the need for highly precise experimental data in order to specify boundary conditions and for validation purposes. This paper reviews and critically evaluates available methods for the measurement of single and disperse two-phase flows for the study of respiratory airflow and deposition of inhaled particles, performed both in vivo and in replicas of airways. Limitations and possibilities associated with the experimental methods are discussed and aspects of the computational calculations that can be validated are indicated. The review classifies the methods into following categories: 1) point-wise and planar methods for velocimetry in the airways, 2) classic methods for the measurement of the regional distribution of inhaled particles, 3) standard medical imaging methods applicable to the measurement of the regional aerosol distribution and 4) emerging and nonconventional methods. All methods are described, applications in human airways studies are illustrated, and recommendations for the most useful applications of each method are given.

• MeSH
• Respiratory Tract Absorption MeSH
• Aerosols chemistry   MeSH
• Administration, Inhalation MeSH
• Models, Biological MeSH
• Chemistry, Pharmaceutical methods   MeSH
• Hydrodynamics MeSH
• Laryngeal Masks * MeSH
• Drug Delivery Systems methods   MeSH
• Humans MeSH
• Nebulizers and Vaporizers MeSH
• Permeability MeSH
• Lung drug effects   MeSH
• Computer Simulation * MeSH
• Powders chemistry   MeSH
• Particle Size MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.

• MeSH
• Models, Biological MeSH
• Humans MeSH
• Respiratory Mechanics physiology   MeSH
• Lung physiology   MeSH
• Computer Simulation MeSH
• Mouth physiology   MeSH
• Pulmonary Gas Exchange physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Femoropopliteal bypass is a common vascular reconstructive procedure. A significant proportion of bypasses become ineffective within 1 year because of occlusion due to progression of intimal hyperplasia (IH). METHODS: The clinical part of the study involved an analysis of 43 patients with proximal femoropopliteal bypass, which became occluded no later than 1 year from the procedure, who were successfully treated with thrombolysis. Morphological changes of intima in the anastomosis (evaluated angiographically) and the angle of the distal end-to-side anastomosis were evaluated. In the second part of the study, blood flow in the distal end-to-side anastomosis was modeled experimentally (by particle image velocimetry) and numerically (by computational fluid dynamics). The results were correlated with the previously identified locations of IH. RESULTS: We proved that the locations of IH correlate with the locations of disturbed blood flow, increased wall shear stress, and stagnation points as documented by experimental visualization and angiographic findings. We also confirmed that anastomoses with more acute angles are less prone to IH and occlusion of the lumen. CONCLUSION: We suggest that a better understanding of the hemodynamics and its influence on IH should lead to an optimized graft design by adopting a more acute angle of the anastomosis.

• MeSH
• Anastomosis, Surgical MeSH
• Femoral Artery surgery   physiopathology   radiography   MeSH
• Popliteal Artery surgery   physiopathology   radiography   MeSH
• Arterial Occlusive Diseases surgery   physiopathology   radiography   MeSH
• Time Factors MeSH
• Hemodynamics MeSH
• Hyperplasia MeSH
• Humans MeSH
• Stress, Mechanical MeSH
• Models, Cardiovascular MeSH
• Graft Occlusion, Vascular etiology   drug therapy   physiopathology   radiography   MeSH
• Computer Simulation MeSH
• Vascular Patency MeSH
• Recurrence MeSH
• Thrombolytic Therapy MeSH
• Tunica Intima radiography   MeSH
• Vascular Surgical Procedures methods   adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

The geometric shape of the distal anastomosis in an infrainguinal bypass has an influence on its durability. In this article, we compared three different angles of the anastomosis with regard to the hemodynamics. Three experimental models of the distal infrainguinal anastomosis with angles of 25°, 45°, and 60° respectively were constructed according to the similarity theory to assess flow in the anastomoses using particle image velocimetry and computational fluid dynamics. In the toe, heel, and floor of the anastomosis that correspond to the locations worst affected by intimal hyperplasia, adverse blood flow and wall shear stress were observed in the 45° and 60° models. In the 25° model, laminar blood flow was apparent more peripherally from the anastomosis. In conclusions, decreasing the distal anastomosis angle in a femoropopliteal bypass results in more favorable hemodynamics including the flow pattern and wall shear stress in locations susceptible to intimal hyperplasia.

• MeSH
• Anastomosis, Surgical methods   MeSH
• Lower Extremity blood supply   MeSH
• Hemodynamics MeSH
• Humans MeSH
• Hemorheology MeSH
• Vascular Surgical Procedures methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Viruses have been classified as non-living because they require a cellular host to support their replicative processes. Empirical investigations have significantly advanced our understanding of the many strategies employed by viruses to usurp and divert host regulatory and metabolic processes to drive the synthesis and release of infectious particles. The recent emergence of SARS-CoV-2 has permitted us to evaluate and discuss a potentially novel classification of viruses as living entities. The ability of SARS CoV-2 to engender comprehensive regulatory control of integrative cellular processes is strongly suggestive of an inherently dynamic informational registry that is programmatically encoded by linear ssRNA sequences responding to distinct evolutionary constraints. Responses to positive evolutionary constraints have resulted in a single-stranded RNA viral genome that occupies a threedimensional space defined by conserved base-paring resulting from a complex pattern of both secondary and tertiary structures. Additionally, regulatory control of virus-mediated infectious processes relies on extensive protein-protein interactions that drive conformational matching and shape recognition events to provide a functional link between complementary viral and host nucleic acid and protein domains. We also recognize that the seamless integration of complex replicative processes is highly dependent on the precise temporal matching of complementary nucleotide sequences and their corresponding structural and non-structural viral proteins. Interestingly, the deployment of concerted transcriptional and translational activities within targeted cellular domains may be modeled by artificial intelligence (AI) strategies that are inherently fluid, self-correcting, and adaptive at accommodating temporal changes in host defense mechanisms. An in-depth understanding of multiple self-correcting AIassociated viral processes will most certainly lead to novel therapeutic development platforms, notably the design of efficacious neuropharmacological agents to treat chronic CNS syndromes associated with long-COVID. In summary, it appears that viruses, notably SARS-CoV-2, are very much alive due to acquired genetic advantages that are intimately entrained to existential host processes via evolutionarily constrained AI-associated learning paradigms.

• MeSH
• COVID-19 * complications   MeSH
• Genomics MeSH
• Humans MeSH
• SARS-CoV-2 genetics   MeSH
• Machine Learning MeSH
• Artificial Intelligence MeSH
• Viruses * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Chemistry, Physical MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Fyzikální chemie
• NML Fields
• chemie, klinická chemie

• MeSH
• Neoplasms radiotherapy   MeSH
• Nuclear Medicine methods   MeSH
• Radiotherapy methods   MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Učební osnovy. Vyučovací předměty. Učebnice
• Lékařské vědy. Lékařství
• NML Fields
• radiologie, nukleární medicína a zobrazovací metody
• onkologie
• NML Publication type
• kolektivní monografie

• MeSH
• Lasers MeSH
• Publication type
• Meeting Abstract MeSH
• Collected Work MeSH

• Conspectus
• Optika
• NML Fields
• fyzika, biofyzika
• technika