Animal blood in translational research: How to adjust animal blood viscosity to the human standard.

Animal blood is used in mock circulations or in forensic bloodstain pattern analysis. Blood viscosity is important in these settings as it determines the driving pressure through biomedical devices and the shape of the bloodstain. However, animal blood can never exactly mimic human blood due to erythrocyte properties differing among species. This results in the species-specific shear thinning behavior of blood suspensions, and it is therefore not enough to adjust the hematocrit of an animal blood sample to mimic the behavior of human blood over the entire range of shear rates that are present in the body. In order to optimize experiments that require animal blood, we need models to adapt the blood samples. We here offer mathematical models derived for each species using a multi linear regression approach to describe the influence of shear rate, hematocrit, and temperature on blood viscosity. Results show that pig blood cannot be recommended for experiments at low flow conditions (<200 s-1 ) even though erythrocyte properties are similar in pigs and humans. However, pig blood mimics human blood excellently at high flow condition. Horse blood is unsuitable as experimental model in this regard. For several studied conditions, sheep blood was the closest match to human blood viscosity among the tested species.

Assessment of PIV performance in validating CFD models from nasal cavity CBCT scans.

OBJECTIVE: The aim of our study was to investigate how well Particle Image Velocimetry (PIV) measurements could serve Computational Fluid Dynamics (CFD) model validation for nasal airflow. MATERIAL AND METHODS: For the PIV measurements, a silicone model of the nose based on cone beam computed tomography (CBCT) scans of a patient was made. Corresponding CFD calculations were conducted with laminar and two turbulent models (k-ω and k-ω SST). RESULTS: CFD and PIV results corresponded well in our study. Especially, the correspondence of CFD calculations between the laminar and turbulent models was found to be even stronger. When comparing CFD with PIV, we found that the results were most convergent in the wider parts of the nasal cavities. CONCLUSION: PIV measurements in realistically modelled nasal cavities succeed acceptably and CFD calculations produce corresponding results with PIV measurements. Greater model scaling is, however, necessary for better validations with PIV and comparisons of competing CFD models.

Optimizing ophthalmic delivery of a poorly water soluble drug from an aqueous in situ gelling system.

Poorly soluble drugs are often unsuitable to incorporate in ocular in situ gelling systems due to the aqueous based gelling formulations and low volumes administered. For such formulations to be successful, the administered drug must have sufficient solubility to diffuse from the formulation to the eye and should not affect the gelation of the in situ gelling material. Drug salt forms can improve the solubility of poorly soluble drugs, however, as in situ gel forming formulations are often designed to be crosslinked by salts (present the lacrimal fluid) it can make salt forms difficult to formulate. The aim of this study was to develop an in situ gel forming ophthalmic formulation of a poorly soluble drug flurbiprofen (FBP) through cyclodextrin complex formation and to analyse the impact on gelation, release and permeation through the cornea. Hydroxypropyl-beta-cyclodextrin (HßCD) was used as a complexing agent and low acyl gellan gum was added to the FBP- HßCD complex as a water soluble in situ gelling polymer. Measurements were performed using rheo-dissolution, which utilises a rheometer with a modified lower plate that has the unique ability to allow rheological measurement and analysis of drug release simultaneously. An ex-vivo permeation study was also performed using porcine cornea. Rheological measurements in terms of elastic (G') and viscous (G″) modulus showed rapid gelation of the formulation upon contact with simulated lacrimal fluid (SLF). Approximately, 97% FBP was released when 10% HßCD was used and release was decreased to 79% when the amount of HßCD was increased to 20%. The percentage of drug permeation through the cornea was 55% in 300 min whereas the marketed non gelling eye drop formulation containing FBP sodium showed only 37% permeation. The data presented here, revealed that not only could a poorly soluble drug be complexed with cyclodextrin and loaded into an in situ gelling system without interfering with the gelation, but also permeability the of the drug improved.

Comparison of intracranial aneurysm flow quantification techniques: standard PIV vs stereoscopic PIV vs tomographic PIV vs phase-contrast MRI vs CFD.

Image-based hemodynamic simulations to assess the rupture risk or improve the treatment planning of intracranial aneurysms have become popular recently. However, due to strong modeling assumptions and limitations, the acceptance of numerical approaches remains limited. Therefore, validation using experimental methods is mandatory.In this study, a unique compilation of four in-vitro flow measurements (three particle image velocimetry approaches using a standard (PIV), stereoscopic (sPIV), and tomographic (tPIV) setup, as well as a phase-contrast magnetic resonance imaging (PC-MRI) measurement) were compared with a computational fluid dynamics (CFD) simulation. This was carried out in a patient-specific silicone phantom model of an internal carotid artery aneurysm under steady flow conditions. To evaluate differences between each technique, a similarity index (SI) with respect to the velocity vectors and the average velocity magnitude differences among all involved modalities were computed.The qualitative comparison reveals that all techniques are able to provide a reasonable description of the global flow structures. High quantitative agreement in terms of SI and velocity magnitude differences was found between all PIV methods and CFD. However, quantitative differences were observed between PC-MRI and the other techniques. Deeper analysis revealed that the limited resolution of the PC-MRI technique is a major contributor to the experienced differences and leads to a systematic underestimation of overall velocity magnitude levels inside the vessel. This confirms the necessity of using highly resolving flow measurement techniques, such as PIV, in an in-vitro environment to individually verify the validity of the numerically obtained hemodynamic results.

Shape oscillations of single blood drops: applications to human blood and sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder associated with severe anemia, vessel occlusion, poor oxygen transport and organ failure. The presence of stiff and often sickle-shaped red blood cells is the hallmark of SCD and is believed to contribute to impaired blood rheology and organ damage. Most existing measurement techniques of blood and red blood cell physical properties require sample contact and/or large sample volume, which is problematic for pediatric patients. Acoustic levitation allows rheological measurements in a single drop of blood, simultaneously eliminating the need for both contact containment and manipulation of samples. The technique shows that the shape oscillation of blood drops is able to assess blood viscosity in normal and SCD blood and demonstrates an abnormally increased viscosity in SCD when compared with normal controls. Furthermore, the technique is sensitive enough to detect viscosity changes induced by hydroxyurea treatment, and their dependence on the total fetal hemoglobin content of the sample. Thus this technique may hold promise as a monitoring tool for assessing changes in blood rheology in sickle cell and other hematological diseases.

Non-invasive cardiac output measurement with electrical velocimetry in patients undergoing liver transplantation: comparison of an invasive method with pulmonary thermodilution.

BACKGROUND: The goal of this study was to evaluate the accuracy and interchangeability between continuous cardiac output (CO) measured by electrical velocimetry (COEv) and continuous cardiac output obtained using the pulmonary thermodilution method (COPAC) during living donor liver transplantation (LDLT). METHOD: Twenty-three patients were enrolled in this prospective observational study. CO was recorded by both two methods and compared at nine specific time points. The data were analyzed using correlation coefficients, Bland-Altman analysis for the percentage errors, and the concordance rate for trend analysis using a four-quadrant plot. RESULTS: In total, 207 paired datasets were recorded during LDLT. CO data were in the range of 2.8-12.7 L/min measured by PAC and 3.4-14.9 L/min derived from the EV machine. The correction coefficient between COPAC and COEv was 0.415 with p < 0.01. The 95% limitation agreement was - 5.9 to 3.4 L/min and the percentage error was 60%. The concordance rate was 56.5%. CONCLUSIONS: The Aesculon™ monitor is not yet interchangeable with continuous thermodilution CO monitoring during LDLT. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Chang Gung Medical Foundation in Taiwan (registration number: 201600264B0 ).

Airflow Error Measurement Due to Pneumotachograph Mask Rim Leaks.

Airflow during speech production is recorded using a pneumotachograph system wherein typically a mask is placed upon the face. Accurate measures of airflow require mask calibration and a complete seal of the mask rim to the face. Literature frequently cites mask rim leaks as causing flow measurement inaccuracies, but quantitative studies of the inaccuracies are needed. The purpose of this study was to determine the degree of inaccuracy of flow measurement using a Glottal Enterprises aerodynamic system for a variety of mask rim leak conditions. Air was pushed and pulled through the Glottal Enterprises mask system over a wide range of airflow with leaks simulated by small metal tubes of various cross-sectional areas placed between the mask rim and a face-like calibration mold. Two leak locations, single versus multiple leaks, and two different leak tube geometries were used. Results suggest that (1) as leak area increases, the amount of leak flow increases; (2) the amount of flow leak is relatively independent of location; (3) given equivalent leak areas, multiple leak locations provide less leak flow; and (4) quasi-elliptical tubes were more resistive to airflow than rectangular tubes. A general empirical equation was obtained that relates the leak flow between the mask rim and the face, the size of the leak region, and the amount of the upstream airflow toward the mask: Leak(cm3/s) = 0.33 × Area(cm2) × Flow(cm3/s) for the range of ±2000 cm3/s. This equation may provide researchers and clinicians with a tool for generalizing airflow leak effects.

Modeling and Qualification of a Modified Emission Unit for Radioactive Air Emissions Stack Sampling Compliance.

A planned laboratory space and exhaust system modification to the Pacific Northwest National Laboratory Material Science and Technology Building indicated that a new evaluation of the mixing at the air sampling system location would be required for compliance to ANSI/HPS N13.1-2011. The modified exhaust system would add a third fan, thereby increasing the overall exhaust rate out the stack, thus voiding the previous mixing study. Prior to modifying the radioactive air emissions exhaust system, a three-dimensional computational fluid dynamics computer model was used to evaluate the mixing at the sampling system location. Modeling of the original three-fan system indicated that not all mixing criteria could be met. A second modeling effort was conducted with the addition of an air blender downstream of the confluence of the three fans, which then showed satisfactory mixing results. The final installation included an air blender, and the exhaust system underwent full-scale tests to verify velocity, cyclonic flow, gas, and particulate uniformity. The modeling results and those of the full-scale tests show agreement between each of the evaluated criteria. The use of a computational fluid dynamics code was an effective aid in the design process and allowed the sampling system to remain in its original location while still meeting the requirements for sampling at a well mixed location.

Analysis of Transitional and Turbulent Flow Through the FDA Benchmark Nozzle Model Using Laser Doppler Velocimetry.

Transitional and turbulent flow through a simplified medical device model is analyzed as part of the FDA's Critical Path Initiative, designed to improve the process of bringing medical products to market. Computational predictions are often used in the development of devices and reliable in vitro data is needed to validate computational results, particularly estimations of the Reynolds stresses that could play a role in damaging blood elements. The high spatial resolution of laser Doppler velocimetry (LDV) is used to collect two component velocity data within the FDA benchmark nozzle model. Two flow conditions are used to produce flow encompassing laminar, transitional, and turbulent regimes, and viscous stresses, principal Reynolds stresses, and turbulence intensities are calculated from the measured LDV velocities. Axial velocities and viscous stresses are compared to data from a prior inter-laboratory study conducted with particle image velocimetry. Large velocity gradients are observed near the wall in the nozzle throat and in the jet shear layer located in the expansion downstream of the throat, with axial velocity changing as much as 4.5 m/s over 200 µm. Additionally, maximum Reynolds shear stresses of 1000-2000 Pa are calculated in the high shear regions, which are an order of magnitude higher than the peak viscous shear stresses (<100 Pa). It is important to consider the effects of both viscous and turbulent stresses when simulating flow through medical devices. Reynolds stresses above commonly accepted hemolysis thresholds are measured in the nozzle model, indicating that hemolysis may occur under certain flow conditions. As such, the presented turbulence quantities from LDV, which are also available for download at https://fdacfd.nci.nih.gov/ , provide an ideal validation test for computational simulations that seek to characterize the flow field and to predict hemolysis within the FDA nozzle geometry.

A Novel Device for the Evaluation of Hemostatic Function in Critical Care Settings.

Major surgical procedures often result in significant intra- and postoperative bleeding. The ability to identify the cause of the bleeding has the potential to reduce the transfusion of blood products and improve patient care. We present a novel device, the Quantra Hemostasis Analyzer, which has been designed for automated, rapid, near-patient monitoring of hemostasis. The Quantra is based on Sonic Estimation of Elasticity via Resonance Sonorheometry, a proprietary technology that uses ultrasound to measure clot time and clot stiffness from changes in viscoelastic properties of whole blood during coagulation. We present results of internal validation and analytical performance testing of the technology and demonstrate the ability to characterize the key functional components of hemostasis.

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome.

CONTEXT: Elaboration of oral liquid formulations is the best alternative when no marketed forms are available for pediatrics. OBJECTIVE: The development, characterization and stability evaluation of methadone (MI, MII, MIII) and phenobarbital (PI, PII) can be used for the treatment of neonatal abstinence syndrome (NAS). MATERIAL AND METHODS: A standard operating procedure was established and parameters such as appearance, pH, rheological behavior and drug content were evaluated at three temperatures for 90 days. RESULTS AND DISCUSSION: Changes in color of phenobarbital made necessary the storage below 25 °C. pH did not change in methadone solutions and was able to maintain phenobarbital solubilized. Degradation data at 4 °C fitted to Plateau equation followed by one phase decay. MI was stable for 60 days at the three temperatures; MII for 90 days at 4 and 25 °C and 60 days at 40 °C; MIII for 60 days at 4 °C, 15 days at 25 °C and 7 days at 4 °C. PI was stable for 60 days at 4 °C and 30 days at 25 °C. PII was stable for 7 days at 4 and 25 °C. All solutions met microbial specifications. CONCLUSION: A correct dosage for the treatment of NAS was guaranteed.

A novel tool to standardize rheology testing of molten polymers for pharmaceutical applications.

Melt rheology provides information about material properties that are of great importance for equipment design and simulations, especially for novel pharmaceutical manufacturing operations, including extrusion, injection molding or 3d printing. To that end, homogeneous samples must be prepared, most commonly via compression or injection molding, both of which require costly equipment and might not be applicable for shear- and heat-sensitive pharmaceutical materials. Our study introduces a novel vacuum compression molding (VCM) tool for simple preparation of thermoplastic specimens using standard laboratory equipment: a hot plate and a vacuum source. Sticking is eliminated by applying polytetrafluoroethylene (PTFE) coated separation foils. The evacuation of the tool leads to compression of the sample chamber, which is cost-efficient compared to conventional methods, such as compression molding or injection molding that require special equipment. In addition, this compact design reduces the preparation time and the heat load. The VCM tool was used to prepare samples for a rheological study of three pharmaceutical polymers (Soluplus(®), Eudragit(®)E, EVA Rowalit(®) 300-1/28). The prepared samples were without any air inclusions or voids, and the measurements had a high reproducibility. All relative standard deviations were below 3%. The obtained data were fitted to the Carreau-Yasuda model and time-temperature superposition was applied.

Impedance cardiography (electrical velocimetry) and transthoracic echocardiography for non-invasive cardiac output monitoring in pediatric intensive care patients: a prospective single-center observational study.

INTRODUCTION: Electrical velocimetry (EV) is a type of impedance cardiography, and is a non-invasive and continuously applicable method of cardiac output monitoring. Transthoracic echocardiography (TTE) is non-invasive but discontinuous. METHODS: We compared EV with TTE in pediatric intensive care patients in a prospective single-center observational study. Simultaneous, coupled, left ventricular stroke volume measurements were performed by EV using an Aesculon® monitor and TTE (either via trans-aortic valve flow velocity time integral [EVVTI], or via M-mode [EVMM]). H0: bias was less than 10% and the mean percentage error (MPE) was less than 30% in Bland-Altman analysis between EV and TTE. If appropriate, data were logarithmically transformed prior to Bland-Altman analysis. RESULTS: A total of 72 patients (age: 2 days to 17 years; weight: 0.8 to 86 kg) were analyzed. Patients were divided into subgroups: organ transplantation (OTX, n = 28), sepsis or organ failure (SEPSIS, n = 16), neurological patients (NEURO, n = 9), and preterm infants (PREM, n = 26); Bias/MPE for EVVTI was 7.81%/26.16%. In the EVVTI subgroup analysis for OTX, NEURO, and SEPSIS, bias and MPE were within the limits of H0, whereas the PREM subgroup had a bias/MPE of 39.00%/46.27%. Bias/MPE for EVMM was 8.07%/37.26% where the OTX and NEURO subgroups were within the range of H0, but the PREM and SEPSIS subgroups were outside the range. Mechanical ventilation, non-invasive continuous positive airway pressure ventilation, body weight, and secondary abdominal closure were factors that significantly affected comparison of the methods. CONCLUSIONS: This study shows that EV is comparable with aortic flow-based TTE for pediatric patients.

Investigation on dynamic calibration for an optical-fiber solids concentration probe in gas-solid two-phase flows.

This paper presents a review and analysis of the research that has been carried out on dynamic calibration for optical-fiber solids concentration probes. An introduction to the optical-fiber solids concentration probe was given. Different calibration methods of optical-fiber solids concentration probes reported in the literature were reviewed. In addition, a reflection-type optical-fiber solids concentration probe was uniquely calibrated at nearly full range of the solids concentration from 0 to packed bed concentration. The effects of particle properties (particle size, sphericity and color) on the calibration results were comprehensively investigated. The results show that the output voltage has a tendency to increase with the decreasing particle size, and the effect of particle color on calibration result is more predominant than that of sphericity.

Accurate blood flow measurements: are artificial tracers necessary?

Imaging-based blood flow measurement techniques, such as particle image velocimetry, have become an important tool in cardiovascular research. They provide quantitative information about blood flow, which benefits applications ranging from developmental biology to tumor perfusion studies. Studies using these methods can be classified based on whether they use artificial tracers or red blood cells to visualize the fluid motion. We here present the first direct comparison in vivo of both methods. For high magnification cases, the experiments using red blood cells strongly underestimate the flow (up to 50% in the present case), as compared to the tracer results. For medium magnification cases, the results from both methods are indistinguishable as they give the same underestimation of the real velocities (approximately 33%, based on in vitro reference measurements). These results suggest that flow characteristics reported in literature cannot be compared without a careful evaluation of the imaging characteristics. A method to predict the expected flow averaging behavior for a particular facility is presented.

Performance of a continuous flow microbial electrolysis cell (MEC) fed with domestic wastewater.

In this study, MEC performance was investigated in terms of chemical oxygen demand (COD) removal, hydrogen production rate and energy consumption during continuous domestic wastewater (dWW) treatment at different organic loading rates (OLR) and applied voltages (Vapp). While the COD removal efficiency was improved at low OLRs, the electrical energy required to remove 1g of COD was significantly increased with decreasing the OLR. Hydrogen production exhibited a Monod-type trend as function of the OLR reaching a maximum production rate of 0.30 L/(Lrd). Optimal Vapp was found to be highly dependent on the strength of the dWW. The results also confirmed the fact that MEC performance can be optimized by setting Vapp at the onset potential of the diffusion control region. Although low columbic efficiencies and the occurrence of hydrogen recycling limited significantly the reactor performance, these results demonstrate that MEC can be successfully used for dWW treatment.

Performance tests of newly developed adsorption/plasma combined system for decomposition of volatile organic compounds under continuous flow condition.

The adsorption/plasma decomposition with the combination of adsorption honeycomb-sheets and a plasma element is a new technology for small-sized apparatuses to decompose volatile organic compounds (VOCs) at concentrations lower than about 100 ppm. The feasibility of the prototype adsorption/plasma decomposition apparatus was evaluated with the simulated exhausts containing one VOC component and with real exhausts from a painting booth and an adhesion factory. The apparatus decomposed VOCs effectively at the painting booth exhaust but not always satisfactorily at the adhesion factory exhaust. The performance test results with real exhausts were discussed with respect to the concentration and discharge pattern of the exhausts and the basic properties of the system such as cooperation of adsorption and plasma reaction and the concentration dependence of the performance.

Relevance of rheological properties of sodium alginate in solution to calcium alginate gel properties.

The purpose of this study is to determine whether sodium alginate solutions' rheological parameters are meaningful relative to sodium alginate's use in the formulation of calcium alginate gels. Calcium alginate gels were prepared from six different grades of sodium alginate (FMC Biopolymer), one of which was available in ten batches. Cylindrical gel samples were prepared from each of the gels and subjected to compression to fracture on an Instron Universal Testing Machine, equipped with a 1-kN load cell, at a cross-head speed of 120 mm/min. Among the grades with similar % G, (grades 1, 3, and 4), there is a significant correlation between deformation work (L(E)) and apparent viscosity (η(app)). However, the results for the partial correlation analysis for all six grades of sodium alginate show that L(E) is significantly correlated with % G, but not with the rheological properties of the sodium alginate solutions. Studies of the ten batches of one grade of sodium alginate show that η(app) of their solutions did not correlate with L(E) while tan δ was significantly, but minimally, correlated to L(E). These results suggest that other factors--polydispersity and the randomness of guluronic acid sequencing--are likely to influence the mechanical properties of the resultant gels. In summary, the rheological properties of solutions for different grades of sodium alginate are not indicative of the resultant gel properties. Inter-batch differences in the rheological behavior for one specific grade of sodium alginate were insufficient to predict the corresponding calcium alginate gel's mechanical properties.

Avoid cruising on the uroflowmeter: evaluation of cruising artifact on spinning disc flowmeters in an experimental setup.

AIMS: The aim of our study was to access the variability of maximum flow rate (Q(max)), average flow rate (Q(av)) and flow pattern while varying the point of impact of flow on the flowmeter. METHODS: Water was delivered through a motorised tube holder in a standardised experimental set up. Flow was directed in 4 different directions on the funnel; 1) Periphery, 2) Base, 3) Centre and, 4) in a cruising motion from the periphery of the funnel to the centre and back again. The variation in the Q(max), Q(av) and the flow pattern were studied at 4 different flow rates. The variables recorded when the flow was directed at the centre of the funnel was taken as baseline. RESULTS: There was a significant difference in the Q(max) and Q(av)when the point of impact was at the periphery or in a cruising motion compared to the centre. The difference was more marked with cruising motion with a characteristic flow pattern. The maximum percentage difference in Q(av) was 4.1%, whereas the difference in Q(max) was higher at 16.6% on comparing crusing motion with the values from the centre. CONCLUSION: We have demonstrated a significant variation in Q(max), Q(av) and flow pattern with change in the point of impact on the flowmeter. Though the changes in Q(av) were statistically significant, the alteration in the recorded Q(max) values was more striking. Our study emphasizes the importance of combining Q(av) and flow pattern along with Q(max) in interpretation of results of uroflowmetry.

Middle cerebral artery median peak systolic velocity validation: effect of measurement technique.

We sought to validate center-specific published medians and estimate the effects of sonologist and Doppler measurement techniques on middle cerebral artery (MCA) peak systolic velocity (PSV) values. We studied 154 gravidas with normal singletons who underwent MCA PSV measurement at 18 to 35 weeks' gestation by one of three experienced sonologists. Pregnancies complicated by a known fetal anomaly (structural or aneuploidy), amniotic fluid volume disturbance, intrauterine growth restriction, multiple gestation, or isoimmunization were excluded. MCA PSV was measured using both manual caliper and auto-trace techniques. Regression models of log-transformed PSV values and gestational age were developed. Although auto-trace medians were significantly lower than those obtained with manual calipers ( P < 0.0001), they more closely approximated published medians used in clinical practice. Minimal intersonologist differences (maximum mean difference <3 cm/s) were statistically significant ( P < 0.01). Compared with manual caliper, auto-trace measurement yielded significantly lower medians. However, center-specific medians obtained by our sonologists using auto-trace more closely approximated published standards. Estimated interobserver variability suggested that different sonologists may utilize the same median values. We suggest that centers that utilize Doppler velocimetry for the prediction of fetal anemia examine their measurement protocol and consider formal confirmation of their own center-specific median values.