Surface Reaction of Electroosmotic Flow-Driven Free Antigens With Immobilized Magnetic-Microbeads-Tagged-Antibodies in Microchannels.

Immunoassays based on reactions between target pathogen (antigen; Ag) and antibody (Ab) are frequently used for Ag detection. An external magnetic field was used to immobilize magnetic microbeads-tagged-antibodies (mMB-Ab) on the surface of a microchannel in the capture zone. The mMB-Ab was subsequently used for Ag detection. The objective of this numerical study, with experimental validation, is to assess the surface reaction between mMB-Ab and Ag in the presence of electro-osmotic flow (EOF). First, immobilization of mMB-Ab complex in the wall of the capture zone was achieved. Subsequently, the Ag was transported by EOF toward the capture zone to bind with the immobilized mMB-Ab. Lastly, mMB-Ab:Ag complex was formed and immobilized in the capture zone. A finite volume solver was used to implement the above steps. The surface reaction between the mMB-Ab and Ag was investigated in the presence of electric fields (E): 150 V/cm-450 V/cm and Ag concentrations: 0.001 M-1000 M. The depletion of mMB-Ab increases with time as the E decreases. Furthermore, as the concentration of Ag decreases, the depletion of mMB-Ab increases with time. These results quantify the detection of Ag using the EOF device; thus, signifying its potential for rapid throughput screening of Ag. This platform technology can lead to the development of portable devices for the detection of target cells, pathogens, and biomolecules for testing water systems, biological fluids, and biochemicals.

Use of a Negative Pressure Containment Pod Within Ambulance-Workspace During Pandemic Response.

Emergency medical service (EMS) providers have a higher potential exposure to infectious agents than the general public (Nguyen et al., 2020, "Risk of COVID-19 Among Frontline Healthcare Workers and the General Community: A Prospective Cohort Study," Lancet Pub. Health, 5(9), pp. e475-e483; Brown et al., 2021, "Risk for Acquiring Coronavirus Disease Illness Among Emergency Medical Service Personnel Exposed to Aerosol-Generating Procedures," Emer. Infect. Disease J., 27(9), p. 2340). The use of protective equipment may reduce, but does not eliminate their risk of becoming infected as a result of these exposures. Prehospital environments have a high risk of disease transmission exposing EMS providers to bioaerosols and droplets from infectious patients. Field intubation procedures may be performed causing the generation of bioaerosols, thereby increasing the exposure of EMS workers to pathogens. Additionally, ambulances have a reduced volume compared to a hospital treatment space, often without an air filtration system, and no control mechanism to reduce exposure. This study evaluated a containment plus filtration intervention for reducing aerosol concentrations in the patient module of an ambulance. Aerosol concentration measurements were taken in an unoccupied research ambulance at National Institute for Occupational Safety and Health (NIOSH) Cincinnati using a tracer aerosol and optical particle counters (OPCs). The evaluated filtration intervention was a containment pod with a high efficiency particulate air (HEPA)-filtered extraction system that was developed and tested based on its ability to contain, capture, and remove aerosols during the intubation procedure. Three conditions were tested (1) baseline (without intervention), (2) containment pod with HEPA-1, and (3) containment pod with HEPA-2. The containment pod with HEPA-filtered extraction intervention provided containment of 95% of the total generated particle concentration during aerosol generation relative to the baseline condition, followed by rapid air cleaning within the containment pod. This intervention can help reduce aerosol concentrations within ambulance patient modules while performing aerosol-generating procedures.

Comparison Between 5- and 1-Year Outcomes Using Cutoff Values of Pressure Drop Coefficient and Fractional Flow Reserve for Diagnosing Coronary Artery Diseases.

BACKGROUND: The current pressure-based coronary diagnostic index, fractional flow reserve (FFR), has a limited efficacy in the presence of microvascular disease (MVD). To overcome the limitations of FFR, the objective is to assess the recently introduced pressure drop coefficient (CDP), a fundamental fluid dynamics-based combined pressure-flow index. METHODS: We hypothesize that CDP will result in improved clinical outcomes in comparison to FFR. To test the hypothesis, chi-square test was performed to compare the percent major adverse cardiac events (%MACE) at 5 years between (a) FFR < 0.75 and CDP > 27.9 and (b) FFR < 0.80 and CDP > 25.4 groups using a prospective cohort study. Furthermore, Kaplan-Meier survival curves were compared between the FFR and CDP groups. The results were considered statistically significant for p < 0.05. The outcomes of the CDP arm were presumptive as clinical decision was solely based on the FFR. RESULTS: For the complete patient group, the %MACE in the CDP > 27.9 group (10 out of 35, 29%) was lower in comparison to the FFR < 0.75 group (11 out of 20, 55%), and the difference was near significant (p = 0.05). The survival analysis showed a significantly higher survival rate (p = 0.01) in the CDP > 27.9 group (n = 35) when compared to the FFR < 0.75 group (n = 20). The results remained similar for the FFR = 0.80 cutoff. The comparison of the 5-year MACE outcomes with the 1-year outcomes for the complete patient group showed similar trends, with a higher statistical significance for a longer follow-up period of 5 years. CONCLUSION: Based on the MACE and survival analysis outcomes, CDP could possibly be an alternate diagnostic index for decision-making in the cardiac catheterization laboratory. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT01719016.

Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous.

The present research investigates the pharmacokinetics and toxicity of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes. PLGA and CS-based micro-implants containing 400 µg of MTX were surgically inserted in the vitreous of twenty-four New Zealand rabbits using minimally invasive procedures. The PLGA-coated CS-MTX micro-implant and the placebo micro-implant were inserted in the right eye and in the left eye, respectively, of each rabbit. The intravitreal MTX concentration was evaluated on Days 1, 3, 7, 14, 28 and 56. A therapeutic concentration of MTX (0.1-1.0 µM) in the rabbit vitreous was observed for 56 days. The release of MTX in the therapeutic release phase followed first-order kinetics. Histopathologic evaluation on Days 14, 28 and 56 of the enucleated eyes demonstrated no signs of toxicity or any anatomical irregularity in the vitreoretinal domain. Additionally, the micro-implants were stationary at the position of their implantation throughout the duration of the study. The PLGA-coated CS-MTX micro-implant can serve as a potential alternative to the current treatment modality of intravitreal MTX injections based on its performance, thereby avoiding associated complications and the treatment burden of multiple injections.

A computational model for predicting changes in infection dynamics due to leakage through N95 respirators.

In the absence of fit-testing, leakage of aerosolized pathogens through the gaps between the face and N95 respirators could compromise the effectiveness of the device and increase the risk of infection for the exposed population. To address this issue, we have developed a model to estimate the increase in risk of infection resulting from aerosols leaking through gaps between the face and N95 respirators. The gaps between anthropometric face-geometry and N95 respirators were scanned using computed tomography. The gap profiles were subsequently input into CFD models. The amount of aerosol leakage was predicted by the CFD simulations. Leakage levels were validated using experimental data obtained using manikins. The computed amounts of aerosol transmitted to the respiratory system, with and without leaks, were then linked to a risk-assessment model to predict the infection risk for a sample population. An influenza outbreak in which 50% of the population deployed respirators was considered for risk assessment. Our results showed that the leakage predicted by the CFD model matched the experimental data within about 13%. Depending upon the fit between the headform and the respirator, the inward leakage for the aerosols ranged between 30 and 95%. In addition, the non-fit-tested respirator lowered the infection rate from 97% (for no protection) to between 42 and 80%, but not to the same level as the fit-tested respirators (12%). The CFD-based leakage model, combined with the risk-assessment model, can be useful in optimizing protection strategies for a given population exposed to a pathogenic aerosol.

Non-invasive evaluation of toxicity in vitreoretinal domain following insertion of sustained release methotrexate micro-implant.

PURPOSE: To evaluate the safety and toxicity profile of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based sustained release methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes using non-invasive testing that included electroretinography (ERG), ultrasound biomicroscopy (US), slit-lamp biomicroscopy (SLB), funduscopy, and intraocular pressure (IOP). METHODS: PLGA-coated CS-based micro-implants containing 400 µg of MTX and placebo (without drug) micro-implants were surgically-implanted in the vitreous of the right and the left eyes, respectively, in each of the thirty New Zealand rabbits. ERG, US, SLB, funduscopy, and IOP were assessed in both eyes at pre-determined time points (days: 1, 3, 7, 14, 28 and 56). The safety of micro-implants was assessed by analyzing the ERG data using different statistical models, to quantify and compare the functional integrity of the retina. Further, US, funduscopy, SLB and IOP determined the condition of the retina, the micro-implant and associated intraocular features. RESULTS: Statistical analyses of the ERG data showed unchanged functional integrity of retina between eyes with the PLGA-coated CS-based MTX micro-implant and the placebo micro-implant. US analysis showed that micro-implants were stationary throughout the study. SLB, funduscopy and IOP further confirmed that there were no abnormalities in the intraocular physiology. CONCLUSION: The findings from ERG, US, SLB, funduscopy, and IOP showed no detectable adverse effects caused by our biodegradable micro-implants. These non-invasive techniques appeared to show lack of significant ocular toxicity over time in spite of degradation and changes in morphology of the micro-implants following intraocular implantation.

Influence of near-wall PIV data on recirculation hemodynamics in a patient-specific moderate stenosis: Experimental-numerical comparison.

BACKGROUND: Recirculation zones within the blood vessels are known to influence the initiation and progression of atherosclerotic lesions. Quantification of recirculation parameters with accuracy remains subjective due to uncertainties in measurement of velocity and derived wall shear stress (WSS). OBJECTIVE: The primary aim is to determine recirculation height and length from PIV experiments while validating with two different numerical methods: finite-element (FE) and -volume (FV). Secondary aim is to analyze how FE and FV compare within themselves. METHODS: PIV measurements were performed to obtain velocity profiles at eight cross sections downstream of stenosis at flow rate of 200 ml/min. WSS was obtained by linear/quadratic interpolation of experimental velocity measurements close to wall. RESULTS: Recirculation length obtained from PIV technique was 1.47 cm and was within 2.2% of previously reported in-vitro measurements. Derived recirculation length from PIV agreed within 6.8% and 8.2% of the FE and FV calculations, respectively. For lower shear rate, linear interpolation with five data points results in least error. For higher shear rate either higher order (quadratic) interpolation with five data points or lower order (linear) with lesser (three) data points leads to better results. CONCLUSION: Accuracy of the recirculation parameters is dependent on number of near wall PIV data points and the type of interpolation algorithm used.

Electroosmotic flow driven microfluidic device for bacteria isolation using magnetic microbeads.

The presence of bacterial pathogens in water can lead to severe complications such as infection and food poisoning. This research proposes a point-of-care electroosmotic flow driven microfluidic device for rapid isolation and detection of E. coli in buffered solution (phosphate buffered saline solution). Fluorescent E. coli bound to magnetic microbeads were driven through the microfluidic device using both constant forward flow and periodic flow switching at concentrations ranging from 2 × 105 to 4 × 107 bacteria/mL. A calibration curve of fluorescent intensity as a function of bacteria concentration was created using both constant and switching flow, showing an increase in captured fluorescent pixel count as concentration increases. In addition, the use of the flow switching resulted in a significant increase in the capture efficiency of E. coli, with capture efficiencies up to 83% ± 8% as compared to the constant flow capture efficiencies (up to 39% ± 11%), with a sample size of 3 µL. These results demonstrate the improved performance associated with the use of the electroosmotic flow switching system in a point-of-care bacterial detection assay.

Influence of coupled hemodynamics-arterial wall interaction on compliance in a realistic pulmonary artery with variable intravascular wall properties.

Pulmonary hypertension is characterized by elevation of pulmonary artery (PA) pressure (p) and structural remodeling of the PA wall, leading to reduction in arterial compliance (c). As a step towards improving diagnosis of pulmonary disease, we use the PA branch geometry (main pulmonary artery (MPA) branching into left (LPA) and right (RPA) pulmonary arteries) obtained from MRI in conjunction with an inverse algorithm to obtain the pre-stress level in the artery walls. Next, a coupled blood-wall interaction (BWI) calculation provides hemodynamic information as well as compliance of the PA walls. We show that the computed load-free geometry from the inverse algorithm exhibits a 27.8% lower inner diameter (d) and 18.5% lower outer d compared to the in vivo geometry from MRI. Further, the mean p computed from the BWI computation in the main PA (pMPA-n) is within 4% of the mean pMPA-e (n-numerical; e-experimental). Also, the mean Q computed in the left PA (QLPA-n) is within 10% of the mean QLPA-e. Finally, the compliance cMPA-n is computed to be 27% lower than cMPA-e, while the cLPA-n is computed to be 20.4% lower than cLPA-e. Importantly, the PA shows significant intra-vascular variation in compliance, with the MPA showing higher overall compliance compared to the LPA (3.5-4 times).

Evaluation of pulmonary artery stenosis in congenital heart disease patients using functional diagnostic parameters: An in vitro study.

Congenital pulmonary artery (PA) stenosis is often associated with abnormal PA hemodynamics including increased pressure drop (Δp) and reduced asymmetric flow (Q), which may result in right ventricular dysfunction. We propose functional diagnostic parameters, pressure drop coefficient (CDP), energy loss (Eloss), and normalized energy loss (E¯loss) to characterize pulmonary hemodynamics, and evaluate their efficacy in delineating stenosis severity using in vitro experiments. Subject-specific test sections including the main PA (MPA) bifurcating into left and right PAs (LPA, RPA) with a discrete LPA stenosis were manufactured from cross-sectional imaging and 3D printing. Three clinically-relevant stenosis severities, 90% area stenosis (AS), 80% AS, and 70% AS, were evaluated at different cardiac outputs (COs). A benchtop flow loop simulating pulmonary hemodynamics was used to measure Q and Δp within the test sections. The experimental Δp-Q characteristics along with clinical data were used to obtain pathophysiologic conditions and compute the diagnostic parameters. The pathophysiologic QLPA decreased as the stenosis severity increased at a fixed CO. CDPLPA, Eloss,LPA (absolute), and E¯loss,LPA (absolute) increased with an increase in LPA stenosis severity at a fixed CO. Importantly, CDPLPA and E¯loss,LPA had reduced variability with CO, and distinct values for each LPA stenosis severity. Under variable CO, a) CDPLPA values were 14.5-21.0 (70% AS), 60.7- 2.2 (80% AS), ≥ 261.6 (90% AS), and b) E¯loss,LPA values (in mJ per QLPA) were -501.9 to -1023.8 (70% AS), -1247.6 to -1773.0 (80% AS), -1934.5 (90% AS). Hence, CDPLPA and E¯loss,LPA are expected to assess the true functional severity of PA stenosis.

Correction to "Clinical outcomes of combined flow-pressure drop measurements using newly developed diagnostic endpoint: Pressure drop coefficient in patients with coronary artery dysfunction".

[This corrects the article on p. 283 in vol. 8, PMID: 27022460.].

Comparison of Heat Transfer Enhancement Between Magnetic and Gold Nanoparticles During HIFU Sonication.

Long procedure times and collateral damage remain challenges in high-intensity focused ultrasound (HIFU) medical procedures. Magnetic nanoparticles (mNPs) and gold nanoparticles (gNPs) have the potential to reduce the acoustic intensity and/or exposure time required in these procedures. In this research, we investigated relative advantages of using gNPs and mNPs during HIFU thermal-ablation procedures. Tissue-mimicking phantoms containing embedded thermocouples (TCs) and physiologically acceptable concentrations (0.0625% and 0.125%) of gNPs were sonicated at acoustic powers of 5.2 W, 9.2 W, and 14.5 W, for 30 s. It was observed that when the concentration of gNPs was doubled from 0.0625% to 0.125%, the temperature rise increased by 80% for a power of 5.2 W. For a fixed concentration (0.0625%), the energy absorption was 1.7 times greater for mNPs than gNPs for a power of 5.2 W. Also, for the power of 14.5 W, the sonication time required to generate a lesion volume of 50 mm3 decreased by 1.4 times using mNPs, compared with gNPs, at a concentration of 0.0625%. We conclude that mNPs are more likely than gNPs to produce a thermal enhancement in HIFU ablation procedures.

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases.

Evaluation of lesion flow coefficient for the detection of coronary artery disease in patient groups from two academic medical centers.

BACKGROUND: In this study, lesion flow coefficient (LFC: ratio of % area stenosis [%AS] to the square root of the ratio of the pressure drop across the stenosis to the dynamic pressure in the throat region), that combines both the anatomical (%AS) and functional measurements (pressure and flow), was assessed for application in a clinical setting. METHODS AND RESULTS: Pressure, flow, and anatomical values were obtained from patients in 251 vessels from two different centers. Fractional flow reserve (FFR), Coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR) and hyperemic microvascular index (HMR) were calculated. Anatomical data was corrected for the presence of guidewire and the LFC values were calculated. LFC was correlated with FFR, CFR, HSR, HMR, individually and in combination with %AS. The p<0.05 was used for statistical significance. LFC correlated significantly when the FFR (pressure-based), CFR (flow-based), and anatomical measure %AS were combined (r=0.64; p<0.05). Similarly, LFC correlated significantly when HSR, HMR, and %AS were combined (r=0.72; p<0.05). LFC was able to significantly (p<0.05) distinguish between the two concordant and the two discordant groups of FFR and CFR, corresponding to the clinically used cut-off values (FFR=0.80 and CFR=2.0). The LFC could also significantly (p<0.05) distinguish between the normal and abnormal microvasculature conditions in the presence of non-significant epicardial stenosis, while the comparison was borderline significant (p=0.09) in the presence of significant stenosis. CONCLUSION: LFC, a parameter that combines both the anatomical and functional end-points, has the potential for application in a clinical setting for CAD evaluation.

The mechanism of nanoparticle-mediated enhanced energy transfer during high-intensity focused ultrasound sonication.

In this combined experimental and theoretical research, magnetic nano-particle (mNP) mediated energy transfer due to high intensity-focused ultrasound (HIFU) sonication has been evaluated. HIFU sonications have been performed on phantoms containing three different volume percentages (0%, 0.0047%, and 0.047%) of mNPs embedded in a tissue mimicking material (TMM). A theoretical model has been developed to calculate the temperature rise in the phantoms during HIFU sonication. It is observed from theoretical calculation that the phonon layer at the interface of the mNPs and TMM dominates the attenuation for higher (0.047%) concentration. However, for a lower concentration (0.0047%) of mNPs, intrinsic absorption is the dominating mechanism. Attenuation due to the viscous drag becomes the dominating mechanism for larger size mNPs (>1000 nm). At a higher concentration (0.047%), it is observed from theoretical calculations that the temperature rise is 25% less for gold nano-particles (gNPs) when compared to mNPs. However, at lower concentrations (0.0047% and 0.002%), the difference in temperature rise for the mNPs and gNPs is less than 2%.

Assessment of Gold Nanoparticle-Mediated-Enhanced Hyperthermia Using MR-Guided High-Intensity Focused Ultrasound Ablation Procedure.

High-intensity focused ultrasound (HIFU) has gained increasing popularity as a noninvasive therapeutic procedure to treat solid tumors. However, collateral damage due to the use of high acoustic powers during HIFU procedures remains a challenge. The objective of this study is to assess the utility of using gold nanoparticles (gNPs) during HIFU procedures to locally enhance heating at low powers, thereby reducing the likelihood of collateral damage. Phantoms containing tissue-mimicking material (TMM) and physiologically relevant concentrations (0%, 0.0625%, and 0.125%) of gNPs were fabricated. Sonications at acoustic powers of 10, 15, and 20 W were performed for a duration of 16 s using an MR-HIFU system. Temperature rises and lesion volumes were calculated and compared for phantoms with and without gNPs. For an acoustic power of 10 W, the maximum temperature rise increased by 32% and 43% for gNPs concentrations of 0.0625% and 0.125%, respectively, when compared to the 0% gNPs concentration. For the power of 15 W, a lesion volume of 0, 44.5 ± 7, and 63.4 ± 32 mm3 was calculated for the gNPs concentration of 0%, 0.0625%, and 0.125%, respectively. For a power of 20 W, it was found that the lesion volume doubled and tripled for concentrations of 0.0625% and 0.125% gNPs, respectively, when compared to the concentration of 0% gNPs. We conclude that gNPs have the potential to locally enhance the heating and reduce damage to healthy tissue during tumor ablation using HIFU.

Evaluation of Hemodynamics in a Prestressed and Compliant Tapered Femoral Artery Using an Optimization-Based Inverse Algorithm.

The important factors that affect the arterial wall compliance are the tissue properties of the arterial wall, the in vivo pulsatile pressure, and the prestressed condition of the artery. It is necessary to obtain the load-free geometry for determining the physiological level of prestress in the arterial wall. The previously developed optimization-based inverse algorithm was improved to obtain the load-free geometry and the wall prestress of an idealized tapered femoral artery of a dog under varying arterial wall properties. The compliance of the artery was also evaluated over a range of systemic pressures (72.5-140.7 mmHg), associated blood flows, and artery wall properties using the prestressed arterial geometry. The results showed that the computed load-free outer diameter at the inlet of the tapered artery was 6.7%, 9.0%, and 12% smaller than the corresponding in vivo diameter for the 25% softer, baseline, and 25% stiffer arterial wall properties, respectively. In contrast, the variations in the prestressed geometry and circumferential wall prestress were less than 2% for variable arterial wall properties. The computed compliance at the inlet of the prestressed artery for the baseline arterial wall property was 0.34%, 0.19%, and 0.13% diameter change/mmHg for time-averaged pressures of 72.5, 104.1, and 140.7 mmHg, respectively. However, the variation in compliance due to the change in arterial wall property was less than 6%. The load-free and prestressed geometries of the idealized tapered femoral artery were accurately (error within 1.2% of the in vivo geometry) computed under variable arterial wall properties using the modified inverse algorithm. Based on the blood-arterial wall interaction results, the arterial wall compliance was influenced significantly by the change in average pressure. In contrast, the change in arterial wall property did not influence the arterial wall compliance.

Uncertainty Analysis of the Core Body Temperature Under Thermal and Physical Stress Using a Three-Dimensional Whole Body Model.

Heat stress experienced by firefighters is a common consequence of extreme firefighting activity. In order to avoid the adverse health conditions due to uncompensable heat stress, the prediction and monitoring of the thermal response of firefighters is critical. Tissue properties, among other parameters, are known to vary between individuals and influence the prediction of thermal response. Further, measurement of tissue properties of each firefighter is not practical. Therefore, in this study, we developed a whole body computational model to evaluate the effect of variability (uncertainty) in tissue parameters on the thermal response of a firefighter during firefighting. Modifications were made to an existing human whole body computational model, developed in our lab, for conducting transient thermal analysis for a firefighting scenario. In conjunction with nominal (baseline) tissue parameters obtained from literature, and physiologic conditions from a firefighting drill, the Pennes bioheat and energy balance equations were solved to obtain the core body temperature of a firefighter. Subsequently, the uncertainty in core body temperature due to variability in the tissue parameters (input parameters), metabolic rate, specific heat, density, and thermal conductivity was computed using the sensitivity coefficient method. On comparing the individual effect of tissue parameters on the uncertainty in core body temperature, the metabolic rate had the highest contribution (within ±0.20°C) followed by specific heat (within ±0.10°C), density (within ±0.07°C), and finally thermal conductivity (within ±0.01 °C). A maximum overall uncertainty of ±0.23 °C in the core body temperature was observed due to the combined uncertainty in the tissue parameters. Thus, the model results can be used to effectively predict a realistic range of thermal response of the firefighters during firefighting or similar activities.

Delineation of epicardial stenosis in patients with microvascular disease using pressure drop coefficient: A pilot outcome study.

AIM: To investigate the patient-outcomes of newly developed pressure drop coefficient (CDP) in diagnosing epicardial stenosis (ES) in the presence of concomitant microvascular disease (MVD). METHODS: Patients from our clinical trial were divided into two subgroups with: (1) cut-off of coronary flow reserve (CFR) < 2.0; and (2) diabetes. First, correlations were performed for both subgroups between CDP and hyperemic microvascular resistance (HMR), a diagnostic parameter for assessing the severity of MVD. Linear regression analysis was used for these correlations. Further, in each of the subgroups, comparisons were made between fractional flow reserve (FFR) < 0.75 and CDP > 27.9 groups for assessing major adverse cardiac events (MACE: Primary outcome). Comparisons were also made between the survival curves for FFR < 0.75 and CDP > 27.9 groups. Two tailed chi-squared and Fischer's exact tests were performed for comparison of the primary outcomes, and the log-rank test was used to compare the Kaplan-Meier survival curves. P < 0.05 for all tests was considered statistically significant. RESULTS: Significant linear correlations were observed between CDP and HMR for both CFR < 2.0 (r = 0.58, P < 0.001) and diabetic (r = 0.61, P < 0.001) patients. In the CFR < 2.0 subgroup, the %MACE (primary outcomes) for CDP > 27.9 group (7.7%, 2/26) was lower than FFR < 0.75 group (3/14, 21.4%); P = 0.21. Similarly, in the diabetic subgroup, the %MACE for CDP > 27.9 group (12.5%, 2/16) was lower than FFR < 0.75 group (18.2%, 2/11); P = 0.69. Survival analysis for CFR < 2.0 subgroup indicated better event-free survival for CDP > 27.9 group (n = 26) when compared with FFR < 0.75 group (n = 14); P = 0.10. Similarly, for the diabetic subgroup, CDP > 27.9 group (n = 16) showed higher survival times compared to FFR group (n = 11); P = 0.58. CONCLUSION: CDP correlated significantly with HMR and resulted in better %MACE as well as survival rates in comparison to FFR. These positive trends demonstrate that CDP could be a potential diagnostic endpoint for delineating MVD with or without ES.

Noninvasive Electroretinography Assessment of Intravitreal Sustained-Release Methotrexate Microimplants in Rabbit Eyes.

PURPOSE: The purpose of this study is to noninvasively evaluate the safety and toxicity of a chitosan (CS) and polylactic acid (PLA)-based sustained-release methotrexate (MTX) intravitreal microimplant in normal rabbit eyes using electroretinography (ERG). METHODS: PLA-coated CS-based microimplants containing 400 µg of MTX and placebo microimplants (without drug) were surgically implanted in the vitreous of the right and the left eyes, respectively, in each of the 8 New Zealand rabbits using minimally invasive technique. At each predetermined time points (days 5, 12, 19, and 33), ERG was conducted on 2 rabbits to evaluate the safety of the microimplants administered in each eye. ERG was carried out using 2 protocols, scotopic and photopic, on each eye prior to surgery (PS) and prior to euthanasia (PE) conditions. The safety of the microimplants was assessed using statistical analysis of the ERG data (B/A ratio analysis, oscillatory potential analysis, and Naka-Rushton analysis) and subsequently quantifying and comparing functional integrity of the retina between the PS and PE conditions of each eye. RESULTS: Statistical analysis of the ERG data showed no change in retinal functional integrity because of the PLA-coated CS-based MTX microimplant and the placebo microimplant. ERG analysis also revealed absence of any evident bioelectrical dysfunction caused by the microimplants. CONCLUSION: ERGs were performed to determine whether the microimplants containing MTX and the placebo microimplants were associated with any profound retinal bioelectrical dysfunction that might be attributable to toxicity not apparent on histological studies of such eyes. The results shown in this report indicate that there were no such evident adverse effects of the microimplants or contained drug.