Validation of a Monte Carlo Modelling Based Dosimetry of Extraoral Photobiomodulation

An in vivo validation study was performed to confirm the accuracy of extraoral photobiomodulation therapy (PBMT) dosimetry determined by modelling. The Monte Carlo technique was utilized to calculate the fluence rate and absorbed power of light delivered through multi-layered tissue. Optical properties used during Monte Carlo simulations were taken from the literature. Morphological data of four study volunteers were acquired using magnetic resonance imaging (MRI) scans. Light emitting diode (LED) coupled to a power meter were utilized to measure transmitted power through each volunteer’s cheek, in vivo. The transmitted power determined by Monte Carlo modelling was compared to the in vivo measurements to determine the accuracy of the simulations. Experimental and simulation results were in good agreement for all four subjects. The difference between the mean values of the measured transmission was within 12% from the respective transmission obtained using Monte Carlo simulations. The results of the study indicate that Monte Carlo modelling is a robust and reliable method for light dosimetry.

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Comparison of Monte Carlo and Fuzzy Math Simulation Methods for Quantitative Microbial Risk Assessment

Journal of Food Protection ◽

10.4315/0362-028x-66.10.1900 ◽

2003 ◽

Vol 66 (10) ◽

pp. 1900-1910 ◽

Cited By ~ 6

Author(s):

VALERIE J. DAVIDSON ◽

JOANNE RYKS

Keyword(s):

Risk Assessment ◽

Monte Carlo ◽

Monte Carlo Simulations ◽

Interval Arithmetic ◽

Food Systems ◽

Probability Distributions ◽

Economic Cost ◽

Fuzzy Mathematics ◽

Quantitative Microbial Risk Assessment ◽

Mean Values

The objective of food safety risk assessment is to quantify levels of risk for consumers as well as to design improved processing, distribution, and preparation systems that reduce exposure to acceptable limits. Monte Carlo simulation tools have been used to deal with the inherent variability in food systems, but these tools require substantial data for estimates of probability distributions. The objective of this study was to evaluate the use of fuzzy values to represent uncertainty. Fuzzy mathematics and Monte Carlo simulations were compared to analyze the propagation of uncertainty through a number of sequential calculations in two different applications: estimation of biological impacts and economic cost in a general framework and survival of Campylobacter jejuni in a sequence of five poultry processing operations. Estimates of the proportion of a population requiring hospitalization were comparable, but using fuzzy values and interval arithmetic resulted in more conservative estimates of mortality and cost, in terms of the intervals of possible values and mean values, compared to Monte Carlo calculations. In the second application, the two approaches predicted the same reduction in mean concentration (−4 log CFU/ml of rinse), but the limits of the final concentration distribution were wider for the fuzzy estimate (−3.3 to 5.6 log CFU/ml of rinse) compared to the probability estimate (−2.2 to 4.3 log CFU/ml of rinse). Interval arithmetic with fuzzy values considered all possible combinations in calculations and maximum membership grade for each possible result. Consequently, fuzzy results fully included distributions estimated by Monte Carlo simulations but extended to broader limits. When limited data defines probability distributions for all inputs, fuzzy mathematics is a more conservative approach for risk assessment than Monte Carlo simulations.

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A hydroxyapatite phantom material for the calibration of in vivo x-ray fluorescence systems of bone strontium and lead quantification

10.32920/ryerson.14663742.v1 ◽

2021 ◽

Author(s):

Eric Da Silva

Keyword(s):

Monte Carlo ◽

Soft Tissue ◽

Monte Carlo Simulations ◽

Calibration Procedure ◽

X Rays ◽

X Ray ◽

Total Phosphate Concentration ◽

High Concentrations ◽

Phantom Material

A hydroxyaptite [HAp; Ca5(PO4)3OH] phantom material was developed with the goal of improving the calibration protocol of the 125I-induced in vivo X-ray fluorescence (IVXRF) system of bone strontium quantification with further application to other IVXRF bone metal quantification systems, particulary those associated with bone lead quantification. It was found that calcium can be prepared pure of inherent contamination from strontium (and other elements) through a hydroxide precipitation producing pure Ca(OH)2, thereby, allowing for the production of a blank phantom which has not been available previously. The pure Ca(OH)2 can then be used for the preparation of pure CaHPO4 ⋅ 2H2O. A solid state pure HAp phantom can then be prepared by reaction of Ca(OH)2 and CaHPO4 ⋅ 2H2O mixed as to produce a Ca/P mole ratio of 1.67, that in HAp and the mineral phase of bone, in the presence of a setting solution prepared as to raise the total phosphate concentration of the solution by increasing the solubility CaHPO4 ⋅ 2H2O and thereby precipitating HAp. The procedure can only be used to prepare phantoms in which doping with the analyte does not disturb the Ca/P ratio substantially. In cases in which phantoms are to be prepared with high concentrations of strontium, the cement mixture can be modified as to introduce strontium in the form of Sr(OH)2 ⋅ 8H2O as to maintain a (Ca + Sr)/P ratio of 1.67. It was found by both X-ray diffraction spectrometry and Raman spectroscopy studies that strontium substitutes for calcium as in bone when preparing phantoms by this route. The necessity for the blank bone phantoms was assessed through the first blank bone phantom measurement and Monte Carlo simulations. It was found that for the 125I-induced IVXRF system of bone strontium quantification, the source, 125I brachytherapy seeds may be contributing coherently and incoherently scattered zirconium X-rays to the measured spectra, thereby requiring the use of the blank bone phantom as a means of improving the overall quantification methodology. Monte Carlo simulations were employed to evaluate any improvement by the introduction of HAp phantoms into the coherent normalization-based calibration procedure. It was found that HAp phantoms remove the need for a coherent conversion factor (CCF) thereby potentially increasing accuracy of the quantification. Further, it was found that in order for soft tissue attenuation corrections to be possible using spectroscopic information alone, HAp along with a suitable soft tissue surrogate material need to be employed. The HAp phantom material was used for the evaluations of portable X-ray analyzer systems for their potential for IVXRF quantification of lead and strontium with a focus on a comparison between tungsten, silver and rhodium target systems. Silver and rhodium target X-ray tube systems were found to be comparable for this quantification.

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Effect of Sodium-Transport Inhibitors on Bronchial Reactivity in Vivo

Clinical Science ◽

10.1042/cs0790325 ◽

1990 ◽

Vol 79 (4) ◽

pp. 325-330 ◽

Cited By ~ 11

Author(s):

Alan J. Knox ◽

John R. Britton ◽

Anne E. Tattersfield

Keyword(s):

Confidence Intervals ◽

Sodium Transport ◽

Geometric Mean ◽

Normal Subjects ◽

Bronchial Reactivity ◽

Mean Values ◽

Doubling Dose ◽

The Difference

1. We have recently shown that ouabain, an inhibitor of Na+/K+-adenosine triphosphatase, causes contraction of bovine and human airways in vitro, and that amiloride causes relaxation and inhibits receptor-operated contraction in bovine trachealis. 2. To determine whether such drugs alter bronchial reactivity in vivo, we have studied the effect of oral digoxin (an inhibitor of Na+/K+-adenosine triphosphatase) and oral and inhaled amiloride on bronchial reactivity to histamine in three double-blind, placebo-controlled studies. 3. Histamine reactivity was measured as the provocative dose causing a 20% reduction in the forced expiratory volume in 1 s (PD20FEV1) or, when normal subjects were included, the provocative dose causing a 35% reduction in the specific airways conductance (PD35sGaw); the results are given as geometric mean values. 4. In study 1, 13 atopic asthmatic subjects were given 20 mg of oral amiloride or placebo on separate days. Two hours after the drug, the geometric mean PD20FEV1 for histamine was 0.43 μmol after amiloride and 0.54 μmol after placebo (95% confidence intervals for the difference: 0.9 to −0.2 doubling doses of histamine; P = 0.2). 5. In study 2, six normal and 24 atopic asthmatic men inhaled 10 ml of 10−2 mol/l amiloride or diluent control in a crossover study. The mean values of PD35sGaw for histamine immediately after inhalation of amiloride and placebo were 3.0 μmol and 4.3 μmol, respectively, in the normal subjects (95% confidence intervals for the difference: −0.53 to 1.52 doubling doses, P = 0.2), and 0.33 μmol and 0.29 μmol in the asthmatic subjects (95% confidence intervals for the difference: −0.95 to 0.57 doubling doses; P = 0.6). 6. In study 3, 24 atopic asthmatic men were treated for 7 days with placebo or oral digoxin (1.5 mg loading dose plus 0.25 mg twice daily for 6 days). The PD20FEV1 for histamine was measured before, 12 h after the loading dose and on day 7 of treatment. The change in PD20FEV1 did not differ significantly after digoxin and placebo, after either 1 day's treatment [mean (95% confidence intervals) difference: 0.56 doubling dose (−0.37 to 1.5 doubling dose)] or 7 day's treatment [mean (95% confidence intervals) difference: 0.3 doubling dose (−1.23 to 1.8 doubling doses)]. 7. Although our work in vitro has suggested that membrane sodium transport may play an important role in determining airway smooth muscle contractility, we have been unable to demonstrate any effect of the sodium-transport inhibitors amiloride and digoxin on histamine reactivity in these studies.

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Age-dependent calibration factors for in-vivo monitoring of 131I in thyroid using Monte Carlo simulations

Radiation Measurements ◽

10.1016/j.radmeas.2019.04.022 ◽

2019 ◽

Vol 125 ◽

pp. 96-105 ◽

Cited By ~ 1

Author(s):

J.M. Gómez-Ros ◽

M. Moraleda ◽

P. Teles ◽

K. Tymińska ◽

M.A. Saizu ◽

...

Keyword(s):

Monte Carlo ◽

Monte Carlo Simulations ◽

In Vivo Monitoring ◽

Age Dependent

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Population pharmacokinetic (PK)/pharmacodynamic (PD) modeling and simulations for exposure‐;tumor response relationships: Motesanib in a phase II thyroid cancer (TC) trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14528 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14528-e14528

Author(s):

J. Lu ◽

L. Claret ◽

L. Sutjandra ◽

M. Kuchimanchi ◽

D. Stepan ◽

...

Keyword(s):

Monte Carlo ◽

Thyroid Cancer ◽

Monte Carlo Simulations ◽

Tumor Size ◽

Tumor Response ◽

Area Under The Curve ◽

Population Pharmacokinetic ◽

Phase 2 ◽

Population Pk ◽

The Difference

e14528 Background: Motesanib is a highly selective, oral inhibitor of VEGF receptors 1, 2, and 3; PDGFR; and Kit that is being investigated for its antitumor activity. In a phase 2 monotherapy study, a response rate of 14% (per RECIST) was observed in patients (pts) with differentiated thyroid cancer (DTC; NEJM 359:31–42, 2008) compared with 1% in pts with medullary TC (MTC; Endocr Soc Ann Meeting 2007, abstract OR39–3). We evaluated the relationship between motesanib PK and tumor response, investigated whether differences in PK between MTC and DTC pts contributed to the observed difference in response, and simulated tumor response with different dose regimens in pts with TC. Methods: Data from the phase 2 TC trial were used for PK/PD modeling. The study enrolled 93 DTC and 91 MTC pts who received motesanib 125 mg once daily (QD). Motesanib concentrations were fitted to a 2- compartment population PK model. Estimates of pts’ PK parameters were used to calculate concentration and steady-state area under the curve values for motesanib, which were used as the exposure measures in population PK/PD modeling (ie, longitudinal exposure-tumor response modeling of drug effect on tumor growth dynamics). Monte Carlo simulations were used to evaluate the potential effect of doses other than 125 mg QD (75 mg and 100 mg QD) on tumor response in TC pts. Results: Clearance in MTC pts was 40% faster than in DTC pts (74 vs 44 L/h). The fit was significantly improved (P<0.001) when exposure instead of dose was used in the model. The exposure-tumor response model that incorporated the difference in exposure described change in tumor size well in both MTC and DTC populations. Clinical trial simulations using the preliminary model based on week 24 data predicted that DTC pts would achieve 19.7%, 15.7%, and 11.3% reductions in tumor size at week 24 following doses of 125 mg QD, 100 mg QD, and 75 mg QD, respectively. The actual change in median tumor size at week 24 following 125-mg QD dosing in DTC pts included in the PK/PD analysis was 17.9%. Conclusions: The use of 125 mg QD motesanib in DTC pts was supported by PK/PD modeling and Monte Carlo simulations. Differences in PK may explain the difference in tumor response observed in MTC and DTC patient populations. [Table: see text]

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