scholarly journals Tumor Hypoxia Heterogeneity Affects Radiotherapy: Inverse-Percolation Shell-Model Monte Carlo Simulations

Entropy ◽  
2022 ◽  
Vol 24 (1) ◽  
pp. 86
Author(s):  
Argyris Dimou ◽  
Panos Argyrakis ◽  
Raoul Kopelman

Tumor hypoxia was discovered a century ago, and the interference of hypoxia with all radiotherapies is well known. Here, we demonstrate the potentially extreme effects of hypoxia heterogeneity on radiotherapy and combination radiochemotherapy. We observe that there is a decrease in hypoxia from tumor periphery to tumor center, due to oxygen diffusion, resulting in a gradient of radiative cell-kill probability, mathematically expressed as a probability gradient of occupied space removal. The radiotherapy-induced break-up of the tumor/TME network is modeled by the physics model of inverse percolation in a shell-like medium, using Monte Carlo simulations. The different shells now have different probabilities of space removal, spanning from higher probability in the periphery to lower probability in the center of the tumor. Mathematical results regarding the variability of the critical percolation concentration show an increase in the critical threshold with the applied increase in the probability of space removal. Such an observation will have an important medical implication: a much larger than expected radiation dose is needed for a tumor breakup enabling successful follow-up chemotherapy. Information on the TME’s hypoxia heterogeneity, as shown here with the numerical percolation model, may enable personalized precision radiation oncology therapy.

2021 ◽  
Author(s):  
Shunsuke Oyamada ◽  
Shih-Wei Chiu ◽  
Takuhiro Yamaguchi

Abstract Background: There are currently no methodological studies on the performance of the statistical models for estimating intervention effects based on the time-to-recurrent-event (TTRE) in stepped wedge cluster randomised trial (SWCRT) using an open cohort design. This study aims to address this by evaluating the performance of these statistical models using an open cohort design with the Monte Carlo simulation in various settings and their application using an actual example.Methods: Using Monte Carlo simulations, we evaluated the performance of the existing extended Cox proportional hazard models, i.e., the Andersen-Gill (AG), Prentice-Williams-Peterson Total-Time (PWP-TT), and Prentice-Williams-Peterson Gap-time (PWP-GT) models, using the settings of several event generation models and true intervention effects, with and without stratification by clusters. Unidirectional switching in SWCRT was represented using time-dependent covariates.Results: Using Monte Carlo simulations with the various described settings, the PWP-GT model with stratification by clusters showed the best performance in most settings and reasonable performance in the others. The only situation in which the performance of the PWP-TT model with stratification by clusters was not inferior to that of the PWP-GT model with stratification by clusters was when there was a certain amount of follow-up period, and the timing of the trial entry was random within the trial period, including the follow-up period. The AG model performed well only in a specific setting. By analysing actual examples, it was found that almost all the statistical models suggested that the risk of events during the intervention condition may be somewhat higher than in the control, although the difference was not statistically significant.Conclusions: The PWP-GT model with stratification by clusters had the most reasonable performance when estimating intervention effects based on the TTRE in SWCRT in various settings using an open cohort design.


2009 ◽  
Vol 80 (1) ◽  
Author(s):  
N. T. Zinner ◽  
K. Mølmer ◽  
C. Özen ◽  
D. J. Dean ◽  
K. Langanke

Author(s):  
Ulla Slothuus ◽  
Mette L. Larsen ◽  
Peter Junker

Objective: To compare two methods of measuring willingness to pay (WTP): closed-ended questions with and without follow-up.Methods: A measurement experiment based on dichotomous choice contingent valuation survey data is reported. Marginal WTP estimates for alleviation of rheumatoid arthritis symptoms resulting from treatment with a novel anti-rheumatic agent, cA2 (TNF-α blockade), were calculated. Monte Carlo simulations were undertaken to evaluate the methods with respect to their statistical power.Results: The estimated marginal WTP values using closed-ended questions with and without follow-up were DKK 637 (US $91) and DKK 1,268 (US $181), respectively. A Wilcoxon's signed-rank test showed that the difference of DKK 631 was significant. Moreover, including a follow-up question increases the precision of the result. Monte Carlo simulations showed that trade-offs between power (i.e., the probability of a correct rejection of a false null hypothesis), efficiency, and size may exist in the two models.Conclusions: There was a significant difference between the WTP estimates when using closed-ended questions with and without follow-up. When choosing between the models, however, power, efficiency, and size could be used as selection criteria.


2008 ◽  
Vol 4 (S253) ◽  
pp. 506-507
Author(s):  
Brandon Tingley ◽  
Frank Grundahl ◽  
Hans Kjeldsen

AbstractThe radial velocity technique is commonly used to classify transiting exoplanet candidates. However, stars are intrinsically noisy in radial velocity. No good description of this noise has yet been proffered, although activity in general has been suggested as the source, making it impossible to evaluate its effect on signal detection. In this poster, we propose an activity-based model that incorporates both light and dark stellar spots, capable of producing both photometric and radial velocity time series. We demonstrate its consistency with both SOHO/VIRGO photometry and SOHO/GOLF radial velocities. We then use this model to establish lower and upper limits on the effects of intrinsic stellar noise on the metal lines used to follow up transit candidates, making use of Monte Carlo simulations. Based on these results, we can suggest an optimal observational sampling rate.


Author(s):  
Matthew T. Johnson ◽  
Ian M. Anderson ◽  
Jim Bentley ◽  
C. Barry Carter

Energy-dispersive X-ray spectrometry (EDS) performed at low (≤ 5 kV) accelerating voltages in the SEM has the potential for providing quantitative microanalytical information with a spatial resolution of ∼100 nm. In the present work, EDS analyses were performed on magnesium ferrite spinel [(MgxFe1−x)Fe2O4] dendrites embedded in a MgO matrix, as shown in Fig. 1. spatial resolution of X-ray microanalysis at conventional accelerating voltages is insufficient for the quantitative analysis of these dendrites, which have widths of the order of a few hundred nanometers, without deconvolution of contributions from the MgO matrix. However, Monte Carlo simulations indicate that the interaction volume for MgFe2O4 is ∼150 nm at 3 kV accelerating voltage and therefore sufficient to analyze the dendrites without matrix contributions.Single-crystal {001}-oriented MgO was reacted with hematite (Fe2O3) powder for 6 h at 1450°C in air and furnace cooled. The specimen was then cleaved to expose a clean cross-section suitable for microanalysis.


1979 ◽  
Vol 40 (C7) ◽  
pp. C7-63-C7-64
Author(s):  
A. J. Davies ◽  
J. Dutton ◽  
C. J. Evans ◽  
A. Goodings ◽  
P.K. Stewart

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