scholarly journals Evolutionary Dynamics in Vascularised Tumours under Chemotherapy: Mathematical Modelling, Asymptotic Analysis and Numerical Simulations

2020 ◽  
Author(s):  
Chiara Villa ◽  
Mark A. J. Chaplain ◽  
Tommaso Lorenzi
Keyword(s):  
Numerical Simulations ◽  
Evolutionary Dynamics ◽  
Phenotypic Variability ◽  
Tumour Cells ◽  
Phenotypic Heterogeneity ◽  
Asymptotic Results ◽  
Mathematical Basis ◽  
Phenotypic Distribution ◽  
Development Of Resistance ◽  
The Impact

Abstract We consider a mathematical model for the evolutionary dynamics of tumour cells in vascularised tumours under chemotherapy. The model comprises a system of coupled partial integro-differential equations for the phenotypic distribution of tumour cells, the concentration of oxygen and the concentration of a chemotherapeutic agent. In order to disentangle the impact of different evolutionary parameters on the emergence of intra-tumour phenotypic heterogeneity and the development of resistance to chemotherapy, we construct explicit solutions to the equation for the phenotypic distribution of tumour cells and provide a detailed quantitative characterisation of the long-time asymptotic behaviour of such solutions. Analytical results are integrated with numerical simulations of a calibrated version of the model based on biologically consistent parameter values. The results obtained provide a theoretical explanation for the observation that the phenotypic properties of tumour cells in vascularised tumours vary with the distance from the blood vessels. Moreover, we demonstrate that lower oxygen levels may correlate with higher levels of phenotypic variability, which suggests that the presence of hypoxic regions supports intra-tumour phenotypic heterogeneity. Finally, the results of our analysis put on a rigorous mathematical basis the idea, previously suggested by formal asymptotic results and numerical simulations, that hypoxia favours the selection for chemoresistant phenotypic variants prior to treatment. Consequently, this facilitates the development of resistance following chemotherapy.

scholarly journals Eco-evolutionary dynamics: disentangling phenotypic, environmental and population fluctuations

2009 ◽  
Vol 364 (1523) ◽  
pp. 1491-1498 ◽  
Author(s):  
Thomas H.G. Ezard ◽  
Steeve D. Côté ◽  
Fanie Pelletier
Keyword(s):  
Population Growth ◽  
Evolutionary Dynamics ◽  
Environmental Variability ◽  
Phenotypic Variability ◽  
Ecological Change ◽  
Population Fluctuations ◽  
Rapid Responses ◽  
Evolutionary Response ◽  
Anthropogenic Threats ◽  
The Impact

Decomposing variation in population growth into contributions from both ecological and evolutionary processes is of fundamental concern, particularly in a world characterized by rapid responses to anthropogenic threats. Although the impact of ecological change on evolutionary response has long been acknowledged, the converse has predominantly been neglected, especially empirically. By applying a recently published conceptual framework, we assess and contrast the relative importance of phenotypic and environmental variability on annual population growth in five ungulate populations. In four of the five populations, the contribution of phenotypic variability was greater than the contribution of environmental variability, although not significantly so. The similarity in the contributions of environment and phenotype suggests that neither is worthy of neglect. Population growth is a consequence of multiple processes, which strengthens arguments advocating integrated approaches to assess how populations respond to their environments.

scholarly journals Evidence for hypoxia increasing the tempo of evolution in glioblastoma

2020 ◽  
Vol 123 (10) ◽  
pp. 1562-1569
Author(s):  
David Robert Grimes ◽  
Marnix Jansen ◽  
Robert J. Macauley ◽  
Jacob G. Scott ◽  
David Basanta
Keyword(s):  
Cell Division ◽  
Cancer Progression ◽  
Metastatic Disease ◽  
Evolutionary Dynamics ◽  
Treatment Resistance ◽  
Tumour Cells ◽  
Ecological Niches ◽  
Tumour Hypoxia ◽  
Low Oxygen ◽  
The Impact

Abstract Background Tumour hypoxia is associated with metastatic disease, and while there have been many mechanisms proposed for why tumour hypoxia is associated with metastatic disease, it remains unclear whether one precise mechanism is the key reason or several in concert. Somatic evolution drives cancer progression and treatment resistance, fuelled not only by genetic and epigenetic mutation but also by selection from interactions between tumour cells, normal cells and physical micro-environment. Ecological habitats influence evolutionary dynamics, but the impact on tempo of evolution is less clear. Methods We explored this complex dialogue with a combined clinical–theoretical approach by simulating a proliferative hierarchy under heterogeneous oxygen availability with an agent-based model. Predictions were compared against histology samples taken from glioblastoma patients, stained to elucidate areas of necrosis and TP53 expression heterogeneity. Results Results indicate that cell division in hypoxic environments is effectively upregulated, with low-oxygen niches providing avenues for tumour cells to spread. Analysis of human data indicates that cell division is not decreased under hypoxia, consistent with our results. Conclusions Our results suggest that hypoxia could be a crucible that effectively warps evolutionary velocity, making key mutations more likely. Thus, key tumour ecological niches such as hypoxic regions may alter the evolutionary tempo, driving mutations fuelling tumour heterogeneity.

scholarly journals Naringenin Sensitizes Resistant C6 Glioma Cells with a Repressive Impact on the Migrating Ability

2020 ◽  
pp. 097275312095005
Author(s):  
Jayalakshmi J ◽  
Arambakkam Janardhanam Vanisree
Keyword(s):  
Term Treatment ◽  
Tumour Cells ◽  
C6 Glioma Cells ◽  
Migration And Invasion ◽  
Tumour Control ◽  
Protein Levels ◽  
Enhanced Sensitivity ◽  
Development Of Resistance ◽  
Long Term Treatment ◽  
The Impact

Background: Glioma, the most common form of a malignant brain tumour is characterised by a poor prognosis, which is attributable to its resistance against current therapeutic approaches. Temozolomide (TMZ), a DNA alkylating agent, is the first-line drug for glioma treatment. Long-term treatment using TMZ was reported to culminate in the development of resistance with overexpression of multidrug resistance 1 gene coded protein P-glycoprotein, which in turn releases the drugs from the tumour cells. Purpose: Thus, to circumvent such resistance issues, the current study attempted to explore the effect of naringenin (a flavanone) with proven antiglial tumour potential, in mitigating the features of TMZ resistance. Methods: Colony-forming assay, invasion assay and scratch wound assay were performed among the groups, namely tumour control (C6), vehicle control (V), naringenin (NGEN)-treated, drug-resistant tumour cells (C6R), and drug resistance cells added with NGEN (C6R+NGEN), to examine the impact of NGEN on migration and invasion. The effect of NGEN on filopodia length and density during cell migration was also studied in addition to the matrix metalloproteinases (MMP-2 and MMP-9) and p-ERK levels. Results and Conclusion: NGEN and C6R+NGEN groups had shown significant reduction ( P < .01) in length and density of filopodia, colony formation, invasion and wound healing. Further, NGEN could also modify the assessed protein levels ( P < .001), which were involved in migration and invasion in sensitive and resistant cells. Our study had provided the first evidence on NGEN-induced enhanced sensitivity against TMZ resistance with profound influence as an antimigratory and anti-invasive agent.

scholarly journals Benchmarking Quantum Computers and the Impact of Quantum Noise

2021 ◽  
Vol 54 (7) ◽  
pp. 1-35
Author(s):  
Salonik Resch ◽  
Ulya R. Karpuzcu
Keyword(s):  
Numerical Simulations ◽  
Computer Architecture ◽  
Quantum Noise ◽  
Computing System ◽  
Quantum Computers ◽  
Complicating Factors ◽  
The Impact

Benchmarking is how the performance of a computing system is determined. Surprisingly, even for classical computers this is not a straightforward process. One must choose the appropriate benchmark and metrics to extract meaningful results. Different benchmarks test the system in different ways, and each individual metric may or may not be of interest. Choosing the appropriate approach is tricky. The situation is even more open ended for quantum computers, where there is a wider range of hardware, fewer established guidelines, and additional complicating factors. Notably, quantum noise significantly impacts performance and is difficult to model accurately. Here, we discuss benchmarking of quantum computers from a computer architecture perspective and provide numerical simulations highlighting challenges that suggest caution.

scholarly journals The Impact of Initial Conditions in N-Body Simulations of Debris Discs

2015 ◽  
Vol 32 ◽  
Author(s):  
E. Thilliez ◽  
S. T. Maddison
Keyword(s):  
Numerical Simulations ◽  
Initial Conditions ◽  
Parent Body ◽  
Dust Trapping ◽  
Physical Context ◽  
Disc Width ◽  
Wide Range ◽  
Belt Width ◽  
New Generation ◽  
The Impact

AbstractNumerical simulations are a crucial tool to understand the relationship between debris discs and planetary companions. As debris disc observations are now reaching unprecedented levels of precision over a wide range of wavelengths, an appropriate level of accuracy and consistency is required in numerical simulations to confidently interpret this new generation of observations. However, simulations throughout the literature have been conducted with various initial conditions often with little or no justification. In this paper, we aim to study the dependence on the initial conditions of N-body simulations modelling the interaction between a massive and eccentric planet on an exterior debris disc. To achieve this, we first classify three broad approaches used in the literature and provide some physical context for when each category should be used. We then run a series of N-body simulations, that include radiation forces acting on small grains, with varying initial conditions across the three categories. We test the influence of the initial parent body belt width, eccentricity, and alignment with the planet on the resulting debris disc structure and compare the final peak emission location, disc width and offset of synthetic disc images produced with a radiative transfer code. We also track the evolution of the forced eccentricity of the dust grains induced by the planet, as well as resonance dust trapping. We find that an initially broad parent body belt always results in a broader debris disc than an initially narrow parent body belt. While simulations with a parent body belt with low initial eccentricity (e ~ 0) and high initial eccentricity (0 < e < 0.3) resulted in similar broad discs, we find that purely secular forced initial conditions, where the initial disc eccentricity is set to the forced value and the disc is aligned with the planet, always result in a narrower disc. We conclude that broad debris discs can be modelled by using either a dynamically cold or dynamically warm parent belt, while in contrast eccentric narrow debris rings are reproduced using a secularly forced parent body belt.

scholarly journals Surgeon-led 7-VINCut Antibiotic Stewardship Intervention Decreases Duration of Treatment and Carbapenem Use in a General Surgery Service

Antibiotics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 11
Author(s):  
Josep M. Badia ◽  
Maria Batlle ◽  
Montserrat Juvany ◽  
Patricia Ruiz-de León ◽  
Maria Sagalés ◽  
...  
Keyword(s):  
Antibiotic Stewardship ◽  
Sharp Decrease ◽  
Antibiotic Consumption ◽  
Source Control ◽  
Duration Of Treatment ◽  
Development Of Resistance ◽  
Multiresistant Bacteria ◽  
The Impact ◽  
Improve Patient ◽  
Therapy Treatment

Antibiotic stewardship programs optimize the use of antimicrobials to prevent the development of resistance and improve patient outcomes. In this prospective interventional study, a multidisciplinary team led by surgeons implemented a program aimed at shortening the duration of antibiotic treatment <7 days. The impact of the intervention on antibiotic consumption adjusted to bed-days and discharges, and the isolation of multiresistant bacteria (MRB) was also studied. Furthermore, the surgeons were surveyed regarding their beliefs and feelings about the program. Out of 1409 patients, 40.7% received antibiotic therapy. Treatment continued for over 7 days in 21.5% of cases, and, as can be expected, source control was achieved in only 48.8% of these cases. The recommendations were followed in 90.2% of cases, the most frequent being to withdraw the treatment (55.6%). During the first 16 months of the intervention, a sharp decrease in the percentage of extended treatments, with R2 = 0.111 was observed. The program was very well accepted by surgeons, and achieved a decrease in both the consumption of carbapenems and in the number of MRB isolations. Multidisciplinary stewardship teams led by surgeons seem to be well received and able to better manage antibiotic prescription in surgery.

scholarly journals The importance of species interactions in eco-evolutionary community dynamics under climate change

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna Åkesson ◽  
Alva Curtsdotter ◽  
Anna Eklöf ◽  
Bo Ebenman ◽  
Jon Norberg ◽  
...  
Keyword(s):  
Climate Change ◽  
Species Interactions ◽  
Community Dynamics ◽  
Evolutionary Dynamics ◽  
Negative Impact ◽  
Trophic Levels ◽  
Temperature Dependent ◽  
Modeling Framework ◽  
Impact Of Climate Change ◽  
The Impact

AbstractEco-evolutionary dynamics are essential in shaping the biological response of communities to ongoing climate change. Here we develop a spatially explicit eco-evolutionary framework which features more detailed species interactions, integrating evolution and dispersal. We include species interactions within and between trophic levels, and additionally, we incorporate the feature that species’ interspecific competition might change due to increasing temperatures and affect the impact of climate change on ecological communities. Our modeling framework captures previously reported ecological responses to climate change, and also reveals two key results. First, interactions between trophic levels as well as temperature-dependent competition within a trophic level mitigate the negative impact of climate change on biodiversity, emphasizing the importance of understanding biotic interactions in shaping climate change impact. Second, our trait-based perspective reveals a strong positive relationship between the within-community variation in preferred temperatures and the capacity to respond to climate change. Temperature-dependent competition consistently results both in higher trait variation and more responsive communities to altered climatic conditions. Our study demonstrates the importance of species interactions in an eco-evolutionary setting, further expanding our knowledge of the interplay between ecological and evolutionary processes.

The penetration and ricochet of ogive-nosed rigid projectiles obliquely impacting metallic targets

2021 ◽  
pp. 204141962110377
Author(s):  
Yaniv Vayig ◽  
Zvi Rosenberg
Keyword(s):  
Experimental Data ◽  
Numerical Simulations ◽  
Dynamic Pressure ◽  
Oblique Impacts ◽  
Simulation Results ◽  
The Impact ◽  
Penetration Depths ◽  
Resistance To Penetration ◽  
Good Agreement

A large number of 3D numerical simulations were performed in order to follow the trajectory changes of rigid CRH3 ogive-nosed projectiles, impacting semi-infinite metallic targets at various obliquities. These trajectory changes are shown to be related to the threshold ricochet angles of the projectile/target pairs. These threshold angles are the impact obliquities where the projectiles end up moving in a path parallel to the target’s face. They were found to depend on a non-dimensional entity which is equal to the ratio between the target’s resistance to penetration and the dynamic pressure exerted by the projectile upon impact. Good agreement was obtained by comparing simulation results for these trajectory changes with experimental data from several published works. In addition, numerically-based relations were derived for the penetration depths of these ogive-nosed projectiles at oblique impacts, which are shown to agree with the simulation results.

Trapping patterns during capillary displacements in disordered media

2022 ◽  
Vol 933 ◽  
Author(s):  
Fanli Liu ◽  
Moran Wang
Keyword(s):  
Numerical Simulations ◽  
Pore Size Distribution ◽  
Pore Size ◽  
Size Distribution ◽  
Disordered Media ◽  
Pore Geometry ◽  
Control Parameters ◽  
Pore Throat ◽  
The Impact ◽  
Theoretical Analyses

We investigate the impact of wettability distribution, pore size distribution and pore geometry on the statistical behaviour of trapping in pore-throat networks during capillary displacement. Through theoretical analyses and numerical simulations, we propose and prove that the trapping patterns, defined as the percentage and distribution of trapped elements, are determined by four dimensionless control parameters. The range of all possible trapping patterns and how the patterns are dependent on the four parameters are obtained. The results help us to understand the impact of wettability and structure on trapping behaviour in disordered media.

Numerical simulation of humidification and heating during inspiration within an adult nose

2012 ◽  
Vol 50 (2) ◽  
pp. 157-164
Author(s):  
F. Sommer ◽  
R. Kroger ◽  
J. Lindemann
Keyword(s):  
Numerical Simulations ◽  
High Speed ◽  
Middle Turbinate ◽  
Multislice Ct ◽  
Respiratory Cycle ◽  
In Vivo Measurements ◽  
Airflow Distribution ◽  
The Impact ◽  
Human Nose

Background: The temperature of inhaled air is highly relevant for the humidification process. Narrow anatomical conditions limit possibilities for in vivo measurements. Numerical simulations offer a great potential to examine the function of the human nose. Objective: In the present study, the nasal humidification of inhaled air was simulated simultaneously with temperature distribution during a respiratory cycle. Methods: A realistic nose model based on a multislice CT scan was created. The simulation was performed by the Software Fluent(r). Boundary conditions were based on previous in vivo measurements. Inhaled air had a temperature of 20(deg)C and relative humidity of 30%. The wall temperature was assumed to be variable from 34(deg)C to 30(deg)C with constant humidity saturation of 100% during the respiratory cycle. Results: A substantial increase in temperature and humidity can be observed after passing the nasal valve area. Areas with high speed air flow, e.g. the space around the turbinates, show an intensive humidification and heating potential. Inspired air reaches 95% humidity and 28(deg)C within the nasopharynx. Conclusion: The human nose features an enormous humidification and heating capability. Warming and humidification are dependent on each other and show a similar spacial pattern. Concerning the climatisation function, the middle turbinate is of high importance. In contrast to in vivo measurements, numerical simulations can explore the impact of airflow distribution on nasal air conditioning. They are an effective method to investigate nasal pathologies and impacts of surgical procedures.

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