scholarly journals Patient-specific parameter estimates of glioblastoma multiforme growth dynamics from a model with explicit birth and death rates

2019 ◽  
Vol 16 (5) ◽  
pp. 5307-5323 ◽  
Author(s):  
Lifeng Han ◽  
◽  
Steffen Eikenberry ◽  
Changhan He ◽  
Lauren Johnson ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Growth Dynamics ◽  
Patient Specific ◽  
Parameter Estimates ◽  
Death Rates ◽  
Specific Parameter

scholarly journals Limitations in the Assessment of Prosthesis-Patient Mismatch

2019 ◽  
Vol 68 (07) ◽  
pp. 550-556 ◽  
Author(s):  
Paulo A. Amorim ◽  
Mahmoud Diab ◽  
Mario Walther ◽  
Gloria Färber ◽  
Andreas Hagendorff ◽  
...  
Keyword(s):  
Flow Velocity ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Patient Specific ◽  
Effective Orifice Area ◽  
Pressure Gradients ◽  
Specific Parameter ◽  
Impact On Survival ◽  
The Individual

Abstract Background Prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) may affect survival but data are conflicting. It is assessed by relating effective orifice area (EOA) to body surface area (EOAi). EOA is patient-specific as the result of flow-velocity times area at the individual patient's outflow tract levels (LVOTA) divided by trans-prosthetic flow velocity. However, some studies use projected EOAs (i.e., valve size associated EOAs from other patient populations) to assess how PPM affects outcome. Methods We analyzed 76 studies addressing hemodynamic outcome and/or mortality after bioprosthetic AVR. Results In 48 studies, projected or measured EOA for calculation of EOAi and PPM assessment was used (of which 25 demonstrated an effect on survival). We identified 28 additional studies providing measured EOA values and the corresponding Bernoulli's pressure gradients after AVR. Despite EOA being a patient-specific parameter, 77% of studies assessing a PPM impact on survival used projected EOAs. The 28 studies are providing measured EOA values and the corresponding Bernoulli's pressure gradients in patients after AVR showed a highly significant, linear relationship between EOA and Bernoulli's gradient. Considering this relationship, it is surprising that relating EOA to body surface area (BSA) (EOAi) is standard but relating pressure gradients to BSA is not. Conclusion We conclude that the majority of studies assessing PPM have used false assumptions because EOA is a patient-specific parameter and cannot be transferred to other patients. In addition, the use of EOAi to assess PPM may not be appropriate and could explain the inconsistent relation between PPM and survival in previous studies.

scholarly journals Glioblastoma Multiforme Stem Cells

2011 ◽  
Vol 11 ◽  
pp. 930-958 ◽  
Author(s):  
Irena Dimov ◽  
Deasanka Tasic-Dimov ◽  
Irena Conic ◽  
Vladisav Stefanovic
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Paradigm Shift ◽  
Patient Specific ◽  
The Novel ◽  
Genome Wide ◽  
Adequate Understanding ◽  
The Central Nervous System ◽  
Tumor Pathogenesis ◽  
The Relationship

Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

Age and growth dynamics of spiny dogfish, Squalus acanthias, in the Adriatic Sea (Eastern Mediterranean Sea)

2016 ◽  
Vol 67 (3) ◽  
pp. 357 ◽  
Author(s):  
Romana Gračan ◽  
Scott A. Heppell ◽  
Gordana Lacković ◽  
Bojan Lazar
Keyword(s):  
Adriatic Sea ◽  
Growth Models ◽  
Eastern Mediterranean ◽  
Growth Dynamics ◽  
Fishing Effort ◽  
Age And Growth ◽  
Percentage Error ◽  
Parameter Estimates ◽  
Spiny Dogfish ◽  
Average Percentage

This research provides the first information on age and growth estimates for the endangered Mediterranean subpopulation of spiny dogfish, a commercially exploited shark, highly sensitive to overexploitation. We collected samples from 206 specimens caught by commercial bottom trawls in the Adriatic Sea, and utilising three ageing protocols achieved good agreement between the readings (average percentage error=1.65%). Four growth models were fitted to length-at-age and weight-at-age data, for each sex separately. The Gompertz growth model produced the statistically best fit resulting in the following parameters: k values for males and females were 0.09 and 0.04 year–1, size-at-birth ranged from 22.9 to 24.1-cm total length, with a theoretical asymptotic length of 103.3cm for males and 173.3cm for females. The age at 50% maturity was 10.5 years for males and 20.1 years for females. The maximum age was estimated at 23 years for males and 36 years for females, with natural mortality estimates of 0.12 for males and 0.07 for females. As a result of reported demographic parameter estimates, high fishing effort and particularly low resilience of the species to exploitation, it is important to produce proper species-specific management strategy for the spiny dogfish in the region.

Functional pathway mapping of human glioblastoma multiforme and brain metastases for patient tailored therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2076-2076
Author(s):  
M. Khalil ◽  
J. Wulfkuhle ◽  
H. Fillmore ◽  
J. Deng ◽  
L. Liotta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Brain Metastases ◽  
Protein Microarrays ◽  
Patient Specific ◽  
Critical Pathway ◽  
Human Glioblastoma ◽  
Pathway Mapping ◽  
Human Glioblastoma Multiforme ◽  
Pathway Activation

2076 Background: Genome scanning analysis of human glioblastoma multiforme (GBM) has suggested that this form of cancer is a protein pathway disease. Since genomic analysis cannot directly predict protein activation, analysis of protein pathway activation is required. With the current focus on targeted translational therapeutic modalities, a functional understanding of the GBM signaling repertoire is critical, and yet largely unknown. Methods: Twelve tumors were included in this study: 10 GBMs (9 primary, 1 recurrent) and two brain metastases (1 breast and 1 lung). Pure tumor cell populations were obtained from fixed frozen tissue sections using Laser Capture Microdissection. Protein pathway mapping was performed using Reverse Phase Protein Microarrays (RPMA) whereby the activation of 85 key signaling proteins was quantitatively measured at once. Unsupervised and supervised analysis was used to explore pathway activation. Results: Unsupervised hierarchical clustering of all tumors in the study set revealed largely patient-specific signaling portraits yet also identified distinct pathway subsets. The two metastatic tumors clustered separately and distinctly from the GBMs. The GBM specimens clustered according to pathway activity. Statistical analysis demonstrated significant correlations between certain phosphorylated endpoints detected and overall survival. Phosphorylation of cofilin (S3) was associated with shorter survival time, while Stat1 (Y701) and Shc (Y317) phosphorylation were both positively correlated with longer overall survival. Conclusions: This study represents the most comprehensive proteomic analysis of human GBM pathway mapping to date. Since certain pathway biomarkers are themselves being targeted by current investigational therapies, the ability to map pathway activation and identify critical pathway biomarkers can lead to targeted therapeutics tailored to each patient's tumor. The ability to segregate short from long-term survivors according to protein pathway activation is promising. [Table: see text]

scholarly journals An Easy-to-Use Portable Ultrasound Based Device for the Measurement of the Pelvic Tilt

10.29007/pwhr ◽  
2018 ◽  
Author(s):  
Guillaume Dardenne ◽  
Jean-Philippe Pluchon ◽  
Aziliz Guezou-Philippe ◽  
Hoel Letissier ◽  
Chafiaa Hamitouche ◽  
...  
Keyword(s):  
Pelvic Tilt ◽  
Safe Zone ◽  
Individual Variability ◽  
Daily Activities ◽  
Patient Specific ◽  
Average Error ◽  
Portable Ultrasound ◽  
X Ray ◽  
Non Invasive ◽  
Specific Parameter

The orientation of the cup in Total Hip Arthroplasty plays a major role on the post- operative results. It has been considered for several decades that the cup should be oriented according to the safe zone defined by Lewinnek. However, this safe zone is not always suitable because of the inter-individual variability of the pelvic tilt during daily activities. We propose in this paper a non-invasive ultrasound based solution which can easily measure this patient specific parameter in order to thereafter otimise the cup orientation. The accuracy of this system was assessed with a specific pelvic phantom. A clinical pilot study was also performed on ten patients. The pelvic tilt was measured in three daily positions: the supine, sitting and standing positions. The average error was 1.15°±0.82°. The average pelvic tilt was -97.1°±28.6°, -46.3°±12.8° and -9.0°±8.3° for respectively the supine, the sitting and the standing positions. The high inter-individual variability of the pelvic tilt in different daily positions highlight the need to have a suitable device for the measurement of this patient specific parameter for THA. The proposed system is easy-to-use, portable and allows the pelvic tilt measurement in different positions without any additional x-ray radiation.

scholarly journals A data-model synthesis to explain variability in calcification observed during a CO<sub>2</sub> perturbation mesocosm experiment

2016 ◽  
Author(s):  
Shubham Krishna ◽  
Markus Schartau
Keyword(s):  
Initial Conditions ◽  
Growth Dynamics ◽  
Co2 Enrichment ◽  
Physiological Model ◽  
Total Alkalinity ◽  
Water Volume ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Model Solutions ◽  
Model Approach

Abstract. A series of studies were conducted during the last two decades to investigate effects of ocean acidification (OA) on phytoplankton physiology, plankton ecology, and biogeochemical dynamics of marine ecosystems. Among those studies are experiments with tanks or bags called mesocosms, with some enclosed water volume that typically comprised a natural plankton community found in the surrounding environment. The Pelagic Ecosystem CO2 – Enrichment Study PeECE-I experiment is one such study, where mesocosms were perturbed and exposed to different carbon dioxide (CO2) concentrations to determine responses in growth dynamics of the coccolithophorid Emiliania huxleyi, a marine calcifying algae. The data from replicate mesocosms of PeECE-I show some natural variability and significant differences were revealed in the accumulation of particulate inorganic carbon (PIC) between mesocosms of similar CO2 treatments. In our study we reanalyse PeECE-I data and apply an optimality-based model approach to understand most of the variability observed, with major focus on total alkalinity (TA) and calcification. We explore how much of the observed variability in data can be explained by variations of initial conditions and by the effect of CO2 perturbations. According to our model approach, changes in cellular calcite formation are resolved at the organism-level in response to variations in CO2. With a data assimilation (DA) method we obtain three distinctive ensembles of model solutions, with low, medium and high calcification rates. Optimised values of initial conditions turned out to be correlated with estimates physiological model parameters. The spread of ensemble model solutions captures most of the observed variability, corresponding to the combinations of parameter estimates. Optimised model solutions of the high CO2 treatment are shown to systematically overestimate observed PIC production. Thus, the simulated CO2 effect on calcification is likely too weak. At the same time our model results yield large differences in optimal mass flux estimates of carbon and of nitrogen even between mesocosms exposed to similar CO2 conditions.

scholarly journals Patient-specific parameter estimation in single-ventricle lumped circulation models under uncertainty

2016 ◽  
Vol 33 (3) ◽  
pp. e02799 ◽  
Author(s):  
Daniele E. Schiavazzi ◽  
Alessia Baretta ◽  
Giancarlo Pennati ◽  
Tain-Yen Hsia ◽  
Alison L. Marsden
Keyword(s):  
Parameter Estimation ◽  
Single Ventricle ◽  
Patient Specific ◽  
Specific Parameter

Arrhythmogenic cardiomyopathy is characterized by apex-to-base heterogeneity of right ventricular myocardial contractility and stiffness: an imaging-based patient-specific modeling study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Van Osta ◽  
A Lyon ◽  
F Kirkels ◽  
T Koopsen ◽  
T.A.M Van Loon ◽  
...  
Keyword(s):  
Disease Progression ◽  
Patient Specific ◽  
Funding Source ◽  
Free Wall ◽  
Longitudinal Deformation ◽  
Arrhythmogenic Cardiomyopathy ◽  
Tissue Properties ◽  
Specific Parameter ◽  
Structural Stage ◽  
Modelling Approach

Abstract Introduction Arrhythmogenic Cardiomyopathy (AC) is an inherited cardiac disease, clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Geno-positive subjects with and without symptoms may suffer from sudden cardiac death. Therefore, early disease expression and risk stratification is important. It has been shown that right ventricular (RV) longitudinal deformation abnormalities in early stages is related to disease progression. We propose an inverse patient-specific computer modelling approach, combined with clinical imaging data, to non-invasively quantify regional ventricular tissue abnormalities in AC mutation carriers. Purpose To non-invasively reveal the individual myocardial substrate underlying the regional RV deformation abnormalities in AC mutation carriers. Methods In 74 individuals carrying a plakophilin-2 or desmoglein-2 mutation, regional longitudinal deformation patterns of the RV free wall (RVfw), interventricular septum (IVS) and left ventricular free wall (LVfw) were obtained using speckle-tracking echocardiography (Figure: left column). This cohort was subdivided into 3 consecutive clinical stages i.e. subclinical (concealed, n=19) with no abnormalities, electrical stage (n=13) with only electrocardiographic abnormalities, and structural stage (n=42) with both electrical and structural abnormalities defined by the 2010 Task Force AC criteria. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects (Figure: middle column). Using the individuals' RV strain patterns as model input, this protocol automatically estimated regional RV tissue properties, such as myocardial contractility and stiffness. Results The computational model was able to reproduce the deformation as clinically measured. Patient-specific parameter estimation results (Figure: right column) revealed that clinical AC disease progression is characterized by an increase of base-to-apex heterogeneity in contractility and stiffness of the RV myocardial tissue, with a decreased contractility and an increased stiffness in the basal segment compared to the apex. Although this heterogeneity was most severe in the structural stage group, it was already present in many of the subjects in the subclinical stage. No clear apex-to-base heterogeneity of mechanical activation delay was found in this cohort. Conclusion Our patient-specific modelling approach showed that early abnormalities in RV longitudinal strain are most likely caused by increased heterogeneity in local tissue properties. Strain abnormalities are predominantly caused by decreased basal tissue contractility and increased basal tissue stiffness. Abnormalities in tissue properties may be found already in the subclinical stage. Future studies will investigate how these abnormalities relate to disease progression and arrhythmogenic risk. Characterization of AC Disease Substrate Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

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