A Bayesian hierarchical model for DCE-MRI to evaluate treatment response in a phase II study in advanced squamous cell carcinoma of the head and neck

Object

Pharmacokinetic parameters from dynamic contrast-enhanced MRI (DCE-MRI) were used to assess the perfusion effects due to treatment response using a tyrosine kinase inhibitor. A Bayesian hierarchical model (BHM) is proposed, as an alternative to voxel-wise estimation procedures, to test for a treatment effect while explicitly modeling known sources of variability.

Materials and methods

Nine subjects from a randomized, blinded, placebo-controlled, multicenter, phase II study of lapatinib were examined before and after treatment. Kinetic parameters were estimated, with an extended compartmental model and subject-specific arterial input function, on a voxel-by-voxel basis.

Results

The group treated with lapatinib had a decrease in median K ^trans of 0.17min^??, when averaged across all voxels in the tumor ROIs, compared with no change in the placebo group based on nonlinear regression. A hypothesis test of equality between pre- and posttreatment K ^trans could not be rejected against a one-sided alternative (P = 0.09). Equality between median K ^trans in placebo and lapatinib groups posttreatment could also not be rejected using the BHM (P = 0.32). Across all scans acquired in the study, estimates of K ^trans at one site were greater on average than those at the other site by including a site effect in the BHM. The inter-voxel variability is of similar order (within 15%) when compared to the inter-patient variability.

Conclusion

Though the study contained a small number of subjects and no significant difference was found, the Bayesian hierarchical model provided estimates of variability from known sources in the study and confidence intervals for all estimated parameters. We believe the BHM provides a straightforward and thorough interrogation of the imaging data at the level of voxels, patients or sites in this multicenter clinical study.     

Using affective human-machine interface to increase the operation performance in virtual construction crane training system: A novel approach

In the construction industry, some progress have been achieved by researchers to design and implement environments for task training using VR technology and its derivatives such as Augmented and Mixed Reality. Although, these developments have been well recognized at the application level, however crucial to the virtual training system is the effective and reliable measurement of training performance of the particular skill and handling the experiment for long-run. It is known that motor skills cannot be measured directly, but only inferred by observing behaviour or performance measures. The typical way of measuring performance is through measuring task completion time and accuracy, but can be supported by indirect measurement of some other factors. In this paper, a virtual crane training system has been developed which can be controlled using control commands extracted from facial gestures and is capable to lift up loads/materials in the virtual construction sites. Then, we integrate affective computing concept into the conventional VR training platform for measuring the cognitive load and level of satisfaction during performance using human's forehead bioelectric-signals. By employing the affective measures and our novel control scheme, the designed interface could be adapted to user's affective status during the performance in real-time. This adaptable user interface approach helps the trainee to cope with the training for long-run performance, leads to gaining more expertise and provides more effective transfer of learning to other operation environments. The detailed methodology of the affective control is presented in the paper. The results and future applications of the proposed method for disabled users, especially from neck down are discussed.     

Network switching and voltage evaluation during power system restoration

In this work, voltage evaluation after power components energization such as transmission line, transformer and shunt reactor is analyzed using artificial neural network (ANN)-based approach. Throughout the initial phase of system restoration, unexpected overvoltage may happen due to nonlinear interaction between the unloaded transformer and the transmission system. Such an overvoltage might damage some equipment and delay power system restoration. In the cases of transformer and shunt reactor energization, ANN is trained with the worst case scenario of switching angle and remanent flux which reduce the number of required simulations for training ANN. Moreover, for achieving good generalization capability for developed ANN, equivalent parameters of the network are used as ANN inputs. The simulated results for a partial of 39-bus New England test system show that the proposed technique can estimate the peak values and duration of overvoltages during network switching with good accuracy.     

Effect of lyophilized grapefruit juice on P-glycoprotein-mediated drug transport in-vitro and in-vivo

The administration of grapefruit juice (GFJ) has been postulated to inhibit the activity of P-glycoprotein (P-gp) transport system and thus can enhance the uptake of substrate drugs. However, for various reasons, the results obtained have been always swaying between confirmation and refutation. This study aims at re-evaluating the effect of lyophilized freshly-prepared grapefruit juice (LGFJ) prepared from the whole peeled fruit on P-gp activity using the model drug doxorubicin (DOX) in-vitro and timolol maleate (TM) in-vivo. Human uterine sarcoma MES-SA/DX5v cells, grown under nanomolar concentration of DOX and highly expressing P-gp, were used as model cells for in-vitro studies whereas white New Zealand male rabbits were used for in-vivo studies. Results showed that the accumulation of DOX in MES-SA/DX5v cells was increased by 18.3?±?2.0% in presence of LGFJ compared to control experiments. Results from in-vivo absorption studies showed that the relative oral bioavailability of TM ingested with LGFJ was significantly higher by 70% and 43% compared to the oral bioavailability of TM ingested with saline and a commercial GFJ, respectively. This study as such confirms the inhibitory effects of LGFJ on P-gp efflux proteins and highlights the superiority of using lyophilized freshly prepared juices over the commercially available juices in research studies. Also, the results call for further studies to assess the possibility of co-administrating LGFJ with anti-cancer agents to modulate multidrug resistance in their cellular environment or incorporating LGFJ in solid dosage forms to improve oral bioavailability of drugs.     

Weight function method for transient thermomechanical fracture analysis of a functionally graded hollow cylinder possessing a circumferential crack

This article introduces a weight function method for fracture analysis of a circumferentially cracked functionally graded hollow cylinder subjected to transient thermomechanical loading. Analytical solutions for transient temperature and stress distributions in the uncracked cylinder are derived by applying finite Hankel transformation. These solutions are utilized to determine stress acting on the faces of the circumferential crack in the local perturbation problem. Thermomechanical material properties are assumed to be power functions of the radial coordinate in the derivations. Coefficients of the weight function are found using reference stress intensity factors computed through the finite element method. Domain form of the J-integral is used in the finite element calculations. Comparisons of the numerical results calculated by the proposed weight function method to those generated by finite element analysis demonstrate the high level of accuracy attained by the application of the developed procedures. Further parametric analyses are presented to illustrate the influences of dimensionless time, crack depth to thickness ratio, power law index, and convection coefficient upon transient mode I thermomechanical stress intensity factors.     

Experimental and Numerical Investigation on the macroscopic characteristics of the jet discharging from gaseous direct injector

Injector design is one of the main challenges for development of direct injection and partially stratified gaseous engines. Characteristics of discharged spray from direct gaseous injector influence on combustion and emissions of these engines. In this work axial and radial (lateral) penetration of transient jet of direct gaseous injector are investigated for different nozzle diameters and different pressure ratios numerically and experimentally. High speed Schlieren imaging method is used for jet visualization and image processing technique is utilized for analyzing the images and extracting jet boundaries and its axial and radial penetrations. Finite volume based software is used for numerical calculations. Measuring of the axial and radial penetrations for different cases referred to in this paper provides more accurate formulation for the mentioned parameters for transient direct injection gaseous jet discharged from the injector. Experimental and numerical findings show that higher axial penetrations for larger diameters of nozzle and higher pressure ratios are achievable. Smaller diameter of nozzle gives higher relative lateral expansion while there is no specific distinction for different pressure ratios. Results show that the ratio of radial to axial penetration for transient jet is decreased by time and reaches to a constant value of 0.33±0.05 and the normalized jet axial penetration has a linear dependency on the square root of time for all cases with slope of 2.9±0.4.