Uncertainty quantification in virtual surgery hemodynamics predictions for single ventricle palliation.

The adoption of simulation tools to predict surgical outcomes is increasingly leading to questions about the variability of these predictions in the presence of uncertainty associated with the input clinical data. In the present study, we propose a methodology for full propagation of uncertainty from clinical data to model results that, unlike deterministic simulation, enables estimation of the confidence associated with model predictions. We illustrate this problem in a virtual stage II single ventricle palliation surgery example. First, probability density functions (PDFs) of right pulmonary artery (PA) flow split ratio and average pulmonary pressure are determined from clinical measurements, complemented by literature data. Starting from a zero-dimensional semi-empirical approximation, Bayesian parameter estimation is used to find the distributions of boundary conditions that produce the expected PA flow split and average pressure PDFs as pre-operative model results. To reduce computational cost, this inverse problem is solved using a Kriging approximant. Second, uncertainties in the boundary conditions are propagated to simulation predictions. Sparse grid stochastic collocation is employed to statistically characterize model predictions of post-operative hemodynamics in models with and without PA stenosis. The results quantify the statistical variability in virtual surgery predictions, allowing for placement of confidence intervals on simulation outputs.

A comparison of mutations induced by accelerated iron particles versus those induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis elegans.

The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation frequency as well as the nature of mutations induced by low earth orbit space radiation ambient to Space Shuttle flight STS-76. Recovered mutations were compared to those induced by accelerated iron ions generated by the AGS synchrotron accelerator at Brookhaven National Laboratory. For logistical reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space Center or Brookhaven National Laboratory, flown in space or irradiated, returned to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3-fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were homozygous inviable, suggesting that they were large deletions encompassing fem-3 as well as neighboring, essential genes. Southern blot analyses revealed that one of the 25 contained a polymorphism in fem-3, further evidence that space radiation can induce deletions. While no polymorphisms were detected among the iron ion-induced mutations, three of the 15 mutants were homozygous inviable, which is in keeping with previous observations that high LET iron particles generate deficiencies. These data provide evidence, albeit indirect, that an important mutagenic component of ambient space radiation is high LET charged particles such as iron ions.