## 5 Summary and Conclusions  
The largest challenge in applying CFD simulations in clinical diagnostics and therapy is generating reliable results at a very short time-to-solution and with low hardware requirements. In this study, a pure CFD simulation with appropriate boundary conditions was introduced. Employing LES, the aerodynamics of the phonation process was simulated and validated with results of the experimental synthetic larynx model. The vocal fold motion was prescribed based on the oscillations of the synthetic vocal folds. The numerical model reproduced the relevant aerodynamic parameters with sufficiently good accuracy and small modeling errors. As boundary conditions, the pressure at the inlet was set to be constant, equal to the mean value of the experimental subglottal pressure, whereas the outlet pressure reproduced the temporal evolution determined in the experiments.  
In the next step, the spatial and temporal resolutions of the numerical model were systematically decreased (25%, 45% and finally 55% decreases in the average number of control volumes) to reduce the computational costs. The results with these coarser meshes were compared with those obtained with the fine mesh to evaluate their validity. In general, the coarser meshes showed good agreement with the fine mesh regarding the flow pattern and aerodynamic parameters. Using the coarsest mesh, the average number of control volumes was reduced to 1.1 million cells and accordingly the time step size was increased to \(1.36\times 10^{-6}\) s. As a result, the elapsed simulation time decreased significantly by a factor of four. Finally, it was shown that the optimized use of HPC resources can reduce the wall time of simulating 10 oscillation cycles to 70 h (an approximately 75% improvement from the previous study [50] by using 30% fewer computing units), showing the potential of numerical simulations in clinical applications. However, the potential of reducing the time-to-solution is not exhausted and further improvement is required for an acceptable range of daily clinical routine. As the next steps towards a concrete clinical application, clinical MRI or CT images have to be used to generate a patient-specific geometric flow domain during phonation and the proposed model should be combined with an aeroacoustic model that may then provide new insights into the sound production and propagation process.  
Conceptualization, H.S., S.K., A.S. and M.D.; Formal analysis, H.S., S.K., S.F. and M.D.; Funding acquisition, S.K., M.K. and M.D.; Investigation, H.S.; Methodology, H.S.; Project administration, M.D.; Resources, S.K.; Supervision, S.K., A.S. and M.D.; Writing--original draft, H.S.; Writing--review & editing, S.K., M.K. and M.D.  
This research was funded by the German Research Foundation (DFG) under DO1247/10-1 No. 391215328, the Austrian Research Council (FWF) under No. 13702 and the Else Kroner-Fresenius Foundation (EKFS) under grant agreement No. 2016 A78.  
The authors acknowledge support from the Central Institute for Scientific Computing (ZISC) and the computational resources and support provided by the Erlangen Regional Computing Center (RRZE). We acknowledge support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU) within the funding program Open Access Publishing.  
The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.