Hybrid aeroacoustic approach for the efficient numerical simulation of human phonation.

A hybrid aeroacoustic approach was developed for the efficient numerical computation of human phonation. In the first step, an incompressible flow simulation on a three-dimensional (3 D) computational grid, which is capable of resolving all relevant turbulent scales, is performed using STARCCM+ and finite volume method. In the second step, the acoustic source terms on the flow grid are computed and a conservative interpolation to the acoustic grid is performed. Finally, the perturbed convective wave equation is solved to obtain the acoustic field in 3 D with the finite element solver CFS++. Thereby, the conservative transformation of the acoustic sources from the flow grid to the acoustic grid is a key step to allow coarse acoustic grids without reducing accuracy. For this transformation, two different interpolation strategies are compared and grid convergence is assessed. Overall, 16 simulation setups are compared. The initial (267 000 degrees of freedom) and the optimized (21 265 degrees of freedom) simulation setup were validated by measurements of a synthetic larynx model. To conclude, the total computational time of the acoustic simulation is reduced by 95% compared to the initial simulation setup without a significant reduction of accuracy, being 7%, in the frequency range of interest.

Aeroacoustic source term computation based on radial basis functions.

In low Mach number aeroacoustics, the known disparity of length scales makes it possible to apply well-suited simulation models using different meshes for flow and acoustics. The workflow of these hybrid methodologies include performing an unsteady flow simulation, computing the acoustic sources, and simulating the acoustic field. Therefore, hybrid methods seek for robust and flexible procedures, providing a conservative mesh to mesh interpolation of the sources while ensuring high computational efficiency. We propose a highly specialized radial basis function interpolation for the challenges during hybrid simulations. First, the computationally efficient local radial basis function interpolation in conjunction with a connectivity-based neighbor search technique is presented. Second, we discuss the computation of spatial derivatives based on radial basis functions. These derivatives are computed in a local-global approach, using a Gaussian kernel on local point stencils. Third, radial basis function interpolation and derivatives are used to compute complex aeroacoustic source terms. These ingredients are necessary to provide flexible source term calculations that robustly connect flow and acoustics. Finally, the capabilities of the presented approach are shown in a numerical experiment with a co-rotating vortex pair.

Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment.

Rapidly progressive Alzheimer disease.

Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.