コンパクトスキームとコンパクトフィルタの組み合わせの空力音響非線形問題への適用性評価

空力音や衝撃波は，騒音の原因となる環境問題であり対策が必要とされている．数値計算により音波の発生のメカニズムと伝播する音波を同時に捉える計算法（計算空力音響学）として，非定常圧縮性流れでの微分の計算に適した高解像度性の特徴を持つコンパクトスキームを用いることが有効である．しかしながら，数値境界条件や非定常衝撃波や急峻な波動現象の捕獲を含む非定常流れ場の計算方法における課題があった．そこで， 本研究では，課題である数値境界条件と衝撃波や急峻な波動の伝播や減衰にかかわる非線形問題に対して，コンパクトスキームとコンパクトフィルタの組み合わせの潜在力を生かした具体的な計算手法を提案した．特に壁面近傍に真の物理的音響ソースを持つ数値境界条件の問題点を研究し，その克服法を研究した．また，コンパクト有限差分スキームにおいても不連続領域をまたいで差分ステンシルを設定するときにギブス現象が発生するが，その克服と不連続な波動現象の急峻さを従来の衝撃波捕獲スキームより精度よくとらえる計算法を研究した．以下に本論文の構成について述べる．第1章では，本研究の概要，構成について述べる．第2章では，コンパクトスキームとコンパクトフィルタについて述べる．コンパクトスキームと境界に適したコンパクトスキームとの組み合わせについて計算手法を示し，その組み合わせによる空力音の計算に与える特性ついて述べる．これまでに提案された各種境界スキームでは，精度，解像度，安定性の面から検討がなされているが，空力音の数値計算に適用した事例はないので，各種境界スキームを実装しスキームの解像度に着目して問題点を明らかにし，境界近傍に真の物理的音響ソースをもつ空力音計算に適切であると考えられる組み合わせを示した．第3章では，境界近傍に真の物理的音響ソースをもつ場合に，境界近傍でのフィルタの取り扱い（Visbal and Gaitonde(1998)およびGaitonde and Visbal(2000)）を空力音の数値計算に適用した場合の問題点を明らかにし，空力音計算に適切であると考えられる組み合わせを示した．第4 章では，流体から発生する波動の伝播の非線形現象として代表的な衝撃波にコンパクトスキームとコンパクトフィルタの組み合わせの計算手法を適用した場合について示す．その評価によって欠点を最小化できることが見出されたコンパクトスキームとコンパクトフィルタと近年注目されている局所人工拡散スキームとの結果を比較し，この計算手法が局所人工拡散よりも衝撃波にシャープさを増す一定の長所を作り出すことを見出した．第5 章では，本研究で得られた主要な成果を総括している．電気通信大学201

Harmonization across programmed death ligand 1 (PD-L1) assays for lung cancer by immunohistochemistry using noncontact alternating current electric field mixing

Background Immune checkpoint inhibitors (ICIs) are a promising advance in the treatment of patients with lung cancer. However, each ICI has been tested with an independently designed companion diagnostic assay that is based on a unique antibody. Consequently, the different trial-validated programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays should not be considered interchangeable. Our aim was to compare the performance of each available PD-L1 antibody for its ability to accurately measure PD-L1 expression and to investigate the possibility of harmonization across antibodies through the use of a new rapid IHC system, which uses noncontact alternating current (AC) mixing to achieve more stable staining. Methods First, 58 resected non-small cell lung cancer (NSCLC) specimens were stained using three PD-L1 IHC assays (28-8, SP142, and SP263) to assess the harmonization achieved with AC mixing IHC. Second, specimens from 27 patients receiving ICIs for postoperative recurrent NSCLC were stained using the same IHC method to compare the clinical performance of ICIs to PD-L1 scores. All patients received a tumor proportion score (TPS) with the 22C3 companion diagnostic test. Results Better staining was achieved with the new AC mixing IHC method than the conventional IHC in PD-L1-positive cases, and the interchangeability of some combinations of assays was increased in PD-L1-positive. In addition, AC mixing IHC provided more appropriate overall response rates for ICIs in all assays. Conclusions Stable PD-L1 IHC driven by AC mixing helped to improve TPS scoring and patient selection for ICIs through interchangeable assays

Intraoperative diagnosis of lymph node metastasis during segmentectomy for non-small cell lung cancer by rapid immunohistochemistry using noncontact alternating current electric field mixing

Background: Although lobectomy is considered the standard surgery for any non-small cell lung cancer (NSCLC), recent evidence indicates that for early NSCLCs segmentectomy may be equally effective. For segmentectomy to be oncologically safe, however, adequate intraoperative lymph node staging is essential. The aim of this study was to compare the results of a new rapid-IHC system to the HE analysis for intraoperative nodal diagnosis in lung cancer patients considered for segmentectomy. Methods: This retrospective study analyzed the pathological reports from NSCLC resections over a six-year period between 2014 and 2020. Using a new device for rapid-IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the antipancytokeratin antibody as the voltage is switched on/off. Rapid-IHC can provide a nodal diagnosis within 20 minutes. Results: Frozen sections from 106 resected lymph nodes from 70 patients were intraoperatively evaluated for metastasis. Of those, five nodes were deemed positive based on both HE staining and rapid-IHC. In addition, rapid-IHC alone detected isolated tumor cells in one hilar lymph node. Three cStage IA patients with nodal metastasis detected with HE staining and rapid-IHC received complete lobectomies. Five-year relapse-free survival and overall survival among patients receiving segmentectomy with rapid-IHC were 88.77% and 88.79%, respectively. Conclusions: Rapid-IHC driven by AC mixing is simple, highly accurate, and preserves nodal tissue for subsequent tests. This system can be used effectively for intraoperative nodal diagnosis. Rapid immunohistochemistry based on alternating-current field mixing (completed within 20 minutes) is simple and highly accurate. This system will assist clinicians when making intraoperative diagnoses of lymph node metastasis and deciding upon the appropriate surgical procedure in segmentectomy for lung cancer

Long-term results of modified bentall procedures: 18-year experience of the flanged technique

Objectives: To evaluate the early and late outcomes of the modified Bentall procedure with the flanged technique. Methods: We reviewed the medical records of 63 patients who had undergone root replacement by the modified Bentall procedure at our institute between January 2001 and December 2018. In most cases, we adopted a composite graft constructed with a mechanical valve or bioprosthesis and a Dacron graft by the flanged technique. Since 2011, we have used Valsalva grafts. Results: Mean age 57 ± 16 years, range 16-80, male 43 cases. The mean follow-up was 75 ± 56 months (range 0-216). Through April 1, 2020, we could follow up on 61 cases (97%) within a six-month period. Hospital mortality was 7.9% (4.8% in elective cases). In late follow-up, eight deaths were observed. In the bio-Bentall group (n=26), no deaths or major adverse valve-related events (MARVEs) occurred. In the mechanical Bentall group (n=37), seven cases of MARVEs, including two cerebral hemorrhages and one cerebral embolism, were observed. All patients were free from MARVEs at 5 years post procedure in the bio-Bentall group, and 93.8% and 76.8% were event-free at 5 years and 10 years, respectively, in the mechanical Bentall group. Conclusions: The 18-year results of the modified Bentall procedure were acceptable, providing excellent outcomes in the bio-Bentall group. The flanged technique enabled the use of a larger prosthesis, which may have resulted in good durability with the bio-Bentall procedure

Rapid HER2 cytologic fluorescence in situ hybridization for breast cancer using noncontact alternating current electric field mixing

Background: Human epidermal growth factor receptor 2-in situ hybridization (HER2-ISH) is widely approved for diagnostic, prognostic biomarker testing of formalin- fixed paraffin-embedded tissue blocks. However, cytologic ISH analysis has a potential advantage in tumor samples such as pleural effusion and ascites that are difficult to obtain the histological specimens. Our aim was to evaluate the clinical reliability of a novel rapid cytologic HER2 fluorescence ISH protocol (rapid-CytoFISH). Materials and Methods: Using a new device, we applied a high-voltage/frequency, noncontact alternating current electric field to tissue imprints and needle rinses, which mixed the probe within microdroplets as the voltage was switched on and off (AC mixing). Cytologic samples (n = 143) were collected from patients with immunohistochemically identified HER2 breast cancers. The specimens were then tested using standard dual-color ISH using formalin-fixed paraffin-embedded tissue (FFPE-tissue DISH) for HER2-targeted therapies, CytoFISH, and rapid-CytoFISH (completed within 4 h). Results: All 143 collected cytologic specimens (50 imprinted cytology specimens from resected tumors and 93 liquid-based cytology specimens from needle rinses) were suitable for FISH analysis. The HER2/chromosome enumeration probe (CEP) 17 ratios did not significantly differ between FFPE-tissue DISH and either CytoFISH protocol. Based on HER2 scoring criteria, we found 95.1% agreement between FFPEtissue DISH and CytoFISH (Cohen\u27s kappa coefficient = 0.771 and 95% confidence interval (CI): 0.614–0.927). Conclusion: CytoFISH could potentially serve as a clinical tool for prompt determination of HER2 status in breast cancer cytology. Rapid-CytoFISH with AC mixing will enable cancer diagnoses and HER2 status to be determined on the same day a patient comes to a clinic or hospital