Linkages between sediment composition, wave climate and beach profile variability at multiple timescales

The paper analyses, compares and contrasts cross-shore morphodynamic behaviour of four diverse beaches that have very different regional settings, wave climates and sediment characteristics, with the aid of rarely available long term measurements of beach profiles and incident waves. The beaches investigated are Narrabeen Beach, New South Wales, Australia; Milford-on-Sea Beach, Christchurch Bay, UK; Hasaki Coast, Ibaraki Prefecture, Japan; and Joetsu-Ogata Coast, Niigata Prefecture, Japan. A statistical analysis, equilibrium beach profile analysis and Empirical Orthogonal Function analysis are used to investigate, compare and contrast spatial and temporal variability of cross shore beach profiles of the selected beaches at short-, medium- and long-term timescales. All beaches show evidence of multi-timescale morphodynamic change. Narrabeen Beach profile has the highest sensitivity to local weather patterns. Milford-on-Sea, Joetsu-Ogata and Hasaki profiles are sensitive to seasonal variation of the wave climate however, they also show some correlations with regional climate variabilities. The nature of sediment exchange across the profile, which contributes to profile shape change with time, is found to be related to sediment characteristics across the profile. At Milford-on-Sea and Joetsu-Ogata, both of which have composite profiles, sediment exchange between the upper beach and the inter-tidal zone dominates profile change, irrespective of the distinct differences in sediment composition found in the two beaches. On the other hand in Narrabeen and Hasaki where beach sediment comprises medium to find sand, sediment exchange and hence profile change occur mainly in intertidal and subtidal zones

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

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

Genetic Background Strongly Modifies the Severity of Symptoms of Hirschsprung Disease, but Not Hearing Loss in Rats Carrying Ednrbsl Mutations

Hirschsprung disease (HSCR) is thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. However, it remains unknown whether the single complete deletion of important HSCR-associated genes is sufficient to result in HSCR disease. In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrbsl mutations. Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4). Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. We found that the same genetic background markedly changed the aganglionosis, but resulted in only slight changes to hearing loss and pigment disorder. This provided the important evidence, in support of previous studies, that different lineages of neural crest-derived cells migrating along with various pathways are regulated by different signal molecules. This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome