Special wave finite and infinite elements for the solution of the Helmholtz equation

The theory and the formulation of the special wave finite elements are discussed, and the special integration schemes for the elements are developed. Then the special wave infinite elements, a new concept of the mapped wave infinite elements with multiple wave directions, are developed. Computational models using these elements coupled together are tested by the applications of wave problems. In the special wave finite elements, the potential at each node is expanded in a discrete series of approximating plane waves propagating in different directions. Because of this a single element can contain many wavelengths, unlike the standard finite elements. This is a great advantage in the reduction of the degree of freedom of the problem, however the computational cost of the numerical integration over an element becomes high due to the oscillatory shape functions. Therefore the special semi-analytical integration schemes for the special wave finite elements are developed. The schemes are independent of wavenumber and efficient for short waves problems. In many cases of wave problems, it is practical to consider the domain as being infinite. However the finite element method can not deal with infinite domains. Infinite elements are an extension of the concept of finite elements in which the element has an infinite extent in one or more directions to address this limitation. In the special wave infinite element developed in this study multiple waves propagating in different directions are considered, in contrast to conventional infinite elements in which only a single wave propagating in the radial direction is considered. The shape functions of the special wave infinite elements contain trigonometric functions to describe multiple waves, and the amplitude decay factor to satisfy the radiation condition. The special wave infinite elements become a straightforward extension to the special wave finite elements for wave problems in an unbounded domain

IOP elevation after STTA

Purpose To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). Methods This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age: 63.8 ± 12.9 years) who received STTA in participating centres between April 2013 and July 2017. Results IOP elevation was observed in 206 eyes (14.7%) and IOP increase ≥ 6 mmHg was found in 328 eyes (23.3%). In total, 106 eyes (7.5%) needed medication and two eyes (0.14%) needed surgical procedures. Younger age, higher baseline IOP, and steroid dose were risk factors associated with IOP elevation. Risk factors associated with IOP increase ≥ 6 mmHg were younger age, lower baseline IOP, steroid dose, and higher incidences of diabetic macular oedema (DME) and uveitis. In contrast, with steroid dose fixed at 20 mg, a lower incidence of DME was a risk factor for increased IOP, suggesting that STTA had dose-dependent effects on IOP increase, especially in patients with DME. Conclusion Our real-world evidence from a large sample of Japanese patients who received STTA showed that the incidence of IOP elevation after STTA was 14.7%, and was associated with younger age, higher baseline IOP, and steroid dose. Thus, IOP should be monitored, especially in patients with younger age, higher baseline IOP, and higher incidences of DME and uveitis

A randomized, quadruple crossover single-blind study on immediate action of chewed and unchewed low-dose acetylsalicylic acid tablets in healthy volunteers

金沢大学附属病院薬剤部In the initial treatment of acute myocardial infarction, it is important to administer oral low-dose acetylsalicylic acid (ASA) within 10 min of arrival at the hospital. However, ASA is supplied as an enteric-coated tablet or buffered tablet to prevent gastric irritation. Although current guidelines recommended that patients should chew their initial dose of ASA, there is little evidence as to whether this is efficacious. Therefore, we aimed to make a direct comparison of the pharmacokinetics and pharmacodynamics of ASA after ingestion of intact and chewed nonenteric-coated buffered ASA tablet (NBA) and enteric-coated ASA tablet (ECA) in a quadruple crossover study in healthy volunteers. Chewing ECA accelerated tmax of ASA absorption, which became equivalent to that after ingestion of intact or chewed NBA. A significant decrease in serum thromboxane B2 was observed 20 min after ingestion of chewed ECA, or intact or chewed NBA, and inhibition of platelet aggregation was also observed within 20 min. Thus, chewing of the ECA appears to result in a similar timing of ASA action to that in the case of chewed or unchewed NBA. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci Copyright © 2011 Wiley-Liss, Inc.発行後1年より全文公開

欄外注意喚起表記されている市販加工食品中特定原材料タンパク質の含有量調査

Food containing allergen proteins such as egg, wheat, milk, peanut, buckwheat, shrimp andcrab at greater than 10mg/kg must be mandatorily labeled on food products in Japan since 2002and/or 2008. To protect the health and safety of food-allergic people, a marginal labelingsystem is recommended for labeling them voluntarily on food products when minute amountsunintentionally contaminated the final product during manufacturing process without using anyallergen proteins as raw materials. In this survey from this point, the content of seven foodallergenic proteins in 76 food products was investigated using immunochromatography assayand ELISA. Positive results were obtained from 10 food samples (13%) by usingimmunochromatography, and wheat proteins were most frequently detected from 6 samples(60%). Allergen proteins of 1.2ppm~48.5ppm were detected from 5 samples (7%) usingELISA, all of which showed positive results by immunochromatography. When 15 samplescontaining <1 ppm of any kinds of allergen proteins were included, 21 from 76 samples (27%)were detected. Our results showed that in spite of low detection rate of about thirty % in foodproducts labeled with any allergen proteins voluntary, several food products contained morethan 10ppm of egg, crustacean or wheat proteins. It was found that the alert system was usefulfor allergenic subjects

Efficacy and safety of cold forceps polypectomy utilizing the jumbo cup: a prospective study

Background/Aims There are few prospective studies on cold forceps polypectomy (CFP) using jumbo cup forceps. Therefore, we examined patients with diminutive polyps (5 mm or smaller) treated with CFP using jumbo cup forceps to achieve an adenoma-free colon and also assessed the safety of the procedure and the recurrence rate of missed or residual polyp after CFP by performing follow-up colonoscopy 1 year later. Methods We included patients with up to 5 adenomas removed at initial colonoscopy and analyzed data from a total of 361 patients with 573 adenomas. One-year follow-up colonoscopy was performed in 165 patients, at which 251 lesions were confirmed. Results The one-bite resection rate with CFP was highest for lesions 3 mm or smaller and decreased significantly with increasing lesion size. Post-procedural hemorrhage was observed in 1 of 573 lesions (0.17%). No perforation was noted. The definite recurrence rate was 0.8% (2/251 lesions). The probable recurrence rate, which was defined as recurrence in the same colorectal segment, was 17%. Adenoma-free colon was achieved in 55% of patients at initial resection. Multivariate analysis revealed that achievement of an adenoma-free colon was significantly associated with number of adenomas and years of endoscopic experience. Conclusions CFP using jumbo biopsy forceps was safe and showed a high one-bite resection rate for diminutive lesions of 3 mm or smaller. The low definite recurrence rate confirms the reliability of CFP using jumbo biopsy forceps. Number of adenomas and years of endoscopic experience were key factors in achieving an adenoma-free colon

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche

In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for a limited supply of FGFs. We show that the quantitative dependence of stem cell density on FGF dosage, the biased localization of stem cells toward FGF sources, and stem cell dynamics during regeneration following injury can all be predicted and explained within the framework of a minimal theoretical model based on “mitogen competition.” We propose that this model provides a generic and robust mechanism to support stem cell homeostasis in open, or facultative, niche environments

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target