Concrete Shield Performance of the VSC-17 Spent Nuclear Fuel Cask

In 2003, representatives from the Central Research Institute of Electric Power Industry (CRIEPI) requested development of a project with the objective of determining the performance of a concrete spent nuclear fuel storage cask. Radiation and environmental effects may cause chemical alteration of the concrete that could result in excessive cracking, spalling, and loss of compressive strength. The Idaho National Laboratory (INL) project team and CRIEPI representatives identified the Ventilated Storage Cask (VSC-17) spent nuclear fuel storage cask as a candidate to study cask performance, because it had been used to store fuel as part of a dry cask storage demonstration project for more than 15 years. The project involved investigating the properties of the concrete shield. INL performed a survey of the cask in the summers of 2003 and 2004. Preliminary cask evaluations performed in 2003 indicated that the cask has no visual degradation. However, a 4-5 mrem/hr step-change in the radiation levels about halfway up the cask and a localized hot spot beneath an upper air vent indicate that there may be variability in the density of the concrete or localized cracking. In 2005, INL and CRIEPI scientists performed additional surveys on the VSC-17 cask. This document summarizes the methods used on the VSC-17 to evaluate the cask for compressive strength, concrete cracking, concrete thickness, and temperature distribution

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

A spinal cord infarction that occurred after laparoscopic gastrectomy performed under general anesthesia and epidural analgesia

Abstract Background Spinal cord infarction (SCI) after epidural anesthesia is quite rare. Although most cases of perioperative SCI are associated with aortic, cardiac, or spinal surgery, and/or abnormal preoperative conditions, such as spinal stenosis or hypercoagulopathy, intraoperative events, such as severe hypotension or epidural puncture and catheterization, can be contributory factors. Case presentation A 52-year-old male was underwent laparoscopic gastrectomy. Before induction of general anesthesia, an epidural catheter was placed without any problems. The patient had no pain and no complaint just after the operation, but suddenly complained of back pain and anuria, and could not move either of his lower limbs 30 h after the operation. As we thought that the incident would be caused by the migration of the epidural catheter into the subarachnoid space, we removed the catheter, but there was no recovery of the symptoms even 20 h later. The magnetic resonance imaging (MRI) scan showed no hematoma in the epidural space but an abnormal signal within the spinal cord, extending from the Th3 to Th8 levels, which was consistent with the SCI. Unfortunately, the patient’s recovery from the paraplegia and abnormal sensation was poor. Conclusions When a patient complains of lower limb muscle weakness and/or abnormal sensations, it is important to perform an MRI examination and treatment as early as possible to avoid permanent paraplegia, especially after epidural puncture and catheterization

Incidence survey of acute otitis media in children in Sado Island, Japan--Sado Otitis Media Study (SADOMS).

BACKGROUND: Acute otitis media (AOM) is one of the most common forms of bacterial infection and cause for clinic visits in children. The incidence of AOM was 0.9-1.2 episodes per person-year during the first 2 years of life in previous reports conducted before 2000. The aim of this study was to 1) evaluate the latest AOM incidence in pediatric outpatients and 2) identify the bacterial pathogens from these patients and ascertain their serotypes and resistance. METHODS: The study was conducted in a closed population, involving all pediatricians and otolaryngologists in Sado Island allowing accurate determination of AOM incidence. In each month, one week was assigned as "surveillance week", and all outpatients with acute illness aged 0-18 years examined during the surveillance weeks were enrolled. AOM was diagnosed on the basis of otoscopic findings and clinical symptoms were recorded. Specimens were collected from the nasopharynx or middle ear cavity of AOM patients and examined for bacteria. Antimicrobial susceptibilities, serotypes, and molecular typing for resistance were determined among Streptococcus pneumoniae and Haemophilus influenzae. RESULTS: In total, 8,283 clinic visits were conducted, and 354 episodes (4.3%, 95% CI: 3.9-4.7%) among 312 children were diagnosed as AOM. The incidence of AOM was highest in children of 1 year of age (0.54 episodes/child/year, 95% CI: 0.44-0.64). Serotype coverage of 7- and 13-valent pneumococcal conjugate vaccines in this study were 38.0% (95% CI: 29.3-47.3) and 62.8% (95% CI: 53.6-71.4), respectively. Of 122 H.influenzae isolates available for typing, 120 were nontypeable and 2 were type b. A high proportion of S. pneumoniae isolates (46%) showed resistance to penicillin. Approximately half of H. influenzae isolates had genetic markers for beta-lactamase-negative ampicillin-resistance. CONCLUSIONS: Approximately 4-5% of pediatric outpatients, even without AOM-related symptoms, had AOM in our study. Pediatricians as well as otolaryngologists should check the tympanic membrane findings of all pediatric outpatients

Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic is widespread; however, accurate predictors of refractory cases have not yet been established. Circulating extracellular vesicles, involved in many pathological processes, are ideal resources for biomarker exploration. Methods To identify potential serum biomarkers and examine the proteins associated with the pathogenesis of refractory COVID-19, we conducted high-coverage proteomics on serum extracellular vesicles collected from 12 patients with COVID-19 at different disease severity levels and 4 healthy controls. Furthermore, single-cell RNA sequencing of peripheral blood mononuclear cells collected from 10 patients with COVID-19 and 5 healthy controls was performed. Results Among the 3046 extracellular vesicle proteins that were identified, expression of MACROH2A1 was significantly elevated in refractory cases compared to non-refractory cases; moreover, its expression was increased according to disease severity. In single-cell RNA sequencing of peripheral blood mononuclear cells, the expression of MACROH2A1 was localized to monocytes and elevated in critical cases. Consistently, single-nucleus RNA sequencing of lung tissues revealed that MACROH2A1 was highly expressed in monocytes and macrophages and was significantly elevated in fatal COVID-19. Moreover, molecular network analysis showed that pathways such as “estrogen signaling pathway,” “p160 steroid receptor coactivator (SRC) signaling pathway,” and “transcriptional regulation by STAT” were enriched in the transcriptome of monocytes in the peripheral blood mononuclear cells and lungs, and they were also commonly enriched in extracellular vesicle proteomics. Conclusions Our findings highlight that MACROH2A1 in extracellular vesicles is a potential biomarker of refractory COVID-19 and may reflect the pathogenesis of COVID-19 in monocytes

PCR-based genotyping and susceptibility of acute otitis media isolates.

<p>gPSSP, genetically penicillin susceptible <i>S. pneumoniae</i>; gPISP, genetically penicillin intermediate <i>S. pneumoniae</i>; gPRSP, genetically penicillin resistant <i>S. pneumoniae</i>;</p><p>MLS_B, Macrolide-lincosamide-streptogramin B.</p><p><i>S. pneumoniae.</i></p

Incidence and severity of AOM by age, and vaccination coverage during 2 years surveillance.

*<p>Average of January 2010 and January 2011 in Sado Island.</p>**<p>Vaccination coverage in Sado Island on November 2011.</p><p>AOM, acute otitis media; PCV7, 7-valent pneumococcal conjugate vaccine; Hib, <i>H. influenzae</i> type b; N.A., not available.</p