Monetary and Fiscal Policy in a Liquidity Trap: The Japanese Experience 1999-2004

We characterize monetary and fiscal policy rules to implement optimal responses to a substantial decline in the natural rate of interest, and compare them with policy decisions made by the Japanese central bank and government in 1999-2004. First, we find that the Bank of Japan's policy commitment to continuing monetary easing until some prespecified conditions are satisfied lacks history dependence, a key feature of the optimal monetary policy rule. Second, the term structure of the interest rate gap (the spread between the actual real interest rate and its natural rate counterpart) was not downward sloping, indicating that the Bank of Japan's commitment failed to have suffcient influence on the market's expectations about the future course of monetary policy. Third, we find that the primary surplus in 1999-2002 was higher than predicted by the historical regularity, implying that the Japanese government deviated from the Ricardian rule toward fiscal tightening. These findings suggest that inappropriate conduct of monetary and fiscal policy during this period delayed the timing to escape from the liquidity trap.

ショウニ センコウセイ チュウスイエン ニタイスル カイフク シュジュツ ト ヒシタ フククウキョウ シュジュツ ノ ユウヨウセイ ノ ケントウ

【Background】 The role of laparoscopy in the management of perforated appendicitis in children is still somewhat controversial. We evaluated outcomes between open and laparoscopic surgery for perforated appendicitis in children. 【Patients and methods】 The medical records which underwent appendectomy for perforated appendicitis in children less than 15 years old from April 2003 to March 2015 were retrospectively reviewed. 【Results】 A total of 78 patients were enrolled. Twenty-five children underwent open appendectomy（OA）and 53 had laparoscopic appendectomy（LA） for perforated appendicitis. The mean operative time for LA（80.4±40.2 minutes for OA vs 109.0±29.7 minutes for LA, p＜0.01）was significantly longer. Patients in the LA group returned to oral intake earlier（2.3±1.1 days for LA vs 3.6±1.7 days for OA, p＜0.01）and had a shorter length of hospital stay（8.5±4.9 days for LA vs 12.7±6.3 days for OA, p＜0.01）. The incidence of postoperative complication in LA group was lower（6 cases for LA vs 8 cases for OA, p＜0.05）. 【Conclusions】 Laparoscopic appendectomy for perforated appendicitis in children was a feasible procedure which effects early postoperative oral intake, shortened length of hospital stay, and reducepostoperative complications

A case of cardiac sarcoidosis masquerading as arrhythmogenic right ventricular cardiomyopathy awaiting heart transplant

SummaryWe report a case of 45-year-old man, who was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) and presented with right ventricular (RV) enlargement with a global decrease in RV contractility accompanied by impairment of left ventricular function. He was placed on the heart transplant waiting list. Endomyocardial biopsy from RV septal wall did not show any evidence of sarcoidosis or inflammatory change. Four years after he was put on the heart transplant waiting list, a computed tomography chest scan for the purpose of anatomical evaluation for coronary sinus prior to biventricular pacing lead implantation incidentally showed bilateral hilar lymphadenopathy, which suggested the possibility of sarcoidosis. Biopsy of the inguinal lymph node pathologically was consistent with sarcoidosis. The 2[18F]fluoro-2-deoxy-d-glucose positron emission tomography scanning (FDG-PET) demonstrated intense uptake in the myocardium, and the patient was finally diagnosed as having cardiac sarcoidosis. After steroid treatment, the abnormal FDG-PET uptake disappeared. The patient therefore represented a case of cardiac sarcoidosis masquerading as ARVC. It should be recognized that RV involvement is one of the manifestations in cardiac sarcoidosis

Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest

BACKGROUND: Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro. RESULTS: Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition. CONCLUSION: Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer

Restoration of Contralateral Representation in the Mouse Somatosensory Cortex after Crossing Nerve Transfer

Avulsion of spinal nerve roots in the brachial plexus (BP) can be repaired by crossing nerve transfer via a nerve graft to connect injured nerve ends to the BP contralateral to the lesioned side. Sensory recovery in these patients suggests that the contralateral primary somatosensory cortex (S1) is activated by afferent inputs that bypassed to the contralateral BP. To confirm this hypothesis, the present study visualized cortical activity after crossing nerve transfer in mice through the use of transcranial flavoprotein fluorescence imaging. In naïve mice, vibratory stimuli applied to the forepaw elicited localized fluorescence responses in the S1 contralateral to the stimulated side, with almost no activity in the ipsilateral S1. Four weeks after crossing nerve transfer, forepaw stimulation in the injured and repaired side resulted in cortical responses only in the S1 ipsilateral to the stimulated side. At eight weeks after crossing nerve transfer, forepaw stimulation resulted in S1 cortical responses of both hemispheres. These cortical responses were abolished by cutting the nerve graft used for repair. Exposure of the ipsilateral S1 to blue laser light suppressed cortical responses in the ipsilateral S1, as well as in the contralateral S1, suggesting that ipsilateral responses propagated to the contralateral S1 via cortico-cortical pathways. Direct high-frequency stimulation of the ipsilateral S1 in combination with forepaw stimulation acutely induced S1 bilateral cortical representation of the forepaw area in naïve mice. Cortical responses in the contralateral S1 after crossing nerve transfer were reduced in cortex-restricted heterotypic GluN1 (NMDAR1) knockout mice. Functional bilateral cortical representation was not clearly observed in genetically manipulated mice with impaired cortico-cortical pathways between S1 of both hemispheres. Taken together, these findings strongly suggest that activity-dependent potentiation of cortico-cortical pathways has a critical role for sensory recovery in patients after crossing nerve transfer

The Ganymede Laser Altimeter (GALA) for the Jupiter Icy Moons Explorer (JUICE): Mission, science, and instrumentation of its receiver modules

The Jupiter Icy Moons Explorer (JUICE) is a science mission led by the European Space Agency, being developed for launch in 2023. The Ganymede Laser Altimeter (GALA) is an instrument onboard JUICE, whose main scientific goals are to understand ice tectonics based on topographic data, the subsurface structure by measuring tidal response, and small-scale roughness and albedo of the surface. In addition, from the perspective of astrobiology, it is imperative to study the subsurface ocean scientifically. The development of GALA has proceeded through an international collaboration between Germany (the lead), Japan, Switzerland, and Spain. Within this framework, the Japanese team (GALA-J) is responsible for developing three receiver modules: the Backend Optics (BEO), the Focal Plane Assembly (FPA), and the Analog Electronics Module (AEM). Like the German team, GALA-J also developed software to simulate the performance of the entire GALA system (performance model). In July 2020, the Proto-Flight Models of BEO, FPA, and AEM were delivered from Japan to Germany. This paper presents an overview of JUICE/GALA and its scientific objectives and describes the instrumentation, mainly focusing on Japan’s contribution

Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial

BackgroundTo investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test.MethodsCORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020–October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200  μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models.ResultsOverall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70–1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0–16.0) and 14.0 (12.0–16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively.ConclusionIn patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test.Clinical Trial RegistrationClinicalTrials.gov, NCT04703205

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