Abstract
We report the discovery of GRB 221009A, the highest flux gamma-ray burst (GRB) ever observed by the Fermi Gamma-ray Burst Monitor (Fermi-GBM). This GRB has continuous prompt emission lasting ...more than 600 s, which smoothly transitions to afterglow emission visible in the Fermi-GBM energy range (8 keV–40 MeV), and total energetics higher than any other burst in the Fermi-GBM sample. By using a variety of new and existing analysis techniques we probe the spectral and temporal evolution of GRB 221009A. We find no emission prior to the Fermi-GBM trigger time (
t
0
; 2022 October 9 at 13:16:59.99 UTC), indicating that this is the time of prompt emission onset. The triggering pulse exhibits distinct spectral and temporal properties suggestive of the thermal, photospheric emission of shock breakout, with significant emission up to ∼15 MeV. We characterize the onset of external shock at
t
0
+ 600 s and find evidence of a plateau region in the early-afterglow phase, which transitions to a slope consistent with Swift-XRT afterglow measurements. We place the total energetics of GRB 221009A in context with the rest of the Fermi-GBM sample and find that this GRB has the highest total isotropic-equivalent energy (
E
γ
,iso
= 1.0 × 10
55
erg) and second highest isotropic-equivalent luminosity (
L
γ
,iso
= 9.9 × 10
53
erg s
–1
) based on its redshift of
z
= 0.151. These extreme energetics are what allowed us to observe the continuously emitting central engine of Fermi-GBM from the beginning of the prompt emission phase through the onset of early afterglow.
This study investigates the asymmetric effects of housing price on consumption in 35 major Chinese cities, having regard to heterogeneity of the housing and financial markets. Unlike previous ...studies, this study employs the threshold regression model in analyzing the two important effects: namely wealth effect and substitution effect. The findings suggest that both markets (and their status) are vital to explain the linkage between housing price and consumption. In particular, for the regime where the housing price-to-income ratio is below 5.0882 and the indicator of financial development is above 1.8827, the wealth effect is significant. By contrast, for the regime where the housing price-to-income ratio lies between 5.0882 and 5.9625, the substitution effect will become dominant. This study provides a better understanding of the thresholds and transmission channels through which housing price affects consumption. That is largely ignored in the existing literature. On the other hand, the study offers meaningful implications for policy makers in formulating relevant measures that transfers housing wealth into consumption, with a view to developing a healthier and more stable housing market and bolstering better economic development in China.
•This study investigates the asymmetric effects of housing price on consumption in 35 major Chinese cities.•Housing assets exert wealth effects on consumption when the housing market is healthy and the financial market develops to a high degree.•Housing assets exert substitution effects on consumption when the housing market is unhealthy and financial market is less developed.•The influence of housing price on consumption in China altered in 2009.
Background
There is increasing use of anti‐osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse ...reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)‐SCAR.
Objective
To characterize patients with AOA‐SCAR and investigate the HLA association and utility of in vitro diagnostic methods.
Methods
We enrolled 16 cases with AOA‐cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens–Johnson syndrome SJS and 2 with drug rash with eosinophilia and systemic symptoms DRESS) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA‐SCAR, and tolerability to alternative drugs. We further performed literature review and meta‐analysis on the HLA association of AOA‐SCAR.
Results
Our data showed strontium ranelate is the most common causality of AOA‐SCAR in Asian populations. There was no cross‐hypersensitivity of SR‐SCAR with other AOA. HLA genotyping showed that SR‐SJS was most significantly associated with HLA‐A*33:03 (Pc = 5.17 × 10−3, OR: 25.97, 95% CI: 3.08–219.33). Meta‐analysis showed that HLA‐A*33:03 was associated with SR‐SJS (P = 5.01 × 10−5; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR‐SJS was 83.3%.
Conclusions
Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA‐A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR‐SCAR in patients whose reaction developed while taking multiple drugs.
Linked Commentary: T. Shiohara. J Eur Acad Dermatol Venereol 2021; 35: 567‐568. https://doi.org/10.1111/jdv.17138.
Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein‐Barr virus (EBV). We reported that suberoylanilide hydroxamic acid (SAHA) induced EBV lytic cycle in EBV‐positive gastric carcinoma ...cells and mediated enhanced cell death. However, expression of EBV lytic proteins was thought to exert antiapoptotic effect in EBV‐infected cells. Here, we examined the in vitro and in vivo effects of SAHA on EBV lytic cycle induction in NPC cells and investigated the cellular consequences. Micromolar concentrations of SAHA significantly induced EBV lytic cycle in EBV‐positive NPC cells. Increased apoptosis and proteolytic cleavage of poly(ADP‐ribose) polymerase and caspase‐3, ‐7 and ‐9 in EBV‐positive versus EBV‐negative NPC cells were observed. More than 85% of NPC cells expressing immediate‐early (Zta), early (BMRF1) or late (gp350/220) lytic proteins coexpressed cleaved caspase‐3. Tracking of expression of EBV lytic proteins and cleaved caspase‐3 over time demonstrated that NPC cells proceeded to apoptosis following EBV lytic cycle induction. Inhibition of EBV DNA replication and late lytic protein expression by phosphonoformic acid did not impact on SAHA's induced cell death in NPC, indicating that early rather than late phase of EBV lytic cycle contributed to the apoptotic effect. In vivo effects of SAHA on EBV lytic cycle induction and tumor growth suppression were also observed in NPC xenografts in nude mice. Taken together, our data indicated that activation of lytic cycle from latent cycle of EBV by SAHA leads to apoptosis and tumor growth suppression of NPC thereby providing experimental evidence for virus‐targeted therapy against EBV‐positive cancer.
Over the past few decades, numerous attempts have been made to examine ripple effects using housing prices. What seems to be lacking, however, is a return to investor behaviour in terms of how it ...inspires inter-city spillovers. We thus propose the price-to-rent (P/R) ratio as a quantitative anchor in regard to how investor sentiment affects future housing values. By utilising a time-varying spillover approach based on monthly housing prices and rents across first-tier cities in China, it becomes clear that the characteristics of investment-driven diffusions are short-lived and more sensitive to economic policy changes in 2014 (the new normal initiative) and 2018 (strict housing control measures). Finally, in addition to good and bad perspectives, there is asymmetric evidence to show that negative outlooks such as a great fear of loss generally play a dominant role in the information transmission process, while a strong repercussion of good news in 2019 has subsequently been dampened by the COVID-19 pandemic.
This study explored the valuation effect of clawback adoption in the REIT market and identified possible channels through which clawback may generate benefits to REITs. We first found that the stock ...market reacts positively to the announcement of clawback adoption, and that market response is more pronounced when the clawback policy is strong, based on a sample of initial clawback adoptions in REITs between 2007 and 2018. The valuation effect of clawback adoption is stronger among those REITs with higher likelihood of restatements and greater disclosure opacity prior to adoption, suggesting that REIT investors anticipate that the adopted clawbacks will reduce financial restatement risks and improve disclosure quality. Our further analysis found that clawback adoption reduces the chance that REITs will receive comment letters from the regulator, improve financial reporting readability and decrease investment aggressiveness in REITs. Compared with weak clawback adopters, strong adopters have lower incidences of financial restatements in the post-adoption period. Our findings indicate that clawback is a value-relevant corporate governance mechanism in REITs.
•We study the relationship between metropolitan scale expansion and land use intensity.•The agglomerate effect between land and capital is positive.•The substitution effect between land and capital ...is negative.•The combined effect between urban scale and land-use intensity in China is positive.
The relationship between metropolitan scale expansion and land use intensity has been a hot research topic in Mainland China in the recent years. Even though many scholars have already discussed this topic from a theoretical standpoint, unfortunately, empirical research in this regard has been woefully lacking. In light of this, this study proffers an empirical investigation of 120 major Chinese cities in 2009, by first establishing an urban land use intensity index by means of a principal component analysis, followed by the application of the structural equation model (SEM) to verify said relationship. The findings show that urban land use intensity has both positive and negative effects on urban scale. In particular, while the agglomerate effect of land and capital is positive, the substitution effect between them is negative. The findings of this study particularly address the coupling relationship of urban scale and land use intensity in Mainland China. The results imply that when the levels of non-land factors rise, urban land use intensity will improve. In other words, following the implementation of the new urbanization policy in China, and the ever-growing significance of the dynamic agglomeration effect, there is a positive coupling relationship between urban scale and land use intensity.
Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that ...can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.
Cognitive impairment is a core feature of schizophrenia. Its relationship with duration of untreated psychosis (DUP), a potentially malleable prognostic factor, has been less studied, with ...inconsistent findings being observed in the literature. Previous research investigating such a relationship was mostly cross-sectional and none of those prospective studies had a follow-up duration beyond 2 years. Method A total of 93 Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. DUP and pre-morbid adjustment were measured using a structured interview incorporating multiple sources of information. Psychopathological evaluation was administered at intake, after clinical stabilization of the first psychotic episode, and at 12, 24 and 36 months. Cognitive functions were measured at clinical stabilization, and at 12, 24 and 36 months.
DUP exerted differential effects on various cognitive domains, with memory deficits being the most related to DUP even when potential confounders including pre-morbid adjustment and sex were adjusted. Prolonged DUP was associated with more severe impairment in visual memory at clinical stabilization and verbal memory at 24 and 36 months. Further, patients with a long DUP were found to have worse outcomes on negative symptoms at 36 months. The effects of DUP on verbal memory remained significant even when negative symptoms were taken into consideration.
Our findings provided further supportive evidence that delayed treatment to first-episode psychosis is associated with poorer cognitive and clinical outcomes. In addition, DUP may specifically affect memory function and its adverse impact on verbal memory may only become evident at a later stage of the recovery process.
•This research aims to investigate the price anomaly and the role of macro-control policies in China's housing markets during 1998–2012.•Findings suggest that housing markets in Beijing and Shanghai ...are less efficient.•Different market structures render complete opposite impulse responses of price to income in two cities.•In Beijing and Shanghai, the house prices are considered reasonable for most of the time.•Government interventions regulate the market ineffectively at current stage.
Since the housing market reform in 1998, China has experienced a rapid growth. Continuous surges in housing prices have been criticized by the public. In light of deviation of the price from its intrinsic value, the central government implements a series of policies to intervene the housing market, but makes little difference. Little vigorous academic work on the price anomaly and impact of macro-control measures has been conducted for housing markets in urban China. This research employs econometric methodologies to investigate the interactions between housing price and market fundamentals, in order to identify the existence of price anomaly in the housing markets of Beijing and Shanghai during 1998–2012. In addition, we conduct asymmetry analysis based on an advanced econometric model to investigate the impact of macro-control measures on price and volume. Our findings suggest that the market inefficiency is indicated by lack of interaction between housing supply and demand in Beijing and Shanghai. The opposite directions of impulse responses of price to income in the two cities are mainly attributed to the different market structures. While price anomalies are found occasionally, the housing prices are considered reasonable in Beijing and Shanghai for most of the time. Furthermore, the analysis on the role of macro-control policies in Chinese housing markets reveals that government interventions regulate the market ineffectively at the current stage.
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