STL polyomavirus (STLPyV) was recently identified in human specimens. To determine seropositivity for STLPyV, we developed an ELISA and screened patient samples from 2 US cities (Denver, Colorado [500]; St. Louis, Missouri [419]). Overall seropositivity was 68%-70%. The age-stratified data suggest that STLPyV infection is widespread and commonly acquired during childhood.
Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone.In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group.Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).
Different from the well established markets such as the dollar-Euro market, recent CIP deviations observed in the onshore dollar-RMB forward market were caused by conversion restrictions in the spot market rather than changes in credit risk and/or liquidity constraint. This paper proposes a theoretical framework under which the Chinese authorities impose conversion restrictions in the spot market in an attempt to achieve capital flow balance, but faces the tradeoff between achieving such balance and disturbing current account transactions when determining the level of conversion restriction. Such conversion restriction in turn places a binding constraint on forward traders’ ability to cover their forward positions, resulting in the observed CIP deviation. In particular, the model predicts that onshore forward rate is equal to a weighted average of CIP-implied forward rate and the market’s expectation of future spot rate, with the weight determined by the level of conversion restriction. As a secondary result, the model also implies that offshore non-deliverable forwards reflect to the market’s expectation of future spot rate. Empirical results are consistent with these predictions.
North American triple reassortant swine (TRS) influenza A viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. These viruses have six gene segments (PB2, PB1, PA, HA, NP, and NS) closely related to those of the 2009 H1N1 pandemic viruses. Therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 H1N1 pandemic viruses and to elucidate potential human health threats posed by the TRS viruses. Here we evaluated in a ferret model the pathogenicity and transmissibility of three groups of North American TRS viruses containing swine-like and/or human-like HA and NA gene segments. The study was designed only to detect informative and significant patterns in the transmissibility and pathogenicity of these three groups of viruses. We observed that irrespective of their HA and NA lineages, the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets via direct contact. However, their transmissibility by respiratory droplets was related to their HA and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like HA and human-like NA (N2) showed intermediate transmissibility. We conclude that the lineages of HA and NA may play a crucial role in the respiratory droplet transmissibility of these viruses. These findings have important implications for pandemic planning and warrant confirmation.
Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI).We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo.The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]).In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI.URL: https://www.gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.
We applied azimuthal anisotropy of amplitude versus offset (AzAVO) inversion technique to land 3D seismic data at an east Texas gas field. In general, AzAVO provides geologically interpretable anisotropy anomalies that correlate with previously interpreted faults and also correlate with the few subsurface data (FMI and cross‐dipole sonic) that we have. The inversion quality is affected by signal/noise in the data and the application of random noise attenuation in the pre‐processing enhances the results. We are encouraged to have developed an integrated workflow for the processing and interpretation of azimuthal seismic anisotropy.
Stroke happens to people of all ages and has become the leading cause of disability in the world.1 It is also the leading cause of death in China and fifth-leading cause of death in the USA.2 3 Prevention of stroke is the best treatment. The use of antiplatelet therapy is one of the main prevention strategies. Aspirin is the only antiplatelet drug indicated for primary or secondary stroke prevention. Since the invention of aspirin nearly 120 years ago, more antiplatelet agents are available. Clinicians can select one antiplatelet drug or the combination for a specific patient with a specific subtype of ischaemic stroke. This kind of precision antiplatelet therapy can maximise the benefit and lower the risk of haemorrhagic complications.
By acetylating serine 530 of cyclooxygenase-1, aspirin inhibits platelet generated thromboxane A2 and renders its antiplatelet effect. Aspirin is indicated for primary prevention of cardiovascular events in population between the age 40 and 59 with >10% risk over 10 years and low risk of gastrointestinal or intracranial haemorrhage.4
For secondary ischaemic stroke prevention, there are many choices, used either as a mono or dual therapy. The antiplatelet effect of dipyridamole is through its inhibition of phosphodiesterase activated through platelet cyclic AMP. From the European Stroke Prevention Study 2 trial, the combination of aspirin plus extended-release dipyridamole (ASA-ERDP) was 23% more effective than aspirin alone in secondary stroke prevention.5 However, the findings in the Aspirin and Extended-Release Dipyridamole vs Clopidogrel for Recurrent Stroke trial showed that ASA-ERDP and clopidogrel had similar rate of stroke recurrence …
Kaposi's sarcoma-associated herpes virus (KSHV) infects B cells and microvascular endothelium,and is linked to both lymphoid and endothelial neoplasms. KSHV encodes a G protein-coupled receptor (v-GPCR) that can bind several CC and CXC chemokines but is able to signal in the absence of known ligands. This signaling can transform cultured fibroblasts, promote angiogenesis in vitro and in vivo, and activate the mitogen-activated protein kinase, c-Jun-NH(2)-terminal kinase, and p38 pathways. To assess the potential impact of v-GPCR signaling on host cell biology we have examined cellular gene expression in v-GPCR-transfected cells using DNA microarrays. v-GPCR expression up-regulated numerous cellular transcripts in both BJAB B cells and SLK endothelial cells, but with a remarkable degree of cell-type specificity. Among the most highly regulated genes in endothelial cells were the cytokines interleukin 6 and GRO alpha; several genes affecting endothelial/vascular growth and remodeling were also induced, including plasminogen, thrombomodulin, the urokinase-type plasminogen activator receptor, and to a modest extent vascular endothelial growth factor C. By contrast, the most highly regulated genes in B cells were the CC chemokines macrophage inflammatory protein 1 alpha and macrophage inflammatory protein 1 beta. No genes other than members of the dual-specificity phosphatase family were induced in both cell lines. The results indicate that the effects of KSHV GPCR expression in these two target cell types differ considerably and suggest that signaling by this molecule may make different contributions to the pathogenesis of KSHV-related endothelial and lymphoproliferative lesions.
This paper compares the forecasting performance of the conditional autoregressive range (CARR) model with the commonly adopted GARCH model.Two major stock indices, FTSE 100 and Nikkei 225, are studies using the daily range data and daily close price data over the period 1990 to 2000.Our results suggest that improvements of the overall estimation are achieved when the CARR models are used.Moreover, we find that the CARR model gives better volatility forecasts than GARCH, as it can catch the extra informational contents of the intra-daily price variations.Finally, we also find that the inclusion of the lagged return and the lagged trading volume can significantly improve the forecasting ability of the CARR models.Our empirical results also significantly suggest the existence of a leverage effect in the U.K. and Japanese stock markets.
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