Summary Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor ...clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.
Abstract Introduction Robot-assisted surgery has been rapidly adopted in the U.S. for prostate cancer (PCa). Its adoption has been driven by market forces and patient preference, and debate continues ...regarding whether it offers improved outcomes to justify higher cost relative to open surgery. We examined comparative effectiveness of robot assisted (RARP) versus open radical prostatectomy (ORP) in cancer control and survival in a nationally representative population. Materials and Methods Population based observational cohort study of PCa patients undergoing RARP and ORP during 2003-2012 captured in Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Propensity score matching and time to event analysis was used to compare all-cause mortality, prostate cancer-specific mortality and use of additional treatment following surgery. Results 6,430 RARP and 9,161 ORP performed during 2003-2012 were identified. RARP increased in use from 13.6% to 72.6% in 2003-2004 to 72.6% in 2011-2012. After median follow-up of 6.5 years (IQR 5.2-7.9), RARP was associated with equivalent risk of all-cause mortality (Hazard Ratio HR 0.85, 0.72-1.01) and similar cancer-specific mortality (HR 0.85, 0.50-1.43) versus ORP. RARP was also associated with less use of additional treatment (HR 0.78, 0. 70-0.86). Conclusions RARP has comparable intermediate cancer control, as evidenced by less use of additional postoperative cancer therapies and equivalent cancer-specific and overall survival. Longer-term follow-up is needed to assess for differences in PCa-specific survival, which was similar during intermediate follow-up. Our findings have significant quality and cost implications and provide reassurance regarding the adoption of more expensive technology in absence of randomized controlled trials.
Psychiatric morbidities have been associated with a risk of severe infections through compromised immunity, health behaviours, or both. However, data are scarce on the association between multiple ...types of pre-pandemic psychiatric disorders and COVID-19. We aimed to assess the association between pre-pandemic psychiatric disorders and the subsequent risk of COVID-19 using UK Biobank.
For this cohort analysis, we included participants from UK Biobank who were registered in England and excluded individuals who died before Jan 31, 2020, (the start of the COVID-19 outbreak in the UK) or had withdrawn from UK Biobank. Participants diagnosed with a psychiatric disorder before Jan 31 were included in the group of individuals with pre-pandemic psychiatric disorders, whereas participants without a diagnosis before the outbreak were included in the group of individuals without pre-pandemic psychiatric disorders. We used the Public Health England dataset, UK Biobank hospital data, and death registers to collect data on COVID-19 cases. To examine the relationship between pre-pandemic psychiatric disorders and susceptibility to COVID-19, we used logistic regression models to estimate odds ratios (ORs), controlling for multiple confounders and somatic comorbidities. Key outcomes were all COVID-19, COVID-19 specifically diagnosed in inpatient care, and COVID-19-related deaths. ORs were also estimated separately for each psychiatric disorder and on the basis of the number of pre-pandemic psychiatric disorders. As a positive disease control, we repeated analyses for hospitalisation for other infections.
We included 421 014 UK Biobank participants in our study and assessed their COVID-19 status between Jan 31 and July 26, 2020. 50 809 participants were diagnosed with psychiatric disorders before the outbreak, while 370 205 participants had no psychiatric disorders. The mean age at outbreak was 67·80 years (SD 8·12). We observed an elevated risk of COVID-19 among individuals with pre-pandemic psychiatric disorders compared with that of individuals without such conditions. The fully adjusted ORs were 1·44 (95% CI 1·28–1·62) for All COVID-19 cases, 1·55 (1·34–1·78) for Inpatient COVID-19 cases, and 2·03 (1·59–2·59) for COVID-19-related deaths. We observed excess risk, defined as risk that increased with the number of pre-pandemic psychiatric disorders, across all diagnostic categories of pre-pandemic psychiatric disorders. We also observed an association between psychiatric disorders and elevated risk of hospitalisation due to other infections (OR 1·74, 95% CI 1·58–1·93).
Our findings suggest that pre-existing psychiatric disorders are associated with an increased risk of COVID-19. These findings underscore the need for surveillance of and care for populations with pre-existing psychiatric disorders during the COVID-19 pandemic.
National Natural Science Foundation of China.
Precision spectroscopy of molecular hydrogen can be used to test the quantum electrodynamics theory and determine the proton-to-electron mass ratio in a four-body system. Cavity-enhanced ...double-resonance spectroscopy is proposed to determine highly-excited rotation-vibration energies of HD with high precision. As a demonstration, the V-type comb-locked cavity-assisted double resonance (COCA-DR) spectroscopy of HD is measured by pumping the P(1) (2-0) line and probing the R(1) line in the same overtone band. The sum value of the two transition frequencies is determined to be 426 889 423 917 (26) kHz, representing a new test of theoretical calculations.
Objectives This study evaluated the use of an injectable hydrogel derived from ventricular extracellular matrix (ECM) for treating myocardial infarction (MI) and its ability to be delivered ...percutaneously. Background Injectable materials offer promising alternatives to treat MI. Although most of the examined materials have shown preserved or improved cardiac function in small animal models, none have been specifically designed for the heart, and few have translated to catheter delivery in large animal models. Methods We have developed a myocardial-specific hydrogel, derived from decellularized ventricular ECM, which self-assembles when injected in vivo. Female Sprague-Dawley rats underwent ischemia reperfusion followed by injection of the hydrogel or saline 2 weeks later. The implantation response was assessed via histology and immunohistochemistry, and the potential for arrhythmogenesis was examined using programmed electrical stimulation 1 week post-injection. Cardiac function was analyzed with magnetic resonance imaging 1 week pre-injection and 4 weeks post-MI. In a porcine model, we delivered the hydrogel using the NOGA-guided MyoStar catheter (Biologics Delivery Systems, Irwindale, California), and utilized histology to assess retention of the material. Results We demonstrate that injection of the material in the rat MI model increases endogenous cardiomyocytes in the infarct area and maintains cardiac function without inducing arrhythmias. Furthermore, we demonstrate feasibility of transendocardial catheter injection in a porcine model. Conclusions To our knowledge, this is the first in situ gelling material to be delivered via transendocardial injection in a large animal model, a critical step towards the translation of injectable materials for treating MI in humans. Our results warrant further study of this material in a large animal model of MI and suggest this may be a promising new therapy for treating MI.
hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel ...tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3' untranslated region (3'UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3' UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.
We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in ...the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th} ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3} eV^{2} in the three-neutrino framework.
Background Because the prevalence of connective tissue disease (CTD)-associated interstitial lung disease (ILD; CTD-ILD) in China is unknown, we wanted to analyze the clinical characteristics of this ...disease in Chinese patients. Methods The medical records of patients who received a diagnosis of ILD and treated in Shanghai Pulmonary Hospital from January 1999 to January 2013 were reviewed. Based on the records, patients who also received a diagnosis of CTD were identified, and their records of follow-up examinations for a minimum of 12 months until the end of December 2013 were reviewed. Results Of the 2,678 patients who received a diagnosis of ILD, 1,798 (67%) were identified as having CTD-ILD; 299 (11.2%) had idiopathic pulmonary fibrosis (IPF). Complete clinical data were available for 1,044 patients with CTD-ILD and 178 with IPF. We found that 332 of the 1,044 patients with CTD-ILD (32%) did not receive an accurate diagnosis at the initial hospital admission, 195 (18.7%) of the 1,044 patients showed persistent negative test results for autoantibodies, and 262 (25.1%) of the 1,044 patients had negative autoantibodies at the initial hospital admission and then became positive at follow-up examinations. Of the 288 patients who had confirmed CTD-ILD, 41 (14%) showed pulmonary symptoms as the initial clinical manifestation (PSIM) and 247 (86%) showed extrapulmonary symptoms as the initial clinical manifestation (EPSIM). For the 756 patients who had undifferentiated CTD-ILD, the proportion of PSIM and EPSIM was 44% and 56%, respectively. For patients who presented with PSIM, 23 who had confirmed CTD-ILD (56%) and 216 who had unconfirmed CTD-ILD (65%) did not receive an accurate diagnosis at the initial visit but were ultimately diagnosed at subsequent follow-up examinations. Conclusions Patients with CTD-ILD do not receive an accurate diagnosis at the initial hospital admission possibly because of negative serologic test results for autoantibodies and the absence of obvious extrapulmonary symptoms. Thus, patients with ILD should be examined for extrapulmonary symptoms and tested for autoantibodies at follow-up examinations.
The material point method (MPM) has attracted increasing attention from the graphics community, as it combines the strengths of both particle‐ and grid‐based solvers. Like the smoothed particle ...hydrodynamics (SPH) scheme, MPM uses particles to discretize the simulation domain and represent the fundamental unknowns. This makes it insensitive to geometric and topological changes, and readily parallelizable on a GPU. Like grid‐based solvers, MPM uses a background mesh for calculating spatial derivatives, providing more accurate and more stable results than a purely particle‐based scheme. MPM has been very successful in simulating both fluid flow and solid deformation, but less so in dealing with multiple fluids and solids, where the dynamic fluid‐solid interaction poses a major challenge. To address this shortcoming of MPM, we propose a new set of mathematical and computational schemes which enable efficient and robust fluid‐solid interaction within the MPM framework. These versatile schemes support simulation of both multiphase flow and fully‐coupled solid‐fluid systems. A series of examples is presented to demonstrate their capabilities and performance in the presence of various interacting fluids and solids, including multiphase flow, fluid‐solid interaction, and dissolution.
Improving photothermal conversion efficiency (PCE) is critical to facilitate therapeutic performance during photothermal therapy (PTT). However, current strategies of prompting PCE always involve ...complex synthesis or modification of photothermal agents, thereby significantly inhibiting the practical applications and fundamental understanding of photothermal conversion. A facile strategy is herein present for boosting PCE by transforming photothermal agents from aggregated state to dispersed state. Compared to aggregated state, the developed photothermal agents with semiconducting nature can rotate freely in dispersed state, which allows for an efficient nonradiative dissipation through twisted intramolecular charge transfer (TICT) effect, consequentially offering excellent photothermal performance. Noteworthy, the state transformation can be achieved by virtue of releasing photothermal molecules from nanoparticles on the basis of a pH‐responsive polymer nanocarrier, and the PCE is elevated from 43% to 60% upon changing the pH values from 7.4 to 5.0. Moreover, the nanoparticle disassembly and state transformation behaviors can also smoothly proceed in lysosome of cancer cells, demonstrating a distinct photothermal therapeutic performance for cancer ablation. It is hoped that this strategy of transforming state to boost PCE would be a new platform for practical applications of PTT technique.
A facile strategy of improving photothermal conversion efficiency (PCE) is presented through transforming photothermal agents from aggregated to dispersed state, where the intramolecular motions are completely liberated, allowing for supra‐efficient heat generation. This state transformation can be achieved by virtue of a releasing process from nanoparticles in cancer cells, demonstrating a distinct photothermal therapeutic performance for cancer ablation.
PDF
