Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort

Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens

Political connections, media monitoring and long-term loans

We analyze data on Chinese non-state-listed firms and find that it is easier for firms with political connections to obtain long-term loans with extended debt maturities than it is for firms without political connections. Our investigation indicates that this phenomenon is significantly less common with increased media monitoring. Houston et al. (2011) find strong evidence that the state ownership of media is associated with higher levels of bank corruption in China, but our study shows that, to a certain extent, media monitoring can curb corruption

How do firms react to the prohibition of long-lived asset impairment reversals? Evidence from China

New Chinese Accounting Standards (CAS) released on February 15, 2006, prohibit the reversal of long-lived asset impairments, effective for reporting periods beginning January 1, 2007 and later. This development in the Chinese market provides a unique experimental setting to directly investigate how firms react to the ban on previously-allowed long-lived asset impairment reversals, especially firms that use impairment charges as "cookie jar reserves." By contrasting write-off recognition and reversal across the pre- and post- new CAS announcement regimes, we show that firms listed on Chinese stock exchanges recognized less impairment charges during the "transition" period--after announcement of the new standard and before the effective date--than in pre-announcement periods. Meanwhile, firms with substantial previous write-downs reversed more impairment charges to achieve their earnings targets in the transition period. The new CAS also constraints "big bath" reporting by loss firms. As US GAAP prohibits these reversals and IFRS allows them, our empirical evidence depicts firms' possible reactions in other regimes contemplating doing away with such reversals.

An acoustic method (Spectral Flux) to analyze ECG signals for optimizing timing for defibrillation in a porcine model of ventricular fibrillation

Aim: Spectral Flux (SF), which is based on common algorithms in the audio processing field, was applied to quantitatively analyze ECG signals to optimize the timing of defibrillation. With the aim of proving the performance in optimizing the timing of defibrillation, SF was compared with Amplitude Spectrum Area (AMSA) in a porcine model of ventricular fibrillation (VF) in a retrospective analysis experiment. Methods: A total of 56 male domestic pigs, weighing 40 ± 5 kg, were induced to undergo VF. Animals were then left untreated for 10 min, and after 6 min of cardiopulmonary resuscitation (CPR) defibrillation was performed. The respective SF and AMSA values were calculated every minute during VF and CPR. Comparisons were made through receiver operating characteristic (ROC) curves, one-way analyses of variance (one-way ANOVA), and scatterplots for the successful initial defibrillation sample (positive samples, Group R) and the failed initial defibrillation sample (negative samples, Group N) to illustrate the performance in optimizing the timing of defibrillation for the AMSA and SF methods. Result: Values of SF and AMSA gradually decreased during the 10 min VF period and increased in during the 6 min CPR period. The scatterplots showed that both metrics had the ability to distinguish positive and negative samples (p < .001). Meanwhile, ROC curves showed that SF (area under the curve, AUC = 0.798, p < .001) had the same ability as AMSA (AUC = 0.737, p < .001) to predict the successful defibrillation (Z = 1.35, p = 0.177). Moreover, when comparing the values for AMSA and SF between the successful initial defibrillation samples (Group R) and the failed initial defibrillation samples (Group N), the results showed that the values of both AMSA and SF in Group R were significantly higher than those in Group N (p < .001). Conclusion: In the present study, SF method had the same ability as AMSA to predict successful defibrillation with significantly higher values in cases of successful defibrillation than the instances in which defibrillation failed. Additionally, SF method might be more stable than AMSA for filtering out the higher frequency interference signals due to the narrower frequency range and had higher specificity and predictive accuracy than AMSA. So SF method had high clinical potential to optimize the timing of defibrillation. Nevertheless, further animal and clinical studies are still needed to confirm the effectiveness and practicality of SF as a predictive module for defibrillators in clinical practice

A Traditional Chinese Medicine Traceability System Based on Lightweight Blockchain

BackgroundRecently, the problem of traditional Chinese medicine (TCM) safety has attracted attention worldwide. To prevent the spread of counterfeit drugs, it is necessary to establish a drug traceability system. A traditional drug traceability system can record the whole circulation process of drugs, from planting, production, processing, and warehousing to use by hospitals and patients. Once counterfeit drugs are found, they can be traced back to the source. However, traditional drug traceability systems have some drawbacks, such as failure to prevent tampering and facilitation of sensitive disclosure. Blockchain (including Bitcoin and Ethernet Square) is an effective technology to address the problems of traditional drug traceability systems. However, some risks impact the reliability of blockchain, such as information explosion, sensitive information leakage, and poor scalability. ObjectiveTo avoid the risks associated with the application of blockchain, we propose a lightweight block chain framework. MethodsIn this framework, both horizontal and vertical segmentations are performed when designing the blocks, and effective strategies are provided for both segmentations. For horizontal segmentation operations, the header and body of the blockchain are separated and stored in the blockchain, and the body is stored in the InterPlanetary File System. For vertical segmentation operations, the blockchain is cut off according to time or size. For the addition of new blocks, miners only need to copy the latest part of the blockchain and append the tail and vertical segmentation of the block through the consensus mechanism. ResultsOur framework could greatly reduce the size of the blockchain and improve the verification efficiency. ConclusionsExperimental results have shown that the efficiency improves compared with ethernet when a new block is added to the blockchain and a search is conducted

Three-dimensional Investigation of Retention Time Distribution of Waste Stabilisation Ponds

Abstract: Waste stabilisation ponds (WSPs) use natural microbiological, photosynthetic, biochemical, physico-chemical and hydrodynamic processes to treat wastewater. They require little technical attention during operation and are less demanding in terms of construction cost and energy consumption than other engineered wastewater treatment systems. Practical engineering experience and research over the past few decades have established that hydrodynamics is crucial in determining the treatment efficiency of WSPs. After reviewing a large number of pond systems operated in Australia, Wood et al. (1995) stated that many systems were found to operate below an optimal level due to a reduced retention time of wastewater. It is therefore required that the hydrodynamic retention time distribution be precisely understood so that the hydrodynamic behaviour and the overall treatment efficiency of WSPs can be accurately evaluated.Griffith Sciences, Griffith School of EngineeringFull Tex

Integrated generative networks embedded with ensemble classifiers for fault detection and diagnosis under small and imbalanced data of building air condition system

Faults in building Heating, Ventilation, and Air-condition (HVAC) system create an uncomfortable indoor environment and cause energy waste. The data-driven method has been widely applied for Fault Detection and Diagnosis (FDD) in the complex building HVAC system. This method relies on the availability of many fault data which is difficult to collect. This makes it quite challenging to apply the data-driven methods for the FDD of the HVAC system. Thus, a novel data-driven FDD method that only utilizes small fault data collected from a Variable Refrigerant Flow air condition system has been proposed. Under different conditions, the fault and normal data are collected in an enthalpy difference laboratory to create small and imbalanced data. A generative network is developed by combining Wasserstein Generative Adversarial Network with Gradient Penalty and Variational Auto-Encoder. To improve the FDD classifier’s accuracy and to train an end-to-end network model using small and imbalanced data, two ensemble classifiers are embedded into the generative network. The dataset includes normal and fault data have been applied to train the modified generative network, and two ensemble classifiers are used to detect and diagnose the fault, respectively. The performance indexes show that the proposed method is much better than the SMOTE-based methods in almost all training groups. Besides, the comparison between the proposed method and generative network with a single classifier indicates that the ensemble classifiers can improve the F1-score of fault detection and the accuracy of fault diagnosis

Lithiation-induced non-noble metal nanoparticles for Li-O₂ batteries

Low-cost and highly active electrocatalysts are attractive for Li-O₂ applications. Herein, a 3D interconnected plate architecture consisting of ultrasmall Co-Ni grains embedded in lithium hydroxide nanoplates (Co₂Ni@LiOH) is designed and prepared by a lithiation strategy at room temperature. This catalyst exhibits a remarkably reduced charge potential of ∼3.4 V at 50 μA cm⁻², which leads to the high roundtrip efficiency of ∼79%, among the best levels reported and a cycle life of up to 40 cycles. The well-aligned network facilitates the oxygen diffusion and the electrolyte penetration into the electrode. The enhanced electrical conductivity network improves the charge transport kinetics and more active sites are exposed, which facilitate the adsorption and dissociation of oxygen during the oxygen reduction reaction and the oxygen evolution reaction. This new catalyst design inspires the development of an effective non-noble metal catalyst for Li-O₂ batteries.Ministry of Education (MOE)National Research Foundation (NRF)This work was supported by the U.S. Department of Energy (DOE) under Contract DE-AC0206CH11357 with the support provided by the Vehicle Technologies Office, DOE, Office of Energy Efficiency and Renewable Energy. SEM was accomplished at the Center for Nanoscale Materials, an Office of Science user facility, and was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357. The authors gratefully acknowledge Singapore MOE AcRF Tier 1 under grant nos. RG113/15 and 2016-T1-002-065, Singapore EMA project EIRP 12/NRF2015EWT-EIRP002-008, Singapore MOE Tier 2 MOE2017-T2-2-069 and National Research Foundation of Singapore (NRF) Investigatorship award number NRF2016NRF-NRFI001-22, National Research Foundation of Singapore (NRF) Investigatorship award number NRFI2017-08/NRF2016NRF-NRFI001-22

The repetitive portion of the Xenopus IgH Mu switch region mediates orientation-dependent class switch recombination

Vertebrates developed immunoglobulin heavy chain (IgH) class switch recombination (CSR) to express different IgH constant regions. Most double-strand breaks for Ig CSR occur within the repetitive portion of the switch regions located upstream of each set of constant domain exons for the Igγ, Igα or Igϵ heavy chain. Unlike mammalian switch regions, Xenopus switch regions do not have a high G-density on the non-template DNA strand. In previous studies, when Xenopus Sμ DNA was moved to the genome of mice, it is able to support substantial CSR when it is used to replace the murine Sγ1 region. Here, we tested both the 2kb repetitive portion and the 4.6 kb full-length portions of the Xenopus Sμ in both their natural (forward) orientation relative to the constant domain exons, as well as the opposite (reverse) orientation. Consistent with previous work, we find that the 4.6 kb full-length Sμ mediates similar levels of CSR in both the forward and reverse orientations. Whereas, the forward orientation of the 2kb portion can restore the majority of the CSR level of the 4.6 kb full-length Sμ, the reverse orientation poorly supports R-looping and no CSR. The forward orientation of the 2kb repetitive portion has more GG dinucleotides on the non-template strand than the reverse orientation. The correlation of R-loop formation with CSR efficiency, as demonstrated in the 2kb repetitive fragment of the Xenopus switch region, confirms a role played by R-looping in CSR that appears to be conserved through evolution

Connectivity of the insular subdivisions differentiates posttraumatic headache-associated from nonheadache-associated mild traumatic brain injury: an arterial spin labelling study

Abstract Objective The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. Methods Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. Results The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. Conclusions Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression