I study whether managers use real activities manipulation and accrual-based earnings management as substitutes in managing earnings. I find that managers trade off the two earnings management methods ...based on their relative costs and that managers adjust the level of accrual-based earnings management according to the level of real activities manipulation realized. Using an empirical model that incorporates the costs associated with the two earnings management methods and captures managers' sequential decisions, I document large-sample evidence consistent with managers using real activities manipulation and accrual-based earnings management as substitutes.
We document that textual discussions in a sample of 363,952 analyst reports provide information to investors beyond that in the contemporaneously released earnings forecasts, stock recommendations, ...and target prices, and also assist investors in interpreting these signals. Cross-sectionally, we find that investors react more strongly to negative than to positive text, suggesting that analysts are especially important in propagating bad news. Additional evidence indicates that analyst report text is more useful when it places more emphasis on nonfinancial topics, is written more assertively and concisely, and when the perceived validity of other information signals in the same report is low. Finally, analyst report text is shown to have predictive value for future earnings growth in the subsequent five years.
MicroRNA-155 (miR-155) overexpression is often found in malignancies including lung cancer. The objective of this study is to verify the hypothesis, based on the results of bioinformatics analysis, ...that miR-155 modulates cellular apoptosis and DNA damage through the regulation of Apaf-1 and is thus involved in the development and progression of lung cancer. First, we measured the expression of miR-155 and the Apaf-1 protein in lung cancer tissues. The results showed that expression of miR-155 was significantly higher in lung cancer tissues than in paracancerous and normal tissues; whereas Apaf-1 expression was lower in the lung cancerous tissues. We then established miR-155-silenced and Apaf-1-overexpressed A549 cell lines by transfection with pMAGic2.0-BIC-siRNA and pcDNA3.1-Apaf-1, respectively. These cell lines were then treated with cisplatin, and apoptosis and DNA damage were assessed, with non-transfected A549 cells used as negative controls. The results showed that, relative to controls, the silencing of miR-155 resulted in elevated expression of the Apaf-1 protein, whereas Apaf-1 mRNA levels remained unchanged. Both the silencing of miR-155 and the overexpression Apaf-1 greatly increased the sensitivity of A549 cells to cisplatin treatment, as evidenced by elevated rates of apoptosis and DNA damage. Furthermore, dual-transfection of A549 cells with miR-155 siRNA and Apaf-1 siRNA resulted in the attenuation of apoptosis and DNA damage. In conclusion, the inhibition of miR-155 can enhance the sensitivity of A549 cells to cisplatin treatment by modulation of cellular apoptosis and DNA damage through an Apaf-1-mediated pathway.
The cause of chronic inflammatory periodontitis, which leads to the destruction of periodontal ligament and alveolar bone, is multifactorial. An increasing number of studies have shown the clinical ...significance of NLRP3-mediated low-grade inflammation in degenerative disorders, but its causal linkage to age-related periodontitis has not yet been elucidated. In this study, we investigated the involvement of the NLRP3 inflammasome and the therapeutic potential of NLRP3 inhibition in age-related alveolar bone loss by using in vivo and in vitro models. The poor quality of alveolar bones in aged mice was correlated with caspase-1 activation by macrophages and elevated levels of IL-1β, which are mainly regulated by the NLRP3 inflammasome, in periodontal ligament and serum, respectively. Aged mice lacking Nlrp3 showed better bone mass than age-matched wild-type mice via a way that affects bone resorption rather than bone formation. In line with this finding, treatment with MCC950, a potent inhibitor of the NLRP3 inflammasome, significantly suppressed alveolar bone loss with reduced caspase-1 activation in aged mice but not in young mice. In addition, our in vitro studies showed that the addition of IL-1β encourages RANKL-induced osteoclastogenesis from bone marrow–derived macrophages and that treatment with MCC950 significantly suppresses osteoclastic differentiation directly, irrelevant to the inhibition of IL-1β production. Our results suggest that the NLRP3 inflammasome is a critical mediator in age-related alveolar bone loss and that targeting the NLRP3 inflammasome could be a novel option for controlling periodontal degenerative changes with age.
Highlights • Addressing the neural basis of motor feedback with a continuous design paradigm. • Revealing differences in network connectivity between real and sham feedbacks. • Left frontal–parietal ...network plays a key functional role in the feedback process.
Spatiotemporal variations of dissolved organic carbon (DOC) and inorganic carbon (DIC) in 26 waters across the semi-humid/semi-arid Songnen Plain, China, were examined with data collected during ...2008–2011. Fresh (n = 14) and brackish (n = 12) waters were grouped according to electrical conductivity (threshold = 1000 μS cm−1) Significant differences in the average DOC and DIC concentrations were observed between the fresh (5.63 mg L−1, 37.39 mg L−1) and the brackish waters (15.33 mg L−1, 142.93 mg L−1). Colored dissolved organic matter (CDOM) and DOC concentrations were mainly controlled by climatic–hydrologic conditions. The investigation indicated that the outflow conditions in the semi-arid region had condensed effects on the dissolved carbon, resulting in close relationships between salinity vs. DOC (R2 = 0.66), and salinity vs. DIC (R2 = 0.94). An independent data set collected in May 2012 also confirmed this finding (DOC: R2 = 0.79, DIC: R2 = 0.91), highlighting the potential of quantifying DOC and DIC via salinity measurements for waters dispersed in the plain. Indices based on the CDOM absorption spectra (e.g., the DOC-specific CDOM absorption (SUVA254), absorption ratio a250 : a365 (E250 : E365) and the spectral slope ratio (Sr, S275−295/S350−400) were applied to characterize CDOM composition and quality. Our results indicate that high molecular weight CDOM fractions are more abundant in the fresh waters than the brackish waters.
Corticothalamic networks are considered core pathologic substrates for idiopathic generalized epilepsy; however, the predominant epileptogenic epicenters within these networks are still largely ...unknown. The current study aims to identify these epicenters by resting-state functional connectivity.
To identify epicenters within the corticothalamic networks in idiopathic generalized epilepsy, we retrospectively studied a large cohort of patients with this condition (n = 97) along with healthy controls (n = 123) by resting-state functional MR imaging. The thalamus was functionally divided into subregions corresponding to distinct cortical lobes for 5 parallel corticothalamic networks. The functional connectivity between each voxel in the cortical lobe and the corresponding thalamic subregion was calculated, and functional connectivity strength was used to evaluate the interconnectivity of voxels in the cortex and thalamus.
The projection of 5 cortical lobes to the thalamus is consistent with previous histologic findings in humans. Compared with controls, patients with idiopathic generalized epilepsy showed increased functional connectivity strength in 4 corticothalamic networks: 1) the supplementary motor area, pulvinar, and ventral anterior nucleus in the prefrontal-thalamic network; 2) the premotor cortex and ventrolateral nucleus in motor/premotor-thalamic networks; 3) the visual cortex, posterior default mode regions, and pulvinar in parietal/occipital-thalamic networks; and 4) the middle temporal gyrus in the temporal-thalamic network.
Several key nodes were distinguished in 4 corticothalamic networks. The identification of these epicenters refines the corticothalamic network theory and provides insight into the pathophysiology of idiopathic generalized epilepsy.
Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this ...treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013.
The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.
A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001 was observed with salvage chemotherapy.
When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel.
This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.
Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing ...partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.
We previously observed that diets with reduced starch concentration decreased yields of milk and milk protein in dairy cows fed low metabolizable protein diets. Supplementation of reduced-starch ...diets with a lipid source may attenuate or eliminate production losses. Our objective was to investigate the effects of partially replacing ground corn with soyhulls plus a palmitic acid-enriched supplement on dry matter (DM) intake, milk yield and composition, plasma AA concentration, and N and energy utilization in cows fed low metabolizable protein diets (mean = −68 g/d balance) with or without rumen-protected Met, Lys, and His (RP-MLH). Sixteen multiparous Holstein cows averaging (mean ± standard deviation) 112 ± 28 d in milk, 724 ± 44 kg of body weight, and 46 ± 5 kg/d of milk in the beginning of the study were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Each period lasted 21 d, consisting of 14 d for diet adaptation and 7 d for data and sample collection. Diets were fed as follows: (1) high starch (HS), (2) HS plus RP-MLH (HS+AA), (3) reduced starch plus a palmitic acid-enriched supplement (RSPA), and (4) RSPA plus RP-MLH (RSPA+AA). The HS diet contained (DM basis) 26% ground corn and 7% soyhulls, and the RSPA diet had 10% ground corn, 22% soyhulls, and 1.5% palmitic acid. The HS diet averaged (DM basis) 32.6% starch and 4% ether extract, while starch and ether extract concentrations of the RSPA diet were 21.7 and 5.9%, respectively. All 4 diets had (DM basis) 40% corn silage, 5% mixed-mostly grass haylage, 5% grass hay, and 50% concentrate. Diets did not affect DM intake and milk yield. Contrarily, feeding RSPA and RSPA+AA increased yields of energy-corrected milk (47.0 vs. 44.8 kg/d) and milk fat (1.65 vs. 1.50 kg/d) compared with HS and HS+AA. Milk fat concentration tended to decrease when RP-MLH was supplemented to HS, but no change was seen when added to RS (starch level × RP-MLH interaction). Milk and plasma urea N increased, and milk N efficiency decreased in cows fed RSPA and RSPA+AA versus HS and HS+AA. Apparent total-tract digestibilites of crude protein and neutral detergent fiber, as well as urinary urea N and total N excretion, were greater in cows offered RSPA and RSPA+AA than HS and HS+AA. Plasma Met and His concentrations increased with supplemental RP-MLH. Intake of gross energy and digestible energy and the output of urinary and milk energy were all greater with feeding RSPA and RSPA+AA versus HS and HS+AA. In summary, partially replacing ground corn with soyhulls plus palmitic acid in diets supplemented or not with RP-MLH increased milk fat yield and fiber digestibility and maintained DM intake and milk yield, but with decreased milk N efficiency and elevated urinary N excretion.
PDF
