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This work aims at investigating the fracture evolution and energy characteristics of marble subjected to fatigue cyclic loading and confining pressure unloading (FC-CPU) conditions. Although rocks under separated fatigue cyclic loading and triaxial unloading conditions have been well studied, little is known about the dependence of the fatigue damage accumulation on the subsequent confining pressure unloading condition that influences the rock fracture behaviors. In this work, the servo-controlled GCTS 2000 rock mechanical system combined with the post-test X-ray computed tomography (CT) scanning technique were used to reveal the fracture behaviors of the marble samples. The samples were tested at three stages: the static loading stage, the fatigue cyclic loading stage, and the confining pressure unloading stage. Results show that the damage index-cycle number curve shows a different pattern—the damage increasing rate is different for the samples experiencing different fatigue damage. The damage accumulation at the fatigue cyclic stage influences the final failure mode and energy conversion. In addition, post-test CT scanning further reveals the effects of fatigue cycles on the crack pattern, as well as the stimulated crack scale and density after FC-CPU testing depending on the fatigue cycle. Furthermore, the stored elastic energy decreases and the dissipated energy increases with increasing fatigue cycle at the fatigue loading stage, and the energy conversion is consistent with the crack pattern analysis. By investigating the failure mechanism of marble under FC-CPU conditions, a theoretical basis for rock dynamic disaster prediction can be created.

Background: Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial. Methods: In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian-specific BMI (kg m −2 ) cutoff values. The impact of BMI on overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. We performed a meta-analysis to examine the association of BMI with OS and postoperative complication. Results: Patients with higher BMI had more postoperative complication ( P =0.002), such as anastomotic leakage ( P =0.016) and cardiovascular diseases ( P <0.001), but less incidence of chylous leakage ( P =0.010). Logistic regression analysis showed that BMI ( P =0.005) was a confounding factor associated with postoperative complication. Multivariate analysis showed that overweight and obese patients had a more favourable survival than normal weight patients (HR (hazard ratio) = 0.80, 95% CI (confidence interval): 0.70–0.92, P =0.001). Subgroup analysis showed that the association with higher BMI and increased OS was observed in patients with oesophageal squamous cell carcinoma (ESCC) ( P <0.001), oesophageal adenocarcinoma (EA) ( P =0.034), never-smoking ( P =0.035), ever-smoking ( P =0.035), never alcohol consumption ( P =0.005), weight loss ( P =0.003) and advanced pathological stage ( P <0.001). The meta-analysis further corroborated that higher BMI was associated with increased complication of anastomotic leakage (RR (risk ratio)=1.04, 95% CI: 1.02–1.06, P =0.001), wound infection (RR=1.03, 95% CI: 1.00–1.05, P =0.031) and cardiovascular diseases (RR=1.02, 95% CI: 1.00–1.05, P =0.039), but decreased incidence of chylous leakage (RR=0.98, 95% CI: 0.96–0.99, P <0.001). In addition, high BMI could significantly improved OS (HR=0.78, 95% CI: 0.71–0.85, P <0.001). Conclusion: Preoperative BMI was an independent prognostic factor for survival, and strongly associated with postoperative complications in oesophageal cancer.

The previous observational studies could not overcome the effects of confounding variables and reverse causality. We aimed to determine whether there is a causal relationship between systemic lupus erythematosus and osteoporosis in East Asian and European populations, respectively, by two-sample Mendelian Randomization analysis. We obtained and downloaded data from publicly available genome-wide association study databases and analyses for East Asian and European populations, including systemic lupus erythematosus (SLE), osteoporosis (OP), multisite bone mineral density (BMD), and OP with fracture. After screening for instrumental single-nucleotide polymorphisms (SNPs) significantly correlated to SLE, the inverse-variance weighted (IVW) method was used for calculating the ratio and 95% confidence interval, besides utilizing MR-Egger, weighted median, and weighted mode to assess the robustness of the primary outcome. Moreover, multiple analyses, including MR-PRESSO, MR-Egger intercept, Cochran's Q test, as well as \"leave-one-out\" sensitivity, were used for evaluating horizontal pleiotropy, heterogeneity, and stability. Finally, we exchanged exposure and outcome and performed a reverse MR analysis. IVW (OR = 1.05, 95% CI = 1.01–1.09, P = 0.009) indicated a significant positive correlation between genetically predicted SLE and OP in East Asians. Furthermore, neither heterogeneity nor horizontal pleiotropy was observed. In Europe, there was no significant genetically predicted causal relation between SLE and OP. Bi-directional MR analysis showed no reverse causality between SLE and OP. In the East Asian population, genetically predicted SLE may have had a positive causal relationship with OP. In Europe, there is insufficient evidence for a potential causal relation between SLE and OP or BMD and fracture, and the correlations currently observed may be attributed to a variety of confounder variables.

Reservoir bays, at the terrestrial and water boundary, where water fluidity slows down and self-purification ability turns weak, hence they are especially sensitive to terrestrial exogenous pollutants, even resulting in eutrophication. According to N:P, water nutrient types can be divided into N limited, P limited and N + P limited classes. Phytoplankton biomass is represented by chlorophyll a, which is one of the sensitive indicators of water eutrophication. Comprehensively tracing non-point pollution from terrestrial exogenous pollutants (fertilizer, soil release, anthropogenic discharge) to water nutrients that happen in reservoir bays is of great significance. This paper identified the dominant environmental variables and nutrients' limited types of reservoir bays at storage and discharge periods, and constructed a partial least squares structural equation model (PLS-SEM) to explore the impacts of terrestrial exogenous pollutants. Results showed that in the storage period, water contamination mainly came from residential discharge and soil endogenous release, and the total contribution rate reached 61%. In the discharge period, with the increase of rainfall–runoff erosion, the explanatory ability of land use, topography and landscape pattern to water quality increased, up to 58%. The dominant nutrient limited types of reservoir bays were P limited (35%–47%) and N + P limited (35%–59%) at both stages, N limited situations were less than 20% and generally appeared in the storage period. Whatever the nutrient limited type was, phosphorus always had a higher effect on phytoplankton biomass. In the N limited situation, nitrogen came mainly from soil release (total effect = 0.6) and phosphorus from fertilizer (total effect = 0.22) and soil release (total effect = 0.17). In the P limited situation, all three sources had almost high effects on nitrogen, phosphorus, and phytoplankton biomass. In the N + P limited situation, anthropogenic discharge was the main source of nutrients and the primary threat factor for phytoplankton biomass. The approaches employed in this study could be generalized to other basins and the results were significant for early warning and controlling water eutrophication.

Sinonasal malignant melanoma is a relatively rare malignancy with poor prognosis, and effective treatments remain elusive. This analysis aimed to explore whether post-operative radiotherapy conferred any survival advantages in patients with this disease when compared with surgery alone. Published studies were identified by searching four electronic databases. The endpoints evaluated were: rates of overall survival, disease-free survival and local control. Twenty-eight studies including 1392 patients were identified. The results indicated that post-operative radiotherapy led to a significantly better three-year overall survival rate (p = 0.02), and suggested a borderline significant benefit for five-year overall survival (p = 0.05), when compared with surgery alone. However, no statistical advantage was found for disease-free survival, local control or one-year overall survival. This meta-analysis indicated that adjuvant radiotherapy prolonged survival, but showed no benefit for disease-free survival or local control.

Aims/hypothesis FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods All studies published on the association between FTO -rs9939609 (or proxy [ r 2  > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results The FTO -rs9939609 minor allele increased risk of obesity by 1.25-fold/allele ( p  = 9.0 × 10 −19 ), overweight by 1.13-fold/allele ( p  = 1.0 × 10 −11 ) and type 2 diabetes by 1.15-fold/allele ( p  = 5.5 × 10 −8 ). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p  = 6.6 × 10 −5 ). The FTO -rs9939609 minor allele increased BMI by 0.26 kg/m 2 per allele ( p  = 2.8 × 10 −17 ), WHR by 0.003/allele ( p  = 1.2 × 10 −6 ), and body fat percentage by 0.31%/allele ( p  = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

The purpose of this study was to investigate the relationship between the time to positivity (TTP) of blood cultures and outcome in patients with bloodstream infections (BSIs). Between January 1st, 2011 and December 31st, 2013, the blood cultures of inpatients with BSI or catheter-related BSI were collected at Peking University Third Hospital. The TTP of different isolates was analyzed, and the relationship between the TTP of isolates and outcome of patients with Enterobacter BSI was retrospectively analyzed. We analyzed the TTP of 886 isolates. Escherichia coli has the shortest (11.97 ± 10.06 h) and Candida has the longest first TTP (61.62 ± 42.77 h). 68.01 % of isolates reached positivity within 24 h and 88.33 % within 48 h. Over 90 % of E. coli isolates reached positivity within 24 h. Over 50 % of Candida isolates reached positivity within 48 h. The TTP differed significantly between cultures that were single or double positive for coagulase-negative staphylococci isolates, Enterobacteriaceae, and Pseudomonas aeruginosa , and between aerobic and anaerobic cultures of E. coli ( p  < 0.05). However, the TTP did not differ significantly between coagulase-negative staphylococci (double positivity) and Staphylococcus aureus . The best TTP threshold for prediction of mortality from Enterobacter species BSI was 16.3 h [area under the curve (AUC) 0.730, 95 % confidence interval (CI) 0.557, 0.864, sensitivity 100 %, specificity 44.4 %]. The TTP of clinical isolates may represent a valuable marker of the clinical significance of BSIs. Laboratories and clinics should consider using the TTP to predict the prognosis of patients with BSI by bacteria, including Enterobacter and other species.

This paper presents a hysteretic water retention curve (WRC) and unsaturated hydraulic conductivity model for deformable soils based on the change in pore-size distribution (PSD). The PSD plays a decisive role in the water retention behaviour of soils. Although its evolution during deformation is rather complicated, experimental data showed that the overall shapes and distribution characteristics of the PSD function are not significantly altered. Based on these findings, the PSD function at a deformed state is obtained by horizontal shifting and vertical scaling of the corresponding PSD function at a reference state. On this basis, a hysteretic WRC model is formulated to account for the influences of deformation and hysteresis on the variation of saturation, using seven model parameters with clear physical meanings. The proposed model is then incorporated in the Mualem model to predict the unsaturated hydraulic conductivity for deformable soils, using only one additional parameter. A large number of published laboratory tests are used to validate the proposed model, showing that it can reasonably capture important features of retention and permeability properties for deformable soils in most cases under consideration.

In this study the potential of an inversion approach based on hydraulic travel time and hydraulic attenuation tomography was assessed. Both hydraulic travel time and hydraulic attenuation tomography are based on the transformation of the transient groundwater flow equation into the eikonal equation using an asymptotic approach. The eikonal equation allows the calculation of pressure propagation and attenuation along trajectories, which is computationally efficient. The attenuation and travel time‐based inversion approaches are naturally complementary: hydraulic travel times are determined by the hydraulic diffusivity, a combination of hydraulic conductivity and specific storage, whereas the attenuation is determined solely by specific storage. The potential of our hydraulic tomographical approach was investigated at a well‐characterized sand and gravel aquifer located in the Leine River valley near Göttingen, Germany. The database for the hydraulic inversion consists of 392 cross‐well slug interference tests performed between five wells, in which the positions of the sources (injection ports) and the receivers (observation ports), isolated with double packer systems, were varied between tests. The results have shown that the combination of hydraulic travel time and hydraulic attenuation tomography allows the reconstruction of the diffusivity and storage distribution in two and three dimensions with a resolution and accuracy superior to that possible with type curve analysis.

Hypoxia induces the expansion of glioblastoma stem cells (GSCs), but the mechanism underlying it is still unclear. Here, we supply evidence that hypoxia-inducible factor-1 α (HIF-1 α ) induced activation of Notch pathway is essential for hypoxia-mediated maintenance of GSC. Either depletion of HIF-1 α or inactivation of Notch signaling partly inhibits the hypoxia-mediated maintenance of GSC. Further data suggest a role for HIF-1 α in the interaction and stabilization of intracellular domain of Notch (NICD), and activation of Notch signaling. The mRNA level of HIF-1 α and Notch target gene FABP7 was elevated in GSC. And the STAT3 pathway responsible for the HIF-1α gene transcription, the phosphatidylinositol 3-kinase-Akt and ERK1/2, both of which are contributed to HIF-1 α protein translation, are also preferentially activated in GSC. Inhibition of these pathways partly reduces the hypoxia-induced activation of the Notch pathway and subsequent GSC maintenance. Taken together, our findings suggest that HIF-1 α requires Notch pathway to drive the maintenance of GSC. The activated regulation of HIF-1 α makes GSC more sensitive to hypoxia-mediated maintenance. These findings enhance our understanding of mechanism of hypoxia-mediated GSC expansion and provide HIF-1 α as an attractive target for glioblastoma therapy.