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Hydraulic fracturing in combination with horizontal well has been widely used to stimulate shale oil and gas from reservoirs. Numerical simulation of hydraulic fracturing is a great challenge due to the geological complexity of reservoirs. In this paper, a fully coupled fluid flow, plastic deformation and fracture propagation model is presented based on cohesive zone method. An implicit algorithm to discretize and integrate the fully coupled differential equations is presented. Plastic deformation is observed in the vicinity of hydraulic fracture during the stimulation process. The effect of plastic and stimulation parameters on fracture propagation behaviors has been investigated. The energy dissipation induced by the plastic deformation increases the fracture width. The fracture propagation behaviors both in viscosity and toughness dominated regimes are discussed. The evolution formula of non-dimensional fracture length at different regimes is presented by fitting numerical results. [ABSTRACT FROM AUTHOR]

In this paper, nanocrystalline Nd[(Zn0.925Co0.075)1/2Ti1/2]O3 (NZCT75) powders were synthesized through glycine–nitrate combustion method with the intent of reducing the sintering temperature and improving the microwave dielectric properties of NZCT75 ceramics. Phase composition, structure, and morphology of the powders were analyzed by thermogravimetric analysis–differential thermal analysis (TG–DTA), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The XRD results showed that the as-synthesized powder after rapid self-propagating combustion was highly crystallized and was mainly composed of NZCT75 phase and small amount of unknown phase. The unknown phase could be vanished through the calcination process of 600 °C. Compared to solid-state reaction route, a reduction of about 600 °C in the synthesis temperature for pure phase NZCT75 was realized. A large amount of pores with inhomogeneous distribution in size and shape was found from the SEM image of the as-synthesized powder due to the rapid combustion reaction between glycine and nitrates. The TEM study revealed that the average particle size of the calcined powder is around 31.9 nm. The bulk sample prepared by the nanosized powder could be sintered to 98.8% of the theoretical density at 1250 °C, reducing about 160 °C more than the solid-state reaction method. Meanwhile, excellent microwave dielectric properties of NZCT75 ceramics presented a dielectric constant of 37.17, a quality factor of 257,600 GHz, and a temperature coefficient of resonant frequency of – 29.48 ppm/oC. This study develops a facile approach to synthesize nanocrystalline powder for a promising application in microwave dielectric ceramics. [ABSTRACT FROM AUTHOR]

We report a successful fabrication of 0.6Ca0.61Nd0.26TiO3–0.4Nd(Zn0.5Ti0.5)O3 (hereinafter abbreviated as 6CNT–4NCT) microwave ceramics with good sintering activity and desired dielectric properties from EDTA-gel combustion synthesized powders in this paper. The as-synthesized nanopowders have been characterized by X–ray diffraction (XRD), Fourier transformation infrared (FT–IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques, respectively. The sintering behavior and dielectric performance have been evaluated on the sintered ceramics. The as-obtained product with amorphous structure could be directly crystallized and produced pure 6CNT–4NCT solid solution phase with orthorhombic perovskite structure at a relatively low temperature of 700 °C, without formation of any intermediate phase. TEM images revealed that homogeneous and well dispersed spherical-shaped nanostructure with an average particle size of 23.8 nm was formed at 800 °C. Well-dense 6CNT–4NCT bulk ceramics with 98.8% relative density were obtained at a relatively low sintering temperature of 1225 °C due to high sintering activity of nanopowders. Moreover, the bulk ceramics exhibited a higher quality factor (Q × f) value than those prepared via the conventional solid-state reaction method. Desired microwave dielectric properties were achieved at 1200 °C: dielectric constant εr = 57.2, Q × f = 59,360 GHz, and temperature coefficient of resonant frequency τf = + 1.95 ppm/°C. This study indicates that the EDTA-gel combustion route is a convenient, low-cost, and interesting route to fabricate high-quality microwave ceramics for practical applications. [ABSTRACT FROM AUTHOR]

Background and Objective: Ramucirumab is a novel antiangiogenic agent approved as second-line therapy for patients with advanced stomach cancer and gastroesophageal junction adenocarcinoma. Although existing evidence from clinical trials has demonstrated hypertension is one of the major adverse events of this agent, overall risks have yet to be reported. Methods: We carried out a meta-analysis of published studies to determine the overall incidence and relative risk (RR) of hypertension associated with ramucirumab. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95 % confidence intervals (CIs) by using a random effects model. Results: Eleven studies with a total of 3,851 patients with multiple cancers were included. The overall incidence of all-grade hypertension was 20.0 % (95 % CI 15.0-26.0) with 8.6 % (95 % CI 6.3-11.7) being high-grade hypertension. The risk of developing hypertension was greater in ramucirumab-treated patients (RR for all grades 2.77, 95 % CI 1.94-3.94, p < 0.001, RR for high-grade 3.58, 95 % CI 2.45-5.23, p < 0.001). Conclusions: Administration of ramucirumab to patients with cancer is associated with increased risk of hypertension. [ABSTRACT FROM AUTHOR]

Purpose: We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer. Methods: PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs) for dichotomous data with 95 % confidence intervals (CIs) were derived. Results: Eight studies including 2,077 participants were analyzed. Compared to chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk reduction of PFS events. However, the benefit did not reach statistical significance (HR 0.86; 95 % CI 0.70-1.04, P = 0.126). Also, no OS benefit was observed (HR 1.03; 95 % CI 0.89-1.18, P = 0.724). The addition of MATKIs significantly increased the ORR (OR 1.57; 95 % CI 1.30-1.91, P = 0.000). Subgroup analysis revealed that sorafinib showed a significantly greater effect on PFS in patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55-0.82, P = 0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to have no substantial efficacy for metastatic breast cancer. Toxicities were more frequent in patients receiving MATKIs. Conclusion: Overall, regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS, although significant improvement in ORR was observed. However, the addition of sorafenib significantly improved PFS. Further studies are needed to corroborate this finding. [ABSTRACT FROM AUTHOR]

FAS and FAS ligand (FASL) play crucial roles in apoptotic signaling, and deregulation of this pathway may facilitate carcinogenesis. Studies on the association between the FAS/FASL polymorphisms (FAS-1377G/A rs2234767, FAS-670A/G rs1800682, and FASL-844C/T rs763110) and breast cancer risk have reported inconsistent results. Therefore, to characterize the relationship between those polymorphisms and breast cancer risk, we undertook a meta-analysis of those studies. Several electronic databases were searched for articles on the FAS/FASL polymorphisms and breast cancer risk. The genotype data were extracted; pooled odds ratios (OR) with 95 % confidence intervals (CIs) were used to estimate the strength of the association. Five studies were eligible for our meta-analysis. Overall, we observed significant associations of the FAS-1377G/A polymorphism with breast cancer susceptibility (AG vs. GG: OR = 1.15, 95 % CI 1.02-1.30; AA vs. GG: OR = 1.39, 95 % CI 1.12-1.72; AG/AA vs. GG: OR = 1.18, 95 % CI, 1.16-1.32; A vs. G: OR = 1.16, 95 % CI 1.06-1.26), but we did not observe significant association of the Fas-670A/G and FasL-844C/T polymorphisms with breast cancer risk. In the subgroup analysis, we observed that the FAS-1377G/A and FASL-844C/T polymorphisms were associated with breast cancer risk in Chinese but not Whites; we still did not observed association of the FAS-670A/G polymorphism with breast cancer risk. Our meta-analysis revealed that FAS-1377G>A polymorphism was associated with an increased risk of breast cancer. FASL-844C>T polymorphism might be associated with a reduced breast cancer risk in Chinese. However, FAS-670A/G had no any effect on breast carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Regorafenib is a novel multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). Hypertension is one of the major adverse events of this agent, but to date the incidence and risk of hypertension with regorafenib have not been systematically investigated. We have conducted a systematic review and meta-analysis of published clinical trials to determine its overall incidence and risk. Methods: PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies published up to September 9, 2013. Eligible studies were prospective phase II or III clinical trials using regorafenib in cancer patients with data on hypertension available. The incidence and relative risk (RR) of hypertension were calculated using a random-effects model. Results: Data from a total of 1,069 patients (regorafenib n = 750; controls n = 319) from five clinical trials were included for analysis. The overall incidence of all-grade and high-grade hypertension were 44.4 % [95 % confidence interval (CI) 30.8-59.0 %) and 12.5 % (95 % CI 5.2-27.1 %), respectively. The use of regorafenib in cancer patients was associated with a significantly increased risk of all-grade (RR 3.76, 95 % CI 2.35-5.99) and high-grade (RR, 8.39, 95 % CI 3.10-22.71) hypertension. The risk might vary with tumor types ( P = 0.000). Conclusions: Patients with cancer receiving regorafenib have a significantly higher risk of developing hypertension. Close monitoring and appropriate management of this hypertension are strongly recommended. [ABSTRACT FROM AUTHOR]