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Abstract Background The cost efficient two-stage design is often used in genome-wide association studies (GWASs) in searching for genetic loci underlying the susceptibility for complex diseases. Replication-based analysis, which considers data from each stage separately, often suffers from loss of efficiency. Joint test that combines data from both stages has been proposed and widely used to improve efficiency. However, existing joint analyses are based on test statistics derived under an assumed genetic model, and thus might not have robust performance when the assumed genetic model is not appropriate. Results In this paper, we propose joint analyses based on two robust tests, MERT and MAX3, for GWASs under a two-stage design. We developed computationally efficient procedures and formulas for significant level evaluation and power calculation. The performances of the proposed approaches are investigated through the extensive simulation studies and a real example. Numerical results show that the joint analysis based on the MAX3 test statistic has the best overall performance. Conclusions MAX3 joint analysis is the most robust procedure among the considered joint analyses, and we recommend using it in a two-stage genome-wide association study.

In this study, in order to reveal the effect of different bioactive glass matrix on magnetic bioactive glass-ceramics (MBGCs), the interfaces between magnetite and three most often used bioactive glass systems, 80SiO2-15CaO-5P2O5 (80S), 58SiO2-36CaO-6P2O5 (58S), and 35SiO2-50CaO-7P2O5-7MgO-1CaF2 (35SM), were prepared and analyzed. Moreover, the phase composition, magnetic structure, and in vitro reactivity of the corresponding glass/ferrite composites with 29 wt% ferrite were investigated. The results showed that Fe migrated into the glass matrix much faster than Si moved into the ferrite phase. Moreover, 58S and 80S glass displayed much stronger interfacial reactions with the ferrite than 35SM glass. Furthermore, the Mössbauer spectra revealed that the 35SM/ferrite composite, showing a saturation magnetization of 3.88 A·m2/kg, had about 29% Fe ions remained the magnetic structure and MgFe2O4 was detected, while all Fe ions were found to be in the paramagnetic structure in the other two composites. Additionally, continuous deposit layers covered all the three composite surfaces after being soaked in simulated body fluid for 14 days. Therefore, when used as MBGC glass matrix, the 35SM glass seemed to be more beneficial to the magnetism. The results of this study are helpful in the design and optimization of MBGCs. [ABSTRACT FROM AUTHOR]

In this work, chopped basalt fibres were used as reinforcing and toughening phase to enhance the mechanical properties of calcium phosphate bone cement. The microstructure, mechanical properties, and cytocompatibility of the composite cement were evaluated thoroughly. The results revealed that the addition of fibres did not significantly change the cement setting process but markedly improved the toughness. The fracture work of cement with 1 wt% fibres was 10 times higher than that of the pure control due to pulling out of the fibres. Moreover, the flexural strength of composite cement was also promoted with a certain amount of fibres. Additionally, the composite cementscement showed no cytotoxicity to MG63 cells, and the osteoblasts could adhere and proliferate well on the cements. Therefore, basalt fibres could be potentially used as a reinforcing phase for calcium phosphate bone cement. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between expression of mitogen-activated protein kinase kinase 4 (MKK4) and metastasis of oral squamous cell carcinoma (OSCC). Methods: Expression levels of MKK4 mRNA and protein were examined in surgically resected oral squamous cell carcinoma specimens and corresponding lymph nodes by semi-quantitative reverse Transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results: The expression of MKK4 in 48 cases of metastasis of lymph node group was significantly higher than 27 cases of without metastasis of lymph node group in 75 cases of paraffin-embedded OSCC samples (P<0.05). The expression of MKK4 in 48 cases of metastatic lymph node lesions was higher than 48 cases of primary site of OSCC (JP<0.05). There was no correlation between the expression of MKK4 and primary site, size of tumor, histological grade (P>0.05). The expres-sion of MKK4 mRNA in 16 cases of metastasis of lymph node group was significantly higher than 22 cases of without metastasis of lymph node group in 38 cases of fresh OSCC samples (P<0.01). The expression of MKK4 in 6 cases of matched metastatic lymph node lesions was higher than 16 cases of primary tumour (P<0.05). Conclusion: The up-regulation of MKK4 protein and mRNA may be related with the invasion and metastasis of OSCC. MKK4 maybe played a promoting role in the progression and metastasis of OSCC. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between expression of mitogen-activated protein kinase kinase 4 (MKK4) and metastasis of oral squamous cell carcinoma (OSCC)., Methods: Expression levels of MKK4 mRNA and protein were examined in surgically resected oral squamous cell carcinoma specimens and corresponding lymph nodes by semi-quantitative reverse Transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry., Results: The expression of MKK4 in 48 cases of metastasis of lymph node group was significantly higher than 27 cases of without metastasis of lymph node group in 75 cases of paraffin-embedded OSCC samples (P < 0.05). The expression of MKK4 in 48 cases of metastatic lymph node lesions was higher than 48 cases of primary site of OSCC (P < 0.05). There was no correlation between the expression of MKK4 and primary site, size of tumor, histological grade ( P > 0.05). The expression of MKK4 mRNA in 16 cases of metastasis of lymph node group was significantly higher than 22 cases of without metastasis of lymph node group in 38 cases of fresh OSCC samples (P < 0.01). The expression of MKK4 in 6 cases of matched metastatic lymph node lesions was higher than 16 cases of primary tumour (P < 0.05), Conclusion: The up-regulation of MKK4 protein and mRNA may be related with the invasion and metastasis of OSCC. MKK4 maybe played a promoting role in the progression and metastasis of OSCC.