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ABSTRACT: A common problem in the longitudinal data analysis is the missing data problem. Two types of missing patterns are generally considered in statistical literature: monotone and non-monotone missing data. Nonmonotone missing data occur when study participants intermittently miss scheduled visits, while monotone missing data can be from discontinued participation, loss to follow-up, and mortality. Although many novel statistical approaches have been developed to handle missing data in recent years, few methods are available to provide inferences to handle both types of missing data simultaneously. In this article, a latent random effects model is proposed to analyze longitudinal outcomes with both monotone and non-monotone missingness in the context of missing not at random. Another significant contribution of this article is to propose a new computational algorithm for latent random effects models. To reduce the computational burden of high-dimensional integration problem in latent random effects models, we develop a new computational algorithm that uses a new adaptive quadrature approach in conjunction with the Taylor series approximation for the likelihood function to simplify the E-step computation in the expectation-maximization algorithm. Simulation study is performed and the data from the scleroderma lung study are used to demonstrate the effectiveness of this method.
Statistical Methods in Medical Research 05/2012; · 2.44 Impact Factor
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Xueling Li,
Hong Cao,
Qiang Wang,
Biao Di,
Ming Wang,
Jianxi Lu,
Lijie Pan,
Li Yang,
Mingzhu Mei,
Xingfei Pan, Gang Li,
Lili Wang
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ABSTRACT: The envelope protein of dengue virus is involved in host cell attachment for entry and induction of protective immunity. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we developed a genetic vaccine based on a novel adeno-associated viral (AAV) vector expressing the carboxy-terminal truncated envelope protein (79E) of dengue virus. The expression of the recombinant 79E protein in HEK 293 cells was confirmed by Western blot. Vectors packaged with novel AAV capsids (AAV2/8 or AAV2/rh32.33) were injected into C57BL/6 mice intramuscularly. Dengue virus antigen was produced in the mice and induced long-lasting antibody responses against the dengue virus still detectable 20 weeks after immunization. AAV2/8 vaccine induced higher anti-dengue virus antibody levels than AAV2/rh32.33 vaccine or AAV plasmid. Furthermore, the anti-dengue antibodies could neutralize homogeneous dengue virus. These results demonstrated that the AAV vaccines possessed appropriate immunogenicity and could be used for the development of an effective dengue vaccine.
Microbes and Infection 05/2012; 14(11):1000-7. · 3.10 Impact Factor
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ABSTRACT: The study is aimed to evaluate the differentiation potential of human adipose-derived stem cells (hADSCs) into urothelial lineage, and to assess possibility of constructing ureteral grafts using the differentiated hADSCs and a novel polylactic acid (PLA)/collagen scaffolds. HADSCs were indirectly cocultured with urothelial cells in a transwell coculture system for urothelial differentiation. After 14 days coculturing, differentiation was evaluated by detecting urothelial lineage markers (cytokeratin-18 and uroplakin 2) in mRNA and protein level. Then the differentiated hADSCs were seeded onto PLA/collagen ureteral scaffolds and cultured in vitro for 1 week. The biocompatibility of the scaffolds was tested by scanning electron microscopy (SEM) and MTT analysis. At last, the cell/scafflod grafts were subcutaneously implanted into 4-week-old female athymic mice for 14 days. The results demonstrated that the hADSCs could be efficiently induced into urothelial lineage by indirect coculture. The differentiated cells seeded onto the PLA/collagen ureteral scaffolds survived up to 7 days and maintained proliferation in vitro, which indicated that the scaffolds displayed good biocompatibility. In vivo study showed that the differentiated cells in the grafts survived, formed multiple layers on the scaffolds and expressed urothelial lineage markers. In conclusion, hADSCs may serve as an alternative cell resource in cell-based tissue engineering for ureteral reconstruction. These cells could be employed to construct a model of ureteral engineering grafts and be effectively applied in vivo, which could be a new strategy on ureteral replacement with applicable potential in clinical research.
Journal of Biomedical Materials Research Part A 05/2012; 100(10):2612-22. · 2.63 Impact Factor
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ABSTRACT: Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet.
Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established.
Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis.
These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines.
Chinese medical journal 04/2012; 125(8):1381-8. · 0.86 Impact Factor
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ABSTRACT: To explore a new method for repair of concurrent skin and nerve defect at palm and carpal on ulnar side.
From April 2000 to August 2009, five cases with concurrent skin and nerve defect at palm and carpal on ulnar side were reconstructed with free medial plantar flaps. Palmar nervous proprii defect at ulnar side of little finger was repaired by the first toe tibia nervous proprii in one case. The superficial branch of radial nerve was applied to repair the defect of ulnar nerve, as well as its deep or superficial branch in two cases. The superficial branch of radial nerve was also used to repair the defect of superficial branch of ulnar nerve, common palmar digital nerve of the fourth finger, Little finger ulnar palmar nervous proprii in one case. The dorsal branch of ulnar nerve was applied to repair the defect of superficial branch of ulnar nerve, common palmar digital nerve of the fourth finger, little finger ulnar palmar nervous proprii in one case. The vascular bundle of medial plantar flap was anastomozised with ulnar vascular bundle. The wounds at donor sites were covered with free skin grafts which were obtained from upper leg.
All the flaps and skin grafts were survived completely. The five patients were followed up for six months to four years with no muscular atrophy or claw hand deformity. The esthetic result was satisfied. The Sensory of flaps and fingers recovered to S3 to S3+. The two-point discrimination distance on flaps was range from 7 mm to 10 mm. The postoperative comprehensive evaluation was excellent in the cases whose superficial and deep branches of ulnar nerve were repaired.
Free medial plantar flap is an effective method to repair concurrent skin and nerve defect at palm and carpal on the ulnar side.
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery 03/2011; 27(2):98-101.
