Paliperidone Extended Release Versus Olanzapine in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Multicenter Study.

PURPOSE: Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy. METHODS: This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference. RESULTS: Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated. CONCLUSIONS: Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure-activity relationship, crystal structural characterization and in vivo study.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with in vitro metabolic stability tests and in vivo pharmacokinetic profiling, a representative compound (35) was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor 35 was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

Numerical Modelling of the Effect of Filler/Matrix Interfacial Strength on the Fracture of Cementitious Composites.

The interface between filler and hydration products can have a significant effect on the mechanical properties of the cement paste system. With different adhesion properties between filler and hydration products, the effect of microstructural features (size, shape, surface roughness), particle distribution and area fraction of filler on the fracture behavior of a blended cement paste system is supposed to be different, as well. In order to understand the effect of the microstructural features, particle distribution and area fraction of filler on the fracture behavior of a blended cement paste system with either strong or weak filler-matrix interface, microscale simulations with a lattice model are carried out. The results show that the strength of the filler-matrix interface plays a more important role than the microstructural features, particle distribution and area fraction of filler in the crack propagation and the strength of blended cement paste. The knowledge acquired here provides a clue, or direction, for improving the performance of existing fillers. To improve the performance of fillers in cement paste in terms of strength, priority should be given to improving the bond strength between filler particles and matrix, not to modifying the microstructural features (i.e., shape and surface roughness) of the filler.

Cyclic Behavior of Low Rise Concrete Shear Walls Containing Recycled Coarse and Fine Aggregates.

In this study, the cyclic behaviors of low rise concrete shear walls using recycled coarse or fine aggregates were investigated. Eight low rise Recycled Aggregates Concrete (RAC) shear wall specimens were designed and tested under a cyclic loading. The following parameters were varied: replacement percentages of recycled coarse or fine aggregates, reinforcement ratio, axial force ratio and X-shaped rebars brace. The failure characteristics, hysteretic behavior, strength and deformation capacity, strain characteristics and stiffness were studied. Test results showed that the using of the Recycled Coarse Aggregates (RCA) and its replacement ratio had almost no influence on the mechanical behavior of the shear wall; however, the using of Recycled Fine Aggregates (RFA) had a certain influence on the ductility of the shear wall. When the reinforcement ratio increased, the strength and ductility also increased. By increasing the axial force ratio, the strength increased but the ductility decreased significantly. The encased brace had a significant effect on enhancing the RAC shear walls. The experimental maximum strengths were evaluated with existing design codes, it was indicated that the strength evaluation of the low rise RAC shear walls can follow the existing design codes of the conventional concrete shear walls.

Modeling Framework for Fracture in Multiscale Cement-Based Material Structures.

Multiscale modeling for cement-based materials, such as concrete, is a relatively young subject, but there are already a number of different approaches to study different aspects of these classical materials. In this paper, the parameter-passing multiscale modeling scheme is established and applied to address the multiscale modeling problem for the integrated system of cement paste, mortar, and concrete. The block-by-block technique is employed to solve the length scale overlap challenge between the mortar level (0.1-10 mm) and the concrete level (1-40 mm). The microstructures of cement paste are simulated by the HYMOSTRUC3D model, and the material structures of mortar and concrete are simulated by the Anm material model. Afterwards the 3D lattice fracture model is used to evaluate their mechanical performance by simulating a uniaxial tensile test. The simulated output properties at a lower scale are passed to the next higher scale to serve as input local properties. A three-level multiscale lattice fracture analysis is demonstrated, including cement paste at the micrometer scale, mortar at the millimeter scale, and concrete at centimeter scale.

Experimental Study on Cementitious Composites Embedded with Organic Microcapsules.

The recovery behavior for strength and impermeability of cementitious composites embedded with organic microcapsules was investigated in this study. Mortar specimens were formed by mixing the organic microcapsules and a catalyst with cement and sand. The mechanical behaviors of flexural and compression strength were tested. The results showed that strength could increase by up to nine percent with the addition of a small amount of microcapsules and then decrease with an increasing amount of microcapsules. An orthogonal test for investigating the strength recovery rate was designed and implemented for bending and compression using the factors of water/cement ratio, amount of microcapsules, and preloading rate. It is shown that the amount of microcapsules plays a key role in the strength recovery rate. Chloride ion permeability tests were also carried out to investigate the recovery rate and healing effect. The initial damage was obtained by subjecting the specimens to compression. Both the recovery rate and the healing effect were nearly proportional to the amount of microcapsules. The obtained cementitious composites can be seen as self-healing owing to their recovery behavior for both strength and permeability.