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Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
Recruitment of mesenchymal stem cells (MSCs) to damaged tissue is a crucial step to modulate tissue regeneration. Here, the migration of human adipose-derived stem cells (hADSCs) responding to thermal and mechanical stimuli was investigated using programmable shape-memory polymer actuator (SMPA) sheets. Changing the temperature repetitively between 10 and 37 °C, the SMPA sheets are capable of reversibly changing between two different pre-defined shapes like an artificial muscle. Compared to non-actuating sheets, the cells cultured on the programmed actuating sheets presented a higher migration velocity (0.32 ± 0.1 vs. 0.57 ± 0.2 μm/min). These results could motivate the next scientific steps, for example, to investigate the MSCs pre-loaded in organoids towards their migration potential.
Cellular senescence, a driver of aging and age-related diseases, is a stable state found in metabolically active cells characterized by irreversible cell growth arrest and dramatic changes in metabolism, gene expression and secretome profile. Endogenous regeneration efficacy of mesenchymal stem cells (MSCs) could be attenuated due to senescence. MSCs can be modulated by not only biochemical signals but also by physical cues such as substrate topography. To provide a cell culture substrate that can prevent MSC senescence over an extended period of in vitro cultivation, here, the cell- and immunocompatible poly(ether imide) (PEI) substrate was used. Two distinct levels of roughness were created on the bottom surfaces of PEI inserts via injection molding: Low-R (similar to the thickness of attached single MSC, Rq: 3.9 ± 0.2 µm) and High-R (larger than single MSC thickness. Rq: 22.7 ± 0.8 µm). Cell expansion, lysosomal enzymatic activity, apoptosis and paracrine effects of senescent MSCs were examined by cell counting, detection of senescence-associated β-galactosidase (SA β-gal), Caspase 3/7, and CFSE labeling. MSCs showed high cell viability and similar spindle-shaped morphology on all investigated surfaces. Cells on Low-R presented the highest expansion (80000 ± 1805 cells), as compared to cells on smooth PEI and High-R. The low apoptosis level (0.08 vs 0.12 from smooth PEI) and senescence ratio (35% vs. 54% from smooth PEI) were observed in MSCs cultured on Low-R. The secretome from Low-R effectively prevents senescence and supports the proliferation of neighboring cells (1.5-fold faster) as compared to the smooth PEI secretome. In summary, the Low-R PEI provided a superior surface environment for MSCs, which promoted proliferation, inhibited apoptosis and senescence, and effectively influenced the proliferation of neighboring cells via their paracrine effect. Such microroughness can be considered as a key parameter for improving the therapeutic potential of endogenous regeneration, anti-organismal aging and anti-age-related pathologies via directly promoting cell growth and modulating paracrine effects of the senescence associated secretome.
Although numerous studies have used functional neuroimaging to identify executive dysfunction in patients with bipolar disorder (BD), the findings are not consistent. The aim of this meta-analysis is to identify the most reliable functional anomalies in BD patients during performance of Executive Function (EF) tasks.
A web-based search was performed on publication databases to identify functional magnetic resonance imaging studies of BD patients performing EF tasks and a voxel-based meta-analytic method known as anisotropic Effect Size Signed Differential Mapping (ES-SDM) was used to identify brain regions which showed anomalous activity in BD patients compared with healthy controls (HC).
Twenty datasets consisting of 463 BD patients and 484 HC were included. Compared with HC, BD patients showed significant hypo-activation or failure of activation in the left striatum (p = 0.00007), supplementary motor area (BA 6, p = 0.00037), precentral gyrus (BA 6, p = 0.0014) and cerebellum (BA 37, p = 0.0019), and hyper-activation in the left gyrus rectus (BA 11, p ≈ 0) and right middle temporal gyrus (BA 22, p = 0.00031) during performance of EF tasks. Sensitivity and subgroup analyses showed that the anomaly of left striatum is consistent across studies and present in both euthymic and BD I patients.
Patients with BD consistently showed abnormal activation in the cortico-striatal system during performance of EF tasks compared with HC. Failure of activation of the striatum may be a reliable marker for impairment in performance of especially inhibition tasks by patients with BD.
Activated carbon (AC) has been widely used as catalyst for oxygen reduction reaction (ORR) in air-cathode microbial fuel cells (MFCs). Here we demonstrate a new method to improve the AC air-cathode by blending it with reduced graphene oxide (rGO). rGO sheets are first deposited on Ni foam and AC is then brushed onto it with controlled mass loading. rGO sheets not only improve the electrical conductivity of AC, but also provide a large number of ORR areas. Rotating ring disk electrode measurements reveal that the number of transferred electrons at rGO-AC cathode is 3.5, indicating the four-electron pathway is the dominant process. Significantly, the MFC with rGO-AC cathode delivers a maximum power density of 2.25 ± 0.05 W/m2, which is substantially higher than that of plain AC cathode (1.35 ± 0.07 W/m2) and those for other air-cathode MFCs using AC as ORR catalyst under the same mass loading.
In this work, o-phenylenediamine-m-phenylenediamine copolymer dots (omCPs) with designed surface groups are synthesized and characterized. Here, we explored a simple, rapid semiquantitative detection system for Cu2+ with a wide detection range (5–7 orders of magnitude) based on the fluorescence in the solid state of omCPs and their tunable detection limits. The construction and application of the rapid semiquantitative detection system for Cu2+ are developed and demonstrated for the practical applications. What’s more, the detection limit can be modulated easily by adjusting the surface groups of these dots through the monomer dose control before the co-polymerization. Moreover, we demonstrated that this new technological approach is suitable for the semiquantitative determination of other ions pollutants (i.e., Na+, K+, Cu2+, Pb2+, Hg2+, and NO2−) in environmental water.
A consistent dual-mesh hybrid LES/RANS framework for turbulence modeling has been proposed recently (H. Xiao, P. Jenny, A consistent dual-mesh framework for hybrid LES/RANS modeling, J. Comput. Phys. 231 (4) (2012)). To better enforce componentwise Reynolds stress consistency between the LES and the RANS simulations, in the present work the original hybrid framework is modified to better exploit the advantage of more advanced RANS turbulence models. In the new formulation, the turbulent stresses in the filtered equations in the under-resolved regions are directly corrected based on the Reynolds stresses provided by the RANS simulation. More precisely, the new strategy leads to implicit LES/RANS consistency, where the velocity consistency is achieved indirectly via imposing consistency on the Reynolds stresses. This is in contrast to the explicit consistency enforcement in the original formulation, where forcing terms are added to the filtered momentum equations to achieve directly the desired average velocity and velocity fluctuations. The new formulation keeps the averaging procedure for the filtered quantities and at the same time preserves the ability of the original formulation to conform with the physical differences between LES and RANS quantities. The modified formulation is presented, analyzed, and then evaluated for plane channel flow and flow over periodic hills. Improved predictions are obtained compared with the results obtained using the original formulation.
The therapeutic effect of mesenchymal stem cells (MSCs) has been investigated in various clinical applications, in which their functional benefits are mainly attributed to the secretion of soluble factors. The enhancement of their therapeutic potential by physical and chemical properties of cell culture substrate is a safe and effective strategy, since they are highly sensitive to their microenvironment such as the elasticity and surface topography. In this study, we demonstrated that the geometry of polymeric substrate regulated the interleukin-6 (IL-6) secretion of human adipose derived MSCs. Polystyrene substrates comprising arrays of square-shaped (S50) or round-shaped (R50) microwells (side length or diameter of 50 μm and depth of 10 μm) were prepared by injection molding. Cellular apoptototic rate of MSCs was not affected by the microwell geometry, while the upregulated secretion of IL-6 and the enhancement of nuclear transcription factor STAT3 were detected in MSCs seeded on S50 substrate. The geometry-dependent modulatory effect was highly associated with ROCK signaling cascade. The inhibition of ROCK abolished the disparity in IL-6 secretion. These findings highlight the possibility to steer the secretion profile of stem cells via microwell geometry in combination with the manipulation of ROCK signaling pathway.
We present calculation of critical voltage for AlGaN/GaN high electron mobility transistors (HEMTs) with GaN cap layer. The calculation includes mechanical stress and relaxable energy in the GaN/AlGaN barrier layer. Under high voltage conditions, the high electric field results in an increase in stored relaxable energy. If this exceeds a critical value, crystallographic defects are formed. This degradation mechanism is voltage driven and characterized by a critical voltage beyond which non-reversible degradation takes place. The dependence of the GaN cap layer’s thickness on the critical voltage has been discussed. The calculated results indicate that thicker GaN cap layer results in higher critical voltage.
In China, rapid economic growth and increasing social problems constitute the two basic characteristics underlying contemporary social change. With dramatic social change, loneliness in older adults may have changed across birth cohorts, thus altering older adults’ mental health. The present study aims to identify birth cohort changes in Chinese older adults’ loneliness and the social indicators underlying these changes.
Cross-temporal meta-analysis was utilized to investigate changes in Chinese older adults’ loneliness from 1995 to 2011. We analyzed 25 studies (N = 13,280 adults; age ≥ 60 years) employing the University of California at Los Angeles Loneliness Scale. We correlated loneliness scores with social indicators and matched these correlations for three periods: ten years before the data collection, five years before data collection, and during the year of data collection.
Loneliness levels in Chinese older adults have increased by 1.02 standard deviations from 1995 to 2011. Social indicators such as increased urbanization level, personal medical expenditure, divorce rate, the Gini coefficient, and unemployment rate significantly predicted loneliness in Chinese older adults. Decrease in social connectedness and increase in levels of health threat may be responsible for the observed increase in levels of loneliness.
Cross-temporal meta-analysis revealed a birth cohort increase in loneliness among Chinese older adults. We conclude that changes in social connectedness and levels of health threat likely play an important role in predicting loneliness in the population of Chinese elderly adults.
A theoretical study of transconductance characteristics (gm − Vgs profile) of AlGaN/GaN high electron mobility transistors (HEMTs) with a graded AlGaN layer is given in this paper. The calculations were made using a self-consistent solution of the Schrödinger-Poisson equations and an AlGaN/GaN HEMTs numerical device model. Transconductance characteristics of the devices are discussed while the thickness and Al composition of the graded AlGaN layer are optimized. It is found that graded AlGaN layer structure can tailor device’s gm − Vgs profile by improving polar optical phonon mobility and interface roughness mobility. Good agreement is obtained between the theoretical calculations and experimental measurements over the full range of applied gate bias.
To prospectively investigate the incidence and prevalence of Wilson disease (WD) in Chinese Han population in Anhui Province, to analyze the genetic mutations in individuals with WD, and to provide basic epidemiological data regarding WD in this Chinese Han population.
Between November 2008 and June 2010, individuals aged from 7 to 75 years were screened for the cornea K-F ring in both eyes using slit lamp examination and random sampling methods based on age stratification and cluster level 1. The participants were from Anhui Province's Hanshan County, Jinzhai County, and Lixin County. The clinical manifestations of the brain, liver, kidney, skin, and other organs in each individual were also determined. Individuals with positive K-F rings and clinical manifestations indicative of WD underwent copper biochemistry evaluations, abdominal ultrasound testing, and ATP7B gene mutation screening to confirm or exclude the diagnosis of WD.
Of 153,370 individuals investigated in this study, nine were diagnosed with WD. In these WD individuals, three cases had neurological symptoms, one has hepatic symptoms, one was hepatic and neurological combined, and the other four cases were presymptomatic. Of the eight individuals in whom genetic mutations were detected, seven individuals had mutations in the ATP7B gene. The other individual had no ATP7B gene mutations but her copper biochemical test results met the diagnostic criteria for WD. The incidence and prevalence of WD in this population were approximately 1.96/100,000 and 5.87/100,000 respectively.
The Chinese Han population had a higher average prevalence of WD than the populations of the United States or Europe.
The aim of the present study was to evaluate the effects of lutein and lycopene supplementation on carotid artery intima–media thickness (CAIMT) in subjects with subclinical atherosclerosis. A total of 144 subjects aged 45–68 years were recruited from local communities. All the subjects were randomly assigned to receive 20 mg lutein/d (n 48), 20 mg lutein/d+20 mg lycopene/d (n 48) or placebo (n 48) for 12 months. CAIMT was measured using Doppler ultrasonography at baseline and after 12 months, and serum lutein and lycopene concentrations were determined using HPLC. Serum lutein concentrations increased significantly from 0·34 to 1·96 μmol/l in the lutein group (P< 0·001) and from 0·35 to 1·66 μmol/l in the combination group (P< 0·001). Similarly, serum lycopene concentrations increased significantly from 0·18 to 0·71 μmol/l in the combination group at month 12 (P< 0·001), whereas no significant change was observed in the placebo group. The mean values of CAIMT decreased significantly by 0·035 mm (P= 0·042) and 0·073 mm (P< 0·001) in the lutein and combination groups at month 12, respectively. The change in CAIMT was inversely associated with the increase in serum lutein concentrations (P< 0·05) in both the active treatment groups and with that in serum lycopene concentrations (β = − 0·342, P= 0·031) in the combination group. Lutein and lycopene supplementation significantly increased the serum concentrations of lutein and lycopene with a decrease in CAIMT being associated with both concentrations. In addition, the combination of lutein and lycopene supplementation was more effective than lutein alone for protection against the development of CAIMT in Chinese subjects with subclinical atherosclerosis, and further studies are needed to confirm whether synergistic effects of lutein and lycopene exist.
The AlGaN/GaN/InGaN/GaN double heterojunction high electron mobility transistors (DH-HEMTs) sample has been grown by MOCVD on (0 0 0 1) sapphire substrate. The structure features a 7 nm In0.046Ga0.954N interlayer determined by Rutherford backscattering (RBS). Since the polarization field in the InGaN interlayer is opposite to it in the AlGaN layer, an additional potential barrier is introduced between the two-dimensional electron gas (2DEG) channel and buffer, leading to enhanced carrier confinement and improved buffer isolation. The GaN layers between the AlGaN layer and InGaN interlayer are divided into two layers consisting of GaN channel layer which provides high mobility 2DEG grown at 1070 °C and GaN spacer layer grown at the same temperature as InGaN interlayer (800 °C) to prevent indium diffusion. RBS measurement confirms that the 3 nm GaN spacer layer isolates the InGaN interlayer well and free from diffusion. Hall measurement has been performed, the mobility as high as 1552 cm2/V s at room temperature is obtained and the sheet carrier density is 1.55 × 1013 cm−2. The average sheet resistance is 331 Ω/sq, respectively. The mobility obtained in this paper is about 20% higher than similar structures reported.
The driving mechanism of solar flares and coronal mass ejections is a topic of ongoing debate, apart from the consensus that magnetic reconnection plays a key role during the impulsive process. While present solar research mostly depends on observations and theoretical models, laboratory experiments based on high-energy density facilities provide the third method for quantitatively comparing astrophysical observations and models with data achieved in experimental settings. In this article, we show laboratory modeling of solar flares and coronal mass ejections by constructing the magnetic reconnection system with two mutually approaching laser-produced plasmas circumfused of self-generated megagauss magnetic fields. Due to the Euler similarity between the laboratory and solar plasma systems, the present experiments demonstrate the morphological reproduction of flares and coronal mass ejections in solar observations in a scaled sense, and confirm the theory and model predictions about the current-sheet-born anomalous plasmoid as the initial stage of coronal mass ejections, and the behavior of moving-away plasmoid stretching the primary reconnected field lines into a secondary current sheet conjoined with two bright ridges identified as solar flares.
We report the fabrication of AlGaN/GaN high electron mobility transistors (MIS-HEMTs) with a high breakdown voltage by employing a metal-insulator-semiconductor (MIS) gate structure using Si3N4 insulator. The Si3N4 films were deposited by plasma enhanced chemical vapor deposition (PECVD) as the surface passivation, interlayer films and the gate dielectric. In comparison with Schottky-gate HEMTs, the gate leakage currents of MIS-HEMTs exhibited three orders of magnitude reduction. With similar device structures, the off-state breakdown voltage of MIS-HEMTs was 1050 V with a specific on-resistance of 4.0 mΩ cm2, whereas the breakdown voltage and specific on-resistance of SG-HEMTs were 740 V and 4.4 mΩ cm2, respectively. In addition, the MIS-HEMTs exhibited little current slump in the pulsed measurements and possessed faster switch speed than Si MOSFET. We demonstrate that AlGaN/GaN MIS-HEMTs are promising not only for microwave applications but also for high power switching applications.
Interspecies intracytoplasmic sperm injection has been carried out to understand species-specific differences in oocyte environments and sperm components during fertilization. While sperm aster organization during cat fertilization requires a paternally derived centriole, mouse and hamster fertilization occur within the maternal centrosomal components. To address the questions of where sperm aster assembly occurs and whether complete fertilization is achieved in cat oocytes by interspecies sperm, we studied the fertilization processes of cat oocytes following the injection of cat, mouse, or hamster sperm. Male and female pronuclear formations were not different in the cat oocytes at 6 h following cat, mouse or hamster sperm injection. Microtubule asters were seen in all oocytes following intracytoplasmic injection of cat, mouse or hamster sperm. Immunocytochemical staining with a histone H3-m2K9 antibody revealed that mouse sperm chromatin is incorporated normally with cat egg chromatin, and that the cat eggs fertilized with mouse sperm enter metaphase and become normal 2-cell stage embryos. These results suggest that sperm aster formation is maternally dependent, and that fertilization processes and cleavage occur in a non-species specific manner in cat oocytes.
The material characterization toolbox has recently experienced a number of parallel revolutionary advances, foreshadowing a time in the near future when material scientists can quantify material structure evolution across spatial and temporal space simultaneously. This will provide insight to reaction dynamics in four-dimensions, spanning multiple orders of magnitude in both temporal and spatial space. This study presents the authors’ viewpoint on the material characterization field, reviewing its recent past, evaluating its present capabilities, and proposing directions for its future development. Electron microscopy; atom probe tomography; x-ray, neutron and electron tomography; serial sectioning tomography; and diffraction-based analysis methods are reviewed, and opportunities for their future development are highlighted. Advances in surface probe microscopy have been reviewed recently and, therefore, are not included [D.A. Bonnell et al.: Rev. Modern Phys. in Review]. In this study particular attention is paid to studies that have pioneered the synergetic use of multiple techniques to provide complementary views of a single structure or process; several of these studies represent the state-of-the-art in characterization and suggest a trajectory for the continued development of the field. Based on this review, a set of grand challenges for characterization science is identified, including suggestions for instrumentation advances, scientific problems in microstructure analysis, and complex structure evolution problems involving material damage. The future of microstructural characterization is proposed to be one not only where individual techniques are pushed to their limits, but where the community devises strategies of technique synergy to address complex multiscale problems in materials science and engineering.
Experiments using a biased multiblock limiter in the KT-5C tokamak show that positive biasing is more effective than negative biasing in modifying the edge electric field, suppressing fluctuations and improving plasma confinement. The biasing effect varies with the limiter area, the toroidal magnetic field and the biasing voltage. By positive biasing, the edge profiles of the plasma potential, the electron temperature and the density become steeper, resulting in a reduced edge particle flux, an increased global particle confinement time and lower fluctuation levels of the edge plasma.