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The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2 = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2 = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.
The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.
The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.
In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.
Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).
Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.
Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.
We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).
Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.
Psychomotor retardation (PMR) in depression is analogous to the hypokinesia in Parkinson's disease, which is associated with the unbalanced direct and indirect pathways of cortico-basal ganglia-thalamo-cortical (CBTC) circuitry. This study hypothesized PMR in major depressive disorder (MDD) should be associated with the hyperactivity of CBTC indirect pathways.
To substantiate the hypothesis that the PMR symptom of MDD might attribute to the hyperactivity of the ortico-basal ganglia-thalamo-cortical indirect pathway which could inhibit psychomotor performance.
We investigated the intrinsic stiato-subthalamic nucleus (STN)-thalamic functional connectivity (FC), three pivotal hubs of the indirect pathway, in 30 MDD patients with PMR (PMR group) and well matched 30 patients without PMR (NPMR group) at baseline, and 11 patients of each group at follow-up who remitted after antidepressant treatment.
The results showed increased STN-striatum FC of PMR group at baseline and no more discrepancy at follow-up, and significant correlation between PMR severity and thalamo-STN FC.
Our findings suggested the increased STN- striatum FC should be considered as a state biomarker to distinguish MDD patients with PMR from patients without PMR at acute period, and thalamo-STN FC could be identified as the predictor of the PMR severity for MDD patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The coronal heating problem is a long-standing perplexing issue. In this study, 13 solar activity indexes are used to investigate their phase relation with the sunspot number (SSN). Only three of them are found to statistically significantly lag the SSN (large-scale magnetic activity) by about one solar rotation period; the three indexes are total solar irradiance (TSI), the modified coronal index, and the solar wind velocity; the former two indexes may represent the long-term variation of energy quantity of the heated photosphere and corona, respectively. The Mount Wilson Sunspot Index (MWSI) and the Magnetic Plage Strength Index (MPSI), which reflect the large- and small-scale magnetic field activities, respectively, are also utilised to investigate their phase relations with the three indexes. The three indexes are found to be much more intimately related to MPSI than to MWSI, and MWSI statistically significantly leads TSI by about one rotation period. The heated corona is found to pulse perfectly in step with the small-scale magnetic activity rather than the large-scale magnetic activity; furthermore, combined with observations, our statistical evidence should thus attribute coronal heating firmly to small-scale magnetic activity phenomena, such as spicules, micro-flares, nano-flares, and others. The photosphere and the corona are synchronously heated, which should seemingly prefer magnetic reconnection heating to wave heating. In the long term, such a coronal heating way is inferred effective. Statistically, it is also small-scale magnetic activity phenomena that produce TSI enhancement. Coronal heating and solar wind acceleration are found to be synchronous, as standard models require.
Two-dimensional particle-in-cell (PIC) simulations have been used to investigate the interaction between a laser pulse and a foil exposed to an external strong longitudinal magnetic field. Compared with that in the absence of the external magnetic field, the divergence of proton with the magnetic field in radiation pressure acceleration (RPA) regimes has improved remarkably due to the restriction of the electron transverse expansion. During the RPA process, the foil develops into a typical bubble-like shape resulting from the combined action of transversal ponderomotive force and instabilities. However, the foil prefers to be in a cone-like shape by using the magnetic field. The dependence of proton divergence on the strength of magnetic field has been studied, and an optimal magnetic field of nearly 60 kT is achieved in these simulations.
Finite-amplitude wave groups with multiple near-resonances are investigated to extend the existing results due to Liu et al. (J. Fluid Mech., vol. 835, 2018, pp. 624–653) from steady-state wave groups in deep water to steady-state wave groups in finite water depth. The slow convergence rate of the series solution in the homotopy analysis method and extra unpredictable high-frequency components in finite water depth make it hard to obtain finite-amplitude wave groups accurately. To overcome these difficulties, a solution procedure that combines the homotopy analysis method-based analytical approach and Galerkin method-based numerical approaches has been used. For weakly nonlinear wave groups, the continuum of steady-state resonance from deep water to finite water depth is established. As nonlinearity increases, the frequency bands broaden and more steady-state wave groups are obtained. Finite-amplitude wave groups with steepness no less than
are obtained and the resonant sets configuration of steady-state wave groups are analysed in different water depths. For waves in deep water, the majority of non-trivial components appear around the primary ones due to four-wave, six-wave, eight-wave or even ten-wave resonant interactions. The dominant role of four-wave resonant interactions for steady-state wave groups in deep water is demonstrated. For waves in finite water depth, additional non-trivial high-frequency components appear in the spectra due to three-wave, four-wave, five-wave or even six-wave resonant interactions with the components around the primary ones. The amplitude of these high-frequency components increases further as the water depth decreases. Resonances composed by components only around the primary ones are suppressed while resonances composed by components around the primary ones and from the high-frequency domain are enhanced. The spectrum of steady-state resonant wave groups changes with the water depth and the significant role of three-wave resonant interactions in finite water depth is demonstrated.
A multi-scale strategy is employed in the paper to investigate the thermo-mechanical properties of 2.5D angle-interlock woven shape memory polymer composites (SMPCs). In the study, the mesoscopic model of 2.5D woven SMPCs and microscopic model of yarns are firstly developed. After that, the themo-viscoelastic constitutive relationship of the yarn is described in the form of hereditary integral and the parameters of relaxation moduli are obtained from nonlinear fitting of Prony series based on the results of finite element method (FEM). Based on the multi-scale models and the constitutive relationship, the effects of warp and weft arranged densities on viscoelastic properties of 2.5D woven SMPCs are studied in detail. Finally, the shape memory behavior along the warp direction in small strain region is also analyzed. The research in the paper lays a foundation for design and application of woven SMPCs in engineering.
We study the shape and motion of gas bubbles in a liquid flowing through a horizontal or slightly inclined thin annulus. Experimental data show that in the horizontal annulus, bubbles develop a unique ‘tadpole-like’ shape with a semi-circular cap and a highly stretched tail. As the annulus is inclined, the bubble tail tends to vanish, resulting in a significant decrease of bubble length. To model the bubble evolution, the thin annulus is conceptualised as a ‘Hele-Shaw’ cell in a curvilinear space. The three-dimensional flow within the cell is represented by a gap-averaged, two-dimensional model, which achieved a close match to the experimental data. The numerical model is further used to investigate the effects of gap thickness and pipe diameter on the bubble behaviour. The mechanism for the semi-circular cap formation is interpreted based on an analogous irrotational flow field around a circular cylinder, based on which a theoretical solution to the bubble velocity is derived. The bubble motion and cap geometry is mainly controlled by the gravitational component perpendicular to the flow direction. The bubble elongation in the horizontal annulus is caused by the buoyancy that moves the bubble to the top of the annulus. However, as the annulus is inclined, the gravitational component parallel to the flow direction becomes important, causing bubble separation at the tail and reduction in bubble length.
Good canopy structure is essential for optimal maize (Zea mays L.) production. However, creating appropriate maize canopy structure can be difficult, because the characteristics of individual plants are altered by changes in plant age, density and interactions with neighbouring plants. The objective of the current study was to find a reliable method for building good maize canopy structure by analysing changes in canopy structure, light distribution and grain yield (GY). A modern maize cultivar (ZhengDan958) was planted at 12 densities ranging from 1.5 to 18 plants/m2 at two field locations in Xinjiang, China. At the silking stage (R1), plant and ear height increased with plant density as well as leaf area index (LAI), whereas leaf area per plant decreased logarithmically. The fraction of light intercepted by the plant (F) increased with increasing plant density, but the light extinction coefficient (K) decreased linearly from 0.61 to 0.39. Taking the optimum value of F (95%) as an example, and using measured values of K for each plant density at R1 and the equation from Beer's law, the corresponding (theoretical) LAI for each plant density was calculated and optimum plant density (9.72 plants/m2) obtained by calculating the difference between theoretical LAIs and actual observations. Further analysis showed that plant density ranging from 10.64 to 11.55 plants/m2 yielded a stable GY range. Therefore, taking into account the persistence time for maximum LAI, the plant density required to obtain an ideal GY maize canopy structure should be increased by 10–18% from 9.72 plants/m2.
This paper aims to build the finite element model of the composite sinusoidal specimens and to carry out the parametric analysis. In this paper, the damage behaviour and the energy-absorbing results of composite sinusoidal specimens have been studied by quasi-static crushing experiments. The failure mechanisms of specimens under quasi-static crushing is further analysed. A numerical simulation has been performed by using the finite element model code LS-DYNA. The numerical results, in terms of load -displacement data, have been compared against experimental data, and good agreement has been found. Moreover, a sensitivity study has been carried out by varying material properties in order to assess their influence on the numerical results, and the material parameter selection scheme is optimised based on the constructed corresponding response surfaces. The results show that the response surface model has passed the test of goodness of fit, and the optimisation method can effectively assist the finite element modelling, and greatly decrease the numbers of trial and error.
Introduction: In high-income countries, vomiting often impedes oral rehydration therapy, leading to intravenous rehydration fluid administration to children with acute gastroenteritis. Ondansetron administration reduces vomiting and intravenous fluid administration in this population. We evaluated whether ondansetron is similarly effective when employed in Pakistan. Methods: In this 2-hospital, double-blind, placebo-controlled, emergency department-based, randomized trial, we recruited children aged 0·5 to 5·0 years, without dehydration, who had diarrhea and 1 episode of vomiting within 4 hours of arrival. Patients were randomly assigned (1:1), via an internet-based randomization service, using a stratified, variable block randomization scheme, to receive a single dose of oral ondansetron or placebo. The primary endpoint was intravenous rehydration (administration of 20 ml/kg over 4 hours of an isotonic fluid) within 72 hours of randomization. All randomized children were analysed. Results: From July 3, 2014, to January 12, 2017, 626 children were randomized. Intravenous rehydration was provided to 10.8% (34/314) and 10.3% (27/312) of children administered placebo and ondansetron, respectively (OR: 0.946; 95% CI: 0.564, 1.587; P=0.834). A regression model fitted with treatment group and adjusted for antiemetic administration and vomiting frequency in the preceding 24 hours, yielded similar results; OR=0.952; 95% CI: 0.570, 1.589; P=0.850. There was no evidence of interaction between treatment group and age (P=0.974), 3 diarrheal stools in the preceding 24 hours (P=0.983) or 3 vomits in the preceding 24 hours (P=0.554). During the 4-hour study observation period, 24.0% (75/314) and 19.6% (61/312) of children in the placebo and ondansetron groups vomited, respectively; OR: 0.774; 95%CI: 0.528, 1.133; P=0.187. Conclusion: Ondansetron administration did not significantly reduce intravenous rehydration use, suggesting that in children without dehydration, ondansetron administration does not significantly alter the disease course and should not be administered to this group of children.
The triplite LiFeSO4F displays both the highest potential ever reported for an Fe-based compound, as well as a comparable specific energy with that of popular LiFePO4. The synthesis is still a challenge because the present approaches are connected with long time, special equipments or organic reagents, etc. In this work, the triplite LiFeSO4F powder was synthesized through an ambient two-step solid-state route. The reaction process and phase purity were analyzed, coupled with structure refinement and electrochemical test.
Four complete platysiagid fish specimens are described from the Luoping Biota, Anisian (Middle Triassic), Yunnan Province, southwest China. They are small fishes with bones and scales covered with ganoine. All characters observed, such as nasals meeting in the midline, a keystone-like dermosphenotic, absence of post-rostral bone, two infraorbitals between dermosphenotic and jugal, large antorbital, and two postcleithra, suggest that the new materials belong to a single, new Platysiagum species, P. sinensis sp. nov. Three genera are ascribed to Platysiagidae: Platysiagum, Helmolepis and Caelatichthys. However, most specimens of the first two genera are imprints or fragmentary. The new, well-preserved specimens from the Luoping Biota provide more detailed anatomical information than before, and thus help amend the concept of the Platysiagidae. The Family Platysiagidae was previously classed in the Perleidiformes. Phylogenetic analysis indicates that the Platysiagidae is a member of basal Neopterygii, and its origin seems to predate that of Perleidiformes. Moreover, platysiagid fishes are known from the Middle Triassic of the western Tethys region. The newly found specimens of platysiagids from Luoping provide additional evidence that both eastern and western sides of the Tethys Ocean were biogeographically more connected than previously thought.
The study of the mechanical properties of polycrystalline alloy materials under dynamic impact, namely, the prediction of mechanical behavior after yield stress and the establishment of a constitutive model, has attracted much attention in the field of engineering. The stress-strain curves of 5083 aluminum alloy were obtained under strain rates varying from 0.0002 s-1 to 7130 s-1 through uniaxial compression experiments. The equipment used included a CRIMS RPL100 tester, Instron tester, and split Hopkinson test system. In addition, based on dislocation dynamics and the strengthening mechanism of metals, the plastic flow of the 5083 aluminum alloy was systematically analyzed under a wide range of strain rates. It was found that the abnormal yield behavior of the 5083 aluminum alloy under a wide range of strain rates increased, and the experimental phenomenon of hardening rate decreased with an increase in strain rate. This study also revealed that the abnormal yield behavior is caused by the different dislocation mechanisms of two-phase alloy elements under different strain rates. Based on the thermal activation theory and the experimental data, a constitutive model was developed. A comparison showed good agreement between the experimental and model curves. This indicates that this model has good plastic flow stress prediction ability for such types of materials.
Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006–2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36–27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21–36·68%) in urban area to −1·90% (95 eCI −25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1–4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4–31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.
Global, first-principles study of the kinetic ballooning mode (KBM) is crucial to understand tokamak edge physics in high-confinement mode (H-mode). In contrast to the ion temperature gradient mode and trapped electron mode, the KBM is found to be very sensitive to the equilibrium implementations in gyrokinetic codes. In this paper, we show that a second-order difference in Shafranov shift or geometric coordinates, or a difference between local and global profile implementations can bring a factor of two or more discrepancy in real frequency and growth rate. This suggests that an accurate global equilibrium is required for validation of gyrokinetic KBM simulations.