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Vast improvements have been made to the capabilities of advanced manufacturing (AM), yet there are still limitations on which materials can effectively be used in the technology. To this end, parts created using AM would benefit from the ability to be developed from feedstock materials incorporating additional functionality. A common three-dimensional (3D) printing polymer, acrylonitrile butadiene styrene, was combined with bismuth and polyvinylidene fluoride via a solvent treatment to fabricate multifunctional composite materials for AM. Composites of varying weight percent loadings were extruded into filaments, which were subsequently 3D printed into blocks via fused filament fabrication. Investigating the material properties demonstrated that in addition to the printed blocks successfully performing as radiation shields, the chemical, thermal, and mechanical properties are suitable for AM. Thus, this work demonstrates that it is possible to enhance AM components with augmented capabilities while not significantly altering the material properties which make AM possible.
Asenapine is indicated in adults for acute treatment of schizophrenia and bipolar I disorder. We describe the efficacy and tolerability of adjunctive asenapine in bipolar patients showing incomplete response to lithium or valproate monotherapy.
In a 12-week core study, patients were randomized to flexible-dose asenapine (5 or 10 mg BID) or placebo as an adjunct to continued mood stabilizer therapy. Patients completing the core study without protocol violations could enter a 40-week extension. Changes from core study baseline on the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores were assessed at week 3 of the core study and at week 52 in the extension. Efficacy in the core study was assessed using ANCOVA with LOCF to impute missing data. The extension was not powered for statistical comparisons; descriptive statistics were employed.
The intent-to-treat population comprised 318 patients (asenapine, 155; placebo, 163) in the core study and 71 (38; 33) in the extension. Mean±SD changes at week 3 with asenapine and placebo, respectively, were -9.7±10.1 versus -7.7±9.6 (P=0.0257) on YMRS and -2.8±7.2 versus -2.2±6.8 (P=0.3684) on MADRS. Mean±SD changes at week 52 with asenapine and placebo were -17.2±13.7 versus -19.7±11.8 on YMRS and -3.3±9.8 versus -3.9±7.7 on MADRS. The incidence of treatment-emergent AEs with asenapine and placebo was 73% and 69% in the core study, 78% and 69% in the extension.
Asenapine was effective as an adjunct to mood stabilizer in bipolar I disorder and was well tolerated.
To compare efficacy and medical costs of typital and atypical antipsychotics in treating schizophrenic patients.
250 in patients in general hospital and psychiatric hospital were randomly allocated to one of the two groups, one treated with typital antipsychotics as chlorpromazine, haloperidol and so on with a mean daily dose of 500∼800 mg in chlorpromazine equivalents, and the other with atypical agents in cluding clozapine (mean daily dose of 400∼800mg ), risperidone of 6 mg, or olanzapine of 20 mg.
The total costs of the treatment were (3157±253) Yuan RMB for patients treated with typical agents in general hospital, and (3673±294) Yuan RMB for patients treated with typical agents in psychiatric hospital respectively. the costs for medicine were (774±903) Yuan RMB, (1061±903) Yuan RMB respectively. the costs in atypical group were(1120±390) Yuan RMB and (1637±325) Yuan RMB, and (108±157) Yuan RMB and (240±317) Yuan RMB respectively. the duration of patients treated with typical agents in hospital is longer than that with atypical agents.
It indicates that atypical antipsychotics have similar efficacy to typical agents in treating schizophrenic patients with less costs.
Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.
To assess the incidence of suicidal ideation, violent behaviour, and deliberate self-harm in patients with schizophrenia 12-months after initiating treatment with risperidone long-acting injection (RLAI) who are enrolled in the electronic-Schizophrenia Treatment Adherence Registry (e-STAR) in the Netherlands.
e-STAR is an international, prospective, observational study of patients with schizophrenia who have been initiated with RLAI. Data are collected retrospectively (1 year) and prospectively (2 years). The incidence of suicidal ideation, violent behaviour, and self-injury was evaluated by the treating physician based on the presence or absence of these events at baseline and prospectively every 3 months. Patients with at least 12 months of available follow-up data from the Netherlands were included in this analysis.
To date a total of 190 patients have been enrolled in the Netherlands and 118 patients with 12 months of available data were analyzed. The majority were male (62.7%) with a mean age of 37.7±11.5 years and a mean time since schizophrenia diagnosis of 11.1±21.5 years. Compared to baseline, statistically significant decreases were observed in the occurrence of suicidal ideation (15.1% to 4.3%, p=0.006) and violent behaviour (12.9% to 2.2%, p=0.006) at 12 months. The incidence of self-injury also decreased from 4.3% to 3.2%, but the reduction was not statistically significant.
These 12-month interim results showed significant decrease in the incidence of suicidal ideation and violent behaviour was observed in patients with schizophrenia after initiating treatment with risperidone long-acting injection.
To assess changes in illness severity (Clinical Global Impression-Severity scale, CGI-S) and functioning (Global Assessment of Functioning, GAF) in patients initiated on risperidone long-acting injection (RLAI) during routine clinical practice and followed up for at least 12 months in the Netherlands.
e-STAR is an international, prospective, observational study of patients with schizophrenia who have been initiated with RLAI. Data are collected both retrospectively (1 year) and prospectively (2 years). Results presented in this report were based on data from patients with at least 12 months of available data in the Netherlands.
There are 190 patients currently enrolled in the Netherlands and 118 patients have at least 12 months of available data. Of the 118 patients, the majority were male (62.7%) with a mean age of 37.7±11.5 years and a mean time since schizophrenia diagnosis of 11.1±21.5 years. The main reasons for switching to RLAI were lack of compliance (42.4%), adverse events (25.4%) and lack of efficacy (24.6%) with previous therapy. At 12 months, 66.9% of patients were still on RLAI treatment. Of the patients who discontinued RLAI, the mean time to discontinuation was 157.8±76.5 days. Mean CGI-S score significantly improved from 4.05±1.14 at baseline to 3.15±1.38 at 12 months (p<0.001). Additionally, the mean GAF score significantly improved from 43.8±12.0 at baseline to 55.2±14.7 at 12 months (p<0.001).
These interim results showed that treatment with RLAI in patients with schizophrenia was associated with significant improvements in disease severity and functioning.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
GABRB2, the gene for β2 subunit of the gamma-aminobutyric acid type A (GABAA) receptor, is known to display two splicing isoforms in the brain, namely β2L containing Exon 10 and β2S devoid of Exon 10. Previously, the expressions of these isoforms were correlated with both schizophrenia and various sequence polymorphisms of the gene. in the present study, a series of deletions made on Intron 9 of a minigene construct affected the expression of Exon 10, and generated additional splicing variations suggesting the existence of additional splicing variants of β2subunit. A search among brain cDNAs uncovered the two novel short forms: β2S1which is devoid of Exons 10 and 11 and bears an extended Exon 9, and β2S2 which is devoid of Exon 10 and bears a shortened Exon 11.Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics, 30 bipolar disorder and 31 controls of US population, showed that the level of β2S2 was significantly decreased in bipolar disorder, and marginally decreased in schizophrenia, while β2S1 was marginally increased in both of these psychotic disorders. Significant genotypic effects of rs1816071, rs1816072 and rs187269 on β2S2 level were observed in male schizophrenic and bipolar patients. These findings pointed to the neighborhood of Exon 10 as an alternate-splicing hot-spot, and underlined the relevance of β2 subunit isoforms to the etiology of psychotic disorders.
Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.
Objectives and aims
The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.
The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.
PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).
PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).
Previous studies have shown that the polymorphisms in COMT gene and environmental factors affect the risk of drug dependence, but there’s no research shown in relapse of heroin dependence, and the mechanism underlying remains uncertain.
Examine the interaction between allelic variants of the catechol-O- methlytransferase (COMT) gene and environmental factors (encountering drug-related environmental situations, social support) in contribution to relapse in heroin dependence.
Construct the gene-environment interaction model in order to understand the mechanism for relapse in heroin dependence.
The 249 heroin dependent subjects who followed up at one year after abstinent by using the natural history interview (NHI), social support rateing Scale (SSRS), and other questionnaires were genotyped for eight tagging single nucleotide polymorphisms (SNP) on the COMT gene. General Multifactor Dimensionality Reduction (GMDR) was used to construct the gene-environment interaction model which impacting relapse in heroin dependence.
The relapse group had higher frequencies of encountering drug-related environment (EDE) and G allele and GG genotype frequencies on COMT gene rs4680 locus and less Social Support Scale scores than that in the abstinence group. Logistic regression analysis showed that encountering more drug-related environment and GG genotype carriers were the risk factors for relapse in heroin dependence. GMDR analysis showed that the COMT gene was interact with the frequency of EDE and social support level to impact the relapse in heroin dependence.
Gene-environment interaction between COMT gene and the frequency of EDE and social support were related to heroin dependence relapse.
Studies have convinced that the rodents' exposure to prenatal stress (PNS) may induce depression and anxiety to their offspring. We focused on the glutamatergic system to explore the mechanisms.
Objectives and aims:
By examining EAAT2,EAAT3 (Excitatory Amino Acid Transporter 2,3), which are the only substances to inactivate glutamate in nervous system, we explored the effect of PNS on glutamatergic system.
Pregnant rats were assigned to Control group (CON), Middle period of PNS group (MPS) and Late period of PNS group (LPS). MPS and LPS rats were exposed to restraint stress on days 7–13, 14–20 of pregnancy three times daily for 45 min. EAAT2 and EAAT3 mRNA expression in the hippocampus, frontal cortex, and striatum of one month rat offspring were checked by RT-PCR.
For the female offspring, EAAT2 mRNA expression of hippocampus in LPS and MPS was significantly lower compared to CON(P = 0.008,p = 0.003); EAAT2 and EAAT3 mRNA expression of frontal cortex in LPS were significantly lower than CON (p = 0.003,p = 0.013). for the male offspring, EAAT2 and EAAT3 mRNA expression of hippocampus in LPS and MPS were significantly lower (p = 0.005, p = 0.05); EAAT2 mRNA expression of frontal cortex was significantly lower in LPS (p = 0.022); EAAT2 mRNA in LPS group and MPS were significantly lower (p = 0.009, p = 0.014), and EAAT3 mRNA expression of striatum in MPS was significantly lower (p = 0.049).
Decreased EAAT2 and EAAT3 of PNS may explain the increase of glutamate in synaptic cleft and its downstream excitotoxicity. (Supported by National Natural Science Foundation of China, No: 30970952)
Epidemiological studies have convinced that prenatal stress (PS) might cause offspring depression.
Objectives and aims:
Our pervious research work certified that PS can increases the glutamate level of hippocampus of rat offspring, which inspired us to explore the pathogenesis of depression by focusing on glutamatergic system.
Pregnant rats were randomly assigned to control group (CON), mid prenatal stress group (MPS) and late prenatal stress group (LPS). The pregnant rats of MPS and LPS were exposed to restraint stress on days 7–13, 14–20 of pregnancy three times for 45 min respectively. Tail suspension test (TST) was performed to examine the depression like behavior and Western-blot were used to test phosphorylated GluR1(pGluR1) of AMPAR expression in the hippocampus, striatum and frontal cortex of one month rat offspring.
For both male and female offspring, the time of immobility of TST in LPS (156±11, 155±12) and MPS (173±15, 155±12) was significantly longer (P< 0.05) than CON(118±8,113±12), the latency in MPS (18±3, 24±3) was significantly shorter (P< 0.05) than CON (30±5, 58±11). The pGluR1 expression in hippocampus and frontal cortex in LPS (1.77±0.45, 1.00±0.09) and MPS (1.65±0.51, 1.05±0.18) were significantly lower (P< 0.05) than CON (3.72±0.86, 2.05±0.34) in male rat offspring.
It is suggested that the PS may induce depression like behavior in rat offspring, and glutamate receptors subunit pGluR1 might be involved in the etiology of depression.
(The research is supported by National Natural Science Foundation of China, No: 30970952, 18110059).
Many MRI studies have cited major depression, with or without anti-depressive treatment, associated with structural plasticity changing in several brain regions. Few of these studies researched the effect of the anti-depressive treatment, electroconvulsive therapy (ECT), on depression.
To assess the influence of ECT on the brain structure change during the treatment process by utilizing the voxel-based morphometry (VBM) analysis.
To determine whether ECT alter brain structure.
We performed HAMD ratings and MRI scans on 12 depressive patients during ECT, analyzing the data by VBM with SPM8 software's family-wise error correction (FWE).
The researchers found volumes changes in white matter in 37 regions between pre-ECT and post-ECT1, but only one region changing between pre-ECT and post-ECT8. Seven regions changing in grey matter between pre-ECT and post-ECT 1⌧but none regions changing between pre-ECT and post-ECT8.
The density changes in several brain regions after a single ECT stimuli, but return to the original level after completing the eighth ECT. Our finding supports that ECT may play a temporary role in treating major depression but do not permanently alter the structures of brain.
Childhoods in urban or rural environments may differentially affect risk for neuropsychiatric disorders. Here, we leveraged on dramatic urbanization and rural-urban migration since the 1980s in China to explore the hypothesis that rural or urban childhoods may differentially influence memory processing and neural responses to neutral and aversive stimuli.
Explore the underlying mechanisms of childhood environment effect on brain function and neuropsychiatric risk.
We examined 420 adult subjects with similar current socioeconomic status and living in Beijing, China, but with differing rural (n = 227) or urban (n = 193) childhoods. In an episodic memory paradigm scanned in a 3 T GE MRI, subjects viewed blocks of neutral or aversive pictures in the encoding and retrieval sessions.
Episodic memory accuracy for neutral stimuli was less than for aversive stimuli (P < 0.001). However, subjects with rural childhoods apparently performed less accurately for memory of aversive but not neutral stimuli (P < 0.01). In subjects with rural childhoods, there was relatively increased engagement of bilateral striatum at encoding, increased engagement of bilateral hippocampus at retrieval of neutral and aversive stimuli, and increased engagement of amygdala at aversive retrieval (P < 0.05 FDR corrected, cluster size > 50).
Rural or urban childhoods appear associated with physiological and behavioural differences, particularly in the neural processing of aversive episodic memory at medial temporal and striatal brain regions. It remains to be explored the extent to which these effects relate to individual risk for neuropsychiatric or stress-related disorders.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Based on the missiles with adjustable thrust, a distributed synergetic guidance law for multiple missiles with angle-of-attack constraint is designed to achieve a cooperative attack by multiple missiles on a moving target. Divide the guidance law into two parts: the line of sight (LOS) direction and the normal direction of LOS. The guidance law is designed in LOS direction based on the multi-agent system cooperative control theory and super-twisting algorithm, which can control missiles’ time-to-go converging in finite time. In the normal direction of LOS, the other guidance law is designed to control missiles hitting the target with impact angle constraint based on zeroing LOS rate thought and finite-time sliding mode control theory. The two non-homogeneous disturbance observers are designed to estimate the target manoeuvring information in the two parts of the guidance law. The simulation results show that the guidance law designed by this paper can complete the cooperative attack task while suppressing the chattering phenomenon effectively.
In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.
Aiming at the issue of missiles attacking on-ground maneuvering targets in three-dimensional space, a three-dimensional finite-time guidance law with impact-angle constraints is proposed. In order to improve convergence speed and restrain chattering phenomenon, the nonsingular fast terminal three-dimensional second-order sliding mode guidance law with coupling terms is designed based on the theory of nonhomogeneous fast terminal sliding surface and second-order sliding mode control. The system model need not be linearized during the design process, and the singular problem is avoided. A nonhomogeneous disturbance observer is designed to estimate and compensate the total disturbance, which is caused by target maneuvering information and coupling terms of line of sight. And the stability and finite-time convergence of the guidance law are proved strictly and mathematically. Finally, simulation results have verified the effectiveness and superiority of the proposed guidance law.
The spatial and temporal structure of the resonant fluid response in a narrow gap (the so-called gap resonance) between two identical fixed boxes is investigated experimentally. Transient wave groups are used to excite the gap resonance from different wave approach directions. This shows a strong beating pattern and a very long duration, reflecting that gap resonance is a multi-mode resonant and weakly damped phenomenon. For head sea excitation the linear transfer function of the
gap mode is as significant as that of the
mode. Gap resonance can be driven through different mechanisms, e.g. linear excitation and a nonlinear frequency-doubling process. Significant wave group structure is shown in the gap, and the group structure is more distinct in the case with frequency doubling, i.e. long wave, excitation. Then it is clearer visually that the groups originate at the end of the gap, propagate along the gap and are then partially reflected from the other end. The groups within the gap are very clear because the group velocity is close to constant for the first few gap resonance modes, and much smaller than that for free waves on the open sea. In contrast, the phase speed of waves in the gap is larger than that for free waves outside. Only in the limit of short waves do the group velocity and phase speed of the gap modes tend to those of deep-water free waves. The group and phase speeds from these experiments match well the theoretical forms given by Molin et al. (Appl. Ocean Res., vol. 24 (5), 2002, pp. 247–260), albeit for a slightly different box cross-sectional shape.