To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Individual with internet gaming disorder (IGD) often experience a high level of loneliness, and neuroimaging studies have demonstrated that amygdala function is associated with both IGD and loneliness. However, the neurobiological basis underlying these relationships remains unclear.
In the current study, Granger causal analysis was performed to investigate amygdalar subdivision-based resting-state effective connectivity differences between 111 IGD subjects and 120 matched participants with recreational game use (RGUs). We further correlated neuroimaging findings with clinical measures. Mediation analysis was conducted to explore whether amygdalar subdivision-based effective connectivity mediated the relationship between IGD severity and loneliness.
Compared with RGUs, IGD subjects showed inhibitory effective connections from the left pregenual anterior cingulate cortex (pACC) to the left laterobasal amygdala (LBA) and from the right medial prefrontal cortex (mPFC) to the left LBA, as well as an excitatory effective connection from the left middle prefrontal gyrus (MFG) to the right superficial amygdala. Further analyses demonstrated that the left pACC-left LBA effective connection was negatively correlated with both Internet Addiction Test and UCLA Loneliness scores, and it mediated the relationship between the two.
IGD subjects and RGUs showed different connectivity patterns involving amygdalar subdivisions. These findings support a neurobiological mechanism for the relationship between IGD and loneliness, and suggest targets for therapeutic approaches that could be used to treat IGD.
The dendrite morphologies of the cast nickel-based superalloy CMSX-4® (CMSX-4® is registered trademarks of the Cannon-Muskegon Corporation) and the austenitic stainless steel HP microalloy have been obtained via an automated serial-sectioning process which allows three-dimensional (3D) microstructural characterization. The dendrite arm spacing, volume fraction of segregation, and fraction of porosity have been determined. This technique not only increases the depth, scope, and level of detailed microstructural characterization but also delivers microstructural data for modeling and simulation.
Combinational creativity can play a significant role in supporting designers to produce creative ideas during the early stages of new product development. This paper explores conceptual distances in combinational creativity from computational perspectives. A study conducted indicates that different computational measurements show different conceptual distance results. However, the study suggests far-related ideas could lead to outcomes that are more creative than closely-related ones. This paper provides useful insights into exploring future computational design support tools.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Ovarian follicle selection is a natural biological process in the pre-ovulatory hierarchy in birds that drives growing follicles to be selected within the ovulatory cycle. Follicle selection in birds is strictly regulated, involving signaling pathways mediated by dietary nutrients, gonadotrophic hormones and paracrine factors. This study aimed to test the hypothesis that dietary Ca may participate in regulating follicle selection in laying ducks through activating the signaling pathway of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/extracellular signal-regulated kinase (ERK), possibly mediated by gonadotrophic hormones. Female ducks at 22 weeks of age were initially fed one of two Ca-deficient diets (containing 1.8% or 0.38% Ca) or a Ca-adequate control diet (containing 3.6% Ca) for 67 days (depletion period), then all birds were fed the Ca-adequate diet for an additional 67 days (repletion period). Compared with the Ca-adequate control, ducks fed 0.38% Ca during the depletion period had significantly decreased (P < 0.05) numbers of hierarchical follicles and total ovarian weight, which were accompanied by reduced egg production. Plasma concentration of FSH was decreased by the diet containing 1.8% Ca but not by that containing 0.38%. The ovarian content of cAMP was increased with the two Ca-deficient diets, and phosphorylation of PKA and ERK1/2 was increased with 0.38% dietary Ca. Transcripts of ovarian estradiol receptor 2 and luteinizing hormone receptor (LHR) were reduced in the ducks fed the two Ca-deficient diets (P < 0.05), while those of the ovarian follicle stimulating hormone receptor (FSHR) were decreased in the ducks fed 0.38% Ca. The transcript abundance of ovary gap junction proteins, A1 and A4, was reduced with the Ca-deficient diets (P < 0.05). The down-regulation of gene expression of gap junction proteins and hormone receptors, the increased cAMP content and the suppressed hierarchical follicle numbers were reversed by repletion of dietary Ca. These results indicate that dietary Ca deficiency negatively affects follicle selection of laying ducks, independent of FSH, but probably by activating cAMP/PKA/ERK1/2 signaling pathway.
Background: Ketorolac has long been used to manage pain in the Emergency Department and has the advantage of being the only parenteral NSAID formulation. Despite multiple studies demonstrating an analgesic ceiling dose of 10mg for intravenous ketorolac, higher doses (30-60mg) are commonly ordered. Use of optimal doses of ketorolac (10mg) has the advantage of lower side effects and cost. Aim Statement: The aim of this project was to increase the usage of the optimal dose parenteral ketorolac (10mg) without increasing the use of additional, concomitant or rescue opioids (balancing measures). Measures & Design: This pre-/post-intervention comparison study (May 1, 2016 to April 30, 2018) included all patients ≥18 years of age that received parenteral ketorolac at one of 4 EDs in the Calgary zone. All data was captured via administrative data records. Stakeholders (ED leadership, analgesia committee, nursing and pharmacy) provided feedback and support for the project. Our multi-modal intervention included modifying all ED computerized order sets such that the default parenteral ketorolac dose was 10mg (post-intervention) from 30mg (pre-intervention), education (dissemination of evidence to support the changes to clinicians) and our pharmacy securing 10mg vials of ketorolac. At their discretion, physicians’ were still able to order other doses of ketorolac. Evaluation/Results: During the 2 year study period, 19290 patient records were identified where parenteral ketorolac was administered during the ED visit. Baseline characteristics were similar between the pre/post periods. Prior to the change in default dosing, 10.5% of orders were for ketorolac 10mg compared to 87% in the post-intervention period (p < 0.000). Statistical process charts support the above results and demonstrate that the changes have been sustained. There were no differences in patients receiving ketorolac as the only analgesic between the pre/post periods (42% vs 42%, p = 0.396), nor where there significant changes in concomitant opioid usage (46% vs 46%, p = 0.817), or rescue analgesia (11% vs 12%, p = 0.097). Discussion/Impact: In this large cohort, our multi-modal intervention, resulted in a significant increase in optimal ketorolac parenteral dosing without a significant change in additional opioid use. The results support the utility of computerized order set changes as the cornerstone of an effective and rapid knowledge translation strategy to align physician practice with best evidence.
An increasing number of studies have described the relationship between celiac disease and schizophrenia. Based on the reported correlations and the overlapping linkage regions on 19p13, the myosin IXB gene (MYO9B) can be considered a highly relevant positional and functional candidate gene for schizophrenia. The present work was undertaken to investigate the association of the MYO9B gene with schizophrenia in a Chinese population.
A total of 329 patients with schizophrenia and 350 healthy control subjects in a Chinese population were recruited. A PCR-based RFLP protocol was applied to genotype 7 single nucleotide polymorphisms (SNPs), including rs7249490, rs7256689, rs2279007, rs8113494, rs2305767, rs1545620 and rs2305764, in the MYO9B gene to investigate their association with schizophrenia.
The X2 goodness-of-fit test showed that the genotypic distributions of all 7 SNPs were in Hardy-Weinberg equilibrium in both the patient group and the control group. Disease association was shown for rs8113494 (X2=12.77, P=0.0003, OR=1.89, 95% CI 1.33-2.68) and rs1545620 (X2=15.44, P=8.379e-5, OR=1.65, 95% CI 1.29-2.12), while rs2279007 was associated with schizophrenia in the female subjects (X2=4.637, P=0.031, OR=0.69, 95% CI 0.49-0.97) but not in the male subjects (X2=1.082, P=0.299, OR=0.85, 95% CI 0.63-1.15).
The present work shows that the polymorphisms of the MYO9B gene are likely to confer susceptibility to schizophrenia. Because the MYO9B gene has been found to be highly expressed in the tight junction gate, it could be considered as a meeting point for the interaction between environmental and genetic factors in the pathogenesis of schizophrenia.
The extra pyramidal effects related to the use of neuroleptics are a limiting factor in schizophrenia treatment.
The aim of this study was to identify the neuroleptics prescribed for schizophrenic patients in a public health service, the extra pyramidal symptoms (EPS) incidence and its treatment.
Our restrospective study included 40 patients with mean age of 39.13 ± 2.19 in a treatment period of of 134.17 ± 16.83 days. The data were randomly collected from medical records of these patients.
The patients under study received typical neuroleptics (31.03%),atypical agents (37.93%) or association of both (31.03%). EPS was observed in 65.52% patients of which, 44.83% even though receiving biperiden 2mg, still have EPS. 20.69% were not receiving anticolinergic drug treatment for EPS, but promethazine or anticonvulsants. From the 34.48% who did not showed EPS, 20.69% had biperiden prescription and 13.79 % had been treated with olanzapine, clozapine or risperidone associated or not to clonazepam 2mg. Weigth gain of 5.20 ± 1.14 kg was observed in our total sample.
We suggest the use of EPS evaluation scale (Sympson - Angus or Barnes). 65.52 % of the patients under study had EPS and 20.69% of them had no prescription of central acting anticholinergic drug. 44.83% even though receiving biperiden 2mg, still have EPS.
An increasing number of studies have described the relationship between velo-cardio-facial syndrome (VCFS) and schizophrenia. in a family-based study, we found that rs10314, a single nucleotide polymorphism (SNP) present in the 3’-flanking region of the CLDN5 gene, was associated with schizophrenia among a Chinese population. High false positive rate is a common problem with the association study of human diseases. It is very important to replicate an initial finding with different samples and experimental designs.
A total of 749 patients with schizophrenia and 383 age and sex matched healthy control subjects in Chinese population were recruited. PCR-based RFLP protocol was applied to genotype rs10314 to see its disease association.
The χ2 goodness-of-fit test showed that the genotypic distributions of rs10314 were in Hardy-Weinberg equilibrium in both the patient group (χ2=1.12, P=0.289) and the control group (χ2=0.22, P=0.639). rs10314 was associated with schizophrenia with an odds ratio (OR) of 1.32 in the male subjects (χ2=5.45, P=0.02, 95% CI 1.05-1.67) but not in the female subjects (χ2=0.64, P=0.425, OR=1.14, 95% CI 0.83-1.57). the χ2 test showed a genotypic association only for combined samples (χ2=7.80, df=2, P=0.02). SNP rs10314 is a G to C base change. Frequency of the genotypes containing the C allele was significantly higher in the patient group than in the control group.
The present work shows that the CLDN5 gene polymorphism is more likely to be involved in schizophrenic men than women, suggesting that this gene may contribute to the gender differences in schizophrenia.
To investigate the relationships between work environmental factors and the risk of major depressive disorder (MDD) over one year and to identify factors associated with the outcomes of individuals with MDD.
We conducted a population-based longitudinal study of employees who were randomly selected in Alberta (n = 4239). MDD was assessed using the World Health Organization's Composite International Diagnostic Interview - Auto 2.1.
The one-year incidence of MDD was 3.6% (95% CI: 2.8%-4.6%) overall. It was 2.9% (95% CI: 1.9% - 4.2%) in men and 4.5% (95% CI: 3.3% - 6.2%) in women. The relationships between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35-40 hours per week; job insecurity and family-work conflict were predictive of MDD. Women who worked 35-40 hours, who reported job insecurity, high effort-reward imbalance and work-family conflict were at higher risk of MDD. Long working hours, negative thinking and having comorbid social phobia were predictive of MDD. Perceived work-family conflict, severity of major depressive episode and symptom of depressed mood were significantly associated with recurrence of MDD.
Job strain, effort-reward imbalance, job insecurity and work-family conflicts are important risk factors for the onset of MDD, and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women. Clinical and psychosocial factors are important in the prognosis of MDD. The factors associated with persistence and recurrence of MDD may be different.
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).
The aim of this study was to compare the effectiveness of attribution retraining group therapy (ARGT) versus selective serotonin reuptake inhibitors (SSRI) in the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD).
109 patients with MDD, GAD and OCD were recruited from the outpatient department of a tertiary referral hospital between 2007 and 2008. Subjects were sequentially recruited and randomized into ARGT group (n=63) and SSRI group (n=66) for an 8-week treatment period. 54 outpatients in ARGT group and 55 outpatients in SSRI group completed the study. All subjects were assessed using Hamilton Depression Scale, Hamilton Anxiety Scale before and after treatment. Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects. Plasma hormone levels of serotonin, norepinephrine, cortisol, adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) were measured at baseline and at 8 weeks.
Symptom scores were reduced significantly in both ARGT and SSRI treatment groups (p< 0.001) at the end of the treatment course. However the patients in the ARGT group had significantly lower plasma cortisol concentrations compared to baseline (p< 0.05). on the other hand, patients receiving the SSRIs showed significantly increased plasma levels of serotonin (p< 0.05) and BDNF (p< 0.01).
Our findings suggest that ARGT may modulate plasma cortisol levels and take effect to the HPA axis as opposed to SSRIs which may up-regulate plasma serotonin and BDNF levels via a different pathway to produce an overall improvement in the clinical condition of patients.
More than 80 % of patients experiencing their first depressive episode will have at least one new episode. Effective interventions to reduce the risk of relapse and recurrence are needed. Psychoeducation is a form of interactive education enhancing knowledge about patients’ illness, including its course, symptoms and treatment. Psychoeducational methods can also act as family intervention – already an evidence-based practice in schizophrenia and bipolar disorder. Only few studies have focused on the effect of psychoeducation, including family psychoeducation, in the prevention of new depressive episodes.
Purpose is to evaluate whether an intervention of psychoeducation for family members, compared to a control intervention, is effective in reducing the risk of new depressive episodes among patients that have achieved remission or partial remission of depressive symptoms after the acute phase of antidepressive treatment.
The project is based on a double-centre, randomized controlled trial where investigator and raters conducting psychometric assessments, will be blinded to treatment allocation. A total of 130 patients with unipolar depression in remission or partial remission will be included together with their closest relative. After baseline assessments, relatives will be randomized to either 4 sessions of a family psychoeducation program or 4 sessions in a social support group without any psychoeducational intervention. Patients will not participate in group sessions and they will continue their outpatient-treatment as usual.
Primary outcome is evaluated after 9 months and include rates of relapse as measured by HAM-D17 and rates of recurrence according to DMS-VI-R and HAM-D17.
Increasing evidence indicates that major depressive disorder (MDD) is associated with cognitive as well as mood disturbances.
To evaluate cognitive function and white matter structure, resting-state brain function in first-episode, treatmentnaive patients with MDD.
To explore brain structure and function mechanisms of cognitive impairment in MDD.
46 Han Chinese MDD patients aged 18–45 year and 46 controls were assessed by a series of validated test procedures.Then, 30 patients and 30 controls were obtained by MRI scan.White matter abnormalities evaluated using diffusion tensor imaging (DTI) were analyzed using tract based spatial statistics (TBSS) and resting-state brain function was evaluated using regional homogeneity (ReHo) analysis.
Cognitive impairment in patients with MDD was demonstrated by reduced accuracy in the Wisconsin Card Sorting test (WSCT) and to a lesser extent the Continuous Performance test (CPT) and Trail Making tests (TMT). White matter abnormalities found in the left cerebellum, and resting-state abnormalities present in the left inferior parietal gyrus, left anterior cingulate nucleus and left hippocampal gyrus were associated with impaired performance in the WSCT and CPT tests. We also showed that poor WSCT performance was associated with increased interconnectivity between the left ventral anterior cingulate nucleus and the medial frontal lobe areas.
The present study indicates cognitive disturbances in patients with MDD are associated with white matter and resting-state changes and altered interconnections in specific brain areas.
To develop and validate a prognostic model for predicting recurrence of major depression using data from a population-based, nationally representative cohort.
Wave 1 and wave 2 longitudinal data from the US National Epidemiological Survey on Alcohol and Related Condition. Participants with a major depressive disorder at baseline and who had visited health professionals for depression were included in this analysis. Mental disorders were assessed based on the DSM-IV criteria. For this study, we included the wave 1 (baseline) participants who reported current or lifetime major depressive episode. We included eligible participants from South and West region in the training data (n = 1,518). Eligible participants from Northeast and Mid-West region were kept in validation data (n = 1,195).
With the training data, a prediction model with 19 unique factors had a C statistics of 0.7504 and excellent calibration. The model had a C statistics of 0.7195 in external validation data (n = 1195) and 0.7365 in combined data. The algorithm calibrated very well in validation data. In the combined data, the 3-year observed and predicted risk of recurrence was 25.40% and 25.34%, respectively.
The developed prediction model for recurrence of major depression has acceptable discrimination and excellent calibration and is feasible to be used by physicians. The prognostic model may assist physicians and patients in quantifying the probability of recurrence so that physicians can develop specific treatment plans for those who are at high risk of recurrence, leading to personalized treatment and better use of resources.
Ketamine exerts fast acting, robust, and lasting antidepressant effects in a sub-anesthetic dose, however, the underlying mechanisms are still not fully elucidated. Recent studies have suggested that ketamine's antidepressant effects are probably attributed to the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The present study aimed to observe the effects of AMPA receptor modulators on mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF) expression during the procedure of ketamine exerting antidepressant effects. Therefore, we pretreated rats with NBQX, an AMPA receptor antagonist, or CX546, an AMPA receptor agonist, and subsequently observed the immobility time during the forced swimming test (FST) and the hippocampal and prefrontal cortical levels of mTOR and BDNF. The results showed ketamine decreased the immobility time of rats during the FST and increased the hippocampal and prefrontal cortical mTOR and BDNF. NBQX pretreatment significantly increased the immobility time and decreased the levels of mTOR and BDNF when compared with vehicle 1 (DMSO) pretreatment. CX546 pretreatment significantly decreased the immobility time and increased the levels of mTOR and BDNF when compared with vehicle 2 (DMSO + ethanol) pretreatment. Our results suggest ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex.
Emerging research evidence suggested that attributional style is one of the main predictors of schizophrenia symptoms.
This study aimed to develop and validate Attribution Questionnaire on Symptom for Schizophrenia (AQSS) in response to the deficiencies in current scales.
The AQSS was developed based on subscales relating to several psychopathological domains included in diagnostic categories in the Diagnostic and Statistical Manual of Mental Disorders IV version. The test items were checked by experienced clinicians for face validity and were tested through a pilot study. The final questionnaire included nine events reflecting four dimensions in each: controllability, internality, stability and globality. Attributional Style Questionnaire (ASQ) was used to assess the concurrent validity of the AQSS.
A four factor structure was extracted from the data using exploratory factor analysis: controllability, internality, stability and globality. Internal consistency of Cronbach’s alphas ranges from 0.84, 0.89, 0.90 and 0.91 respectively, with a total Cronbach’s alpha level is 0.92. The test-retest reliability ranged from 0.72 to 0.82. Three dimensions of AQSS (i.e.internality, stability and globality) significantly correlated with the same dimensions of the Attributation Style Questionnaire, with correlation coefficients of 0.33, 0.65 amd 0.61 for internality, stability and globality respectively. Confirmatory factor analysis confirmed the excellent level of model fit in the four factor structure.
The AQSS has high level of reliability and validity. It is a satisfactory instrument to assess attributional style in patients with schizophrenia.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.