We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save 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 saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Methods
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
Results
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Conclusions
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
The physical picture of interacting magnetic islands provides a useful paradigm for certain plasma dynamics in a variety of physical environments, such as the solar corona, the heliosheath and the Earth's magnetosphere. In this work, we derive an island kinetic equation to describe the evolution of the island distribution function (in area and in flux of islands) subject to a collisional integral designed to account for the role of magnetic reconnection during island mergers. This equation is used to study the inverse transfer of magnetic energy through the coalescence of magnetic islands in two dimensions. We solve our island kinetic equation numerically for three different types of initial distribution: Dirac delta, Gaussian and power-law distributions. The time evolution of several key quantities is found to agree well with our analytical predictions: magnetic energy decays as $\tilde {t}^{-1}$, the number of islands decreases as $\tilde {t}^{-1}$ and the averaged area of islands grows as $\tilde {t}$, where $\tilde {t}$ is the time normalised to the characteristic reconnection time scale of islands. General properties of the distribution function and the magnetic energy spectrum are also studied. Finally, we discuss the underlying connection of our island-merger models to the (self-similar) decay of magnetohydrodynamic turbulence.
Background: Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods: Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results: At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions: Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding: Sanofi Genzyme
To reduce fan noise and weight, according to the structural characteristics of a turbofan engine, a fan rotor with an ultra-low rotating speed is designed in this study by using a new concept of diffusion blade profiles in which the rotating speed of an ultra-highly loaded rotor is only 0.58 times that of a normally loaded rotor. To further examine the applicability of this rotor, its matching stator is also designed. The flow fields in the ultra-highly and normally loaded fan stages are simulated using the same numerical method to conduct an aerodynamic characteristic comparison. Compared with the normally loaded rotor, the sizes of the boundary layers on the blade surfaces, the wakes behind the blades and the flow losses of the ultra-highly loaded rotor are smaller. At the design point, the efficiency of the ultra-highly loaded fan stages is higher than that of the normally loaded stage; moreover, the surge margin of the former is evidently larger than that of the latter. The ultra-highly loaded fan could be a good candidate for use in Ultra-High Bypass Ratio Geared Turbofan (UHBRGT) technology.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
Methods
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
Results
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Conclusions
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
This paper mainly focuses on the cooperative control of formation configuration for multiple flight vehicles in the three-dimensional space. Considering the external disturbance of the system, the adaptive non-singular terminal sliding mode control law (NTSMC) is designed based on the virtual leader-follower method, which aims to ensure that each flight vehicle reaches the expected terminal position in a limited time and meet the configuration constraints. Further considering the first-order dynamic characteristic of the autopilot, a novel second-order sliding mode control (SOSMC) law is deduced with using the estimated information of sliding mode disturbance observer. The proposed control method ensures that all flight vehicles form the required space formation configuration simultaneously at a pre-designed time, and the chattering phenomenon of the sliding mode surface and acceleration response that nears the equilibrium point is effectively weaken. The stability of the proposed control law is verified by theoretical analysis and lots of mathematical simulations. The results show that the control algorithm in this paper can be used to guidance the formation controller design of multiple flight vehicles in the mid-guidance phase to some extent, and thus the cooperative flight stability of the system can be effectively improved.
Modern electron microscopy permits scientists to study the fine detail of cells and tissues, using both two-dimensional and three-dimensional imaging modalities. However, achieving optimal preservation of ultrastructure for a variety of biological samples remains a challenge. Here, we describe practical methods to preserve the fine structure of mouse skeletal muscle and sciatic nerve and to obtain high-resolution images of mitochondria in cultured cells, flow-sorted T-cells, and mouse urothelium. We also propose an effective and economical workflow for three-dimensional electron microscopy in the context of a microscopy core facility.
The current study investigated associations between variation in the bovine perilipin-2 gene (PLIN2) and milk traits (milk fat content, milk protein content, milk yield and milk fatty acid (FA) component levels) in 409 New Zealand pasture-grazed Holstein-Friesian × Jersey-cross (HF × J-cross or Kiwicross™) cows. Five nucleotide sequence variants were found in three regions of the gene, including c.17C>T in exon 2, c.53A>G in exon 3, c.595+23G>A and c.595+104_595+108del in intron 5, and c.*302T>C in the 3′-untranslated region. The c.*302T>C substitution produces two nucleotide sequence variants (A5 and B5), and this variation was associated with variation in milk protein content and milkfat composition for C10:0, C11:0, C12:0, C13:0 and C16:0 FA and medium-chain fatty acid (MCFA) and long-chain fatty acid (LCFA) groups. After correcting for the effect of variation in the diacylglycerol acyl-CoA acyltransferase 1 gene (DGAT1) that results in the amino acid substitution p.K232A, variation in the FA binding protein 4 gene (FABP4) and variation in the stearoyl-CoA desaturase (Δ-9-desaturase) gene (SCD) that results in the amino acids substitution p.A293V, significant differences between A5A5 and B5B5 cows were found for C10:0, C11:0, C12:0, C13:0, C16:0, and the MCFA, LCFA, total saturated FA and C10:1 index groups. This suggests that nucleotide sequence variation in PLIN2 may be affecting milk FA component levels.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Considering the decision-making requirements of airport, airlines and passengers, a bilevel programming model which contains two parts was proposed in this paper. One part is to improve the utilization of gates of the airport (upper level), so the objective function of the upper level to the minimum overall variance of slack time between two consecutive air crafts at the same gate. The other part looks at maximize the airline revenue and passengers more conveniently and comfortably (lower level). The lower level has two objective functions — the minimum passenger transfer failure and the minimum passenger average transfer time, respectively. According to the latest data of an airport in Eastern China, the adaptive genetic algorithm is used to solve the above-mentioned bilevel optimisation problems. The numerical experiment shows that the model not only reduces the variance of the relaxation time, but also optimises the flight gate allocation and achieves the initial goal.
Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Methods.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Results.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
Conclusion.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
Most previous researches indicated that impaired inhibition to emotional stimuli could be one of the important cognitive characteristics of depression individuals. The antisaccade tasks which composed of prosaccade task (PS) and antisaccade task (AS) were often used to investigate response inhibition.
Aims
This study aimed to investigate the volition inhibition toward emotional stimuli in depressed mood undergraduates (DM).
Methods
Subjects were grouped as 21 DM and 25 non-depressed undergraduates (ND) on the Beck Depression Inventory and Self-rating Depression Scale. The antisaccade tasks were conducted to examine the inhibition abilities by varying the arousal level of volition (low and high) of the tasks, with happy, neutral and sad facial expressions as stimuli.
Results
The results showed that at the low volition level in the AS condition, the correct saccade latency in the DM were significant slower than the ND; The DM had reliable higher direction error rates in response to emotional facial expressions, especially for sad expressions. However, all of the differences disappeared in the high volition level antisaccade tasks. The amplitude errors data were not influenced by emotional facial expressions, and there were no group differences across tasks.
Conclusions
These results indicated the DM showed slower speed of cognitive processing and impaired inhibition abilities toward emotional faces than the ND, particularly for sad faces, but these abilities will be repaired in the high arousal level of volition, which enlighten us that training the DM's volition level of inhibition could prove to be an effective strategy to alleviate depression.
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.
Methods:
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.
Results:
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.
Conclusions:
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.
To explore the feature of functional connectivity of default mode network (DMN), central-executive network(CEN), and salience network (SN) in patients with schizophrenia during a resting state by functional magnetic resonance imaging (fMRI).
Methods
The SPM8, DPARSFA, conn, REST softwares combined with data-driven region of interest analysis were used to compare the functional connectivity (FC) of the DMN, CEN, and SN in 74 patients with schizophrenia(SZ) and 79 age- and gender-matched normal controls(NC). Medial prefrontal cortex(MPFC)was selected as seed region for identifying DMN and CEN; right anterior insula(rAI) for SN.
Results
Compared with NC, SZ showed increased FC with bilateral dorsolateral prefrontal cortex(DLPFC) and bilateral putamen of the MPFC, and increased FC with left middle frontal cortex and precuneus/ posterior cingulate cortex(Pcu/PCC) of the rAI. SZ also showed enhanced interconnectivity strengths of CEN-DMN, CEN-SN, and DMN-SN(p>0.05). Correlation analyses showed that the increased FC between MPFC and left DLPFC significantly negatively correlated with PANSS-negative symptoms(r=-0.224,p=0.030) and increased FC between rAI and Pcu/PCC significantly correlated with PANSS-positve symptoms (r=0.243,p=0.020).
Conclusion
This study provides evidence for resting state functional abnormalities of DMN, CEN, and SN in schizophrenia patients. These aberrant functional connectivities in some key brain regions of the three network could be responsible for the schizophrenic symptoms.
Planning ability as a critical component of executive function has been used to investigate prefrontal cortex (PFC) function in Schizophrenia patients by several neuroimaging studies. However, the changes of PFC activation after effective antipsychotic treatment are still unclear.
Objective:
The aim of this study is to explore whether there is any variation in the prefrontal hemodynamic response during Tower of London test after 6 weeks’ antipsychotic treatment in schizophrenia patients, and the relationship between the changes in PFC activation and some demographic factors as well as the severity of the patients’ psychiatric symptoms.
Method:
40 patients with first-episode schizophrenia were recruited for the present study. 28-channel NIRS (near infrared spectroscopy) was used to measure changes in hemoglobin concentration in the prefrontal cortical surface area during Tower of London (TOL) test—a classic neuropsychological test for planning abilities. The patients were examined before treatment and after six weeks’ treatment with second-generation antipsychotic medicines.
Results:
After the short-term treatment, the patients’ TOL test performance and the activations in PFC during the task period did not differ from baseline (P>0.05), although the psychiatric symptoms of the patients were improved significantly(positive subscale score 18.25±2.86 & 12.75±2.60; general psychopathology 33.67±3.65 & 27.00±3.67; PANSS total score 72.25±7.07 & 55.42±7.53; P<0.001).
Conclusion:
It suggests that the impairment of cognitive function and the function of the PFC of schizophrenia patients would not be improved with the improvement of psychiatric symptoms, as further support the hypothesis that PFC damage is a durable impairment for schizophrenia.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
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.
Compared to healthy controls, adults with major depressive disorder (MDD) showed stronger activation in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in resolving emotional conflict. Whether subthreshold depression (StD) at an advanced age is also accompanied by similar changes in brain activation in coping with emotional conflict remained unknown.
Objectives
By using face-word Stroop task, the current study explored the neural correlates of emotional interference processing in old adults with StD.
Methods
Participants were 19 community-dwelling older adults with StD assessed by the Center for Epidemiologic Studies Depression scale (CES-D) scores. We collected magnetic resonance images of their brain compared to images of 18 healthy aged-matched adults. We used SPM to analyze differences in brain activations in emotional interference processing between the two groups.
Results
Results showed that elderly individuals with StD have stronger activation in DLPFC, ACC, default mode network (DMN) and visual extrastriate cortex compared to healthy controls. Furthermore, the brain activations of the DLPFC, DMN and visual extrastriate cortex were significantly associated with participants’ behavioral interference effect in StD.
Conclusions
Stronger brain activation in DLPFC, ACC, DMN and extrastriate cortex in old adults with StD suggests that the working efficiency of their brain is quite low and their cognitive control is impaired to some extent.
Disclosure of interest
The authors have not supplied their declaration of competing interest.