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The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED).
Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses of dasotraline (4 and 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating (BE) days per week at week 12. Secondary efficacy endpoints included week 12 change on the BE CGI-Severity Scale (BE-CGI-S) and the Yale-Brown Obsessive–Compulsive Scale Modified for BE (YBOCS-BE).
At week 12, treatment with dasotraline was associated with significant improvement in number of BE days per week on the dose of 6 mg/d (N = 162) vs placebo (N = 162; −3.47 vs −2.92; P = .0045), but not 4 mg/d (N = 161; −3.21). Improvement vs placebo was observed for dasotraline 6 and 4 mg/d, respectively, on the BE-CGI-S (effect size [ES]: 0.37 and 0.27) and on the YBOCS-BE total score (ES: 0.43 and 0.29). The most common adverse events on dasotraline were insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in blood pressure and pulse were minimal.
Treatment with dasotraline 6 mg/d (but not 4 mg/d) was associated with significantly greater reduction in BE days per week. Both doses of dasotraline were generally safe and well-tolerated and resulted in global improvement on the BE-CGI-S, as well as improvement in BE related obsessional thoughts and compulsive behaviors on the YBOCS-BE. These results confirm the findings of a previous flexible dose study.
White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) diseases from diffusion tensor imaging (DTI) studies respectively, while the empirical evidences about the diagnostic specificity of white matter abnormalities in these disorders are still limited.
25 patients with paranoid schizophrenia and 18 patients with bipolar mania were recruited from the in-patient unit of the Mental Health Centre, West China Hospital, China.
Patients were diagnosed according to the criteria of Diagnostic and Statistical Manual of Mental Disorders-Version IV (DSM- IV). 30 healthy controls were recruited from the community by means of leaflets distributed throughout Chengdu city.
This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania.
Diffusion tensor imaging (DTI) was used to assess white matter integrity in patients with paranoid schizophrenia and bipolar mania, as well as in normal controls. The differences in FA were measured by use of voxel-based analysis.
Reduced FA was found in the left posterior corona radiate (PCR) in patients with bipolar mania and paranoid schizophrenia compared to the controls. Patients with bipolar mania also showed a significant reduction in FA in right posterior corona radiate and in right anterior thalamic radiation (ATR).
Common abnormalities in the left PCR might imply an overlap in white matter pathology of both diseases and might be related to the shared risk factors for both disorders.
Although the deviations of brain volume deficits in sporadic and familial first-episode schizophrenia patients (FEP) had been presented, the difference of brain asymmetries remained unidentified.
To assess the potential differences of volumetric asymmetries of gray matter (GM) and white matter (WM) between groups.
To find out the different injury alteration of sporadic FEP and familial FEP.
42 sporadic and 30 familiar drug-naïve FEP with and 72 matched normal controls (NC) were recruited. Participants were assessed with neuropsychological tests and scanned by a 3.0T MRI to obtain T1-weighted and DTI images. Lateralization distribution maps of GM and WM volume were generated by employing optimized voxel-based morphometry. The asymmetries were analyzed by comparing calculating Laterality Index (LI) voxel by voxel.
All three groups showed similar overall brain torque. Familiar FEP have more regional extensive GM asymmetry brain lesions compared to sporadic FEP. There was no shared regional lesion between two groups. LIGM and LIWM in right superior temporal were negatively correlated. Significant negative correlations were also found between LIGM of left superior parietal lobule and LIWM of right superior parietal lobule, and between LIGM of right inferior parietal lobule and LIWM of left inferior parietal lobule. The asymmetry in distinct brain regions were related to cognitive deficits especially in the domains of language and memory.
The two patient groups had different alteration in injuries of brain asymmetry. Familiar FEP has more GM extensive asymmetry brain region, which may correlate with their high genetic burdens.
To investigate the difference of visual pattern memory among first-episode treatment-naive patients with deficit and nondeficit schizophrenia.
199 first-episode treatment-naive patients with schizophrenia, and 148 controls were recruited. Schedule for the Deficit Syndrome (SDS) was used to categorize the patients into deficit or nondeficit subtype. Pattern Recognition Memory (PRM) was used to test the immediate and delayed mode of visual pattern memory. Positive and Negative Symptom Scale PANSS was used to assess the degree of patients symptoms.
The PRM immediate mode and delayed mode percent correct was significant lower and time latency was significant longer in two subtypes of patients. There were no significant difference in the performance of immediate mode of PRM between deficit and nondeficit patients[(86.49 ± 15.34) vs. (87.28 ± 16.00), P=0.960]. But the impairment was more severe in patients with deficit schizophrenia [percent correct (63.10 ± 19.17) vs. (70.69 ± 15.34), P< 0.001 time latency 5086.80 ± 7528.54 vs. 3527.40 ± 3649.08 P=0.024] in the delayed mode. and PRM has no significant correlation with the negative symptoms of deficit schizophrenia.
There were significant difference in the performance of immediate and delayed mode of PRM between patients and controls. The difference between first-episode treatment-naïve deficit schizophrenia and nondeficit schizophrenia was only in delayed mode of PRM, and has no correlation with the primary negative symptoms. The deficit schizophrenia is a subtype of schizophrenia with unique impairment of cognitive functions.
Dasotraline is a long-acting dopamine/norepinephrine reuptake inhibitor with a PK profile characterized by slow absorption and a t½ of 47-77 hours, permitting once-daily dosing. In a previous flexible dose study, dasotraline demonstrated significant efficacy in the treatment of binge-eating disorder (BED). The aim of this confirmatory fixed-dose study was to evaluate efficacy and safety of dasotraline in the treatment of patients with BED.
Patients meeting DSM-5 criteria for BED were randomized to 12 weeks of double-blind treatment with dasotraline (4 mg/d or 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating days per week at week 12. Secondary efficacy endpoints included changes at Week 12 on the Binge Eating Clinical Global Impression of Severity Scale (BE-CGI-S), the Yale-Brown Obsessive-Compulsive Scale Modified for Binge Eating (Y-BOCS-BE), and the proportion of patients with 100% cessation of binge-eating episodes during the final 4 weeks of treatment. Efficacy was assessed using an MMRM analysis (and a logistic regression model for cessation) with a pre-specified sequential testing procedure used to control overall type I error rate.
A total of 486 were in the ITT population (dasotraline 6 mg/d (N=162), 4 mg/d (N=161), or placebo (N=163). At week 12, treatment with dasotraline was associated with significant reduction in number of binge-eating days per week in the 6 mg/d group vs. placebo (-3.5 vs. -2.9; P=0.0045), but non-significant improvement in the 4 mg/d group vs. placebo (-3.2; P=0.12). Greater improvement was observed vs. placebo for dasotraline 6 mg/d and 4 mg/d, respectively, on the BE-CGI-S (P<0.01 and P<0.03) and the Y-BOC-BE (P<0.001 and P<0.02; all P-values were nominal, not adjusted for multiplicity). The proportion of patients who achieved 4-week cessation of binge-eating episodes was only significant for the dasotraline 6 mg in the completer population (P<0.05; post-hoc analysis) but was not significant for either dose of dasotraline vs. placebo when drop-outs were included in the analysis. The most common adverse events on dasotraline 6 mg/d and 4 mg/d were combined insomnia (early, middle, late), dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in systolic and diastolic blood pressure were minimal. Mean baseline to endpoint changes in supine pulse rate on dasotraline 6 mg/d and 4 mg/d vs. placebo was +6.2 bpm and +4.8 vs. +0.2 bpm.
In this 12-week, placebo-controlled, fixed-dose study, treatment with dasotraline 6 mg/d was associated with a significant reduction in frequency of binge-eating days per week; efficacy was not demonstrated for the 4 mg dose. Treatment with both doses of dasotraline resulted in improvement in the Y-BOCS-BE and the BE-CGI-S. Dasotraline was safe and generally well-tolerated at both doses; most common adverse events were insomnia, dry mouth and headache.
Supported by funding from Sunovion Pharmaceuticals Inc.
The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.
Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.
Adults with congenital heart disease face psychological challenges although an understanding of depression vs. anxiety symptoms is unclear. We analyzed the prevalence of elevated symptoms of anxiety and depression and explored associations with demographic and medical factors as well as quality of life.
Adults with congenital heart disease enrolled from an outpatient clinic completed the Hospital Anxiety and Depression Scale and two measures of quality of life: the Linear Analogue Scale and the Satisfaction with Life Scale. Medical data were obtained by chart review.
Of 130 patients (median age = 32 years; 55% female), 55 (42%) had elevated anxiety symptoms and 16 (12%) had elevated depression symptoms on subscales of the Hospital Anxiety and Depression Scale. Most patients with elevated depression symptoms also had elevated anxiety symptoms (15/16; 94%). Of 56 patients with at least one elevated subscale, 37 (66%) were not receiving mental health treatment. Compared to patients with 0 or 1 elevated subscales, patients with elevations in both (n=15) were less likely to be studying or working (47% vs. 81%; p=0.016) and reported lower scores on the Linear Analogue Scale (60 vs. 81, p<0.001) and the Satisfaction with Life Scale (14 vs. 28, p<0.001).
Among adults with congenital heart disease, elevated anxiety symptoms are common and typically accompany elevated depressive symptoms. The combination is associated with unemployment and lower quality of life. Improved strategies to provide psychosocial care and support appropriate engagement in employment are required.
Muons produced by the Bethe–Heitler process from laser wakefield accelerated electrons interacting with high
materials have velocities close to the laser wakefield. It is possible to accelerate those muons with laser wakefield directly. Therefore for the first time we propose an all-optical ‘Generator and Booster’ scheme to accelerate the produced muons by another laser wakefield to supply a prompt, compact, low cost and controllable muon source in laser laboratories. The trapping and acceleration of muons are analyzed by one-dimensional analytic model and verified by two-dimensional particle-in-cell (PIC) simulation. It is shown that muons can be trapped in a broad energy range and accelerated to higher energy than that of electrons for longer dephasing length. We further extrapolate the dependence of the maximum acceleration energy of muons with the laser wakefield relativistic factor
and the relevant initial energy
. It is shown that a maximum energy up to 15.2 GeV is promising with
on the existing short pulse laser facilities.
We present first results from pilot observations using a phased array feed (PAF) mounted on the Parkes 64-m radio telescope. The observations presented here cover a frequency range from 1 150 to 1 480 MHz and are used to show the ability of PAFs to suppress standing wave problems by a factor of ~10, which afflict normal feeds. We also compare our results with previous HIPASS observations and with previous H i images of the Large Magellanic Cloud. Drift scan observations of the GAMA G23 field resulted in direct H i detections at z = 0.0043 and z = 0.0055 of HIPASS galaxies J2242-30 and J2309-30. Our new measurements generally agree with archival data in spectral shape and flux density, with small differences being due to differing beam patterns. We also detect signal in the stacked H i data of 1 094 individually undetected galaxies in the GAMA G23 field in the redshift range 0.05 ⩽ z ⩽ 0.075. Finally, we use the low standing wave ripple and wide bandwidth of the PAF to set a 3σ upper limit to any positronium recombination line emission from the Galactic Centre of <0.09 K, corresponding to a recombination rate of <3.0 × 1045 s−1.
During 2016 February, CSIRO Astronomy and Space Science and the Max-Planck-Institute for Radio Astronomy installed, commissioned, and carried out science observations with a phased array feed receiver system on the 64-m diameter Parkes radio telescope. Here, we demonstrate that the phased array feed can be used for pulsar observations and we highlight some unique capabilities. We demonstrate that the pulse profiles obtained using the phased array feed can be calibrated and that multiple pulsars can be simultaneously observed. Significantly, we find that an intrinsic polarisation leakage of −31 dB can be achieved with a phased array feed beam offset from the centre of the field of view. We discuss the possibilities for using a phased array feed for future pulsar observations and for searching for fast radio bursts with the Parkes and Effelsberg telescopes.
This paper focuses on the attitude dynamics and control of liquid filled spacecraft, and the large amplitude fuel slosh dynamics is included by using an improved moving pulsating ball model. The moving pulsating ball model is an equivalent mechanical model that is capable of imitating the whole liquid reorientation process, specifically for the occurrence of large amplitude slosh. This model is improved by incorporating a static capillary force and an effective mass factor. The improvements on this model are validated with previously published experiment results. The spacecraft attitude maneuver is implemented by the momentum transfer technique, and the feedback control strategy is designed based on Lyapunov theory. The effects of liquid viscosity, tank location and desired steady time on sloshing torque and control torque are investigated. The attitude control strategy applied in this paper is proved to be applicable for the coupled liquid filled spacecraft system. The obtained conclusions are useful to aid in liquid filled spacecraft overall design.
The genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits.
We recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities.
We found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L–THA.L), left rectus to right thalamus (REC.L–THA.R), left superior orbital cortex to left thalamus (ORBsup.L–THA.L) and left superior orbital cortex to right thalamus (ORBsup.L–THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10−8) using REC.L–THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10–6, corrected p = 0.05).
Overall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.
Ten leading varieties of winter wheat released during 1950–2009 in North China were tested in a free-air temperature increase (FATI) facility. The FATI facility mimicked the local air temperature pattern well, with an increase of 1·1 °C in the daily mean temperature. For all the tested varieties, warming caused a significant reduction in the total length of wheat growth period by 5 days and especially in the pre-anthesis period, where it was reduced by 9 days. However, warming increased wheat biomass production and grain yield by 8·4 and 11·4%, respectively, on an average of all the tested varieties. There was no significant difference in the warming-led reduction in the entire growth period among the tested varieties. Interestingly, the warming-led increments in biomass production and grain yield increased along with the variety release year. Significantly higher warming-led increases in post-anthesis biomass production and 1000-grain weight were found in the new varieties compared to the old ones. Meanwhile, a significant improvement in plant productivity was noted due to wheat breeding during the past six decades, while no significant difference in the length of entire growth period was found among the varieties released in different eras. The results demonstrate that historical wheat breeding might have enhanced winter wheat productivity and adaptability through exploiting the positive effects rather than mitigating the negative impacts of warming on wheat growth in North China.
To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally?
Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus.
Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct.
MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.