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Patients with schizophrenia have a significantly elevated risk of mortality. Clozapine is effective for treatment-resistant schizophrenia, but its use is limited by side-effects. Understanding its association with mortality risk is crucial.
Aims
To investigate the associations of clozapine with all-cause and cause-specific mortality risk in schizophrenia patients.
Method
In this 18-year population-based cohort study, we retrieved electronic health records of schizophrenia patients from all public hospitals in Hong Kong. Clozapine users (ClozUs) comprised schizophrenia patients who initiated clozapine treatment between 2003 and 2012, with the index date set at clozapine initiation. Comparators were non-clozapine antipsychotic users (Non-ClozUs) with the same diagnosis who had never received a clozapine prescription. They were 1:2 propensity score matched with demographic characteristics and physical and psychiatric comorbidities. ClozUs were further defined according to continuation of clozapine use and co-prescription of other antipsychotics (polypharmacy). Accelerated failure time (AFT) models were used to estimate the risk of all-cause and cause-specific mortality (i.e. suicide, cardiovascular disease, infection and cancer).
Results
This study included 9,456 individuals (mean (s.d.) age at the index date: 39.13 (12.92) years; 50.73% females; median (interquartile range) follow-up time: 12.37 (9.78–15.22) years), with 2020 continuous ClozUs, 1132 discontinuous ClozUs, 4326 continuous non-ClozUs and 1978 discontinuous Non-ClozUs. Results from adjusted AFT models showed that continuous ClozUs had a lower risk of suicide mortality (acceleration factor 3.01; 99% CI: 1.41–6.44) compared with continuous Non-ClozUs. Continuous ClozUs with co-prescription of other antipsychotics exhibited lower risks of suicide mortality (acceleration factor 3.67; 1.41–9.60) and all-cause mortality (acceleration factor 1.42; 1.07–1.88) compared with continuous Non-ClozUs. No associations were found between clozapine and other cause-specific mortalities.
Conclusions
These results add to the existing evidence on the effectiveness of clozapine, particularly its anti-suicide effects, and emphasise the need for continuous clozapine use for suitable patients and the possible benefit of clozapine polypharmacy.
Aims: Psychoeducation for patients with anxiety disorders has been associated with reduced symptoms, improved quality of life, and increased response to treatment. However, there is much heterogeneity in such interventions. Patients with anxiety disorders can have maladaptive cognitive patterns such as catastrophic thinking, attentional biases toward threat, and cognitive avoidance. These patterns can interfere with the processing and assimilation of psychoeducational content, potentially reducing its effectiveness. Our hypothesis is that psychological safety plays a key role in increasing the effectiveness of psychoeducational interventions for patients with anxiety disorders. We aim to critically review the role of psychological safety in such interventions and to explore its impact on medical education in psychiatry.
Methods: Sources were identified through searches via databases including PubMed, PsycINFO, Scopus, Cochrane Library, and Google Scholar. Results were then critically analysed with key themes extracted to evaluate the role of psychological safety in psychoeducation. A narrative synthesis was then performed, exploring the influence of this on medical education in psychiatry.
Results: Several key themes were identified. Psychological safety has a mediating role between the quality of doctor-patient communication and patients’ self-disclosure, which can be limited by various fears, including a fear of negative judgment in this population. Patient engagement, which has a multidimensional construct, is also impacted by the presence of psychological safety which increases patient openness and comfort. Psychological safety also aids collaborative efforts within the healthcare ecosystem, positively impacting the outcomes of psychoeducational processes. The influence of psychological safety on the concept of the therapeutic interpersonal relationship in psychoeducation was also explored, with implications for open communication and the perception of threats. Proposed enhancements to assessments and curriculum for educational efforts in anxiety disorders and corresponding psychoeducational interventions through the active provision of psychological safety concepts were discussed.
Conclusion: This critical review highlights the pivotal role of psychological safety in enhancing the effectiveness of psychoeducational interventions for patients with anxiety disorders. By equipping clinicians to create safe environments, these efforts can optimize psychoeducational interventions and ultimately improve care for patients with anxiety disorders. Targeted studies on specific subgroups of patients with anxiety disorders should be performed to better qualify and quantify the impact of psychological safety in psychoeducational interventions in these subgroups.
Firefighters are frequently exposed to traumatic events and stressful environments and are at particularly high risk of depressive symptoms.
Aims:
The present study aimed to examine the impact of a combined internet-delivered cognitive behavioral therapy (iCBT) and attention bias modification (ABM) intervention to reduce depressive symptoms in firefighters.
Method:
The study was a randomized controlled trial carried out in Kunming, China, and involved the recruitment of 138 active firefighters as participants. The intervention lasted for an 8-week duration, during which participants participated in ABM exercises on alternating days and concurrently underwent eight modules of iCBT courses delivered through a smartphone application. Baseline and post-intervention assessments were conducted to evaluate the effects of the intervention.
Results and Discussion:
Results indicated that the combined iCBT and ABM intervention was significantly effective in reducing symptoms of depression compared with the no intervention control group (U=1644, p<0.001, Wilcoxon r=0.280). No significant change was observed in attention bias post-intervention (U=2460, p=0.737, Wilcoxon r=0.039), while a significant increase was observed in attention-bias variability (U=3172, p<0.001, Wilcoxon r=–0.287). This study provides evidence for the effectiveness of the combined iCBT and ABM intervention in reducing depressive symptoms among firefighters. This study provides conceptual support and preliminary evidence for the effectiveness of the combined iCBT and ABM intervention in reducing depressive symptoms among firefighters.
The spatio-temporal scales, as well as a comprehensive self-sustained mechanism of the reattachment unsteadiness in shock wave/boundary layer interaction, are investigated in this study. Direct numerical simulations reveal that the reattachment unsteadiness of a Mach 7.7 laminar inflow causes over $26\,\%$ variation in wall friction and up to $20\,\%$ fluctuation in heat flux at the reattachment of the separation bubble. A statistical approach, based on the local reattachment upstream movement, is proposed to identify the spanwise and temporal scales of reattachment unsteadiness. It is found that two different types, i.e. self-induced and random processes, dominate different regions of reattachment. A self-sustained mechanism is proposed to comprehend the reattachment unsteadiness in the self-induced region. The intrinsic instability of the separation bubble transports vorticity downstream, resulting in an inhomogeneous reattachment line, which gives rise to baroclinic production of quasi-streamwise vortices. The pairing of these vortices initiates high-speed streaks and shifts the reattachment line upstream. Ultimately, viscosity dissipates the vortices, triggering instability and a new cycle of reattachment unsteadiness. The temporal scale and maximum vorticity are estimated with the self-sustained mechanism via order-of-magnitude analysis of the enstrophy. The advection speed of friction, derived from the assumption of coherent structures advecting with a Blasius-type boundary layer, aligns with the numerical findings.
As a required sample preparation method for 14C graphite, the Zn-Fe reduction method has been widely used in various laboratories. However, there is still insufficient research to improve the efficiency of graphite synthesis, reduce modern carbon contamination, and test other condition methodologies at Guangxi Normal University (GXNU). In this work, the experimental parameters, such as the reduction temperature, reaction time, reagent dose, Fe powder pretreatment, and other factors, in the Zn-Fe flame sealing reduction method for 14C graphite samples were explored and determined. The background induced by the sample preparation process was (2.06 ± 0.55) × 10–15, while the 12C– beam current were better than 40μA. The results provide essential instructions for preparing 14C graphite of ∼1 mg at the GXNU lab and technical support for the development of 14C dating and tracing, contributing to biology and environmental science.
A new vacuum line to extract CO2 from carbonate and dissolved inorganic carbon (DIC) in water was established at Guangxi Normal University. The vacuum line consisted of two main components: a CO2 bubble circulation region and a CO2 purification collection region, both of which were made of quartz glass and metal pipelines. To validate its reliability, a series of carbonate samples were prepared using this system. The total recovery rate of CO2 extraction and graphitization exceeded 80%. Furthermore, the carbon content in calcium carbonate exhibited a linear relationship with the CO2 pressure within the system, demonstrating its stability and reliability. The system was also employed to prepare and analyze various samples, including calcium carbonate blanks, foraminiferal, shell, groundwater, and subsurface oil-water samples. The accelerator mass spectrometry (AMS) results indicated that the average beam current for 12C- in the samples exceeded 40 μA. Additionally, the contamination introduced during the liquid sample preparation process was approximately (1.77 ± 0.57) × 10−14. Overall, the graphitized preparation system for carbonate and DIC in water exhibited high efficiency and recovery, meeting the requirements for samples dating back to approximately 30,000 years.
This paper proposes a nonparametric test to assess whether there exist heterogeneous quantile treatment effects (QTEs) of an intervention on the outcome of interest across different sub-populations defined by covariates of interest. Specifically, a consistent test statistic based on the Cramér–von Mises type criterion is developed to test if the treatment has a constant quantile effect for all sub-populations defined by covariates of interest. Under some regularity conditions, the asymptotic behaviors of the proposed test statistic are investigated under both the null and alternative hypotheses. Furthermore, a nonparametric Bootstrap procedure is suggested to approximate the finite-sample null distribution of the proposed test; then, the asymptotic validity of the proposed Bootstrap test is theoretically justified. Through Monte Carlo simulations, we demonstrate the power properties of the test in finite samples. Finally, the proposed testing approach is applied to investigate whether there exists heterogeneity for the QTE of maternal smoking during pregnancy on infant birth weight across different age groups of mothers.
Very-large-scale motions are commonly observed in moderate- and high-Reynolds-number wall turbulence, constituting a considerable portion of the Reynolds stress and skin friction. This study aims to investigate the behaviour of these motions in high-speed and high-Reynolds-number turbulent boundary layers at varying Mach numbers. With the aid of high-precision numerical simulations, numerical experiments and theoretical analysis, it is demonstrated that the very-large-scale motions are weakened in high-Mach-number turbulence at the same friction Reynolds numbers, leading to the reduction in turbulent kinetic energy in the outer region. Conversely, the lower wall temperature enhances the very-large-scale motions but shortens the scale separation between the structures in the near-wall and outer regions.
Compared with nitrogen and argon, helium is lighter and can better reduce the beam loss caused by angular scattering during beam transmission. The molecular dissociation cross-section in helium is high and stable at low energies, which makes helium the prevalent stripping gas in low-energy accelerator mass spectrometry (AMS). To study the stripping behavior of 14C ions in helium at low energies, the charge state distributions of carbon ion beams with −1, +1, +2, +3, and +4 charge states were measured at energies of 70–220 keV with a compact 14C-AMS at Guangxi Normal University (GXNU). The experimental data were used to analyze the stripping characteristics of C-He in the energy range of 70–220 keV, and new charge state yields and exchange cross-sections in C-He were obtained at energies of 70–220 keV.
Two thrips, Megalurothrips usitatus (Bagnall) and Frankliniella intonsa (Trybom) are major pests of cowpea in South China. To realistically compare the growth, development and reproductive characteristics of these two thrips species, we compared their age-stage, two-sex life tables on cowpea pods under summer and winter natural environmental regimes. The results showed that the total preadult period of M. usitatus was 8.09 days, which was significantly longer than that of F. intonsa (7.06 days), while the adult female longevity of M. usitatus (21.14 days) was significantly shorter than that of F. intonsa (25.77 days). Significant differences were showed in male adult longevity (10.68 days for F. intonsa and 16.95 days for M. usitatus) and the female ratio of offspring (0.67 for F. intonsa and 0.51 for M. usitatus), and the total preadult period of M. usitatus (16.20 days) was significantly longer than that of F. intonsa (13.66 days) in the winter regime. The net reproductive rate (summer: R0 = 85.62, winter: R0 = 105.22), intrinsic rate of increase (summer: r = 0.3020 day−1, winter: r = 0.2115 day−1), finite rate of increase (summer: λ = 1.3526 day−1, winter: λ = 1.2356 day−1) and gross reproduction rate (summer: GRR = 139.34, winter: GRR = 159.88) of F. intonsa were higher than those of M. usitatus (summer: R0 = 82.91, r = 0.2741, λ = 1.3155, GRR = 135.71; winter: R0 = 80.62, r = 0.1672, λ = 1.1820, GRR = 131.26), and the mean generation times (summer: T = 14.73 days, winter: T = 22.01 days) of F. intonsa were significantly shorter than those of M. usitatus (summer: T = 16.11 days, winter: T = 26.25 days). These results may contribute to a better understanding of the bioecology of different thrips species, especially the interspecific competition between two economically important cowpea thrips with the same ecological niche in a changing environment.
We present the results of two population surveys conducted 10 years apart (December 2010–February 2011 and December 2020–January 2021) of the Critically Endangered white-headed langur Trachypithecus leucocephalus in the Chongzuo White-Headed Langur National Nature Reserve, Guangxi Province, China. In the first survey, we recorded 818 individuals in 105 groups and 16 solitary adult males. In the second survey, we recorded 1,183 individuals in 128 groups and one solitary adult male. As a result of government policies, poaching for food and traditional medicine is no longer a primary threat to these langurs. However, severe forest loss and fragmentation caused by human activities could limit any future increase of this langur population.
A single-stage accelerator mass spectrometer (GXNU-AMS) developed for radiocarbon and tritium measurements was installed and commissioned at Guangxi Normal University in 2017. After several years of operational and methodological upgrades, its performance has been continuously improved and applied in multidisciplinary fields. Currently, the measurement sensitivity for radiocarbon and tritium is 14C/12C ∼ (3.14 ± 0.05) ×10–15 and 3H/1H ∼ (1.23 ± 0.17)×10–16, respectively, and the measurement accuracy is ∼0.6%, which can meet the measurement requirements in the nuclear, earth, environmental and life science fields. This study presents the performance characteristics of GXNU-AMS and several interesting application studies.
The oblique shock impinging on the supersonic turbulent boundary layer leads to a mixing layer and the emergence of large-scale coherent structures within the interaction zone which leave significant velocity defect and turbulence amplification downstream. In the present study, we investigate the turbulence recovery in the post-shock region by exploiting direct numerical simulation data of the oblique-shock/turbulent boundary layer interaction flow at the incoming Mach number of $2.28$ and the shock angle of $33.2^\circ$, with special attention paid to the contribution of the mixing layer and large-scale structures to flow dynamics. For that purpose, we propose to split the mean velocity, Reynolds stresses and spanwise spectra into a canonical portion that is constructed according to the statistics of canonical turbulent boundary layers, and a mixing-layer-induced portion. We found that the hidden mixing layer grows with the boundary layer thickness and that the induced mean shear and Reynolds stresses decay at different rates. The mean velocity recovers to the canonical profiles at a distance of 13 boundary layer thicknesses downstream where the mixing-layer-induced mean shear ceases to have strong impacts. The recovery of Reynolds stresses requires 10 boundary layer thicknesses in the near-wall region but a much longer streamwise extent in the outer region due to the slow decay of large-scale motions. These large-scale motions superpose on the near-wall turbulence, intensifying the turbulent fluctuations, yet having a trivial impact on the skin friction, for the contribution of the mixing-layer-induced mean shear and Reynolds shear stress are balanced by the advection term. We further establish a simple physical model capable of approximately predicting the streamwise evolution of mixing-layer-induced mean shear and turbulent kinetic energy. This model suggests that the complete recovery of turbulence in the outer region requires a streamwise extent of approximately 50 boundary layer thicknesses.
Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients.
Methods:
Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmic mislocalization of mutant FUS protein.
Results:
We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at C-terminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells.
Conclusions:
We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.
Turbulence amplification and the large-scale coherent structures in shock wave/turbulent boundary layer interaction flows have been studied at length in previous research, while the direct association between these two flow features is still lacking. In the present study, the transport equation of turbulent kinetic energy spectra is derived and utilized to analyse the scale-by-scale energy budget across the interaction zone, enabling us to reveal the association between the genesis of the large-scale motions and the turbulence amplification. For the presently considered flow with incipient shock-induced separation, we identified in turbulent kinetic energy spectra distribution that the most energetic motions are converted from the near-wall small-scale motions to large-scale motions consisting of velocity streaks and cross-stream circulations as they go through the interaction zone. The amplification of streamwise velocity fluctuation is triggered first, resulting in the emergence of large-scale velocity streaks, which is attributed to the adverse pressure gradient, as indicated by the spectra of the production term. The energy carried by large-scale velocity streaks is transferred to other velocity components by the pressure-strain term, producing large-scale cross-stream circulations. When large-scale motions are convected downstream, their energy is transferred via turbulent cascade to smaller scales and dissipated by viscosity. The spanwise uniform fluctuations, reminiscent of the unsteadiness of the separation bubble, are contributed primarily by the inter-scale energy transfer from the finite spanwise scale motions.
A new system for preparing 14C samples was established for a compact accelerator mass spectrometer (GXNU-AMS) at Guangxi Normal University. This sample preparation system consists of three units: a vacuum maintenance unit, a CO2 purification unit, and a CO2 reduction unit, all of which were made of quartz glass. A series of radiocarbon (14C) preparation experiments were conducted to verify the reliability of the system. The recovery rate of graphite obtained was more than 80%. The carbon content in the commercial toner and wood sample was linearly fitted to the CO2 pressure in the measurement unit of the system. The results showed a good linear relationship, indicating that the reliability of the sample preparation system. AMS measurements were conducted on a batch of standard, wood, and dead graphite samples prepared using this system. The results showed that the beam current of 12C- for each sample was more than 40 μA, the carbon contamination introduced during the sample preparation process was ∼ 2 × 10–15, and that the new sample preparation system is compact, low-contamination, and efficient and meets the GXNU-AMS requirements for 14C samples.
The occurrence of chalkiness has decreased in new hybrid rice cultivars in China. As both chalkiness occurrence and starch granule size are associated with the biosynthesis of starch, we hypothesized that there may be a correlation between chalkiness occurrence and starch granule size, and this may partially explain the decreased chalkiness occurrence in the new hybrid rice cultivars. To test this hypothesis, a field experiment was conducted over eight environments (two years × four sowing dates) with two hybrid rice cultivars: one recently developed with low chalkiness occurrence, Jingliangyou 1468 (JLY1468) and a relatively older cultivar with high chalkiness occurrence, Liangyoupeijiu (LYPJ). Results showed that JLY1468 had a higher cumulative distribution of large-diameter (7.51–19.50 μm) starch granules and a lower grain weight of milled rice compared to LYPJ. As a consequence, mean and relative starch granule diameters were 6% and 21% higher in JLY1468 than in LYPJ, respectively. Although both the chalky grain rate and chalkiness degree were negatively correlated with mean and relative starch granule diameter, they were more closely correlated with the relative granule diameter. These results support our hypothesis regarding the relationship between chalkiness occurrence and starch granule size and suggest that the relative starch granule diameter is a relevant parameter in understanding the occurrence of chalkiness in hybrid rice.
Many waterflooding oil fields, injecting water into an oil-bearing reservoir for pressure maintenance, are in their middle to late stages of development. To explore the geological conditions and improve oilfield recovery of the most important well group of the Hu 136 block, located on the border areas of three provinces (Henan, Shandong, and Hebei), Zhongyuan Oilfield, Sinopec, central China, a 14C cross-well tracer monitoring technology was developed and applied in monitoring the development status and recognize the heterogeneity of oil reservoirs. The tracer response in the production well was tracked, and the water drive speed, swept volume of the injection fluid were obtained. Finally, the reservoir heterogeneity characteristics, such as the dilution coefficient, porosity, permeability, and average pore-throat radius, were fitted according to the mathematical model of the heterogeneous multi-layer inter-well theory. The 14C-AMS technique developed in this work is expected to be a potential analytical method for evaluating underground reservoir characteristics and providing crucial scientific guidance for the mid to late oil field recovery process.
The Bangong–Nujiang suture zone (BNSZ), which separates the Gondwana-derived Qiangtang and Lhasa terranes, preserves limited geological records of the Bangong–Nujiang Ocean (BNO). The timing of opening of this ocean has been hotly debated due to the rare and complicated rock records in the suture zones, which span over 100 Ma from Carboniferous–Permian to Early Jurassic time, based on geological, palaeontological and palaeomagnetic data. A combination of geochemical, geochronological and isotopic data are reported for the Riasairi trachytes, central BNSZ, northern Tibet, to constrain its petrogenesis and tectonic settings. Zircon U–Pb dating by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) yields mean ages of 236 Ma. Geochemically, these rocks are high-K calc-alkaline with moderate SiO2 (59.1–67.5 wt%) and high K2O + Na2O (8.1–11.6 wt%) contents. They are enriched in light rare earth elements with negative Eu anomalies, and show enrichments in high-field-strength elements with positive ‘Nb, Ta’ anomalies, similar to the intra-continental rift setting-related felsic lavas from the African Rift System. The high positive zircon ϵHf(t) and bulk ϵNd(t) values, as well as high initial Pb isotopes, imply a heterogeneous source involving both asthenospheric and subcontinental lithospheric mantle. The field and geochemical data jointly suggest that the Riasairi trachytes within the Mugagangri Group were formed in a continental rift setting. We interpret that the continental-rift-related Riaisairi trachytic lavas as derived from the southern margin of the Qiangtang terrane, implying that the BNO would have opened by Middle Triassic time, well after the commonly interpreted break-up of the Qiangtang terrane from Gondwana.