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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed to comprehensively investigate and characterize these neuropsychiatric AEs with GLP-1RAs.
Methods
We analyzed GLP-1RA adverse reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis using reporting odds ratio (ROR) identified eight categories of neuropsychiatric AEs associated with GLP-1RAs. We conducted descriptive and time-to-onset (TTO) analyses and explored neuropsychiatric AE signals among individual GLP-1RAs for weight loss and diabetes mellitus (DM) indications.
Results
We identified 25,110 cases of GLP-1RA-related neuropsychiatric AEs. GLP-1RAs showed an association with headache (ROR 1.74, 95% confidence interval [CI] 1.65–1.84), migraine (ROR 1.28, 95%CI 1.06–1.55), and olfactory and sensory nerve abnormalities (ROR 2.44, 95%CI 1.83–3.25; ROR 1.69, 95%CI 1.54–1.85). Semaglutide showed a moderate suicide-related AEs signal in the weight loss population (ROR 2.55, 95%CI 1.97–3.31). The median TTO was 16 days (interquartile range: 3–66 days).
Conclusions
In this study, we identified eight potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs and, for the first time, detected positive signals for migraine, olfactory abnormalities, and sensory abnormalities. We also observed positive suicide-related signals of semaglutide, in weight loss population. This study provides a reliable basis for further investigation of GLP-1RA-related neuropsychiatric AEs. However, as an exploratory study, our findings require confirmation through large-scale prospective studies.
Our study aimed to develop and validate a nomogram to assess talaromycosis risk in hospitalized HIV-positive patients. Prediction models were built using data from a multicentre retrospective cohort study in China. On the basis of the inclusion and exclusion criteria, we collected data from 1564 hospitalized HIV-positive patients in four hospitals from 2010 to 2019. Inpatients were randomly assigned to the training or validation group at a 7:3 ratio. To identify the potential risk factors for talaromycosis in HIV-infected patients, univariate and multivariate logistic regression analyses were conducted. Through multivariate logistic regression, we determined ten variables that were independent risk factors for talaromycosis in HIV-infected individuals. A nomogram was developed following the findings of the multivariate logistic regression analysis. For user convenience, a web-based nomogram calculator was also created. The nomogram demonstrated excellent discrimination in both the training and validation groups [area under the ROC curve (AUC) = 0.883 vs. 0.889] and good calibration. The results of the clinical impact curve (CIC) analysis and decision curve analysis (DCA) confirmed the clinical utility of the model. Clinicians will benefit from this simple, practical, and quantitative strategy to predict talaromycosis risk in HIV-infected patients and can implement appropriate interventions accordingly.
Previous studies suggest a link between vitamin D status and COVID-19 susceptibility in hospitalised patients. This study aimed to investigate whether vitamin D concentrations in elderly individuals were associated with their susceptibility to Omicron COVID-19 incidence, the severity of the disease and the likelihood of reoccurrence during the era of the post-‘zero-COVID-19’ policies in China.
Design:
In this retrospective study, participants were categorised into three groups based on their 25(OH)D concentrations: deficiency (< 20 ng/ml), insufficiency (20 to < 30 ng/ml) and sufficiency (≥ 30 ng/ml). The demographic and clinical characteristics, comorbidities and the incidence rate, reoccurrence rate and severity of Omicron COVID-19 were retrospectively recorded and analysed by using hospital information system data and an online questionnaire survey.
Setting:
China.
Participants:
222 participants aged 60 years or older from a health management centre.
Results:
Our findings revealed significant differences in the incidence (P = 0·03) and recurrent rate (P = 0·02) of Omicron COVID-19 among the three groups. Participants with lower 25(OH)D concentrations (< 20 ng/ml) exhibited higher rates of initial incidence and reoccurrence and a greater percentage of severe and critical cases. Conversely, individuals with 25(OH)D concentrations ≥ 30 ng/ml had a higher percentage of mild cases (P = 0·003). Binary and ordinal logistic regression models indicated that vitamin D supplementation was not a significant risk factor for COVID-19 outcomes.
Conclusions:
In the elderly population, pre-infection vitamin D deficiency was associated with increased susceptibility to incidence, severity of illness and reoccurrence rates of Omicron COVID-19.
We present a systematic study on the effects of small aspect ratios $\varGamma$ on heat transport in liquid metal convection with a Prandtl number of $Pr=0.029$. The study covers $1/20\le \varGamma \le 1$ experimentally and $1/50\le \varGamma \le 1$ numerically, and a Rayleigh number $Ra$ range of $4\times 10^3 \le Ra \le 7\times 10^{9}$. It is found experimentally that the local effective heat transport scaling exponent $\gamma$ changes with both $Ra$ and $\varGamma$, attaining a $\varGamma$-dependent maximum value before transition-to-turbulence and approaches $\gamma =0.25$ in the turbulence state as $Ra$ increases. Just above the onset of convection, Shishkina (Phys. Rev. Fluids, vol 6, 2021, 090502) derived a length scale $\ell =H/(1+1.49\varGamma ^{-2})^{1/3}$. Our numerical study shows $Ra_{\ell }$, i.e. $Ra$ based on $\ell$, serves as a proper control parameter for heat transport above the onset with $Nu-1=0.018(1+0.34/\varGamma ^2)(Ra/Ra_{c,\varGamma }-1)$. Here $Ra_{c,\varGamma }$ represents the $\varGamma$-dependent critical $Ra$ for the onset of convection and $Nu$ is the Nusselt number. In the turbulent state, for a general scaling law of $Nu-1\sim Ra^\alpha$, we propose a length scale $\ell = H/(1+1.49\varGamma ^{-2})^{1/[3(1-\alpha )]}$. In the case of turbulent liquid metal convection with $\alpha =1/4$, our measurement shows that the heat transport will become weakly dependent on $\varGamma$ with $Ra_{\ell }\equiv Ra/(1+1.49\varGamma ^{-2})^{4/3} \ge 7\times 10^5$. Finally, once the flow becomes time-dependent, the growth rate of $Nu$ with $Ra$ declines compared with the linear growth rate in the convection state. A hysteresis is observed in a $\varGamma =1/3$ cell when the flow becomes time-dependent. Measurements of the large-scale circulation suggest the hysteresis is caused by the system switching from a single-roll-mode to a double-roll-mode in an oscillation state.
In 2018, an Ionplus 200 kV MIni-CArbon DAting System (MICADAS) accelerator mass spectrometer (AMS) was installed at the Laboratory of AMS Dating and the Environment, Nanjing University (NJU-AMS Laboratory), China. The NJU-AMS Laboratory is largely devoted to research on radiocarbon dating and 14C analysis in fields of earth, environmental and archaeological sciences. The laboratory has successfully employed various pretreatment methods, including routine pretreatment of tree rings, buried wood and subfossil wood, seeds, charcoal, pollen concentrates, organic matter, and shells. In this study, operational status of the NJU-AMS is presented, and results of radiocarbon measurements made on different sample types are reported. Measurements on international standards, references of known age, and blank samples demonstrate that the NJU-AMS runs stably and has good reproducibility on measurement of single samples. The facility is capable of measuring 14C in samples with the precision and accuracy that meet the requirements for investigating annual 14C changes, history-prehistory age dating, and Late Quaternary stratigraphic chronology research.
Few studies have evaluated the joint effect of trace elements on spontaneous preterm birth (SPTB). This study aimed to examine the relationships between the individual or mixed maternal serum concentrations of Fe, Cu, Zn, Se, Sr and Mo during pregnancy, and risk of SPTB. Inductively coupled plasma MS was employed to determine maternal serum concentrations of the six trace elements in 192 cases with SPTB and 282 controls with full-term delivery. Multivariate logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to evaluate the individual and joint effects of trace elements on SPTB. The median concentrations of Sr and Mo were significantly higher in controls than in SPTB group (P < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted OR (aOR) of 0·432 (95 CI < 0·05). In multivariate logistic regression analysis, compared with the lowest quartile levels of individual trace elements, the third- and fourth-quartile Sr or Mo concentrations were significantly associated with reduced risk of SPTB with adjusted aOR of 0·432 (95 % CI 0·247, 0·756), 0·386 (95 % CI 0·213, 0·701), 0·512 (95 % CI 0·297, 0·883) and 0·559 (95 % CI 0·321, 0·972), respectively. WQSR revealed the inverse combined effect of the trace elements mixture on SPTB (aOR = 0·368, 95 % CI 0·228, 0·593). BKMR analysis confirmed the overall mixture of the trace elements was inversely associated with the risk of SPTB, and the independent effect of Sr and Mo was significant. Our findings suggest that the risk of SPTB decreased with concentrations of the six trace elements, with Sr and Mo being the major contributors.
The burden of mental disorders is increasing worldwide, thus, affecting society and healthcare systems. This study investigated the independent influences of age, period and cohort on the global prevalence of mental disorders from 1990 to 2019; compared them by sex; and predicted the future burden of mental disorders in the next 25 years.
Methods
The age-specific and sex-specific incidence of mental disorders worldwide was analysed according to the general analysis strategy used in the Global Burden of Disease Study in 2019. The incidence and mortality trends of mental disorders from 1990 to 2019 were evaluated through joinpoint regression analysis. The influences of age, period and cohort on the incidence of mental disorders were evaluated with an age–period–cohort model.
Results
From 1990 to 2019, the sex-specific age-standardized incidence and disability-adjusted life years (DALY) rate decreased slightly. Joinpoint regression analysis from 1990 to 2019 indicated four turning points in the male DALY rate and five turning points in the female DALY rate. In analysis of age effects, the relative risk (RR) of incidence and the DALY rate in mental disorders in men and women generally showed an inverted U-shaped pattern with increasing age. In analysis of period effects, the incidence of mental disorders increased gradually over time, and showed a sub-peak in 2004 (RR, 1.006 for males; 95% CI, 1.000–1.012; 1.002 for women, 0.997–1.008). Analysis of cohort effects showed that the incidence and DALY rate decreased in successive birth cohorts. The incidence of mental disorders is expected to decline slightly over the next 25 years, but the number of cases is expected to increase.
Conclusions
Although the age-standardized burden of mental disorders has declined in the past 30 years, the number of new cases and deaths of mental disorders worldwide has increased, and will continue to increase in the near future. Therefore, relevant policies should be used to promote the prevention and management of known risk factors and strengthen the understanding of risk profiles and incidence modes of mental disorders, to help guide future research on control and prevention strategies.
To adapt to the development of the industry, universities actively explore the training mode of applied financial investment talents. However, whether students with social anxiety disorder can adjust and grow smoothly in this new teaching environment has not been thoroughly studied. This study aims to analyze the specific impact of a new applied financial investment talent training model on students with social anxiety disorder.
Subjects and Methods
Six hundred students majoring in financial investment from a particular university were selected, of which 100 were diagnosed with social anxiety disorder. In a 6-month new teaching model experiment, students’ learning attitudes, social abilities, and emotional fluctuations were comprehensively evaluated using the Social Anxiety Scale (LSAS).
Results
Research has found that students with social anxiety disorder significantly improve their learning engagement and initiative under the new training mode. Among them, 73% of patients stated that they experienced a significant sense of achievement in group collaboration and practical applications, and social anxiety symptoms were alleviated to a certain extent. However, some students still feel pressure during large-scale public demonstrations or speeches.
Conclusions
The new model of cultivating applied financial investment talents in universities can, to some extent, help students with social anxiety disorders establish confidence, improve social skills, and encourage them to participate more actively in learning. However, at the same time, in response to their specific needs, universities still need to strengthen mental health education and personalized guidance to ensure the comprehensiveness and fairness of education.
We present an experimental study of Rayleigh–Bénard convection using liquid metal alloy gallium-indium-tin as the working fluid with a Prandtl number of $Pr=0.029$. The flow state and the heat transport were measured in a Rayleigh number range of $1.2\times 10^{4} \le Ra \le 1.3\times 10^{7}$. The temperature fluctuation at the cell centre is used as a proxy for the flow state. It is found that, as $Ra$ increases from the lower end of the parameter range, the flow evolves from a convection state to an oscillation state, a chaotic state and finally a turbulent state for $Ra>10^5$. The study suggests that the large-scale circulation in the turbulent state is a residual of the cell structure near the onset of convection, which is in contrast with the case of $Pr\sim 1$, where the cell structure is transiently replaced by high order flow modes before the emergence of the large-scale circulation in the turbulent state. The evolution of the flow state is also reflected by the heat transport characterised by the Nusselt number $Nu$ and the probability density function (p.d.f.) of the temperature fluctuation at the cell centre. It is found that the effective local heat transport scaling exponent $\gamma$, i.e. $Nu\sim Ra^{\gamma }$, changes continuously from $\gamma =0.49$ at $Ra\sim 10^4$ to $\gamma =0.25$ for $Ra>10^6$. Meanwhile, the p.d.f. at the cell centre gradually evolves from a Gaussian-like shape before the transition to turbulence to an exponential-like shape in the turbulent state. For $Ra>10^6$, the flow shows self-similar behaviour, which is revealed by the universal shape of the p.d.f. of the temperature fluctuation at the cell centre and a $Nu=0.19Ra^{0.25}$ scaling for the heat transport.
To address the shortcomings of existing methods for rotorcraft searching, positioning, tracking and landing on a ship at sea, a dual-channel LIDAR searching, positioning, tracking and landing system (DCLSPTLS) is proposed in this paper, which utilises the multi-pulse laser echoes accumulation method and the physical phenomenon that the laser reflectivity of the ship deck in the near-infrared band is four orders of magnitude higher than that of the sea surface. The DCLSPTLS searching and positioning model, tracking model and landing model are established, respectively. The searching and positioning model can provide estimates of the azimuth angle, the distance of the ship relative to the rotorcraft and the ship's course. With the above parameters as inputs, the total tracking time and the direction of the rotorcraft tracking speed can be obtained by using the tracking model. The landing model can calculate the pitch and the roll angles of the ship's deck relative to the rotorcraft by using the least squares method and the laser irradiation coordinates. The simulation shows that the DCLSPTLS can realise the functions of rotorcraft searching, positioning, tracking and landing by using the above parameters. To verify the effectiveness of the DCLSPTLS, a functional test is performed using a rotorcraft and a model ship on a lake. The test results are consistent with the results of the simulation.
In this paper, a novel self-adaptive underactuated robot hand with rigid-flexible coupling fingers (SAU-RFC hand) is proposed. The seven degrees of freedom (DOFs) SAU-RFC hand is driven by four servomotors, consists of three fingers, including two side-turning (ST) fingers and one non-side-turning finger. Specially, the ST fingers can perform synchronous reverse rotation laterally with each other. Each finger with three joints and two DOFs introduces a flexible structure, and the inner part of the proximal phalanx that makes most of the contact with the object is replaced by a flexible belt. The fingers can generate flexion/extension under the pull of the flexible belt, and the middle and distal phalanxes are mechanically coupled through a four-bar linkage. In particular, the flexible belt in the inner direction of the finger will deform, while it will not deform in the outer direction since the outer is a rigid structure. The flexible belt not only plays the role of transmitting power but also has the effect of uniformizing the contact force. Due to the rigid-flexible finger structure, the developed robot hand has a higher self-adaptive grasping ability for objects with different shapes, sizes, and hardness. In addition, the kinematic and kinetic analyses of SAU-RFC hand are performed. A contact force distribution model is established for the flexible belt, which demonstrates its effect of promoting uniform force distribution theoretically. In the end, experiments are conducted on different objects to verify the performance of SAU-RFC hand.
“Picking out the impurities” is a typical scenario in production line which is both time consuming and laborious. In this article, we propose a target-oriented robotic push-grasping system which is able to actively discover and pick the impurities in dense environments with the synergies between pushing and grasping actions. First, we propose an attention module, which includes target saliency detection and density-based occluded-region inference. Without the necessity of expensive labeling of semantic segmentation, our attention module can quickly locate the targets in the view or predict the candidate regions where the targets are most likely to be occluded. Second, we propose a push–grasp synergy framework to sequentially select proper actions in different situations until all targets are picked out. Moreover, we introduce an active pushing mechanism based on a novel metric, namely Target-Centric Dispersion Degree (TCDD) for better grasping. TCDD describes whether the targets are isolated from the surrounding objects. With this metric, the robot becomes more focused on the actions around the targets and push irrelevant objects away. Experimental results on both simulated environment and real-world environment show that our proposed system outperforms several baseline approaches,which also has the capability to be generalized to new scenarios.
Attentional bias toward health-threat may theoretically contribute to the development and maintenance of health anxiety, but the empirical findings have been controversial. This study aimed to synthesize and explore the heterogeneity in a health-threat related attentional bias of health-anxious individuals, and to determine the theoretical model that better represents the pattern of attentional bias in health anxiety. Four databases (Web of Science, PubMed, PsycINFO, and Scopus) were searched for relevant studies, with 17 articles (N = 1546) included for a qualitative review and 16 articles (18 studies) for a three-level meta-analysis (N = 1490). The meta-analytic results indicated that the health anxiety group, compared to the control group, showed significantly greater attentional bias toward health-threat (g = 0.256). Further analyses revealed that attentional bias type, paradigm, and stimuli type were significant moderators. Additionally, compared to the controls, health-anxious individuals displayed significantly greater attention maintenance (g = 0.327) but nonsignificant attention vigilance to health-threat (g = −0.116). Our results provide evidence for the attention maintenance model in health-anxious individuals. The implications for further research and treatment of elevated health anxiety in the context of coronavirus disease-2019 (COVID-19) were also discussed.
An 8-week feeding trial was conducted to investigate the effects of dietary vitamin D3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. A total of 720 shrimp (initial weight 0·50 ± 0·01 g) were randomly distributed into six treatments, each of which had three duplicates of forty shrimp per duplicate. Six isonitrogenous and isolipidic diets were formulated to contain graded vitamin D3 (0·18, 0·23, 0·27, 0·48, 0·57 and 0·98 mg/kg of vitamin D3, measured) supplementation levels. The results revealed that L. vannamei fed diet containing 0·48 mg/kg of vitamin D3 achieved the best growth performance. Compared with the control group, supplementing 0·48 mg/kg of vitamin D3 significantly increased (P < 0·05) the activities of catalase, total antioxidative capacity, alkaline phosphatase and acid phosphatase in serum and hepatopancreas. Expression levels of antioxidant and immune-related genes were synchronously increased (P < 0·05). Carapace P and Ca concentrations were increased (P < 0·05) with the increased vitamin D3 supplementation levels. Further analysis of lipid metabolism-related genes expression showed that shrimp fed 0·48 mg of vitamin D3 per kg diet showed the highest value in the expression of lipid synthesis-related genes, while shrimp fed 0·98 mg of vitamin D3 per kg diet showed the highest value in the expression of lipolysis-related genes. In conclusion, the results of present study indicated that dietary supplementation of 0·48 mg/kg of vitamin D3 could increase Ca and P concentrations, improve antioxidant capacity and immune response, and influence lipid metabolism in L. vannamei.
Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
Vehicle state estimation and path prediction, which usually involve Kalman filter and motion model, are critical tasks for intelligent driving. In vehicle state estimation, the comparative performance assessment, regarding accuracy and efficiency, of the unscented Kalman filter (UKF) and the extended Kalman filter (EKF) is rarely discussed. This paper is devoted to empirically evaluating the performance of UKF and EKF incorporating different motion models and investigating the models’ properties and the affecting factors in path prediction. Extensive real world experiments have been carried out and the results show that EKF and UKF have roughly identical accuracy in state estimation; however, EKF is faster than UKF generally; the fastest filter is about 2⋅6 times faster than the slowest. The path prediction experiments reveal that the velocity estimate and the used motion model affect path prediction; the more realistically the model reflects the vehicle's driving status, the more reliable its predictions.
The impact of diet on the metabolic syndrome (MetS) and CVD has been investigated widely, but few studies have investigated the association between dietary patterns (DP) and the predicted CVD, derived from reduced rank regression (RRR). The objectives of this study were to derive DP using RRR and principal component analysis (PCA) and investigate their associations with the MetS and estimated 10-year atherosclerotic CVD (ASCVD). We used the baseline dataset from the Xinjiang multi-ethnic cohort study in China, collected from June 2018 to May 2019. A total of 14 982 subjects aged 35–74 years from Urumqi, Huo Cheng and Mo Yu were included in the analysis. The 10-year ASCVD risk was estimated using the Chinese ASCVD risk equations. The associations of DP with the MetS and 10-year ASCVD were determined using multivariable logistic regression models. In Urumqi and Mo Yu, the increased RRR DP score was associated with a higher OR of having the MetS and with a higher OR of elevated 10-year ASCVD risk. However, only the first DP determined by PCA in Urumqi was inversely associated with the MetS and elevated 10-year ASCVD risk. The prevalence of the MetS and elevated ASCVD risk in urban population is higher than that in rural areas. Our results may help nutritionists develop more targeted dietary strategies to prevent the MetS and ASCVD in different regions in China.