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Double-zero-event studies (DZS) pose a challenge for accurately estimating the overall treatment effect in meta-analysis (MA). Current approaches, such as continuity correction or omission of DZS, are commonly employed, yet these ad hoc methods can yield biased conclusions. Although the standard bivariate generalized linear mixed model (BGLMM) can accommodate DZS, it fails to address the potential systemic differences between DZS and other studies. In this article, we propose a zero-inflated bivariate generalized linear mixed model (ZIBGLMM) to tackle this issue. This two-component finite mixture model includes zero inflation for a subpopulation with negligible or extremely low risk. We develop both frequentist and Bayesian versions of ZIBGLMM and examine its performance in estimating risk ratios against the BGLMM and conventional two-stage MA that excludes DZS. Through extensive simulation studies and real-world MA case studies, we demonstrate that ZIBGLMM outperforms the BGLMM and conventional two-stage MA that excludes DZS in estimating the true effect size with substantially less bias and comparable coverage probability.
Matching-adjusted indirect comparison (MAIC) has been increasingly applied in health technology assessments (HTA). By reweighting subjects from a trial with individual participant data (IPD) to match the summary statistics of covariates in another trial with aggregate data (AgD), MAIC enables a comparison of the interventions for the AgD trial population. However, when there are imbalances in effect modifiers with different magnitudes of modification across treatments, contradictory conclusions may arise if MAIC is performed with the IPD and AgD swapped between trials. This can lead to the “MAIC paradox,” where different entities reach opposing conclusions about which treatment is more effective, despite analyzing the same data. In this paper, we use synthetic data to illustrate this paradox and emphasize the importance of clearly defining the target population in HTA submissions. Additionally, we recommend making de-identified IPD available to HTA agencies, enabling further indirect comparisons that better reflect the overall population represented by both IPD and AgD trials, as well as other relevant target populations for policy decisions. This would help ensure more accurate and consistent assessments of comparative effectiveness.
Network meta-analysis (NMA), also known as mixed treatment comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of NMA within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This article introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including an NMA comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.
The rural-oriented tuition-waived medical education program in China, started in 2010, provides free medical education to students committed to serving in rural areas to address medical staff shortages. Despite its success in training and deploying graduates, retaining them post-obligation remains challenging. This study explores the mechanisms behind the turnover intentions of rural-oriented medical students in Western China, offering insights for their retention.
Methods:
Semi-structured interviews were conducted with 47 rural-oriented medical students and 30 health clinic directors in Nanning City. Interview data were analysed using grounded theory, and open, axial and selective coding was applied.
Results:
Through three levels of coding analysis, 34 tree nodes, 13 sub-categories and 3 main categories were identified from the interviews with rural-oriented medical students and health clinic directors. 3 main categories were Subjective Norms, Behavioural Attitudes, and Perceived Behavioural Control.
Conclusion:
A model of turnover intention among rural-oriented medical students was developed. This model can serve as a valuable reference for future policy optimization concerning China’s rural order-directed medical students.
The inverse dynamics model of an industrial robot can predict and control the robot’s motion and torque output, improving its motion accuracy, efficiency, and adaptability. However, the existing inverse rigid body dynamics models still have some unmodelled residuals, and their calculation results differ significantly from the actual industrial robot conditions. The bootstrap aggregating (bagging) algorithm is combined with a long short-term memory network, the linear layer is introduced as the network optimization layer, and a compensation method of hybrid inverse dynamics model for robots based on the BLL residual prediction algorithm is proposed to meet the above needs. The BLL residual prediction algorithm framework is presented. Based on the rigid body inverse dynamics of the Newton–Euler method, the BLL residual prediction network is used to perform error compensation on the inverse dynamics model of the Franka robot. The experimental results show that the hybrid inverse dynamics model based on the BLL residual prediction algorithm can reduce the average residuals of the robot joint torque from 0.5651 N·m to 0.1096 N·m, which improves the accuracy of the inverse dynamics model compared with those of the rigid body inverse dynamics model. This study lays the foundation for performing more accurate operation tasks using industrial robots.
The influence of the SNP rs174575 (C/G) within the fatty acid desaturase 2 gene on the levels of long-chain PUFA was determined through statistical meta-analysis. Six databases were searched to retrieve the relevant literature. Original data were analysed using Stata 17·0, encompassing summary statistics, tests for heterogeneity, assessment of publication bias, subgroup analysis and sensitivity analysis. A total of ten studies were identified and grouped into twelve trials. Our results showed that individuals who carried the minor G allele of rs174575 had significantly higher dihomo-γ-linolenic acid levels (P = 0·005) and lower arachidonic acid levels (P = 0·033) than individuals who were homozygous for the major allele. The subgroup analysis revealed that the G-allele carriers of rs174575 were significantly positively correlated with linoleic acid (P = 0·002) and dihomo-γ-linolenic acid (P < 0·001) and negatively correlated with arachidonic acid (P = 0·004) in the European populations group. This particular SNP showed a potential association with higher concentrations of dihomo-γ-linolenic acid (P = 0·050) and lower concentrations of arachidonic acid (P = 0·030) within the breast milk group. This meta-analysis has been registered in the PROSPERO database (ID: CRD42023470562).
A 60-d feeding trial was conducted to explore the potential regulatory effects of dietary Clostridium butyricum cultures (CBC) supplementation in high-carbohydrate diet (HCD) on carbohydrate utilisation, antioxidant capacity and intestinal microbiota of largemouth bass. Triplicate groups of largemouth bass (average weight 35·03 ± 0·04 g), with a destiny of twenty-eight individuals per tank, were fed low-carbohydrate diet and HCD supplemented with different concentration of CBC (0 %, 0·25 %, 0·50 % and 1·00 %). The results showed that dietary CBC inclusion alleviated the hepatic glycogen accumulation induced by HCD intake. Additionally, the expression of hepatic ampkα1 and insulin signaling pathway-related genes (ira, irb, irs, p13kr1 and akt1) increased linearly with dietary CBC inclusion, which might be associated with the activation of glycolysis-related genes (gk, pfkl and pk). Meanwhile, the expression of intestinal SCFA transport-related genes (ffar3 and mct1) was significantly increased with dietary CBC inclusion. In addition, the hepatic antioxidant capacity was improved with dietary CBC supplementation, as evidenced by linear decrease in malondialdehyde concentration and expression of keap1, and linear increase in antioxidant enzyme activities (total antioxidative capacity, total superoxide dismutase and catalase) and expression of antioxidant enzyme-related genes (nrf2, sod1, sod2 and cat). The analysis of bacterial 16S rRNA V3–4 region indicated that dietary CBC inclusion significantly reduced the enrichment of Firmicutes and potential pathogenic bacteria genus Mycoplasma but significantly elevated the relative abundance of Fusobacteria and Cetobacterium. In summary, dietary CBC inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota of largemouth bass fed HCD.
To accurately calculate the turbulent exchange coefficient, the contribution of multi-scale turbulent transportation needs to be considered, especially in the complex terrain of the coastal area. In September 2019, a comprehensive observation experiment on the offshore atmospheric boundary layer was carried out at the Yangmeikeng Ecological Monitoring Station and Sai Chung Gulf. Through scale decomposition, it is shown that the turbulent motion in the atmospheric boundary layer in the coastal area is affected by the underlying surface, such as that of the coastal land or the sea–land boundary. This is the main reason behind the phenomenon whereby different scales make different contributions to momentum flux. Different multi-scale characteristics of turbulent structures on the underlying surface affect the drag coefficient. Through wavelet transform and finite element method, the characteristics of the multi-scale flow structures produced by the complicated offshore terrain are analysed. It is found that large-scale flow structures enhance the pulsating intensity at the small scale, but the large-scale coherence characteristics are different from those at the small scale. In summary, in comparing these three sites, the flux exchange on the roof is greatest, followed by that on the tower. In the Gulf, the flux exchange is mainly dependent on small-scale structures, which are linked with the smallest values.
In detonation engines and accidental explosions, a detonation may propagate in an inhomogeneous mixture with non-uniform reactant concentration. In this study, one- and two-dimensional simulations are conducted for detonation propagation in hydrogen/oxygen/nitrogen mixtures with periodic sinusoidal or square wave distribution of the reactant concentration. The objective is to assess the properties of detonation propagation in such inhomogeneous mixtures. Specifically, detonation quenching and reinitiation, cellular structure, cell size and detonation speed deficit are investigated. It is found that there exists a critical amplitude of the periodic mixture composition distribution, above which the detonation quenches. When the amplitude is below the critical value, detonation quenching and reinitiation occur alternately. A double cellular structure consisting of substructures and a large-scale structure is found for a two-dimensional detonation propagating in inhomogeneous mixtures with a periodic reactant concentration gradient. The detonation reinitiation process and the formation of the double cellular structure are interpreted. To quantify the properties of detonation propagation in different inhomogeneous mixtures, the large cell size, critical amplitude, transition distance and detonation speed deficit are compared for hydrogen/air without and with nitrogen dilution and for periodic sine wave and square wave distributions of the reactant concentration. The large-scale cell size is found to be linearly proportional to the wavelength, and both the critical amplitude and the transition distance decrease with the wavelength. The small detonation speed deficit is shown to be due to the incomplete combustion of the reactant. This work provides helpful understanding of the features of detonation propagation in inhomogeneous mixtures.
The identification of herbicide tolerance is essential for effective chemical weed control. According to whole-plant dose–response assays, none of 29 pond lovegrass [Eragrostis japonica (Thunb.) Trin.] populations were sensitive to penoxsulam. The effective dose values of penoxsulam causing 50% inhibition of fresh weight (GR50: 105.14 to 148.78 g ai ha−1) in E. japonica populations were much higher than the label rate of penoxsulam (15 to 30 g ai ha−1) in the field. This confirmed that E. japonica was tolerant to penoxsulam. Eragrostis japonica populations showed 52.83- to 74.76-fold higher tolerance to penoxsulam than susceptible barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.]. The mechanisms of tolerance to penoxsulam in E. japonica were also identified. In vitro activity assays revealed that the penoxsulam concentration required to inhibit 50% of the acetolactate synthase (ALS) activity (IC50) was 12.27-fold higher in E. japonica than in E. crus-galli. However, differences in the ALS gene, previously found to endow target-site resistance in weeds, were not detected in the sequences obtained. Additionally, the expression level of genes encoding ALS in E. japonica was approximately 2-fold higher than in E. crus-galli after penoxsulam treatment. Furthermore, penoxsulam tolerance can be significantly reversed by three cytochrome P450 monooxygenase (CytP450) inhibitors (1-aminobenzotriazole, piperonyl butoxide, and malathion), and the activity of NADPH-dependent cytochrome P450 reductase toward penoxsulam in E. japonica increased significantly (approximately 7-fold higher) compared with that of treated E. crus-galli. Taken together, these results indicate that lower ALS sensitivity, relatively higher ALS expression levels, and stronger metabolism of CytP450s combined to bring about penoxsulam tolerance in E. japonica.
This article outlines the research progress on radiocarbon (14C) dating of the Erlitou site. The Erlitou site, belonging to the Bronze Age, located in Yanshi, Henan province, China, was discovered by archaeologists in 1959 when they investigated the Xia people’s remains in the area where the Xia people lived according to the records of ancient documents. Since then, there has been a standing debate about whether the site belongs to the Xia or Shang dynasty. By the mid-1990s, several hundred discussion articles on the issue had been published, but the question was still unresolved. Therefore, evidence from the chronology has attracted a great amount of attention. The dating of the Erlitou site began in the 1970s, and since the Xia-Shang-Zhou Chronology Project began in the mid-1990s, by application of wiggle-matching on the basis of improving the dating accuracy, the date of the Erlitou site has gradually become clear, which provides a basis for the archaeological research on the Xia and Shang dynasties.
Antibiotics rank as the most powerful weapons against bacterial infection, but their use is often limited by antibiotic-associated diarrhoea (AAD). Here, we reported that glutamine deficiency might act as a new link between clindamycin-induced dysbiosis and intestinal barrier dysfunction during AAD progression. Using a mouse model, we demonstrated that glutamine became a conditionally essential amino acid upon persistent therapeutic-dose clindamycin exposure, evidenced by a dramatic decrease in intestinal glutamine level and glutaminase expression. Mechanistically, clindamycin substantially confounded the abundance of butyrate-producing strains, leading to the deficiency of faecal butyrate which is normally a fundamental fuel for enterocytes, and in turn increased the compensatory use of glutamine. In addition to its pivotal roles in colonic epithelial cell turnover, glutamine was required for nitric oxide production in classic macrophage-driven host defence facilitating pathogen removal. Importantly, oral administration of glutamine effectively attenuated clindamycin-induced dysbiosis and restored intestinal barrier dysfunction in mice. Collectively, the present study highlighted the importance of gut microbiota in host energy homoeostasis and provided a rationale for introducing glutamine supplementation to patients receiving long-term antibiotic treatment.
Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. In vitro susceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment of T. asahii infection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of T. asahii infection.
This paper proposes a set of novel indices for evaluating the kinematic performance of a 3-RRS (R and S denote revolute and spherical joint respectively, R denotes active joint.), parallel mechanism whose translational and rotational movements are strongly coupled. First, the indices are formulated using the decoupled overall Jacobian matrix, which is developed using coordinate transformation. Then, the influences of the homogeneous dimensionless parameters on these indices are investigated. In addition, the dimension synthesis of the 3-RRS parallel mechanism is carried out by minimizing the mean value of the kinematic performance indices and their standard deviation. The results demonstrate that the established approach facilitates good global kinematic performance of the parallel mechanism.
With the development of remote sensing and geostatistical technology, complex environmental variables are increasingly easily quantified and applied in modelling soil organic carbon (SOC). However, this emphasizes data redundancy and multicollinearity problems adding to the difficulty in selecting dominant influential auxiliary variables and uncertainty in estimating SOC stocks. The current paper considers the spatial characteristics of SOC density (SOCD) to construct prediction models of SOCD on the basis of reducing the data dimensionality and complexity using the principal component analysis (PCA) method. A total of 260 topsoil samples were collected from Chahe town, China. Eight environmental variables (elevation, aspect, slope, normalized difference vegetation index, normalized difference moisture index, nearest distance to construction area and road, and land use degree comprehensive index) were pre-analysed by PCA and then extracted as the main principal component variables to construct prediction models. Two geostatistical approaches (ordinary kriging and ordinary co-kriging) and two regression approaches (ordinary least squares and geographically weighted regression (GWR)) were used to estimate SOCD. Results showed that PCA played an important role in reducing the redundancy and multicollinearity of the auxiliary variables and GWR achieved the highest prediction accuracy in these four models. GWR considered not only the spatial characteristics of SOCD but also the related valuable information of the auxiliary attributes. In summary, PCA-GWR is a promising spatial method used here to predict SOC stocks.
We analyzed climate proxies from loessic-soil sections of the southern Chinese Loess Plateau. The early Holocene paleosol, S0, is 3.2 m thick and contains six sub-soil units. Co-eval soils from the central Loess Plateau are thinner (~ 1 m). Consequently higher-resolution stratigraphic analyses can be made on our new sections and provide more insight into Holocene temporal variation of the East Asian monsoon. Both summer and winter monsoon evolution signals are recorded in the same sections, enabling the study of phase relationships between the signals. Our analyses consist of (i) measurements of magnetic properties sensitive to the production of fine-grained magnetic minerals which reflect precipitation intensity and summer monsoon strength; and (ii) grain-size analyses which reflect winter monsoon strength. Our results indicate that the Holocene precipitation maximum occurred in the mid-Holocene, ~ 7.8–3.5 cal ka BP, with an arid interval at 6.3–5.3 cal ka BP. The winter monsoon intensity declined to a minimum during 5.0–3.4 cal ka BP. These results suggest that the East Asian summer and winter monsoons were out of phase during the Holocene, possibly due to their different sensitivities to ice and snow coverage at high latitudes and to sea-surface temperature at low latitudes.
Numerical investigation of the underexpanded sonic coaxial jets is carried out using large eddy simulation for three typical inner nozzle lip-thicknesses. Various fundamental mechanisms dictating the flow phenomena including shock structure, shear layer evolution and sound production are investigated. It is found that the inner nozzle lip induces a recirculation zone between inner and outer jets, which significantly influences the behaviors of shock structures and shear layers. The sound properties of the coaxial jets are further analyzed in detail. As the inner lip-thickness increases, the helical screech mode switches to an axisymmetric one and high-frequency screech also occurs with an oscillation frequency of recirculation zone. Based on the temporal Fourier transform and correlation analysis, the primary sources of low- and high-frequency screeches are associated with the downstream shock cells in the jet column and the secondary shock structures in the outer annular jet, respectively. The proper orthogonal decomposition analysis reveals that the dominant structures constructed by the most energetic modes shift from the downstream shock cells region to the upstream secondary shock region as the lip-thickness increases. The results obtained in this study provide physical insight into the understanding of the mechanisms relevant to the coherent structures and sound properties in sonic coaxial jets.
In this paper, we consider a singularly perturbed convection-diffusion problem. The problem involves two small parameters that gives rise to two boundary layers at two endpoints of the domain. For this problem, a non-monotone finite element methods is used. A priori error bound in the maximum norm is obtained. Based on the a priori error bound, we show that there exists Bakhvalov-type mesh that gives optimal error bound of (N−2) which is robust with respect to the two perturbation parameters. Numerical results are given that confirm the theoretical result.
In this paper, an adaptive force reflection scheme is proposed for bilateral teleoperation. In order to achieve an ideal telepresence performance while keeping the system stable, the force reflection algorithm needs to take both the human force and the contact force into consideration. An observer based on the feature of the human operator is designed to estimate the force applied on the master device. The reflected force is calculated by performing the orthogonal decomposition of the contact force, and is adjusted adaptively according to the estimated human force. The direction of the reflected force becomes a key consideration in the design process, so the proposed approach has an advantage in the guiding contact task. Based on the small gain theorem, the master device with the force reflection scheme is proved to be input-to-output stable, and the derivation for stability criterion of the closed-loop teleoperation system is also given. The results of simulations and experiments on a 6-degree of freedom teleoperation system demonstrate the effectiveness of the proposed scheme.
We report here investigations on the superstructure modulation induced by the ordering of carbon vacancies in the nonstoichiometric zirconium carbide of ZrC0.61, which was prepared by spark plasma sintering (SPS) of the mechanochemically synthesized ZrCx nanopowders. The sintered ZrC0.61 is found to exhibit an interesting microstructure of interlaced laminated sheets. In contrast to the previous long duration post annealing for realization of the ordered carbon vacancies in the rocksalt-structured transition metal carbide, the ordered carbon vacancies are directly obtained during the SPS process, and no post-annealing period is necessary. With the help of transmission electron microscopy, the superstructural nanodomains with the average size of ∼30 nm are identified.