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This paper establishes a new version of integration by parts formula of Markov chains for sensitivity computation, under much lower restrictions than the existing researches. Our approach is more fundamental and applicable without using Girsanov theorem or Malliavin calculus as did by past papers. Numerically, we apply this formula to compute sensitivity regarding the transition rate matrix and compare with a recent research by an IPA (infinitesimal perturbation analysis) method and other approaches.
It is essential to investigate the experiences behind why adolescents start and continue to self-harm in order to develop targeted treatment and prevent future self-harming behaviours.
The aims of this study are to understand the motivations for initiating and repeating nonfatal self-harm, the different methods used between first-time and repeated self-harm and the reasons that adolescents do not seek help from health services.
Adolescents with repeated nonfatal self-harm experiences were recruited to participate in individual, semi-structured qualitative interviews. The interviews were analysed with interpretative phenomenological analysis.
We found that nonfatal self-harm among adolescents occurred comparatively early and was often triggered by specific reasons. However, the subsequent nonfatal self-harm could be causeless, with repeated self-harm becoming a maladaptive coping strategy to handle daily pressure and negative emotions. The choice of tools used was related to the ease of accessibility, the life-threatening risk and the size of the scars. Adolescents often concealed their scars on purpose, which made early identification insufficient. Peer influence, such as online chat groups encouraging self-harm by discussing and sharing self-harm pictures, could also lead to increased self-harm. The results also included participants’ opinions on how to stop nonfatal self-harm and their dissatisfaction with the current healthcare services.
The current study provides important implications both for early identification and interventions for adolescents who engage in repeated nonfatal self-harm, and for individualising treatment planning that benefits them. It is also worthwhile to further investigate how peer influence and social media may affect self-harm in adolescents.
A recently developed pneumonia caused by SARS-CoV-2 has quickly spread across the world. Unfortunately, a simplified risk score that could easily be used in primary care or general practice settings has not been developed. The objective of this study is to identify a simplified risk score that could easily be used to quickly triage severe COVID-19 patients. All severe and critical adult patients with laboratory-confirmed COVID-19 on the West campus of Union Hospital, Wuhan, China, from 28 January 2020 to 29 February 2020 were included in this study. Clinical data and laboratory results were obtained. CURB-65 pneumonia score was calculated. Univariate logistic regressions were applied to explore risk factors associated with in-hospital death. We used the receiver operating characteristic curve and multivariate COX-PH model to analyse risk factors for in-hospital death. A total of 74 patients (31 died, 43 survived) were finally included in the study. We observed that compared with survivors, non-survivors were older and illustrated higher respiratory rate, neutrophil-to-lymphocyte ratio, D-dimer and lactate dehydrogenase (LDH), but lower SpO2 as well as impaired liver function, especially synthesis function. CURB-65 showed good performance for predicting in-hospital death (area under curve 0.81, 95% confidence interval (CI) 0.71–0.91). CURB-65 ⩾ 2 may serve as a cut-off value for prediction of in-hospital death in severe patients with COVID-19 (sensitivity 68%, specificity 81%, F1 score 0.7). CURB-65 (hazard ratio (HR) 1.61; 95% CI 1.05–2.46), LDH (HR 1.003; 95% CI 1.001–1.004) and albumin (HR 0.9; 95% CI 0.81–1) were risk factors for in-hospital death in severe patients with COVID-19. Our study indicates CURB-65 may serve as a useful prognostic marker in COVID-19 patients, which could be used to quickly triage severe patients in primary care or general practice settings.
Predictors of compliance with aspirin in children following cardiac catheterisation have not been identified. The aim of this study is to identify the caregivers’ knowledge, compliance with aspirin medication, and predictors of compliance with aspirin in children with Congenital Heart Disease (CHD) post-percutaneous transcatheter occlusion.
A cross-sectional explorative design was adopted using a self-administered questionnaire and conducted between May 2017 and May 2018. Recruited were 220 caregivers of children with CHD post-percutaneous transcatheter occlusion. Questionnaires included child and caregivers’ characteristics, a self-designed and tested knowledge about aspirin scale (scoring scale 0–2), and the 8-item Morisky Medication Adherence Scale (scoring scale 0–8). Data were analysed using multivariate binary logistic regression analysis to identify predictors of compliance with aspirin.
Of the 220 eligible children and caregivers, 210 (95.5%) responded and 209 surveys were included in the analysis. The mean score of knowledge was 7.25 (standard deviation 2.27). The mean score of compliance was 5.65 (standard deviation 1.36). Child’s age, length of aspirin use, health insurance policies, relationship to child, monthly income, and knowledge about aspirin of caregivers were independent predictors of compliance with aspirin (p < 0.05).
Caregivers of children with CHD had an adequate level of knowledge about aspirin. Compliance to aspirin medication reported by caregivers was low. Predictors of medium to high compliance with aspirin were related to the child’s age and socio-economic reasons. Further studies are needed to identify effective strategies to improve knowledge, compliance with medication, and long-term outcomes of children with CHD.
Effects of dietary supplemental stachyose on caecal skatole concentration, hepatic cytochrome P450 (CYP450, CYP) mRNA expressions and enzymatic activities in broilers were evaluated. Arbor Acre commercial mixed male and female chicks were assigned randomly into six treatments. The positive control (PC) diet was based on maize–soyabean meal, and the negative control (NC) diet was based on maize–non-soyabean meal. The NC diet was then supplemented with 4, 5, 6 and 7 g/kg stachyose to create experimental diets, named S-4, S-5, S-6 and S-7, respectively. Each diet was fed to six replicates of ten birds from days 1 to 49. On day 49, the caecal skatole concentrations in the PC, S-4, S-5, S-6 and S-7 groups were lower than those in the NC group by 42·28, 23·68, 46·09, 15·31 and 45·14 % (P < 0·01), respectively. The lowest pH value was observed in the S-5 group (P < 0·05). The stachyose-fed groups of broilers had higher caecal acetate and propionate levels compared with control groups, and propionate levels in the S-6 and S-7 groups were higher than those in the S-4 and S-5 groups (P < 0·001). The highest CYP3A4 expression was found in the S-7 group (P < 0·05), but this was not different from PC, S-4, S-5 and S-6 treatments. There was no significant difference in CYP450 (1A2, 2D6 and 3A4) enzymatic activities among the groups (P > 0·05). In conclusion, caecal skatole levels can be influenced by dietary stachyose levels, and 5 g/kg of stachyose in the diet was suggested.
In the present work, the ankle rehabilitation robot (ARR) dynamic model that implements a new series of connection control strategies is introduced. The dynamic models are presented in this regard. This model analyzes the robot LuGre friction model and the nonlinear disturbance model. To improve the ARR system’s rapidity and robustness, a composite 2-degree of freedom (2-DOF) internal model control (IMC) controller is presented. The control performance of the compound 2-DOF IMC controller is simulated and analyzed in the present work. The simulation shows that the composite 2-DOF IMC controller has high following performance. For practical testing purposes, 1-DOF passive training and predetermined trajectory following have been completed for different swing amplitudes and frequencies. Moreover, the thrust and tension torque of the robotic dynamic and static loading characteristics are studied in active control mode. The experimental results show the effectiveness of passive training of the given trajectory and impedance training active control strategy. This paper gives the specific functions of ARR.
Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted β = −49·4 g, 95 % CI −91·1, −7·8, P < 0·05; for severe VDD: adjusted β = −79·8 g, 95 % CI −127·2, −32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted β = −44·5 g, 95 % CI −82·6, −6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted β = −124·7 g, 95 % CI −194·6, −54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.
Aiming at the influence of coupling coefficient variation on the output voltage of a high-power LCC-S topology inductively coupled power transfer (ICPT) system, a synchronous three-phase triple-parallel Buck converter is used as the voltage adjustment unit. The control method for the three-phase current sharing of synchronous three-phase triple-parallel Buck converter and the constant voltage output ICPT system under the coupling coefficient variation is studied. Firstly, the hybrid model consisting of the circuit averaging model of the three-phase triple-parallel Buck converter and the generalized state-space average model for the LCC-S type ICPT system is established. Then, the control methods for three-phase current sharing of the synchronous three-phase triple-parallel Buck converter and constant voltage output of ICPT system are studied to achieve the multi-objective integrated control of the system. Finally, a 3.3 kW wireless charging system platform is built, the experimental results have verified the effectiveness of the proposed modeling and control method, and demonstrated the stability of the ICPT system.
Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.
Alzheimer’s Disease (AD), characterized by deficits in memory and cognition and by behavioral impairment, is a progressive neurodegenerative disorder that influences more than 47 million people worldwide. Currently, no available drug is able to stop AD progression. Therefore, novel therapeutic strategies need to be investigated.
We analyzed the RNA sequencing data (RNA-seq) derived from the Gene Expression Omnibus (GEO) database to identify the differentially expressed mRNAs in AD. The AD mouse model Tg2576 was used to verify the effects of IGF-2. The Morris Water Maze was administered to test the role of IGF-2 in memory consolidation. In addition, we quantified cell apoptosis by the TUNEL assay. The levels of amyloid plaques and the levels of Aβ40 and Aβ42 in the hippocampus were also determined by immunohistochemistry and ELISA, respectively.
RNA-seq analysis revealed that IGF-2 was remarkably reduced in AD. The expression of the upstream genes PI3K and AKT and the downstream gene CREB in the PI3K signaling pathway was significantly increased in the hippocampus of Tg2576 mice cells treated with IGF-2. The Morris water maze test showed that IGF-2 improved memory consolidation in Tg2576 mice. The activity of caspase-3 was decreased in Tg2576 mice treated with IGF-2. Amyloid plaques in the hippocampus were reduced, and the levels of Aβ40 and Aβ42 were decreased. The above effects of IGF-2 on AD were blocked when the PI3K signaling pathway inhibitor wortmannin was added.
IGF-2 attenuates memory decline, oxidative stress, cell apoptosis and amyloid plaques in the AD mouse model Tg2576 by activating the PI3K/AKT/CREB signaling pathway.
Nowadays social entrepreneurship is recognized as a two-way process, addressing
both social and economic concerns that can bring social inclusion, equity, and
development to disadvantaged groups in society. This aspect is particularly
important and desirable within emerging economies. In these markets, which are
constantly faced with profound economic and social challenges, we see the
growing importance of social entrepreneurs as they take upon themselves the
provision of welfare services and progressive activities. However, our
understanding of the mechanisms underlying the creation of social and economic
values in social enterprises, and the factors contributing to the establishment
of these value creation objectives, is still rather fragmented. Our article
contributes to this gap in the literature by decoding the process via which
for-profit social entrepreneurs from China and India create social and economic
value. In addition, by combining a deductive and an inductive approach of
analysis, we offer novel insights into the context-dependent processual patterns
deciphered within the two countries. A new entrepreneurial process framework
that reflects the contextualized social value creation process by social
entrepreneurs is thus provided.
We propose a statistical model for homogeneous turbulence undergoing distortions, which improves and extends the MCS model by Mons, Cambon & Sagaut (J. Fluid Mech., vol. 788, 2016, 147–182). The spectral tensor of two-point second-order velocity correlations is predicted in the presence of arbitrary mean-velocity gradients and in a rotating frame. For this, we numerically solve coupled equations for the angle-dependent energy spectrum
that includes directional anisotropy, and for the deviatoric pseudo-scalar
, that underlies polarization anisotropy (
is the wavevector,
the time). These equations include two parts: (i) exact linear terms representing the viscous spectral linear theory (SLT) when considered alone; (ii) generalized transfer terms mediated by two-point third-order correlations. In contrast with MCS, our model retains the complete angular dependence of the linear terms, whereas the nonlinear transfer terms are closed by a reduced anisotropic eddy damped quasi-normal Markovian (EDQNM) technique similar to MCS, based on truncated angular harmonics expansions. And in contrast with most spectral approaches based on characteristic methods to represent mean-velocity gradient terms, we use high-order finite-difference schemes (FDSs). The resulting model is applied to homogeneous rotating turbulent shear flow with several Coriolis parameters and constant mean shear rate. First, we assess the validity of the model in the linear limit. We observe satisfactory agreement with existing numerical SLT results and with theoretical results for flows without rotation. Second, fully nonlinear results are obtained, which compare well to existing direct numerical simulation (DNS) results. In both regimes, the new model improves significantly the MCS model predictions. However, in the non-rotating shear case, the expected exponential growth of turbulent kinetic energy is found only with a hybrid model for nonlinear terms combining the anisotropic EDQNM closure and Weinstock’s return-to-isotropy model.
The aim of this meta-analysis was to provide a comprehensive overview of human immunodeficiency virus (HIV)-1 subtypes and to investigate temporal and geographical trends of the HIV-1 epidemic among men who have sex with men (MSM) in China. Chinese and English articles published between January 2007 and December 2017 were systematically searched. Pooled HIV-1 prevalence was calculated, and its stability was analysed using sensitivity analysis. Subgroups were based on study time period, sampling area and prevalence. Publication bias was measured using Funnel plot and Egger's test. A total of 68 independent studies that included HIV-1 molecular investigations were eligible for meta-analysis. Circulating recombinant form (CRF) 01_AE (57.36%, 95% confidence interval (CI) 53.76–60.92) was confirmed as the most prevalent HIV-1 subtype among MSM in China. Subgroup analysis for time period found that CRF01_AE steadily increased prior to 2012 but decreased during 2012–2016. Further whereas CRF07_BC increased over time, B/B′ decreased over time. CRF55_01B has increased in recent years, with higher pooled estimated rate in Guangdong (12.22%, 95% CI 10.34–13.17) and Fujian (8.65%, 95% CI 4.98–13.17) provinces. The distribution of HIV-1 subtypes among MSM in China has changed across different regions and periods. HIV-1 strains in MSM are becoming more complex. Long-term molecular monitoring in this population remains necessary for HIV-1 epidemic control and prevention.
There is emerging evidence that glycaemic variability (GV) plays an important role in the development of diabetic complications. The current study aimed to compare the effects of lifestyle intervention (LI) with and without partial meal replacement (MR) on GV. A total of 123 patients with newly diagnosed and untreated type 2 diabetes (T2D) were randomised to receive either LI together with breakfast replacement with a liquid formula (LI+MR) (n 62) or LI alone (n 61) for 4 weeks and completed the study. Each participant was instructed to have three main meals per d and underwent 72-h continuous glucose monitoring (CGM) both before and after intervention. Measures of GV assessed by CGM included the incremental AUC of postprandial blood glucose (AUCpp), standard deviation of blood glucose (SDBG), glucose CV and mean amplitude of glycaemic excursions (MAGE). After a 4-week intervention, the improvements in systolic blood pressure (P=0·046) and time in range (P=0·033) were more pronounced in the LI+MR group than in the LI group. Furthermore, LI+MR caused significantly greater improvements in all GV metrics including SDBG (P=0·005), CV (P=0·002), MAGE (P=0·016) and AUCpp (P<0·001) than did LI. LI+MR (v. LI) was independently associated with improvements in GV after adjustment of covariates (all P<0·05). Our study showed that LI+MR led to significantly greater improvements in GV compared with LI, suggesting that LI+MR could be an effective treatment to alleviate glucose excursions.
Identifying the relative importance of urban and non-urban land-use types for potential denitrification derived N2O at a regional scale is critical for quantifying the impacts of human activities on nitrous oxide (N2O) emission under changing environments. In this study we used a regional dataset from China including 197 soil samples and six land-use types to evaluate the main predictors (land use, heavy metals, soil pH, soil moisture, substrate availability, functional and broad microbial abundances) of potential denitrification using multivariate and pathway analysis. Our results provide empirical evidence that soils on farms have the greatest potential denitrifying ability (PDA) (10.92±6.08ng N2O-N·g–1 dry soil·min–1) followed by urban soil (6.80±5.35ng N2O-N·g–1 dry soil·min–1). Our models indicate that land use (low vs. high human activity), followed by total nitrogen (TN) and heavy metals (Cu, Zn, Pb, Cd) was the most important driver of PDA. In addition, our path analysis suggests that at least part of the impacts of land use on potential denitrification were mediated via microbial abundance, soil pH and substrates including TN, dissolved organic carbon and nitrate. This study identifies the main predictors of denitrification at a regional scale which is needed to quantify the impact of human activities on ecosystem functionality under changing conditions.
The microbiota-gut-brain axis and membrane dysfunction in the brain has attracted increasing attention in the field of psychiatric research. However, the possible interactive role of gut microbiota and brain function in the prodromal stage of schizophrenia has not been studied yet.
To explore this, we collected fecal samples and performed Magnetic Resonance Spectroscopy (MRS) scans in 81 high risk (HR) subjects, 19 ultra-high risk (UHR) subjects and 69 health controls (HC). Then we analyzed the differences in gut microbiota and choline concentrations in the anterior cingulate cortex (ACC).
Presences of the orders Clostridiales, Lactobacillales and Bacteroidales were observed at increase levels in fecal samples of UHR subjects compared to the other two groups. The composition changes of gut microbiota indicate the increased production of Short Chain Fatty Acids (SCFAs), which could activate microglia and then disrupt membrane metabolism. Furthermore, this was confirmed by an increase of choline levels, a brain imaging marker of membrane dysfunction, which is also significantly elevated in UHR subjects compared to the HR and HC groups.
Both gut microbiome and imaging studies of UHR subjects suggest the membrane dysfunction in the brain and hence might support the membrane hypothesis of schizophrenia.
The mass-balance of Muztag Ata No. 15 (MZ15) glacier in the eastern Pamir is reconstructed between 1980 and 2012 using an energy-based mass-balance model. The results show that this glacier has been characterized by obvious interannual mass-balance changes during 1980–2012 with a slightly positive mass balance during 1998–2012. Precipitation in the ablation season is a primary driver of these mass-balance fluctuations. Distinct changes in the mass-balance of MZ15 glacier between 1980–1997 and 1998–2012 are thought to be associated with changes in the regionally averaged meridional wind speed and corresponding precipitation in the ablation season. The negative and positive mass-balance phases during 1980–1997 and 1998–2012, respectively, were associated with northerly and southerly wind anomalies in the eastern Pamir and their corresponding decreasing and increasing precipitation. These changes in circulation appear to be linked to the mid-latitude climate. Finally, contrary to the variation of most glaciers on the Tibetan Plateau, glaciers in the Karakoram-western Kunlun-eastern Pamir appear to have retreated more slowly over the past 10 years than during the 1970s-2000. This contrasting trend may be caused by different changes in snowfall and different topography factors in different regions under warming and increased precipitation.
Previous neuroimaging studies demonstrated that retinal detachment (RD) subjects were associated with abnormal spontaneous brain activities; however, whether the altered interhemispheric functional connectivity (FC) occurred in RD patients remains unknown. The current study tried to explore the alternations of interhemispheric FC of the whole brain in unilateral RD patients using the voxel-mirrored homotopic connectivity (VMHC) method and their connections to clinical features. Methods: We recruited 30 patients with RD (16 males and 14 females) and 30 healthy controls (HCs) (16 males and 14 females) whose age and sex were closely matched. All subjects underwent the rs-fMRI scans. The VMHC method was applied to directly assess the hemispheres’ functional interaction. The VMHC in these brain areas, which could be used as biomarkers to differentiate RD from HC, was identified by the receiver operating characteristic (ROC) curve analyses. The relations between these patients’ clinical features and their mean VMHC signal values in multiple brain regions were calculated by Pearson correlation analysis. Results: RD patients had significantly lower VMHC values than HCs in the bilateral occipital lobe (Brodmann areas, BA 18), bilateral superior temporal gyrus (BA 39), and bilateral cuneus (BA 19). Moreover, the mean VMHC signal values of the bilateral cuneus were in positive correlation with the duration of the RD (r = 0.446, P = 0.013). Conclusion: Our results provided an evidence of disturbed interhemispheric FC in the visual area occurred in RD patients, which might provide some useful information to understand the neural mechanism of RD patients with acute vision loss. Furthermore, the VMHC values might indicate the progress of the RD.