We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Persistent malnutrition is associated with poor clinical outcomes in cancer. However, assessing its reversibility can be challenging. The present study aimed to utilise machine learning (ML) to predict reversible malnutrition (RM) in patients with cancer. A multicentre cohort study including hospitalised oncology patients. Malnutrition was diagnosed using an international consensus. RM was defined as a positive diagnosis of malnutrition upon patient admission which turned negative one month later. Time-series data on body weight and skeletal muscle were modelled using a long short-term memory architecture to predict RM. The model was named as WAL-net, and its performance, explainability, clinical relevance and generalisability were evaluated. We investigated 4254 patients with cancer-associated malnutrition (discovery set = 2977, test set = 1277). There were 2783 men and 1471 women (median age = 61 years). RM was identified in 754 (17·7 %) patients. RM/non-RM groups showed distinct patterns of weight and muscle dynamics, and RM was negatively correlated to the progressive stages of cancer cachexia (r = –0·340, P < 0·001). WAL-net was the state-of-the-art model among all ML algorithms evaluated, demonstrating favourable performance to predict RM in the test set (AUC = 0·924, 95 % CI = 0·904, 0·944) and an external validation set (n 798, AUC = 0·909, 95 % CI = 0·876, 0·943). Model-predicted RM using baseline information was associated with lower future risks of underweight, sarcopenia, performance status decline and progression of malnutrition (all P < 0·05). This study presents an explainable deep learning model, the WAL-net, for early identification of RM in patients with cancer. These findings might help the management of cancer-associated malnutrition to optimise patient outcomes in multidisciplinary cancer care.
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.
Parental psychopathology is a known risk factor for child autistic-like traits. However, symptom-level associations and underlying mechanisms are poorly understood.
Methods
We utilized network analyses and cross-lagged panel models to investigate the specific parental psychopathology related to child autistic-like traits among 8,571 adolescents (mean age, 9.5 years at baseline), using baseline and 2-year follow-up data from the Adolescent Brain Cognitive Development study. Parental psychopathology was measured by the Adult Self Report, and child autistic-like traits were measured by three methods: the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 autism spectrum disorder (ASD) subscale, the Child Behavior Checklist ASD subscale, and the Social Responsiveness Scale. We also examined the mediating roles of family conflict and children’s functional brain connectivity at baseline.
Results
Parental attention-deficit/hyperactivity problems were central symptoms and had a direct and the strongest link with child autistic-like traits in network models using baseline data. In longitudinal analyses, parental attention-deficit/hyperactivity problems at baseline were the only significant symptoms associated with child autistic-like traits at 2-year follow-up (β = 0.014, 95% confidence interval [0.010, 0.018], FDR q = 0.005), even accounting for children’s comorbid behavioral problems. The observed association was significantly mediated by family conflict (proportion mediated = 11.5%, p for indirect effect <0.001) and functional connectivity between the default mode and dorsal attention networks (proportion mediated = 0.7%, p for indirect effect = 0.047).
Conclusions
Parental attention-deficit/hyperactivity problems were associated with elevated autistic-like traits in offspring during adolescence.
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 seminal Bolgiano–Obukhov (BO) theory established the fundamental framework for turbulent mixing and energy transfer in stably stratified fluids. However, the presence of BO scalings remains debatable despite their being observed in stably stratified atmospheric layers and convective turbulence. In this study, we performed precise temperature measurements with 51 high-resolution loggers above the seafloor for 46 h on the continental shelf of the northern South China Sea. The temperature observation exhibits three layers with increasing distance from the seafloor: the bottom mixed layer (BML), the mixing zone and the internal wave zone. A BO-like scaling $\alpha =-1.34\pm 0.10$ is observed in the temperature spectrum when the BML is in a weakly stable stratified ($N\sim 0.0018$ rad s$^{-1}$) and strongly sheared ($Ri\sim 0.0027$) condition, whereas in the unstably stratified convective turbulence of the BML, the scaling $\alpha =-1.76\pm 0.10$ clearly deviated from the BO theory but approached the classical $-$5/3 scaling in isotropic turbulence. This suggests that the convective turbulence is not the promise of BO scaling. In the mixing zone, where internal waves alternately interact with the BML, the scaling follows the Kolmogorov scaling. In the internal wave zone, the scaling $\alpha =-2.12 \pm 0.15$ is observed in the turbulence range and possible mechanisms are provided.
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.
Sediments within accretionary complexes, preserving key information on crust growth history of Central Asian Orogenic Belt, did not get enough attention previously. Here, we conduct comprehensive geochemical study on the turbidites from the North Tianshan Accretionary Complex (NTAC) in the Chinese West Tianshan orogen, which is a good example of sediments derived from juvenile materials. The turbidites, composed of sandstone, siltstone, and argillaceous siliceous rocks, are mainly Carboniferous. All the investigated samples have relatively low Chemical Index of Alteration values (35–63) and Plagioclase Index of Alteration values (34–68), indicating relatively weak weathering before erosion and deposition. The sandstone and siltstone, and slate samples display high Index of Compositional Variability values of 0.89–1.50 and 0.89–0.93, suggesting a relatively immature source. The sandstones and siltstones were mainly derived from intermediate igneous rocks, and the slates from felsic igneous rocks, formed in oceanic/continental arc settings. The investigated samples roughly display high positive εNd(t) values (mainly at +5.5 to +7.9, except one spot at +0.8), with corresponding Nd model ages at 672 Ma–522 Ma (except one at ∼1.1 Ga). Combined with the previous studies, we suggest that the turbidites in the NTAC were mainly derived from intermediate to felsic igneous rocks with juvenile arc signature, and thus the northern Chinese West Tianshan is a typical site with significant Phanerozoic crust growth.
Methionine (Met) can activate the mechanistic target of rapamycin (mTOR) to promote milk synthesis in mammary epithelial cells. However, it is largely unknown which G protein-coupled receptor can mediate the stimulation of Met on mTOR activation. In this study, we employed transcriptome sequencing to analyse which G protein-coupled receptors were associated with the role of Met and further used gene function study approaches to explore the role of G protein-coupled receptor 183 (GPR183) in Met stimulation on mTOR activation in HC11 cells. We identified nine G protein-coupled receptors including GPR183 whose expression levels were upregulated by Met treatment through RNA sequencing and subsequent quantitative real-time PCR analysis. Using GPR183 knockdown and overexpression technology, we demonstrate that GPR183 is a positive regulator of milk protein and fat synthesis and proliferation of HC11 cells. Met affected GPR183 expression in a dose-dependent manner, and GPR183 mediated the stimulation of Met (0·6 mM) on milk protein and fat synthesis, cell proliferation and mTOR phosphorylation and mRNA expression. The inhibition of phosphoinositide 3-kinase blocked the phosphorylation of mTOR and AKT stimulated by GPR183 activation. In summary, through RNA sequencing and gene function study, we uncover that GPR183 is a key mediator for Met to activate the phosphoinositide 3-kinase-mTOR signalling and milk synthesis in mouse mammary epithelial cells.
Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.
Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11 125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were −0·70 (–2·49, 1·09) for rarely drinks, −0·82 (–2·62, 0·97) for < 1 cup/week and −0·86 (–2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.
Dilatational motions in the shape of travelling wave packets have been identified recently to be dynamically significant in hypersonic turbulent boundary layers. The present study investigates the mechanisms of their generation and their association with the solenoidal motions, especially the well-recognized near-wall self-sustaining process of the regeneration cycle between the velocity streaks and quasi-streamwise vortices. By exploiting the direct numerical simulation databases and orchestrating numerical experiments, we explore systematically the near-wall flow dynamics in the processes of the formation and transient growth of low-speed streaks. We conclude via theoretical ansatz that the nonlinearity related to the parallel density and pressure gradients close to the wall due to the restriction of the isothermal boundary condition is the primary cause of the generation of the dilatational structures at small scales. In fully developed turbulence, the formation and the existence of healthy dilatational travelling wave packets require the participation of the turbulence at scales larger than those of the near-wall regeneration cycles, especially the occurrence of the bursting events that generate vortex clusters. This is proven by the less intensified dilatational motions in the numerical experiments in which the Orr mechanism is alleviated and the vortical structures and turbulent bursts are weakened.
Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.
Methods
We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.
Results
Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent–child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (β = −0.640, p = 0.005).
Conclusion
Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent–child reading in moderating the association between screen time and topological brain restructuring in early childhood.
Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.
Energy loss of protons with 90 and 100 keV energies penetrating through a hydrogen plasma target has been measured, where the electron density of the plasma is about 1016 cm−3 and the electron temperature is about 1-2 eV. It is found that the energy loss of protons in the plasma is obviously larger than that in cold gas and the experimental results based on the Bethe model calculations can be demonstrated by the variation of effective charge of protons in the hydrogen plasma. The effective charge remains 1 for 100 keV protons, while the value for 90 keV protons decreases to be about 0.92. Moreover, two empirical formulae are employed to extract the effective charge.
Fast neutron absorption spectroscopy is widely used in the study of nuclear structure and element analysis. However, due to the traditional neutron source pulse duration being of the order of nanoseconds, it is difficult to obtain a high-resolution absorption spectrum. Thus, we present a method of ultrahigh energy-resolution absorption spectroscopy via a high repetition rate, picosecond duration pulsed neutron source driven by a terawatt laser. The technology of single neutron count is used, which results in easily distinguishing the width of approximately 20 keV at 2 MeV and an asymmetric shape of the neutron absorption peak. The absorption spectroscopy based on a laser neutron source has one order of magnitude higher energy-resolution power than the state-of-the-art traditional neutron sources, which could be of benefit for precisely measuring nuclear structure data.
We show theoretically that the usual estimated investment strategies will not achieve the optimal Sharpe ratio when the dimensionality is high relative to sample size, and the $ 1/N $ rule is optimal in a 1-factor model with diversifiable risks as dimensionality increases, which explains why it is difficult to beat the $ 1/N $ rule in practice. We also explore conditions under which it can be beaten, and find that we can outperform it by combining it with the estimated rules when $ N $ is small, and by combining it with anomalies or machine learning portfolios, conditional on the profitability of the latter, when $ N $ is large.
In the present study, we investigate the compressibility effects in supersonic and hypersonic turbulent boundary layers under the influence of wall disturbances by exploiting direct numerical simulation databases at Mach numbers up to 6. Such wall disturbances enforce extra Reynolds shear stress on the wall and induce mean streamline curvature in rough wall turbulence that leads to the intensification of turbulent motions in the outer region. The turbulent and fluctuating Mach numbers, the density and the velocity divergence fluctuation intensities suggest that the compressibility effects are enhanced by the increment of the free-stream Mach number and the implementation of the wall disturbances. The differences between the Reynolds and Favre average due to the density fluctuations constitute approximately $9\,\%$ of the mean velocity close to the wall and $30\,\%$ of the Reynolds stress near the edge of the boundary layer, indicating their non-negligibility in turbulent modelling strategies. The comparatively strong compressive events behaving as eddy shocklets are observed at the free-stream Mach number of $6$ only in the cases with wall disturbances. By further splitting the velocity into the solenoidal and dilatational components with the Helmholtz decomposition, we found that the dilatational motions are organized as travelling wave packets in the wall-parallel planes close to the wall and as forward inclined structures in the form of radiated waves in the vertical planes. Despite their increased magnitudes and higher portion in the Reynolds normal and shear stresses, the dilatational motions show no tendency of contributing significantly to the skin friction and the production of turbulent kinetic energy due to their mitigation by the cross-correlation between the solenoidal and dilatational velocity components.
The age-related heterogeneity in major depressive disorder (MDD) has received significant attention. However, the neural mechanisms underlying such heterogeneity still need further investigation. This study aimed to explore the common and distinct functional brain abnormalities across different age groups of MDD patients from a large-sample, multicenter analysis.
Methods
The analyzed sample consisted of a total of 1238 individuals including 617 MDD patients (108 adolescents, 12–17 years old; 411 early-middle adults, 18–54 years old; and 98 late adults, > = 55 years old) and 621 demographically matched healthy controls (60 adolescents, 449 early-middle adults, and 112 late adults). MDD-related abnormalities in brain functional connectivity (FC) patterns were investigated in each age group separately and using the whole pooled sample, respectively.
Results
We found shared FC reductions among the sensorimotor, visual, and auditory networks across all three age groups of MDD patients. Furthermore, adolescent patients uniquely exhibited increased sensorimotor-subcortical FC; early-middle adult patients uniquely exhibited decreased visual-subcortical FC; and late adult patients uniquely exhibited wide FC reductions within the subcortical, default-mode, cingulo-opercular, and attention networks. Analysis of covariance models using the whole pooled sample further revealed: (1) significant main effects of age group on FCs within most brain networks, suggesting that they are decreased with aging; and (2) a significant age group × MDD diagnosis interaction on FC within the default-mode network, which may be reflective of an accelerated aging-related decline in default-mode FCs.
Conclusions
To summarize, these findings may deepen our understanding of the age-related biological and clinical heterogeneity in MDD.
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.
We aimed to investigate the association of metabolic obesity phenotypes with all-cause mortality risk in a rural Chinese population. This prospective cohort study enrolled 15 704 Chinese adults (38·86 % men) with a median age of 51·00 (interquartile range: 41·00–60·00) at baseline (2007–2008) and followed up during 2013–2014. Obesity was defined by waist circumference (WC: ≥ 90 cm for men and ≥ 80 cm for women) or waist-to-height ratio (WHtR: ≥ 0·5). The hazard ratio (HR) and 95 % CI for the risk of all-cause mortality related to metabolic obesity phenotypes were calculated using the Cox hazards regression model. During a median follow-up of 6·01 years, 864 deaths were identified. When obesity was defined by WC, the prevalence of participants with metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO) and metabolically unhealthy obesity (MUO) at baseline was 12·12 %, 2·80 %, 41·93 % and 43·15 %, respectively. After adjusting for age, sex, alcohol drinking, smoking, physical activity and education, the risk of all-cause mortality was higher with both MUNO (HR = 1·20, 95 % CI 1·14, 1·26) and MUO (HR = 1·20, 95 % CI 1·13, 1·27) v. MHNO, but the risk was not statistically significant with MHO (HR = 0·99, 95 % CI 0·89, 1·10). This result remained consistent when stratified by sex. Defining obesity by WHtR gave similar results. MHO does not suggest a greater risk of all-cause mortality compared to MHNO, but participants with metabolic abnormality, with or without obesity, have a higher risk of all-cause mortality. These results should be cautiously interpreted as the representation of MHO is small.