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The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.
Methods
We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.
Results
Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.
Conclusions
Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.
The phenomenon of bulge evolution under the action of gravity on shallow water is prevalent both in natural occurrences and engineering industries. However, despite its ubiquity, its physical process remains largely unexplored. The evolution of bulge contains two fundamental physical processes: collapse and propagation. The collapse process can be further divided into two sub-processes: squeezing process and diffusion process. Based on the weakly nonlinear shallow water assumption with the classical perturbation method, the governing equations controlling the surface elevations in the diffusion process and the propagation process have been theoretically derived, where a bulge-induced surface pressure is modeled for the propagation process. Moreover, their scaling laws for the decay of wave height are also established, which have been validated by direct numerical simulation results. The derived scaling laws for wave height attenuation of bulge evolution provide profound insights, which hold the potential to applications in the engineering industry.
A generalised multiparameter model for linear modal stability and sensitivity analysis is developed. The stability and sensitivity equations are derived from a generalised vector-form governing equation comprised of multiple dimensionless parameters that represent different physical forces affecting the system’s stability. By introducing adjoint variables and constructing the Lagrangian identity, a differential relationship between the eigenvalue of the perturbation mode and dimensionless parameters is determined and defined as the global sensitivity gradient. It provides the constraint that must be satisfied for changes in different dimensionless parameters along the isoeigenvalue curve, which aids in the fast computation of the neutral curve. Moreover, the global sensitivity gradient can directly and intuitively evaluate the competitive relationship among the influences of various parameters on system instability. Based on the global sensitivity gradient, an optimal stability control strategy for transitioning from an unstable state to a stable state is discussed. Additionally, the relative sensitivity function is also introduced to investigate the influence of relative parameter variations on instability. To demonstrate the effectiveness of this method, three applications are presented: two-dimensional flow around a circular cylinder with a single dimensionless parameter Re; three-dimensional axisymmetric magnetohydrodynamic (MHD) flow around a sphere with two parameters Re and $N$; and two-dimensional MHD mixed convection with three parameters Re, ${\textit{Gr}}$ and $\textit{Ha}$.
Working memory deficit, a key feature of schizophrenia, is a heritable trait shared with unaffected siblings. It can be attributed to dysregulation in transitions from one brain state to another.
Aims
Using network control theory, we evaluate if defective brain state transitions underlie working memory deficits in schizophrenia.
Method
We examined average and modal controllability of the brain's functional connectome in 161 patients with schizophrenia, 37 unaffected siblings and 96 healthy controls during a two-back task. We use one-way analysis of variance to detect the regions with group differences, and correlated aberrant controllability to task performance and clinical characteristics. Regions affected in both unaffected siblings and patients were selected for gene and functional annotation analysis.
Results
Both average and modal controllability during the two-back task are reduced in patients compared to healthy controls and siblings, indicating a disruption in both proximal and distal state transitions. Among patients, reduced average controllability was prominent in auditory, visual and sensorimotor networks. Reduced modal controllability was prominent in default mode, frontoparietal and salience networks. Lower modal controllability in the affected networks correlated with worse task performance and higher antipsychotic dose in schizophrenia (uncorrected). Both siblings and patients had reduced average controllability in the paracentral lobule and Rolandic operculum. Subsequent out-of-sample gene analysis revealed that these two regions had preferential expression of genes relevant to bioenergetic pathways (calmodulin binding and insulin secretion).
Conclusions
Aberrant control of brain state transitions during task execution marks working memory deficits in patients and their siblings.
Major psychiatric disorders (MPDs) are delineated by distinct clinical features. However, overlapping symptoms and transdiagnostic effectiveness of medications have challenged the traditional diagnostic categorisation. We investigate if there are shared and illness-specific disruptions in the regional functional efficiency (RFE) of the brain across these disorders.
Methods
We included 364 participants (118 schizophrenia [SCZ], 80 bipolar disorder [BD], 91 major depressive disorder [MDD], and 75 healthy controls [HCs]). Resting-state fMRI was used to caclulate the RFE based on the static amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality and corresponding dynamic measures indicating variability over time. We used principal component analysis to obtain static and dynamic RFE values. We conducted functional and genetic annotation and enrichment analysis based on abnormal RFE profiles.
Results
SCZ showed higher static RFE in the cortico-striatal regions and excessive variability in the cortico-limbic regions. SCZ and MDD shared lower static RFE with higher dynamic RFE in sensorimotor regions than BD and HCs. We observed association between static RFE abnormalities with reward and sensorimotor functions and dynamic RFE abnormalities with sensorimotor functions. Differential spatial expression of genes related to glutamatergic synapse and calcium/cAMP signaling was more likely in the regions with aberrant RFE.
Conclusions
SCZ shares more regions with disrupted functional integrity, especially in sensorimotor regions, with MDD rather than BD. The neural patterns of these transdiagnostic changes appear to be potentially driven by gene expression variations relating to glutamatergic synapses and calcium/cAMP signaling. The aberrant sensorimotor, cortico-striatal, and cortico-limbic integrity may collectively underlie neurobiological mechanisms of MPDs.
Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.
The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.
The global linear stability analysis for the magnetohydrodynamic liquid metal flow past an insulated sphere subjected to a constant streamwise magnetic field is investigated in the range of the Reynolds number $Re\leq 400$ and the interaction number $N\leq 40$ coupled with direct numerical simulations, where $N$ stands for strength of the electromagnetic force. The stability of the steady axisymmetric base flow to independent time-azimuthal modes is discussed. Five critical curves associated with various wake transitions are obtained in the $\{Re, N\}$ phase diagram. These critical curves reveal the stabilising effect of a weak magnetic field, the destabilising effect of a strong magnetic field and re-stabilising effect of a much stronger magnetic field. To explore the impact of the magnetic field on flow instability, a sensitivity analysis utilizing an adjoint method is performed for the first regular bifurcation. Sensitivity functions of growth rate to base-flow modifications and Lorentz force are defined to identify the region that has the most significant influence on flow instability, such as the recirculation region responsible for the stabilising effect at a weak magnetic field and the shear layer region responsible for the destabilising effect at a strong magnetic field. Furthermore, a competition between the stabilising and shear destabilising effects of the magnetic field is discussed. This analysis provides valuable insights into the non-monotonic effect of the magnetic field on flow instability.
A new approach to target development for laboratory astrophysics experiments at high-power laser facilities is presented. With the dawn of high-power lasers, laboratory astrophysics has emerged as a field, bringing insight into physical processes in astrophysical objects, such as the formation of stars. An important factor for success in these experiments is targetry. To date, targets have mainly relied on expensive and challenging microfabrication methods. The design presented incorporates replaceable machined parts that assemble into a structure that defines the experimental geometry. This can make targets cheaper and faster to manufacture, while maintaining robustness and reproducibility. The platform is intended for experiments on plasma flows, but it is flexible and may be adapted to the constraints of other experimental setups. Examples of targets used in experimental campaigns are shown, including a design for insertion in a high magnetic field coil. Experimental results are included, demonstrating the performance of the targets.
The quantum defect (QD) is an important issue that demands prompt attention in high-power fiber lasers. A large QD may aggravate the thermal load in the laser, which would impact the frequency, amplitude noise and mode stability, and threaten the security of the high-power laser system. Here, we propose and demonstrate a cladding-pumped Raman fiber laser (RFL) with QD of less than 1%. Using the Raman gain of the boson peak in a phosphorus-doped fiber to enable the cladding pump, the QD is reduced to as low as 0.78% with a 23.7 W output power. To our knowledge, this is the lowest QD ever reported in a cladding-pumped RFL. Furthermore, the output power can be scaled to 47.7 W with a QD of 1.29%. This work not only offers a preliminary platform for the realization of high-power low-QD fiber lasers, but also proves the great potential of low-QD fiber lasers in power scaling.
The relationship between SFA consumption and the risk of overweight/obesity remains unclear. Epidemiological evidence is lacking among Chinese population. This study aimed to investigate the association between individual dietary SFA intake and the risk of overweight/obesity in Chinese adults. Data from 8465 adults with BMI < 24 kg/m2 at entry in the China Health and Nutrition Survey (1989–2011) were analysed. Three-day 24-h dietary records were used to collect dietary data. Cox proportional hazards regression models were constructed to estimate hazard ratios (HR) and 95 % CI for the risk of developing overweight or obesity. A total of 3171 incident cases of overweight/obesity were identified (1649 for women and 1522 for men) during a median of 11 years of follow-up. Compared with the lowest category, the intake of total SFA (TSFA) showed no significant association with the risk of overweight/obesity. However, an increased risk of overweight/obesity was observed with a higher intake of medium chain SFA (MCSFA) (Ptrend = 0·004), especially decanoic acid (10:0) (HR was 1·25 (95 % CI 1·10, 1·42) comparing the highest category with the reference group; Ptrend < 0·001), whereas an inverse relationship was observed for hexanoic acid (6:0) consumption; compared with non-consumers, 6:0 intake was associated with 32 % lower risk of overweight/obesity (HR: 0·68 (95 % CI 0·56, 0·84); Ptrend < 0·001). Overall, the intake of subtypes of MCSFA but not TSFA was associated with the risk of overweight/obesity. Increasing hexanoic acid (6:0) and limiting decanoic acid (10:0) consumption may be protective for overweight/obesity among Chinese population.
Multi-device radio frequency power amplifiers (PAs) often exhibit strongly non-linear behavior in combination with long-term memory effects, leading to an extremely challenging model development cycle. This paper presents a new, dynamic, behavioral modeling technique, based on a combination of the real-valued decomposed piecewise method and concepts from the field of machine learning. The underlying theory of the proposed modeling technique is provided, along with a detailed modeling procedure. Experimental results show that the proposed decomposed piecewise support vector regression (SVR) model leads to significant performance improvements when compared with standard SVR models for both single transistor and multi-transistor PAs. Different model thresholds are used to test the proposed model performance for both PA types. For the single-transistor PA, modeled using only one partition, an approximately 10 dB normalized mean square error (NMSE) reduction is seen when compared with the standard SVR model. For the same PA, when utilizing two partitions, the reduction improves to 14 dB. When applied to a multi-device Doherty PA, the NMSE between model and measurement data is −50 dB, representing more than 10 dB improvement compared with the standard SVR model.
Drug use disorders are an important issue worldwide. Systematic attempts to estimate the global incidence of drug use disorders are rare. We aimed to determine the incidence of drug use disorders and their trends.
Methods
We obtained the annual incident cases and age-standardised incidence rate (ASR) of drug use disorders from 1990 to 2017 using the Global Health Data Exchange query tool. The estimated annual percentage changes of the ASR were used to quantify and evaluate the trends in the incidence rate. Gaussian process regression and the Pearson's correlation coefficient were used to assess the relationship between the ASR and socio-demographic index (SDI).
Results
The number of drug use disorders’ cases increased by 33.5% from 1990 to 2017 globally, whereas the ASR exhibited a stable trend. The ASR was higher in men than in women. Most cases (53.1%) of drug use disorders involved opioid. A positive association (ρ=0.35, p < 0.001) was found between ASR and SDI. Teenagers aged 15–19 years had the highest incidence rate.
Conclusions
The incident cases of drug use disorders were increasing, but the incidence rate did not change significantly from 1990 to 2017. Current preventive measures and policies for drug use disorders might have little effect. The present results suggest that future strategies should focus on men, teenagers and high-risk regions in order to improve the current status of drug use disorders.
We document the central role of collateral in the pricing of tri-party repos. Markets are competitive for repos with safe collateral but are severely segmented for repos with risky collateral, such as equities and low-grade corporate bonds. Fund families are the sole contributors to the segmentation, and collateral concentration is the main determinant in the substantial variation in repo pricing, both across and within segments. The segmented structure points to Fidelity as a systemically important player and the markets potential fragility. Facing market segmentation, dealers optimize financing costs by allocating their collateral across fund families.
In December 2019, a new type of coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared in Wuhan, China. Serious outbreaks of coronavirus disease 2019 (COVID-19), related to the SARS-CoV-2 virus, have occurred throughout China and the world. Therefore, we intend to shed light on its potential clinical and epidemiological characteristics.
Methods:
In this retrospective study, we included 50 confirmed fatal cases of SARS-CoV-2 reported on Chinese official media networks from January 16, 2020, to February 5, 2020. All the cases were confirmed by local qualified medical and health institutions. Specific information has been released through official channels. According to the contents of the reports, we recorded in detail the gender, age, first symptom date, death date, primary symptoms, chronic fundamental diseases, and other data of the patients, and carried out analyses and discussion.
Results:
In total, 50 fatal cases were reported: median age was 70 y old, and males were 2.33 times more likely to die than females. The median number of days from the first symptom to death was 13, and that length of time tended to be shorter among people aged 65 and older compared with those younger than 65 (12 days vs 17 days; P = 0.046). Therefore, the older patients had fewer number of days from the first symptom to death (r = -0.40; P = 0.012).
Conclusions:
In our study, we found that most of the deaths were elderly men with chronic fundamental diseases, and their COVID-19 progression to death time was shorter. At the same time, we demonstrated that older men are more likely to become infected with COVID-19, and the risk of death is positively correlated with age.
The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.
Iodine intake and excretion vary widely; however, these variations remain a large source of geometric uncertainty. The present study aims to analyse variations in iodine intake and excretion and provide implications for sampling in studies of individuals or populations. Twenty-four healthy women volunteers were recruited for a 12-d sampling period during the 4-week experiment. The duplicate-portion technique was used to measure iodine intake, while 24-h urine was collected to estimate iodine excretion. The mean intra-individual variations in iodine intake, 24-h UIE (24-h urinary iodine excretion) and 24-h UIC (24-h urinary iodine concentration) were 63, 48 and 55 %, respectively, while the inter-individual variations for these parameters were 14, 24 and 32 %, respectively. For 95 % confidence, approximately 500 diet samples or 24-h urine samples should be taken from an individual to estimate their iodine intake or iodine status at a precision range of ±5%. Obtaining a precision range of ±5% in a population would require twenty-five diet samples or 150 24-h urine samples. The intra-individual variations in iodine intake and excretion were higher than the inter-individual variations, which indicates the need for more samples in a study on individual participants.
Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals’ 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01–0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals’ long-term exposures.