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In this paper, on–off switching digitization of a W-band variable gain power amplifier (VGPA) with above 60 dB dynamic range is introduced for large-scale phased array. Digitization techniques of on–off switching modified stacking transistors with partition are proposed to optimize configuration of control sub-cells. By the proposed techniques, gain control of a radio frequency variable gain amplifier (VGA) could be highly customized for both coarse and fine switching requirements instead of using additional digital-to-analog converters to tune the overall amplifier bias. The designed VGA in 130 nm SiGe has achieved switchable gain range from −46.4 to 20.6 dB and power range from −25.0 to 15.7 dBm at W band. The chip size of the fabricated VGPA is about 0.31 mm × 0.1 mm.
This paper proposes an online robust self-learning terminal sliding mode control (RS-TSMC) with stability guarantee for balancing control of reaction wheel bicycle robots (RWBR) under model uncertainties and disturbances, which improves the balancing control performance of RWBR by optimising the constrained output of TSMC. The TSMC is designed for a second-order mathematical model of RWBR. Then robust adaptive dynamic programming based on an actor-critic algorithm is used to optimise the TSMC only by data sampled online. The system closed-loop stability and convergence of the neural network weights are guaranteed based on the Lyapunov analysis. The effectiveness of the proposed algorithm is demonstrated through simulations and experiments.
Our study aimed to develop and validate a nomogram to assess talaromycosis risk in hospitalized HIV-positive patients. Prediction models were built using data from a multicentre retrospective cohort study in China. On the basis of the inclusion and exclusion criteria, we collected data from 1564 hospitalized HIV-positive patients in four hospitals from 2010 to 2019. Inpatients were randomly assigned to the training or validation group at a 7:3 ratio. To identify the potential risk factors for talaromycosis in HIV-infected patients, univariate and multivariate logistic regression analyses were conducted. Through multivariate logistic regression, we determined ten variables that were independent risk factors for talaromycosis in HIV-infected individuals. A nomogram was developed following the findings of the multivariate logistic regression analysis. For user convenience, a web-based nomogram calculator was also created. The nomogram demonstrated excellent discrimination in both the training and validation groups [area under the ROC curve (AUC) = 0.883 vs. 0.889] and good calibration. The results of the clinical impact curve (CIC) analysis and decision curve analysis (DCA) confirmed the clinical utility of the model. Clinicians will benefit from this simple, practical, and quantitative strategy to predict talaromycosis risk in HIV-infected patients and can implement appropriate interventions accordingly.
Imitation from Observation (IfO) prompts the robot to imitate tasks from unlabeled videos via reinforcement learning (RL). The performance of the IfO algorithm depends on its ability to extract task-relevant representations since images are informative. Existing IfO algorithms extract image representations by using a simple encoding network or pre-trained network. Due to the lack of action labels, it is challenging to design a supervised task-relevant proxy task to train the simple encoding network. Representations extracted by a pre-trained network such as Resnet are often task-irrelevant. In this article, we propose a new approach for robot IfO via multimodal observations. Different modalities describe the same information from different sides, which can be used to design an unsupervised proxy task. Our approach contains two modules: the unsupervised cross-modal representation (UCMR) module and a self-behavioral cloning (self-BC)-based RL module. The UCMR module learns to extract task-relevant representations via a multimodal unsupervised proxy task. The Self-BC for further offline policy optimization collects successful experiences during the RL training. We evaluate our approach on the real robot pouring water task, quantitative pouring task, and pouring sand task. The robot achieves state-of-the-art performance.
Studies on obesity and risk factors from a life-course perspective among residents in the Tibet Plateau with recent economic growth and increasing obesity are important and urgently needed. The birth cohort in this area provides a unique opportunity to examine the association between maternal dietary practice and neonatal obesity. The study aims to detect the prevalence of obesity among neonates, associated with maternal diet and other factors, supporting life-course strategies for obesity control. A cohort of pregnant women was enrolled in Tibet Plateau and followed till childbirth. Dietary practice during pregnancy was assessed using the Chinese FFQ – Tibet Plateau version, food items and other variables were associated with the risk for obesity of neonates followed by logistic regression, classification and regression trees (CART) and random forest. Of the total 1226 mother–neonate pairs, 40·5 % were Tibetan and 5·4 % of neonates with obesity. Consuming fruits as a protective factor for obesity of neonates with OR (95 % CI) = 0·61 (0·43, 0·87) from logistic regression; as well as OR = 0·20 (0·12, 0·35) for consuming fruits (≥ weekly) from CART. Removing fruit consumption to avoid overshadowing effects of other factors, the following were influential from CART: maternal education (more than middle school, OR = 0·22 (0·13, 0·37)) and consumption of Tibetan food (daily, OR = 3·44 (2·08, 5·69). Obesity among neonates is prevalent in the study population. Promoting healthy diets during pregnancy and strengthening maternal education should be part of the life-course strategies for obesity control.
Traditional therapies are crucial in maintaining and improving human well-being. China’s healthcare policymakers are attempting to use health technology assessment (HTA) as a decision-making supportive tool. The value assessment framework for Chinese patent medicine (CPM) has been developed and is being adopted and validated widely by research institutions. Subsequently, the healthcare decision-makers particularly hanker for the value framework of traditional non-pharmacological therapies.
Methods
To construct a practical value framework for traditional non-pharmacological therapies, a scoping review methodology was adopted to identify the evaluation domains and obstacles. A search, screening, and analysis process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Evidence was retrieved from scientific databases and HTA agencies’ websites.
Results
The search strategy identified 5 guidelines records and 17 acupuncture HTA reports. By synthesizing the valuable reports of CPM and acupuncture evaluation in representative countries, this study found that Mainland China was promoting the comprehensive value assessment of CPM, whereas the United Kingdom, Singapore, Canada, the United States, and Malaysia had carried out the HTA evaluation of acupuncture for various conditions among which chronic pain was the most common. UK and Singapore applied the HTA results to support acupuncture reimbursement decisions. Three domains, including safety, effectiveness, and economy, were commonly adopted. The identified biggest challenge of evaluating traditional non-pharmacological therapies is the scarce high-quality clinical evidence.
Conclusions
This study identified value domains and issues of traditional therapies, and pointed out future research implications, to promote the development value framework of traditional therapies.
Direct numerical simulations are performed to explore the effects of the rotating direction of the vertically asymmetric rough wall on the transport properties of Taylor–Couette (TC) flow, up to a Taylor number of ${Ta} = 2.39\times 10^{7}$. It is shown that, compared with the smooth wall, the rough wall with vertical asymmetric strips can enhance the dimensionless torque ${Nu}_{\omega }$. More importantly, at high Ta, clockwise rotation of the inner rough wall (where the fluid is sheared by the steeper slope side of the strips) results in a significantly greater torque enhancement compared to counter-clockwise rotation (where the fluid is sheared by the smaller slope side of the strips), due to the larger convective contribution to the angular velocity flux. However, the rotating direction has a negligible effect on the torque at low Ta. The larger torque enhancement caused by the clockwise rotation of the vertically asymmetric rough wall at high Ta is then explained by the stronger coupling between the rough wall and the bulk, attributed to the larger biased azimuthal velocity towards the rough wall at the mid-gap of the TC system, the increased turbulence intensity manifested by larger Reynolds stress and a thinner boundary layer, and the more significant contribution of the pressure force on the surface of the rough wall to the torque.
A wideband tunable balanced phase shifter is achieved by utilizing varactor-loaded coupled lines (VLCLs)-embedded multistage branch-line structure. The tunable phase shift with low in-band phase deviation is attributed to the regulation in phase shift of the VLCLs and the horizontal microstrip lines in series. The wideband differential-mode (DM) impedance matching and common-mode (CM) suppression are due to multiple DM transmission poles and CM transmission zeros, which are brought about by the cascade of VLCLs and a microstrip line with short-circuited stubs in the DM-equivalent circuit and open-circuited stubs in the CM-equivalent circuit, respectively. Compared with the state-of-the-art tunable balanced phase shifters, the proposed design not only has the advantages of wide operating bandwidth (BW) with low in-band phase deviation but also has low insertion loss and easily fabricated structure. Theoretical analysis and design procedure were conducted, resulting in a prototype covering the frequency of 1.8 GHz. This prototype offers a tunable phase shift capability ranging from 0° to 90°. The prototype exhibits an operating BW of 45%, with a maximum phase deviation of ±6°. It also achieves a 10 dB DM return loss and CM suppression, while maintaining a maximum insertion loss of 2.5 dB.
The relationship between magmatism and gold mineralization has been a topic of interest in understanding the formation of ore deposits. The Baizhangzi gold deposit, located in the northern margin of the North China Craton, is hosted by the Baizhangzi granite (BZG) and provides a case to evaluate the relation between granite and gold mineralization in Late Triassic. In this study, we present petrography, bulk geochemistry, zircon U-Pb isotope and trace elements data, as well as major elements of biotite and plagioclase for the BZG to evaluate the petrogenesis and link with gold mineralization. The BZG comprises biotite monzogranite, biotite-bearing monzogranite and monzogranite (BZGs). Zircon U-Pb geochronology shows that all the granitoids of BZGs were coeval with a formation age of 232 Ma. The granitoids, with high SiO2, Al2O3 and Sr, while low Y and Yb, show adakitic affinity. They are enriched in LILFs (e.g., Rb, Ba, Th, U and Sr) and LREEs, while depletion in HFSEs (e.g., Nb, Ta, P and Ti). The geochemical and mineral chemical data suggest that the granitoids have experienced the fractional crystallization of biotite + plagioclase + K- feldspar + apatite. Crystallization temperature is estimated as ca. 700°C, and pressure is between 0.71 kbar and 1.60 kbar. The monzogranite shows higher values of logfO2, △FMQ and △NNO than the biotite-bearing monzogranite, ranging from −19.76 to −11.71, −4.93 to +3.67 and −5.48 to +3.11, respectively. The fractional crystallization, together with high fO2, K-metasomatism and low evolution degree, provided favourable conditions for gold mineralization.
OBJECTIVES/GOALS: Determine if the Conserved Transcriptional Response to Adversity transcriptomic profile established in primary blood mononuclear cells (PBMC) of chronically stress caregivers, is present in individuals with early Alzheimer’s disease. Chronic stress is a risk factor for Alzheimer’s, and may be an untapped biomarker for disease risk and pathology. METHODS/STUDY POPULATION: To collect preliminary data on the Conserved Transcriptional Response to Adversity profile in individuals with Alzheimer’s disease, we were able to utilize primary blood mononuclear cell samples from a small open label pilot study called Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease, designed to clear stressed senescent cells. We hypothesized senolytics may beneficially reverse this stress profile. We developed a NanoString assay (measuring 19 inflammatory, 31 type-1 interferon, and 3 antibody synthesis genes) to compare these transcriptomic changes within 4 individuals measured at baseline, post-treatment with an intermittent 12-week senolytic therapy, and at an optional extended post-treatment follow-up time point > 3 months after their post treatment visit. RESULTS/ANTICIPATED RESULTS: There was relative downregulation of expression in transcription in 7 of 19 measured inflammatory genes (FOS, PTGS2, IL8, FOS, Il1b, JUNB, and JUN) in Alzheimer’s disease participants after receiving senolytic treatment (baseline vs. post-treatment). This is consistent with a decrease in the inflammatory arm of the Conserved Transcriptional Response to Adversity profile. These differences were not significant between baseline and the extended follow-up, indicative of a transient effect of senolytic. There were no changes in type 1 interferon or antibody synthesis genes. This data provides preliminary evidence for larger controlled studies to further establish this profile in Alzheimer’s disease, providing exciting evidence for transcript changes that may be reproducible with senolytic therapy. DISCUSSION/SIGNIFICANCE: Literature relevant to Alzheimer’s disease indicates global increases in inflammation paired with deficits in immune response, capturing some genes associated with the Conserved Transcriptional Response to Adversity. This profile may be a useful biomarker for prediction of disease severity or risk of dementia due to chronic stress.
Exploiting two quasi-natural experiments, we find that firms increase emissions of toxic pollution following decreases in analyst coverage. The effects are stronger for firms with low initial analyst coverage, poor corporate governance, and firms subject to less stringent monitoring by environmental regulators. Decreases in environmental-related questions raised in conference calls, an increased cost of monitoring to institutional shareholders, reductions in pollution abatement investment, and the weakening of internal governance related to environmental performance are channels through which reduced analyst coverage contributes to increases in firm pollution. Our study highlights the monitoring role analysts play in shaping corporate environmental policies.
Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD).
Methods
In this case–control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities.
Results
In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC.
Conclusions
The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.
Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.
Prolonged parturition duration has been widely demonstrated to be a risk factor for incidence of stillbirth. This study evaluated the supply of dietary fibre on the parturition duration, gut microbiota and metabolome using sows as a model. A total of 40 Yorkshire sows were randomly given diet containing normal level of dietary fibre (NDF, 17·5 % dietary fibre) or high level of dietary fibre (HDF, 33·5 % dietary fibre). Faecal microbiota profiled with 16S rRNA amplicon sequencing, SCFA and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results showed that HDF diet significantly improved the parturition process as presented by the shorter parturition duration. HDF diet increased the abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFA levels in the faeces and plasma of sows at parturition were elevated in HDF group. The abundances of fifteen and twelve metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in energy metabolism and bacterial metabolism. Correlation analysis also showed associations between specific bacteria taxa and metabolites. Collectively, our study indicates that the improvement of parturition duration by high fibre intake in late gestation is associated with gut microbiota, production of SCFA and other metabolites, potentially serving for energy metabolism.
Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear.
Aims
To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age.
Method
The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed.
Results
The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014).
Conclusions
The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.
Primitive lamprophyres in orogenic belts can provide crucial insights into the nature of the subcontinental lithosphere and the relevant deep crust–mantle interactions. This paper reports a suite of relatively primitive lamprophyre dykes from the North Qiangtang, central Tibetan Plateau. Zircon U–Pb ages of the lamprophyre dykes range from 214 Ma to 218 Ma, with a weighted mean age of 216 ± 1 Ma. Most of the lamprophyre samples are similar in geochemical compositions to typical primitive magmas (e.g. high MgO contents, Mg no. values and Cr, with low FeOt/MgO ratios), although they might have experienced a slightly low degree of olivine crystallization, and they show arc-like trace-element patterns and enriched Sr–Nd isotopic composition ((87Sr/86Sr)i = 0.70538–0.70540, ϵNd(t) = −2.96 to −1.65). Those geochemical and isotopic variations indicate that the lamprophyre dykes originated from partial melting of a phlogopite- and spinel-bearing peridotite mantle modified by subduction-related aqueous fluids. Combining with the other regional studies, we propose that slab subduction might have occurred during Late Triassic time, and the rollback of the oceanic lithosphere induced the lamprophyre magmatism in the central Tibetan Plateau.
The article aims to estimate and forecast the transmissibility of shigellosis and explore the association of meteorological factors with shigellosis. The mathematical model named Susceptible–Exposed–Symptomatic/Asymptomatic–Recovered–Water/Food (SEIARW) was used to explore the feature of shigellosis transmission based on the data of Wuhan City, China, from 2005 to 2017. The study applied effective reproduction number (Reff) to estimate the transmissibility. Daily meteorological data from 2008 to 2017 were used to determine Spearman's correlation with reported new cases and Reff. The SEIARW model fit the data well (χ2 = 0.00046, p > 0.999). The simulation results showed that the reservoir-to-person transmission of the shigellosis route has been interrupted. The Reff would be reduced to a transmission threshold of 1.00 (95% confidence interval (CI) 0.82–1.19) in 2035. Reducing the infectious period to 11.25 days would also decrease the value of Reff to 0.99. There was a significant correlation between new cases of shigellosis and atmospheric pressure, temperature, wind speed and sun hours per day. The correlation coefficients, although statistically significant, were very low (<0.3). In Wuhan, China, the main transmission pattern of shigellosis is person-to-person. Meteorological factors, especially daily atmospheric pressure and temperature, may influence the epidemic of shigellosis.
As the corona virus disease 2019 (COVID-19) pandemic continues around the world, understanding the transmission characteristics of COVID-19 is vital for prevention and control. We conducted the first study aiming to estimate and compare the relative risk of secondary attack rates (SARs) of COVID-19 in different contact environments. Until 26 July 2021, epidemiological studies and cluster epidemic reports of COVID-19 were retrieved from SCI, Embase, PubMed, CNKI, Wanfang and CBM in English and Chinese, respectively. Relative risks (RRs) were estimated in pairwise comparisons of SARs between different contact environments using the frequentist NMA framework, and the ranking of risks in these environments was calculated using the surface under the cumulative ranking curve (SUCRA). Subgroup analysis was performed by regions. Thirty-two studies with 68 260 participants were identified. Compared with meal or gathering, transportation (RR 10.55, 95% confidence interval (CI) 1.43–77.85), medical care (RR 11.68, 95% CI 1.58–86.61) and work or study places (RR 10.15, 95% CI 1.40–73.38) had lower risk ratios for SARs. Overall, the SUCRA rankings from the highest to the lowest were household (95.3%), meal or gathering (81.4%), public places (58.9%), daily conversation (50.1%), transportation (30.8%), medical care (18.2%) and work or study places (15.3%). Household SARs were significantly higher than other environments in the subgroup of mainland China and sensitive analysis without small sample studies (<100). In light of the risks, stratified personal protection and public health measures need to be in place accordingly, so as close contacts categorising and management.
The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15 066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.
Chapters 5 and 6 focus on generation and memory in group interactions. In Chapter 5, I describe different patterns of group memory – including “socialist nostalgia,” “rightful resistance,” and “people but not the event” – which are manifested in narratives, symbols, rituals, speech norms, and other practices. I explain those patterns by examining the interaction between memory entrepreneurs’ class positions and habitus and their group processes.