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The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.
We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers (
kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.
In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI.
We conducted a prospective cohort study of inpatients aged 2–17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available.
We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL (P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL (P < .001).
Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.
The effect of sheared E × B flow on the blob dynamics in the scrape-off layer (SOL) of HL-2A tokamak has been studied during the plasma current ramp-up in ohmically heated deuterium plasmas by the combination of poloidal and radial Langmuir probe arrays. The experimental results indicate that the SOL sheared E × B flow is substantially enhanced as the plasma current exceeds a certain value and the strong sheared E × B flow has the ability to slow the blob radial motion via stretching its poloidal correlation length. The locally accumulated blobs are suggested to be responsible for the increase of plasma density just outside the Last Closed Flux Surface (LCFS) observed in this experiment. The results presented here reveal the significant role played by the strong sheared E × B flow on the blob dynamics, which provides a potential method to control the SOL width by modifying the sheared E × B flow in future tokamak plasmas.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
The high-altitude landscape of western Tibet is one of the most extreme environments in which humans have managed to introduce crop cultivation. To date, only sparse palaeoeconomic data have been reported from this region. The authors present archaeobotanical evidence from five sites (dating from the late first millennium BC and the early first millennium AD) located in the cold-arid landscape of western Tibet. The data indicate that barley was widely grown in this region by c. 400 BC but probably fulfilled differing roles within local ecological constraints on cultivation. Additionally, larger sites are characterised by more diverse crop assemblages than smaller sites, suggesting a role for social diversity in the development of high-altitude agriculture.
Accurate geometrical calibration between the scan coordinates and the camera coordinates is critical in four-dimensional scanning transmission electron microscopy (4D-STEM) for both quantitative imaging and ptychographic reconstructions. For atomic-resolved, in-focus 4D-STEM datasets, we propose a hybrid method incorporating two sub-routines, namely a J-matrix method and a Fourier method, which can calibrate the uniform affine transformation between the scan-camera coordinates using raw data, without a priori knowledge of the crystal structure of the specimen. The hybrid method is found robust against scan distortions and residual probe aberrations. It is also effective even when defects are present in the specimen, or the specimen becomes relatively thick. We will demonstrate that a successful geometrical calibration with the hybrid method will lead to a more reliable recovery of both the specimen and the electron probe in a ptychographic reconstruction. We will also show that, although the elimination of local scan position errors still requires an iterative approach, the rate of convergence can be improved, and the residual errors can be further reduced if the hybrid method can be firstly applied for initial calibration. The code is made available as a simple-to-use tool to correct affine transformations of the scan-camera coordinates in 4D-STEM experiments.
To evaluate hospital-level variation in using first-line antibiotics for Clostridioides difficile infection (CDI) based on the burden of laboratory-identified (LabID) CDI.
Using data on hospital-level LabID CDI events and antimicrobial use (AU) for CDI (oral/rectal vancomycin or fidaxomicin) submitted to the National Healthcare Safety Network in 2019, we assessed the association between hospital-level CDI prevalence (per 100 patient admissions) and rate of CDI AU (days of therapy per 1,000 days present) to generate a predicted value of AU based on CDI prevalence and CDI test type using negative binomial regression. The ratio of the observed to predicted AU was then used to identify hospitals with extreme discordance between CDI prevalence and CDI AU, defined as hospitals with a ratio outside of the intervigintile range.
Among 963 acute-care hospitals, rate of CDI prevalence demonstrated a positive dose–response relationship with rate of CDI AU. Compared with hospitals without extreme discordance (n = 902), hospitals with lower-than-expected CDI AU (n = 31) had, on average, fewer beds (median, 106 vs 208), shorter length of stay (median, 3.8 vs 4.2 days), and higher proportion of undergraduate or nonteaching medical school affiliation (48% vs 39%). Hospitals with higher-than-expected CDI AU (n = 30) were similar overall to hospitals without extreme discordance.
The prevalence rate of LabID CDI had a significant dose–response association with first-line antibiotics for treating CDI. We identified hospitals with extreme discordance between CDI prevalence and CDI AU, highlighting potential opportunities for data validation and improvements in diagnostic and treatment practices for CDI.
There is a paucity of evidence about the prevalence and risk factors for symptomatic infection among children. This study aimed to describe the prevalence of symptomatic coronavirus disease 2019 (COVID-19) and its risk factors in children and adolescents aged 0–18 years in Qatar. We conducted a cross-sectional study of all children aged 0–18 years diagnosed with COVID-19 using polymerase chain reaction in Qatar during the period 1st March to 31st July 2020. A generalised linear model with a binomial family and identity link was used to assess the association between selected factors and the prevalence of symptomatic infection. A total of 11 445 children with a median age of 8 years (interquartile range (IQR) 3–13 years) were included in this study. The prevalence of symptomatic COVID-19 was 36.6% (95% confidence interval (CI) 35.7–37.5), and it was similar between children aged <5 years (37.8%), 5–9 years (34.3%) and 10 + years (37.3%). The most frequently reported symptoms among the symptomatic group were fever (73.5%), cough (34.8%), headache (23.2%) and sore throat (23.2%). Fever (82.8%) was more common in symptomatic children aged <5 years, while cough (38.7%) was more prevalent in those aged 10 years or older, compared to other age groups. Variables associated with an increased risk of symptomatic infection were; contact with confirmed cases (RD 0.21; 95% CI 0.20–0.23; P = 0.001), having visited a health care facility (RD 0.54; 95% CI 0.45–0.62; P = 0.001), and children aged under 5 years (RD 0.05; 95% CI 0.02–0.07; P = 0.001) or aged 10 years or older (RD 0.04; 95% CI 0.02–0.06; P = 0.001). A third of the children with COVID-19 were symptomatic with a higher proportion of fever in very young children and a higher proportion of cough in those between 10 and 18 years of age.
Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.
Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).
We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.
Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
In recent years, men who have sex with men (MSM) constitute a major group of HIV transmission in China. High primary drug-resistance (PDR) rate in MSM also represents a serious challenge for the Chinese antiretroviral therapy (ART) program. To assess the efficiency of ART in controlling HIV/AIDS infection among MSM, we developed a compartmental model for the annually reported HIV/AIDS MSM from 2007 to 2019 in the Zhejiang Province of China. R0 was 2.3946 (95% CI (2.2961–2.4881)). We predict that 90% of diagnosed HIV/AIDS individuals will have received treatment till 2020, while the proportion of the diagnosed remains as low as 40%. Even when the proportion of the diagnosed reaches 90%, R0 is still larger than the level of AIDS epidemic elimination. ART can effectively control the spread of HIV, even in the presence of drug resistance. The 90-90-90 strategy alone may not eliminate the HIV epidemic in Chinese MSM. Behavioural and biologic interventions are the most effective interventions to control the HIV/AIDS epidemic among MSM.
An increasing number of studies have described the relationship between velo-cardio-facial syndrome (VCFS) and schizophrenia. in a family-based study, we found that rs10314, a single nucleotide polymorphism (SNP) present in the 3’-flanking region of the CLDN5 gene, was associated with schizophrenia among a Chinese population. High false positive rate is a common problem with the association study of human diseases. It is very important to replicate an initial finding with different samples and experimental designs.
A total of 749 patients with schizophrenia and 383 age and sex matched healthy control subjects in Chinese population were recruited. PCR-based RFLP protocol was applied to genotype rs10314 to see its disease association.
The χ2 goodness-of-fit test showed that the genotypic distributions of rs10314 were in Hardy-Weinberg equilibrium in both the patient group (χ2=1.12, P=0.289) and the control group (χ2=0.22, P=0.639). rs10314 was associated with schizophrenia with an odds ratio (OR) of 1.32 in the male subjects (χ2=5.45, P=0.02, 95% CI 1.05-1.67) but not in the female subjects (χ2=0.64, P=0.425, OR=1.14, 95% CI 0.83-1.57). the χ2 test showed a genotypic association only for combined samples (χ2=7.80, df=2, P=0.02). SNP rs10314 is a G to C base change. Frequency of the genotypes containing the C allele was significantly higher in the patient group than in the control group.
The present work shows that the CLDN5 gene polymorphism is more likely to be involved in schizophrenic men than women, suggesting that this gene may contribute to the gender differences in schizophrenia.
This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.
Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.
305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).
Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.
Increasing evidence indicates that major depressive disorder (MDD) is associated with cognitive as well as mood disturbances.
To evaluate cognitive function and white matter structure, resting-state brain function in first-episode, treatmentnaive patients with MDD.
To explore brain structure and function mechanisms of cognitive impairment in MDD.
46 Han Chinese MDD patients aged 18–45 year and 46 controls were assessed by a series of validated test procedures.Then, 30 patients and 30 controls were obtained by MRI scan.White matter abnormalities evaluated using diffusion tensor imaging (DTI) were analyzed using tract based spatial statistics (TBSS) and resting-state brain function was evaluated using regional homogeneity (ReHo) analysis.
Cognitive impairment in patients with MDD was demonstrated by reduced accuracy in the Wisconsin Card Sorting test (WSCT) and to a lesser extent the Continuous Performance test (CPT) and Trail Making tests (TMT). White matter abnormalities found in the left cerebellum, and resting-state abnormalities present in the left inferior parietal gyrus, left anterior cingulate nucleus and left hippocampal gyrus were associated with impaired performance in the WSCT and CPT tests. We also showed that poor WSCT performance was associated with increased interconnectivity between the left ventral anterior cingulate nucleus and the medial frontal lobe areas.
The present study indicates cognitive disturbances in patients with MDD are associated with white matter and resting-state changes and altered interconnections in specific brain areas.
In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation.
Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group.
11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1.
The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.
Cigarette smoking is strongly associated with major depressive disorder (MDD). However, any genetic etiology of such comorbidity and causal relations is poorly understood, especially at the genome-wide level.
In the present in silico research, we analyzed summary data from the genome-wide association study of the Psychiatric Genetic Consortium for MDD (n = 191 005) and UK Biobank for smoking (n = 337 030) by using various biostatistical methods including Bayesian colocalization analysis, LD score regression, variant effect size correlation analysis, and Mendelian randomization (MR).
By adopting a gene prioritization approach, we identified 43 genes shared by MDD and smoking, which were significantly enriched in membrane potential, gamma-aminobutyric acid receptor activity, and retrograde endocannabinoid signaling pathways, indicating that the comorbid mechanisms are involved in the neurotransmitter system. According to linkage disequilibrium score regression, we found a strong positive correlation between MDD and current smoking (rg = 0.365; p = 7.23 × 10−25) and a negative correlation between MDD and former smoking (rg = −0.298; p = 1.59 × 10−24). MR analysis suggested that genetic liability for depression increased smoking.
These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.