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Direct numerical simulation of the Navier–Stokes equations is carried out to investigate the interaction of a conical shock wave with a turbulent boundary layer developing over a flat plate at free-stream Mach number
and Reynolds number
, based on the upstream boundary layer momentum thickness. The shock is generated by a circular cone with half opening angle
. As found in experiments, the wall pressure exhibits a distinctive N-wave signature, with a sharp peak right past the precursor shock generated at the cone apex, followed by an extended zone with favourable pressure gradient, and terminated by the trailing shock associated with recompression in the wake of the cone. The boundary layer behaviour is strongly affected by the imposed pressure gradient. Streaks are suppressed in adverse pressure gradient (APG) zones, but re-form rapidly in downstream favourable pressure gradient (FPG) zones. Three-dimensional mean flow separation is only observed in the first APG region associated with the formation of a horseshoe vortex, whereas the second APG region features an incipient detachment state, with scattered spots of instantaneous reversed flow. As found in canonical geometrically two-dimensional wedge-generated shock–boundary layer interactions, different amplification of the turbulent stress components is observed through the interacting shock system, with approach to an isotropic state in APG regions, and to a two-component anisotropic state in FPG. The general adequacy of the Boussinesq hypothesis is found to predict the spatial organization of the turbulent shear stresses, although different eddy viscosities should be used for each component, as in tensor eddy-viscosity models, or in full Reynolds stress closures.
In this contribution, we devoted ourselves to fabricating aggregation-induced emission (AIE) activity copolymers via one-pot combination of RAFT polymerization and Biginelli reaction for the first time. When the feeding ratio of TPB was 33.5%, the molar fraction of TPB was, respectively, about 14.2 and 22.5% in PEG-PTE1 copolymers by two-step strategy and PEG-PTE2 copolymers by one-pot strategy with the similar structure. The Mn of PEG-PTE1 increased to 59,300 from 52,800 of PEG-AE presoma with narrow PDI, which was more than Mn of PEG-PTE2 with 52,300. As compared with PEG-PTE2, when the feeding ratio of TPB was 48.6%, the molar fraction of TPB increased to 32.6% in PEG-PTE3. In aqueous solution, the as-obtained PEG-PTE2 copolymers can self-assemble into fluorescent organic nanoparticles (FONs) with 100–180 nm spherical morphology, the maximal emission peak of which presented at 460 nm with the obvious AIE phenomenon. Moreover, due to the low toxicity and excellent cell dyeing behavior, the as-prepared PEG-PTE2 copolymers displayed great potential for biomedical applications.
Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges.
In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders.
After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36–0.42, respectively.
GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.
In order to increase the speed, precision and robustness against the engine failure in solving optimal endo-atmospheric ascent trajectory of a launch vehicle, a rapid multi-layer solving method with improved numerical algorithms was proposed. The proposed method is capable of decomposing a large number of intervals into multiple layers with advantageous convergence property. Firstly, the problem of solving optimal endo-atmospheric ascent trajectory, which was subjected to path constraints and terminal constraints, was transformed into a Hamilton Two Point Boundary Value Problem (TPBVP). Then, through the finite difference method and numerical solving algorithm, the Hamilton TPBVP was iteratively solved with fewer initial discrete intervals. The initial values of higher-layer iterations were obtained by interpolating convergent solutions at sparse nodes into the doubly discrete nodes of high layers. The process was repeatedly performed until the solving precision met the requirements. To decrease the calculation load in solving TPBVPs, two improved solving algorithms without and with fewer Jacobian calculations were studied, respectively the Derivative-free Spectral Algorithm for Nonlinear Equations(DF-SANE) combined with the improved derivative-free nonmonotone line search strategy, and the Modified Newton method with a relaxation factor in combination with the Inverse Broyden Quasi-Newton method, denoted as ‘MN-IBQ’. Simulation verifications showed that the multi-layer method had significantly higher solving speed than the single-layer method. For the improved numerical algorithms, the DF-SANE was trapped in the local convergence problem. While using the proposed MN-IBQ can further increase the solving rate. Typical engine failure simulations showed that the multi-layer method with the MN-IBQ algorithm had not only significantly higher solving speed but also stronger robustness, where the traditional single-layer method could not adapt. In addition, the thrust loss tolerance limits for the multi-layer solving method were given for different engine failure times. The results show promising potential of the proposed approach in trajectory online generation and closed-loop guidance of launch vehicles at the endo-atmospheric ascent stage.
Gallstone disease (GSD) represents a significant health burden and is reported to be strongly related to obesity. This study examined the effect of sex on the association of BMI, waist circumference (WC) and percentage body fat mass (%FM) with GSD. We enrolled 15 671 middle-aged Taiwanese adults undergoing a physical check-up at a health examination centre. Multiple logistic regression analysis was conducted to identify the association of BMI, WC and %FM with the presence of GSD. AUC of the receiver–operating characteristic (ROC) curves were calculated for BMI, WC and %FM to compare their respective ability to correctly classify patients with GSD. From our findings, GSD prevalence was 8·1 % in men and 6·3 % in women. The percentage of markedly increased obesity indicators was significantly higher in patients with GSD than in those without GSD. Multivariate analysis showed that all obesity indicators were significant predictors of the presence of GSD in women after adjustment. In men, only BMI and WC were significantly associated with the presence of GSD. In the ROC curve analysis, BMI and WC were the best predictors of GSD risk in women and men, respectively. The obesity indicators better predicted the presence of GSD in women than in men. In conclusion, the best obesity indicator of GSD risk differed by sex. In addition to body weight, fat mass and central obesity were associated with GSD risk in women. In men, central obesity may play a more important role in predicting GSD risk.
Nutrition therapy is considered an important treatment of burn patients. The aim of the study was to delineate the nutritional support in severe burn patients and to investigate association between nutritional practice and clinical outcomes. Severe burn patients were enrolled (n 100). In 90 % of the cases, the burn injury covered above 70 % of the total body surface area. Mean interval from injury to nutrition start was 2·4 (sd 1·1) d. Sixty-seven patients were initiated with enteral nutrition (EN) with a median time of 1 d from injury to first feed. Twenty-two patients began with parenteral nutrition (PN). During the study, thirty-two patients developed EN intolerance. Patients received an average of about 70 % of prescribed energy and protein. Patients with EN providing <30 % energy had significantly higher 28- d and in-hospital mortality than patients with EN providing more than 30 % of energy. Mortality at 28 d was 11 % and in-hospital mortality was 45 %. Multiple regression analysis demonstrated that EN providing <30 % energy and septic shock were independent risk factors for 28- d prognosis. EN could be initiated early in severe burn patients. Majority patients needed PN supplementation for energy requirement and EN feeding intolerance. Post-pyloric feeding is more efficient than gastric feeding in EN tolerance and energy supplement. It is difficult for severe burn patients to obtain enough feeding, especially in the early stage of the disease. More than 2 weeks of underfeeding is harmful to recovery.
The association between opportunistic infection (OI) and anaemia among HIV-infected patients remains to be studied. We investigated the prevalence and risk factors of anaemia in hospitalised HIV-infected patients to reveal the association between OI and anaemia. We conducted a retrospective study of HIV-positive hospitalised patients from June 2016 to December 2017 in Mengchao Hepatobiliary Hospital of Fujian Medical University. Patients’ information on socio-demographic and clinical characteristics were carefully collected. The comparison of anaemia prevalence between groups was conducted with χ2 test. A logistic regression model was carried out to analyse the predictors of anaemia. The total prevalence of anaemia in hospitalised HIV-infected patients was 55.15%. The prevalence of mild, moderate and severe anaemia was 41.42%, 11.08% and 2.64%, respectively. Predictors independently associated with anaemia were: CD4 counts <50 cells/μl (odds ratio (OR): 6.376, 95% confidence interval (CI) = 1.916–21.215, P = 0.003), CD4 counts 50–199 cells/μl (OR: 6.303, 95% CI = 1.874–21.203, P = 0.003), co-infection with tuberculosis (TB) (OR: 2.703, 95% CI = 1.349–5.414, P = 0.005) or Penicillium marneffei (PM) (OR: 7.162, 95% CI = 3.147–15.299, P < 0.001). In Fujian, China, more than half inpatients with HIV were anaemic, but severe anaemia is infrequent. Lower CD4 counts, co-infection with TB or PM were independent risk factors for anaemia. Chinese HIV patients especially with TB, PM infection and low CD4 level should be routinely detected for anaemia to improve therapy.
Using whole-genome sequence (WGS) data are supposed to be optimal for genome-wide association studies and genomic predictions. However, sequencing thousands of individuals of interest is expensive. Imputation from single nucleotide polymorphisms panels to WGS data is an attractive approach to obtain highly reliable WGS data at low cost. Here, we conducted a genotype imputation study with a combined reference panel in yellow-feather dwarf broiler population. The combined reference panel was assembled by sequencing 24 key individuals of a yellow-feather dwarf broiler population (internal reference panel) and WGS data from 311 chickens in public databases (external reference panel). Three scenarios were investigated to determine how different factors affect the accuracy of imputation from 600 K array data to WGS data, including: genotype imputation with internal, external and combined reference panels; the number of internal reference individuals in the combined reference panel; and different reference sizes and selection strategies of an external reference panel. Results showed that imputation accuracy from 600 K to WGS data were 0.834±0.012, 0.920±0.007 and 0.982±0.003 for the internal, external and combined reference panels, respectively. Increasing the reference size from 50 to 250 improved the accuracy of genotype imputation from 0.848 to 0.974 for the combined reference panel and from 0.647 to 0.917 for the external reference panel. The selection strategies for the external reference panel had no impact on the accuracy of imputation using the combined reference panel. However, if only an external reference panel with reference size >50 was used, the selection strategy of minimizing the average distance to the closest leaf had the greatest imputation accuracy compared with other methods. Generally, using a combined reference panel provided greater imputation accuracy, especially for low-frequency variants. In conclusion, the optimal imputation strategy with a combined reference panel should comprehensively consider genetic diversity of the study population, availability and properties of external reference panels, sequencing and computing costs, and frequency of imputed variants. This work sheds light on how to design and execute genotype imputation with a combined external reference panel in a livestock population.
Dilated Cardiomyopathy is a serious heart disorder that may induce sudden cardiac death and heart failure. Significant progress has been made in understanding the molecular basis of dilated cardiomyopathy. In previous studies, mutations in more than fifty genes have been identified in dilated cardiomyopathy patients. The purpose of this study was to detect the genetic lesion in a family from the central south of China affected by severe dilated cardiomyopathy.
Whole-exome sequencing combined with cardiomyopathy-related genes list were used to analyse the mutations of the proband. Co-segregation analysis was performed by Sanger sequencing.
Results and conclusions
Two novel heterozygous mutations – Myosin Binding Protein C: p.L1014RfsX6 and Titin: p.R9793X – were identified in the proband. The deletion mutation c.3041delT/p.L1014RfsX6 caused a premature stop codon at position 1020 in exon 28 of the Myosin Binding Protein C. The nonsense mutation, c.29377 C>T/ p. R9793X, of Titin was located in the highly evolutionarily conserved domain, resulting in truncation of the Titin protein as well. Co-segregation analysis further revealed that the Myosin Binding Protein C mutation came from his mother and the Titin mutation came from his father. Both mutations are reported in dilated cardiomyopathy patients for the first time. Our study not only provides a unique example of the genes and molecular mechanisms involved in dilated cardiomyopathy but also expands the spectrum of Myosin Binding Protein C and Titin mutations and contributes to the genetic diagnosis and counselling of dilated cardiomyopathy patients.
To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.
Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.
The study included 27 transplant centers in freestanding children’s hospitals.
The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.
Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.
Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.
SCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.
Genomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.
Results and conclusions
A novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.
The hot deformation behavior of Nb–V–Ti microalloyed ultra-high strength steel was investigated by isothermal compression at 900–1200 °C with strain rates from 0.01 to 10 s−1. The microstructure evolution and precipitation behavior were studied using an optical microscope and a transmission electron microscope Results indicate that the peak stress of experimental steel increases with increasing the strain rate and decreasing the deformation temperature. The constitutive equation of hot deformation was developed with the activation energy Q being about 407.29 kJ/mol. The processing maps were also obtained to identify the instable regions of the flow behavior and to evaluate the efficiency of hot deformation. The size of dynamically recrystallized grains increases gradually with a decrease in the strain rate. Three types of carbides were identified, namely M3C, rich-Ti MC, and rich-Nb MC. With the increase of the deformation rate, the amounts of carbides increase, and the average sizes of the carbides decrease gradually.
OBJECTIVES/SPECIFIC AIMS: Effective HIV therapeutic options for persons with advanced HIV disease whose regimens have failed multiple times are limited. Current clinical practice utilizes regimens comprised of combinations of anti-retroviral (ARV) drugs. Despite the widespread use of ARV medications, optimization of initial treatment composition and subsequent management remains challenging. The goals of this study are (a) to better understand the ARV treatment structuring using prior clinical and patient information including virtual phenotype data and measures of viral load and CD4 cell count. We evaluated the potential impact of ARV strategies on AIDS-defining events and mortality; (b) to assess and understand differences of treatment composition and management when comparing standard ARV strategy (<5 ARVs) with an intensive ARV strategy (at least 5 ARVs). METHODS/STUDY POPULATION: OPTIMA was a tri-national (United States, Canada, and United Kingdom) randomized open label of alternative ARV treatment strategies for patients with advanced HIV disease (CD4≤300 cells/mm3) and evidence of resistance to 3 classes of ARV medications. OPTIMA used a 2×2 factorial design where the 2 factors were an ARV-free period Versus not; and standard Versus intensive ARV regimen. In this study, we focus on participants enrolled in OPTIMA at US participating sites and utilize demographic and clinical data including baseline virtual phenotype, ARV-related data (initial assignments and changes with drugs and dosages), follow-up lab data, AIDS-defining events, and vital status. RESULTS/ANTICIPATED RESULTS: Among 278 US-OPTIMA participants, 146 were randomly assigned to the standard ARV strategy and the rest were assigned to the intensive ARV strategy. Although not the sole factor, baseline virtual phenotype was used in selecting ARV medications within each assigned strategy. Participants in the standard arm exhibited better agreement between virtual phenotype results and the individual drugs selected for their regimen compared with participants in the intensive arm. This agreement had an almost statistically significant impact on survival time. No significant difference was detected in the frequency of ARV changes between standard and intensive ARV groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Even though per design, OPTIMA assigned participants to an ARV strategy using a binary factor (standard vs. intensive ARV) and assessed its effect on HIV-related disease at a coarse level, the trial’s design and rich database allowed for a closer examination of the ARV drug initial selection and subsequent management. Our findings summarize the patterns and discuss the effects of ARV and their management, on AIDS-defining events and survival. Such findings could provide preliminary, yet important insight, in understanding ARV use practice and could inform the conduct of future HIV treatment trials. Since the trial’s randomization was at the ARV strategy level and not the individual ARV drugs, findings cannot be described in terms of causal pathways for specific ARVs.
Proton radiography is a key diagnostics to measure and image the electric/magnetic field in laser-produced plasmas. A thin solid target is irradiated with an intense laser pulse to produce a proton beam. The accelerated proton can achieve higher energy with thinner target. In order to produce an extremely thin target, we have developed a large-area suspended graphene as a laser target for energetic ion sources. We describe the manufacturing process of the suspended graphene, and show the results of quality evaluations.
The objective of this study was to evaluate the potential of using Multiplex 3, a hand-held canopy fluorescence sensor, to determine rice nitrogen (N) status at different growth stages. In 2013, a paddy rice field experiment with five N fertilizer treatments and two varieties was conducted in Northeast China. Field samples and fluorescence data were collected simultaneously at the panicle initiation (PI), stem elongation (SE), and heading (HE) stages. Four N status indicators, leaf N concentration (LNC), plant N concentration (PNC), plant N uptake (PNU) and N nutrition index (NNI), were determined. The preliminary results indicated that different N application rates significantly affected most of the fluorescence variables, especially the simple fluorescence ratios (SFR_G, SFR_R), flavonoid (FLAV), and N balance indices (NBI_G, NBI_R). These variables were highly correlated with N status indicators. More studies are needed to further evaluate the accuracy of rice N status diagnosis using fluorescence sensing at different growth stages.
Precipitates and grain sizes in non-oriented silicon steel samples, which were hot-rolled (HR), continuously annealed (CA), and stress-relief-annealed (SA), were characterized using scanning electron microscopy (SEM) equipped with electron back-scattered diffraction. The average grain sizes of the HR, CA, and SA samples were 28, 46, and 46 μm, respectively. SEM observations revealed that the precipitates were mainly dispersed inside grains in the HR and the CA samples, but mainly at grain boundaries in the SA sample. The density of precipitates was highest in the SA sample and lowest in the HR sample. Precipitates at the grain boundaries, which were identified as manganese sulfides, were nearly spherical, their diameter ranging from 0.3 to 0.7 μm. We calculated the pining force exerted by grain-boundary precipitates and found that it outweighed the driving force of the grain growth that was controlled by boundary curvature.
What kind of content do citizens in a developing and authoritarian country like to acquire from Western free media? What are the effects of their potentially selective exposure? In a survey experiment involving 1,200 Chinese internet users from diverse socio-demographic backgrounds, this study finds that Chinese citizens with higher pro-Western orientations and lower regime evaluations are more inclined to read content that is positive about foreign countries or negative about China. More importantly, reading relatively positive foreign media content about foreign countries can improve rather than worsen the domestic evaluations of citizens who self-select such content. The article argues that this is because reputable Western media outlets’ reports are generally more realistic than overly rosy information about foreign socio-economic conditions that popularly circulates in China. Consequently, foreign media may have a corrective function and enhance regime stability in an authoritarian country by making regime critics less critical. The article also introduces a new variant of the patient preference trial design that integrates self-selection and random assignment of treatments in a way that is useful for studying information effects.
Using the data from the LAMOST Galactic spectroscopic surveys and some other surveys, we have started a series of work to measure the mass distribution of our Galaxy. As a result of the first-stage, we have constructed the Galactic rotation curve out to 100 kpc and the Galactic escape velocity curve between 5 and 14 kpc. From the two curves, we have built parametrized mass models for our Galaxy, respectively. Both models yield a similar result for the Milky Way's virial mass: ~ 0.9 × 1012 M⊙.
The LAMOST Galactic surveys provide robust stellar atmospheric parameters, abundances, masses and ages of millions of stars, allowing a unprecedented mapping of matter distribution, spatial structure, star formation rate, chemistry and kinematics of the Galaxy. In this proceeding we present structure and metallicity of the Galactic disk revealed by mono-age stellar populations within a few kilo-parsec of the solar neighborhood.