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This Element presents a unified computational fluid dynamics framework from rarefied to continuum regimes. The framework is based on the direct modelling of flow physics in a discretized space. The mesh size and time step are used as modelling scales in the construction of discretized governing equations. With the variation-of-cell Knudsen number, continuous modelling equations in different regimes have been obtained, and the Boltzmann and Navier-Stokes equations become two limiting equations in the kinetic and hydrodynamic scales. The unified algorithms include the discrete velocity method (DVM)–based unified gas-kinetic scheme (UGKS), the particlebased unified gas-kinetic particle method (UGKP), and the wave and particle–based unified gas-kinetic wave-particle method (UGKWP). The UGKWP is a multi-scale method with the particle for non-equilibrium transport and wave for equilibrium evolution. The particle dynamics in the rarefied regime and the hydrodynamic flow solver in the continuum regime have been unified according to the cell's Knudsen number.
During the last few decades, bed-elevation profiles from radar sounders have been used to quantify bed roughness. Various methods have been employed, such as the ‘two-parameter’ technique that considers vertical and slope irregularities in topography, but they struggle to incorporate roughness at multiple spatial scales leading to a breakdown in their depiction of bed roughness where the relief is most complex. In this article, we describe a new algorithm, analogous to wavelet transformations, to quantify the bed roughness at multiple scales. The ‘Self-Adaptive Two-Parameter’ system calculates the roughness of a bed profile using a frequency-domain method, allowing the extraction of three characteristic factors: (1) slope, (2) skewness and (3) coefficient of variation. The multi-scale roughness is derived by weighted-summing of these frequency-related factors. We use idealized bed elevations to initially validate the algorithm, and then actual bed-elevation data are used to compare the new roughness index with other methods. We show the new technique is an effective tool for quantifying bed roughness from radar data, paving the way for improved continental-wide depictions of bed roughness and incorporation of this information into ice flow models.
We have proposed and experimentally demonstrated a novel scheme for efficient mid-infrared difference-frequency generation based on passively synchronized fiber lasers. The adoption of coincident seeding pulses in the nonlinear conversion process could substantially lower the pumping threshold for mid-infrared parametric emission. Consequently, a picosecond mid-infrared source at 3.1 μm was prepared with watt-level average power, and a maximum power conversion efficiency of 77% was realized from pump to down-converted light. Additionally, the long-term stability of generated power was manifested with a relative fluctuation as low as 0.17% over one hour. Thanks to the all-optical passive synchronization and all-polarization-maintaining fiber architecture, the implemented laser system was also featured with simplicity, compactness and robustness, which would favor subsequent applications beyond laboratory operation.
The scientific application of clinical evidence-based guidelines can reduce the variability of clinical practice, and standardize clinical diagnosis and treatment pathways. At present, many evidence-based guidelines on Chronic Obstructive Pulmonary Disease (COPD) prevention have been issued in countries around the world, but the procedures and evaluation strategies developed by different guidelines are not the same. This study aimed to evaluate the quality of published clinical practice guidelines (CPGs) relating to COPD using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.
Databases were systematically searched PubMed, EMBASE, Wan Fang, and CNKI as well as guidelines websites on COPD prevention and treatment. The search period was from inception of the database up to May 2019. The inclusion criteria for this study are as follows: (i) published and in accordance with the definition of the practice guidelines; (ii)the main target population is COPD patients with the diagnostic criteria of the 2019 edition of the global initiative for COPD (GOLD), and the content of the guideline is related to the prevention and treatment practice of COPD; (ii) the same guide is included in the latest updated version; (iv) the published language is English or Chinese. Guidelines that met these inclusion criteria were evaluated for the quality of the AGREE II guidelines. Then, a descriptive analysis was made of the consensus that exists in the guidelines.
A total of fifteen guidelines/Consensuses Statements were included in the study. Two guidelines were assessed as recommended, eleven guidelines were assessed as recommended with modifications and two guidelines were not recommended. The mean scores of the included guidelines in the six domains (scope and purpose, personnel involved in guideline development, rigor of development, clarity, applicability, independence) were 90 percent, 72 percent, 49 percent, 96 percent, 60 percent, 69 percent, respectively. Thus, the study identified a consensus that disease risk factors and recommended interventions were mentioned in the guidelines, and that they comprehensively evaluated the quality of guideline reporting to provide reference for standardizing the development of practice guidelines for COPD in China.
The overall methodological quality of COPD CPGs should be improved. The key recommended areas for improvement include standardization of guideline report writing and synthesis of the latest and best evidence, to develop CPGs for COPD to improve the quality of clinical diagnosis and treatment for COPD.
Ankylosing spondylitis (AS) is a common disease that causes pain and affects productivity. Tumor necrosis factor-α (TNF-α) like adalimumab can bring better clinical efficacy and improve quality of life. Adalimumab is likely to be covered by health insurance. It is necessary to assess the impact of adalimumab for patients with AS on the medical insurance budget in China. Our research aims to give support evidence for policy-making.
From the perspective of medical insurance payers, a budget impact model was established to evaluate the impact of adalimumab for the treatment of adults with severe active AS that has responded inadequately to conventional therapy. The time horizon was 5 years (2020–2024). The cost of measurement included drug and treatment costs for adverse events. Scenario analysis was conducted to evaluate the results under different drug price reimbursement ratios and treatment ratios.
Based on the current price of adalimumab (CNY 3,160 [USD 446]/unit), under the reimbursement ratio of 70 percent, adalimumab will increase medical insurance expenditure by CNY 162 [USD 22] million, CNY 152 [USD 21] million, CNY 114 [USD 16] million, CNY 100 [USD 14] million and CNY 88.11 [USD 12] million in the next 1–5 years, respectively. The increased medical insurance expenditure accounts for 0.091, 0.085, 0.064, 0.056, and 0.049 percent of the annual medical insurance expenditure in the next 1–5 years, respectively, which is assumed to be equivalent to the expenditure in 2018 of CNY 1782.2 [USD 251] billion.
The budget impact of adalimumab for AS on medical insurance expenditure is limited, and including adalimumab in the medical insurance catalogue can reduce the burden on individuals, enrich treatment options, and satisfy clinical needs better.
Spinal muscular atrophy (SMA) is a rare, life-threatening, and seriously debilitating neuromuscular disorder, which has a heavy burden on patients, caregivers and the health system. Technological advances have improved clinical effect, but have also increased the financial burden. There is limited information in the literature on the resource utilization and economic burden of SMA. Our research aims to summarize the current literature on resource use, cost and economic evaluations of treatments for SMA, to inform further research and policy decision making.
Databases, including PubMed, Embase, Cochrane Library and CRD Database, were searched from inception. Two reviewers undertook title and abstract screening followed by full-text screening, and any disagreement was resolved in consensus. Data extraction was conducted using a customized form. Included studies were summarized using narrative synthesis structured around general and economic characteristics. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to where applicable.
We reviewed 552 abstracts and included twenty-six from 2015 to 2019. Four-fifths were published in the United States and Europe. Five full economic evaluations and one budget impact analysis compared nusinersen with AVXS-101 or best supportive care, and the remaining evaluated the economic burden of SMA. The most common outcomes were healthcare resource utilization and direct medical costs, only a few studies evaluated direct non-medical costs or indirect cost.
SMA patients have significant medical expenditures and high utilization of healthcare services, including nusinersen-treated patients. The results highlight the substantial burden of treatment for SMA, not only for patients but also for their caregivers. SMA represents a significant hidden cost that society should be made aware of, and that should be considered in the design, implementation and evaluation of support programs for people who suffer from this disease and their families, as well as in the economic evaluation of new treatments.
The South Altyn Orogenic Belt (SAOB) is one of the most important orogenic belts in NW China, consisting of the South Altyn Continental Block and the Apa–Mangya Ophiolitic Mélange Belt. However, its Palaeozoic tectonic evolution is still controversial. Here, we present petrological, geochemical, zircon U–Pb and Lu–Hf isotopic data for the Mangya plutons with the aim of establishing the Palaeozoic tectonic evolution. We divide the Early Palaeozoic magmatism in the Apa–Mangya Ophiolitic Mélange Belt into four episodes and propose a plate tectonic model for the formation of these rocks. During 511–494 Ma, the South Altyn Ocean (SAO) was in a spreading stage, and some shoshonite series, I-type granitic rocks were generated. From 484 to 458 Ma, the oceanic crust of the SAO subducted northward, accompanied by large-scale magmatic events resulting in the generation of vast high-K calc-alkaline series, I-type granitic rocks. During 450–433 Ma, the SAO closed, and break-off of the subducted oceanic slab occurred, with the generation of some high-K calc-alkaline series, I–S transitional type granites. The SAOB was in post-orogenic extensional environment from 419 to 404 Ma, and many A-type granites were generated.
Low-dimensional superconductors have been at the forefront of physics research due to their rich physical properties such as high-temperature (Tc) superconductivity. In this article, we review the field of emergent high-Tc superconductivity at interfaces of heterostructures, focusing on the experimental advances and its physical mechanism. Charge transfer between constituent materials leads to two-dimensional carrier confinement that facilitates occurrence of superconductivity at the interface. We discuss the similarities between bulk high-Tc superconductors and interface systems, as well as implications from a survey of interface superconductors. We expect that the hybrid heterostructures and the ability to manipulate them on an atomic scale could be an enormously fertile ground to explore superconductivity with higher critical temperature Tc.
Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2–3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2–3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.
Seed reserves play vital roles in seed germination and seedling growth and their variation may be related to various environment factors, plant traits and phylogenetic history. Here, the evolutionary correlation associated with seed mass and altitude and carbon (C), nitrogen (N) and phosphorus (P) allocation of seeds among 253 alpine herbaceous plants was tested. In this study, phylogeny had strong limitations on nutrient allocation of seeds across species, and species from younger phylogenetic groups tended to have higher N and P contents, which might be considered as the evolutionary selection of seed plants. Higher seed N and P content would help seedlings to gain more survival chance and stronger competitive capacity, and their progeny would be more likely to be preserved. When phylogeny was considered, altitude only had a significant positive effect on P content, but the negative effects on seed mass were all expressed. The independent effects of altitude and seed mass suggest that the nutrient allocation of seeds might be affected by both environment and plant traits. In addition, altitude and seed mass displayed partial overlapping effects on nutrient allocation of seeds. The negative effects of seed mass were affected slightly by altitude, whereas altitude only had a significant positive effect on P content when seed mass was controlled. Above all, seed P content showed obvious and general correlations with seed mass, altitude and age of clade, which indicated that higher seed P content might be an adaptive selection of species associated with growth and survival of progeny.
Given the global water challenges, solar-driven steam generation has become a renewed topic recently as an energy-efficient way for clean water production. Here, a hybrid plasmonic structure consisting of a top layer of TiN nanoparticles (NPs) and a bottom layer of mesoporous anodized alumina membrane (AAM) was rationally designed and fabricated. The top TiN NPs with broadband light absorption acted as a plasmonic heating layer, which converted the absorbed light to heat efficiently for interfacial water heating. The AAM acted as the mechanical support layer, guaranteeing the heat isolation and continuous water replenishment. With optimized thickness of the TiN top layer, a solar steam generation efficiency of 87.7% was achieved in this study. This efficiency is comparable or even higher than prior studies. The current work proves the capability of the TiN NPs as an alternative photothermal material.
Congenital heart disease (CHD) is one of the most common birth defects. More than 200 susceptibility loci have been identified for CHDs, yet a large part of the genetic risk factors remain unexplained. Monozygotic (MZ) twins are thought to be completely genetically identical; however, discordant phenotypes have been found in MZ twins. Recent studies have demonstrated genetic differences between MZ twins. We aimed to test whether copy number variants (CNVs) and/or genetic mutation differences play a role in the etiology of CHDs by using single nucleotide polymorphism (SNP) genotyping arrays and whole exome sequencing of twin pairs discordant for CHDs. Our goal was to identify mutations present only in the affected twins, which could identify novel candidates for CHD susceptibility loci. We present a comprehensive analysis for the CNVs and genetic mutation results of the selected individuals but detected no consistent differences within the twin pairs. Our study confirms that chromosomal structure or genetic mutation differences do not seem to play a role in the MZ twins discordant for CHD.
As a continuation of developing multiscale method for the transport phenomena, a unified gas kinetic scheme (UGKS) for multi-scale and multi-component plasma simulation is constructed. The current scheme is a direct modeling method, where the time evolution solutions from the Vlasov-BGK equations of electron and ion and the Maxwell equations are used to construct a scale-dependent plasma simulation model. The modeling scale used in the UGKS is the mesh size scale, which can be comparable to or much larger than the local mean free path. As a result, with the variation of modeling scales in space and time through the so-called cell's Knudsen number and normalized Larmor radius, the discretized governing equations can recover a wide range of plasma evolution from the Vlasov equation in the kinetic scale to different-type of magnetohydrodynamic (MHD) equations in the hydrodynamic scale. The UGKS provides a general evolution model, which goes to the Vlasov equation in the kinetic scale and many types of MHD equations in the hydrodynamic scale, such as the two fluids model, the Hall, the resistive, and the ideal MHD equations. All current existing governing equations become the subsets of the UGKS, and the UGKS bridges these distinguishable governing equations seamlessly. The construction of UGKS is based on the implementation of physical conservation laws and the un-splitting treatment of particle collision, acceleration, and transport in the construction of a scale-dependent numerical flux across a cell interface. At the same time, the discretized plasma evolution equations are coupled with the Maxwell equations for electro-magnetic fields, which also cover a scale-dependent transition between the Ampére's law and the Ohm's law for the calculation of electric field. The time step of UGKS is not limited by the relaxation time, the cyclotron period, and the speed of light in the ideal-MHD regime. Our scheme is able to give a physically accurate solution for plasma simulation with a wide range of Knudsen number and normalized Larmor radius. It can be used to study the phenomena from the Vlasov limit to the scale of plasma skin depth for the capturing of two-fluid effect, and the phenomena in the plasma transition regime with a modest Knudsen number and Larmor radius. The UGKS is validated by numerical test cases, such as the Landau damping and two stream instability in the kinetic regime, and the Brio-Wu shock tube problem, and the Orszag-Tang MHD turbulence problem in the hydrodynamic regime. The scheme is also used to study the geospace environment modeling (GEM), such as the challenging magnetic reconnection problem in the transition regime. At the same time, the magnetic reconnection mechanism of the Sweet-Parker model and the Hall effect model can be connected smoothly through the variation of Larmor radius in the UGKS simulations. Overall, the UGKS is a physically reliable multi-scale plasma simulation method, and it provides a powerful and unified approach for the study of plasma physics.
There have been great efforts on the development of higher-order numerical schemes for compressible Euler equations in recent decades. The traditional test cases proposed thirty years ago mostly target on the strong shock interactions, which may not be adequate enough for evaluating the performance of current higher-order schemes. In order to set up a higher standard for the development of new algorithms, in this paper we present a few benchmark cases with severe and complicated wave structures and interactions, which can be used to clearly distinguish different kinds of higher-order schemes. All tests are selected so that the numerical settings are very simple and any higher order scheme can be straightforwardly applied to these cases. The examples include highly oscillatory solutions and the large density ratio problem in one dimensional case. In two dimensions, the cases include hurricane-like solutions; interactions of planar contact discontinuities with asymptotic large Mach number (the composite of entropy wave and vortex sheets); interaction of planar rarefaction waves with transition from continuous flows to the presence of shocks; and other types of interactions of two-dimensional planar waves. To get good performance on all these cases may push algorithm developer to seek for new methodology in the design of higher-order schemes, and improve the robustness and accuracy of higher-order schemes to a new level of standard. In order to give reference solutions, the fourth-order gas-kinetic scheme (GKS) will be used to all these benchmark cases, even though the GKS solutions may not be very accurate in some cases. The main purpose of this paper is to recommend other CFD researchers to try these cases as well, and promote further development of higher-order schemes.
This paper is about the construction of a unified gas-kinetic scheme (UGKS) for a coupled system of radiative transport and material heat conduction with different diffusive limits. Different from the previous approach, instead of including absorption/emission only, the current method takes both scattering and absorption/emission mechanism into account in the radiative transport process. As a result, two asymptotic limiting solutions will appear in the diffusive regime. In the strong absorption/emission case, an equilibrium diffusion limit is obtained, where the system is mainly driven by a nonlinear diffusion equation for the equilibrium radiation and material temperature. However, in the strong scattering case, a non-equilibrium limit can be obtained, where coupled nonlinear diffusion system with different radiation and material temperature is obtained. In addition to including the scattering term in the transport equation, an implicit UGKS (IUGKS) will be developed in this paper as well. In the IUGKS, the numerical flux for the radiation intensity is constructed implicitly. Therefore, the conventional CFL constraint for the time step is released. With the use of a large time step for the radiative transport, it becomes possible to couple the IUGKS with the gas dynamic equations to develop an efficient numerical method for radiative hydrodynamics. The IUGKS is a valid method for all radiative transfer regimes. A few numerical examples will be presented to validate the current implicit method for both optical thin to optical thick cases.
With the use of temporal derivative of flux function, a two-stage temporal discretization has been recently proposed in the design of fourth-order schemes based on the generalized Riemann problem (GRP)  and gas-kinetic scheme (GKS) . In this paper, the fourth-order gas-kinetic scheme will be extended to solve the compressible multicomponent flow equations, where the two-stage temporal discretization and fifth-order WENO reconstruction will be used in the construction of the scheme. Based on the simplified two-species BGK model , the coupled Euler equations for individual species will be solved. Each component has its individual gas distribution function and the equilibrium states for each component are coupled by the physical requirements of total momentum and energy conservation in particle collisions. The second-order flux function is used to achieve the fourth-order temporal accuracy, and the robustness is as good as the second-order schemes. At the same time, the source terms, such as the gravitational force and the chemical reaction, will be explicitly included in the two-stage temporal discretization through their temporal derivatives. Many numerical tests from the shock-bubble interaction to ZND detonative waves are presented to validate the current approach.
Previous studies have supported the theory that there is a positive association between ferritin and carotid atherosclerosis in Western people. Diet plays an important role in determining serum ferritin concentration. Asian dietary patterns are different from Western dietary patterns, implying that there may be a difference in the association of ferritin with carotid atherosclerosis between Asian and Western people. However, few studies focus on the association between ferritin and carotid atherosclerosis among Asians. The aim of this study was to investigate how serum ferritin levels are associated with carotid atherosclerosis in an Asian adult population. A cross-sectional assessment was performed in 8302 adults in Tianjin, China. Carotid intima-media thickness (IMT) and plaques were assessed using ultrasonography, and serum ferritin was measured using the protein chip-chemiluminescence method. Multiple logistic regression analysis was used to examine the association between quartiles of serum ferritin concentration and carotid atherosclerosis. In the present study, the overall prevalence of IMT and carotid plaques in participants is 29·2 and 22·7 %, respectively. In women, after adjustments for potentially confounding factors, the OR of IMT and carotid plaques by increasing serum ferritin quartiles were 1·00, 1·39 (95 % CI 0·98–1·99), 1·39 (95 % CI 0·99–1·97), 1·81 (95 % CI 1·30–2·55) (Pfor trend<0·001) and 1·00, 1·24 (95 % CI 0·89–1·73), 1·18 (95 % CI 0·85–1·65), 1·59 (95 % CI 1·15–2·20) (Pfor trend<0·01), respectively. However, no association was found between serum ferritin and carotid atherosclerosis in men. The study demonstrated that increased serum ferritin levels are independently associated with IMT and carotid plaques in Asian women but not in Asian men.
The apparent gas permeability of a porous medium is an important parameter in the prediction of unconventional gas production, which was first investigated systematically by Klinkenberg in 1941 and found to increase with the reciprocal mean gas pressure (or equivalently, the Knudsen number). Although the underlying rarefaction effects are well known, the reason that the correction factor in Klinkenberg’s famous equation decreases when the Knudsen number increases has not been fully understood. Most of the studies idealize the porous medium as a bundle of straight cylindrical tubes; however, according to the gas kinetic theory, this only results in an increase of the correction factor with the Knudsen number, which clearly contradicts Klinkenberg’s experimental observations. Here, by solving the Bhatnagar–Gross–Krook equation in simplified (but not simple) porous media, we identify, for the first time, two key factors that can explain Klinkenberg’s experimental results: the tortuous flow path and the non-unitary tangential momentum accommodation coefficient for the gas–surface interaction. Moreover, we find that Klinkenberg’s results can only be observed when the ratio between the apparent and intrinsic permeabilities is
; at large ratios (or Knudsen numbers) the correction factor increases with the Knudsen number. Our numerical results could also serve as benchmarking cases to assess the accuracy of macroscopic models and/or numerical schemes for the modelling/simulation of rarefied gas flows in complex geometries over a wide range of gas rarefaction. Specifically, we point out that the Navier–Stokes equations with the first-order velocity-slip boundary condition are often misused to predict the apparent gas permeability of the porous medium; that is, any nonlinear dependence of the apparent gas permeability with the Knudsen number, predicted from the Navier–Stokes equations, is not reliable. Worse still, for some types of gas–surface interactions, even the ‘filtered’ linear dependence of the apparent gas permeability with the Knudsen number is of no practical use since, compared to the numerical solution of the Bhatnagar–Gross–Krook equation, it is only accurate when the ratio between the apparent and intrinsic permeabilities is
Evaluating quality traits is important to the selection of elite lines in Brassica napus L. In this study, the quality traits of 488 global collections of B. napus L were evaluated for two consecutive years under central Chinese growing conditions, and a series of phenotypic data was obtained. The measured total glucosinolate content (GLC) and erucic acid content (ERU) values for 95.5% of the accessions were consistent with the original values, and large variations in quality traits were found among these accessions, thus enabling selection for these characters. In general, Chinese accessions tended to have a higher oil content (OC) than foreign accessions, while compared with winter and spring accessions, semi-winter accessions tended to have the highest OC. The mean GLC and ERU of Chinese rapeseed accessions showed gradual downward trends over time, and the genotypic variation in ERU accounted for 98.44% of the total variation, which was the highest among all 10 of the quality traits. Additionally, the heritability for ERU was largest among all 10 of the quality traits. Significant correlations were observed between different traits; OC had significantly (P < 0.01) negative correlation coefficients with oleic acid content, whereas OC had significantly (P < 0.01) positive correlation coefficients with ERU. Principal component analysis revealed that there was no clear boundary among materials of different geographic origins and different ecotypes according to the first two principal coordinates, respectively. This information about variations in quality traits revealed in this study could identify parents for improved rapeseed breeding.