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There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.
In this article, Al75Cu25 (at.%) ribbons were dealloyed by HCl, H2C2O4, H3PO4, and NaOH solutions, respectively, to prepare nanoporous copper (NPC). The dealloying behavior is varied with dealloying solutions, allowing modulating the microstructure and porosity of the NPC. Al75Cu25 ribbons are fully dealloyed in HCl, H2C2O4, and NaOH solutions, whereas they are partially dealloyed in H3PO4 solution. Except the NPC prepared in the NaOH solution, no obvious cracks are traced in other samples. The surface diffusivity (Ds) of Cu atoms along the alloy/solution interfaces is varied with solutions, producing the NPC with different microstructure. NPC with higher specific surface area can be obtained by dealloying the Al75Cu25 ribbons in the HCl solution. Compared with the dealloying in H2C2O4, H3PO4, and NaOH solutions, the dealloying in 10 wt% HCl solution for 25 min at 90 ± 1 °C facilitates the best NPC in this work.
Freshwater habitats in China are potentially suitable for invasive alien turtle species and, consequently, raising turtles in aquaculture facilities and the trade in turtles this supplies pose risks to habitats and native wetland communities when exotic turtles escape or are released deliberately. Online trade (e-commerce) is making an increasing contribution to turtle sales in China, seemingly driving demand and thus potentially exacerbating the risk of release. We document the scale and spatial pattern of online sales of non-native turtles over 90 days on China's Taobao.com e-commerce site. The majority of sales were in the ecologically sensitive middle and lower Yangtze river basin (82.35% of > 840,000 slider turtles Trachemys scripta elegans, and 68.26% of > 100,000 snapping turtles, Chelydridae spp.). These species are native to the Americas. Concurrently, over 2008–2018, we found 104 mentions of feral turtle issues listed on Baidu News where, among the 53 prefectures mentioned, issues with invasive turtle populations also focused predominantly in the middle and lower Yangtze river basin. Although circumstantial, this association suggests that the substantial online sale of alien turtles could be having detrimental effects in China's Yangtze river basin. It is important to safeguard these wetland habitats, which are of global importance, by improving policies for detecting and regulating invasive alien turtle issues and by warning consumers about the ecological hazard of their purchases.
Wildlife is an essential component of all ecosystems. Most places in the globe do not have local, timely information on which species are present or how their populations are changing. With the arrival of new technologies, camera traps have become a popular way to collect wildlife data. However, data collection has increased at a much faster rate than the development of tools to manage, process and analyse these data. Without these tools, wildlife managers and other stakeholders have little information to effectively manage, understand and monitor wildlife populations. We identify four barriers that are hindering the widespread use of camera trap data for conservation. We propose specific solutions to remove these barriers integrated in a modern technology platform called Wildlife Insights. We present an architecture for this platform and describe its main components. We recognize and discuss the potential risks of publishing shared biodiversity data and a framework to mitigate those risks. Finally, we discuss a strategy to ensure platforms like Wildlife Insights are sustainable and have an enduring impact on the conservation of wildlife.
Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders.
Here we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes.
Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase.
Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.
We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD).
We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of ‘TNF-α × treatment’ in the regions with between-group FC difference.
Compared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of ‘TNF-α × treatment’ was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease.
These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
A Pneumatic Muscle Actuator (PMA) is a new pneumatic component sharing similar characteristics with biological muscles, and the flexible manipulator actuated by PMAs can better reflect the flexibility of the mechanism. First and foremost, based on the study of the characteristics of human shoulder joints, the configuration design of the flexible manipulator is analyzed, and its kinematics and dynamics models are established. Furthermore, with regard to the nonlinearity, time-invariance and uncertainty of the control system, three aspects of improvement are proposed, which are based on the Radial Basis Function (RBF) network torque control algorithm. The Genetic Algorithm is used to optimize the initial values of RBF network parameters; RBF network parameters are adjusted dynamically by using the additional momentum method; the Levenberg--Marquardt (LM) algorithm, instead of the gradient descent method, is adopted to adjust Proportion Integration Differentiation (PID) parameters online in real time. At last, to test the effects that the improved algorithm exerts on the flexible manipulator control system, some physical platform experiments are carried out. It turns out that the control accuracy and robustness of the improved algorithm are well improved, and the mechanism can be controlled better to track the circular arc trajectory. It lays fundamental importance to the practical application for the working environment.
Advanced alloys with both high strength and ductility are highly desirable for a wide range of engineering applications. Conventional alloy design strategies based on the single-principle element are approaching their limits in further optimization of their performances. Precipitation-hardened high-entropy alloys (HEAs), especially those strengthened by coherent L12-nanoparticles, have received considerable interest in recent years, enabling a new space for the development of advanced structural materials with superior mechanical properties. In this review, we highlight recent important advances of the newly developed L12-strengthened HEAs, including the aspects of computation-aided alloy design, unique properties, atomic-level characterization, phase evolution, and stability. In particular, we focus our attention on elucidating fundamental scientific issues involving the alloying effects, precipitation behaviors, mechanical performances, and the corresponding deformation mechanisms, all of which provide a comprehensive metallurgical understanding and guidance for the design of this new class of HEAs. Finally, future research directions and prospects are also critically assessed.
Astrophysical collisionless shocks are amazing phenomena in space and astrophysical plasmas, where supersonic flows generate electromagnetic fields through instabilities and particles can be accelerated to high energy cosmic rays. Until now, understanding these micro-processes is still a challenge despite rich astrophysical observation data have been obtained. Laboratory astrophysics, a new route to study the astrophysics, allows us to investigate them at similar extreme physical conditions in laboratory. Here we will review the recent progress of the collisionless shock experiments performed at SG-II laser facility in China. The evolution of the electrostatic shocks and Weibel-type/filamentation instabilities are observed. Inspired by the configurations of the counter-streaming plasma flows, we also carry out a novel plasma collider to generate energetic neutrons relevant to the astrophysical nuclear reactions.
OBJECTIVES/SPECIFIC AIMS: Tissue engineered tracheal grafts (TETG) could provide a life-saving cure for children with long segment airway defects. Computational fluid dynamics (CFD) is a novel and promising technique used to evaluate TETG performance. This pilot study examines the correlation of objective CFD simulations with subjective respiratory symptoms in a TETG large animal model. METHODS/STUDY POPULATION: Three-dimensional geometries of 1 TETG implanted sheep trachea were reconstructed from serial fluoroscopic images, allowing analysis with CFD simulations. Peak flow velocity (PFV) and peak wall shear stress (PWSS) across the graft as well as changes secondary to stenting were determined. CFD metrics were compared with respiratory symptoms seen on exam. RESULTS/ANTICIPATED RESULTS: Two weeks after implantation, the animal developed respiratory distress, which correlated with PFV and PWSS elevations. Although the intraluminal graft appearance changed minimally after dilation, PFV and PWSS decreased across the graft (4.5–0.8 m/s and 0.9–0.1 Pa, respectively). Long-term TETG stenting with dilation returned PFV and PWSS to baseline (0.8–0.3 m/s and 0.1–0.01 Pa, respectively), which correlated with immediate symptom resolution. DISCUSSION/SIGNIFICANCE OF IMPACT: CFD is a noninvasive modality, which allows the evaluation of airflow metrics of symptomatic TETG recipients. This diagnostic tool will permit planned interventions and graft design optimization.
CVD remains the leading cause of mortality worldwide, with abnormal lipid metabolism as a major risk factor. The aim of this study was to investigate associations between spicy food consumption and serum lipids in Chinese adults. Data were extracted from the 2009 phase of the China Health and Nutrition Survey, consisting of 6774 apparently healthy Chinese adults aged 18–65 years. The frequency of consumption and degree of pungency of spicy food were self-reported, and regular spicy food consumption was assessed using three consecutive 24-h recalls. Total cholesterol, TAG, LDL-cholesterol and HDL-cholesterol in fasting serum were measured. Multilevel mixed-effects models were constructed to estimate associations between spicy food consumption and serum lipid profiles. The results showed that the frequency and the average amount of spicy food intake were both inversely associated with LDL-cholesterol and LDL-cholesterol:HDL-cholesterol ratio (all Pfor trend<0·05) after adjustment for potential confounders and cluster effects. HDL-cholesterol in participants who usually consumed spicy food (≥5 times/week) and who consumed spicy food perceived as moderate in pungency were significantly higher than those who did not (both P<0·01). The frequency and the average amount of spicy food intake and the degree of pungency in spicy food were positively associated with TAG (all Pfor trend<0·05). Spicy food consumption was inversely associated with serum cholesterol and positively associated with serum TAG, and additional studies are needed to confirm the findings as well as to elucidate the potential roles of spicy food consumption in lipid metabolism.
The surfacing welding has been widely utilized in the industrial equipment manufacturing and repairs. The wear properties of surfacing alloys have an important effect on the whole performance of repaired components. The solution treatment (T4) and solution treatment followed by aging (T6) effects on the dry sliding wear behavior of surfacing AZ91 magnesium alloys with tungsten inert gas welding were investigated in this work. The results demonstrated that the surfacing alloy without treatment exhibited poor wear resistance, due to the massive intermetallic β-phases (Mg17Al12). These phases were believed to produce stress concentrations in the particle-to-matrix interface and tended to generate cracks during friction. The T4 alloy had more improved wear resistance than the as-received alloy. The T6 treatment improved the wear resistance further, resulting from the high density dispersed fine β-phase precipitation in the α-Mg matrix, which enhanced the alloy strength and hardness and decreased the subsurface metal deformation degree caused by friction.
The present study examines the characteristics of clay minerals in shale gas reservoirs and their influence on reservoir properties based on X-ray diffraction and scanning electron microscopy. These analyses were combined with optical microscopy observations and core and well-log data to investigate the genesis, distribution characteristics, main controlling factors and pore features of clay minerals of the Lower Silurian Longmaxi Formation in the East Sichuan area, China. The clay mineral assemblage consists of illite + mixed-layer illite-smectite (I-S) + chlorite. This assemblage includes three sources of clay minerals: detrital, authigenic and diagenetic minerals. The lower section of the Longmaxi Formation in the Jiaoshiba area has sealing ability which resulted in abnormal high pressures during hydrocarbon generation which inhibited illitization. Therefore, an anomalous transformation sequence is present in which the mixed-layer I-S content increases with depth. This anomalous transformation sequence can be used to infer the existence of abnormal high pressures. The detrital components of the formation also affect the clay-minerals content indirectly, especially the abundance of K-feldspar. The transformation of mixed-layer I-S to illite is limited due to the limited availability of K+, which determines the extent of transformation. Three types of pores were observed in the shale reservoir rocks of the Longmaxi Formation: interparticle (interP) pores, intraparticle (intraP) pores and organic-matter pores. The clay-mineral content controls the development of intraP pores, which are dominated by pores within clay particles. For a given clay mineral content, smectite and mixed-layer I-S were more conducive to the development of shale-gas reservoirs than other clay minerals.
The Honggong pluton is the largest ferroan alkalic (A-type) granite intrusion emplaced along the Jiangshan–Shaoxing fault zone in southwestern Zhejiang Province, and has important implications for understanding the Late Mesozoic tectonic evolution of SE China. U–Pb ages of 138.7 ± 0.8, 134.2 ± 1.1, 128.5 ± 1.5 and 126.1 ± 0.9 Ma were obtained from zircon by laser ablation–inductively coupled plasma–mass spectrometry, indicating that the Honggong pluton formed in the Early Cretaceous. The Honggong pluton has a clear ferroan alkalic (A-type) granite geochemical signature with, for example, high total alkali contents and FeOt/(FeOt + MgO) values. The Sr–Nd–Hf isotopic compositions suggest that there was juvenile material in the magma source. Geochemical evidence indicates that the pluton was derived through extensive fractionation of melts that contained both asthenospheric mantle and Mesoproterozoic crustal components. These rare granites in southern China were emplaced during five episodes at 235–225, 190, 165–155, 100–90 and 140–120 Ma. The age of the Honggong pluton suggests that localized extension in southwestern Zhejiang Province began as early as ~138 Ma and continued to 126 Ma. This Early Cretaceous extensional event was triggered by localized rollback of the subducting Pacific Plate.
Facilitated by recent establishment of terrestrial networks and satellite constellations of Automatic Identification System (AIS) receivers, ship trajectories are becoming increasingly available and the size of recorded trajectories is getting larger. Large sets of trajectories create problems of storing, transmitting and processing data. Using appropriate methods, an accurate representation of the original trajectories can be obtained by compressing redundant information, while maintaining the main characteristic elements. In this paper, a new scheme and the implementation of the Douglas-Peucker (DP) algorithm are presented, which can simplify AIS trajectories by extracting characteristic points. As for the simplification threshold, the solo parameter of the DP algorithm, a new AIS-based minimum ship domain evaluation method is proposed and acts as criteria for simplification threshold determination. Finally, a validation is made to examine the effectiveness of the DP simplification algorithm and the rationality of the simplification threshold. The result indicates that the DP algorithm can simplify AIS trajectories effectively; the simplification threshold is scientific and reasonable.
This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, μ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell–cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.
The prevalence and factors associated with delays in help seeking for people with dementia in China are unknown.
Within 1,010 consecutively registered participants in the Clinical Pathway for Alzheimer's Disease in China (CPAD) study (NCT01779310), 576 persons with dementia (PWDs) and their informants reported the estimated time from symptom onset to first medical visit seeking diagnosis. Univariate analysis of general linear model was used to examine the potential factors associated with the delayed diagnosis seeking.
The median duration from the first noticeable symptom to the first visit seeking diagnosis or treatment was 1.77 years. Individuals with a positive family history of dementia had longer duration (p = 0.05). Compared with other types of dementia, people with vascular dementia (VaD) were referred for diagnosis earliest, and the sequence for such delays was: VaD < Alzheimer's disease (AD) < frontotemporal dementia (FTD) (p < 0.001). Subtypes of dementia (p < 0.001), family history (p = 0.01), and education level (p = 0.03) were associated with the increased delay in help seeking.
In China, seeking diagnosis for PWDs is delayed for approximately 2 years, even in well-established memory clinics. Clinical features, family history, and less education may impede help seeking in dementia care.