Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Prospective associations between joint categories of physical activity and insomnia symptoms with onset of poor mental health in a population-based cohort

Background:Physical inactivity and insomnia symptoms are independently associated with increased risk of depression and anxiety;however,few studies jointly examine these risk factors.This study aimed to prospectively examine the joint association of physical activity(PA)and insomnia symptoms with onset of poor mental health in adults.Methods:Participants from the 2013 to 2018 annnual waves of the Household Income and Labour Dynamics in Australia panel study who had good mental health(Mental Health Inventory-5>54)in 2013,and who completed at least 1 follow-up survey(2014-2018),were included(n=10,977).Poor mental health(Mental Health Inventory-5≤54)was assessed annually.Baseline(2013)PA was classified as high/moderate/low,and insomnia symptoms(i.e.,trouble sleeping)were classified as no insomnia symptoms/insomnia symptoms,with 6 mutually exclusive PAinsomnia symptom groups derived.Associations of PA-insomnia symptom groups with onset of poor mental health were examined using discrete-time proportional-hazards logit-hazard models.Results:There were 2322 new cases of poor mental health(21.2%).Relative to the high PA/no insomnia symptoms group,there were higher odds(odds ratio and 95%confidence interval(95%CI))of poor mental health among the high PA/insomnia symptoms(OR=1.87,95%CI:1.57-2.23),moderate PA/insomnia symptoms(OR=1.93,95%CI:1.61-2.31),low PA/insomnia symptoms(OR=2.33,95%CI:1.96-2.78),and low PA/no insomnia symptoms(OR=1.14,95%CI:1.01-1.29)groups.Any level of PA combined with insomnia symptoms was associated with increased odds of poor mental health,with the odds increasing as PA decreased.Conclusion:The se findings highlight the potential benefit of interventions targeting both PA and insomnia symptoms for promoting mental health.

Clinical utilities and end-user experience of pharmacogenomics:39 mo of clinical implementation experience in an Australian hospital setting

BACKGROUND Pharmacogenomics(PG)testing is under-utilised in Australia.Our research provides Australia-specific data on the perspectives of patients who have had PG testing and those of the clinicians involved in their care,with the aim to inform wider adoption of PG into routine clinical practice.AIM To investigate the frequency of actionable drug gene interactions and assess the perceived utility of PG among patients and clinicians.METHODS We conducted a retrospective audit of PG undertaken by 100 patients at an Australian public hospital genetics service from 2018 to 2021.Via electronic surveys we compared and contrasted the experience,understanding and usage of results between these patients and their clinicians.RESULTS Of 100 patients who had PG,84% were taking prescription medications,of which 67% were taking medications with actionable drug-gene interactions.Twenty-five out of 81 invited patients and 17 out of 89 invited clinicians completed the surveys.Sixty-eight percent of patients understood their PG results and 48% had medications changed following testing.Paired patient-clinician surveys showed patient-perceived utility and experience was positive,contrasting their clinicians’hesitancy on PG adoption who identified insufficient education/training,lack of clinical support,test turnaround time and cost as barriers to adoption.CONCLUSION Our dichotomous findings between the perspectives of our patient and clinician cohorts suggest the uptake of PG is likely to be driven by patients and clinicians need to be prepared to provide information and guidance to their patients.

Strategies for translating proteomics discoveries into drug discovery for dementia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

Extended finite element-based cohesive zone method for modeling simultaneous hydraulic fracture height growth in layered reservoirs

In this study,a fully coupled hydromechanical model within the extended finite element method(XFEM)-based cohesive zone method(CZM)is employed to investigate the simultaneous height growth behavior of multi-cluster hydraulic fractures in layered porous reservoirs with modulus contrast.The coupled hydromechanical model is first verified against an analytical solution and a laboratory experiment.Then,the fracture geometry(e.g.height,aperture,and area)and fluid pressure evolutions of multiple hydraulic fractures placed in a porous reservoir interbedded with alternating stiff and soft layers are investigated using the model.The stress and pore pressure distributions within the layered reservoir during fluid injection are also presented.The simulation results reveal that stress umbrellas are easily to form among multiple hydraulic fractures’tips when propagating in soft layers,which impedes the simultaneous height growth.It is also observed that the impediment effect of soft layer is much more significant in the fractures suppressed by the preferential growth of adjoining fractures.After that,the combined effect of in situ stress ratio and fracturing spacing on the multi-fracture height growth is presented,and the results elucidate the influence of in situ stress ratio on the height growth behavior depending on the fracture spacing.Finally,it is found that the inclusion of soft layers changes the aperture distribution of outmost and interior hydraulic fractures.The results obtained from this study may provide some insights on the understanding of hydraulic fracture height containment observed in filed.

Effects of insoluble Zn,Cd,and EDTA on the growth,activities of antioxidant enzymes and uptake of Zn and Cd in Vetiveria zizanioides

A root-bag experiment was conducted to study the effects of insoluble Zn, Cd, and ethylenediaminetetraacetic acid （EDTA） on the plant growth, activities of antioxidant enzymes, proline, glutathione （GSH）, water-soluble proteins and malondialdehyde （MDA） of Vetiveria zizanioides. The V. zizanioides uptake capacity of Zn and Cd also determined. The results showed that plant growth of V. zizanioides was inhibited by Zn and Cd. The shoot dry weight （SDW） and root dry weight （RDW） decrease by 14.2%, 14.1%, 17.0% and 17.3%, 32.5%, 35.7%, respectively, compared to the control without EDTA addition. After adding EDTA, shoot and root dry weight decreased over 10% and 15%, respectively. The toxicity from insoluble Zn and Cd in soil on SDW and RDW of V. zizanioides was in order： Zn＋Cd 〉 Cd 〉 Zn. The activities of superoxide dismutase （SOD）, peroxidase （POD） and catalase （CAT）, and contents of MDA and proline increased significantly, while the contents of GSH and water-soluble proteins decreased markedly with increasing Zn and Cd toxicity. With EDTA, shoot and root Zn concentrations increased in the Zn treatment by 7.3% and 37.4%, and Cd concentrations in the combined Zn and Cd treatment increased by 18.6% and 391.9% compared to the treatment without EDTA. However, Zn and Cd concentrations in shoot and roots decreased in the Cd treatment compared to the plants grown in absence of EDTA, with exception of root Cd concentration in the presence of EDTA.

STUDY ON THE INTERACTION OF SEDIMENTING CYLINDRICAL PARTICLES IN STILL FLUID

The sedimentations of two cylindrical particles in three different initial relative po- sitions are numerically simulated using the lattice Boltzmann method.The movement characteristics and particle interactions during their sedimentation are presented and discussed in detail.The results show that,(i)if the two particles are released parallel but separated horizontally,they push away each other,rotate inwards and separate horizontally as they fall;(ii)if the two particles are released par- allel but separated vertically,the sedimentation behavior can be classified into three stages:trailing, tumbling and separating;(iii)if the two particles are released perpendicular but separated vertically, the sedimentation behavior can be characterized as:trailing and rotating,touching and sliding.In order to validate our simulation,experiments were also conducted and the results agree well with the numerical ones.

Inhalation of nanoparticle-based drug for lung cancer treatment:Advantages and challenges

Ever since the success of developing inhalable insulin,drug delivery via pulmonary administration has become an attractive route to treat chronic diseases.Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy.Nano-based systems such as liposome,polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability,stability and residency at targeted lung regions.Along with these benefits,nano-based systems also provide additional diagnostic advantages during lung cancer treatment,including imaging,screening and drug tracking.Nevertheless,delivery of nanobased drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected.Pharmacology,immunology,toxicology and largescale manufacturing(stability and activity of drugs)are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs.This review will focus on the current inhalable nano-based drugs for lung cancer treatment.

Bayesian geological and geophysical data fusion for the construction and uncertainty quantification of 3D geological models

Traditional approaches to develop 3D geological models employ a mix of quantitative and qualitative scientific techniques,which do not fully provide quantification of uncertainty in the constructed models and fail to optimally weight geological field observations against constraints from geophysical data.Here,using the Bayesian Obsidian software package,we develop a methodology to fuse lithostratigraphic field observations with aeromagnetic and gravity data to build a 3D model in a small(13.5 km×13.5 km)region of the Gascoyne Province,Western Australia.Our approach is validated by comparing 3D model results to independently-constrained geological maps and cross-sections produced by the Geological Survey of Western Australia.By fusing geological field data with aeromagnetic and gravity surveys,we show that 89%of the modelled region has>95%certainty for a particular geological unit for the given model and data.The boundaries between geological units are characterized by narrow regions with<95%certainty,which are typically 400-1000 m wide at the Earth's surface and 500-2000 m wide at depth.Beyond~4 km depth,the model requires geophysical survey data with longer wavelengths(e.g.,active seismic)to constrain the deeper subsurface.Although Obsidian was originally built for sedimentary basin problems,there is reasonable applicability to deformed terranes such as the Gascoyne Province.Ultimately,modification of the Bayesian engine to incorporate structural data will aid in developing more robust 3D models.Nevertheless,our results show that surface geological observations fused with geophysical survey data can yield reasonable 3D geological models with narrow uncertainty regions at the surface and shallow subsurface,which will be especially valuable for mineral exploration and the development of 3D geological models under cover.

Balance Control of a Biped Robot on a Rotating Platform Based on Efficient Reinforcement Learning

In this work,we combined the model based reinforcement learning(MBRL)and model free reinforcement learning(MFRL)to stabilize a biped robot(NAO robot)on a rotating platform,where the angular velocity of the platform is unknown for the proposed learning algorithm and treated as the external disturbance.Nonparametric Gaussian processes normally require a large number of training data points to deal with the discontinuity of the estimated model.Although some improved method such as probabilistic inference for learning control(PILCO)does not require an explicit global model as the actions are obtained by directly searching the policy space,the overfitting and lack of model complexity may still result in a large deviation between the prediction and the real system.Besides,none of these approaches consider the data error and measurement noise during the training process and test process,respectively.We propose a hierarchical Gaussian processes(GP)models,containing two layers of independent GPs,where the physically continuous probability transition model of the robot is obtained.Due to the physically continuous estimation,the algorithm overcomes the overfitting problem with a guaranteed model complexity,and the number of training data is also reduced.The policy for any given initial state is generated automatically by minimizing the expected cost according to the predefined cost function and the obtained probability distribution of the state.Furthermore,a novel Q(λ)based MFRL method scheme is employed to improve the policy.Simulation results show that the proposed RL algorithm is able to balance NAO robot on a rotating platform,and it is capable of adapting to the platform with varying angular velocity.

Diagenesis and Fluid Flow History in Sandstones of the Upper Permian Black Jack Formation, Gunnedah Basin, Eastern Australia

The fluid flow history during diagenesis of sandstones in the Upper Permian Black Jack Formation of the Gunnedah Basin has been investigated through integrated petrographic observations, fluid inclusion investigations and stable isotope analyses. The early precipitation of mixed-layer illite/smectite, siderite, calcite, ankerite and kaolin proceeded at the presence of Late Permian connate meteoric waters at temperatures of up to 60℃. These evolved connate pore waters were also parental to quartz, which formed at temperatures of up to 87℃. The phase of maximum burial was characterized by development of filamentous illite and late calcite at temperatures of up to -90℃. Subsequent uplifting and cooling led to deep meteoric influx from surface, which in turn resulted in dissolution of labile grains and carbonate cements, and formation of second generation of kaolin. Dawsonite was the last diagenetic mineral precipitated and its formation is genetically related to deep-seated mamagtic sourced CO2.

Review of Global Ocean Intermediate Water Masses: 1.Part A, the Neutral Density Surface (the ‘McDougall Surface’) as a Study Frame for Water-Mass Analysis

This review article commences with a comprehensive historical review of the evolution and application of various density surfaces in atmospheric and oceanic studies. The background provides a basis for the birth of the neutral density idea. Attention is paid to the development of the neutral density surface concept from the nonlinearity of the equation of state of seawater. The definition and properties of neutral density surface are described in detail as developed from the equations of state of seawater and the buoyancy frequency when the squared buoyancy frequency N2 is zero, a neutral state of stability. In order to apply the neutral density surface to intermediate water-mass analysis, this review also describes in detail its practical oceanographic application. The mapping technique is focused for the first time on applying regularly gridded data in this review. It is reviewed how a backbone and ribs framework was designed to flesh out from a reference cast and first mapped the global neutral surfaces in the world’s oceans. Several mapped neutral density surfaces are presented as examples for each world ocean. The water-mass property is analyzed in each ocean at mid-depth. The characteristics of neutral density surfaces are compared with those of potential density surfaces.

Microbiologically Induced Corrosion of Concrete and Protective Coatings in Gravity Sewers

Microbiologically induced corrosion of concrete （MICC） and its protective coatings has a high eco-nomic impact on sewer maintenance and rehabilitation. A better understanding of the micro-organisms and the bio- genie acids that are generated in the sewer is essential in controlling the corrosion of concrete pipes and protective coatings. The role of succession of micro-organisms growth in the corrosion of concrete and protective coatings was evaluated in this study. Examination of various sewer pipe materials exhibiting various extents of degradation, including concrete, cement based and epoxy based coating revealed the presence of both organic and biogenic sulphuric acids. This reflects the activity of fungi and the thiobacilli strains. Organism growth and metabolism were strongly related to the substrate pH. Fungi were found to grow and metabolise organic acids at pH from 2.0-8.0. Whilst the thiobacilli strains grew and generated sulohuric acids at oH below 3.0. The successive growth of the organisms provides an impgrtant bearing in deyeloping improved strateegies.to better manage sewers.

TOPOLOGY SYNTHESIS OF GEOMETRICALLY NONLINEAR COMPLIANT MECHANISMS USING MESHLESS METHODS

This paper presents a new method for topology optimization of geometrical nonlinear compliant mechanisms using the element-free Galerkin method （EFGM）. The EFGM is employed as an alternative scheme to numerically solve the state equations by fully taking advantage of its capability in dealing with large displacement problems. In the meshless method, the imposition of essential boundary conditions is also addressed. The popularly studied solid isotropic material with the penalization （SIMP） scheme is used to represent the nonlinear dependence between material properties and regularized discrete densities. The output displacement is regarded as the objective function and the adjoint method is applied to finding the sensitivity of the design functions. As a result, the optimization of compliant mechanisms is mathematically established as a nonlinear programming problem, to which the method of moving asymptotes （MMA） belonging to the sequential convex programming can be applied. The availability of the present method is finally demonstrated with several widely investigated numerical examples.

Multiple Chromatographic and Chemometric Methods for Quality Standardization of Chinese Herbal Medicines

Quality standardization of complementary medicine is fundamental for industry and practice as it underpins the quality,safety and efficacy of Chinese herbal medicines.Current herbal standardizations are often based on the quantitative analysis of a single compound,which may not reflect the total characteristic,bioactive and toxic nature of the herbs or products.Therefore,there is a need to establish an internationally recognized methodology for quality standardization of Chinese herbal medicines.The analytical methods reviewed in this article are pharmacognosy,TLC,HPLC,LCMS,CE and chemo-metrics.This article also covers the developments and applications of these methods in quality standardization.Recent advances show that a combination of these methods creates an overall chemical profile of each herb.This is supported by results reviewed in this article and obtained in our laboratory tests on medicinal herbs including Hypericum perforatum,Morinda officinalis and Centella asiatica.Significant variations in active components have been observed between herbal samples and products.It is proposed that the identification of active components,pharmacological activities and eventual clinical applications are required for a comprehensive quality standardization system.Our findings indicate that the combination of various chromatographic and chemometric methods will advance the methodology of quality standardization and enhance the overall confidence in herbal medicine for the health practitioner and the public.

Dynamic Simulation of Shear-induced Particle Migration in a Two-dimensional Circular Couette Device

The shear-induced migration of neutrally-buoyant non-colloidal circular particles in a two-dimensional circular Couette flow is investigated numerically with a distributed Lagrange multiplier based fictitious domain method.The effects of inertia and volume fraction on the particle migration are examined.The results indicate that inertia has a negative effect on the particle migration.In consistence with the experimental observations,the rapid migration of particles near the inner cylinder at the early stage is observed in the simulation,which is believed to be related to the chain-like clustering of particles.The migration of circular particles in a plane Poiseuille flow is also examined in order to further confirm the effect of such clustering on the particle migration at early stage.There is tendency for the particles in the vicinity of outer cylinder in the Couette device to pack into concentric rings at late stage in case of high particle concentration.

Mapping of an Approximate Neutral Density Surface with Ungridded Data

A neutral density surface is a logical study frame for water-mass mixing since water parcels spread along such a surface without doing work against buoyancy restoring force. Mesoscale eddies are believed to stir and subsequently mix predominantly along such surfaces. Because of the nonlinear nature of the equation of state of seawater, the process of accurately mapping a neutral density surface necessarily involves lateral computation from one conductivity, temperature and depth (CTD) cast to the next in a logical sequence. By contrast, the depth of a potential density surface on any CTD cast is found solely from the data on this cast. The lateral calculation procedure causes a significant inconvenience. In a previous paper by present author published in this journal (You, 2006), the mapping of neutral density surfaces with regularly gridded data such as Levitus data has been introduced. In this note, I present a new method to find the depth of a neutral density surface from a cast without having to specify an integration path in space. An appropriate reference point is required that is on the neutral density surface and thereafter the neutral density surface can be de- termined by using the CTD casts in any order. This method is only approximate and the likely errors can be estimated by plotting a scatter diagram of all the pressures and potential temperatures on the neutral density surfaces. The method assumes that the variations of potential temperature and pressure (with respect to the values at the reference point) on the neutral density surface are proportional. It is important to select the most appropriate reference point in order to approximately satisfy this assumption, and in practice this is found by inspecting the θ-p plot of data on the surface. This may require that the algorithm be used twice. When the straight lines on the θ-p plot, drawn from the reference point to other points on the neutral density surface, enclose an area that is external to the clus- ter of θ-p points of the neutral density surface, errors will occur, and these errors can be quantified from this diagram. Examples showing the use of the method are presented for each of the world’s main oceans.

Generalization of predator recognition:Velvet geckos display anti-predator behaviours in response to chemicals from non-dangerous elapid snakes

Many prey species detect chemical cues from predators and modify their behaviours in ways that reduce their risk ofpredation. Theory predicts that prey should modify their anti-predator responses according to the degree of threat posed by thepredator. That is, prey should show the strongest responses to chemicals of highly dangerous prey, but should ignore or respondweakly to chemicals from non-dangerous predators. However, if anti-predator behaviours are not costly, and predators are rarelyencountered, prey may exhibit generalised antipredator behaviours to dangerous and non-dangerous predators. In Australia, mostelapid snakes eat lizards, and are therefore potentially dangerous to lizard prey. Recently, we found that the nocturnal velvetgecko Oedura lesueurii responds to chemicals from dangerous and non-dangerous elapid snakes, suggesting that it displays generalisedanti-predator behaviours to chemicals from elapid snakes. To explore the generality of this result, we videotaped the behaviourof velvet geckos in the presence of chemical cues from two small elapid snakes that rarely consume geckos: the nocturnalgolden-crowned snake Cacophis squamulosus and the diurnal marsh snake Hemiaspis signata. We also videotaped geckos in trialsinvolving unscented cards (controls) and cologne-scented cards (pungency controls). In trials involving Cacophis and Hemiaspischemicals, 50% and 63% of geckos spent long time periods (> 3 min) freezing whilst pressed flat against the substrate, respectively.Over half the geckos tested exhibited anti-predator behaviours (tail waving, tail vibration, running) in response to Cacophis(67%) or Hemiaspis (63%) chemicals. These behaviours were not observed in control or pungency control trials. Our resultssupport the idea that the velvet gecko displays generalised anti-predator responses to chemical cues from elapid snakes.Generalised responses to predator chemicals may be common in prey species that co-occur with multiple, ecologically similar,dangerous predators [Current Zoology 56 (3): 337-342, 2010].

A NUMERICAL STUDY ON THE UNSTEADY EVOLUTION OF WEAK AXISYMMETRIC FOUNTAIN FLOWS IN A HOMOGENEOUS AMBIENT

Weak axisymmetrical fountains resulting from the injection of a dense fluid upwards into a large container of homogeneous fluid of lower density has been studied numerically in this paper using a time-accurate finite volume scheme. The behaviour of fountains for both the uniform and parabolic profiles of the discharge velocity at the fountain source has been investigated. The evolution of transient fountain flow has been analysed and two distinct stages of evolution have been identified. The time trace of the position of the fountain front has been presented and the initial, temporary and final fountain height and fountain width have been determined.

Key technique of a detection sensor for coal mine wire ropes

Wire ropes,employed extensively in coal mine hoists and transportation systems are subject to damage due to wear,corrosion and fatigue.The extent of damage and the carrying capacity of ropes are closely related to the sense of safety by staff and equipments.Magnetic flux leakage detection method(MFL),as an effective method,is these days widely used in detection of broken strands of wire ropes.In order to improve the accuracy of detection of flaws in wire ropes by magnetic flux leakage(MFL),the effect of the distance between a sensor and the surface of a wire rope(i.e.,lift-off) on detection by magnetic flux leakage was in-vestigated.An analysis of the main principles for the choice of lift-off is described by us and a new method that improves the structure of the detector is proposed from the point of view of the design of a magnetic circuit,to restrain the impact of fluctuations of sensor lift-off.The effect of this kind of method is validated by simulation and computation.The results show that the detection sensitivity is markedly increased by this method.Furthermore,the signal-to-noise ratio(SNR) can be increased by over 28%.This method will lend itself to offer reliable scientific information to optimize the structure of excitation devices and improve the accuracy of MFL detection.