Development of diabetic complications and influencing factors among 32653 type 2 diabetes patients:retrospective cohort study using a multi-state Markov

Background:Patients with type 2 diabetes are at high risk for developing multiple chronic complications.However,there is a lack of studies of the cumulative number of diabetic complications in China.Methods:A retrospective cohort study was performed from 2009 to 2021.Type 2 diabetes patients who were first diagnosed after the age of 35 years between January 1,2009,and December 31,2017,were included.Five states were defined according to the number of chronic complications:no(S0),one(S1),two(S2),three(S3),and four or more complications(S4).A multi-state Markov model was constructed to estimate transition probability,transition intensity,mean sojourn time,and the possible factors for each state.Results:The study included 32653 type 2 diabetes patients(mean age,59.59 years;15929(48.8%)male),and mean follow-up time of 7.75 years.In all,4375 transitions were observed.The 12-year transition probability of from state S0 to S1 was the lowest at 16.4%,while that from S2 to S3 was the highest,at 45.6%.Higher fasting blood glucose,lower high-density lipoprotein cholesterol,higher total cholesterol,and an unhealthy diet were associated with higher risk of progression from S0 to S1.Being female,less than 60 years old,weekly physical activity,and vegetarian diet decreased this risk.Being female and less than 60 years old reduced the likelihood of transition from S1 to S2,whereas lower high-density lipoprotein cholesterol increased this likelihood.Conclusions:Following the occurrence of two complications in type 2 diabetes patients,the risk for accumulating a third complication within a short time is significantly increased.It is important to take advantage of the stable window period when patients have fewer than two complications,strengthen the monitoring of blood glucose and blood lipids,and encourage patients to maintain good living habits to prevent further deterioration.

A Two-Step Algorithm to Estimate Variable Importance for Multi-State Data:An Application to COVID-19

Survival data with amulti-state structure are frequently observed in follow-up studies.An analytic approach based on a multi-state model(MSM)should be used in longitudinal health studies in which a patient experiences a sequence of clinical progression events.One main objective in the MSM framework is variable selection,where attempts are made to identify the risk factors associated with the transition hazard rates or probabilities of disease progression.The usual variable selection methods,including stepwise and penalized methods,do not provide information about the importance of variables.In this context,we present a two-step algorithm to evaluate the importance of variables formulti-state data.Three differentmachine learning approaches(randomforest,gradient boosting,and neural network)as themost widely usedmethods are considered to estimate the variable importance in order to identify the factors affecting disease progression and rank these factors according to their importance.The performance of our proposed methods is validated by simulation and applied to the COVID-19 data set.The results revealed that the proposed two-stage method has promising performance for estimating variable importance.

Reliability Modeling and Evaluation of Complex Multi-State System Based on Bayesian Networks Considering Fuzzy Dynamic of Faults

In the traditional reliability evaluation based on the Bayesian method,the failure probability of nodes is usually expressed by the average failure rate within a period of time.Aiming at the shortcomings of traditional Bayesian network reliability evaluation methods,this paper proposes a Bayesian network reliability evaluation method considering dynamics and fuzziness.The fuzzy theory and the dynamic of component failure probability are introduced to construct the dynamic fuzzy set function.Based on the solving characteristics of the dynamic fuzzy set and Bayesian network,the fuzzy dynamic probability and fuzzy dynamic importance degree of the fault state of leaf nodes are solved.Finally,through the dynamic fuzzy reliability analysis of CNC machine tool hydraulic system balance circuit,the application of this method in system reliability evaluation is verified,which provides support for fault diagnosis of CNC machine tools.

Importance measure of system reliability upgrade for multi-state consecutive k-out-of-n systems

Importance measures in reliability systems are used to identify weak components in contributing to a proper function of the system. Traditional importance measures mainly concerned the changing value of the system reliability caused by the change of the reliability of the component, and seldom considered the joint effect of the probability distribution, improvement rate of the object component. This paper studies the rate of the system reliability upgrading with an improvement of the component reliability for the multi-state consecutive k-out-of-n system. To verify the multi-state consecutive k-out-of-n system reliability upgrading by improving one component based on its improvement rate, an increasing potential importance （IPI） and its physical meaning are described at first. Secondly, the relationship between the IPI and Birnbaum importance measures are discussed. And the IPI for some different improvement actions of the component is further discussed. Thirdly, the characteristics of the IPI are analyzed. Finally, an application to an oil pipeline system is given.

Capacitated stochastic coloured Petri net-based approach for computing two-terminal reliability of multi-state network

Classical network reliability problems assume both net- works and components have only binary states, fully working or fully failed states. But many actual networks are multi-state, such as communication networks and transportation networks. The nodes and arcs in the networks may be in intermediate states which are not fully working either fully failed. A simulation ap- proach for computing the two-terminal reliability of a multi-state network is described. Two-terminal reliability is defined as the probability that d units of demand can be supplied from the source to sink nodes under the time threshold T. The capacities of arcs may be in a stochastic state following any discrete or continuous distribution. The transmission time of each arc is also not a fixed number but stochastic according to its current capacity and de- mand. To solve this problem, a capacitated stochastic coloured Petri net is proposed for modelling the system behaviour. Places and transitions respectively stand for the nodes and arcs of a net- work. Capacitated transition and self-modified token colour with route information are defined to describe the multi-state network. By the simulation, the two-terminal reliability and node importance can be estimated and the optimal route whose reliability is highest can also be given. Finally, two examples of different kinds of multi- state networks are given.

A voltage support control strategy based on three-port flexible multi-state switch in distribution networks

Voltage sags in power system may lead to serious problems such as the off-grid of distributed generation and electrical equipment failures.As a novel type of power electronic equipment,a flexible multi-state switch(FMSS)is capable to support the voltage during the grid faults.In this paper,a voltage control strategy to support the voltage in a distribution network is proposed by introducing three-port FMSS.The positive-negative-sequence compensation(PNSC)scheme is adopted to control the active and reactive current.This control scheme eliminates active power oscillations at the port of voltage sags and reduces coupling oscillations of other ports.Based on the characteristics of the voltage support under PNSC scheme,two voltage support strategies are proposed.A proportional-integral controller is introduced to provide the reactive power references,which eliminates the errors when estimating the grid voltage and impedance.A current limiting scheme is adopted to keep the port current in a safe range by adjusting the active and reactive power references.The voltage support strategies in two different voltage sags are simulated,and results show the feasibility and effectiveness of the proposed control strategies.

Integrated importance measure for multi-state coherent systems of k level

To verify the effectiveness of the integrated importance measure （IIM） for multi-state coherent systems of k level, the definition and physical meaning of IIM are demonstrated. Then, the improvement potential and Δ-importance measures are generalized to multi-state coherent systems based on the system performance level, and the relationships between IIM and traditional importance measures are discussed. The characteristics of IIM are demonstrated in both series and parallel systems. Also, an application to an oil transportation system is given. The comparison results show that： （i） IIM has some useful properties that are not possessed by traditional importance measures; （ii） IIM is effective in evaluating the component role in multi-state systems when the component reliability and the failure rate are simultaneously considered.

Importance Analysis of a Multi-state System Based on Direct Partial Logic Derivatives and Multi-valued Decision Diagrams

Importance analysis quantifies the critical degree of individual component. Compared with the traditional binary state system,importance analysis of the multi-state system is more aligned with the practice. Because the multi-valued decision diagram( MDD) can reflect the relationship between the components and the system state bilaterally, it was introduced into the reliability calculation of the multi-state system( MSS). The building method,simplified criteria,and path search and probability algorithm of MSS structure function MDD were given,and the reliability of the system was calculated. The computing methods of importance based on MDD and direct partial logic derivatives( DPLD) were presented. The diesel engine fuel supply system was taken as an example to illustrate the proposed method. The results show that not only the probability of the system in each state can be easily obtained,but also the influence degree of each component and its state on the system reliability can be obtained,which is conducive to the condition monitoring and structure optimization of the system.

The Mechanical Stabilization and Multi-States of the Stretched VWF A2 Domain

At the vascular injury sites,the ultra-large (UL) multimeric von willebrand Factor (VWF) is released in response to physiological and pathophysiological stimuli,and mediates platelet adhesion,aggregation,and cross-linking to maintain hemostasis.This UL-VWF is specifically cleaved by ADAMTS13(A Disintegrin And Metalloprotease with a ThromboSpondintype-1 motif,member 13)to prevent microvascular thrombosis.Each VWF monomer consists of five types of repeat domains in the order of D1-D2-D’-D3-A1-A2-A3-D4-C1-C2-C3-C4-C5-C6-CK,in which the A2 domain contains the ADAMTS13cleavage site(Tyr1605-Met1606),exposure of which requires mechanical or chemical stimuli.Under flows,fluid shear stress regulates VWF degradation and size distribution through opening the A2 domain and exposing its cleavage site for ADAMTS13.VWF A2 domain contains a C-terminal vicinal disulfide bond,a calcium binding sites,and a flexibleα4-less-loop.These unique structure features together make A2 more sensitive to mechanical signal than other VWF A subdomains,i.e.A1 and A3 domains.It is believed that A2 is first bound with and then cleaved by ADAMTS13,together with force-induced conformation transformation.To reveal molecular basis of this two-step model of VWF hydrolyzation by ADAMTS13,we here examined stretch-induced unfolding processes of VWF A2 domain in more detail by Steered molecular dynamics(SMD)simulations,with the use of crystal structure of VWF A2(PDB ID 3GXB),and observed that there were multiple quasi-stable conformations of stretched A2 until itsβ4-strand and a3-helix were pulled away the central hydrophobic core and the cleavage sites were fully accessible to solvent.Our MD simulation data showed that,in unfolding,at first,the cleavage site residue Tyr1605 was exposed partially and binding sites for Spacer domain of ADAMTS13 were exposed to a high level whenα6-helix was separated from A2 body;then,withβ6-strand and a5-helix been pulled away,the binding sites for Cysrich domain of ADAMTS13 was exposed completely while the exposure degree of Tyr1605 was not improved;further,separation ofβ5-strand andα4-less-loop made Tyr1605 and Met1606 and the respective binding sites for ADAMTS13 Spacer domain,Cys-rich domain,and Disintegrin-like domain be fully exposed to reach the optimal catalytic state;lastly,withβ4-strand separation,the cleavage sites and binding sites all were overstretched,leading to mismatch of ADAMTS13 and A2 conformation especially in the binding sites.This conformational mismatch may cause reduction of ADAMTS13 hydrolysis efficiency.Furthermore,the data of SMD simulations under constant forces demonstrated that,the stretched A2 conformation had different quasi-stable states,which all had the better mechanical stability within simulation time of 100 ns;and the conformational transformation from one state to another must overcome their respective potential barriers.The hydrolysis efficiency should depend on each state of the stretched A2 conformation,because of the exclusive matched-degree of A2 and ADMATS13.This computer prediction on the mechanical stability and multi-states of stretched A2 provides a novel insight into the mechano-chemical regulation on cleavage of A2 by ADAMTS13.It would be helpful for design of related drug targeting the binding sites on A2 and exosites on ADAMTS13 for the treatment of patients with acquired TTP.

Reliability Improvement of Large Multi-state Series-parallel Systems

In the paper, excess methods for improving the reliability of multi-state series-parallel systems are presented： for the hot reserve of single components, the cold reserve of single components, and the mixed （hot and cold） reserve of single components. A process is also introduced to improve the reliability of these methods by replacing their components with more reliable ones. New theorems for multi-state limit reliability functions in homogeneous and non-homogeneous series-parallel large systems composed of components with improved reliability are presented, and applied to compare the effects of these systems in different reliability improving methods.

Reliability Evaluation and Sensitivity Analysis for Multi-state System Based on Time Degradation Measures

The performance and state of multi-state system depend on its structure and different state combinations of the components. In order to evaluate the reliability of multi-state system effectively,a reliability evaluation and sensitivity analysis method based on the time degradation measures was proposed. The equivalence sets of the multi-state system under different output performances were established. The state combinations were classified according to the performance level. The degradation probability models under different states were established,and the new reliability measures,such as dynamic probability of multi-state system,holding time in each state,dynamic expectation function and integrated expectation function of the performance,were proposed and used to implement the dynamic reliability evaluation and sensitivity analysis. A certain diesel engine fuel feeding system was taken as an application example to illustrate the proposed method. The results show that not only the holding time in the desired state of the components and the system can be predicted,but also the best state component in a certain time period can be obtained.

烧嘴ON-OFF控制在罩式退火炉温度控制中的应用

退火炉是冷轧生产的关键工艺设备,罩式退火炉因其投资小、产品多样、产能灵活调整等优点被广泛使用。介绍了烧嘴ON-OFF控制在罩式退火炉温度控制中的实现方法。通过现场的实践应用,表明ON-OFF控制方式具有投入费用低、控制灵活、调节范围广、精度准确等优点。

On the use of residual dipolar couplings in multi-state structure calculation of two-domain proteins

Residual dipolar couplings(RDCs)are powerful nuclear magnetic resonance(NMR)probes for the structure calculation of biomacromolecules.Typically,an alignment tensor that defines the orientation of the entire molecule relative to the magnetic field is determined either before refinement of individual bond vectors or simultaneously with this refinement.For single-domain proteins this approach works well since all bond vectors can be described within the same coordinate frame,which is given by the alignment tensor.However,novel approaches are sought after for systems where no universal alignment tensor can be used.Here,we present an approach that can be applied to two-domain proteins that enables the calculation of multiple states within each domain as well as with respect to the relative positions of the two domains.

“On-off”switch for H_(2)and O_(2)generation from HCOOH resp.H_(2)O_(2)

In spite of the numerous advances in the development of H_(2)and O_(2)evolutions upon water splitting,the separation of H_(2)from O_(2)still remains a severe challenge.Herein,the novel dual-functional nanocatalysts Pd/carbon nanosphere(CNS),obtained via immobilization of ultrafine Pd nanoparticles onto CNS,are developed and employed for both selective H_(2)generation from HCOOH dehydrogenation and O_(2)evolution from H_(2)O_(2)decomposition.In these reactions,the highest activities for Pd/CNS-800(i.e.,calcinated at 800℃)are 2478 h−1 and 993 min^(−1)for H_(2)and O_(2)evolution,respectively.The highly efficient and selective“on-off”switch for selective H_(2)generation from HCOOH is successfully realized by pH adjustment.This novel and highly efficient nanocatalyst Pd/CNS-800 not only provides new approaches for the promising application of HCOOH and H_(2)O_(2)as economic and safe H_(2)and O_(2)carriers,respectively,for fuel cells,but also promotes the development of“on-off”switch for on-demand H_(2)evolution.

基于天棚On-Off控制的磁流变半主动悬架研究

以平行平板流动模型和Bingham模型为理论基础,推导了磁流变减振器的阻尼力计算公式.在车辆悬架动态性能模拟试验台上对磁流变减振器的示功特性和速度特性进行了试验验证.最后基于天棚on-off控制,利用dSPACE搭建了实车试验平台,并进行了实际越野路面的道路试验.试验结果表明:与传统被动悬架对比,磁流变半主动悬架能够很好地抑制车身以及驾驶员座椅的低频共振峰值,降低车身垂向振动幅值,提高车辆行驶平顺性和乘坐舒适性.

On-off控制对高速动车组综合动力学性能的影响分析

利用ADAMS-Matlab联合仿真的方法研究了on-off半主动控制对高速动车组的横向平稳性、运动稳定性和安全性的影响。根据国内某型号高速动车组的参数,利用多体动力学软件ADAMS/Rail建立了满载工况下的单车动车组模型。随后,运用ADAMS-Matlab联合仿真的方法对被动控制和on-off半主动控制条件下的动车组模型进行了仿真分析,仿真考虑了不同运行速度和不同线路条件等工况。最后,分别计算了两种控制条件下高速动车组模型的横向平稳性、运动稳定性和安全性能。从分析结果可知:与被动控制相比,on-off控制下车辆的横向平稳性指标可大幅提升35.5%,但非线性临界速度降低了16.6%,高速运行工况下的安全性指标也严重下降。因此,on-off控制策略在高速动车组上应用时存在严重缺陷,需要对其进行改良方可应用。

物联网中基于信任抗On-off攻击的自适应安全机制

为了降低静态安全机制中不必要的数据源认证开销和防御信任阈值机制中存在的On-off攻击,在物联网(IoT)环境下提出了一种基于信任的自适应安全机制。首先,根据节点在信息交互中的行为表现建立节点间的信任评估模型,进而给出节点总体信任值的度量方法;然后,对于总体信任值高于信任阈值的节点,采用基于信任的自适应检测算法实时地检测这些节点总体信任值的变化情况;最终,中继节点根据自适应检测的结果决定是否验证接收到的消息。仿真实验结果和分析表明,该机制降低了中继节点的能量开销,同时对物联网中的On-off攻击起到较好的防御作用。

一种基于BETA分布抗On-off攻击的信任机制

在无线传感器网络(WSNs)中,加密和认证机制只能预防外部攻击,对于内部攻击的防御,信任管理机制则是一种较好的方法。On-off攻击作为内部攻击的一种,由于其节点信誉值动态调整,具有更大的隐蔽性与攻击性。通过在BETA分布下采用差值判决与趋势分析方法,提出了一种有效抗On-off攻击的信任机制。仿真结果证明该机制能够很好的抵御On-off攻击,且易于实现。

ATM网络中Pareto分布的ON-OFF业务源对CBR业务时延性能的影响

持续时间长度服从Pareto分布的ON-OFF源，是比指数分布的ON-OFF源更为接近实际业务统计特性的业务模型．本文研究了背景业务为ParetoON－OFF源时，CBR业务的时延性能．结果表明，Pareto分布中的β值决定了ParetoON－OFF业务对CBR业务性能影响程度的大小当β值不大于2时，ON（OFF）持续时间方差为无穷大，此时CBR业务的时延性能十分差，需要对ON－OFF源进行平滑处理。

刺激大鼠杏仁外侧核对皮层AⅠ区ON-OFF神经元反应及调谐曲线的影响

在30只氨基甲酸乙酯麻醉的SD大鼠上记录神经元单位放电,观察短纯音诱发的皮层AⅠ区神经元ON-OFF反应的特性及电刺激杏仁外侧核(lateral amygdaloid nucleus,LA)对ON-OFF反应以及调谐曲线的影响。实验证实,AⅠ区神经元ON-OFF反应的模式与纯音刺激的强度、频率及作用时程有关;刺激LA可以抑制ON-OFF反应的放电频数,使反应的阈值升高,或使反应放电构型发生变化;此外,刺激LA能使ON-OFF神经元的调谐曲线变窄,Q_(10)数值增大。研究结果不仅表明ON-OFF神经元能对纯音刺激的时程、强度和频率等多种信息进行编码,而且还证明杏仁外侧核可以在皮层水平参与听觉信息的调制,削弱或衰减某些听觉信息,导致整个调谐曲线上移变窄,从而提高AⅠ区ON-OFF神经元的频率选择性能,有利于检测外界嘈杂环境中特定的听觉信息。