Probabilistic Saliency Approach for Elongated Structure Detection using Deformable Models

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Electric Power Systems Research

1. Introduction Trying to cut down the budget spent on maintenance every year, utilities need to come up with optimized maintenance schedules with limited budget. This task involves quantifying maintenance impact, which is a bit challenging task. Existing system level maintenance strategies such as RCM approach, Risk-Based approach etc. reported in Refs. [1–6] require considering the effect of component maintenance quantitatively through models such as probabilistic maintenance models [7–10] and/or failure rate estimation models. These models depend on condition-based data and history of operation of power system equipment such as transmission lines, transformers or circuit breakers (CBs). This paper proposes a probabilistic methodology to quantify the effect of device maintenance for circuit breakers. The proposed methodology utilizes the control circuit data of CB to deﬁne several performance indices. Fig. 1 shows the electrical representation of CB control circuit and the data consists of several voltage and current wave forms measured across trip coil, close coil and auxiliary contacts captured when the CB operates (either open or close operation). A sample representation of these signal waveforms

卵园孔未闭介入封堵指针今天还是明天

➢ 随访4年。
Байду номын сангаас
结果
➢ 与药物治疗组比较，经皮封堵组患者联合终点（死亡、卒中和TIA）发生率趋于降低（8.5 % vs 24.3%，P=0.05）；
➢ 对于脑血管事件发生不止1次的患者，经皮介入完全封堵PFO的患者反复卒中和TIA发生率比药物治疗患者明显减少（7.3% vs 33.2%, P=0.01）。
20%患者经颅超声仍有微泡； ➢ 结论：经颅对比剂多普勒对选择介入治疗很有价
值，介入封堵对合并CS的PFO患者有效。
自身对照研究
➢ 76例症状明显的PFO患者； ➢ 症状及表现形式：16卒中、32例反复TIA、28例偏头痛并
经MRI证实有脑缺血； ➢ 平均随访13.7±2.4个月； ➢ 结果： ➢ 所有病例无卒中和其他神经系统症状发生； ➢ 卒中和TIA患者中总偏头痛积分无变化； ➢ 所有病例中，偏头痛积分好转，其中35例（46%）不发作、
27例（36%）明显缓解、14例（18%）无好转。 ➢ 结论：对绝大多数症状严重的PFO患者介入治疗有效。
证明介入手术安全性的研究
➢1994-2003年对457例PFO（其中169例伴有 ASA）进行了封堵；
➢事件（包括卒中/TIA）发生率为1.9%； ➢手术并发症很低。（Schrader R，et al.J Interv Cardiol,2003;16:543-51)
率更高。
结论
➢经导管介入封堵PFO有可能对预防反常性卒中更为有效；
➢还需要进行随机临床试验进行比较。
来自希腊的最新研究报告
➢ 103例ASD和PFO患者接受封堵治疗； ➢ 其中33例为反复卒中的PFO患者； ➢ 平均随访24.3±14.5个月； ➢ 结果：成功封堵102例（PFO全部成功），并发症

Probabilistic model checking of an anonymity system

Probabilistic Model Checking ofan Anonymity SystemVitaly ShmatikovSRI International333Ravenswood AvenueMenlo Park,CA94025U.S.A.shmat@AbstractWe use the probabilistic model checker PRISM to analyze the Crowds system for anonymous Web browsing.This case study demonstrates howprobabilistic model checking techniques can be used to formally analyze se-curity properties of a peer-to-peer group communication system based onrandom message routing among members.The behavior of group mem-bers and the adversary is modeled as a discrete-time Markov chain,and thedesired security properties are expressed as PCTL formulas.The PRISMmodel checker is used to perform automated analysis of the system and ver-ify anonymity guarantees it provides.Our main result is a demonstration ofhow certain forms of probabilistic anonymity degrade when group size in-creases or random routing paths are rebuilt,assuming that the corrupt groupmembers are able to identify and/or correlate multiple routing paths originat-ing from the same sender.1IntroductionFormal analysis of security protocols is a well-establishedﬁeld.Model checking and theorem proving techniques[Low96,MMS97,Pau98,CJM00]have been ex-tensively used to analyze secrecy,authentication and other security properties ofprotocols and systems that employ cryptographic primitives such as public-key en-cryption,digital signatures,etc.Typically,the protocol is modeled at a highly ab-stract level and the underlying cryptographic primitives are treated as secure“black boxes”to simplify the model.This approach discovers attacks that would succeed even if all cryptographic functions were perfectly secure.Conventional formal analysis of security is mainly concerned with security against the so called Dolev-Yao attacks,following[DY83].A Dolev-Yao attacker is a non-deterministic process that has complete control over the communication net-work and can perform any combination of a given set of attacker operations,such as intercepting any message,splitting messages into parts,decrypting if it knows the correct decryption key,assembling fragments of messages into new messages and replaying them out of context,etc.Many proposed systems for anonymous communication aim to provide strong, non-probabilistic anonymity guarantees.This includes proxy-based approaches to anonymity such as the Anonymizer[Ano],which hide the sender’s identity for each message by forwarding all communication through a special server,and MIX-based anonymity systems[Cha81]that blend communication between dif-ferent senders and recipients,thus preventing a global eavesdropper from linking sender-recipient pairs.Non-probabilistic anonymity systems are amenable to for-mal analysis in the same non-deterministic Dolev-Yao model as used for veriﬁca-tion of secrecy and authentication protocols.Existing techniques for the formal analysis of anonymity in the non-deterministic model include traditional process formalisms such as CSP[SS96]and a special-purpose logic of knowledge[SS99].In this paper,we use probabilistic model checking to analyze anonymity prop-erties of a gossip-based system.Such systems fundamentally rely on probabilistic message routing to guarantee anonymity.The main representative of this class of anonymity systems is Crowds[RR98].Instead of protecting the user’s identity against a global eavesdropper,Crowds provides protection against collaborating local eavesdroppers.All communication is routed randomly through a group of peers,so that even if some of the group members collaborate and share collected lo-cal information with the adversary,the latter is not likely to distinguish true senders of the observed messages from randomly selected forwarders.Conventional formal analysis techniques that assume a non-deterministic at-tacker in full control of the communication channels are not applicable in this case. Security properties of gossip-based systems depend solely on the probabilistic be-havior of protocol participants,and can be formally expressed only in terms of relative probabilities of certain observations by the adversary.The system must be modeled as a probabilistic process in order to capture its properties faithfully.Using the analysis technique developed in this paper—namely,formalization of the system as a discrete-time Markov chain and probabilistic model checking of2this chain with PRISM—we uncovered two subtle properties of Crowds that causedegradation of the level of anonymity provided by the system to the users.First,if corrupt group members are able to detect that messages along different routingpaths originate from the same(unknown)sender,the probability of identifyingthat sender increases as the number of observed paths grows(the number of pathsmust grow with time since paths are rebuilt when crowd membership changes).Second,the conﬁdence of the corrupt members that they detected the correct senderincreases with the size of the group.Theﬁrstﬂaw was reported independently byMalkhi[Mal01]and Wright et al.[W ALS02],while the second,to the best ofour knowledge,was reported for theﬁrst time in the conference version of thispaper[Shm02].In contrast to the analysis by Wright et al.that relies on manualprobability calculations,we discovered both potential vulnerabilities of Crowds byautomated probabilistic model checking.Previous research on probabilistic formal models for security focused on(i)probabilistic characterization of non-interference[Gra92,SG95,VS98],and(ii)process formalisms that aim to faithfully model probabilistic properties of crypto-graphic primitives[LMMS99,Can00].This paper attempts to directly model andanalyze security properties based on discrete probabilities,as opposed to asymp-totic probabilities in the conventional cryptographic sense.Our analysis methodis applicable to other probabilistic anonymity systems such as Freenet[CSWH01]and onion routing[SGR97].Note that the potential vulnerabilities we discovered inthe formal model of Crowds may not manifest themselves in the implementationsof Crowds or other,similar systems that take measures to prevent corrupt routersfrom correlating multiple paths originating from the same sender.2Markov Chain Model CheckingWe model the probabilistic behavior of a peer-to-peer communication system as adiscrete-time Markov chain(DTMC),which is a standard approach in probabilisticveriﬁcation[LS82,HS84,Var85,HJ94].Formally,a Markov chain can be deﬁnedas consisting in aﬁnite set of states,the initial state,the transition relation such that,and a labeling functionfrom states to aﬁnite set of propositions.In our model,the states of the Markov chain will represent different stages ofrouting path construction.As usual,a state is deﬁned by the values of all systemvariables.For each state,the corresponding row of the transition matrix de-ﬁnes the probability distributions which govern the behavior of group members once the system reaches that state.32.1Overview of PCTLWe use the temporal probabilistic logic PCTL[HJ94]to formally specify properties of the system to be checked.PCTL can express properties of the form“under any scheduling of processes,the probability that event occurs is at least.”First,deﬁne state formulas inductively as follows:where atomic propositions are predicates over state variables.State formulas of the form are explained below.Deﬁne path formulas as follows:Unlike state formulas,which are simplyﬁrst-order propositions over a single state,path formulas represent properties of a chain of states(here path refers to a sequence of state space transitions rather than a routing path in the Crowds speci-ﬁcation).In particular,is true iff is true for every state in the chain;is true iff is true for all states in the chain until becomes true,and is true for all subsequent states;is true iff and there are no more than states before becomes true.For any state and path formula,is a state formula which is true iff state space paths starting from satisfy path formula with probability greater than.For the purposes of this paper,we will be interested in formulas of the form ,evaluated in the initial state.Here speciﬁes a system con-ﬁguration of interest,typically representing a particular observation by the adver-sary that satisﬁes the deﬁnition of a successful attack on the protocol.Property is a liveness property:it holds in iff will eventually hold with greater than probability.For instance,if is a state variable represent-ing the number of times one of the corrupt members received a message from the honest member no.,then holds in iff the prob-ability of corrupt members eventually observing member no.twice or more is greater than.Expressing properties of the system in PCTL allows us to reason formally about the probability of corrupt group members collecting enough evidence to success-fully attack anonymity.We use model checking techniques developed for veriﬁca-tion of discrete-time Markov chains to compute this probability automatically.42.2PRISM model checkerThe automated analyses described in this paper were performed using PRISM,aprobabilistic model checker developed by Kwiatkowska et al.[KNP01].The toolsupports both discrete-and continuous-time Markov chains,and Markov decisionprocesses.As described in section4,we model probabilistic peer-to-peer com-munication systems such as Crowds simply as discrete-time Markov chains,andformalize their properties in PCTL.The behavior of the system processes is speciﬁed using a simple module-basedlanguage inspired by Reactive Modules[AH96].State variables are declared in thestandard way.For example,the following declarationdeliver:bool init false;declares a boolean state variable deliver,initialized to false,while the followingdeclarationconst TotalRuns=4;...observe1:[0..TotalRuns]init0;declares a constant TotalRuns equal to,and then an integer array of size,indexed from to TotalRuns,with all elements initialized to.State transition rules are speciﬁed using guarded commands of the form[]<guard>-><command>;where<guard>is a predicate over system variables,and<command>is the tran-sition executed by the system if the guard condition evaluates to mandoften has the form<expression>...<expression>, which means that in the next state(i.e.,that obtained after the transition has beenexecuted),state variable is assigned the result of evaluating arithmetic expres-sion<expression>If the transition must be chosen probabilistically,the discrete probability dis-tribution is speciﬁed as[]<guard>-><prob1>:<command1>+...+<probN>:<commandN>;Transition represented by command is executed with probability prob,and prob.Security properties to be checked are stated as PCTL formulas (see section2.1).5Given a formal system speciﬁcation,PRISM constructs the Markov chain and determines the set of reachable states,using MTBDDs and BDDs,respectively. Model checking a PCTL formula reduces to a combination of reachability-based computation and solving a system of linear equations to determine the probability of satisfying the formula in each reachable state.The model checking algorithms employed by PRISM include[BdA95,BK98,Bai98].More details about the im-plementation and operation of PRISM can be found at http://www.cs.bham. /˜dxp/prism/and in[KNP01].Since PRISM only supports model checking ofﬁnite DTMC,in our case study of Crowds we only analyze anonymity properties ofﬁnite instances of the system. By changing parameters of the model,we demonstrate how anonymity properties evolve with changes in the system conﬁguration.Wright et al.[W ALS02]investi-gated related properties of the Crowds system in the general case,but they do not rely on tool support and their analyses are manual rather than automated.3Crowds Anonymity SystemProviding an anonymous communication service on the Internet is a challenging task.While conventional security mechanisms such as encryption can be used to protect the content of messages and transactions,eavesdroppers can still observe the IP addresses of communicating computers,timing and frequency of communi-cation,etc.A Web server can trace the source of the incoming connection,further compromising anonymity.The Crowds system was developed by Reiter and Ru-bin[RR98]for protecting users’anonymity on the Web.The main idea behind gossip-based approaches to anonymity such as Crowds is to hide each user’s communications by routing them randomly within a crowd of similar users.Even if an eavesdropper observes a message being sent by a particular user,it can never be sure whether the user is the actual sender,or is simply routing another user’s message.3.1Path setup protocolA crowd is a collection of users,each of whom is running a special process called a jondo which acts as the user’s proxy.Some of the jondos may be corrupt and/or controlled by the adversary.Corrupt jondos may collaborate and share their obser-vations in an attempt to compromise the honest users’anonymity.Note,however, that all observations by corrupt group members are local.Each corrupt member may observe messages sent to it,but not messages transmitted on the links be-tween honest jondos.An honest crowd member has no way of determining whether6a particular jondo is honest or corrupt.The parameters of the system are the total number of members,the number of corrupt members,and the forwarding probability which is explained below.To participate in communication,all jondos must register with a special server which maintains membership information.Therefore,every member of the crowd knows identities of all other members.As part of the join procedure,the members establish pairwise encryption keys which are used to encrypt pairwise communi-cation,so the contents of the messages are secret from an external eavesdropper.Anonymity guarantees provided by Crowds are based on the path setup pro-tocol,which is described in the rest of this section.The path setup protocol is executed each time one of the crowd members wants to establish an anonymous connection to a Web server.Once a routing path through the crowd is established, all subsequent communication between the member and the Web server is routed along it.We will call one run of the path setup protocol a session.When crowd membership changes,the existing paths must be scrapped and a new protocol ses-sion must be executed in order to create a new random routing path through the crowd to the destination.Therefore,we’ll use terms path reformulation and proto-col session interchangeably.When a user wants to establish a connection with a Web server,its browser sends a request to the jondo running locally on her computer(we will call this jondo the initiator).Each request contains information about the intended desti-nation.Since the objective of Crowds is to protect the sender’s identity,it is not problematic that a corrupt router can learn the recipient’s identity.The initiator starts the process of creating a random path to the destination as follows: The initiator selects a crowd member at random(possibly itself),and for-wards the request to it,encrypted by the corresponding pairwise key.We’ll call the selected member the forwarder.The forwarderﬂips a biased coin.With probability,it delivers the request directly to the destination.With probability,it selects a crowd member at random(possibly itself)as the next forwarder in the path,and forwards the request to it,re-encrypted with the appropriate pairwise key.The next forwarder then repeats this step.Each forwarder maintains an identiﬁer for the created path.If the same jondo appears in different positions on the same path,identiﬁers are different to avoid inﬁnite loops.Each subsequent message from the initiator to the destination is routed along this path,i.e.,the paths are static—once established,they are not altered often.This is necessary to hinder corrupt members from linking multiple7paths originating from the same initiator,and using this information to compromise the initiator’s anonymity as described in section3.2.3.3.2Anonymity properties of CrowdsThe Crowds paper[RR98]describes several degrees of anonymity that may be provided by a communication system.Without using anonymizing techniques, none of the following properties are guaranteed on the Web since browser requests contain information about their source and destination in the clear.Beyond suspicion Even if the adversary can see evidence of a sent message,the real sender appears to be no more likely to have originated it than any other potential sender in the system.Probable innocence The real sender appears no more likely to be the originator of the message than to not be the originator,i.e.,the probability that the adversary observes the real sender as the source of the message is less thanupper bound on the probability of detection.If the sender is observed by the adversary,she can then plausibly argue that she has been routing someone else’s messages.The Crowds paper focuses on providing anonymity against local,possibly co-operating eavesdroppers,who can share their observations of communication in which they are involved as forwarders,but cannot observe communication involv-ing only honest members.We also limit our analysis to this case.3.2.1Anonymity for a single routeIt is proved in[RR98]that,for any given routing path,the path initiator in a crowd of members with forwarding probability has probable innocence against collaborating crowd members if the following inequality holds:(1)More formally,let be the event that at least one of the corrupt crowd members is selected for the path,and be the event that the path initiator appears in8the path immediately before a corrupt crowd member(i.e.,the adversary observes the real sender as the source of the messages routed along the path).Condition 1guarantees thatproving that,given multiple linked paths,the initiator appears more often as a sus-pect than a random crowd member.The automated analysis described in section6.1 conﬁrms and quantiﬁes this result.(The technical results of[Shm02]on which this paper is based had been developed independently of[Mal01]and[W ALS02],be-fore the latter was published).In general,[Mal01]and[W ALS02]conjecture that there can be no reliable anonymity method for peer-to-peer communication if in order to start a new communication session,the initiator must originate theﬁrst connection before any processing of the session commences.This implies that anonymity is impossible in a gossip-based system with corrupt routers in the ab-sence of decoy trafﬁc.In section6.3,we show that,for any given number of observed paths,the adversary’s conﬁdence in its observations increases with the size of the crowd.This result contradicts the intuitive notion that bigger crowds provide better anonymity guarantees.It was discovered by automated analysis.4Formal Model of CrowdsIn this section,we describe our probabilistic formal model of the Crowds system. Since there is no non-determinism in the protocol speciﬁcation(see section3.1), the model is a simple discrete-time Markov chain as opposed to a Markov deci-sion process.In addition to modeling the behavior of the honest crowd members, we also formalize the adversary.The protocol does not aim to provide anonymity against global eavesdroppers.Therefore,it is sufﬁcient to model the adversary as a coalition of corrupt crowd members who only have access to local communication channels,i.e.,they can only make observations about a path if one of them is se-lected as a forwarder.By the same token,it is not necessary to model cryptographic functions,since corrupt members know the keys used to encrypt peer-to-peer links in which they are one of the endpoints,and have no access to links that involve only honest members.The modeling technique presented in this section is applicable with minor mod-iﬁcations to any probabilistic routing system.In each state of routing path construc-tion,the discrete probability distribution given by the protocol speciﬁcation is used directly to deﬁne the probabilistic transition rule for choosing the next forwarder on the path,if any.If the protocol prescribes an upper bound on the length of the path(e.g.,Freenet[CSWH01]),the bound can be introduced as a system parameter as described in section4.2.3,with the corresponding increase in the size of the state space but no conceptual problems.Probabilistic model checking can then be used to check the validity of PCTL formulas representing properties of the system.In the general case,forwarder selection may be governed by non-deterministic10runCount goodbad lastSeen observelaunchnewstartrundeliver recordLast badObserve4.2Model of honest members4.2.1InitiationPath construction is initiated as follows(syntax of PRISM is described in section 2.2):[]launch->runCount’=TotalRuns&new’=true&launch’=false;[]new&(runCount>0)->(runCount’=runCount-1)&new’=false&start’=true;[]start->lastSeen’=0&deliver’=false&run’=true&start’=false;4.2.2Forwarder selectionThe initiator(i.e.,theﬁrst crowd member on the path,the one whose identity must be protected)randomly chooses theﬁrst forwarder from among all group mem-bers.We assume that all group members have an equal probability of being chosen, but the technique can support any discrete probability distribution for choosing for-warders.Forwarder selection is a single step of the protocol,but we model it as two probabilistic state transitions.Theﬁrst determines whether the selected forwarder is honest or corrupt,the second determines the forwarder’s identity.The randomly selected forwarder is corrupt with probability badCbe next on the path.Any of the honest crowd members can be selected as the forwarder with equal probability.To illustrate,for a crowd with10honest members,the following transition models the second step of forwarder selection: []recordLast&CrowdSize=10->0.1:lastSeen’=0&run’=true&recordLast’=false+0.1:lastSeen’=1&run’=true&recordLast’=false+...0.1:lastSeen’=9&run’=true&recordLast’=false;According to the protocol,each honest crowd member must decide whether to continue building the path byﬂipping a biased coin.With probability,the forwarder selection transition is enabled again and path construction continues, and with probability the path is terminated at the current forwarder,and all requests arriving from the initiator along the path will be delivered directly to the recipient.[](good&!deliver&run)->//Continue path constructionPF:good’=false+//Terminate path constructionnotPF:deliver’=true;The speciﬁcation of the Crowds system imposes no upper bound on the length of the path.Moreover,the forwarders are not permitted to know their relative position on the path.Note,however,that the amount of information about the initiator that can be extracted by the adversary from any path,or anyﬁnite number of paths,isﬁnite(see sections4.3and4.5).In systems such as Freenet[CSWH01],requests have a hops-to-live counter to prevent inﬁnite paths,except with very small probability.To model this counter,we may introduce an additional state variable pIndex that keeps track of the length of the path constructed so far.The path construction transition is then coded as follows://Example with Hops-To-Live//(NOT CROWDS)////Forward with prob.PF,else deliver13[](good&!deliver&run&pIndex<MaxPath)->PF:good’=false&pIndex’=pIndex+1+notPF:deliver’=true;//Terminate if reached MaxPath,//but sometimes not//(to confuse adversary)[](good&!deliver&run&pIndex=MaxPath)->smallP:good’=false+largeP:deliver’=true;Introduction of pIndex obviously results in exponential state space explosion, decreasing the maximum system size for which model checking is feasible.4.2.4Transition matrix for honest membersTo summarize the state space of the discrete-time Markov chain representing cor-rect behavior of protocol participants(i.e.,the state space induced by the abovetransitions),let be the state in which links of the th routing path from the initiator have already been constructed,and assume that are the honestforwarders selected for the path.Let be the state in which path constructionhas terminated with as theﬁnal path,and let be an auxiliary state. Then,given the set of honest crowd members s.t.,the transi-tion matrix is such that,,(see section4.2.2),i.e.,the probability of selecting the adversary is equal to the cumulative probability of selecting some corrupt member.14This abstraction does not limit the class of attacks that can be discovered using the approach proposed in this paper.Any attack found in the model where indi-vidual corrupt members are kept separate will be found in the model where their capabilities are combined in a single worst-case adversary.The reason for this is that every observation made by one of the corrupt members in the model with separate corrupt members will be made by the adversary in the model where their capabilities are combined.The amount of information available to the worst-case adversary and,consequently,the inferences that can be made from it are at least as large as those available to any individual corrupt member or a subset thereof.In the adversary model of[RR98],each corrupt member can only observe its local network.Therefore,it only learns the identity of the crowd member imme-diately preceding it on the path.We model this by having the corrupt member read the value of the lastSeen variable,and record its observations.This cor-responds to reading the source IP address of the messages arriving along the path. For example,for a crowd of size10,the transition is as follows:[]lastSeen=0&badObserve->observe0’=observe0+1&deliver’=true&run’=true&badObserve’=false;...[]lastSeen=9&badObserve->observe9’=observe9+1&deliver’=true&run’=true&badObserve’=false;The counters observe are persistent,i.e.,they are not reset for each session of the path setup protocol.This allows the adversary to accumulate observations over several path reformulations.We assume that the adversary can detect when two paths originate from the same member whose identity is unknown(see sec-tion3.2.2).The adversary is only interested in learning the identity of theﬁrst crowd mem-ber in the path.Continuing path construction after one of the corrupt members has been selected as a forwarder does not provide the adversary with any new infor-mation.This is a very important property since it helps keep the model of the adversaryﬁnite.Even though there is no bound on the length of the path,at most one observation per path is useful to the adversary.To simplify the model,we as-sume that the path terminates as soon as it reaches a corrupt member(modeled by deliver’=true in the transition above).This is done to shorten the average path length without decreasing the power of the adversary.15Each forwarder is supposed toﬂip a biased coin to decide whether to terminate the path,but the coinﬂips are local to the forwarder and cannot be observed by other members.Therefore,honest members cannot detect without cooperation that corrupt members always terminate paths.In any case,corrupt members can make their observable behavior indistinguishable from that of the honest members by continuing the path with probability as described in section4.2.3,even though this yields no additional information to the adversary.4.4Multiple pathsThe discrete-time Markov chain deﬁned in sections4.2and4.3models construc-tion of a single path through the crowd.As explained in section3.2.2,paths have to be reformulated periodically.The decision to rebuild the path is typically made according to a pre-determined schedule,e.g.,hourly,daily,or once enough new members have asked to join the crowd.For the purposes of our analysis,we sim-ply assume that paths are reformulated someﬁnite number of times(determined by the system parameter=TotalRuns).We analyze anonymity properties provided by Crowds after successive path reformulations by considering the state space produced by successive execu-tions of the path construction protocol described in section4.2.As explained in section4.3,the adversary is permitted to combine its observations of some or all of the paths that have been constructed(the adversary only observes the paths for which some corrupt member was selected as one of the forwarders).The adversary may then use this information to infer the path initiator’s identity.Because for-warder selection is probabilistic,the adversary’s ability to collect enough informa-tion to successfully identify the initiator can only be characterized probabilistically, as explained in section5.4.5Finiteness of the adversary’s state spaceThe state space of the honest members deﬁned by the transition matrix of sec-tion4.2.4is inﬁnite since there is no a priori upper bound on the length of each path.Corrupt members,however,even if they collaborate,can make at most one observation per path,as explained in section4.3.As long as the number of path reformulations is bounded(see section4.4),only aﬁnite number of paths will be constructed and the adversary will be able to make only aﬁnite number of observa-tions.Therefore,the adversary only needsﬁnite memory and the adversary’s state space isﬁnite.In general,anonymity is violated if the adversary has a high probability of making a certain observation(see section5).Toﬁnd out whether Crowds satisﬁes16。

每天两次氮斯汀喷鼻剂治疗季节性过敏性鼻炎的药用疗效外文翻译原文

R E V I E W Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitisFriedrich HorakMedical University Vienna,ENT – Univ. Clinic, Vienna, Austria Correspondence: Friedrich Horak HNO – Univ. Klinik Wien, Waehringer Guertel 18–20, A-1090 Vienna, A ustria T el +43 1 404 003 336Fax +43 1 789 76 76Email friedrich.horak@vienna.at Abstract: Azelastine nasal spray (Allergodil®, Lastin®, Aﬂ uon®; Meda AB, Stockholm, Sweden) is a fast-acting, efﬁ cacious and well-tolerated H1-receptor antagonist for the treatment of rhinitis. In addition it also has mast-cell stabilizing and anti-inﬂ ammatory properties, reducing the concentration of leukotrienes, kinins and platelet activating factor in vitro and in vivo, as well as inﬂ ammatory cell migration in rhinitis patients. Well-controlled studies in patients with seasonal allergic rhinitis (SAR), perennial rhinitis (PR) or vasomotor rhinitis (VMR) conﬁ rm that azelastine nasal spray has a rapid onset of action, and improves nasal symptoms associated with rhinitis such as nasal congestion and post-nasal drip. Azelastine nasal spray is effective at the lower dose of 1 spray as well at a dose of 2 sprays per nostril twice daily, but with an improved tolerability proﬁ le compared to the 2-spray per nostril twice daily regimen. Compared with intranasal corticosteroids, azelastine nasal spray has a faster onset of action and a better safety proﬁ le, showing at least comparable efﬁ cacy with ﬂ uticasone propionate (Flonase®; GSK, USA), and a superior efﬁ cacy to mometasone furoate (Nasonex®; Schering Plough, USA). In combination with ﬂ uticasone propionate, azelastine nasal spray exhibits greater efﬁ cacy than either agent used alone, and this combination may provide beneﬁ t for patients with difﬁ cult to treat seasonal allergic rhinitis. In addition, azelastine nasal spray can be used on an as-needed basis without compromising clinical efﬁ cacy. Compared with oral antihistamines, azelastine nasal spray also demonstrates superior efﬁ cacy and a more rapid onset of action, and is effective even in patients who did not respond to previous oral antihistamine therapy. Unlike most oral antihistamines, azelastine nasal spray is effective in alleviating nasal congestion, a particularly bothersome symptom for rhinitis sufferers. Azelastine nasal spray is well tolerated in both adults and children with allergic rhinitis. Bitter taste which seems to be associated with incorrect dosing technique is the most common side effect reported by patients, but this problem can be minimized by correct dosing technique.Keywords: azelastine nasal spray, rhinitis, intranasal corticosteroids, oral antihistamines, seasonal allergic rhinitisIntroductionRhinitis is an inflammatory disease of the upper airways, affecting approximately 58 million people only in the United States alone (Settipane 2001) and its prevalence is increasing. The cost of the disease is signiﬁ cant with between US$2 and US$5 billion incurred annually in both direct and indirect costs (Ray et al 1999; Reed et al 2004). In the US, the number of lost workdays is estimated as approximately 3.5 million a year (Mahr and Sheth 2005). It can be classiﬁ ed as allergic, non-allergic or mixed upper respiratory disorder (Berstein 2007). It is classiﬁ ed as allergic if symptoms occur in association with a speciﬁ c IgE-mediated response; as non-allergic if symptoms are induced by irritant triggers, but without an IgE-mediated response; and as of mixed etiology if IgE-mediated responses occur in conjunction with symptoms induced by both allergens and non-allergic irritant triggers. Allergic rhinitis (AR) is further classiﬁ ed as seasonal or perennial (Dykewicz et al 1998). Seasonal allergic rhinitis© 2008 Dove Medical Press Limited. A ll rights reservedTherapeutics and Clinical Risk Management 2008:4(5) 1009–10221009Horak(SAR) symptoms are induced by exposure to pollens from trees, grass, weeds or seasonal mould spores, whilst peren-nial rhinitis (PR) is associated with environmental allergens which are generally present on a year-round basis such as house dust, animal dander and insect droppings (Dykewicz et al 1998). In contrast, the “Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines” recommend a classiﬁ cation in intermittent allergic rhinitis and persistent allergic rhinitis according to the frequency and persistence of symptoms (Bousquet et al 2001).Symptoms of SAR include nasal congestion, runny nose, nasal and nasopharyngeal itching, ear symptoms, sneezing and ocular symptoms in many patients, including itchy and watery eyes (Bielory and Ambrosio 2002). The symptoms of sneezing, itching and rhinorrhea are less common with PR (Economides and Kaliner 2002). As many as half of all patients diagnosed with rhinitis have non-allergic disease (sometimes called vasomotor rhinitis [VMR]) where an allergic component cannot be identiﬁ ed (Dykewicz et al 1998). Symptoms are often induced by irritant triggers such as tobacco smoke, strong odors and temperature and pres-sure changes (Devyani and Corey 2004). The symptoms of VMR are similar to those of AR (Devyani and Corey 2004). To further complicate rhinitis classiﬁ cation, as many as half of all patients with AR are also sensitive to non-allergic triggers; a condition referred to as mixed rhinitis (Settipane and Settipane 2002; Liberman et al 2005). Symptoms of rhinitis can have a major impact on patients’ quality of life (QoL) by interfering with sleep which causes fatigue, and impairing daily activities and cognitive function (Dykewicz et al 1998). Patients often complain of an inability to concentrate, and in the case of SAR often avoid outdoor activities in order to avoid exposure to symptom-inducing allergen(s). The Joint Task Force on Allergy Practice and Parameters advises that improving the negative impact on daily life in rhinitis patients deﬁ nes successful treatment as much as providing symptom relief (Dykewicz et al 1998). Indeed, Juniper (1997) recommends that for most patients with rhinitis, improving patient well-being and QoL should be the primary goal of treatment.Treatment guidelines from the Joint Task Force and WHO recommend that antihistamines, both topical (eg, azelastine [Allergodil®; Meda AB, Stockholm, Sweden]) and oral second-generation (eg, loratadine [Claritin®, Schering Plough, USA], desloratadine [Clarinex®; Schering Plough, USA], fexofenadine [Allegra®; Sanoﬁ Aventis, USA] or cetirizine [Zyrtec®; Pﬁ zer, USA], and levocetirizine [Xyzall®; UCB, EU]) be used as ﬁ rst-line therapy for AR (Dykewicz et al 1998; Bousquet et al 2001). Intranasal corticosteroids (eg, ﬂ uticasone propionate [Flonase®, GSK, USA], mometasone furoate [Nasonex®; Schering Plough, USA]) may also be considered as initial therapy for AR in patients with more severe symp-toms, particularly nasal congestion [(Dykewicz et al 1998; LaForce 1999). The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines recommend a stepped approach to therapy based upon the frequency and severity of symptoms (Table 1) (Bousquet et al 2001). Interestingly, a recent US nationwide survey incorporating approximately 2500 adult allergy suf-ferers, revealed that 66% were dissatisﬁ ed with their current allergy medication due to lack of effectiveness (Anon 2006). Furthermore, more than two-thirds of primary care physicians reported patient dissatisfaction with therapy as the main reason for stopping or switching medications (Anon 2001). Clearly, effective therapies with a good safety proﬁ le are needed to treat AR sufferers.AzelastineAzelastine nasal spray is a topically administered second-generation antihistamine and selectively antagonizes the H1-receptor (Zechel et al 1981) being approximately tenfold more potent than chlorpheniramine in this regard (Casale 1989). It has one of the fastest onsets of action (15 min with nasal spray and up to 3 min with eye drops) among the currently available rhinitis medications (Baumgarten et al 1994; Greiff et al 1997). The effect of azelastine lasts at least 12 hours, thus allowing for a once or twice daily dosing regimen (Greiff et al 1997). It has proven efﬁ cacy in treating both allergic and non-allergic rhinitis, and is the only pre-scription antihistamine approved in the US, Portugal and the Netherlands for the treatment of both SAR (1996) and VMR (1999). In SAR patients azelastine therapy (two sprays per nostril twice daily), improved both total symptom and major symptom complex scores to a signiﬁ cantly greater extent than placebo (McTavish and Sorkin 1989; Storms et al 1994; LaForce et al 1996; Ratner and Sacks 2007). Similarly, in PR patients, azelastine nasal spray signiﬁ cantly improved sleep-ing, reduced daytime somnolence and nasal congestion com-pared with placebo (Golden et al 2000). Liberman et al (2005) were the ﬁ rst to show that azelastine was also effective in the management of VMR and even in mixed rhinitis. Azelastine nasal spray signiﬁ cantly (p Ͻ 0.01) reduced the total VMR symptom score (TVRSS) compared with placebo after 21-day double-blind treatment, and was associated with clinical improvement in each symptom of the TVRSS (ie, rhinorrhea, sneezing, nasal congestion, and post-nasal drip). In a large open-label trial 4364 patients received azelastine nasal sprayTherapeutics and Clinical Risk Management 2008:4(5)1010Azelastine nasal spray(2 sprays per nostril twice daily) as monotherapy for 2 weeks. 78% of VMR patients reported some or complete control of post-nasal drip which rose to 90% of SAR patients for the symptom of sneezing. Of patients reporting sleep difﬁ culties or impaired daytime activities because of rhinitis symptoms, 85% experienced improvements in these parameters with azelastine. Baseline sleep difﬁ culties and impairment of daytime activities were signiﬁ cant (p Ͻ 0.01) predictors of a positive treatment effect with azelastine nasal spray. Female patients (p = 0.02), patients with SAR (p Ͻ 0.01) and patients with SAR plus sensitivity to non-allergic triggers (p = 0.03) were identiﬁ ed as being most likely to respond to azelastine nasal spray (Liberman et al 2005) Due to its rapid onset of action, azelastine nasal spray continues to control rhinitis symptoms when used on an as-needed basis (Ciprandi et al 1997). This property of azelastine is discussed later. First marketed in the UK in 1991 for the treatment of both SAR and PR, it is currently available in more than 70 countries world-wide.Mode of actionH owever, azelastine is more than just an anti-histamine. It exhibits a very fast and long-acting effect based on a triple mode of action, with anti-inﬂ ammatory and mast cell stabilizing properties in addition to its anti-allergic effects (Bernstein 2007; Lee and Corren 2007). For example, azelas-tine inhibits the activation of cultured mast cells and release of interleukin (IL)-6, tryptase, and histamine (Kempuraj et al 2002). It also reduces mediators of mast cell degranu-lation such as leukotrienes which are involved in the late phase allergic response (Howarth 1997), in the nasal lavage ﬂ uid of patients with rhinitis (Shin et al 1992). It does this possibly by reducing the production of leukotriene (LT)B4 and LTC4, inhibiting phospholipase A2and LTC4synthase (H amasaki et al 1996). Leukotrienes are associated with dilation of vessels, increased vascular permeability and edema which results in nasal congestion, mucus production and recruitment of inﬂ ammatory cells (Golden et al 2006). Substance P and bradykinin concentrations which are formed in biological ﬂ uids and tissues during inﬂ ammation, are also reduced by azelastine (Shin et al 1992; Nieber et al 1993; Shinoda et al 1997). These agents are associated with the AR symptoms of nasal itching and sneezing, but may also contribute to the onset of non-allergic VMR symptoms. Other anti-inﬂ ammatory properties of azelastine include inhibition of tumor necrosis factor alpha (TNFα) releaseT able 1 Summary of ARIA allergic rhinitis management guidelinesRhinitis severity ARIA recommendationMild intermittent • Oral/intranasal antihistamines OR• Decongestants (10 days maximum)Moderate/severe intermittent • Intranasal antihistamines• Oral antihistamines AND/OR• Decongestants• Intranasal corticosteroids• CromonesMild persistent • Intranasal antihistamines• Oral antihistamines AND/OR• Decongestants• Intranasal corticosteroids• CromonesA stepwise approach is advised with reassessment after 2 weeks. If symptomsare controlled and the patient is on intranasal corticosteroid, the dose shouldbe reduced, but otherwise treatment continued. If symptoms persist and thepatient is on antihistamines or cromones, a change should be made to anintranasal corticosteroid.Moderate/severe persistent • Intranasal corticosteroid (ﬁ rst line treatment)If symptoms are uncontrolled after 2–4 weeks, medication should be addeddepending on the persistent symptom, eg, add an antihistamine if the majorsymptom is rhinorrhea, pruitis, or sneezing, double the dose of intranasalsteroid for persistent nasal blockage and add ipratropium for prominentcomplaint of rhinorrhea.Therapeutics and Clinical Risk Management 2008:4(5)1011Horak(Hide et al 1997; Matsuo and Takayama 1998), reduction of granulocyte macrophage colony-stimulating factor (GM-CSF) generation, as well as a reduction in the number of a range of inﬂ ammatory cytokines including interleukin (IL)-1β, IL-6, IL-4 and IL-8 (Y oneda et al 1997; Ito et al 1998; Beck et al 2000). These cytokines perpetuate the inﬂ ammatory response (Settipane 2001). Finally, in SAR patients, azelastine nasal spray has been shown to lower neutrophil and eosinophil counts and decrease intercel-lular adhesion molecule-1 (ICAM-1) expression on nasal epithelial cell surfaces in both the early and late phases of the allergic reaction (Ciprandi et al 1996). It also decreases free-radical production by human eosinophils and neutrophils (Busse et al 1989; Umeki 1992) and calcium inﬂ ux induced by platelet-activating factor in vitro (Nakamura et al 1988; Morita et al 1993).The use of a topical treatment has many advantages over a systemic treatment. Firstly, with a nasal spray, medication can be delivered directly to the site of allergic inﬂ ammation. Secondly, the higher concentrations of antihistamines that can be achieved in the nasal mucosa by topical as opposed to oral administration should enhance the anti-allergic and potential anti-inﬂ ammatory effects of these agents. Thirdly, a dose of 0.28 mg intranasally has a faster onset of action than a dose of 2.2 mg administrated orally (Horak et al 1994). And ﬁ nally, with topical administration the risk of interaction with concomitant medication is minimized (Davies et al 1996) and the potential of systemic effects reduced.DosageRecent results from 2 studies have shown that azelastine nasal spray at a dosage of 1 spray per nostril twice daily is effec-tive and has a better tolerability proﬁ le compared to 2 sprays per nostril twice daily in patients (Ն12 years; n = 554) with moderate to severe SAR (Lumry et al 2007). The total nasal symptom score (TNSS) improved by 14.1% in study 1 and by 22.1% in study 2 with azelastine nasal spray (1 spray per nostril twice daily) compared with 4.5% and 12.0% with placebo in study 1 (p = 0.01) and 2 (p Ͻ 0.01) respectively. This compares with a 24%–29% improvement in rhinitis symptoms scores with a 2-spray dosage of azelastine (Ratner et al 1994; Storms et al 1994; LaForce et al 1996). For individual symptoms, itchy nose, runny nose, sneezing, and nasal congestion were all signiﬁ cantly improved after the 1-spray azelastine regimen compared with placebo. One spray per nostril twice daily of azelastine was also associ-ated with signiﬁ cant improvements in the Rhinitis Quality of Life Questionnaire (RQLQ) daily activity and nasal symptoms domains and patient global evaluations compared with placebo. In addition, the incidence of a bitter taste after azelastine application more than halved and the incidence of somnolence decreased almost 30 times in the 1-spray group versus the labeled incidence with the 2-spray regimen (Lumry et al 2007). Although an earlier study showed an improve-ment in rhinitis symptoms versus placebo with azelastine 1 spray per nostril twice daily, this improvement failed to reach statistical signiﬁ cance. However, a global evaluation noted a signiﬁ cant clinical improvement versus placebo (49%) in the 1-spray regimen (75%, p Ͻ 0.001) as well as a 2-spray once daily (89%, p = 0.028) and a 2-spray twice daily regimen (83%, p Ͻ 0.001) (Weiler et al 1994).From these results one can conclude that a greater degree of effectiveness would be expected with two sprays per nostril twice daily. Although one spray per nostril twice daily may provide somewhat less efﬁ cacy this is compensated for by an improved tolerability proﬁ le compared with the 2-spray regimen. Therefore, the choice of dosage of azelastine nasal spray should be based on the severity and persistence of symptoms as well as the patient’s acceptance of the nasal spray (Bernstein 2007). For example, the 2-spray dose could be used as the starting dose for patients with severe symptoms of SAR, and either maintained or tapered to the 1-spray dose as required. The 1-spray dose could be used as a starting dose in patients with mild-to-moderate symptoms, and if necessary the dose increased to 2 sprays per nostril twice daily if symptom control proved to be inadequate (Lumry et al 2007).As-neededBecause azelastine starts working within 15 minutes of application investigators wondered how effective an as-needed regimen would be in controlling the symptoms of rhinitis (Ciprandi et al 1997). A randomized controlled study was car-ried out in 30 patients sensitized to Parietaria pollen or grass. Patients were treated with the standard European dose of azelas-tine (0.56 mg/day), half this dose (0.22 mg/day), or as-needed. Both groups who received the standard and half-standard doses showed an improvement in their rhinitis symptoms, with a concomitant reduction in markers of inﬂ ammation, namely neutrophil and eosinophil counts as well as ICAM-1 expression in nasal scrapings. However, patients who used azelastine nasal spray on an as-needed basis also showed an improvement in their rhinitis symptoms, but without a reduction in the markers of inﬂ ammation. The results of this small study suggest that although regular treatment with azelastine is superior at controlling symptoms, as-needed therapy may beTherapeutics and Clinical Risk Management 2008:4(5)1012Therapeutics and Clinical Risk Management 2008:4(5)1018Horakan improvement in TNSS of 32.5% compared with 24.6% for those patients taking oral cetirizine. The most common side effect reported by patients in the azelastine group was bitter taste (5.7%). Somnolence was reported by 1.5% of patients taking cetirizine (Sher and Sacks 2006).In addition to nasal symptoms, patients with SAR can experience impairment in HRQoL. Two 2-week, double-blind, multicenter studies were conducted during autumn 2004 and spring 2005 comparing the improvement with azelastine nasal spray (2 sprays per nostril twice daily) versus cetirizine (10 mg daily) on symptoms and HRQoL in SAR patients (Meltzer and Sacks 2006). Results from these studies revealed that azelastine nasal spray improved the overall RQLQ score to a signiﬁ cantly (p Ͻ 0.05) greater degree than cetirizine tablets. When results from both studies were pooled, the combined analysis conﬁ rmed the signiﬁ cant superiority of azelastine spray both in terms of the overall RQLQ score (p Ͻ 0.001) as well as each RQLQ domain (p Ͻ 0.03) including the nasal symptoms domain (p Ͻ 0.001). More patients in the azelastine nasal spray group experienced a clinically important improve-ment from baseline in HRQoL (ie, Ն2 units on the 0–6 rating scale) compared with patients in the cetirizine group (35% vs 20% respectively) (Meltzer and Sacks 2006).Berger et al (2006) also showed that azelastine nasal spray (2 sprays per nostril) and oral cetirizine (10 mg once daily) effectively treated nasal symptoms in patients with SAR (n = 360). Rapid relief of rhinitis symptoms was evident in both groups at the ﬁ rst evaluation after initial administration and continued during the 14 study days, with the azelastine patients showing the greatest degree of improvement during the second week of treatment. Improvements in the TNSS and individual symptoms favored azelastine over cetirizine (Figure 7), with signiﬁ cant differences for nasal congestion (p = 0.049) and sneezing (p = 0.01). Azelastine nasal spray improved TNSS by a mean of 4.6 (23.9%) compared with 3.9 (19.6%) with cetirizine. The positive effect of azelastine nasal spray on congestion was observed despite the fact that the cetirizine group had the added beneﬁ t of daily use of a placebo saline spray. Azelastine nasal spray also signiﬁ cantly improved the RQLQ overall (p = 0.002) and individual domain (p Յ 0.05) scores compared with cetirizine (Berger et al 2006). Although oral cetirizine signiﬁ cantly improved RQLQ scores, patients treated with azelastine nasal spray reported additional statistically signiﬁ cant improvement beyond that reported with cetirizine for each individual RQLQ domain including activities, sleep, non-nose/non-eye symp-toms, practical problems, nasal symptoms, eye symptoms, and emotions (Figure 8). Although it is often assumed that patients prefer oral medications to sprays in both the ACT I and ACTII trials, patients reported superior improvements in QoL variables with azelastine nasal spray compared with oral cetirizine (Corren et al 2005).MNSS Rhinorrhea Nasal Itching Sneezing Nasal Congestion1234AzelastineDesloratadine PlaceboA b s o l u t e I m p r o v e m e n t f r o m b a s e l i n e(120 m i n s c o r e –360 m i n s c o r e )Figure 6 Major nasal symptom and mean nasal symptom scores after administration of azelastine nasal spray (1 spray per nostril), desloratadine (5 mg) or placebo in patients with SAR: absolute changes of last value (6 hours after the start of challenge) compared to predose (ie, 2 hours after the start of the challenge). Reprinted with permission from Horak F , Zieglmayer UP , Zidglmayer R, et al 2006. A zelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and ef ﬁ cacy. Curr Med Res Opion , 22:151–7. Copyright © 2006 LibraPharm.as either ‘good’ or ‘very good’ compared with just 76% of levocabastine patients (Falser et al 2001).Safety and tolerabilityThe advantages of intranasal delivery include lower risk of systemic side effects and drug interactions (Salib and Howarth 2003). In controlled studies, azelastine nasal spray was well-tolerated for treatment durations up to 4 weeks in both adults and children (Ն12 years) (Storms et al 1994; Meltzer et al 1994; Ratner et al 1994; Weiler et al 1994; LaForce et al 1996). Bitter taste, headache, somnolence and nasal burning were the most frequently reported adverse events, but most of these were mild or moderate in nature. These studies reported a greater incidence of somnolence compared with placebo (11.5% vs 5.4%, p Ͻ 0.05). How-ever, the incidence of somnolence between azelastine- and placebo-treated patients (3.2% vs 1.0%) did not differ in VMR studies (Banov and Liberman 2001). Post-marketing surveillance studies also reported a similar degree of somnolence (approx 2%) in both azelastine and placebo groups (Berger and White 2003; LaForce et al 2004; Corren et al 2005; Berger et al 2006). The lower incidence of azelastine-related adverse events in later trials is most likely due to correct dosing technique, when the drug is administered without tipping back the head or deeplyinhaling the spray, both of which would increase systemic absorption and could result in bitter taste and somnolence. As the incidence of somnolence whilst using azelastine nasal spray has been reported to be greater than placebo in certain studies, US prescribing recommendations warn against concurrent use of alcohol and/or other CNS sup-pressants. However, to date no studies have been designed to assess speciﬁ cally the effects of azelastine nasal spray on the CNS in humans.DisclosuresThe author has no conﬂ icts of interest to report.AbbreviationsACT 1, first Azelastine Cetirizine Trial; AR, allergic rhinitis; ARIA, allergic rhinitis and its impact on asthma; EEC, environmental exposure chamber; GM-CSF, granu-locyte macrophage-colony stimulating factor; H RQoL, health-related quality of life; ICAM-1, intercellular adhe-sion molecule-1; IL, interleukin; LT, leukotriene; MNSS, major nasal symptom score; NNT, number needed to treat; PR, perennial rhinitis; QoL, quality of life; RQLQ, Rhinoconjunctivitis Quality of Life Questionnaire; SAR, seasonal allergic rhinitis; TNF α, tumor necrosis factor alpha;Azelastine nasal spray Cetirizine21.510.5M e a n i m p r o v e m e n t f r o m b a s e l i n eOverall RQLQ ScoreActivities SleepNon-nasal non-eye symptomsPractical problems Nasal symptoms Eye symptoms EmotionFigure 8 Mean improvement from baseline to day 14 in overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score and individual RQLQ domain scores (intention-to-treat population). *p Յ 0.05 vs cetirizine; **p Ͻ 0.01 vs cetirizine. Reprinted with permission from Berger W , Hampel F , Bernstein J, et al 2006. Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol , 97:375–81. Copyright © 2006 American College of Allergy, A sthma and Immunology.TNSS, total nasal symptom score; TVRSS, Total VMR Symptom Scale; VCC, Vienna Challenge Chamber; VMR, vasomotor rhinitis.ReferencesAl Suleimani YM, Walker MJA. 2007. Allergic rhinitis and its pharmacology.Pharmacol Ther, 114:233–60.Anon. 2001. Physician survey sponsored by the American College of Allergy, Asthma and Immunology. Rochester (NY): Harris Interactive Inc, October 19–21.Anon. 2006. Allergies in America: a landmark survey of nasal allergy sufferers. H ealthSTAR Communications, Inc. Sponsored by Altana Pharma US, Inc. March 1.Banov CH, Liberman P. 2001. Efﬁ cacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis. Ann Allergy Asthma Immunol, 86:28–35.Baumgarten CR, Petzold U, Dokic D, et al. 1994. Modiﬁ cation of allergen-induced symptoms and mediator release by intranasal azelastine.J Pharmacol Ther, 3:43–51.Beck G, Mansur A, Afzal M, et al. 2000. Effect of azelastine nasal spray on mediators of inﬂ ammation in patients with seasonal allergic rhinitis (SAR). American Academy of Allergy, Asthma and Immunology 56th Annual Meeting, San Diego (CA); March 3–8.Behncke VB, Alemar GO, Kaufman DA, et al. 2006. Azelastine nasal spray and ﬂ uticasone nasal spray in the treatment of geriatric patients with rhinitis. J Allergy Clin Immunol, 117:263Berger W, Hampel F, Bernstein J, et al. 2006. Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis. Ann Allergy Asthma Immunol, 97:375–81.Berger WE, White MV. 2003. Efﬁ cacy of azelastine nasal spray in patients with an unsatisfactory response to loratadine. An n Allergy Asthma Immunol, 91:205–11.Berkowitz TB, Bernstein DI, LaForce C, et al. 1999. Onset of action of mometasone furoate nasal spray (NASONEX) in seasonal allergic rhinitis. Allergy, 54:64–9.Bernstein JA. 2007. Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efﬁ cacy and tolerability. Curr Med Res Opin, 23:2441–52.Bielory L, Ambrosio P. 2002. Conjunctivitis and allergic eye diseases. In: Kaliner MA, editor. Current Reviews of Rhinitis. Philadelphia: Current Medicine, Inc. pp. 115–22.Bousquet J, van Cauwenberge PB, Khaltaev N, et al. 2001. Allergic rhinitis and its impact on asthma: ARIA workshop report. J Allergy Clin Immunol, 108:S147–S334.Busse W, Randley B, Sedgwick J, et al. 1989. The effect of azelastine on neutrophil and eosinophil generation of superoxide. J Allergy Clin Immunol, 83:400–5.Casale TB. 1989. The interaction of azelastine with human lung histamine H1, beta, and muscarinic receptor binding sites. J Allergy Clin Immunol, 83:771–6.Charlesworth EN, Kagey-Sobotka A, Norman PS, et al. 1989. Effect of cetirizine on mast cell-mediator release and cellular trafﬁ c during the cutaneous late-phase reaction. J Allergy Clin Immunol, 83:905–12. Cheria-Sammari S, Aloui R, Gormand B, et al. 1995. Leukotriene B4 pro-duction by blood neutrophils in allergic rhinitis: effects of cetirizine.Clin Exp Allergy, 25:729–36.Ciprandi G, Buscaglia S, Pesce G, et al. 1995. Cetirizine reduces inﬂ amma-tory cell recruitment and ICAM-1 (or CD54) expression on conjunctival epithelium in both early-and late-phase reactions after allergen-speciﬁ c challenge. J Allergy Clin Immunol, 95:612–21.Ciprandi G, Pronzato C, Passalacqua G, et al. 1996. Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-I expression on nasal epithelial cells: an anti-allergic activity. J Allergy Clin Immunol, 98:1088–96.Ciprandi G, Ricca V, Passalaqua G, et al. 1997. Seasonal rhinitis and azelastine: long- or short-term treatment? J Allergy Clin Immun ol, 99:301–7.Corren J, Storms W, Bernstein J, et al. 2005. Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis. Clin Ther, 27:543–53.Davies RJ, Bagnall AC, McCabe RN, et al. 1996. Antihistamines: topical vs oral administration. Clin Exp Allergy, 26:S11–S17.Devyani L, Corey JP. 2004. Vasomotor rhinitis update. Curr Opin Otolaryngol Head Neck Surg, 12:243–247.Dykewicz MS, Fineman S, Skoner DP, et al. 1998. Diagnosis and manage-ment of rhinitis: complete guidelines of the Joint ask Force on Practice Parameters in Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol, 81:478–518.Economides A, Kaliner MA. 2002. Allergic rhinitis. In: Kaliner MA, ed.Current Reviews of Rhinitis. Philadelphia: Current Medicine, Inc.pp. 35–51.Falser N, Wober W, Rahlfs VW, et al. 2001. Comparative efﬁ cacy and safety of azelastine and levocabastine nasal sprays in patients with seasonal allergic rhinitis. Arzeimittelforschung, 51:387–93.Golden MP, Gleason MM, Togias A. 2006. Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis. Clin Exp Allergy, 36:689–703.Golden S, Teets SJ, Lehman EB, et al. 2000. Effect of topical nasal azelastine on the symptoms of rhinitis, sleep and daytime somnolence in perennial allergic rhinitis. Ann Allergy Asthma Immunol, 85:53–7.Greiff L, Andersson M, Svensson C, et al. 1997. Topical azelastine has a 12-hour duration of action as assessed by histamine challenge-induced exudation of alpha 2-macroglobulin into human nasal airways. Clin Exp Allergy, 27:438–44.Hamasaki Y, Shaﬁ geh M, Y amamoto S, et al. 1996. Inhibition of leukotriene synthesis by azelastine. Ann Allergy Asthma Immunol, 76:469–75. Herman D, Garay R, Legal M. 1997. A randomized double-blind placebo controlled study of azelastine nasal spray in children with perennial rhinitis. Int J Pediatr Otorhinolaryngol, 39:1–8.H ide I. Toriu N, Nuibe T, et al. 1997. Suppression of TNF-α secre-tion by azelastine in a rat mast (RBL-2H3) cell line. J Immun ol, 159:2932–40.Horak F, Jager S, Toth J, et al. 1994. Azelastine in pollen-induced allergic rhinitis – a pharmacodynamic study of onset of action and efﬁ cacy.Drug Invest, 7:34–40.Horak F, Stübner P, Zieglmayer R, et al. 2003. Comparison of the effect of Desloratadine 5mg daily and placebo on nasal airﬂ ow and seasonal allergic rhinitis symptoms induced by grass pollen exposure. Allergy, 58:481–5.H orak F, Stübner P. 2002. Decongestant activity of deslorata-dine in controlled-allergen-exposure trials. Clin Drug In vest, 22(Suppl 2):13–20.Horak F, Stübner UP, Zieglmayer R, et al. 2002a. Effect of desloratadine versus placebo on nasal airﬂ ow and subjective measures of nasal obstruction in patients with grass pollen-induced allergic rhinitis in an allergen-exposure unit. J Allergy Clin Immunol, 109:956–61.Horak F, Stübner UP, Zieglmayer R, et al. 2002b. Effect of desloratadine versus placebo on nasal airﬂ ow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit. J Allergy Clin. Immunol, 109:956–61.Horak F, Zieglmayer UP, Zieglmayer R, et al. 2006. Azelastine nasal spray and Desloratadine tablets in pollen-induced seasonal allergic rhinitis:a pharmacodynamic study of onset of action and efﬁ cacy. Curr MedRes Opion, 22:151–7.Howarth PH. 1997. Mediators of nasal blockage in allergic rhinitis. Allergy, 52(Suppl 40):12–8.Ito H, Nakamura Y, Takagi S, et al. 1998. Effects of azelastine on the level of serum interluekin-4 and soluble CD23 antigen in the treatment of nasal allergy. Arzneim-Forsch, 48:1143–7.Juniper EF. 1997. Measuring health-related quality of life in rhinitis.J Allergy Clin Immunol, 99:S742–S9.。

Journal of Loss Prevention in the Process Industries

HAZOP e Local approach in the Mexican oil &gas industryM.Pérez-Marín a ,M.A.Rodríguez-Toral b ,*aInstituto Mexicano del Petróleo,Dirección de Seguridad y Medio Ambiente,Eje Central Lázaro Cárdenas Norte No.152,07730México,D.F.,Mexicob PEMEX,Dirección Corporativa de Operaciones,Gerencia de Análisis de Inversiones,Torre Ejecutiva,Piso 12,Av.Marina Nacional No.329,11311México,D.F.,Mexicoa r t i c l e i n f oArticle history:Received 3September 2012Received in revised form 26March 2013Accepted 27March 2013Keywords:HAZOPRisk acceptance criteria Oil &gasa b s t r a c tHAZOP (Hazard and Operability)studies began about 40years ago,when the Process Industry and complexity of its operations start to massively grow in different parts of the world.HAZOP has been successfully applied in Process Systems hazard identi ﬁcation by operators,design engineers and consulting ﬁrms.Nevertheless,after a few decades since its ﬁrst applications,HAZOP studies are not truly standard in worldwide industrial practice.It is common to ﬁnd differences in its execution and results format.The aim of this paper is to show that in the Mexican case at National level in the oil and gas industry,there exist an explicit acceptance risk criteria,thus impacting the risk scenarios prioritizing process.Although HAZOP studies in the Mexican oil &gas industry,based on PEMEX corporate standard has precise acceptance criteria,it is not a signi ﬁcant difference in HAZOP applied elsewhere,but has the advantage of being fully transparent in terms of what a local industry is willing to accept as the level of risk acceptance criteria,also helps to gain an understanding of the degree of HAZOP applications in the Mexican oil &gas sector.Contrary to this in HAZOP ISO standard,risk acceptance criteria is not speci ﬁed and it only mentions that HAZOP can consider scenarios ranking.The paper concludes indicating major implications of risk ranking in HAZOP,whether before or after safeguards identi ﬁcation.Ó2013Elsevier Ltd.All rights reserved.1.IntroductionHAZOP (Hazard and Operability)studies appeared in systematic way about 40years ago (Lawley,1974)where a multidisciplinary group uses keywords on Process variables to ﬁnd potential hazards and operability troubles (Mannan,2012,pp.8-31).The basic prin-ciple is to have a full process description and to ask in each node what deviations to the design purpose can occur,what causes produce them,and what consequences can be presented.This is done systematically by applying the guide words:Not ,More than ,Less than ,etc.as to generate a list of potential failures in equipment and process components.The objective of this paper is to show that in the Mexican case at National level in the oil and gas industry,there is an explicit acceptance risk criteria,thus impacting the risk scenarios priori-tizing process.Although HAZOP methodology in the Mexican oil &gas industry,based on PEMEX corporate standard has precise acceptance criteria,it is not a signi ﬁcant difference in HAZOP studies applied elsewhere,but has the advantage of being fullytransparent in terms of what a local industry is willing to accept as the level of risk acceptance criteria,also helps to gain an under-standing of the degree of HAZOP applications in the Mexican oil &gas sector.Contrary to this in HAZOP ISO standard (ISO,2000),risk acceptance criteria is not speci ﬁed and it only mentions that HAZOP can consider scenarios ranking.The paper concludes indicating major implications of risk prioritizing in HAZOP,whether before or after safeguards identi ﬁcation.2.Previous workHAZOP studies include from original ICI method with required actions only,to current applications based on computerized documentation,registering design intentions at nodes,guide words,causes,deviations,consequences,safeguards,cause fre-quencies,loss contention impact,risk reduction factors,scenarios analysis,ﬁnding analysis and many combinations among them.In the open literature there have been reported interesting and signi ﬁcant studies about HAZOP,like HAZOP and HAZAN differences (Gujar,1996)where HAZOP was identi ﬁed as qualitative hazard identi ﬁcation technique,while HAZAN was considered for the quantitative risk determination.This difference is not strictly valid today,since there are now companies using HAZOP with risk analysis*Corresponding author.Tel.:þ525519442500x57043.E-mail addresses:mpmarin@imp.mx (M.Pérez-Marín),miguel.angel.rodriguezt@ ,matoral09@ (M.A.Rodríguez-Toral).Contents lists available at SciVerse ScienceDirectJournal of Loss Prevention in the Process Industriesjou rn al homepage :/locate/jlp0950-4230/$e see front matter Ó2013Elsevier Ltd.All rights reserved./10.1016/j.jlp.2013.03.008Journal of Loss Prevention in the Process Industries 26(2013)936e 940and its acceptance criteria(Goyal&Kugan,2012).Other approaches include HAZOP execution optimization(Khan,1997);the use of intelligent systems to automate HAZOP(Venkatasubramanian,Zhao, &Viswanathan,2000);the integration of HAZOP with Fault Tree Analysis(FTA)and with Event Tree Analysis(ETA)(Kuo,Hsu,& Chang,1997).According to CCPS(2001)any qualitative method for hazard evaluation applied to identify scenarios in terms of their initial causes,events sequence,consequences and safeguards,can beextended to register Layer of Protection Analysis(LOPA).Since HAZOP scenarios report are presented typically in tabular form there can be added columns considering the frequency in terms of order of magnitude and the probability of occurrence identiﬁed in LOPA.There should be identiﬁed the Independent and the non-Independent Protection Layers,IPL and non-IPL respec-tively.Then the Probability of Failure on Demand(PFDs)for IPL and for non-IPL can be included as well as IPL integrity.Another approach consists of a combination of HAZOP/LOPA analysis including risk magnitude to rank risk reduction actions (Johnson,2010),a general method is shown,without emphasizing in any particular application.An extended HAZOP/LOPA analysis for Safety Integrity Level(SIL)is presented there,showing the quan-titative beneﬁt of applying risk reduction measures.In this way one scenario can be compared with tolerable risk criteria besides of being able to compare each scenario according to its risk value.A recent review paper has reported variations of HAZOP methodology for several applications including batch processes, laboratory operations,mechanical operations and programmable electronic systems(PES)among others(Dunjó,Fthenakis,Vílchez, &Arnaldos,2010).Wide and important contributions to HAZOP knowledge have been reported in the open literature that have promoted usage and knowledge of HAZOP studies.However,even though there is available the IEC standard on HAZOP studies,IEC-61882:2001there is not a worldwide agreement on HAZOP methodology and there-fore there exist a great variety of approaches for HAZOP studies.At international level there exist an ample number of ap-proaches in HAZOP studies;even though the best advanced prac-tices have been taken by several expert groups around the world, there is not uniformity among different consulting companies or industry internal expert groups(Goyal&Kugan,2012).The Mexican case is not the exception about this,but in the local oil and gas industry there exist a national PEMEX corporate standard that is speciﬁc in HAZOP application,it includes ranking risk scenarios (PEMEX,2008),qualitative hazard ranking,as well as the two ap-proaches recognized in HAZOP,Cause by Cause(CÂC)and Devia-tion by Deviation(DÂD).Published work including risk criteria include approaches in countries from the Americas,Europe and Asia(CCPS,2009),but nothing about Mexico has been reported.3.HAZOP variationsIn the technical literature there is no consensus in the HAZOP studies procedure,from the several differences it is consider that the more important are the variations according to:(DÂD)or (CÂC).Table1shows HAZOP variations,where(CQÂCQ)means Consequence by Consequence analysis.The implications of choosing(CÂC)are that in this approach there are obtained unique relationships of Consequences,Safeguards and Recommendations,for each speciﬁc Cause of a given Deviation. For(DÂD),all Causes,Consequences,Safeguards and Recommenda-tions are related only to one particular Deviation,thus producing that not all Causes appear to produce all the Consequences.In practice HAZOP approach(DÂD)can optimize analysis time development.However,its drawback comes when HAZOP includes risk ranking since it cannot be determined easily which Cause to consider in probability assignment.In choosing(CÂC)HAZOP there is no such a problem,although it may take more time on the analysis.The HAZOP team leader should agree HAZOP approach with customer and communicate this to the HAZOP team.In our experience factors to consider when choosing HAZOP approach are:1.If HAZOP will be followed by Layers of Protection Analysis(LOPA)for Safety Integrity Level(SIL)selection,then choose (CÂC).2.If HAZOP is going to be the only hazard identiﬁcation study,it isworth to make it with major detail using(CÂC).3.If HAZOP is part of an environmental risk study that requires aConsequence analysis,then use(DÂD).4.If HAZOP is going to be done with limited time or becauseHAZOP team cannot spend too much time in the analysis,then use(DÂD).Although this is not desirable since may compro-mise process safety.Regarding risk ranking in HAZOP,looking at IEC standard(IEC, 2001)it is found that HAZOP studies there are(DÂD)it refers to (IEC,1995)in considering deviation ranking in accordance to their severity or on their relative risk.One advantage of risk ranking is that presentation of HAZOP results is very convenient,in particular when informing the management on the recommendations to be followedﬁrst or with higher priority as a function of risk evaluated by the HAZOP team regarding associated Cause with a given recommendation.Tables2and3are shown as illustrative example of the convenience of event risk ranking under HAZOP,showing no risk ranking in Table2and risk ranking in Table3.When HAZOP presents a list of recommendations without ranking,the management can focus to recommendations with perhaps the lower resource needs and not necessarily the ones with higher risk.Table1Main approaches in HAZOP studies.Source HAZOP approach(Crowl&Louvar,2011)(DÂD)(ABS,2004)(CÂC)&(DÂD)(Hyatt,2003)(CÂC),(DÂD)&(CQÂCQ) (IEC,2001)(DÂD)(CCPS,2008);(Crawley,Preston,& Tyler,2008)(DÂD),(CÂC)Table2HAZOP recommendations without risk ranking.DescriptionRecommendation1Recommendation2Recommendation3Recommendation4Recommendation5Table3HAZOP recommendations with risk ranking.Scenario risk DescriptionHigh Recommendation2High Recommendation5Medium Recommendation3Low Recommendation1Low Recommendation4M.Pérez-Marín,M.A.Rodríguez-Toral/Journal of Loss Prevention in the Process Industries26(2013)936e940937As can be seen in Tables 2and 3,for the management there will be more important to know HAZOP results as in Table 3,in order to take decisions on planning response according to ranking risk.4.HAZOP standard for the Mexican oil &gas industryLooking at the worldwide recognized guidelines for hazard identi ﬁcation (ISO,2000)there is mentioned that when consid-ering scenarios qualitative risk assignment,one may use risk matrix for comparing the importance of risk reduction measures of the different options,but there is not a speci ﬁc risk matrix with risk values to consider.In Mexico there exist two national standards were tolerable and intolerable risk is de ﬁned,one is the Mexican National Standard NOM-028(NOM,2005)and the other is PEMEX corporate standard NRF-018(PEMEX,2008).In both Mexican standards the matrix form is considered for relating frequency and consequences.Fig.1shows the risk matrix in (NOM,2005),nomenclature regarding letters in this matrix is described in Tables 4e 6.It can be mentioned that risk matrix in (NOM,2005)is optional for risk management in local chemical process plants.For Mexican oil &gas industry,there exist a PEMEX corporate standard (NRF),Fig.2,shows the corresponding risk matrix (PEMEX,2008).Nomenclature regarding letters in this matrix is described in Tables 7e 9for risk concerning the community.It is important to mention that PEMEX corporate standard considers environmental risks,business risks,and corporate image risks.These are not shown here for space limitations.The Mexican National Standard (NOM)as being of general applicability gives the possibility for single entities (like PEMEX)to determine its own risk criteria as this company opted to do.PEMEX risk matrix can be converted to NOM ’s by category ’s grouping infrequency categories,thus giving same ﬂexibility,but with risk speci ﬁc for local industry acceptance risk criteria.One principal consideration in ranking risk is to de ﬁne if ranking is done before safeguards de ﬁnition or after.This de ﬁnition is relevant in:HAZOP kick-off presentation by HAZOP leader,explaining im-plications of risk ranking.HAZOP schedule de ﬁnition.Risk ranking at this point takes shorter time since time is not consumed in estimating risk reduction for each safeguard.If after HAZOP a LOPA is going to be done,then it should be advisable to request that HAZOP leader considers risk ranking before safeguards de ﬁnition,since LOPA has established rules in de ﬁning which safeguards are protections and the given risk reduction.Otherwise if for time or resource limitations HAZOP is not going to be followed by LOPA,then HAZOP should consider risk ranking after safeguards de ﬁnition.Therefore,the HAZOP leader should explain to the HAZOP team at the kick-off meeting a concise explanation of necessary considerations to identify safeguards having criteria to distinguish them as Independent Protection Layers (IPL)as well as the risk reduction provided by each IPL.In HAZOP report there should be make clear all assumptions and credits given to the Protections identi ﬁed by the HAZOP team.Figs.3and 4,shows a vision of both kinds of HAZOP reports:For the case of risk ranking before and after safeguards de ﬁnition.In Figs.3Fig.1.Risk matrix in (NOM,2005).Table 5Probability description (Y -axis of matrix in Fig.1)(NOM,2005).Frequency Frequency quantitative criteria L41in 10years L31in 100years L21in 1000years L1<1in 1000yearsTable 6Risk description (within matrix in Fig.1)(NOM,2005).Risk level Risk qualitative descriptionA Intolerable:risk must be reduced.B Undesirable:risk reduction required or a more rigorous risk estimation.C Tolerable risk:risk reduction is needed.DTolerable risk:risk reduction not needed.Fig.2.Risk matrix as in (PEMEX,2008).Table 7Probability description (Y -axis of matrix in Fig.2)(PEMEX,2008).Frequency Occurrence criteria Category Type Quantitative QualitativeHighF4>10À1>1in 10yearsEvent can be presented within the next 10years.Medium F310À1À10À21in 10years e 1in 100years It can occur at least once in facility lifetime.LowF210À2À10À31in 100years e 1in 1000years Possible,it has never occurred in the facility,but probably ithas occurred in a similar facility.Remote F1<10À3<1in 1000years Virtually impossible.It is norealistic its occurrence.Table 4Consequences description (X -axis of matrix in Fig.1)(NOM,2005).Consequences Consequence quantitative criteriaC4One or more fatalities (on site).Injuries or fatalities in the community (off-site).C3Permanent damage in a speci ﬁc Process or construction area.Several disability accidents or hospitalization.C2One disability accident.Multiple injuries.C1One injured.Emergency response without injuries.M.Pérez-Marín,M.A.Rodríguez-Toral /Journal of Loss Prevention in the Process Industries 26(2013)936e 940938and4“F”means frequency,C means consequence and R is risk as a function of“F”and“C”.One disadvantage of risk ranking before safeguards deﬁnition is that resulting risks usually are found to be High,Intolerable or Unacceptable.This makes difﬁcult the decision to be made by the management on what recommendations should be carried outﬁrst and which can wait.One advantage in risk ranking after safeguards deﬁnition is that it allows to show the management the risk scenario fully classiﬁed, without any tendency for identifying most risk as High(Intolerable or Unacceptable).In this way,the management will have a good description on which scenario need prompt attention and thus take risk to tolerable levels.There is commercial software for HAZOP methodology,but it normally requires the user to use his/her risk matrix,since risk matrix deﬁnition represents an extensive knowledge,resources and consensus to be recognized.The Mexican case is worldwide unique in HAZOP methodology, since it uses an agreed and recognized risk matrix and risk priori-tizing criteria according to local culture and risk understanding for the oil&gas sector.The risk matrix with corresponding risk levels took into account political,economical and ethic values.Advantages in using risk matrix in HAZOP are:they are easy to understand and to apply;once they are established and recognized they are of low cost;they allow risk ranking,thus helping risk reduction requirements and limitations.However,some disad-vantages in risk matrix use are:it may sometimes be difﬁcult to separate frequency categories,for instance it may not be easy to separate low from remote in Table7.The risk matrix subdivision may have important uncertainties,because there are qualitative considerations in its deﬁnition.Thus,it may be advantageous to update Pemex corporate HAZOP standard(PEMEX,2008)to consider a6Â6matrix instead of the current4Â4matrix.5.ConclusionsHAZOP studies are not a simple procedure application that as-sures safe Process systems on its own.It is part of a global design cycle.Thus,it is necessary to establish beforehand the HAZOP study scope that should include at least:methodology,type(CÂC,DÂD, etc.)report format,acceptance risk criteria and expected results.Mexico belongs to the reduced number of places where accep-tance risk criteria has been explicitly deﬁned for HAZOP studies at national level.ReferencesABS.(2004).Process safety institute.Course103“Process hazard analysis leader training,using the HAZOP and what-if/checklist techniques”.Houston TX:Amer-ican Bureau of Shipping.CCPS(Center for Chemical Process Safety).(2001).Layer of protection analysis: Simpliﬁed process risk assessment.New York,USA:AIChE.CCPS(Center for Chemical Process Safety).(2008).Guidelines for hazard evaluation procedures(3rd ed.).New York,USA:AIChE/John Wiley&Sons.CCPS(Center for Chemical Process Safety).(2009).Guidelines for Developing Quan-titative Safety Risk Criteria,Appendix B.Survey of worldwide risk criteria appli-cations.New York,USA:AIChE.Crawley,F.,Preston,M.,&Tyler,B.(2008).HAZOP:Guide to best practice(2nd ed.).UK:Institution of Chemical Engineers.Crowl,D.A.,&Louvar,J.F.(2011).Chemical process safety,fundamentals with ap-plications(3rd ed.).New Jersey,USA:Prentice Hall.Table8Consequences description(X-axis of matrix in Fig.2)(PEMEX,2008).Event type and consequence categoryEffect:Minor C1Moderate C2Serious C3Catastrophic C4 To peopleNeighbors Health and Safety.No impact on publichealth and safety.Neighborhood alert;potentialimpact to public health and safety.Evacuation;Minor injuries or moderateconsequence on public health and safety;side-effects cost between5and10millionMX$(0.38e0.76million US$).Evacuation;injured people;one ormore fatalities;sever consequenceon public health and safety;injuriesand side-consequence cost over10million MX$(0.76million US$).Health and Safetyof employees,serviceproviders/contractors.No injuries;ﬁrst aid.Medical treatment;Minor injurieswithout disability to work;reversible health treatment.Hospitalization;multiple injured people;total or partial disability;moderate healthtreatment.One o more fatalities;Severe injurieswith irreversible damages;permanenttotal or partial incapacity.Table9Risk description(within matrix in Fig.2)(PEMEX,2008).Risk level Risk description Risk qualitative descriptionA Intolerable Risk requires immediate action;cost should not be a limitation and doing nothing is not an acceptable option.Risk with level“A”represents an emergency situation and there should be implements with immediate temporary controls.Risk mitigation should bedone by engineered controls and/or human factors until Risk is reduced to type“C”or preferably to type“D”in less than90days.B Undesirable Risk should be reduced and there should be additional investigation.However,corrective actions should be taken within the next90days.If solution takes longer there should be installed on-site immediate temporary controls for risk reduction.C Acceptablewith control Signiﬁcant risk,but can be compensated with corrective actions during programmed facilities shutdown,to avoid interruption of work plans and extra-costs.Solutions measures to solve riskﬁndings should be done within18months.Mitigation actions should focus operations discipline and protection systems reliability.D ReasonablyacceptableRisk requires control,but it is of low impact and its attention can be carried out along with other operations improvements.Fig.3.Risk ranking before safeguard deﬁnition.Fig.4.Risk ranking after safeguards deﬁnition.M.Pérez-Marín,M.A.Rodríguez-Toral/Journal of Loss Prevention in the Process Industries26(2013)936e940939Dunjó,J.,Fthenakis,V.,Vílchez,J.A.,&Arnaldos,J.(2010).Hazard and opera-bility(HAZOP)analysis.A literature review.Journal of Hazardous Materials, 173,19e32.Goyal,R.K.,&Kugan,S.(2012).Hazard and operability studies(HAZOP)e best practices adopted by BAPCO(Barahin Petroleum Company).In Presented at SPE middle east health,safety,security and environment conference and exhibition.Abu Dhabi,UAE.2e4April.Gujar,A.M.(1996).Myths of HAZOP and HAZAN.Journal of Loss Prevention in the Process Industry,9(6),357e361.Hyatt,N.(2003).Guidelines for process hazards analysis,hazards identiﬁcation and risk analysis(pp.6-7e6-9).Ontario,Canada:CRC Press.IEC.(1995).IEC60300-3-9:1995.Risk management.Guide to risk analysis of techno-logical systems.Dependability management e Part3:Application guide e Section 9:Risk analysis of technological systems.Geneva:International Electrotechnical Commission.IEC.(2001).IEC61882.Hazard and operability studies(HAZOP studies)e Application guide.Geneva:International Electrotechnical Commission.ISO.(2000).ISO17776.Guidelines on tools and techniques for hazard identiﬁcation and risk assessment.Geneva:International Organization for Standardization.Johnson,R.W.(2010).Beyond-compliance uses of HAZOP/LOPA studies.Journal of Loss Prevention in the Process Industries,23(6),727e733.Khan,F.I.(1997).OptHAZOP-effective and optimum approach for HAZOP study.Journal of Loss Prevention in the Process Industry,10(3),191e204.Kuo,D.H.,Hsu,D.S.,&Chang,C.T.(1997).A prototype for integrating automatic fault tree/event tree/HAZOP puters&Chemical Engineering,21(9e10),S923e S928.Lawley,H.G.(1974).Operability studies and hazard analysis.Chemical Engineering Progress,70(4),45e56.Mannan,S.(2012).Lee’s loss prevention in the process industries.Hazard identiﬁca-tion,assessment and control,Vol.1,3rd ed.,Elsevier,(pp.8e31).NOM.(2005).NOM-028-STPS-2004.Mexican National standard:“Norma Oﬁcial Mexicana”.In Organización del trabajo-Seguridad en los procesos de sustancias químicas:(in Spanish),published in January2005.PEMEX.(2008).Corporate Standard:“Norma de Referencia NRF-018-PEMEX-2007“Estudios de Riesgo”(in Spanish),published in January2008. Venkatasubramanian,V.,Zhao,J.,&Viswanathan,S.(2000).Intelligent systems for HAZOP analysis of complex process puters&Chemical Engineering, 24(9e10),2291e2302.M.Pérez-Marín,M.A.Rodríguez-Toral/Journal of Loss Prevention in the Process Industries26(2013)936e940 940。

蜜桃捕猎习性

标题：蜜桃食草动物吗？揭开蜜桃的食性之谜引言：蜜桃是一种美味多汁的水果，其甜美的味道和独特的口感受到了全世界人民的喜爱。

然而，对于蜜桃的食性，人们存在一定的误解。

有人认为蜜桃可能是一种食草动物。

本文将深入探讨蜜桃的食性以及其真实的营养成分，以解答关于蜜桃是否食草的疑问。

一、蜜桃的来源与特点蜜桃原产于中国和中东地区，其历史可以追溯到数千年前。

蜜桃具有柔软的果肉、丰富的汁液和特有的香气，成熟时外皮呈桃红色或黄色，给人带来了美食的享受。

二、蜜桃的食性解析蜜桃是一种植物，完全属于植物性食物。

它的食性属于自养植物，通过光合作用自行制造自身所需的营养物质。

蜜桃的根系吸收土壤中的水分和矿物质，通过叶子中的叶绿素进行光合作用，将二氧化碳和阳光转化为能量，并产生葡萄糖等有机物。

三、蜜桃的营养成分蜜桃富含多种对人体有益的营养物质。

首先，它是一种低热量、高纤维的水果，有助于控制体重和促进消化。

其次，蜜桃富含维生素C、维生素A和维生素E等抗氧化剂，能够保护身体免受自由基的损害。

此外，蜜桃还富含矿物质如钾、镁和铁，对心脏健康和血液循环有益。

四、关于蜜桃食性的误解有人认为蜜桃可能是一种食草动物，这可能源于对蜜桃树的理解。

蜜桃树在土壤中生长，并以阳光和水分为能源，但与草食动物不同，蜜桃并非以摄食植物为主要方式来获取营养。

五、蜜桃的食用方式和好处蜜桃可以生食、制作果汁、制作水果沙拉等多种方式食用。

无论如何食用，蜜桃都能提供丰富的营养和美味的口感。

此外，蜜桃还具有抗菌、抗炎和滋润肌肤的功效。

它被认为有助于改善肠道健康、促进免疫系统功能和提高皮肤弹性和光泽。

六、蜜桃的选择与储存建议选择成熟的蜜桃是确保其食用质量的关键。

成熟的蜜桃应具有均匀的色泽、圆滑的表皮和微软的果肉。

在储存方面，蜜桃应避免长时间暴露在阳光下，最好将其放入冰箱以延长保存时间。

结论：蜜桃是一种非常营养丰富且美味的水果。

虽然存在关于蜜桃是否食草动物的误解，但事实上它是一种完全的植物性食物。

腹膜透析导管腹腔内段末端位置的研究进展

中国血液净化2019年9月第18卷第9期Chin J Blood Purif,September,2019,Vol.18,No.9·专题与讲座·腹膜透析导管腹腔内段末端位置的研究进展宋会男1姜珊1张蕊1【摘要】腹膜透析是尿毒症患者重要的肾脏替代治疗方法之一。

腹膜透析导管成功置入腹腔是保证腹膜透析顺利进行的前提。

目前大多数研究都是根据体表定位置入腹膜透析导管，但针对腹内段导管末端到道格拉斯窝底部的适宜距离、其与置管并发症关系、以及其对腹膜透析充分性的影响的报道较少。

本文对腹膜透析导管置入道格拉斯窝的深度与置管并发症及腹膜透析充分性的关系的研究进展进行综述。

【关键词】腹膜透析；腹膜透析置管；道格拉斯窝中图分类号：R459.5文献标识码：A doi:10.3969/j.issn.1671-4091.2019.09.003血液透析(hemodialysis，HD)和腹膜透析(per-itoneal dialysis，PD)是当今慢性肾衰竭患者的重要肾脏替代治疗方法[1]。

与血液透析相比，腹膜透析具有居家透析、操作简便、经济有效、保护残余肾功能等优势，逐渐被患者了解并接受[2]。

腹膜透析管的成功置入及管路通畅是腹膜透析顺利进行的前提，腹膜透析导管的移位、堵塞以及患者液体进出时腹痛是腹膜透析导管的主要机械性并发症，直接影响到透析安全性和充分性，是导致置管技术失败、患者退出腹膜透析的主要原因[3]，所以在治疗早期注意导管插入技术对提高治疗效果至关重要。

患者早期腹膜透析腹痛(腹膜透析置管术后30天内)可以由于液体进出刺激局部引起，若经保守治疗仍不能缓解，需要手术重新调整导管位置，导管移位及堵管常表现为导管引流不畅，腹残余量相对较多，透析效果差[4]。

若达理想置管位置，可以减少患者痛苦，提高透析充分性，从而提高患者生存质量，降低退出率和病死率[5]。

目前针对不同的导管置入方法及如何确定体表定位的方法较多，但针对腹膜透析导管腹腔内段末端到道格拉斯窝底部的距离与并发症及腹膜透析充分性的关系的报道较少。

柚皮精油提取工艺及抗氧化抑菌活性研究

中国果菜China Fruit &Vegetable第43卷,第10期2023年10月精深加工Deep Processing 收稿日期:2023-03-10基金项目:国家级大学生创新创业项目（202113241007）；湖北省教育厅科研指导性项目（B2022）；校级学生科研项目（2020XSZ19）第一作者简介:李西（1997—），男，本科，主要从事食品加工方面的工作*通信作者简介:严碧云（1984—），女，副教授，博士，主要从事食品微生物及天然产物加工方面的工作柚皮精油提取工艺及抗氧化抑菌活性研究李西1，姜凯1，黄爱妮1，王琴2，张泽英1，严碧云1*（1.武昌工学院食品健康研究所，湖北武汉430065；2.武汉大学人民医院，湖北武汉430065）摘要:为提高柚皮的附加值，采用微波超声协同方法提取柚皮精油，以柚皮精油得率为考察指标，在单因素试验的基础上运用响应面法优化提取工艺。

结果表明，柚皮精油微波超声+溶剂提取最佳工艺为微波功率450W 、微波时间8min 、超声功率400W 、超声时间15min 、石油醚与柚皮的比例为6∶1（mL/g ）、萃取温度36.8℃，在此工艺下提取的精油得率为（8.0±0.33）%。

当精油浓度为10%时，羟自由基清除率为98.29%；低于同浓度的VC ，DPPH 自由基清除率为49.28%，远低于同浓度的VC ，但上升趋势明显；精油对金黄色葡萄球菌、大肠杆菌具有明显的抑制效果。

总之，柚皮精油具有优异的抗氧化和抑菌活性，可进一步开发成天然保鲜剂应用于食品加工与贮藏。

关键词:柚皮精油；抗氧化；抑菌；微波；超声波中图分类号：TS218文献标志码：A文章编号：1008-1038(2023)10-0012-07DOI：10.19590/ki.1008-1038.2023.10.004Study on Extraction Process and Antioxidant,Antibacterial Activityof Essential Oil from Pomelo PeelLI Xi 1,JIANG Kai 1,HUANG Aini 1,WANG Qin 2,ZHANG Zeying 1,YAN Biyun 1*(1.Institute of Food and Health,Wuchang Institute of Technology,Wuhan 430065,China;2.People’s Hospitalof Wuhan University,Wuhan 430065,China)Abstract:In order to improve the utilization value of pomelo peel,essential oil was extracted from pomelo peel bymicrowave-ultrasonic synergistic method.With the yield as the index,the optimal scheme was determined by response surface methodology on the basis of single factor experiment.The optimal process conditions were that microwave power was 450W,microwave time was 8min,ultrasonic power was 400W,ultrasonic time was 15min,the ratio of petroleum ether to pomelo peel was 6∶1(mL/g),and extraction temperature was 36.8℃.Under this condition,the yield of essential oil was (8.0±0.33)%.When the concentration of essential oil was 10%,the hydroxyl radical scavenging rate was 98.29%,which was lower than that of VC at the same concentration,and the DPPH radical scavenging rate was 49.28%,which was much lower than that of VC at the same concentration,but the柚子（）是芸香科柑橘属植物柚的果实，是最常食用的水果之一，2022年中国的柚子年产量高达5.16×106t，居世界首位[1]。

RSR AQP4 Ab Version2 Aquaporin4 (AQP4) Autoantibod

ElisaRSR TM AQP4 Ab Version 2 Aquaporin-4 (AQP4) AutoantibodyELISA Version 2 Kit –Instructions for useRSR LimitedParc Ty Glas, Llanishen, CardiffCF14 5DU United KingdomTel.: +44 29 2068 9299 Fax: +44 29 2075 7770 Email: Website: EC REP Advena Ltd. Tower Business Centre, 2nd Flr., Tower Street, Swatar, BKR 4013 Malta.INTENDED USEThe RSR AQP4 Autoantibody ELISA Version 2 kit is intended for use by professional persons only, for the quantitative determination of AQP4 autoantibodies (AQP4 Ab) in human serum. Neuromyelitis optica (NMO), also known as Devic’s syndrome, is an immune-mediated neurologic disease that involves the spinal cord and optic nerves. It can be considered to be a disorder distinct from multiple sclerosis (MS). A serum immunoglobulin G autoantibody (NMO-IgG) has been shown to be a specific marker for NMO and the water channel aquaporin 4 (AQP4) has been identified as the antigen for NMO IgG. Measurement of AQP4 Ab can be of considerable value in distinguishing NMO from MS when full clinical features may not be apparent and early intervention may prevent or delay disability. REFERENCESV. A. Lennon et al.A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.Lancet 2004 364(9451): 2106 - 2112V. A. Lennon et al.IgG marker of optic-spinal multiple sclerosis bindsto the aquaporin-4 water channel.The Journal of Experimental Medicine 2005 202: 473 - 477B. G. Weinshenker et al.Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis.Annals of Neurology 2006 59: 566 - 569N. Isobe et al.Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica. Multiple Sclerosis Journal 2012 18: 1541 – 155S. Jarius et al.Testing for antibodies to human aquaporin-4 by ELISA: Sensitivity, specificity and direct comparison with immunohistochemistry.Journal of the Neurological Sciences 2012 320:32 - 37PATENTSThe following patents apply:European patent EP 1 700 120 B1, US patents US 7,101,679 B2, US 7,947,254 B2 and US 8,889,102 B2, Chinese patent ZL200480040851.3 and Japanese patent 4538464. ASSAY PRINCIPLEIn RSR’s AQP4 Ab ELISA Version 2 kit, AQP4 Ab in patient s’ sera, calibrators and controls are allowed to interact with AQP4 coated onto ELISA plate wells and liquid phase biotinylated AQP4 (AQP4-Biotin). After incubation at room temperature for 2 hours with shaking, the well contents are discarded. AQP4 Ab bound to the AQP4 coated on the well will also interact with AQP4-Biotin through the ability of AQP4 Ab in the samples to act divalently leaving AQP4-Biotin bound to the well via an AQP4 Ab bridge. The amount of AQP4-Biotin bound is then determined in a second incubation step involving addition of streptavidin peroxidase (SA-POD), which binds specifically to biotin. Excess, unbound streptavidin peroxidase is then washed away and addition of the peroxidase substrate, 3,3’,5,5’-tetramethlybenzidine (TMB), results in formation of a blue colour. This reaction is stopped by the addition of a stop solution, causing the well contents to turn yellow. The absorbance of the yellow reaction mixture at 450nm and 405nm is then read using an ELISA plate reader. A higher absorbance indicates the presence of AQP4 autoantibody in the test sample. Reading at 405nm allows quantitation of high absorbances. It is recommended that values below 10 u/mL should be measured at 450nm. If it is possible to read at only one wavelength 405nm may be used. The measuring interval is 3.0 –80 u/mL (arbitrary RSR units).STORAGE AND PREPARATION OF SERUM SAMPLESSera to be analysed should be assayed soon after separation or stored, preferably in aliquots, at or below –20o C. 100 μL is sufficient for one assay (duplicate 50 μL determinations). Repeated freeze thawing or increases in storage temperature should be avoided. Do not use lipaemic or haemolysed samples. Studies in which EDTA, citrate and heparin plasma samples were spiked with AQP4 Ab positive sera showed minor changes in signal compared with spiked serum from the same donor. In particular OD450values with spiked EDTA, citrate and heparin plasmas were 79% - 128% of spiked serum (15 samples with serum concentrations ranging from 2.6 u/mL – 30 u/mL) or 87% - 130% in terms of u/mL. When required, thaw test sera at room temperature and mix gently to ensure homogeneity. Centrifuge serum prior to assay (preferably for 5 min at 10-15,000 rpm in a microfuge) to remove particulate matter. Please do not omit this centrifugation step if sera are cloudy or contain particulates.SYMBOLSSymbol MeaningEC Declaration of Conformity IVD In Vitro Diagnostic DeviceREF Catalogue NumberLOT Lot NumberConsult InstructionsManufactured bySufficient forExpiry DateStoreNegative ControlPositive ControlMATERIALS REQUIRED AND NOT SUPPLIED Pipettes capable of dispensing 25 μL, 50 μL and 100 μL.Means of measuring various volumes to reconstitute or dilute reagents supplied.Pure water.ELISA Plate reader suitable for 96 well formats and capable of measuring at 450nm and 405nm.ELISA Plate shaker, capable of 500 shakes/min (not an orbital shaker).ELISA Plate cover.PREPARATION OF REAGENTS SUPPLIEDStore unopened kit and all kit components at 2-8o C.A AQP4 Coated Wells12 breakapart strips of 8 wells (96 in total) in a frame and sealed in foil bag. Allow foil bag to stand at room temperature (20-25o C) for 30 minutes before opening.Ensure wells are firmly fitted in the frame provided. After opening return any unused wells to the original foil bag and seal with adhesive tape. Then place foil bag in the self-seal plastic bag with desiccant provided and store at 2-8o C for up to4 months.B1-5 Calibrators1.5, 5, 20, 40, 80 u/mL (arbitrary RSR units)5 x 0.7 mLReady for useC1-2 Positive Controls I & II(see label for concentration range) 2 x 0.7 mLReady for useD Negative Control0.7 mLReady for useEAQP4–Biotin3 vialsLyophilisedImmediately before use, reconstitute withreconstitution buffer for AQP4-Biotin (F),1.5 mL per vial. When more than one vialis to be used, pool the contents of thevials and mix gently.FReconstitution Buffer for AQP4-Biotin10 mLReady for useGStreptavidin Peroxidase (SA-POD)0.8 mLConcentratedDilute 1 in 20 with diluent for diluting SA-POD (H). For example, 0.5 mL (G) + 9.5mL (H). Store for up to 16 weeks at 2-8o Cafter dilution.HDiluent for SA-POD15 mLReady for useIPeroxidase Substrate (TMB)15 mLReady for useJConcentrated Wash Solution120 mLConcentratedDilute 1 in 10 with pure water before use.Store at 2-8o C up to kit expiry date.KStop Solution14 mLReady for useASSAY PROCEDUREAllow all reagents to stand at room temperature (20-25o C) for at least 30 minutes prior to use. Do notreconstitute AQP4-Biotin until step 2 below. AnEppendorf type repeating pipette is recommended forsteps 2, 5, 8, and 9.1. Pipette 50 μL(in duplicate) of patientsera, calibrators (B1-5) and controls (C1-2 and D) into respective wells. Leave onewell empty for blank.2. Reconstitute AQP4-Biotin and pipette25μL into each well (except blank).3. Cover the frame and shake the wells for2 hours at room temperature on an ELISAplate shaker (500 shakes per min).4. Use an ELISA plate washer to aspirateand wash the wells three times withdiluted wash solution (J). If a platewasher is not available, discard the wellcontents by briskly inverting the frame ofwells over a suitable receptacle, washthree times manually and tap the invertedwells gently on a clean dry absorbentsurface to remove excess wash.RESULT ANALYSISA calibration curve can be established by plotting calibrator concentration on the x-axis (log scale) against the absorbance of the calibrators on the y-axis (linear scale). The AQP4 Ab concentrations in patient sera can then be read off the calibration curve [plotted at RSR as a spline log/lin curve (smoothing factor = 0)]. Other data reduction systems can be used. The negative control can be assigned a value of 0.15 u/mL to assist in computer processing of assay results. Samples with AQP4 Ab concentrations above 80 u/mL can be diluted (e.g.10 x and/or 100 x) in AQP4 Ab negative serum. Some sera will not dilute in a linear way. TYPICAL RESULTS (Example only; not forAbsorbance readings at 405nm can be converted to 450nm absorbances by multiplying by the appropriate factor (3.4 in the case of equipment used at RSR).This cut off has been validated at RSR. However each laboratory should establish its own normal and pathological reference ranges for AQP4 Ab levels. Also it is recommended that each laboratory include its own panel of control samples in the assay. CLINICAL EVALUATION(The information below is derived from 450nm data) Clinical SpecificitySera from 358 individual healthy blood donors were tested in the AQP4 Ab ELISA Version 2 kit. 356 (99%) sera were identified as being negative for AQP4 Ab.Clinical SensitivityOf 62 sera from patients with NMO or NMO spectrum disorder (NMOSD) 48 (77%) were positive for AQP4 Ab.Lower Detection LimitThe negative control was assayed 20 times and the mean and standard deviation calculated. The lower detection limit at 2 standard deviations was0.17 u/mL.Clinical AccuracyAnalysis of 205 sera from patients with autoimmune diseases other than neuromyelitis optica spectrum disorders (NMOSD) indicated no interference from autoantibodies to the TSH receptor (n=110), glutamic acid decarboxylase (n=26), 21-hydroxylase (n=12), the acetylcholine receptor (n=10), thyroid peroxidase (n=15), thyroglobulin (n=10), IA-2 (n=7) or from rheumatoid factor (n=15) in the RSR AQP4 Ab ELISA Version 2. InterferenceNo interference was observed when samples were spiked with the following materials; bilirubin at 20 mg/dL or intralipid up to 3000 mg/dL. Interference was seen from haemoglobin at 500 mg/dL. SAFETY CONSIDERATIONSStreptavidin Peroxidase (SA-POD)Signal word: WarningHazard statement(s)H317: May cause an allergic skin reaction Precautionary statement(s)P280: Wear protective gloves/protective clothing/ eye protection/face protectionP302 + P352: IF ON SKIN: Wash with plenty of soap and waterP333 + P313: If skin irritation or rash occurs: Get medical advice/attentionP362 + P364: Take off contaminated clothing and wash it before reusePeroxidase Substrate (TMB)Signal word: DangerHazard statement(s)H360: May damage fertility or the unborn child Precautionary statement(s)P280: Wear protective gloves/protective clothing/eye protection/face protectionP308 + P313: IF exposed or concerned: Get medical advice/attentionThis kit is intended for use by professional persons only. Follow the instructions carefully. Observe expiry dates stated on the labels and the specified stability for reconstituted reagents. Refer to Safety Data Sheet for more detailed safety information. Avoid all actions likely to lead to ingestion. Avoid contact with skin and clothing. Wear protective clothing. Material of human origin used in the preparation of the kit has been tested and found non-reactive for HIV1 and 2 and HCV antibodies and HBsAg but should, none-the-less, be handled as potentially infectious. Wash hands thoroughly if contamination has occurred and before leaving the laboratory. Sterilise all potentially contaminated waste, including test specimens before disposal. Material of animal origin used in the preparation of the kit has been obtained from animals certified as healthy but these materials should be handled as potentially infectious. Some components contain small quantities of sodium azide as preservative. With all kit components, avoid ingestion, inhalation, injection or contact with skin, eyes or clothing. Avoid formation of heavy metal azides in the drainage system by flushing any kit component away with copious amounts of water.ASSAY PLANAllow all reagents and samples to reach room temperature (20-25 o C) before usePipette: 50 μL Calibrators, controls and patient seraPipette: 25 μL AQP4-Biotin (reconstituted) into each well (except blank)Incubate: 2 Hours at room temperature on an ELISA plate shaker at 500 shakes/min Aspirate/Decant: PlateWash: Plate three times and tap dry on absorbent material1Pipette: 100 μL SA-POD (diluted 1:20) into each well (except blank)Incubate: 20 Minutes at room temperature on a ELISA plate shaker at 500 shakes/min Aspirate/Decant: PlateWash: Plate three times and tap dry on absorbent material1, 2Pipette: 100 μL TMB into each well (including blank)Incubate: 20 Minutes at room temperature in the dark without shakingPipette: 100 μL Stop solution into each well (including blank) and shake for 5 seconds Read absorbance at 450nm and 405nm within 10 minutes of adding stop solution31It is not necessary to tap the plates dry after washing when an automatic plate washer is used2Use pure water for the final wash when washing manually3If it is possible to read at only one wavelength, 405nm may be used。

非等位基因

非等位基因概述非等位基因是指同一基因座上的不同等位基因。

等位基因是指在某个给定的基因座上，可以存在多种不同的变体。

每个个体继承了一对等位基因，一对等位基因可能会导致不同的表型表达。

非等位基因的存在使得遗传学研究更加复杂，因为不同的等位基因会对个体的表型产生不同的影响。

背景在生物学中，基因座是指染色体上一个特定的位置，该位置上的基因决定了某个特征的表达方式。

每个基因座上可以有多种不同的等位基因。

等位基因是指在某个特定基因座上的不同基因变体。

每个个体都会继承一对等位基因，通过这对等位基因的不同组合，决定了个体的表型。

然而，并非所有基因座上的等位基因都具有相同的表现型。

非等位基因的影响非等位基因的存在导致不同等位基因会对个体表型产生不同的影响。

有些非等位基因会表现出显性效应，也就是说，当个体继承了一个突变的等位基因时，即使同时继承了一个正常的等位基因，但显性效应会使得突变的等位基因的表型表达得到体现。

相反，有些非等位基因会表现出隐性效应，当个体继承了两个突变的等位基因时，才会表现出突变的表型。

除了显性和隐性效应之外，非等位基因还可能发生两种其他类型的表型效应。

一种是共显效应，当个体继承了两个不同的突变等位基因时，在表型表达上会表现出一种新的特征，这个特征并不是单个突变等位基因所能导致的。

另一种是部分显性效应，当个体继承了两个不同的突变等位基因时，表型表达将介于两个单独突变等位基因的表型之间。

重组和非等位基因重组是指两个不同的染色体交换部分基因序列的过程。

在重组的过程中，非等位基因可能会发生改变，导致新的等位基因组合形成。

这一过程使得非等位基因的表型效应更加复杂，因为新的等位基因可能将不同基因座的效应组合起来。

非等位基因的重要性非等位基因对生物的适应性和多样性起着重要作用。

通过对等位基因的各种组合的研究，人们可以更好地理解基因与表型之间的关系，并揭示遗传变异对物种适应环境的重要性。

总结非等位基因是指同一基因座上的不同等位基因。

基于高斯混合模型的火焰检测算法

0引言近几十年来，由于火灾造成的巨大损失，火灾探测技术越来越受到人们的关注。

为了减少伤害和经济损失，通常要求火灾探测系统提供快速准确的警报[1-2]。

由于传统火灾监测技术的局限性，基于视频的火灾探测方法越来越流行[3-5]。

与基于传感器的方法不同，基于计算机视觉的方法主要利用从光学视频中提取的信息。

现有火焰检测技术除采用火焰的颜色和动态特性外，还采用纹理[6]、形状[7]和其他特征。

这些特征与机器学习类型的分类器一起广泛使用[8-10]，从而实现高效的火灾检测。

虽然现有方法在火灾探测率方面效果良好，然而，大多存在误报率高的问题。

为了解决上述问题，本文提出了一种基于Dirichlet 过程高斯混合模型（DPGMM ）[11-12]，显著性分析和一维小波变换的混合火焰检测框架。

首先根据颜色为每个基于高斯混合模型的火焰检测算法张怡（成都理工大学工程技术学院，四川乐山614000）摘要火灾作为对社会和环境危害最大的灾难，一直是人们重点防范的对象。

但目前现有的火灾预警系统都存在误报率过高的问题。

因此，文中提出了一种基于火焰闪烁动力学的火焰检测框架。

在该框架中，火焰颜色分布模型采用高斯混合模型。

此外，采用概率显著性分析方法和一维小波变换提取运动显著性和滤波后的时间序列作为特征，描述火焰的动态特性和闪烁特性。

通过实验证明了提出的方法对比现有方法具有较好的精确度，能够获得95%以上的精度，并且具有较低的误报率，满足实际需求。

关键词机器视觉；火焰检测；高斯混合模型；Dirichlet 过程中图分类号TP391文献标识码A文章编号1009-2552（2021）01-0074-06DOI10.13274/ki.hdzj.2021.01.013Flame detection algorithm based on Gaussian mixture modelZHANG Yi（The Engineering &Technical College of Chengdu University of Technology ，Leshan 614000,Sichuan Prov⁃ince ，China ）Abstract ：As the most harmful disaster to society and the environment ，fire has always been the focus of attention.However ，the existing fire early warning systems all have the problem of high false alarm rate.Therefore ，a flame detection framework based on flame flicker dynamics is proposed.In this framework ，the flame color distribution model adopts the Gaussian mixture model.In addition ，the probabilistic saliency analysis method and one -dimensional wavelet transform are used to extract motion saliency and filtered time series as features to describe the dynamic characteristics and flicker characteristics of the flame.Ex⁃periments have proved that the proposed method has better accuracy compared with the existing methods ，can obtain an accuracy of more than 95%，and has a lower false alarm rate ，which meets actual needs.Key words ：machine vision ；flame detection ；Gaussian mixture model ；Dirichlet process基金项目：四川省教育厅科技项目（17ZB0062）；乐山市科技局项目（19SZD106）作者简介：张怡（1991-），女，硕士，讲师，研究方向为火灾防治与人员疏散研究、矿井通风与事故防治等。

于慧敏，浙江大学，教授,博士生导师。主要研究方向为图像视频处理与

于慧敏，浙江大学，教授,博士生导师。

主要研究方向为图像/视频处理与分析。

2003年获科学技术三等奖一项，授权发明专利近20项，多篇论文发表在模式识别和计算机视觉领域顶尖学报和会议上。

近年来，在 (3D/2D)视频/图象处理与分析、视频监控、3D视频获取和医学图像处理等方面，主持了多项国家自然科学基金、973子课题、国家国防计划项目、国家863课题、浙江省重大/重点项目的研究和开发。

一、近年主持的科研项目(1)国家自然基金，61471321、目标协同分割与识别技术的研究、2015-2018。

(2) 973子课题，2012CB316406-1、面向公共安全的跨媒体呈现与验证和示范平、2012-2016。

(3)国家自然基金，60872069、基于3D 视频的运动分割与3D 运动估计、2009-2011。

(4) 863项目，2007AA01Z331、基于异构结构的3D实时获取技术与系统、2007-2009。

(5)浙江省科技计划项目，2013C310035 、多国纸币序列号和特殊污染字符识别技、2013-2015。

(6)浙江省科技计划重点项目, 2006C21035 、集成化多模医学影像信息计算和处理平台的研发、2006-2008。

(7)航天基金，***三维动目标的获取与重建、2008-2010。

(8)中国电信，3D视频监控系统、2010。

(9)中兴通讯，跨摄像机的目标匹配与跟踪技术研究、2014.05-2015.05。

(10)浙江大力科技，激光雷达导航与图像读表系统、2015-。

(11)横向，纸币序列号的实时识别技术、2011-2012。

(12)横向，清分机视频处理技术、2010-2012。

（参与）(13)横向，基于多摄像机的目标跟踪、事件检测与行为分析、2010。

(14)横向，红外视频雷达、2010-2012。

(15)横向，客运车辆行车安全视频分析系统、2010-2011。

二、近五年发表的论文期刊论文：1)Fei Chen, Huimin Yu#, and Roland Hu. Shape Sparse Representation for JointObject Classification and Segmentation [J]. IEEE Transactions on Image Processing 22(3): 992-1004 ,2013.2)Xie Y, Yu H#, Gong X, et al. Learning Visual-Spatial Saliency for Multiple-ShotPerson Re-Identification[J].Signal Processing Letters IEEE, 2015, 22:1854-1858.3)Yang, Bai, Huimin Yu#, and Roland Hu. Unsupervised regions basedsegmentation using object discovery, Journal of Visual Communication and Image Representation, 2015,31: 125-137.4)Fei Chen, Roland Hu, Huimin Yu#, Shiyan Wang: Reduced set density estimatorfor object segmentation based on shape probabilistic representation. J. Visual Communication and Image Representation,2012, 23(7): 1085-1094.5)Fei Chen, Huimin Yu#, Jincao Yao , Roland Hu ,Robust sparse kernel densityestimation by inducing randomness[J]，Pattern Analysis and Applications: Volume 18, Issue 2 (2015), Page 367-375.6)赵璐，于慧敏#，基于先验形状信息和水平集方法的车辆检测，浙江大学学报（工学版），pp.124-129,2010.1。

2023年英语中考卷子

2023年英语中考卷子一、You will hear a conversation about a weekend trip. What activity do they plan to do?A. Go hiking in the mountains.B. Visit a museum in the city.C. Have a picnic in the park.D. Attend a music festival.（答案：C）二、In the next dialogue, two friends are discussing their favorite subjects. Which subject does neither of them like?A. MathematicsB. HistoryC. ScienceD. Art（答案：A）三、Listen to the description of a school event. When is the event scheduled?A. Next MondayB. This FridayC. Last weekendD. The following Thursday（答案：D）四、You will hear a news report about environmental protection. What measure is being promoted to reduce pollution?A. Using public transportation more often.B. Cutting down more trees for construction.C. Increasing the use of single-use plastics.D. Encouraging people to waste water.（答案：A）五、In the conversation, two students are talking about their future plans. Where does the second student want to study abroad?A. In the United StatesB. In FranceC. In AustraliaD. In Canada（答案：B）二、Reading Comprehension (阅读理解)六、Read the passage and answer the question: What is NOT mentioned as a benefit of reading?A. Improving vocabulary.B. Reducing stress levels.C. Enhancing creativity.D. Increasing screen time.（答案：D）七、According to the article, which of the following is true about the ancient civilization mentioned?A. It was located in Europe.B. It invented the wheel.C. It had no written language.D. It disappeared without a trace.（答案：B）八、In the text, the author discusses the impact of technology on education. Which statement does NOT reflect the author's view?A. Technology has made learning more accessible.B. Technology has replaced traditional teaching methods entirely.C. Technology can enhance student engagement.D. Technology offers new ways of assessing learning.（答案：B）九、Based on the information in the passage, what is the main challenge faced by wildlife conservationists?A. Lack of funding.B. Overpopulation of certain species.C. Habitat destruction.D. Public opposition to conservation efforts.（答案：C）十、The article talks about the benefits of exercise. Which of the following is NOT listed as a health benefit?A. Improved cardiovascular health.B. Stronger muscles and bones.C. Better mental health.D. Instant weight loss.（答案：D）。

CVPR2013总结

CVPR2013总结前不久的结果出来了，⾸先恭喜我⼀个已经毕业⼯作的师弟中了⼀篇。

完整的⽂章列表已经在CVPR的主页上公布了（），今天把其中⼀些感兴趣的整理⼀下，虽然论⽂下载的链接⼤部分还都没出来，不过可以follow最新动态。

等下载链接出来的时候⼀⼀补上。

由于没有下载链接，所以只能通过题⽬和作者估计⼀下论⽂的内容。

难免有偏差，等看了论⽂以后再修正。

显著性Saliency Aggregation: A Data-driven Approach Long Mai, Yuzhen Niu, Feng Liu 现在还没有搜到相关的资料，应该是多线索的⾃适应融合来进⾏显著性检测的PISA: Pixelwise Image Saliency by Aggregating Complementary Appearance Contrast Measures with Spatial Priors Keyang Shi, Keze Wang, Jiangbo Lu, Liang Lin 这⾥的两个线索看起来都不新，应该是集成框架⽐较好。

⽽且像素级的，估计能达到分割或者matting的效果Looking Beyond the Image: Unsupervised Learning for Object Saliency and Detection Parthipan Siva, Chris Russell, Tao Xiang, 基于学习的的显著性检测Learning video saliency from human gaze using candidate selection , Dan Goldman, Eli Shechtman, Lihi Zelnik-Manor这是⼀个做视频显著性的，估计是选择显著的视频⽬标Hierarchical Saliency Detection Qiong Yan, Li Xu, Jianping Shi, Jiaya Jia的学⽣也开始做显著性了，多尺度的⽅法Saliency Detection via Graph-Based Manifold Ranking Chuan Yang, Lihe Zhang, Huchuan Lu, Ming-Hsuan Yang, Xiang Ruan这个应该是扩展了那个经典的 graph based saliency，应该是⽤到了显著性传播的技巧Salient object detection: a discriminative regional feature integration approach , Jingdong Wang, Zejian Yuan, , Nanning Zheng⼀个多特征⾃适应融合的显著性检测⽅法Submodular Salient Region Detection , Larry Davis⼜是⼤⽜下⾯的⽂章，提法也很新颖，⽤了submodular。

matlab图像处理中英文翻译文献

附录A 英文原文Scene recognition for mine rescue robotlocalization based on visionCUI Yi-an(崔益安), CAI Zi-xing(蔡自兴), WANG Lu(王璐)Abstract：A new scene recognition system was presented based on fuzzy logic and hidden Markov model(HMM) that can be applied in mine rescue robot localization during emergencies. The system uses monocular camera to acquire omni-directional images of the mine environment where the robot locates. By adopting center-surround difference method, the salient local image regions are extracted from the images as natural landmarks. These landmarks are organized by using HMM to represent the scene where the robot is, and fuzzy logic strategy is used to match the scene and landmark. By this way, the localization problem, which is the scene recognition problem in the system, can be converted into the evaluation problem of HMM. The contributions of these skills make the system have the ability to deal with changes in scale, 2D rotation and viewpoint. The results of experiments also prove that the system has higher ratio of recognition and localization in both static and dynamic mine environments.Key words: robot location; scene recognition; salient image; matching strategy; fuzzy logic; hidden Markov model1 IntroductionSearch and rescue in disaster area in the domain of robot is a burgeoning and challenging subject[1]. Mine rescue robot was developed to enter mines during emergencies to locate possible escape routes for those trapped inside and determine whether it is safe for human to enter or not. Localization is a fundamental problem in this field. Localization methods based on camera can be mainly classified into geometric, topological or hybrid ones[2]. With its feasibility and effectiveness, scene recognition becomes one of the important technologies of topological localization.Currently most scene recognition methods are based on global image features and have twodistinct stages: training offline and matching online.During the training stage, robot collects the images of the environment where it works and processes the images to extract global features that represent the scene. Some approaches were used to analyze the data-set of image directly and some primary features were found, such as the PCA method [3]. However, the PCA method is not effective in distinguishing the classes of features. Another type of approach uses appearance features including color, texture and edge density to represent the image. For example, ZHOU et al[4] used multidimensional histograms to describe global appearance features. This method is simple but sensitive to scale and illumination changes. In fact, all kinds of global image features are suffered from the change of environment.LOWE [5] presented a SIFT method that uses similarity invariant descriptors formed by characteristic scale and orientation at interest points to obtain the features. The features are invariant to image scaling, translation, rotation and partially invariant to illumination changes. But SIFT may generate 1 000 or more interest points, which may slow down the processor dramatically.During the matching stage, nearest neighbor strategy(NN) is widely adopted for its facility and intelligibility[6]. But it cannot capture the contribution of individual feature for scene recognition. In experiments, the NN is not good enough to express the similarity between two patterns. Furthermore, the selected features can not represent the scene thoroughly according to the state-of-art pattern recognition, which makes recognition not reliable[7].So in this work a new recognition system is presented, which is more reliable and effective if it is used in a complex mine environment. In this system, we improve the invariance by extracting salient local image regions as landmarks to replace the whole image to deal with large changes in scale, 2D rotation and viewpoint. And the number of interest points is reduced effectively, which makes the processing easier. Fuzzy recognition strategy is designed to recognize the landmarks in place of NN, which can strengthen the contribution of individual feature for scene recognition. Because of its partial information resuming ability, hidden Markov model is adopted to organize those landmarks, which can capture the structure or relationship among them. So scene recognition can be transformed to the evaluation problem of HMM, which makes recognition robust.2 Salient local image regions detectionResearches on biological vision system indicate that organism (like drosophila) often pays attention to certain special regions in the scene for their behavioral relevance or local image cues while observing surroundings [8]. These regions can be taken as natural landmarks to effectively represent and distinguish different environments. Inspired by those, we use center-surround difference method to detect salient regions in multi-scale image spaces. The opponencies of color and texture are computed to create the saliency map.Follow-up, sub-image centered at the salient position in S is taken as the landmark region. The size of the landmark region can be decided adaptively according to the changes of gradient orientation of the local image [11].Mobile robot navigation requires that natural landmarks should be detected stably when environments change to some extent. To validate the repeatability on landmark detection of our approach, we have done some experiments on the cases of scale, 2D rotation and viewpoint changes etc. Fig.1 shows that the door is detected for its saliency when viewpoint changes. More detailed analysis and results about scale and rotation can be found in our previous works[12].3 Scene recognition and localizationDifferent from other scene recognition systems, our system doesn’t need training offline. In other words, our scenes are not classified in advance. When robot wanders, scenes captured at intervals of fixed time are used to build the vertex of a topological map, which represents the place where robot locates. Although the map’s geometric layout is ignored by the localization system, it is useful for visualization and debugging[13] and beneficial to path planning. So localization means searching the best match of current scene on the map. In this paper hidden Markov model is used to organize the extracted landmarks from current scene and create the vertex of topological map for its partial information resuming ability.Resembled by panoramic vision system, robot looks around to get omni-images. FromFig.1 Experiment on viewpoint changeseach image, salient local regions are detected and formed to be a sequence, named as landmark sequence whose order is the same as the image sequence. Then a hidden Markov model is created based on the landmark sequence involving k salient local image regions, which is taken as the description of the place where the robot locates. In our system EVI-D70 camera has a view field of ±170°. Considering the overlap effect, we sample environment every 45° to get 8 images.Let the 8 images as hidden state Si (1≤i≤8), the created HMM can be illustrated by Fig.2. The parameters of HMM, aij and bjk, are achieved by learning, using Baulm-Welch algorithm[14]. The threshold of convergence is set as 0.001.As for the edge of topological map, we assign it with distance information between twovertices. The distances can be computed according to odometry readings.Fig.2 HMM of environmentTo locate itself on the topological map, robot must run its ‘eye’ on environment and extract a landmark sequence L1′ −Lk′ , then search the map for the best matched vertex (scene). Different from traditional probabilistic localization[15], in our system localization problem can be converted to the evaluation problem of HMM. The vertex with the greatest evaluation value, which must also be greater than a threshold, is taken as the best matched vertex, which indicates the most possible place where the robot is.4 Match strategy based on fuzzy logicOne of the key issues in image match problem is to choose the most effective features or descriptors to represent the original image. Due to robot movement, those extracted landmark regions will change at pixel level. So, the descriptors or features chosen should be invariant to some extent according to the changes of scale, rotation and viewpoint etc. In this paper, we use 4 features commonly adopted in the community that are briefly described as follows.GO: Gradient orientation. It has been proved that illumination and rotation changes are likely to have less influence on it[5].ASM and ENT: Angular second moment and entropy, which are two texture descriptors.H: Hue, which is used to describe the fundamental information of the image.Another key issue in match problem is to choose a good match strategy or algorithm. Usually nearest neighbor strategy (NN) is used to measure the similarity between two patterns. But we have found in the experiments that NN can’t adequately exhibit the individual descriptor or feature’s contribution to similarity measurement. As indicated in Fig.4, the input image Fig.4(a) comes from different view of Fig.4(b). But the distance between Figs.4(a) and (b) computed by Jefferey divergence is larger than Fig.4(c).To solve the problem, we design a new match algorithm based on fuzzy logic for exhibiting the subtle changes of each features. The algorithm is described as below.And the landmark in the database whose fused similarity degree is higher than any others is taken as the best match. The match results of Figs.2(b) and (c) are demonstrated by Fig.3. As indicated, this method can measure the similarity effectively between two patterns.Fig.3 Similarity computed using fuzzy strategy5 Experiments and analysisThe localization system has been implemented on a mobile robot, which is built by our laboratory. The vision system is composed of a CCD camera and a frame-grabber IVC-4200. The resolution of image is set to be 400×320 and the sample frequency is set to be 10 frames/s. The computer system is composed of 1 GHz processor and 512 M memory, which is carried by the robot. Presently the robot works in indoor environments.Because HMM is adopted to represent and recognize the scene, our system has the ability to capture the discrimination about distribution of salient local image regions and distinguish similar scenes effectively. Table 1 shows the recognition result of static environments including 5 laneways and a silo. 10 scenes are selected from each environment and HMMs are created for each scene. Then 20 scenes are collected when the robot enters each environment subsequently to match the 60 HMMs above.In the table, “truth” m eans that the scene to be localized matches with the right scene (the evaluation value of HMM is 30% greater than the second high evaluation). “Uncertainty” means that the evaluation value of HMM is greater than the second high evaluation under 10%. “Error match” means that the scene to be localized matches with the wrong scene. In the table, the ratio of error match is 0. But it is possible that the scene to be localized can’t match any scenes and new vertexes are created. Furthermore, the “ratio of truth” about silo is lower because salient cues arefewer in this kind of environment.In the period of automatic exploring, similar scenes can be combined. The process can be summarized as: when localization succeeds, the current landmark sequence is added to the accompanying observation sequence of the matched vertex un-repeatedly according to their orientation (including the angle of the image from which the salient local region and the heading of the robot come). The parameters of HMM are learned again.Compared with the approaches using appearance features of the whole image (Method 2, M2), our system (M1) uses local salient regions to localize and map, which makes it have more tolerance of scale, viewpoint changes caused by robot’s movement and higher ratio of recognition and fewer amount of vertices on the topological map. So, our system has better performance in dynamic environment. These can be seen in Table 2. Laneways 1, 2, 4, 5 are in operation where some miners are working, which puzzle the robot.6 Conclusions1) Salient local image features are extracted to replace the whole image to participate in recognition, which improve the tolerance of changes in scale, 2D rotation and viewpoint of environment image.2) Fuzzy logic is used to recognize the local image, and emphasize the individual feature’s contribution to recognition, which improves the reliability of landmarks.3) HMM is used to capture the structure or relationship of those local images, which converts the scene recognition problem into the evaluation problem of HMM.4) The results from the above experiments demonstrate that the mine rescue robot scene recognition system has higher ratio of recognition and localization.Future work will be focused on using HMM to deal with the uncertainty of localization.附录B 中文翻译基于视觉的矿井救援机器人场景识别CUI Yi-an(崔益安), CAI Zi-xing(蔡自兴), WANG Lu(王璐)摘要：基于模糊逻辑和隐马尔可夫模型（HMM），论文提出了一个新的场景识别系统，可应用于紧急情况下矿山救援机器人的定位。

toward a theory of stakeholder identification and salience (definitive dependent stakeholders)

Since Freeman (1984) published his landmark book. Strategic Management: A Stakeholder Approach, the concept oí "stakeholders" has become embedded in management scholarship and in managers' thinking. Yet, as popular as the term has become and as richly descriptive as it is, there is no agreement on what Freeman (1994) calls "The Principle oí Who or What Really Counts." That is, who (or what) are the stakeholders of the firm? And to whom (or what) do managers pay attention? The first question calls for a normaiive iheory of stakeholder identiiication, to explain logically why managers should consider certain classes oí entities as stakeholders. The second question calls for a descriptive theory oí stakeholder salience, to explain the conditions under which managers do consider certain classes of entities as stakeholders. Stakeholder theory, reviewed in this article, oífers a maddening variety oí signals on how questions oí stakeholder identification might be answered. We will see stakeholders identified as primary or secondary

视频目标分割总结

视频目标分割总结视频目标分割分类最近听了阿里巴巴王文冠老师“基于深度学习技术的视频分割”的讲座（可能需要报名比赛才能观看)，我感到受益匪浅，学习到了许多关于视频目标分割(VOS)的知识，在这里进行整理总结。

关于视频目标分割的分类，有的综述文章分为无监督VOS,半监督VOS，交互式VOS，弱监督VOS等，这里将视频目标分割任务分类成无监督VOS，半监督VOS，交互式VOS，背景移除或运动物体分割，视频语义分割/实例分割。

1.无监督VOS：在测试阶段，不要求任何用户输入，通常是自动分割视频中最关键，最显著的目标。

2.半监督VOS：在测试阶段，用户提供第一帧或者关键帧的目标掩膜(mask)，然后分割剩下帧中的目标。

3.交互式VOS：在测试阶段，依靠用户的迭代交互来分割感兴趣的对象，目的是获取高精度的分割结果，需要大量的人力参与。

4.背景移除或运动目标提取：通常假定摄像机静止或运动缓慢，然后自动分割出运动的前景目标。

5.视频语义分割/实例分割：是图像语义分割/实例分割的拓展，不仅要求分割出视频中感兴趣目标，还要根据语义或者实例关系区分不同目标。

值得注意的是，无监督VOS和半监督VOS的区分并不是根据监督学习和无监督学习的分类方式区分，这两者都可以利用有标签的视频数据进行训练，区分是根据测试阶段的用户参与方式来进行的，并且这两者关注的都是分割前景和背景，并不关注分割目标的类别信息。

此外，单独把背景移除提出来，应该是想强调这里指的是基于深度学习的背景移除方法。

这篇博客简单介绍各个方向的传统方法，着重介绍基于深度学习的视频目标分割。

解决思路总结关于解决思路，这里主要讨论的是无监督VOS，半监督VOS和视频实例分割的基本方法。

随着时间的推移，出现了更多优秀的工作。

RANet结合了基于传播和基于匹配的思路，利用孪生网络encoder结构获取第一帧的模板特征和当前帧特征，通过Correlation操作获取相似性特征图，根据第一帧前景和背景，经过RAM模块筛选前景和背景特征，再与预测的前一帧mask合并，通过decoder结构获取最终分割mask。

Instructional_design

Instructional designFrom Wikipedia, the free encyclopediaInstructional Design(also called Instructional Systems Design (ISD)) is the practice of maximizing the effectiveness, efficiency and appeal of instruction and other learning experiences. The process consists broadly of determining the current state and needs of the learner, defining the end goal of instruction, and creating some "intervention" to assist in the transition. Ideally the process is informed by pedagogically(process of teaching) and andragogically(adult learning) tested theories of learning and may take place in student-only, teacher-led or community-based settings. The outcome of this instruction may be directly observable and scientifically measured or completely hidden and assumed. There are many instructional design models but many are based on the ADDIE model with the five phases: 1) analysis, 2) design, 3) development, 4) implementation, and 5) evaluation. As a field, instructional design is historically and traditionally rooted in cognitive and behavioral psychology.HistoryMuch of the foundations of the field of instructional design was laid in World War II, when the U.S. military faced the need to rapidly train large numbers of people to perform complex technical tasks, fromfield-stripping a carbine to navigating across the ocean to building a bomber—see "Training Within Industry(TWI)". Drawing on the research and theories of B.F. Skinner on operant conditioning, training programs focused on observable behaviors. Tasks were broken down into subtasks, and each subtask treated as a separate learning goal. Training was designed to reward correct performance and remediate incorrect performance. Mastery was assumed to be possible for every learner, given enough repetition and feedback. After the war, the success of the wartime training model was replicated in business and industrial training, and to a lesser extent in the primary and secondary classroom. The approach is still common in the U.S. military.[1]In 1956, a committee led by Benjamin Bloom published an influential taxonomy of what he termed the three domains of learning: Cognitive(what one knows or thinks), Psychomotor (what one does, physically) and Affective (what one feels, or what attitudes one has). These taxonomies still influence the design of instruction.[2]During the latter half of the 20th century, learning theories began to be influenced by the growth of digital computers.In the 1970s, many instructional design theorists began to adopt an information-processing-based approach to the design of instruction. David Merrill for instance developed Component Display Theory (CDT), which concentrates on the means of presenting instructional materials (presentation techniques).[3]Later in the 1980s and throughout the 1990s cognitive load theory began to find empirical support for a variety of presentation techniques.[4]Cognitive load theory and the design of instructionCognitive load theory developed out of several empirical studies of learners, as they interacted with instructional materials.[5]Sweller and his associates began to measure the effects of working memory load, and found that the format of instructional materials has a direct effect on the performance of the learners using those materials.[6][7][8]While the media debates of the 1990s focused on the influences of media on learning, cognitive load effects were being documented in several journals. Rather than attempting to substantiate the use of media, these cognitive load learning effects provided an empirical basis for the use of instructional strategies. Mayer asked the instructional design community to reassess the media debate, to refocus their attention on what was most important: learning.[9]By the mid- to late-1990s, Sweller and his associates had discovered several learning effects related to cognitive load and the design of instruction (e.g. the split attention effect, redundancy effect, and the worked-example effect). Later, other researchers like Richard Mayer began to attribute learning effects to cognitive load.[9] Mayer and his associates soon developed a Cognitive Theory of MultimediaLearning.[10][11][12]In the past decade, cognitive load theory has begun to be internationally accepted[13]and begun to revolutionize how practitioners of instructional design view instruction. Recently, human performance experts have even taken notice of cognitive load theory, and have begun to promote this theory base as the science of instruction, with instructional designers as the practitioners of this field.[14]Finally Clark, Nguyen and Sweller[15]published a textbook describing how Instructional Designers can promote efficient learning using evidence-based guidelines of cognitive load theory.Instructional Designers use various instructional strategies to reduce cognitive load. For example, they think that the onscreen text should not be more than 150 words or the text should be presented in small meaningful chunks.[citation needed] The designers also use auditory and visual methods to communicate information to the learner.Learning designThe concept of learning design arrived in the literature of technology for education in the late nineties and early 2000s [16] with the idea that "designers and instructors need to choose for themselves the best mixture of behaviourist and constructivist learning experiences for their online courses" [17]. But the concept of learning design is probably as old as the concept of teaching. Learning design might be defined as "the description of the teaching-learning process that takes place in a unit of learning (eg, a course, a lesson or any other designed learning event)" [18].As summarized by Britain[19], learning design may be associated with:∙The concept of learning design∙The implementation of the concept made by learning design specifications like PALO, IMS Learning Design[20], LDL, SLD 2.0, etc... ∙The technical realisations around the implementation of the concept like TELOS, RELOAD LD-Author, etc...Instructional design modelsADDIE processPerhaps the most common model used for creating instructional materials is the ADDIE Process. This acronym stands for the 5 phases contained in the model:∙Analyze– analyze learner characteristics, task to be learned, etc.Identify Instructional Goals, Conduct Instructional Analysis, Analyze Learners and Contexts∙Design– develop learning objectives, choose an instructional approachWrite Performance Objectives, Develop Assessment Instruments, Develop Instructional Strategy∙Develop– create instructional or training materialsDesign and selection of materials appropriate for learning activity, Design and Conduct Formative Evaluation∙Implement– deliver or distribute the instructional materials ∙Evaluate– make sure the materials achieved the desired goals Design and Conduct Summative EvaluationMost of the current instructional design models are variations of the ADDIE process.[21] Dick,W.O,.Carey, L.,&Carey, J.O.(2004)Systematic Design of Instruction. Boston,MA:Allyn&Bacon.Rapid prototypingA sometimes utilized adaptation to the ADDIE model is in a practice known as rapid prototyping.Proponents suggest that through an iterative process the verification of the design documents saves time and money by catching problems while they are still easy to fix. This approach is not novel to the design of instruction, but appears in many design-related domains including software design, architecture, transportation planning, product development, message design, user experience design, etc.[21][22][23]In fact, some proponents of design prototyping assert that a sophisticated understanding of a problem is incomplete without creating and evaluating some type of prototype, regardless of the analysis rigor that may have been applied up front.[24] In other words, up-front analysis is rarely sufficient to allow one to confidently select an instructional model. For this reason many traditional methods of instructional design are beginning to be seen as incomplete, naive, and even counter-productive.[25]However, some consider rapid prototyping to be a somewhat simplistic type of model. As this argument goes, at the heart of Instructional Design is the analysis phase. After you thoroughly conduct the analysis—you can then choose a model based on your findings. That is the area where mostpeople get snagged—they simply do not do a thorough-enough analysis. (Part of Article By Chris Bressi on LinkedIn)Dick and CareyAnother well-known instructional design model is The Dick and Carey Systems Approach Model.[26] The model was originally published in 1978 by Walter Dick and Lou Carey in their book entitled The Systematic Design of Instruction.Dick and Carey made a significant contribution to the instructional design field by championing a systems view of instruction as opposed to viewing instruction as a sum of isolated parts. The model addresses instruction as an entire system, focusing on the interrelationship between context, content, learning and instruction. According to Dick and Carey, "Components such as the instructor, learners, materials, instructional activities, delivery system, and learning and performance environments interact with each other and work together to bring about the desired student learning outcomes".[26] The components of the Systems Approach Model, also known as the Dick and Carey Model, are as follows:∙Identify Instructional Goal(s): goal statement describes a skill, knowledge or attitude(SKA) that a learner will be expected to acquire ∙Conduct Instructional Analysis: Identify what a learner must recall and identify what learner must be able to do to perform particular task ∙Analyze Learners and Contexts: General characteristic of the target audience, Characteristic directly related to the skill to be taught, Analysis of Performance Setting, Analysis of Learning Setting∙Write Performance Objectives: Objectives consists of a description of the behavior, the condition and criteria. The component of anobjective that describes the criteria that will be used to judge the learner's performance.∙Develop Assessment Instruments: Purpose of entry behavior testing, purpose of pretesting, purpose of posttesting, purpose of practive items/practive problems∙Develop Instructional Strategy: Pre-instructional activities, content presentation, Learner participation, assessment∙Develop and Select Instructional Materials∙Design and Conduct Formative Evaluation of Instruction: Designer try to identify areas of the instructional materials that are in need to improvement.∙Revise Instruction: To identify poor test items and to identify poor instruction∙Design and Conduct Summative EvaluationWith this model, components are executed iteratively and in parallel rather than linearly.[26]/akteacher/dick-cary-instructional-design-mo delInstructional Development Learning System (IDLS)Another instructional design model is the Instructional Development Learning System (IDLS).[27] The model was originally published in 1970 by Peter J. Esseff, PhD and Mary Sullivan Esseff, PhD in their book entitled IDLS—Pro Trainer 1: How to Design, Develop, and Validate Instructional Materials.[28]Peter (1968) & Mary (1972) Esseff both received their doctorates in Educational Technology from the Catholic University of America under the mentorship of Dr. Gabriel Ofiesh, a Founding Father of the Military Model mentioned above. Esseff and Esseff contributed synthesized existing theories to develop their approach to systematic design, "Instructional Development Learning System" (IDLS).The components of the IDLS Model are:∙Design a Task Analysis∙Develop Criterion Tests and Performance Measures∙Develop Interactive Instructional Materials∙Validate the Interactive Instructional MaterialsOther modelsSome other useful models of instructional design include: the Smith/Ragan Model, the Morrison/Ross/Kemp Model and the OAR model , as well as, Wiggins theory of backward design .Learning theories also play an important role in the design ofinstructional materials. Theories such as behaviorism , constructivism , social learning and cognitivism help shape and define the outcome of instructional materials.Influential researchers and theoristsThe lists in this article may contain items that are not notable , not encyclopedic , or not helpful . Please help out by removing such elements and incorporating appropriate items into the main body of the article. (December 2010)Alphabetic by last name∙ Bloom, Benjamin – Taxonomies of the cognitive, affective, and psychomotor domains – 1955 ∙Bonk, Curtis – Blended learning – 2000s ∙ Bransford, John D. – How People Learn: Bridging Research and Practice – 1999 ∙ Bruner, Jerome – Constructivism ∙Carr-Chellman, Alison – Instructional Design for Teachers ID4T -2010 ∙Carey, L. – "The Systematic Design of Instruction" ∙Clark, Richard – Clark-Kosma "Media vs Methods debate", "Guidance" debate . ∙Clark, Ruth – Efficiency in Learning: Evidence-Based Guidelines to Manage Cognitive Load / Guided Instruction / Cognitive Load Theory ∙Dick, W. – "The Systematic Design of Instruction" ∙ Gagné, Robert M. – Nine Events of Instruction (Gagné and Merrill Video Seminar) ∙Heinich, Robert – Instructional Media and the new technologies of instruction 3rd ed. – Educational Technology – 1989 ∙Jonassen, David – problem-solving strategies – 1990s ∙Langdon, Danny G - The Instructional Designs Library: 40 Instructional Designs, Educational Tech. Publications ∙Mager, Robert F. – ABCD model for instructional objectives – 1962 ∙Merrill, M. David - Component Display Theory / Knowledge Objects ∙ Papert, Seymour – Constructionism, LOGO – 1970s ∙ Piaget, Jean – Cognitive development – 1960s∙Piskurich, George – Rapid Instructional Design – 2006∙Simonson, Michael –Instructional Systems and Design via Distance Education – 1980s∙Schank, Roger– Constructivist simulations – 1990s∙Sweller, John - Cognitive load, Worked-example effect, Split-attention effect∙Roberts, Clifton Lee - From Analysis to Design, Practical Applications of ADDIE within the Enterprise - 2011∙Reigeluth, Charles –Elaboration Theory, "Green Books" I, II, and III - 1999-2010∙Skinner, B.F.– Radical Behaviorism, Programed Instruction∙Vygotsky, Lev– Learning as a social activity – 1930s∙Wiley, David– Learning Objects, Open Learning – 2000sSee alsoSince instructional design deals with creating useful instruction and instructional materials, there are many other areas that are related to the field of instructional design.∙educational assessment∙confidence-based learning∙educational animation∙educational psychology∙educational technology∙e-learning∙electronic portfolio∙evaluation∙human–computer interaction∙instructional design context∙instructional technology∙instructional theory∙interaction design∙learning object∙learning science∙m-learning∙multimedia learning∙online education∙instructional design coordinator∙storyboarding∙training∙interdisciplinary teaching∙rapid prototyping∙lesson study∙Understanding by DesignReferences1.^MIL-HDBK-29612/2A Instructional Systems Development/SystemsApproach to Training and Education2.^Bloom's Taxonomy3.^TIP: Theories4.^Lawrence Erlbaum Associates, Inc. - Educational Psychologist -38(1):1 - Citation5.^ Sweller, J. (1988). "Cognitive load during problem solving:Effects on learning". Cognitive Science12 (1): 257–285.doi:10.1016/0364-0213(88)90023-7.6.^ Chandler, P. & Sweller, J. (1991). "Cognitive Load Theory andthe Format of Instruction". Cognition and Instruction8 (4): 293–332.doi:10.1207/s1532690xci0804_2.7.^ Sweller, J., & Cooper, G.A. (1985). "The use of worked examplesas a substitute for problem solving in learning algebra". Cognition and Instruction2 (1): 59–89. doi:10.1207/s1532690xci0201_3.8.^Cooper, G., & Sweller, J. (1987). "Effects of schema acquisitionand rule automation on mathematical problem-solving transfer". Journal of Educational Psychology79 (4): 347–362.doi:10.1037/0022-0663.79.4.347.9.^ a b Mayer, R.E. (1997). "Multimedia Learning: Are We Asking theRight Questions?". Educational Psychologist32 (41): 1–19.doi:10.1207/s1*******ep3201_1.10.^ Mayer, R.E. (2001). Multimedia Learning. Cambridge: CambridgeUniversity Press. ISBN0-521-78239-2.11.^Mayer, R.E., Bove, W. Bryman, A. Mars, R. & Tapangco, L. (1996)."When Less Is More: Meaningful Learning From Visual and Verbal Summaries of Science Textbook Lessons". Journal of Educational Psychology88 (1): 64–73. doi:10.1037/0022-0663.88.1.64.12.^ Mayer, R.E., Steinhoff, K., Bower, G. and Mars, R. (1995). "Agenerative theory of textbook design: Using annotated illustrations to foster meaningful learning of science text". Educational TechnologyResearch and Development43 (1): 31–41. doi:10.1007/BF02300480.13.^Paas, F., Renkl, A. & Sweller, J. (2004). "Cognitive Load Theory:Instructional Implications of the Interaction between InformationStructures and Cognitive Architecture". Instructional Science32: 1–8.doi:10.1023/B:TRUC.0000021806.17516.d0.14.^ Clark, R.C., Mayer, R.E. (2002). e-Learning and the Science ofInstruction: Proven Guidelines for Consumers and Designers of Multimedia Learning. San Francisco: Pfeiffer. ISBN0-7879-6051-9.15.^ Clark, R.C., Nguyen, F., and Sweller, J. (2006). Efficiency inLearning: Evidence-Based Guidelines to Manage Cognitive Load. SanFrancisco: Pfeiffer. ISBN0-7879-7728-4.16.^Conole G., and Fill K., “A learning design toolkit to createpedagogically effective learning activities”. Journal of Interactive Media in Education, 2005 (08).17.^Carr-Chellman A. and Duchastel P., “The ideal online course,”British Journal of Educational Technology, 31(3), 229-241, July 2000.18.^Koper R., “Current Research in Learning Design,” EducationalTechnology & Society, 9 (1), 13-22, 2006.19.^Britain S., “A Review of Learning Design: Concept,Specifications and Tools” A report for the JISC E-learning Pedagogy Programme, May 2004.20.^IMS Learning Design webpage21.^ a b Piskurich, G.M. (2006). Rapid Instructional Design: LearningID fast and right.22.^ Saettler, P. (1990). The evolution of American educationaltechnology.23.^ Stolovitch, H.D., & Keeps, E. (1999). Handbook of humanperformance technology.24.^ Kelley, T., & Littman, J. (2005). The ten faces of innovation:IDEO's strategies for beating the devil's advocate & driving creativity throughout your organization. New York: Doubleday.25.^ Hokanson, B., & Miller, C. (2009). Role-based design: Acontemporary framework for innovation and creativity in instructional design. Educational Technology, 49(2), 21–28.26.^ a b c Dick, Walter, Lou Carey, and James O. Carey (2005) [1978].The Systematic Design of Instruction(6th ed.). Allyn & Bacon. pp. 1–12.ISBN020*******./?id=sYQCAAAACAAJ&dq=the+systematic+design+of+instruction.27.^ Esseff, Peter J. and Esseff, Mary Sullivan (1998) [1970].Instructional Development Learning System (IDLS) (8th ed.). ESF Press.pp. 1–12. ISBN1582830371. /Materials.html.28.^/Materials.htmlExternal links∙Instructional Design - An overview of Instructional Design∙ISD Handbook∙Edutech wiki: Instructional design model [1]∙Debby Kalk, Real World Instructional Design InterviewRetrieved from "/wiki/Instructional_design" Categories: Educational technology | Educational psychology | Learning | Pedagogy | Communication design | Curricula。

安慰剂检验引用文献

安慰剂检验引用文献安慰剂检验是指在临床试验中使用安慰剂来对照治疗组进行比较，以评估新药物或治疗方法的疗效。

在医学研究中，安慰剂检验通常被用来排除患者对治疗效果的主观影响，从而更准确地评估药物的治疗效果。

关于安慰剂检验的相关文献有很多，以下是一些引用的文献：1. Hróbjartsson A, Gøtzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med. 2001;344(21):1594-1602.2. Miller FG, Colloca L. The placebo phenomenon and medical ethics: rethinking the relationship between informed consent and risk-benefit assessment. Theor Med Bioeth. 2011;32(4):229-243.3. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet. 2010;375(9715):686-695.4. Howick J, Friedemann C, Tsakok M, Watson R, Tsakok T, Thomas J, et al. Are treatments more effective than placebos? A systematic review and meta-analysis. PLoS One. 2013;8(5):e62599.这些文献涵盖了安慰剂检验在临床试验中的应用、安慰剂效应与医学伦理学的关系、安慰剂效应的生物学、临床和伦理学方面的进展，以及安慰剂在治疗中的实际效果等方面的研究成果。

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Probabilistic Saliency Approach for Elongated Structure Detection usingDeformable ModelsXavier Orriols,Ricardo Toledo,Xavier Binefa,Petia Radeva,Jordi Vitri`a and J.J.VillanuevaComputer Vision Center and Dpt.d’Inform`a ticaUniversitat Aut`o noma de BarcelonaEdiﬁci O,08193,Bellaterra,SPAINxevi,ricardo,xavierb,petia,jordi,juanjo@cvc.uab.esAbstractIn this paper we address the object recognition prob-lem in a probabilistic framework to detect and describe ob-ject appearance through image features organized by means of active contour models.We consider the formulation of saliency in terms of visual similarity embedded in the prob-abilistic principal component analysis framework.A like-lihood of object structure detection is obtained using the relation between the visualﬁeld and the internal object rep-resentation.Deformable models are employed introducing a computational methodology for a perceptual organisation of image features as an abstract understanding of the in-tegration between structure and constraints of the visual information-processing problem.Concrete application of the integrated approach for vessels segmentation in angiog-raphy is considered and the results are encouraging.1.IntroductionThe object recognition process via internal representa-tions(abstract models)needs a measure of similarity to compare the responses in visualﬁeld with the learned ob-ject model.Such measure has to relate if it exists a stimu-lus equivalence between the responses in the image and the produced one by the stored model.Unlike bottom-up tech-niques,this process is a high-level and goal-driven task,and considers the context of the visual attention environment[6].The target object-class detection problem affected by vi-sual appearance variability needs,for any object-class,a membership function that is able to identify the degrees of freedom(intrinsic dimensionality)of the category in the in-ternal representation[7].Such a measure is necessary to build a saliency map in order to stand out the regions of This work was supported by CICYT and EU grants TAP98-0631, TEL99-1206-C02-02,TIC98-1100and2FD97-0220.interest,i.e.candidate image co-ordinate points that can allocate the searched structure.The model of internal rep-resentation object categories into a probabilistic framework deﬁnes the approach of target-location problem in terms of maximum likelihood(ML)estimation[3].To obtain the ob-ject shape we need a technique to organize image features with high likelihood estimate.We apply snake technique in order to link image features in object shapes under percep-tual criteria of organization like smoothing,continuity,etc. The advantage of snakes is double:it organizes image fea-tures in object shapes as well as provides a mechnanism to dynamically adjust an initial model to the image features.The outline of this paper is as follows:section2sum-marises the formulation of saliency in terms of visual sim-ilarity,section3focuses on the structure detection as a re-lation between the visualﬁeld and the internal representa-tion.Section4presents the deformable models as a compu-tational methodology for a perceptual organisation of image features.The articleﬁnishes with conclusions and some re-sults are shown.2.Probabilistic Framework for Appearance-Based VisionThe formulation of saliency in terms of visual similarity needs of a probabilistic density framework,where the ob-ject representation model considers the appearance variabil-ity present in the visualﬁeld.The internal representation is introduced by means of Gaussian derivativeﬁlters owing to their well-known mathematical properties and neurophysi-ological reasoning.The measure of similarity is provided by a probabilistic approach of Principal Component Analy-sis(PPCA)[2],in order to capture the intrinsic degrees of freedom of the object category model as well as to give an inherent likelihood measure to the learned object category.2.1.Iconic Representation via Gaussian DerivativeFiltersFollowing the idea that an object can be associated to an abstract representation,the main problem arises in describ-ing its characteristic features.This leads to consider the choice of a suitable basis that allows to handle the informa-tion with a reasonably low cost of data encoding.We choose Gaussian derivativeﬁlters to obtain an iconic representation of image structures,which is motivated by neurophysiolog-ical models of primate cortical receptiveﬁeld proﬁles[9]. Mathematical properties of Gaussian derivatives also con-tribute to justify the choice of our representation,since they form at a centred image point the terms of truncated Tay-lor series expansions of the retinal illuminance function in a certain degree on the scale.In order to comprise the re-sponses on a range of spatial frequencies,we construct the representation space including different scales enough wide to capture the characteristic object features.The use ofﬁlter responses at multiple scales offers on one hand,a more ac-curate description of the object structure than a single one, and on the other hand offers a certain degree of tolerance in view variations.Fixed the representation space,the problem is centred in deﬁning a way to extract theﬁlter responses taking into ac-count that we want to capture the appearance variability of the images corresponding to a particular structure category. However,in the case of focusing the posterior recognition task on oriented objects,we can apply the derivatives along a direction inherent to their shape.Such fact restricts the range of possible appearance variations and keeps the object description invariant to rotations relative to the image point where the object is centred.Speciﬁcally,the analysis of ﬂow like structures(e.g.elongated objects)induces to con-sider the structure tensorﬁeld,which applied to an integra-tion region of the regularized image gradient,mea-sures the coherence between the regions and the searched structure[8]:(1) where are the image coordinates and is a gaus-sian convolution kernel.The eigenvalues of the tensor (1)describe the average contrast variation in the eigendirections.The eigenvector associatedto the lower eigenvalue,is the orientation of lowestﬂuc-tuation,detecting the elongatedﬂow,ﬁgure1(a).Theﬁrst eigenvector describes the directions of maximal grey-level varianceﬁg.1(b).This fact encourages to constraint the de-grees of freedom of theﬁltering orientation.Analogously to the deﬁnition of directional derivative of a function of sev-eral variables,we deﬁne the directional response to aﬁlter along the direction as follows:(a)(b)Figure 1.Directions associated to(a)thelower eigenvalue indicating aﬂow-like struc-ture and larger one(b).where is theﬁlter descomposition into the global Carte-sian basis i.e.,)and has unit norm.We choose asﬁltering directions the vectorﬁeld associated to the bigger structure tensor eigenvalue,since along the elon-gated structure shows uniformity in sense of parallelism among neighbours unlike the gradient vectorﬁeld which in the middle of the tubular structure is null.As a result of ﬁltering the image directionally,we obtain for each pixel a vector of responses,whose dimension depends on the choice of the number of scales and the order of the deriva-tives per scale.2.2.Learning Linear Generative ModelsIn the object recognition task we can assume that all rep-resentations corresponding to a particular object have some-thing in common.The learning process is to deﬁne and de-tect the similarity.This leads to consider a causal approach of the model in order to explain the observations generated by the subjacent phenomena.In the Probabilistic Principal Component Analisys (PPCA)framework[2,3]a small number of causes are con-sidered,that acting in combination generate the complexity of the observed data set.This leads to deﬁne a joint dis-tribution over visible and hidden variables, the corresponding distribution for the observed data is obtained by marginalization:The main goal is toﬁnd the parameters that maximize the joint observed data distribution i.e.the best description un-der a speciﬁc generative model.One of the basic tools is the standard factor anal-ysis(Bartholomew1987)[1],which seeks to relate-dimensional observed data vectors corresponding to -dimensional latent variables by a linear mapping:(2)where latent variables are distributed into an isotropic Gaus-sian distribution,.The noise model,or error,is considered also Gaussian such that,the parameter matrix contains the factors loading,and is a constant which,maximized the likelihood,corresponds to the mean of the data.Given this formulation,the model for is also normal,with mean and covariance matrix.Assuming uniformly distributed noise over the whole image and linearity assumption in(2)lead to the developing of a PPCA[2].In this case endows with equal variance the principal axes(i.e.).Hence,PPCA is a per-missible technique when illuminant variations problem is not analyzed from variance structure.Considering this key assumption leads to consider the conditional independence of observed data.The underlying idea is that the depen-dencies between data variables are explained by a small number of latent variables,while represents the unique variance of each observation variable.Instead,conventional PCA treats both variance and covariance identically.At this point,the problem is centered on parameter es-timation,which,in practice,will be given by data obser-vations.This leads to consider the problem of incomplete data.For this purpose,Dempster et al.(1977)[4]used the EM algorithm,where each observation is associated to an unobserved state,and the main goal is to determine which component generates the observation.In this sense, the unobserved states can be seen as missing data and there-fore the union of observations and is said to be com-plete data,.In this way the likelihood mea-sure to be maximized is the Complete-log-Likelihood,i.e..Maximum-likelihood formula-tion for PPCA also allows a closed solution for the mapping matrix and the noise variance[2].Taking into account that the framework where objects are described is an iconic representation viaﬁlters,the principal directions associ-ated to the learned category model also can be seen asﬁlters. More speciﬁcally,such principal directions are selectiveﬁl-ters to the characteristic features of the stored model,see ﬁg.2.3.Visual Similarity for Structure DetectionThe visual attention process as a relation between the vi-sualﬁeld(external world)and the internal representation is given by a measure of saliency.This measure comes from the similarity between the description of the focus of atten-tion,in terms of the internal representation,and the stored object models.Similarity is obtained by means of the likelihood func-tion in case of considering just only one object -puting this probability requires an inversion of the model covariance matrix:.This canbeFigure2.Selectiveﬁlters to a learned objectcategorydescription.(a)(b)Figure3.(a)Original Image(angiography).(b)Likelihood map of tubular structures.done with low computational cost(instead of) using the Woodbury’s identity:Given a vector as an iconic representation of a local re-gion centred in the image co-ordinate point,its nega-tive log-likelihood(i.e.the distance to the model in prob-abilistic terms)is proportional to.The second summand is precisely where the role of recognition takes relevance. Each quantity represents a matching between the input vector and the principal direction.The way how all correspondences have to be combined is provided by the matrix.In other words,maxi-mum likelihood detection can be done through a correlation process between the principal direction and the observation sample vector.Fig.3shows a likelihood map given that the learning process has been done with the goal of detecting tubular structures using the selectiveﬁlters inﬁg.2.The formulation of saliency into a probabilistic frame-work offers the tempting idea of treating more complex data structures,e.g.the problem of learning different ob-ject categories.Tipping et al.[3]the possibility of an extension to mixture models of PPCA,allowing to apply Bayesian inference for object classiﬁcation.The resulting likelihood distribution function is a linear combination of(a)(b)(c)(d)Figure4.Class conditioned treatment of thedifferent scales in(a)and(b).(c)The result-ing saliency map.(d)Perceptual organitza-tion of saliency responses detecting a morecomplex structure.the prior knowledges with the class conditional probabili-ties:.In our case,the categoriesto be treated are the different scales that the structure can bepresented.This fact allows constructing a saliency map overan extensive range of the structure size.Tipping et al.[3]stand out the fact that the EM algorithm for mixture mod-els is based on the assumption that if there where a set ofindicators,specifying which category was responsible forgenerating each data point,the log likelihood would takethe form:.This observation en-ables to take for each pixel as saliency,the value comingfrom the maximal class-conditioned probability at that im-age point.In other words,for each image point,theresulting probability corresponding to its vectorresponses is given by:(3)4.Deformable Models for Perceptual Organi-sationThe resulting saliency map codes the likelihood of eachimage pixel to represent an image feature characterisingthe learned object.Hence,it forms a continuous topo-graphic surface where lowest points correspond to targetimage features.Still,we need to organize image featureswith high probability in an object shape.Snakes[5]repre-sent a physics-based model that applies perceptual criteriafor organizing image features like continuity,smoothness,approximate shape,etc.Additionally,it incorporates an it-erative procedure based on variational principles to deforman initial model under Newton mechanics laws in order toadjust it towards the image features.In our case,a snake islocated by a user and it deforms on the likelihood map in or-der toﬁnd the image pixels with high probability that forma smooth and continuous shape.Fig.4(d)illustrates the de-formation of the initial deformable model on the likelihoodmap to obtain the object shape in the image.5.Results and ConclusionsA new approach for detecting elongated objects in com-plex backgrounds has been described.The approach com-bines aﬁlter based representation of image neighbourhoodswith learning techniques to obtain an optimal detector.Inorder to organize sparse saliency responses on the image wehave used snakes,a well-known deformable model,whichare naturally integrated on the overall approach.The approach has been succefully tested for segmentat-ing coronary vessels in x-rays images,improving previousresults using classical snakes.References[1] tent Variable Models and Factor Analy-sis.Charles Grifﬁn and Co.Ltd.,1987.[2] C.M.Bishop and M.E.Tipping.Probabilistic principal com-ponent analysis.TR NCGR,1997.[3] C.M.Bishop and M.E.Tipping.A hierarchical latent vari-able model for data visualization.IEEE Trans.on P.A.M.I,20(3),1998.[4] A.Dempster,ir,and D.Rubin.Maximum likelihoodfrom incomplete data via the EM algorithm.J.of the RoyalStatistical Society Series B,39:1–38,1977.[5]M.Kass,A.Witkin,and D.Terzopoulus.Snakes:Activecontour models.In I.C.C.V.,pages259–268,1987.[6] B.Moghaddam and A.Pentland.Probabilistic visual learningfor object representation.IEEE Trans.on P.A.M.I,19(7):696–710,1997.[7]K.Sung and T.Poggio.Example-based learning for view-based human face detection.A.I.Memo1521,C.B.C.L.Paper112,1994.[8]J.Weickert.Coherence-enhancing diffusion of colour images.In Image and Vision Computing,volume17,pages201–212,1999.[9]R.Young.The gaussian derivative theory of spatial vision:Analysis of cortical receptiveﬁeld line-weighting proﬁles.General Motors Research Publication GMR-4920,1985.。

Probabilistic Saliency Approach for Elongated Structure Detection using Deformable Models

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Probabilistic Saliency Approach for Elongated Structure Detection using Deformable Models

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Electric Power Systems Research

卵园孔未闭介入封堵指针今天还是明天

Probabilistic model checking of an anonymity system

每天两次氮斯汀喷鼻剂治疗季节性过敏性鼻炎的药用疗效外文翻译原文

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腹膜透析导管腹腔内段末端位置的研究进展

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RSR AQP4 Ab Version2 Aquaporin4 (AQP4) Autoantibod

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于慧敏，浙江大学，教授,博士生导师。主要研究方向为图像视频处理与

2023年英语中考卷子

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matlab图像处理中英文翻译文献

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