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阿那格雷的合成检索报告
化学反应式（十三）
三、合成检索报告
反应式（十三）检索的文献
① Bristol-Myers Company. US4146718, 1979, A
化学反应式（十四）
三、合成检索报告
反应式（十四）检索的文献
① Bristol-Myers Company. US4146718, 1979, A
化学反应式（十五）
① Yamaguchi, Hitoshi; Ishikawa, Fumiyoshi. Journal of Heterocyclic Chemistry, 1981, vol. 18, p. 67 - 70
化学反应式（十二）
三、合成检索报告
反应式（十二）检索的文献
① Bristol-Myers Company. US4146718, 1979, A
一、阿那格雷简介
CAS号: 68475-42-3 英文名称: Anagrelide 中文名称:阿那格雷
二、使用的检索工具
Reaxys 数据库 Web of Science数据库
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Scifinder数据库
化学反应式（一）
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反应式（一）检索的文献
① SYNTHON BV; GIELING, Reinerus Gerardus; LINDEN van der, Johannes Bastiaan; VERKERK, Pascal Renart; MELŠA, Petr. WO2014/139572, 2014, A1
三、合成检索报告
反应式（十五）检索的文献
① CHEMISCH-PHARMAZEU TISCHES LABOR ROLF SACHSE GMBH. WO2004/63172, 2004, A1
三阴性乳腺癌的治疗现状
II (n=30)
Neoadjuvant TNBC
E-Cis-FP
pCR=40%; ORR=86%
Silver ()
II (n=28)
Neoadjuvant TNBC
Cis
pCR=22%
Leone ()
Retro (n=125)
Sikov ()
Platinum + D
pCR=34%, OS @ 5yr=55%, OS greater with cis vs carbo
Carbo=carboplatin; Cis=cisplatin; D=docetaxel; E=epirubicin; F=5-FU; H=trastuzumab; P=paclitaxel; retro=retrospective.
三阴性乳腺癌的治疗现状
第22页
(7) High dose chemotherapy(HDC ) for TNBC
五、TNBC－分子病理特征
三阴性乳腺癌的治疗现状
第8页
临床表现为侵袭性病程； 远处转移风险较高,内脏转移几率较骨转移高,脑转移几率也较高。预后较差,死亡风险较高。
六、TNBC－临床特征
三阴性乳腺癌的治疗现状
第9页
TNBC: Shorter Median Time from
Distant Relapse to Death
WSG AM 01试验 9个以上淋巴结阳性乳腺癌患者分为两组 A组: 密集EC× 2 序贯 HDC × 2 ( EPI 90 mg/m2,CTX 3 g/m2,塞替派400 mg/m2)B组: 密集EC × 4 序贯 密集CMF × 3结果表明,年轻三阴性乳腺癌患者从HDC中获益最多。
sample_references
AEA Publications Sample ReferencesWe use the Chicago Manual of Style Author-Date system for all common publication types:/16/ch15/ch15_sec009.html.The following examples are intended to provide information for less common sources.DatasetsWhen referencing datasets, please include the author name or name of the provider hosting the data, the year the data were collected or posted, the name or title of the dataset, the name of the database if applicable, and any other information necessary for one to retrieve the data. Please include the date accessed in parentheses at the end. Example 1: Bureau of Labor Statistics. 2000–2010. “Current Employment Statistics: Colorado, Total Nonfarm, Seasonally adjusted - SMS08000000000000001.” United States Department of Labor. /cgi-bin/surveymost?sm+08 (accessed February 9, 2011).Example 2:Leiss, Amelia. 1999. “Arms Transfers to Developing Countries, 1945–1968.” Inter-University Consortium for Political and Social Research, Ann Arbor, MI. ICPSR05404-v1. doi:10.3886/ICPSR05404 (accessed February 8, 2011).For data references specifically associated with a published paper, please include the Author Name(s). Year. “Paper Title: Dataset.” Journal Name. Location of the data.Example 3: Romer, Christina D., and David H. Romer. 2010. “The Macroeconomic Effects of Tax Changes: Estimates Based on a New Measure of Fiscal Shocks: Dataset.” American Economic Review./articles.php?doi=10.1257/aer.100.3.763 (accessed August 22, 2012).Multivolume WorksMultivolume works include works such as encyclopedias, multivolume works published over several years, and multivolume works published in a single year. Below are a few examples.Example 1: Kohama, Hirohisa, ed. 2003. Asian Development Experience. Volume 1. External Factors in Asian Development. Singapore: Institute of Southeast Asian Studies.Example 2: Kusuoka, Shigeo, and Akira Yamazaki, ed. 2006. Advances in Mathematical Economics. Volume 8. New York: Springer.Example 3: Mokyr, Joel, ed. 2003. The Oxford Encyclopedia of Economic History. 5 vols. Oxford: Oxford University Press.Working PapersOnly papers appearing as part of an institution’s working papers series should be classified as working papers. These should always include a specific working paper number as assigned by the institution.Author Last Name, First Name. Year. “Title.” Type of Working Paper (such as institution, working series title) and number.Example 1: Ausubel, Lawrence M. 1997. “An Efficient Ascending-Bid Auction for Multiple Objects.” Universityof Maryland Faculty Working Paper 97–06.Example 2: Heidhues, Paul, and Botond Kőszegi. 2005. “The Impact of Consumer Loss Aversion on Pricing.” Centre for Economic Policy Research Discussion Paper 4849.Unpublished PapersWhen a paper has not been published but can be found on the Web (such as the author’s website or the university website), use the following format: Author Last Name, First Name. Year. “Title.” URL. Please provide a URL that links to the full text of the article.Example 1: Zitzewitz, Eric. 2006. “How Widespread Was Late Trading in Mutual Funds?”/zitzewitz.When a paper has not been published and does not appear on a website (such as the author’s website or university website), use the following format: Author Last Name, First Name. Year. “Title.” Unpublished.Example 2: Acemoglu, Daron, Pol Atràs, and Elhanan Helpman. 2006. “Contracts and Technology Adoption.” Unpublished.Lectures and Papers Presented at MeetingsAuthor Last Name, First Name. Year. “Title.” Paper presented at followed by meeting name, place, and city where the lecture/meeting took place.Example 1: Romer, Christina D., and David H. Romer. 2006. “The Evolution of Economic Understanding and Postwar Stabilization Policy.” Paper presented at the Rethinking Stabilization Policy Federal Reserve Bank of Kansas Symposium, Jackson Hole, WY.Example 2: Goldin, Claudia. 2006. “The Quiet Revolution that Transformed Women’s Employment, Education, and Family.” Paper presented at the annual meeting of the Allied Social Science Associations, Boston. Newspapers, Online Encyclopedias, and Reference WorksBecause newspapers, magazines, and encyclopedias are continuously updated, they should be cited as footnotes in the text. They should not be included in the reference list. Undated sources should always include an access date along with the URL. When possible, use the URL assigned to the specific content you are citing.Author Last Name, First Name. Year. “Title.” Magazine, Month and Day. URL.Example: Becker, Gary S. 1993. “The Evidence against Blacks Doesn’t Prove Bias.” Business Week, April 19. /index.jsp.Books Published ElectronicallyIf a book is available in more than one format, cite the version you consulted. For books consulted online, list a URL. If no fixed page numbers are available, you can include a section title or a chapter or other number.Author Last Name, First Name. Year. Title. City: Publisher. Format.Example 1:Austen, Jane. 2007. Pride and Prejudice. New York: Penguin Classics. Kindle edition.Example 2:Kurland, Philip B., and Ralph Lerner, eds. 1987. The Founders’ Constitution. Chicago: University of Chicago Press. /founders/.。
An Agent-Based Decision Support System for Hospitals Emergency Departments
Available online at 1877–0509 © 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Prof. Mitsuhisa Sato and Prof. Satoshi Matsuoka doi:10.1016/j.procs.2011.04.203Procedia Computer Science 4 (2011) 1870–1879/locate/procediaInternational Conference on Computational Science, ICCS 2011An Agent-Based Decision Support System for Hospitals EmergencyDepartments *Manel Taboada a , Eduardo Cabrera b , Ma Luisa Iglesias c ,Francisco Epelde c , Emilio Luque b **aTomas Cerda Computer Science School , University Autonoma of Barcelona(UAB), Spain bComputer Architecture and Operating Systems Department (CAOS), UAB, SpainCHospital of Sabadell,Consorci Sanitari Parc Taulí, Barcelona, SpainAbstractModeling and simulation have been shown to be useful tools in many areas of the Healthcare operational management, field in which there is probably no area more dynamic and complex than hospital emergency departments (ED). This paper presents the results of an ongoing project that is being carried out by the Research Group in Individual Oriented Modeling (IoM) of the University Autonoma of Barcelona (UAB) with the participation of Hospital of Sabadell ED Staff Team. Its general objective is creating a simulator that, used as decision support system (DSS), aids the heads of the ED to make the best informed decisions possible. The defined ED model is a pure Agent-Based Model, formed entirely of the rules governing the behavior of the individual agents which populate the system. Two distinct types of agents have been identified, active and passive. Active agents represent human actors, meanwhile passive agents represent services and other reactive systems. The actions of agents and the communication between them will be represented using Moore state machines extended to include probabilistic transitions. The model also includes the environment in which agents move and interact. With the aim of verifying the proposed model an initial simulation has been created using NetLogo, an agent-based simulation environment well suited for modeling complex systems.Keywords : Healthcare operational management, agent-based modelling, individual oriented simulation, emergency department, decision support systems.1. IntroductionHealthcare is one of the most important services in modern civilization. In a hospital there are many complex, independent, but interrelated departments [1]. The Emergency Department (ED) may well be one of the most complex and fluid healthcare systems that exists, consuming a large portion of economic budgets for health services. However, patients often feel neglected and that the service is saturated. The activity of ED is not linear, It varies depending on time, day of week and season. For this reason resource planning of ED is complex. The ability to simulate special situations such as seasonal increases in ED demand can be useful for the efficient use of resources. The simulation of complex systems is of considerable importance and is used in a broad spectrum of fields such* This research has been supported by the MICINN Spain, under contract TIN2007-64974**E-mail addresses : manel.taboada@eug.es (Manel Taboada), ecabrera@caos.uab.es (Eduardo Cabrera),Emilio.luque@uab.es (Emilio Luque), MIglesias@tauli.cat (Ma Luisa Iglesias), epelde@comb.es (Francisco Epelde).Manel Taboada et al. / Procedia Computer Science 4 (2011) 1870–18791871 as engineering, biology, economy and health care. There are no standard models to describe these complex systems, but they share many common traits. Agent-Based Modeling (ABM) is an efficient and well utilized technique for simulating this kind of systems. Some of the advantages that offers are an increased detail in experiments based in simulation, a transparent learning process, and the ability to control and easily modify individual behavior.This paper presents the results of an ongoing project that is being carried out by the Research Group in Individual Oriented Modeling (IoM) of the University Autonoma of Barcelona (UAB), with the participation of the ED Staff Team of the Hospital of Sabadell. Its general objective is to develop a simulator that, used as decision support system (DSS), aids the administrators and heads of the ED to allow additional knowledge of patient admission scheduling, physician staff, resource optimization, and decreased patient waiting time, amongst other situations. Following Macal and North [2], and also making use of the considerable expertise existing within the IoM research group, a concrete and continuous development methodology has been devised for the construction of the tool, applying an iterative & spiral process. Each cycle involves 5 phases (system analysis; model design; simulator implementation; simulator execution and results analysis; simulator validation). Once an initial cycle is completed, based on the conclusions obtained during the analysis and validation phase, the model is updated and a new cycle is carried out. The process will be repeated until the objectives are achieved.Through the first cycle it has started the design of an Agent-Based Model for Hospital Emergency Departments, in which all rules within the model concern the agents, no higher level behavior is modeled. The System behavior emerges as a result of local level actions and interactions. This model describes the complex dynamics found in an ED, representing each individual and system as an individual agent. Two distinct kinds of agents have been identified, active and passive. Active agents represent the individuals involved in the ED, in this case all human actors, such as patients and ED Staff (admission staff, nurses, doctors, etc). Passive agents represent services and other reactive systems, such as the information technology (IT) infrastructure or services used for performing tests. State machines are used to represent the actions of each agent. This takes into consideration all the variables that are required to represent the many different states that such individual (a patient, a member of hospital staff, or any other role) may be in throughout the course of their time in a hospital emergency department. The change in these variables, invoked by an input from an external source, is modeled as a transition between states. The communication between individuals is modeled as the Inputs that agents receive and the Outputs they produce, both implicitly and explicitly. In order to control the agent interaction, the physical environment in which these agents interact also has to be modeled, being sufficient do it as a series of interconnected areas, such as admissions, triage box, the waiting room, or consultation suits.The remainder of this article is organized as follows; section 2 describes the related and previous work. The proposed emergency department model is detailed in section 3, while the results of an initial simulation are given in section 4. In section 5 the future work is pointed out. Finally, section 6 closes this paper with conclusions.2.Related and previous workThe modeling and simulation of hospital emergency departments sits at the intersection of a number of distinct fields. In addition Agent-based techniques have been used in the modeling of healthcare operational management, but there are few pure agent-based models to be found in the literature that have been rigorously validated against their real world counterparts.Economics, biology, and social sciences are the three fields in which agent-based models are most utilized [3]. Modeling techniques using agents can bring the most benefit when applied to human systems where agents exhibit complex and stochastic behavior, the interaction between agents are heterogeneous and complex, and agent positions are not fixed [4]. In the particular case of social sciences ABMs are used in situations where human behavior cannot be predicted using classical methods such as qualitative or statistical analysis [5]. Human behavior is also modeled with ABMs in the fields of psychology [6] and epidemiology [7] amongst others.Agent technology is a useful tool when applied to healthcare applications. Previous works modeling healthcare systems have focused on patient scheduling under variable pathways and stochastic process durations [8], the selection of an optimal mix for patient admission in order to optimize resource usage and patient throughput [9]. Work has been performed using differing degrees of agent-based modeling for evaluating patient waiting times under the effects of different ED physician staffing schedules [10] or patient diversion strategies [11].The proposal of the project addresses many of the issues surrounding the modeling and simulation of a hospital1872Manel Taboada et al. / Procedia Computer Science 4 (2011) 1870–1879emergency department using agent-based technologies. In an attempt to understand micro level behavior, the basic rules governing the actions of the individual agents are defined. The macro level behavior, which means the system as a whole, emerges as a result of the actions of these basic building blocks, from which can be derived an understanding of the reasons of the behavior at the system level[12].Comparing the general objectives of the Project presented in this paper with the previous works, two potential improvements may be underlined. In one hand the generality of the model, which means the possibility of applying the model and the tool in different Hospital ED, after adjustments of the configuration parameters achieved through the tuning process that will be described after. In the other hand the variety and typology of agents are richer. The variety of patients in this model is higher and closer to the reality than the models found in the previous works. In addition the model includes ED Staff (admission staff, sanitarian technicians) and devices (Information System Infrastructure, radiology services, laboratory tests, etc) that aren't considered in the consulted works, and finally it takes into account different levels of expertise in the ED Staff. Undoubtedly all these elements may affect the length of stay of patients in the emergency department.3.Emergency department modelThe Emergency Department model defined in this work is a pure Agent-Based Model, formed entirely of the rules governing the behavior of the individual agents which populate the system. Through the information obtained during interviews carried out with ED staff at the Hospital of Mataro (a hospital of medium size) and the Hospital of Sabadell (one of large size), two kinds of agents have been identified; these are active and passive agents. The active agents represent people and other entities that act upon their own initiative: 1) patients; 2) relatives of patients (who have a special relevance in dependent patients like kids, elderly, etc.); 3) admission staff (who receive patients just when they arrive to the Emergency Department); 4) sanitarian technicians (who help certain patients to move from one place to another of the ED); 5) triage and emergency nurses (the former receive patients after their admission for establishing their priority level. The second involved in the diagnosis and treatment phase); 6) and doctors (of two kinds, staff emergency doctors and medical specialties consultants).The passive agents represent systems that are solely reactive, such as the loudspeaker system, patient information system, pneumatic pipes, and central diagnostic services (radiology service and laboratories). This section is dedicated to describe the various components of the general model in detail. Section 3.1 explains the manner in which active agents are modeled. Passive agents are discussed in section 3.2. The communication model is defined in section 3.3. Finally in section 3.4 the details of the environment where the agents move and interact are outlined.3.1 Active AgentsActive agents are described by state machines, specifically Moore machines. A Moore machine has an output for each state; transitions between states are specified by the input. The current state of an active agent is represented by a collection of “state variables”, known as the state vector (T). Each unique combination of values for these variables defines a distinct state. As described below, in each time step the state machine moves to the next state as defined by the current state and the input vector.3.1.1 State variablesIn order for the state machine works, all state variables must be enumerable in some manner. This may be discrete variables or variables representing continuous quantities which have been divided into ranges. As shown Table 1, an initial set of state variables has been defined through the round of interviews performed, based on the minimum amount of information required to model each patient and member of staff. Such initial set of state variables are:∙Name/identifier: for identifying each individual∙Personal details: this variable collects the information of the individual that is relevant in relation with his stay in the ED, such as age, medical history, origin, etc.∙Location: the area of the ED where the individual currently is. The kind of active agents (specifically the ED Staff) who may stay in it and also the kind of interactions that may occur are different in each ED area.∙ Action: what the individual is doing in a particular state. The actions will be different depending on the agent and the place where such agent is. Actions normally have a duration, and thus will influence the total length ofManel Taboada et al. / Procedia Computer Science 4 (2011) 1870–18791873the patient's stay in the Emergency Department.∙ Physical condition: variable used to collect the information that let ED Staff to identify the patient’s disease. Obviously this variable only makes sense for the agent "patient".∙ Symptoms: Information reported by the patient, and classified by ED staff following the Canadian relevant triage and acuity scale. The priority level with which the patient must be attended will be identified through the information collected in this variable.∙ Communication skills: the time spent during the process depends on the agent’s ability to communicate . This variable makes sense for both, patients and ED staff.∙ Level of experience: that only makes sense for ED Staff. The processing time required by the Staff to complete his tasks will depend on his/her experience.Table 1. Initial selection of state variables and their valuesVariablesValuesName/identifier <id> Unique per agentLocation <location> Entrance; admissions; waiting room; triage box; Consultancy Room; Treatment Box; ...ActionIdle; requesting information from <id>; giving information to <id>; searching; moving to <location> Physical condition Hemodynamic-constant; Bartel index (sample)SymptomsHealthy; cardiac/respiratory arrest; severe/moderate trauma; headache; vomiting; diarrhoea; (sample)... Communication skillsLow; medium; highLevel of experience (ED Staff) None; Low; medium; high.Some of the state variables will have a potentially very large set of possible values, e.g. the symptoms or physical condition. Both the variables and their possible values must be improved in future work. 3.1.2 Inputs, outputs & state transitionsUpon each time step the state machine moves to the next state. This may be another state or the same one it was in before the transition. The next state the machine takes is dependent on the input during that state. The input may be more accurately described as an input vector (I) that contains a number of input variables, each one of which may take a number of different values. As this is a Moore machine, the output depends only on the state, so each state has its own output, although various states may have outputs that are identical. Again, the output is more accurately described as an output vector (O), a collection of output variables, each with a number of defined possible values. Transitions between states are dependent on the current state at time t (St) and the input at time t (It).Fig. 1. (a) State transition graph; (b) State transition tableThe state machine will be in a new state (St+1) following the transition. The state machine can be represented as a diagram (shown in figure 1 (a)), but also in form of a state transition table, as shown in figure 1 (b), where each row represents a unique state input combination, showing the output and the state in the next time step (defined by the current state and the input). 3.1.3 Probabilistic state transitionsIn dynamic and complex systems such as EDs, there exists the necessity of a model not entirely deterministic. In these cases a state machine can be modeled with more than one possible next state given a current state and input combination. Which transition is made is chosen randomly at the time of the transition; weights on each transition provide a means for specifying transitions that are more or less likely for a given individual. Each one of the inputCurrent state / Output Input Next state / Output S 0 / O 0 I 0 S i / O i S 0 / O 0 I 1 S j / O j S 0 / O 0 I 2 S k / O k …. …. …. S x / O x I 0 S y / O y S x / O x I 1 S z / O z ….…. ….1874 Manel Taboada et al. / Procedia Computer Science 4 (2011) 1870–1879variable of the input vector (I) may take a number of different values. In these cases the state transition table is defined with probabili ties on the “effect” of the input , as shown in figure 2(b). An agent in state S X receiving input I a may move to either state S y , state S z , or remain in the same state, with a probability of p 1, p 2, and p 3 respectively. One of these transitions will always occur, which is to say p 1 + p 2 + p 3 = 1. The state diagram would then have three different transitions for the “current state -input” combination of this specific example , as shown in figure 2(a).Fig. 2. (a) Probabilistic state transition graph; (b) Probabilistic state transition tableThe exact probabilities may be different for each agent, in this way agent behavior can be probabilistically defined external to their state, representing personality characteristics in different people. 3.2 Passive agentsPassive agents represent services within the hospital system such as the IT infrastructure (that allows to store patient details), radiology services and other laboratory tests as well as specialist systems such as the pneumatic tube networks that some larger hospitals use to quickly transfer samples from one part of a building to another.In some of this kind of agents the state machine will be a simple system for interacting with active agents. The model is not, however, purely a state machine. In order to represent data storage or other systems that may have a very large number of combinational states a simple memory model will be used. A passive agent may (although it is not necessary) have a simple record based memory system, allowing it to store and repeat information provided by active agents.3.3 Communication modelThe interaction between agents is carried out through communication. Such communication is modeled as the Input that agents receive and the Outputs that they produce. Both, Inputs and Outputs may be explicit and implicit. The communication model represents three basic types of communication: 1) 1-to-1, between two individuals (the message has a single source and a single destination, as happens between admission staff and patient, during the admission process); 2) 1-to-n , representing an individual addressing to a group (like a doctor giving information to patient and nurses during the diagnostic process); 3) and 1-to-location , when an individual speaks to all occupants of a specific area (for instance when any staff member uses the speaker system to address a message to all the people who are in a specific waiting room).Implicit or passive communication also exists, where an agent may be producing communication just be remaining in a certain area. This is the manner in which agent vision, what each agent sees, can be represented using the same model. An agent is continuously emitting messages with regard to its visible physical status and location, other agents receive these 1-to-location messages and may act upon them in certain circumstances. For instance an agent waiting for another agent in a certain area will receive communication that the agent has entered and act upon it, representing, for instance, a nurse seeing a patient enter a triage room and attending them.Messages are divided in three parts. The message source is the individual who is communicating, speaking in many cases. The message destination would then be to whomever this individual is speaking to, and thirdly the content, what is being said. These three parts make up the message tuple (<src>, <dst>, <content>). In the case of a 1-to-location message, the destination of the message is an entire location, so the content may need to include the actual indented recipient of the message (for example a patient’s name being called over the loudspeaker system ). 3.4 EnvironmentAll actions and interactions modeled take place within certain locations, collectively known as the environment. The environment itself can be defined in two different levels depending on the positional precision required of the model: at a low or high granularity scale. The former implies to divide the space into a few general areas, where allCurrent state / Output Input Next state / Output S x / O x I a(p 1) S y / O yS x / O x S x / O x -- I a(p 2) I a(p 3) -- S z / O z S x / O x--Manel Taboada et al. / Procedia Computer Science 4 (2011) 1870–18791875 agents in the same area may freely interact. The second requires more precise positioning, using physical Cartesian co-ordinates. In the specific case of the Emergency Department it is enough use a low granularity positioning scale, although it is important to represent distances between distinct areas, to correctly model travel times from one area to another.The different areas identified through the information obtained during the interviews carried out are: Admissions (where patients have to address just when they arrive to the ED, and Admission Staff register their arrival); Triage Box (where a “triage nurse” receives the patient, takes his/her vital signal s and obtains some additional information in order to identify the priority level); Waiting Room (where patients and their companions wait for being triaged, and once they have past the triage process, until be called to enter the treatment zone); diagnostic and treatment zone (where Doctors, nurses and other ED Staff carry out the diagnostic and treatment process with patients). Figure 3 shows a representation of topographical distribution of the Emergency Department.Fig. 3. Simplified emergency department layoutThe environment in which the agents move and interact is passive and discrete. There is little distinction made between agents in the same location. A patient in the waiting room does not have any more specific sense of position than they are in the waiting room. Certain locations may be physically distinct, but functionally identical, for instance there are usually a number of triage rooms, an agent in any one of these will act as if they are in any triage room, however they Simplified ED layout are distinct in order to represent that each available room may only be used by one nurse-patient group at a time. The environment also contains representations of the relative distances between different discrete locations.4.Initial simulationWith the aim of verifying the proposed model designed in the first cycle, an initial simulation has been created using the agent-based simulation environment NetLogo [13], a high level platform particularly well suited for modeling complex systems developing over time [14]. NetLogo lets modelers give instructions to hundreds or thousands of independent agents, all operating concurrently, what makes possible to explore connection between the micro-level behavior of individuals and the macro-level patterns that emerge from the interaction of many individuals. NetLogo also allows visualizations of agent actions and interactions, a very important aspect considering that a primary use of the tool is to garner feedback from the staff who works in ED.The scenario adopted for this initial experiment is to simulate patients moving through a simplified Emergency Department that includes four primary areas: admissions, triage (with a maximum of 3 boxes), 2 waiting rooms (one for patients before triage, and the second for patients who have passed the triage process, and are waiting for treatment), and the diagnosis and treatment area (that include four boxes). The types of active agents represented in this simulation are patients, admission staff (AS), triage nurses (TN), and doctors (D). In the case of the ED Staff, two distinct levels of experience have been considered (low, labeled as junior, and high, labeled as senior). Less experienced staff will need more time to carry out his/her part of the process than the most experienced one. Such time is internally set by modeler through the programming language, but the user can define easily both, the number of each type of ED s taff and their level of experience using a “console of configuration”.With the purpose of making a preliminary demonstration of how accurate a simulation can be produced using only reduced parameters, a simplified set of patient attributes and a less complicated patient flow have been defined. Patient arrives to the1876Manel Taboada et al. / Procedia Computer Science 4 (2011) 1870–1879Emergency Department by their own means, and waits to be attended in the Admission Zone. Once the admission process has been carried out, the patient stays in a first Waiting Room (WR) until he is called by triage nurse. After the triage process patient goes to a different WR and stays there until a doctor is free and calls him to start the process of diagnosis and treatment. Once such process is completed, the patient leaves the ED. Therefore patients are shown following the same path through the ED, even though in reality they are treated differently depending on the level of severity of their condition. The time spent at treatment stage may also represent laboratory tests, which are not shown explicitly. In the real system the arrival of patients to the ED vary depending on time, day of week and season, but in this experiment a constant pattern has been considered due to the unavailability of detailed data of the real system. This means that the patient arrives to the ED after a certain time step which can be easily defined by user through t he “console of configuration” mentioned above. Figure 4 shows a static view of the user interface.Fig. 4. Simulation display in NetlogoNetlogo stores information about all what happens during the running, and lets modeler to create reports with all kind of information which can be exported and treated with statistical and data mining tools. In this initial experiment the report has been designed for including information about the number of patients that have arrived to the ED during the running, the amount of patients that have completed the process, and the time that each patient have spent in each one of the ED zones (absolute values, mean, minimum, maximum and standard error).In order to analyze the behavior of the simulator in front of the variables that have influence in the ED, the simulation has been executed several times for the equivalent to one day of activity. In a first exercise the amount of patients who arrive to the ED has been changed, maintaining invariable the mix of ED Staff (1 AS, 2 TN and 4 D, all of them with a Junior profile). Table 2 shows the results obtained. As expected, an increase in the probability of patient's arrival causes an increase of the number of patients who arrive to the ED. Due to the resources don't change, the system becomes saturated (gradual increase of the average time spent in the service, of the waiting times at the WR1 and WR2, and of the number of patients waiting to be attended at the end of execution). In the first 2 cases (20% and 40% of probability) patients are attended without doing any queue and there are idle resources (staff members who do not attend to any patient during the execution). In the third case it starts to generate some waiting time, although it is insignificant. By c ontrast, for a patient’s arrival probability of the 80%, the average waiting time in WR1 is nearly an hour, and 2.44 in WR2, and there is a significant number of patients who remain in the Waiting Table 2. Results obtained with a invariable mix of ED Staff, for a increasing arrival of patients20% 40% 60% 80%B-Total patients who completed the process during the running 90 184 271 270For patients who have completed the processC-Average of total time of stay in ED (in hours)0,54 0,54 1,08 3,95D-Average of total time of stay in WR 1 (in hours) 0,00 0,00 0,04 0,98E-Average of total time of stay in WR 2 (in hours) 0,00 0,00 0,52 2,44F-Patients in WR1 when execution finalize 0 0 1 46G-Patients in WR2 when execution finalize 0 0 8 74。
审计术语
auditCPAassuranceaudit of financial statementsagreed-upon procedurescompilationhigh levels of assurancemoderate levels of assurancecredibilityreliabilityrelevancecontinuing professional education(CPE)A uniform CPA examinationprofessional skepticismobjectivityprofessional competenceSenior/CPA-in-chargeaudit engagement letterrecurring auditthe clientthe nominated CPAchange CPAthe exsiting CPAthe preceding CPA(The predecessor CPAaudit appointmentthe agreed termaccpet an audit engaementthe objective of the engaementthe scope of the auditissue the audit reportother CPAexpertwithdrawan initial auditthe board of directorsa change in engaementshareholdercomponentknowledge of the entity's businessperforming an audit of financial statementsassess inherent and control risksdetermine the nature, timing and extend of the audit procedures a general knowledge of …, a preminary knowledge ofa more particular knowledge ofprior to accepting an engagementfollowing acceptance of the engagementupdate and revaluate information gathered previouslythe prior year's working papersdirectorsenior operating personelinternal audit personel, internal audit'sinternal audit reportsminutes of meetingmaterial sent to shareholders or filed with regulatory authorities interim financial reportsmanagement policy manualchart of accountsexercise professional judgmentbusiness risks(of the client)mannagement response theretoappropriatenessaccounting estimatemanagement representationsrerated partyrelated party transactiongoing concern assumptionaudit planthe overall audit planthe detailed audit planeffcient auditthe size of the entitythe complexity of the auditthe specific methodology and technologyfinancial performancematerial misstatementsignificant audit areascoordinationreviewstatutory responsibilitytime budgeterrorfraudmodified or additional procedureplan and perform audit procedureadequate accounting and internal control systemreduce but not eliminatemanipulationfalsificationalteration of records or documentsmisappropriation of assetstransactions without substancemisapplication of accounting policiesthe underlying recordsoversight or misinterpretationunusual pressuresaccounting policy alternativeunusual transactionsincomplete filesout of balance control accountslack of proper authorizationcomputer information systems environmentinherent limitations of audit testdisscuss with managementthe remedial actionseek legal advicelaws and regulationsnoncompliancewithdrawal from the engagementsenior managementdetect noncompliance laws and regulationsdeliberate failure to record transctionssenior management override of controlintentional misrepresentations being made to the CPA written representationthe suspected noncomplianceaudit committeesupervisory boardregulatory and enforcement authoritiesmaterialityexceed the materiality levelapproach the materiality levelan acceptably low levelthe overall finacial statement level and in related account balances and transaction levelsthe detected but uncorrected misstatements or omissions misstatements or omissionsthe detected and the projected misstatements or omissions aggregatesubsequent eventscontingenciesextend the scope of the substantive testadjust the financial statementsperform additional audit procedurescarry out extended or additional tests of controlmodify the nature,timing and extendof planned substantive proceduresaudit riskinherent riskcontrol riskdetection riskinappropriate audit opinionmaterial misstatementanalytical procedures risksubstantive tests of the detail risktolerable misstatementthe combined level of inherent and control risks the acceptable of detection riskplanned assessed level of control risksmall businessaccounting systeminternal control systemcontrol environmentcontrol procedurescompliance testtest of controlwalk-through testmanagement lettermaterial weakness in internal controlrisk assessmentcontrol activitiesinformationcommunicationmonitoringprocedures manualjob descriptionsflow chartwritten narrativequestinnairereperformance of internal controlcomputer-assisted audit techniques communication with managementaudit evedencetests of controlsubstantive proceduressufficiency of audit evidenceappropriateness of audit evedenceassertionsexistence or occurrencecompletenessrights and obligationsvaluation or allocationpresentation and disclosurevaliditycutoffmechanical accuracyclassificationdisclosureinspectionsupervision of countingobservationenquiryconfirmationcomputationanalytical proceduresvouchaged trial balancetraceaudit samplingerroranomalous errorexpected errorpopulationsampling risknon-sampling risksampling unitstatistical samplingstratificationtolerable errorthe risk of under reliancethe risk of over reliancethe risk of incorrect rejectionthe risk of incorrect acceptancethe rate of deviationsample sizerequired confidence levelthe number of sampling units in the population methods usedeffective auditefficient auditaudit working papers(documentation)working trial balanceadjusting and reclassification entriesaudit markindexing and cross-referencingpermanent audit filescurrent audit filescomprehensive working papersaudit-oriented working papersreference working papersthe use of standardized working papers checklistscash receiptcash disbursementpetty cashcustodyflowchartinternal control questionnaire walk-through of the system segregation of dutiesdeposit slippurchase orderreceiving reportgeneral ledgerbank statementbank reconciliationbalance sheet datecheck outstandingchange fundcash countkitingfloat periodcutoff bank statement unearned revenuenet realizable valuecollateralsales orderstoreroomstorekeeperperpetual inventory record shipping documentbill of ladingbillingsales invoiceextensfootingprice listaging scheduleaged trial balancebreak downdelinquent account confirmationpositive confirmation request negative confirmation request advancepurchase requisitionpurchase ordervouchers payablevendor's invoicediscrepancydescriptionvouchersremittancegross marginresonablenessauthenticityoverheadmanufacturing overheadbill of materailsinspection recordjob costlabor cost distributionmaterial requisitionpayroll summarypayroll ledgerproduction orderprodution runsrate and deduction authorization form time cardtime ticketaccountabilityrouting sheetsuppliesutilitiesjob orderinventory-takingtest countinventory tagbond certificatestock certificatebroker's advicepaid-in-capitaltreasury stockbond debentureportfolioleaseholdasset retirement orderregistrartransfer agenttrust companynegotiable intrumentcollateralliens and mortgaesminutes of board of directorstrusteerestrictive covenantcontributed capitalstubaudit reportthe truthfulness of the audit reportthe legitimacy of the audit reportentityaddressee of the audit reportunqualified opinionqualified opiniondisclaimer of opinionadverse opinionintrodutory paragraphscope paragraphopinion paragraphexplanatory paragraphmaterialprofessional languagescope limitationunadjusted eventsadquately disclosedthe extent of impact on the finacial statemnts audit report on special purpose engagements审计注册会计师可信性保证财务报表审计执行商定程序编制高保证水平中等保证水平可信性、可信程序可靠性、可靠程序相关、相关性职业后续教育统一注册会计师考试职业谨慎客观，客观性专业胜任能力项目经理业务约定书连续审计、常年审计委托人被提名审计师更换审计师现任审计师后任会计师审计委托约定条款接受业务委托委托目的审计范围出具审计报告其他注册会计师专家撤销初次审计董事会变更约定书股东组成部分了解补审计单位情况实施财务报表审计评估固有风险和内部控制风险决定审计程序的性质、时间和范围初步了解进一步了解接受业务委托之前接受业务委托之后更新并重新评价以前收集的信息以前年度工作底稿董事高级管理人员内部审计人员内部审计报告会议纪要寄送股东或报送临管部门备案的资料中期财务报告管理政策手册会计科目表做出专业判断经营风险管理当局的对策适当性会计估计管理层声明关联方关联方交易持续经营假设审计计划总体审计计划具体审计计划提高审计效率被审计单位的规模审计的复杂性具体的方法和技术财务业绩重大遗漏重点审计领域协调复核法定责任时间预算错误舞弊修改或追加审计程序计划和实施审计程序适当的会计和内部控制系统减少但不能消除篡改伪造更改文件或凭证侵占资产虚构交易滥用会计政策原始凭证疏忽或误解会计政策变更异常交易不完整文件财户余额不平衡缺乏恰当的授权计算机信息系统环境审计测试的固有限制与管理层讨论纠正措施寻求法律咨询法律与规章没有遵守解除业务约定高级管理层发现没有遵守法律与规章的行为故意漏记交易高级管理层逾越控制故意对CPA做出错误陈述管理层声明涉嫌存在违法行为审计委员会监事会临管和执法机构重要性超过重要性水平接近重要性水平可接受的低水平财务报表层面和相关账户、交易层面已发现但尚未调整的错报或漏报错报或漏报已发现和推断的错报或漏报累计期后事项或有事项扩大实质性测试范围调整财务报表执行追加的审计程序实施扩大或追加的控制测试修改实质性程序的性质、时间和范围审计风险固有风险控制风险检查风险不恰当的审计意见风险性测试风险细节测试风险可容忍错报固有风险和控制风险的综合水平可接受的检查风险计划评估的控制风险小规模企业会计系统内部控制系统控制环境控制程序符合性程序控制测试穿行测试管理建议书内部控制的重大缺陷风险评估控制活动信息沟通监督程序手册工作说明流程图文字叙述调查问卷重新执行内部控制计算机辅助审计程序与管理导沟通审计证据控制测试实质性程序审计证据的充分性审计证据的恰当性认定存在或发生完整性权利与义务估价与分摊表达与披露合法性截止机械准备性分类披露检查观察询问函证计算分析性程序核对账龄分析表追查审计抽样错误偶发性错误预期误差总体抽样风险非抽样风险抽样单位统计抽样分层可容忍误差信赖不足风险信赖过度风险误拒风险误受风险偏离程度样本量可信赖水平总体中样本的数量所选用的方法审计效果审计效率审计工作底稿试算平衡表调整和重分类分录审计标识索引和交叉索引永久性档案当期档案综合类工作底稿业务类工作底稿备查类工作底稿使用标准工作底稿核对用清单现金收据现金支出零用现金保管流程图内部控制调查问卷系统的穿行测试职责划分存款凭单采购订单验收报告总分类账银行对账单银行存款余额调节表资产负债表日未兑现支票找零备用金现金盘点开空头支票浮游期截止性银行对账单预收账款可变现净值抵押销售通知单仓库仓库保管员永续盘存记录货运文件提货单开票销售发票小计加总、合计价目表账龄分析表过期账项试算表分解、按细目分类过期账户函证积极式函证消极式孙证预付款请购单订购单应付凭单卖方发票差异货物的说明、种类付款凭单汇款、付款毛利合理性真实性期间费用制造费用用料单验收记录订单成本计算单人工成本分配表领料单工资汇总表工资登记薄生产通知单生产流程工资率及扣减授权表计时卡计时单成本会计流程表机物料消耗公用事业费分批工作通知单存货盘点抽点存货标签债券股票经纪人意见书实收资本库存股债券契约证券组合投资租赁的资产报废通知单注册管理机构过户代理人信托公司流通票据抵押品留置与抵押董事会会议记录受托管理人限制性条款实缴资本存根审计报告的真实性审计报告的合法性被审计单位、客户审计报告的收件人无保留意见保留意见无法表示意见否定意见引言段范围段意见段说明段重要专业术语范围限制未调整事项适当披露对会计报表反映的影响程序特殊目的的审计报告。
Decree 248 Single Window Operation Manuals and Tut
Voluntary Report –Voluntary - Public Distribution Date:December 22, 2021Report Number:CH2021-0174Report Name:Decree 248 Single Window Operation Manuals and Tutorial Country:China - People's Republic ofPost: BeijingReport Category:Agricultural Situation, Agricultural Trade Office Activities, Policy and Program Announcements, National Plan, Beverages, Agriculture in the News, Citrus, Coffee, Dairy and Products, Market Development Reports, Avocado, Canned Deciduous Fruit, Dried Fruit, Fresh Deciduous Fruit, Fresh Fruit, Kiwifruit, Raisins, Stone Fruit, Strawberries, Fishery Products, Grain and Feed, Livestock and Products, MISC-Commodity, Oilseeds and Products, Potatoes and Potato Products, Poultry and Products, Sugar, Tomatoes and Products, Tree Nuts, Vegetables, WinePrepared By:Alan HallmanApproved By:Adam BransonReport Highlights:The report contains FAS China's understanding of the overseas facility registration process as required by the General Administration of Customs of the People's Republic of China (GACC) in Decree 248. In addition, this report contains attachments of unofficial translations of the Competent Authority and Overseas Enterprise Operation Manuals for the GACC Single Window registration website. In addition, the report contains information from recent training sessions and background information on Decree 248 to facilitate self-registration for U.S. food and agribusiness operations affected by Decree 248.General Information:This report provides information related to FAS China’s understanding of the General Administration of Customs of the People’s Republic of China (G ACC) overseas facility registration process. This report includes translations of GACC operation manuals for 1) Competent Authorities; 2) Overseas Enterprises; and 3) a tutorial to the Single Window website self-registration process developed by a third party. In addition, the report has an Excel table attachment that includes the Harmonized System (HS) tariff codes and commodity descriptions affected by Decree 248. FAS China conveys its thanks and appreciation to staff and officers at the Embassies of Australia, Canada, New Zealand, and other colleagues at the United States Embassy in Beijing, China who jointly translated the two GACC manuals.Decree 248 notified by GACC requires the registration of overseas food production and cold storage facilities that produce or handle specific food products exported to China. The regulation sets out two registration pathways for facilities that produce products within its scope – self-registration, and registration by a competent authority located in the exporting country.Article 7 of Decree 248 lists 18 product categories that GACC initially indicated would require an overseas facility to register before having product be presented for customs clearance in China. GACC indicated that it expects facilities producing products in those categories to register through a competent authority. In addition, Article 9 of Decree 248 requires the self-registration of overseas facilities that are outside of the 18 product categories. Since publishing the list of 18 product categories GACC has provided and continues making “systems improvements” to a table of Chin a’s Harmonized System (HS) tariff codes at the 10-digit level inside the Single Window website that are apparently the actual scope of goods that require registration. The table also provides GACC inspection and quarantine codes and additional descriptions for the products affected by Decree 248. However, there are several food and related products that are not in GACC’s table. Moreover, some commodities can fall in or outside the scope of Decree 248 depending upon their end use.For example, although the HS code 0805100000 for “Oranges, Fresh or Dried” is included on the table, the GACC inspection and quarantine code indicates that only those facilities handling “Oranges, Fresh or Dried” that have also been “candied” or “sweetened” need to self-register. In other words, facilities handling “regular” oranges are not required to register with the GACC under Decree 248.Another example is sorghum, which appears in the table under the Chinese HS code 1007900000 with GACC inspection and quarantine codes 102 and 103 – for other edible sorghum, inshell and shelled, respectively. GACC is requesting that facilities handling inshell or shelled sorghum for human consumption register that facility through a competent authority. Based on this information, there is no expectation that U.S. exporters of sorghum for non-food use register under Decree 248. However, the United States Government already provides a complete list, based on a previous agreement, of U.S. grain exporting companies to GACC for food and non-food sorghum. Numerous attempts to seek clarification from GACC have gone unanswered.GACC recently announced that a facility registration number will have to be presented during customs clearance for imports of commodities covered by Decree 248 starting on January 1, 2022. GACC has said that products produced prior to January 1, 2022, will not require facility registration numbers printed on the inner and outer packaging of the products. GACC officials have also said that either the GACC facility registration number or the facility registration number issued by the competent authority in the exporting country must be printed on the inner and outer packaging of products produced on or after January 1, 2022. Because the destination of most products is not known at the time of production or manufacturing, U.S.-based facilities working with these products will need to assess what facility registration number to use on products that could be destined for China.The Single Window self-registration website requires that facilities attempting to register select a Chinese 10-digit HS code and the 3-digit GACC inspection and quarantine code to identify their product(s). The attached Excel table can be a guide for identifying this information. If a facility cannot identify which HS code may be used, they should consider the description and end-use of their product(s) and/or contact their existing or a potential importer to assess the tariff line that will be used for customs clearance. Companies attempting to self-register should contact GACC staff, identified below, when they have questions about the Single Window system and the applicability of the registration requirements to their establishments and product(s). As China continues making “system improvements” to the Single Window website, facilities attempting to self-register should consult official information and conduct a “Product type Query” in the Single Window website. The attached table and the information in the Single Window website also include a column where GACC indicates if facilities producing that product should self-register or be registered by a competent authority.The self-registration process requires a significant amount of information. Registrants may find it helpful to review the rest of this report and the attached translation of GACC’s operation manual for enterprises before commencing.The translation of GACC’s operation manual for competent authorities is attached as a reference. U.S.-based facilities that GACC is requesting register through a competent authority are encouraged to read the U.S. Food and Drug Administration’s (FDA) Constituent Update dated December 6. It can be found at this link.FAS China has published the following reports on Decrees 248 and 249 to inform and educate U.S. food and agricultural stakeholders.∙Decrees 248 and 249 – January 1 Implementation Date [Public Notice 103] – December 14, 2021∙Decree 248 - FDA Constituent Update – December 8, 2021∙Decree 248 Single Window User Manual and Training - November 30, 2021∙Decree 248 HS Codes Published in GACC Single Window – November 30, 2021∙Informing Industry and Supporting Trade Facilitation as China Implements Decrees 248 and 249 –November 10, 2021∙Decree 248 Information Update – November 19, 2021∙GACC Issues Interpretation of Decree 248 - November 6, 2021∙Decree 248 Foreign Facilities Self-Registration Website Launched - November 3, 2021∙Decree 248 Unofficial Self-Registration Guide for Overseas Food Facilities - November 2, 2021∙Notes from Information Sessions on GACC Decrees 248 and 249 - October 22, 2021∙GACC Issues Explanatory Letter on Decree 248 - October 8, 2021∙Interpretative Guidance on Imported Food Labeling Requirements in Decree 249 - August 13, 2021 ∙Decrees 248 and 249 Status Update on Facilities Registration and Food Safety Measures - May 25, 2021∙Administrative Measures on Import and Export Food Safety - Decree 249 - May 7, 2021∙Overseas Facilities Registration Regulation - Decree 248 - April 20, 2021∙China Notified the Draft Administrative Measures on Import and Export Food Safety - December 11, 2020∙China Notifies Revised Overseas Facilities Registration Regulations as TBT 1522 - December 2, 2020∙China Released Draft Administrative Measures for Registration of Overseas Producers of Imported Foods - December 6, 2019Attachments:211221 GACC 248 SW Overseas Enterprise Operation Manual Eng Translation.docx211221 FAS China Third Party SW Self Registration Guide.docx211215 GACC Decree 248 HS Code List English Translation.xlsx211223 GACC 248 SW Competent Authority Operation Manual Eng Translation.docx。
麝香保心丸治疗心脏X综合征的系统评价
麝香保心丸治疗心脏X综合征的系统评价王彤歆1,王心意2,鞠建庆2,刘启予1,贾君迪1,徐 浩2摘要 目的:系统评价麝香保心丸治疗心脏X 综合征的临床疗效㊂方法:检索中国知网(CNKI )㊁中国生物医学文献数据库(CBM )㊁万方数据库㊁PubMed ㊁EMbase ,检索时限为建库至2021年9月,发表的麝香保心丸治疗心脏X 综合征的随机对照试验㊂根据Cochrane 5.1手册推荐的偏倚风险评估工具对纳入的研究进行方法学质量评价,应用Review Manager 5.4软件进行Meta 分析㊂结果:共纳入13项研究,涉及954例病人,多数研究存在一定程度的发表偏倚㊂Meta 分析结果显示,与对照组比较,试验组总有效率升高[RR =1.19,95%CI (1.09,1.31),P =0.0003],ST 段压低最低电压幅度[WMD =-0.15,95%CI (-0.27,-0.02),P =0.03]㊁超敏C 反应蛋白(hs -CRP )[WMD =-2.47,95%CI (-4.27,-0.67),P <0.01]㊁内皮素-1(ET -1)[WMD =-23.26,95%CI (-42.19,-4.34),P =0.02]降低,一氧化氮(NO )[WMD =25.52,95%CI (20.68,30.36),P <0.01]升高㊂漏斗图提示可能存在一定的发表偏倚㊂结论:现有证据表明,应用麝香保心丸治疗心脏X 综合征可提高临床疗效㊂关键词 心脏X 综合征;麝香保心丸;系统评价;Meta 分析d o i :10.12102/j.i s s n .1672-1349.2023.12.004 Systematic Review of Shexiang Baoxin Pills in the Treatment of Cardiac X Syndrome WANG Tongxin,WANG Xinyi,JU Jianqing,LIU Qiyu,JIA Jundi,XU Hao Beijing University of Chinese Medicine,Beijing 100029,ChinaCorresponding Author JU Jianqing,E -mail:******************;XU Hao,E -mail:********************Abstract Objective:To systematically evaluate the clinical efficacy of Shexiang Baoxin Pills in the treatment of cardiac X syndrome.Methods:China General Database of Knowledge Resources(CNKI),China Biomedical Literature Database(CBM),China Academic Journal Database(WanFang),PubMed and EMbase were searched for the published randomized controlled trials of Shexiang Baoxin Pills in the treatment of cardiac X syndrome from the database establishment to September 2021.Methodological quality of the included literatures was evaluated according to the bias risk assessment tool recommended by the Cochrane 5.1manual.Review Manager 5.4software was used for Meta -analysis.Results:A total of 13literatures were included,including 954patients,and most literatures presented some degree of bias.Meta -analysis results showed that compared with the control group,the clinical efficacy in the experimental group was better(RR =1.19,95%CI 1.09-1.31,P =0.0003),the minimum voltage amplitude of ST segment depression (WMD =-0.15,95%CI -0.27--0.02,P =0.03),hypersensitive C -reactive protein(hs -CRP)(WMD =-2.47,95%CI -4.27--0.67,P <0.01),endothelin -1(ET -1)(WMD =-23.26,95%CI -42.19--4.34,P =0.02),and nitric oxide(NO)(WMD =25.52,95%CI 20.68-30.36,P <0.01)were increased.The results of funnel plot suggested that there might be some publication bias.Conclusion:The current evidenceshowed that Shexiang Baoxin Pills could improve the clinical efficacy in the treatment of cardiac X syndrome.Keywords cardiac X syndrome;Shexiang Baoxin Pills;systematic review;Meta -analysis 心脏X 综合征又称微血管性心绞痛,指病人冠状动脉造影正常且未患有其他影响心血管功能的疾病时,发生心绞痛或运动负荷试验中心电图ST 段压低[1]㊂有研究显示,约20%的心绞痛病人冠状动脉造影正常[2]㊂目前关于心脏X 综合征的发病机制尚未明确,有研究表明,心脏X 综合征主要是由于冠状动脉基金项目 中国中西医结合学会和黄药业科研基金项目(No.2018006)作者单位 1.北京中医药大学(北京100029);2.中国中医科学院西苑医院国家中医心血管病临床医学研究中心(北京100091)通讯作者 鞠建庆,E -mail :******************;徐浩,E -mail :xuhaotcm@引用信息 王彤歆,王心意,鞠建庆,等.麝香保心丸治疗心脏X 综合征的系统评价[J ].中西医结合心脑血管病杂志,2023,21(12):2134-2139.内皮和微血管功能障碍引起的,故又称为微血管性心绞痛[3]㊂因心脏X 综合征冠状动脉造影正常,故与冠状动脉疾病相比未受到相应重视,有研究表明,心脏X 综合征与冠状动脉疾病心血管事件风险相当[4]㊂目前,心脏X 综合征尚无公认有效的西医治疗措施,而中医药治疗为临床带来新思路㊂麝香保心丸是一种主要由人工麝香㊁人参提取物㊁人工牛黄㊁肉桂㊁苏合香㊁蟾酥㊁冰片组成的中成药微丸,已广泛用于治疗心肌缺血引起的胸闷㊁心绞痛及心肌梗死㊂本研究通过对麝香保心丸治疗心脏X 综合征的随机对照试验(randomized controlled trial ,RCT )进行Meta 分析,系统评价其对心脏X 综合征的治疗效果,为临床应用提供循证医学证据㊂1 资料与方法1.1纳入与排除标准1.1.1纳入标准 ①研究对象:符合心脏X综合征诊断标准,参照2010年Circulation中关于心脏X综合征的定义[1],症状为典型稳定型心绞痛,以劳力为主要诱发因素;存在心肌缺血,心绞痛发作过程中出现了具有诊断意义的ST段压低;在心肌负荷灌注显像中出现可逆性灌注充盈缺损;记录到与负荷相关的冠状动脉血流灌注异常;找到短暂心肌缺血的证据㊂上述4项证据中需至少包含1项㊂冠状动脉造影结果显示正常,无其他的特定疼痛点㊂②干预措施:试验组在西医常规治疗基础上联合麝香保心丸治疗,对照组采用西医常规治疗或西医常规治疗联合安慰剂㊂③结局指标:至少包括以下结局中1项,临床总有效率㊁ST段压低最低电压幅度㊁超敏C反应蛋白(high sensitivity C-reactive protein,hs-CRP)和一氧化氮(nitric oxide, NO)㊁内皮素-1(endothelin-1,ET-1)水平㊂④研究类型:RCT㊂1.1.2排除标准合并其他疾病如肿瘤及严重肝㊁肾功能不全等;研究设计方案不合理㊁数据错误或数据不全及统计方法不恰当等;重复发表的文献㊂1.2检索策略计算机检索中国知网(China National Knowledge Infrastructure,CNKI)㊁中国生物医学文献数据库(Chinese Biomedical Literature Database,CBM)㊁万方数据库㊁PubMed㊁EMbase,检索时限从建库至2021年9月㊂中文检索词包括麝香保心丸㊁麝香保心㊁微血管性心绞痛㊁微血管㊁冠状动脉微血管疾病㊁冠状动脉微血管疾病㊁微血管功能异常㊁微血管心绞痛㊁心脏X综合征;英文检索词包括Shexiang Baoxin,Shexiang Baoxin pill,microvascular angina,coronary microvascular disease,microvascular dysfunction,cardiac syndrome X,angina X syndrome, angina syndrome X㊂根据各数据库特点制定相应的检索策略㊂1.3纳入文献的质量评价对纳入的研究采用Cochrane5.1手册偏倚风险评估工具进行方法学质量评价,评价内容包括随机序列的产生是否正确㊁分配隐藏是否实施㊁是否采用盲法㊁是否存在缺失数据㊁是否存在选择性报告㊁是否存在其他类型的偏倚㊂由2名研究者单独进行质量评价,双方意见不一致时与第三方协商解决㊂1.4统计学处理采用Review Manager5.4软件进行Meta分析㊂定量资料的合并效应量采用加权均方差(weighted mean difference,WMD);定性资料的合并效应量采用相对危险度(relative risk,RR)㊂运用χ2检验(检验水准α=0.1)评估研究结果间异质性,若异质性检验I2<50%,采用固定效应模型进行分析;若异质性检验I2ȡ50%,采用随机效应模型进行分析㊂区间估计选择95%置信区间(confidence interval,CI)进行㊂以森林图表示Meta分析结果,发表偏倚的风险通过绘制漏斗图进行评估㊂2结果2.1文献检索流程及结果(见图1)图1文献检索流程及结果2.2纳入文献的基本特征根据已制定的文献纳入㊁排除标准,共纳入13篇文献[5-17],均为中文文献,涉及954例病人,其中试验组478例,对照组476例㊂纳入文献的基本特征见表1㊂表1 纳入文献的基本特征纳入研究 样本量(例)试验组对照组 性别(男/女,例)试验组对照组 年龄(岁) 试验组对照组张武宁等[5]2013282823/33陈小林等[6]2016373310/279/2458ʃ1357ʃ15吴彩云等[7]2019383824/1423/1553.7ʃ2.654.1ʃ2.5金惠玲[8]2018505030/2027/2354.5ʃ6.453.6ʃ6.5罗学坚[9]2014232316/3061ʃ6白延涛等[10]2011252515/3550ʃ5张小沛[11]201131319/2211/2052杨艳红等[12]2017353511/2410/2556.8ʃ6.457.1ʃ5.8王林华[13]2020515122/2923/2854.85ʃ6.9454.81ʃ6.91蔡晓栋[14]2017303013/1712/1852.5ʃ6.652.6ʃ6.5苗永国等[15]2008303014/1613/1753ʃ753ʃ8肖景刚等[16]202020229/1112/1054.5ʃ3.853.5ʃ6.5张春香[17]2020808060.23ʃ1.76 纳入研究干预措施试验组 对照组结局指标张武宁等[5]2013麝香保心丸+常规治疗常规治疗临床总有效率陈小林等[6]2016麝香保心丸+常规治疗常规治疗临床总有效率吴彩云等[7]2019麝香保心丸+常规治疗常规治疗临床总有效率㊁hs -CRP ㊁NO ㊁ET -1㊁ST 段压低最低电压幅度金惠玲[8]2018麝香保心丸+常规治疗常规治疗临床总有效率㊁hs -CRP ㊁NO ㊁ET -1罗学坚[9]2014麝香保心丸 常规治疗临床总有效率白延涛等[10]2011麝香保心丸+常规治疗常规治疗临床总有效率张小沛[11]2011麝香保心丸+常规治疗常规治疗临床总有效率杨艳红等[12]2017麝香保心丸+常规治疗常规治疗ST 段压低最低电压幅度王林华[13]2020麝香保心丸 阿司匹林临床总有效率㊁hs -CRP 蔡晓栋[14]2017麝香保心丸+常规治疗常规治疗临床总有效率㊁hs -CRP ㊁NO ㊁ET -1苗永国等[15]2008麝香保心丸+常规治疗常规治疗临床总有效率肖景刚等[16]2020麝香保心丸+常规治疗常规治疗临床总有效率张春香[17]2020麝香保心丸+常规治疗常规治疗临床总有效率2.3 纳入文献的质量评价 共纳入13篇文献[5-17],偏倚风险比例图见图2㊂13篇均使用随机,其中4篇[8,12,15,17]描述了随机化隐藏的方法,12篇[5-7,9-17]使用了盲法㊂图2 纳入文献的偏倚风险比例图2.4 Meta 分析结果2.4.1 临床总有效率 12项研究[5-11,13-17]报道了临床总有效率,异质性检验显示,I 2=63%,P =0.002,采用随机效应模型进行Meta 分析㊂结果显示:试验组总有效率高于对照组,差异有统计学意义[RR=1.19,95%CI(1.09,1.31),P=0.0003]㊂详见图3㊂图3两组临床总有效率比较的森林图2.4.2ST段压低最低电压幅度2项研究[7,12]报道了ST段压低最低电压幅度,异质性检验显示,I2=99%, P<0.01,采用随机效应模型进行Meta分析㊂结果显示:试验组ST段压低最低电压幅度低于对照组,差异有统计学意义[WMD=-0.15,95%CI(-0.27,-0.02), P=0.03]㊂详见表2㊂表2Meta分析部分结果汇总结局指标纳入研究异质性检验I2值(%)P效应模型Meta分析结果WMD(95%CI)PST段压低最低电压幅度2项[7,12]99<0.01随机-0.15[-0.27,-0.02]0.03 hs-CRP4项[7-8,13-14]99<0.01随机-2.47[-4.27,-0.67]<0.01 NO3项[7-8,14]92<0.01随机25.52[20.68,30.36]<0.01 ET-13项[7-8,14]98<0.01随机-23.26[-42.19,-4.34]0.022.4.3hs-CRP4项研究[7-8,13-14]报道了hs-CRP,异质性检验显示,I2=99%,P<0.01,采用随机效应模型进行Meta分析㊂结果显示:试验组hs-CRP水平低于对照组,差异有统计学意义[WMD=-2.47,95%CI (-4.27,-0.67),P<0.01]㊂详见表2㊂2.4.4NO3项研究[7-8,14]报道了NO,异质性检验显示,I2=92%,P<0.01,采用随机效应模型进行Meta 分析㊂结果显示:试验组NO水平高于对照组,差异有统计学意义[WMD=25.52,95%CI(20.68,30.36),P< 0.01]㊂详见表2㊂2.4.5ET-13项研究[7-8,14]报道了ET-1,异质性检验显示,I2=98%,P<0.01,采用随机效应模型进行Meta 分析㊂结果显示:试验组ET-1水平低于对照组,差异有统计学意义[WMD=-23.26,95%CI(-42.19,-4.34),P= 0.02]㊂详见表2㊂2.5发表偏倚对临床总有效率指标绘制漏斗图分析发表偏倚,结果显示,所纳入的研究存在一定程度的发表偏倚㊂详见图4㊂图4临床总有效率的发表偏倚漏斗图3讨论心脏X综合征的主要临床表现为心绞痛,心绞痛归属于中医学 胸痹 心痛 的范畴㊂心脏X综合征的发生与寒邪内侵㊁饮食不节㊁情志失调㊁劳倦内伤㊁年迈体虚等有关,本病病位在心,涉及肝㊁脾㊁肾等,‘金匮要略“认为其以 阳微阴弦 为基本病机,是本虚标实之证,本虚为气血阴阳亏虚,心脉失养;标实为寒凝㊁气滞㊁血瘀㊁痰浊等痹阻心脉㊂麝香保心丸具有芳香温通㊁益气强心之功效,常用于治疗 胸痹 心痛 ㊂目前已广泛应用于多种心血管疾病的治疗及预防,2020版中成药治疗冠心病临床应用指南中推荐麝香保心丸可降低心血管事件发生率,减少心绞痛发作次数,改善中医证候等[18]㊂1973年心脏X综合征由Harvey Kemp提出,目前关于心脏X综合征的发病机制尚未明确,通常认为心脏X综合征是缺血性心脏病的一种形式,且多发于女性㊂相关研究表明,心脏X综合征主要是由冠状动脉内皮和微血管功能障碍引起的[3],与炎症[19]㊁胰岛素抵抗[20]㊁雌激素缺乏[21]㊁社会心理因素[22]㊁单核细胞-高密度脂蛋白胆固醇比率升高[23]㊁心肌能量消耗增加[24]等有关㊂本研究对西医常规联合麝香保心丸治疗心脏X 综合征的RCT进行Meta分析,结果显示,麝香保心丸可提高临床疗效,减小ST段压低最低电压,降低hs-CRP 及ET-1,升高NO水平㊂麝香保心丸作为一种从1974年开始研发的大品种中成药,相关研究证实其对缺血性心脏病具有良好的治疗作用,麝香保心丸可降低冠心病病人主要心血管事件发生率及心绞痛发作频率[25]㊂麝香保心丸可提高冠状动脉慢性完全闭塞病变病人择期介入治疗的成功率,并改善左室功能[26]㊂麝香保心丸可改善心脏X综合征病人ST段压低,从而推断改善心脏X综合征病人的心肌缺血是其作用机制之一㊂有研究显示,除心脏X综合征外,麝香保心丸可改善冠心病病人出现的ST段压低[27]㊂动物实验显示,麝香保心丸可促进缺血心肌内血管新生,在改善心功能同时抑制动脉粥样硬化斑块内血管新生[28]㊂细胞实验发现,麝香保心丸可升高血清20-羟基二十碳四烯酸水平及血管内皮生长因子(vascular endothelial growth factor,VEGF)表达,进而促进血管内皮祖细胞(endothelial progenitor cells,EPC)增殖[29];通过诱导内皮型一氧化氮合酶(eNOS)表达产生NO,进而增加EPC生成血管的能力[30],从而改善心肌供血㊂相关研究显示,麝香保心丸通过影响内皮细胞Hippo-YAP信号通路促进血管新生[31]㊂人参皂苷[32]㊁肉桂醛[33]作为麝香保心丸的生物活性成分,通过刺激促进血管生成的特定分子或通路促进血管生成㊂炎症㊁氧化应激除与心脏X综合征着密切联系,在心血管疾病的发生发展中发挥重要作用[34]㊂麝香保心丸通过减少冠心病病人循环中炎性单核细胞比例和斑块中巨噬细胞含量,改善动脉粥样硬化斑块的炎症反应[35],降低动脉粥样硬化小鼠血管壁中血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)㊁细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)㊁白细胞介素-6(interleukin-6,IL-6)㊁白细胞介素-2(interleukin-2,IL-2)等炎性因子表达水平,升高线粒体融合蛋白2(mitofusin-2,Mfn2)水平,减少丝裂原活化蛋白激酶(p38mitogen-activated protein kinase,p38MAPK)㊁c-Jun N端激酶(c-Jun N-terminal kinase,JNK)和核因子-κB(nuclear factor-kappa B,NF-κB)磷酸化发挥改善炎症的作用[36]㊂改善内皮功能也是麝香保心丸的作用机制之一,有研究证明其通过升高NO㊁超氧化物歧化酶(super oxide dismutase,SOD),降低ET-1㊁丙二醛(malondialdehyde, MDA),改善血管内皮功能,从而发挥心血管保护作用[37]㊂本研究对麝香保心丸治疗心脏X综合征的疗效进行了系统评价,结果表明,麝香保心丸可提高心脏X综合征病人临床有效率㊂通过对病人ST段压低最低电压㊁hs-CRP㊁NO㊁ET-1水平的Meta分析结果,初步推测其作用机制可能与改善冠状动脉循环㊁血管内皮功能及体内炎症反应有关㊂因纳入的研究方法学偏倚风险较高,故对Meta分析结果解读及采用时仍应慎重,今后的研究中应增加设计严谨㊁大样本的高质量临床研究提供充足的证据㊂由于心脏X综合征目前尚无统一治疗方案,本研究结果为心脏X综合征的临床治疗提供了循证医学证据㊂参考文献:[1]LANZA G A,CREA F.Primary coronary microvascular dysfunction:clinical presentation,pathophysiology,and management[J].Circulation,2010,121(21):2317-2325.[2]MUKERJI V,BEITMAN B D,ALPERT M A.Chest pain andangiographically normal coronary arteries.Implications for treatment[J].Texas Heart Institute Journal,1993,20(3):170-179.[3] ÖNAL B,ÖZEN D,DEMIR B,et al.Receptor for advancedglycation end products gene polymorphisms in cardiac syndrome X[J].Biomedical Reports,2019,11(3):123-129.[4]LUTFI M F.Ventricular late potential in cardiac syndrome Xcompared to coronary artery disease[J].BMC CardiovascularDisorders,2017,17(1):35.[5]张武宁,胡著涛,高晓东,等.麝香保心丸对合并高脂血症心脏X综合征患者的临床疗效[J].中国循证心血管医学杂志,2013,5(3):285-287.[6]陈小林,聂叶廷,韩超,等.麝香保心丸对心脏X综合征患者心肌微血管阻力的影响[J].深圳中西医结合杂志,2016,26(21):52-54. [7]吴彩云,王高明,孙志刚.麝香保心丸联合尼可地尔治疗冠状动脉慢血流微血管性心绞痛的疗效[J].上海医药,2019,40(19):26-28;43.[8]金惠玲.麝香保心丸联合尼可地尔治疗微血管心绞痛的临床观察[J].光明中医,2018,33(15):2265-2267.[9]罗学坚.麝香保心丸治疗心脏X综合征疗效观察[J].现代诊断与治疗,2014,25(1):152-153.[10]白延涛,李燕.麝香保心丸治疗心脏X综合征临床观察[J].中国现代药物应用,2011,5(21):75-76.[11]张小沛.麝香保心丸佐治心脏X综合征31例疗效观察[J].国医论坛,2011,26(4):31.[12]杨艳红,李守贤.中西医结合治疗微血管心绞痛的疗效观察[J].中国中西医结合急救杂志,2017,24(1):21-23.[13]王林华.阿司匹林与麝香保心丸治疗心脏X综合征的临床疗效比较[J].实用中西医结合临床,2020,20(6):69-70.[14]蔡晓栋.麝香保心丸联合尼可地尔治疗微血管性心绞痛的疗效观察[J].现代养生,2017(6):90.[15]苗永国,陈金良,任鹏顺,等.麝香保心丸与硫氮酮治疗心脏X综合征[J].中西医结合心脑血管病杂志,2008,6(9):1103-1104. [16]肖景刚,张清潭.麝香保心丸联合尼可地尔对心脏X综合征的短期疗效[J].特别健康,2020(13):36.[17]张春香.麝香保心丸治疗难治性女性微血管病变性心绞痛的临床研究[J].健康大视野,2020(7):97.[18]‘中成药治疗优势病种临床应用指南“标准化项目组.中成药治疗冠心病临床应用指南(2020年)[J].中国中西医结合杂志,2021, 41(4):1409-1435.[19]LI J J,LI Y S,ZHANG Y E,et al.Inflammation:a possiblepathogenic link to cardiac syndrome X[J].Medical Hypotheses, 2006,66(1):87-91.[20]DOMENICA MONTI L,PIATTI P M.Role of endothelialdysfunction and insulin resistance in angina pectoris and normal coronary angiogram[J].Herz Kardiovaskuläre Erkrankungen, 2005,30(1):48-54.[21]KASKI J C.Cardiac syndrome X in women:the role of oestrogendeficiency[J].Heart(British Cardiac Society),2006,92(Suppl3): iii5-iii9.[22]ASBURY E A,COLLINS P.Psychosocial factors associated withnoncardiac chest pain and cardiac syndrome X[J].Herz Kardiovaskuläre Erkrankungen,2005,30(1):55-60. [23]DOGAN A,OYLUMLU M.Increased monocyte-to-HDL cholesterolratio is related to cardiac syndrome X[J].Acta Cardiologica,2017, 72(5):516-521.[24]ÇETIN M S.Increased myocardial energy expenditure in cardiacsyndrome X:more work more pain[J].Turk Kardiyoloji Dernegi Arsivi-Archives of the Turkish Society of Cardiology,2018,46(6): 446-454.[25]GE J B,FAN W H,ZHOU J M,et al.Efficacy and safety ofShexiang Baoxin pill(MUSKARDIA)in patients with stablecoronary artery disease:a multicenter,double-blind,placebo-controlled phaseⅣrandomized clinical trial[J].Chinese MedicalJournal,2021,134(2):185-192.[26]黄建楷,彭蔚,李维杰,等.麝香保心丸对冠状动脉慢性完全闭塞病变病人择期介入治疗成功率及心功能的影响[J].中西医结合心脑血管病杂志,2021,19(15):2593-2596.[27]徐传新,赵业清,胡燕,等.麝香保心丸治疗冠心病心绞痛的系统评价[J].中国药房,2011,22(44):4196-4200.[28]沈伟,范维琥,施海明,等.麝香保心丸对动脉粥样硬化斑块和缺血心肌中血管新生影响的实验研究[J].中国中西医结合杂志,2010,30(12):1284-1287.[29]HUANG F F,LIU Y,YANG X,et al.Shexiang Baoxin pills promotesangiogenesis in myocardial infarction rats via up-regulation of20-HETE-mediated endothelial progenitor cells mobilization[J].Atherosclerosis,2017,263:184-191.[30]LI G,CHEN Y,WU J.Promotion of function of endothelialprogenitor cells with Shexiang Baoxin pill treatment under shearstress[J].Journal of Biomedical Engineering,2015,32(4):847-853.[31]吴帮卫,李剑,金波,等.麝香保心丸促血管新生的机制[J].中成药,2018,40(6):1384-1388.[32]FANG H Y,ZENG H W,LIN L M,et al.A network-based methodfor mechanistic investigation of Shexiang Baoxin Pill's treatmentof cardiovascular diseases[J].Scientific Reports,2017,7:43632. [33]YUAN X,HAN L,FU P,et al.Cinnamaldehyde accelerates woundhealing by promoting angiogenesis via up-regulation of PI3K andMAPK signaling pathways[J].Laboratory Investigation,2018,98(6):783-798.[34]SITI H N,KAMISAH Y,KAMSIAH J.The role of oxidative stress,antioxidants and vascular inflammation in cardiovascular disease(a review)[J].Vascular Pharmacology,2015,71:40-56.[35]陈羽斐,胡亮,张红旗,等.麝香保心丸对ApoE-/-小鼠心肌梗死后动脉粥样硬化进程和循环单核细胞亚群的影响[J].中国中西医结合杂志,2020,40(12):1478-1483.[36]LU L,QIN Y T,ZHANG X X,et al.Shexiang Baoxin pill alleviatesthe atherosclerotic lesions in mice via improving inflammationresponse and inhibiting lipid accumulation in the arterial wall[J].Mediators of Inflammation,2019,2019:6710759.[37]张阳阳,路岩,朱希芳,等.麝香保心丸对合并左室肥厚的高血压患者氧化应激反应及血管内皮功能的影响[J].现代中西医结合杂志,2016,25(16):1718-1721.(收稿日期:2022-04-29)(本文编辑薛妮)。
药学英语TEXT A
Unit1 text A急性缺血性中风的神经保护药物开发的艰辛安全有效的治疗急性缺血性中风的发展仍然是临床研究者和制药行业困难的挑战。
目前，只有急性脑卒中的试验，表明出明确的疗效，是重组组织型纤溶血酶激活剂（rt-PA）试验在美国进行的时间为3小时的病人登记。
在这项研究中的rt-PA组的改善结果导致该药物在美国的治疗急性缺血性中风发病3小时内批准。
利用rt-PA在急性缺血性中风3小时的窗口和其他严格的标准限制了其使用急性缺血性中风人口的比例很小。
出血的风险的担忧，以及如何最好地瞄准这一有效的，但潜在的风险治疗已征收的另一个障碍，它的广泛使用。
RT-PA治疗急性缺血性中风在这个时候，只使用在美国监管机构批准，但这种情况可能很快改变，可能有效的时间窗口，等待第二个欧洲合作急性脑卒中试验结果（ECAST-2）RT-PA。
RT-PA的可用性显然只是在寻求有效的急性中风治疗和溶栓治疗以外的其他介入战略的第一步，必须考虑，其他急性中风治疗的主要方法是，旨在干预后，众多的神经保护治疗细胞和代谢事件发生在缺血区作为一个阻碍脑血管血栓的后果。
神经保护策略之一是抑制和中性粒细胞的招聘活动，因为这是显而易见的，这些炎症的白血细胞被招募到局部缺血区域，并有可能导致组织损伤的进展。
在动物中风模型，干扰多形核白细胞粘附疗法可以减少在临时局部缺血再灌注后梗死面积。
永久阻塞中风模型，有一点如果有证据表明，这些干预措施是有效的。
施耐德等。
报告的剂量递增安全与恩莫单抗，抗小鼠单克隆抗体，在32例急性缺血性中风患者的研究结果。
随后，恩莫单抗接受一个更大的药效试验。
不幸的是，在这个药效试验恩莫单抗被证明是无效的和相关的死亡率增加的速度和功能比安慰剂治疗结果较差。
什么样的安全性试验的意见可能会影响药效试验的设计和实施所遇到的困难可能避免吗？此外，有什么教训，从这个可能了解到，以改善未来急性缺血性中风的神经保护药物开发的安全性试验？这一剂量递增安全性研究是在一个开放标签的方式进行，只有总额的32例，4剂量层之间没有平衡。
高中英语学术论文选题方法单选题40题
高中英语学术论文选题方法单选题40题1. When choosing a topic for an academic paper in English, which of the following should be considered first?A. Your personal interestB. The popularity of the topicC. The availability of research materialsD. The complexity of the topic答案：C。
本题主要考查学术论文选题的基本原则。
选项A，个人兴趣固然重要，但如果没有足够的研究材料支持，难以深入开展研究。
选项B，话题的流行度并非首要考虑因素，关键在于研究的可行性和价值。
选项C，研究材料的可获取性是首先要考虑的，没有充足的材料，研究无法顺利进行。
选项D，话题的复杂性不是最先考虑的，而是在有材料支持的基础上再去衡量。
2. Which principle is the most crucial when selecting a topic for a high school English academic paper?A. Relevance to the curriculumB. Uniqueness of the topicC. Feasibility of researchD. Broadness of the topic答案：C。
在高中英语学术论文选题中，可行性是最为关键的原则。
选项A，与课程的相关性有一定重要性，但如果研究不可行，也无法进行。
选项B，话题的独特性虽然能吸引关注，但如果无法实现研究，也是空谈。
选项C，可行性意味着有条件和能力完成研究，这是保证论文质量的基础。
选项D，话题的宽泛程度不如可行性重要，过于宽泛可能导致研究难以聚焦。
3. In an academic paper topic selection, what should be avoided?A. Overused topicsB. Narrowly focused topicsC. Topics with limited sourcesD. Topics beyond one's knowledge scope答案：D。
奥马哈系统的发展及在护理领域中的应用_刘雪琴(1)
中华护理杂志 2010 年 4 月第 45 卷第 4 期 Chin J Nurs, April 2010, Vol 45, No ．4· 369 ··综 述·奥马哈系统的发展及在护理领域中的应用刘雪琴 谭晓青【关键词】 奥马哈系统；护理记录；评估系统【Key words 】 Omaha System ； N ursing Records ； Assessment System护理程序是现代护理的精髓，是临床护理实践中科学思维的核心。
20世纪80年代传入我国后，推广实施的过程非常艰难。
自1975年开始，美国护理同行在实践中逐渐建立起了一种简化了的护理程序运作系统 —奥马哈系统（Omaha System ）。
目前已在多个国家的公共健康部门、居家照护系统、学校卫生机构，以及社区诊所等多个服务机构证明了它的可靠性、有效性和易用性［1］。
本文就奥马哈系统的发展及在护理领域中的应用做一综述，以期对深化我国护理改革，建立科学的临床护理思维有所促进。
1 奥马哈系统的发展史［2］奥马哈系统是一种简化了的护理程序运作系统，它的发展大体分为3个阶段： ①1975-1980年问题分类系统形成期，多个研究机构用前瞻性和描述性的研究方法，从无数案例中归纳总结出36个常见问题，初步形成问题分类系统；②1984-1986年干预系统形成期，居家照护和公众保健等机构进行多中心临床研究， 补充了问题分类系统并对干预措施进行分类，形成了干预系统及结局的评价尺度；③1989-1993年奥马哈系统完善期，多家护理机构联合对整个奥马哈系统进行信度和效度的测试，完善和改进了奥马哈系统。
2 奥马哈系统的结构框架2.1 问题分类系统问 题分类系统是对评估对象的健康问题进行全面、有序、非具体的多个独立分类。
具体分为4个层面：①将评估出的问题进行范畴的划分；②写出具体的问题；③对问题进行描述；④对评估对象存在的症状和体征做具体的描述。
研究报告釆纳证明
研究报告釆纳证明
研究报告采纳证明
尊敬的教授：
我是贵校XX学院的一名研究生，我在过去一年中进行了一项关于XX领域的研究，特此向您提交本研究的报告，并希望能够得到您的采纳。
本研究的目的是探讨XX对YY的影响，通过采集大量的数据
并进行统计分析，得出了一些重要的结论。
首先，通过对数据的分析，我们发现XX与YY之间存在着明显的相关性，即
XX的改变会对YY产生直接的影响。
这个发现对于我们进一
步了解YY的运行机制以及设计相关的控制方法具有重要的意义。
其次，在本研究中，我们提出了一个新的XX对YY的控制策略，并进行了模拟实验来验证其有效性。
实验结果表明，新的控制策略能够显著降低YY的波动性，并提高其稳定性和可靠性。
这对于提高相关行业的生产效率和降低成本具有重要的应用价值。
此外，本研究还进行了对XX和YY之间其他相关因素的分析，以探讨它们对YY的影响。
通过对大量实验数据的分析，我们发现其他因素对YY的影响相对较小，XX仍然是主要的影响
因素。
这为进一步研究和优化XX控制方法提供了指导。
最后，在研究过程中，我们采用了科学的方法进行数据采集和分析，并借鉴了其他学者在该领域的研究成果。
本研究的实验设计和分析过程严格合理，并得出了一系列有重要意义的结论。
在此，我特此提交本研究报告，并请求贵校教授对该研究进行采纳。
如果获得您的认可，我将感到非常荣幸，并会进一步完善该研究的相关内容，以期在该领域更远一步的研究取得更多的突破。
再次感谢您对我的关注和支持！期待您的回复。
敬礼
XX。
阿尔茨海默病患者预防跌倒措施
㊃综㊀述㊃阿尔茨海默病患者预防跌倒措施于晓雯1,拓西平1,张文俊2,王晓晴2∗,姚均迪1∗(1海军军医大学附属长海医院老年病科,上海200433;2解放军总医院第二医学中心保健八科,北京100091)ʌ摘㊀要ɔ㊀跌倒是老年人损伤致死的首位原因,阿兹海默病患者由于认知功能障碍跌倒发生率更高㊂防止跌倒的具体措施可以分为非药物相关和药物相关措施,非药物相关措施分为刺激导向和行为认知导向等,药理学相关措施包括药物剂量改变,药物联合应用及以降低淀粉样蛋白为目的的免疫相关方法㊂ʌ关键词ɔ㊀意外跌倒;阿兹海默病;预防ʌ中图分类号ɔ㊀R741.05㊀㊀㊀㊀㊀ʌ文献标志码ɔ㊀A㊀㊀㊀㊀ʌDOI ɔ㊀10.11915/j.issn.1671-5403.2021.03.047收稿日期:2020-07-02;接受日期:2020-10-18基金项目:国家自然科学基金青年项目(81801854);上海市浦江人才计划项目(18PJD058);第二军医大学校级青年启动基金(2017QN10)通信作者:王晓晴,E-mail:xiaoqingwang1988@;姚均迪,E-mail:yaojundi411@Measures to prevent falls for patients with Alzheimerᶄs diseaseYU Xiao-Wen 1,TUO Xi-Ping 1,ZHANG Wen-Jun 2,WANG Xiao-Qing 2∗,YAO Jun-Di 1∗(1Department of Geriatrics,Changhai Hospital,Naval Military Medical University,Shanghai 200433,China;2Department of HealthCare Section Eighth,Second Medical Center,Chinese PLA General Hospital,Beijing 100091,China)ʌAbstract ɔ㊀Falls are the leading cause of death from injuries in the elderly.The incidence of falls is high in the patients withAlzheimerᶄs disease due to cognitive impairment.Specific measures to prevent falls can be divided into non-drug-related and drug-related,and the former can be divided into stimulation-oriented and behavior-cognition-oriented.Pharmacological measures includedrug dosage changes,drug combination and immune-related measures aiming at reducing amyloid protein.ʌKey words ɔ㊀accidental falls;Alzheimerᶄs disease;preventionThis work was supported by National Natural Science Foundation of China for Young Scientists (81801854),Shanghai Pujiang TalentsPlan Program (18PJD058),and Starting Foundation for Young Scientists of Second Military Medical University (2017QN10)Corresponding author :WANG Xiao-Qing ,E-mail :xiaoqingwang 1988@ ;YAO Jun-Di ,E-mail :yaojundi 411@㊀㊀世界范围内有超过1200万人患有阿兹海默病(Alzheimerᶄs disease,AD),据估算,到2040年这个数字将会超过4千万㊂而跌倒在AD 患者中的发生率远高于认知功能正常的老年人,且随着病情的进一步加重,跌倒发生的可能性也逐渐增加[1]㊂对跌倒发生率较高的AD 患者进行防跌倒的研究有助于节约医疗开支,提高老年人生活质量[2]㊂本文从非药物手段及药物相关措施两个方面进行阐述㊂1㊀AD 患者防跌倒非药物干预手段㊀㊀非药物干预的治疗策略有着安全无副作用㊁可根据患者实际情况进行有针对性的个体治疗安排等特点㊂这些措施可以分为刺激导向㊁行为导向和认知导向等[3]㊂具体有嗅觉㊁听觉刺激及行为干预等㊂1.1㊀嗅觉刺激剂的应用㊀㊀薰衣草香味在芳香治疗法中可以作为一种弛缓药㊂最近日本的实验研究发现它可以减少AD 患者跌倒的发生㊂以往研究也表明薰衣草芳香精油具有改善老年人平衡功能的作用㊂且另外一些研究也报道了它在改善步态紊乱方面的作用[4,5]㊂尽管这些研究只表现了薰衣草芳香刺激剂的暂时作用,对其长期效果未作研究,但可以预见如果长时间暴露于此种芳香氛围,它对步态的稳定作用可以防止AD 患者跌倒㊂由于患者对药物治疗常常产生焦虑而降低疗效,反而需要加大药物剂量来保证疗效,同时这些药物的负面效应如意识模糊和步态紊乱等又增大跌倒的发生率,所以对非药物干预更应该给予关注[5]㊂关于薰衣草嗅觉刺激剂预防跌倒的机制目前都是猜测性的,其奥秘可能在于它能减少姿势晃动,维持平衡[6]㊂从周围神经系统到皮质感觉-运动区整合起来对姿势和运动进行控制,它们接受前庭传入神经㊁视觉及本体感觉等的信息输入并在岛叶皮质进行信息汇总及处理,嗅觉刺激剂作为大脑皮层刺激素很可能通过岛叶皮质发挥作用,但这需要进一步研究来确证㊂目前薰衣草芳香精油已广泛应用于头疼㊁偏头痛㊁焦虑㊁神经过敏及抑郁症等,也可作为睡眠辅助剂及失眠的非药物替代治疗㊂1.2㊀音乐治疗㊀㊀激素与人们的情绪和行为相关,尤其包括性激素在内的类固醇激素,在阿尔茨海默病患者当中,衰老相关的性激素减少是一个重要的危险因素,尤其是雌激素[7,8]㊂这是由于雌激素能够控制细胞增殖降低β淀粉样肽在神经元中的含量,抑制其沉积,保护身体免受神经毒性β-淀粉样蛋白的影响㊂除了这些对淀粉样蛋白代谢的影响,雌激素还能通过增加脑内胆碱能活性改善认知功能,刺激轴突出芽和树突形成㊂近年来,雄激素特别是睾酮的神经保护作用也逐渐被认识到㊂试验表明,睾酮能增加阿尔茨海默病模型鼠脑内β神经生长因子和p-75神经生长因子受体并减少β淀粉样蛋白,同样,在人类神经元中雄激素抑制神经细胞凋亡的作用已被报道[9],而近期研究表明音乐与这些激素的水平密切相关[10]㊂空间能力㊁音乐能力和睾酮已被证明存在着相关性,听音乐可以影响睾酮和皮质醇水平[8-11],而音乐能力和空间认知力之间的密切关系由来已久,许多研究调查过音乐能力与人类空间感知力和认知能力的相关性㊂音乐治疗可通过恢复正常激素水平并抑制神经细胞损伤减缓AD的进展或者使发病延迟,并通过改善空间认知能力减少跌倒发生率㊂使用音乐疗法还能避免激素替代治疗引起的不良反应,如使用雌激素替代治疗的男性女性化,浸润性乳腺癌,心脏疾病和中风以及男性的睾丸激素替代疗法的前列腺癌风险增加,胆固醇水平升高,痤疮及脱发等[12]㊂1.3㊀AD跌倒相关行为症状的非药理学处理㊀㊀AD患者的行为症状是此病的核心临床特征,其中行为表现(无目的性徘徊㊁抗拒照管及激辩等)及精神病表现(幻觉㊁失眠㊁侵犯及妄想等)均会增加跌倒发生率,如果不进行治疗将加速疾病进展,恶化机能损害,影响生活质量[13]㊂由于现有药物疗效一般,副作用显著,现在尤为推荐一线非药理学处理,包括对看护者提供教育支持,培训问题解决能力以及针对特定行为症状的处理(如贯彻夜间行为管理以解决睡眠障碍)通常这些非药理学处理的前提是将AD患者的行为症状视作未被满足的需要或是患者处理反馈信息的能力和环境之间的不匹配,因而这些处理常常是个体化的[14]㊂医护工作者根据患者的具体临床表现采取不同措施,一些具体措施如:忘记服药可以使用日程表或者分类名录药物分片器;平衡感差要注意移除易绊倒患者的物品摆设㊁减少酒精摄入或对患者进行简易平衡训练;患者离家出走可以给患者佩戴标示了身份信息(包括姓名和家庭住址)的腕带,并明确患者离家出走的触发因素,尽可能减少再发生的可能;梦游㊁存在不安全感(尤其在晚上)则需衡量环境温度㊁噪音㊁光亮㊁阴影等对患者造成的影响,安排一些白天的活动锻炼,限制白天小睡的时间,缓解可能导致夜晚不安全心理的患者日间孤独感和厌烦情绪使用夜灯,雇请夜间看护者[15]㊂2㊀AD患者防跌倒的药物相关处理措施㊀㊀AD患者已批准的治疗药物如乙酰胆碱酯酶抑制剂㊁美金刚等,已用来治疗认知和行为症状,但是由于这些药物都有各自副作用,并通过不同方式增加跌倒发生率,可以通过剂量改变㊁药物联合使用等方式降低副作用㊂针对降低淀粉样蛋白水平的免疫相关治疗,由于临床试验过程中出现的不良反应仍需进一步的探索㊂2.1㊀酌情减少胆碱酯酶抑制剂及抗精神病药物的使用㊀㊀利斯的明㊁盐酸多奈培齐及氢漠酸加兰他敏等胆碱酯酶抑制剂作为治疗AD及相关性痴呆的常规用药有增加跌倒率的可能,这类药物临床药效与成本效益均高,一直以来受人关注,但其副作用方面则相对关注度不足㊂胆碱酯酶抑制剂的心血管效应比较复杂,主要与提高迷走神经效应有关,可以引发心动过缓,短暂性晕厥和心房自主节律改变,这些生理改变均可能引起跌倒,具体的剂量-效应关系值得进一步研究,如何在保留原本治疗作用的基础上规避跌倒的发生需要普遍关注㊂同样的,由于大部分AD患者治疗期间因行为或神经精神症状都使用到了精神药物,如抗精神病药物㊁抗焦虑药物㊁安眠药㊁镇静剂与抗抑郁药等,这些药物的使用同样增加AD患者跌倒的风险[16]㊂目前Sterke等[17]对这些药物与跌倒的剂量效应关系进行了具体的研究,统计分析表明使用抗精神病药物及抗抑郁药的跌倒发生率在0.25倍规定的日剂量时增加了28%,使用抗焦虑药的跌到发生率在0.2倍规定的日剂量时增加了8%,使用安眠药与镇静剂的跌到发生率在0.5倍规定的日剂量时则增加了56%,并且随着这些药物剂量的增加以及不同种类之间的联合使用,跌倒发生率也随之增加,即使在剂量比较低的情况下这些药物也与跌倒的发生密切相关㊂2.2㊀美金刚与维生素D的联合应用㊀㊀AD的显著表现之一就是谷氨酸能兴奋性中毒,这会通过两种不同机制导致神经元死亡:神经元细胞过度钙内流导致细胞的立即死亡以及缓慢钙内流过度和随之而来的氧化性应激导致的神经元凋亡㊂美金刚是一种电压依从性㊁低亲和力的N-甲基-D-天冬氨酸受体拮抗剂,能够减少钙内流相关的氧化应激和凋亡,但是还有其他损伤因素使神经元仍暴露于这些伤害之下,因此美金刚联合应用抗氧化剂可以增加疗效[18,19]㊂维生素D作为一种神经类固醇可以穿过血脑屏障并结合到中枢神经系统内神经元和胶质细胞内的维生素D受体上,通过调节电压门控性钙通道达到细胞内钙离子浓度的稳定,减弱氧化应激反应,表现出神经元保护作用以阻止凋亡㊂维生素D的抗氧化功能在2001年培养大鼠中脑细胞的试验中就被描述了,75岁以上老年人中70%以上都存在维生素D缺乏,纠正维生素D缺乏可以改善患者认知能力下降的情况[20]㊂美金刚与维生素D对神经系统的作用是互补相配的,不仅改善认知能力和记忆力,还能稳定步态㊂AD患者跌倒很大程度上与以慢性步态紊乱和自主功能丧失为主要表现的运动功能障碍相关,这样患者通过同时服用两药以改善认知能力,稳定姿势和步态,从而降低跌倒发生率[21]㊂2.3㊀降低淀粉样蛋白水平的药物研究㊀㊀AD患者由于淀粉样蛋白(Amyloid-β,Aβ)的累积会造成突触的丢失和功能失调,最近的研究表明Aβ衍生的一些可扩散配体可使脊柱一些重要蛋白质丧失,持续的丢失又会导致脊柱形态异常[21]㊂Aβ的沉积可通过突触相关的认知能力损害㊁记忆力下降和骨密度的降低增加跌倒发生率[22],如何降低其在脑内的浓度关系到AD患者降低并发症甚至是治愈的问题㊂在Aβ的合成中起关键作用的γ-分泌酶的抑制代表着降低Aβ的主要治疗措施,但是其临床应用受到机制相关副作用的限制(主要与Notch信号系统损害有关)[23,24]㊂目前发现的γ-分泌酶抑制剂MRK-560体内的耐受性较好,这可能与其对γ-分泌酶PS1亚基的亲和力大于PS2亚基有关,在野生型大鼠的动物实验中MRK-560耐受性较好但在PS2缺乏的模型鼠中却出现剂量依赖性的Notch信号系统损害,这表明PS2在Notch信号肽形成中发挥重要作用,这样选择性抑制PS1而对PS2无抑制作用或抑制作用较小的γ-分泌酶抑制剂有广泛应用的前景[24-26]㊂另一种颇受到关注的降低Aβ的措施就是针对Aβ的主动或被动免疫,主动免疫主要是将Aβ片段结合到载体蛋白和佐剂上,刺激机体细胞免疫和体液免疫产生抗Aβ的抗体㊂被动免疫是直接将Aβ特异性抗体(抗原为Aβ的N-末端,中间区域,C末端)直接注入到寄主体内,以清除脑内Aβ㊂但其临床试验发现接受免疫治疗的患者有6%都发生了脑膜脑炎,免疫治疗若能克服安全性低㊁治疗经费高等问题无疑将成为治疗AD的一大利器[27,28]㊂3㊀小㊀结㊀㊀跌倒是65岁以上老年人发生意外事故后的首位死亡原因,对于跌倒发生率更高的AD患者,防治跌倒更是刻不容缓㊂目前国内外相关研究集中在跌倒危险因素评估手段的改进和防治跌倒的具体措施上,非药理学措施包括芳香嗅觉刺激剂的应用㊁护理与社会支持方面的改良等㊂药物相关防跌倒措施包括用药剂量的改变,药物的联合应用,从淀粉样蛋白的减少着手阻止合成的γ-分泌酶及清除已存在的淀粉样蛋白的免疫治疗㊂这些无疑为防止AD患者跌倒㊁节约医疗成本带来了福音㊂ʌ参考文献ɔ[1]㊀Bao J,Chua KC,Prina M,et al.Multimorbidity and care depen-dence in older adults:a longitudinal analysis of findings from the 10/66study[J].BMC Public Health,2019,19(1):585.DOI:10.1186/s12889-019-6961-4.[2]㊀Hughes JC.Citizenship and authenticity in dementia:a scopingreview[J].Maturitas,2019,125:11-16.DOI:10.1016/j.maturitas.2019.04.001.[3]㊀Silva MVF,Loures CMG,Alves LCV,et al.Alzheimerᶄs disease:risk factors and potentially protective measures[J].J Biomed Sci, 2019,26(1):33.DOI:10.1186/s12929-019-0524-y. [4]㊀Ebihara S,Nikkuni E,Ebihara T,et al.Effects of olfactory stimu-lation on gait performance in frail older adults[J].Geriatr Gerontol Int,2012,12(3):567-568.DOI:10.1111/j.1447-0594.2011.00801.x.[5]㊀Freeman S,Ebihara S,Ebihara T,et al.Olfactory stimuli andenhanced postural stability in older adults[J].Gait Posture, 2009,29(4):658-660.DOI:10.1016/j.gaitpost.2009.02.005. [6]㊀Sakamoto Y,Ebihara S,Ebihara T,et al.Fall prevention usingolfactory stimulation with lavender odor in elderly nursing home residents:a randomized controlled trial[J].J Am Geriatr Soc, 2012,60(6):1005-1011.DOI:10.1111/j.1532-5415.2012.03977.x.[7]㊀Pike CJ.Sex and the development of Alzheimerᶄs disease[J].JNeurosci Res,2017,95(1-2):671-680.DOI:10.1002/jnr.23827.[8]㊀Nebel RA,Aggarwal NT,Barnes LL,et al.Understanding theimpact of sex and gender in Alzheimerᶄs disease:a call to action[J].Alzheimerᶄs Dement,2018,14(9):1171-1183.DOI:10.1016/j.jalz.2018.04.008.[9]㊀Rosario ER,Carroll J,Pike CJ.Testosterone regulation of Alzheimer-like neuropathology in male3xTg-AD mice involves both estrogen and androgen pathways[J].Brain Res,2010,1359:281-290.DOI:10.1016/j.brainres.2010.08.068.[10]Moreno-Morales C,Calero R,Moreno-Morales P,et al.Musictherapy in the treatment of dementia:a systematic review and meta-analysis[J].Front Med(Lausanne),2020,7:160.DOI:10.3389/fmed.2020.00160.[11]Fukui H,Toyoshima K.Music facilitates the neurogenesis,regener-ation and repair of neurons[J].Med Hypotheses,2008,71(5): 765-769.DOI:10.1016/j.mehy.2008.06.019. [12]Nigro N,Christ-Crain M.Testosterone treatment in the aging male:myth or reality?[J].Swiss Med Wkly,2012,142:w13539.DOI:10.4414/smw.2012.13539.[13]Ballard C,Hanney ML,Theodoulou M,et al.The dementia anti-psychotic withdrawal trial(DART-AD):long-term follow-up of a randomised placebo-controlled trial[J].Lancet Neurol,2009,8(2): 151-157.DOI:10.1016/S1474-4422(08)70295-3. [14]Schneider LS,Tariot PN,Dagerman KS,et al.Effectiveness ofatypical antipsychotic drugs in patients with Alzheimerᶄs disease[J].N Engl J Med,2006,355(15):1525-1538.DOI:10.1056/NEJMoa061240.[15]Gitlin LN,Kales HC,Lyketsos CG.Nonpharmacologic manage-ment of behavioral symptoms in dementia[J].JAMA,2012, 308(19):2020-2029.DOI:10.1001/jama.2012.36918.[16]Gill SS,Anderson GM,Fischer HD,et al.Syncope and its conse-quences in patients with dementia receiving cholinesterase inhibi-tors:a population-based cohort study[J].Arch Intern Med,2009, 169(9):867-873.DOI:10.1001/archinternmed.2009.43.[17]Sterke CS,van Beeck EF,van der Velde N,et al.New insights:dose-response relationship between psychotropic drugs and falls:a study in nursing home residents with dementia[J].J Clin Pharmacol,2012,52(6):947-955.DOI:10.1177/0091270011405665. [18]McShane R,Westby MJ,Roberts E,et al.Memantine for demen-tia[J].Cochrane Database Syst Rev,2019,3(3):CD003154.DOI:10.1002/14651858.CD003154.pub6.[19]Cummings JL,Tong G,Ballard C.Treatment combinations forAlzheimerᶄs disease:current and future pharmacotherapy options[J].J Alzheimers Dis,2019,67(3):779-794.DOI:10.3233/JAD-180766.[20]Ibi M,Sawada H,Nakanishi M.et al.Protective effects of1alpha,25-(OH)(2)D(3)against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture[J].Neuro-pharmacology,2001,40(6):761-771.DOI:10.1016/s0028-3908(01)00009-0.[21]Kartalou G,Endres T,Lessmann V,et al.Golgi-Cox impregna-tion combined with fluorescence staining of amyloid plaques reveals local spine loss in an Alzheimer mouse model[J].J Neurosci Methods,2020,341:108797.DOI:10.1016/j.jneumeth.2020.108797.[22]Marcello E,Epis R,Di Luca M.Amyloid flirting with synapticfailure:towards a comprehensive view of Alzheimerᶄs disease patho-genesis[J].Eur J Pharmacol,2008,585(1):109-118.DOI:10.1016/j.ejphar.2007.11.083.[23]Wolfe MS.APP,Notch,and presenilin:molecular pieces in thepuzzle of Alzheimerᶄs disease[J].Int Immunopharmacol,2002, 2(13-14):1919-1929.[24]Panza F,Lozupone M,Seripa D,et al.Amyloid-beta immuno-therapy for Alzheimer disease:is it now a long shot?[J].Ann Neurol,2019,85(3):303-315.DOI:10.1002/ana.25410.[25]Borgegard T,Gustavsson S,Nilsson C,et al.Alzheimerᶄs dis-ease:presenilin2-sparing gamma-secretase inhibition is a tolerable Aβpeptide-lowering strategy[J].J Neurosci,2012,32(48): 17297-17305.DOI:10.1523/JNEUROSCI.1451-12.2012.[26]Zhang X,Huai Y,Cai J,et al.Novel antibody against oligomericamyloid-beta:insight into factors for effectively reducing the aggre-gation and cytotoxicity of amyloid-beta aggregates[J].Int Immuno-pharmacol,2019,67:176-185.DOI:10.1016/j.intimp.2018.12.014.[27]Hoskin JL,Sabbagh MN,Al-Hasan Y,et al.Tau immunotherapiesfor Alzheimerᶄs disease[J].Expert Opin Investig Drugs,2019, 28(6):545-554.DOI:10.1080/13543784.2019.1619694. [28]Pinheiro L,Faustino C.Therapeutic strategies targeting amyloid-beta in Alzheimerᶄs disease[J].Curr Alzheimer Res,2019,16(5): 418-452.DOI:10.2174/1567205016666190321163438.(编辑:温玲玲)。
Health information management
Health information managementFrom Wikipedia, the free encyclopediaJump to: navigation, searchHealth information management (HIM) is the practice of maintenance and care of health records by traditional (paper-based) and electronic means in hospitals, physician's office clinics, health departments, health insurance companies, and other facilities that provide health care or maintenance of health records. With the widespread computerization of health records and other information sources, health informatics and health information technology are being increasingly utilized in information management practices in the health care sector.Health information management professionals plan information systems, develop health policy, and identify current and future information needs. In addition, they may apply the science of informatics to the collection, storage, use, and transmission of information to meet the legal, professional, ethical and administrative records-keeping requirements of health care delivery.[1] They work with clinical, epidemiological, demographic, financial, reference, and coded healthcare data.It has been suggested the proper collection, management and use of information within healthcare systems “will determine the system’s effectiveness in detecting health problems, defining priorities, identifying innovative solutions and allocating resources to improve health outcomes.”[2]For example, health information administrators have been described to "play a critical role in the delivery of healthcare in the United States through their focus on the collection, maintenance and use of quality data to support the information-intensive and information-reliant healthcare system".[3] As the field grows and information technology becomes a more crucial part of the medical world, health information management is experiencing a transition from traditional managing practices with paper to more efficient electronic management, such as with Electronic Health Records (EHRs). But the main goal is still to analyze, manage, and utilize the information that is essential to patient care and making sure the providers can access the information when necessary.[4]Background: History and development of HIM standards in the United StatesHIM standards began with establishment of AHIMAHealth information management's standards history is dated back to the introduction of the American Health Information Management Association, founded in 1928 "when the American College of Surgeons established the Association of Record Librarians of North America (ARLNA) to 'elevate the standards of clinical records in hospitals and other medical institutions.'"[5]In 1938, AHIMA was known as American Association of Medical Record Librarians (AAMRL) and its members were known as medical record experts or librarians who studied medical record science. The goal of this career was to raise the standards of keeping records in hospitals and other healthcare facilities. The individuals involved in this profession were promoters for the successful management of clinical records to guarantee their precision.Over time, the name AHIMA had changed to reflect the evolving field of health information management practices, eventually becoming the American Health Information Management Association. The association's current name is meant to cover the wide variety of areas health professionals work in today.AHIMA members affect the quality of patient information and patient care at every touch point in the healthcare delivery cycle. They often serve in bridge roles, connecting clinical, operational, and administrative functions.[6]HIMSS establishment in 1961 increased industry knowledgeThe Healthcare Information and Management Systems Society (HIMMS) was organized in 1961 as the Hospital Management Systems Society (HMSS), an independent, unincorporated, nonprofit, voluntary association of individuals. It was preceded by increasing amounts of management engineering activity in healthcare during the 1950s, when teachings by Frederick Winslow Taylor and Frank Bunker Gilbreth, Sr.began to attract the attention of health leaders. [7]The HIMMS grew to include chapters, membership categories, publications, conventions, and continues to grow in different parts of the world via its Europe, Asia Pacific, and Middle Eastern branches.[8]Accredited educational program developmentThe Commission on Accreditation for Health Informatics and Information Management Education (CAHIIM) defines standards which higher education health information management and technology programs must meet to qualify for accreditation. Students who graduate from an accredited associate's, bachelor's or certificate program are qualified to sit for their respective exams for certification as a Registered Health Information Technician (RHIT) - via graduation from an accredited associate or certification program - or Registered Health Information Administrator (RHIA), which requires education through an accredited bachelor or certification program. Competency requirements are maintained by CAHIIM in their Associate Degree Entry-Level Competencies and Baccalaureate Degree Entry-Level Competencies definitions.[9][10]Modern development in health information managementElectronic health recordsMain article: Electronic health recordThe electronic health record has been continually expressed as an evolvement of health record-keeping. Because it is electronic, this means of record keeping has been both supported and debated in the health professional community and within the public realm.In the United States, 89% of those who responded to a recent Wall Street Journal poll described themselves as "Very/Somewhat Confident" in their health care provider who used electronic health records compared to 71% of respondents who responded positively about their providers who didn't or don't use electronic health records.[11] As of 2008, more thanfifty-percent of Chief Information Officers polled listed that they wanted ambulatory electronic health records in order to have the health information record available to move across each stage of health care.[12]Health information managers are charged with the protection of patient privacy and are responsible for training their employees in the proper handling and usage of the confidential information entrusted to them. With the rise of technology's importance in healthcare, health information managers must remain competent with the use of information databases that generate crucial reports for administrators and physicians.Educational programsThe requisites and accreditation processes for health information management education and professional activity vary across jurisdictions.In the United States, the CAHIIM requires continued accreditation for accredited programs in health information management. The current standard is that accreditation may be maintained with periodic site visits, submission of an annual report, informing CAHIIM of adverse changes within the program and paying CAHIIM administrative fees.[13][14]HIM students may opt to participate in a full-time bridge program called the Joint Bachelor of Science/Masters Program. With this program, students can achieve both the Bachelor of Science in Health Information Management and the Master of Health Services Administration Program (BSHIM/MHSA). The full-time bridge program allows students to achieve both degrees in five years. Students pursuing the BSHIM/MHSA will be prepared to assume management and executive positions in health-related organizations such as: hospitals, managed care organizations, health information system developers and vendors, and pharmaceutical companies, and bring their knowledge in HIM to these positions.In Canada, graduates of Canadian Health Information Management Association (CHIMA) programs are eligible to write a national certification examination to pursue a profession in HIM.[15]Online program availabilityThere are many programs that are also available online. Online students collaborate with in-class students using internet technology. With online learning, students are allowed to go through the programs at their own pace. Online students are included in class through group lectures that are recorded and put online, discussion boards and are members of groupprojects with in-class students. Some online students are even allowed to attend some classes on campus and take some classes online.The CAHIIM lists accredited online programs on its website.[16] Further education for health information professionalsEducation is an important aspect in being successful in the world of health information management. Aside from initial credentials, health information professionals may wish to pursue a Masters of Business Administration, Masters of Health Administration, or other Masters programs in health data management, information technology and systems, and organization and management. Gaining further education advances the health professional's career and qualifies the individual forupper-management positions.Records and practices used in health information managementHealthcare quality and safety require that the right information be available at the right time to support patient care and health system management decisions. Gaining consensus on essential data content and documentation standards is a necessary prerequisite for high-quality data in the interconnected healthcare system of the future. Continuous quality management of data standards and content is key to ensuring that information is usable and actionable.[17]Records∙The patient health record is the primary legal record documenting the health care services provided to a person in any aspect of the health care system. The termincludes routine clinical or office records, records of care in any health related setting, preventive care, lifestyle evaluation, research protocols and various clinical databases.This repository of information about a single patient is generated by health careprofessionals as a direct result of interaction with a patient or with individuals whohave personal knowledge of the patient.∙The primary patient record is the record that is used by health care professionals while providing patient care services to review patient data or document their ownobservations, actions, or instructions.The secondary patient record is a record that is derived from the primary record and contains selected data elements to aid non clinical persons in supporting, evaluatingand advancing patient care. Patient care support refers to administration, regulation,and payment functions.PracticesMethods to ensure Data QualityThe accuracy of data depends on the manual or computer information system design for collecting, recording, storing, processing, accessing and displaying data as well as the ability and follow- through of the people involved in each phase of these activities. Everyone involved with documenting or using health information is responsible for its quality. According to AHIMA’s Data Quality Management Model, there are four key processes for data:1.Application: the purpose for which the data are collected.2.Collection: the processes by which data elements are accumulated.3.Warehousing: the processes and systems used to store and maintain data and datajournals.4.Analysis: the process of translating data into information utilized for an application. Each aspect is analyzed with 10 different data characteristics:1.Accuracy: Data are the correct values and are valid.2.Accessibility: Data items should be easily obtainable and legal to collect.prehensiveness: All required data items are included. Ensure that the entirescope of the data is collected and document intentional limitations.4.Consistency: The value of the data should be reliable and the same acrossapplications.5.Currency: The data should be up to date. A datum value is up to date if it is currentfor a specific point in time. It is outdate if it was current at some preceding time yetincorrect at a later time.6.Definition: Clear definitions should be provided so that current and future data userswill know what the data mean. Each data element should have clear meaning andacceptable values.7.Granularity: The attributes and values of data should be defined at the correct levelof detail.8.Precision: Data values should be just large enough to support the application orprocess.9.Relevancy: The data are meaningful to the performance of the process or applicationfor which they are collected.10.Timeliness: Timeliness is determined by how the data are being used and theircontext.Health information professionalsHIM is a very broad and successful field for health care professionals. There are several career opportunities in Health Information Management and many different traditional and non-traditional settings for an HIM professional to work within.∙Traditional settings include: Managing an HIM medical records department, cancer registry, coding, trauma registry, transcription, quality improvement, release ofinformation, patient admissions, compliance auditor, physician accreditation,utilization review, physician offices and risk management.∙Non-traditional settings include: consulting firms, government agencies, law firms, insurance companies, correctional facilities, extended care facilities, pharmaceuticalresearch, information technology and medical software companies.[18]Health information managersProfessional health information managers manage and construct health information programs to guarantee they accommodate medical, legal, and ethical standards. They play a crucial role in the maintenance, collection, and analyzing of data that is received by doctors, nurses, and other healthcare players. In return these healthcare data contributors rely on the information to deliver quality healthcare. Managers must work with a group of information technicians to guarantee that the patient's medical records are accurate and are available when needed.In the United States, health information managers are typically certified as a Registered Health Information Administrator (RHIA) after achieving a bachelor's degree in health informatics or health information management from a school accredited by the Commission on Accreditation for Health Informatics and Information Management Education (CAHIIM) and after passing their respective certification exam.[19]The Certified Health Informatics Systems Professional (CHISP) certification offered by American Society of Health Informatics Managers (ASHIM)[20] is to credit an IT professional who is able to support physician adoption of Health IT. A CHISP professional needs to process knowledge of the health care environment, Health IT, IT, and soft skills including communication skills.RHIAs usually assume a managerial position that interacts will all levels of an organization that use patient data in decision making and everyday operations.[21] They may work in a broad range of settings that span the continuum of healthcare including office based physician practices, nursing homes, home health agencies, mental health facilities, and public health agencies.Health information managers may specialize in registry management, data management, and data quality among other areas.Medical records and health information techniciansMedical records and health information technicians (MRHIT) are described as having the following duties according to the U.S. Bureau of Labor Statistics' Occupational Outlook Handbook[22]:assemble patients' health information including medical history, symptoms, examination results, diagnostic tests, treatment methods, and all other healthcare provider services. Technicians organize and manage health information data by ensuring its quality, accuracy, accessibility, and security. They regularly communicate with physicians and other healthcare professionals to clarify diagnoses or to obtain additional information.The International Labour Organization's International Standard Classification of Occupations further notes: "Occupations included in this category require knowledge of medical terminology, legal aspects of health information, health data standards, and computer- or paper-based data management as obtained through formal education and/or prolonged on-the-job training.[23]MRHITs usually work in hospitals. However they also work in a variety of other healthcare settings, including office based physician practices, nursing homes, home health agencies, mental health facilities, and public health agencies. Technicians who specialize in coding are called medical coders or coding specialists.In the United States, Registered Health Information Technologists must pass an accredited Health Information Technology program before they may take their certification exam.[24]Professional organizations∙American Society of Health Informatics Managers (ASHIM)∙American Health Information Management Association (AHIMA)∙Commission on Accreditation of Health Informatics and Information Management Education (CAHIIM)∙Healthcare Information Management and Systems Society (HIMSS) References1.^ World Health Organization. (2010). Classifying health workers. Geneva: WHO.2.^Stansfield S. (2005). “Structuring information and incentives to improve health”.Bulletin of the World Health Organization, 83(8):562.3.^ (LaTour, Kathleen M., & Maki, Shirley Eichenwald. (2010). Health informationmanagement concepts, principles, and practice. Chicago, Illinois: American HealthInformation Management Association.)(LaTour, & Maki, 2010).4.^ LaTour, Kathleen. Health Information Management: Concepts, Principles, andPractice. Chicago: AHIMA, 2006.5.^ AHIMA (2010). "AHIMA History". AHIMA. Retrieved 2010-01-08.6.^Partner in the Delivery of Quality Healthcare. (n.d.). Retrieved November 28, 2009,from American Health Information Management Association.7.^ HIMSS (2008). "AHIMA History". HIMSS Legacy Workgroup. Retrieved2010-01-08.8.^ HIMSS. . Retrieved 1/8/2010.9.^ AHIMA. 6/3/2004 HIM Associate Degree Entry-Level Competencies. AHIMAEducation Strategy Committee. Accessed 1/8/2010.10.^ AHIMA. 4/20/2004 HIM Baccalaureate Degree Entry-Level Competencies.AHIMA Education Strategy Committee. Retrieved 1/8/2010.11.^ Wall Street Journal. "Benefits of Electronic Health Records Seen as OutweighingPrivacy Risks". Retrieved 1/8/2010.12.^Healthcare Integration and Connectivity: Results of a Survey by the EnterpriseInformation Systems Steering Committee page 4. HIMSS. Retrieved 1/8/2010.13.^ CAHIIM. 2005 Interpretation of Standards: Associate Degree section VI.F.Retrieved 1/8/2010.14.^ CAHIIM. Interpretation of Standards: Baccalaureate Degree section VI.F.Retrieved 1/8/2010.15.^ Alberta Occupational Profiles, 2011. Health Information Management Professionalhttp://alis.alberta.ca/occinfo/Content/RequestAction.asp?aspAction=GetHTMLProfile&format=html&OCCPRO_ID=7100253616.^. Retrieved 1/8/2010.17.^Mervat Abdelhak et al.: “Health Information: Management of a Strategic Resource”,Second Edition18.^Medical Records and Health Information Technicians. Retrieved 1/8/2010.19.^ AHIMA. Eligibility Requirements: Registered Health Information Administrator.Retrieved 1/8/2010.20.^ CHISP Healthcare IT certification. CHISP Certification Requirement . Retrieved3/2/2010.21.^ Chicago State University Profession. Retrieved 1/8/2010.22.^ Occupational Outlook Handbook, 2010-11 Edition. Medical Records and HealthInformation Technicians. Retrieved 1/8/2010.23.^ International Standard Classification of Occupations, 2008 revision: Unit Group3252: Medical records and health information technicians./public/english/bureau/stat/isco/index.htm24.^ AHIMA (2008). "Eligibility Requirements". AHIMA./certification/rhia/requirements.aspx. Retrieved 2010-01-08.。
apriori 代码例子
apriori 代码例子Apriori是一种用于关联规则学习的算法，主要用于挖掘频繁项集和关联规则。
下面是一个简单的Python代码示例，演示如何使用Apriori算法进行关联规则学习。
# 导入相关库import pandas as pdfrom mlxtend.preprocessing import TransactionEncoderfrom mlxtend.frequent_patterns import apriorifrom mlxtend.frequent_patterns import association_rules# 加载数据集dataset = [['牛奶', '面包', '黄油'],['面包', '黄油', '花生酱'],['牛奶', '面包', '黄油', '花生酱'],['面包', '黄油'],['牛奶', '面包', '黄油', '鸡蛋']]# 数据预处理te = TransactionEncoder()te_ary = te.fit(dataset).transform(dataset)df = pd.DataFrame(te_ary, columns=te.columns_)# 使用Apriori算法找出频繁项集frequent_itemsets = apriori(df, min_support=0.6, use_colnames=True)# 生成关联规则rules = association_rules(frequent_itemsets, metric="confidence", min_threshold=0.7)# 输出结果print(frequent_itemsets)print(rules)在上面的代码中，我们首先使用Pandas库加载了一个简单的数据集，该数据集包含了5个交易的购物清单。
Panasonic Toughpad FZ-G1 产品说明书
T OUGHPAD FZ-G1 CertificationsMIL-STD-461FThe Toughpad® FZ-G1 is tested to the MIL-STD-461F standard methodology for electromagnetic interference (EMI) and electromagnetic compatibility (EMC) in Panasonic's R&D facility in Japan and certified by a third party. The certification ensures that Panasonic computers are electromagnetically compatible with other nearby electronic equipment. Certified Panasonic computers do not generate unwanted electromagnetic energy that could interfere with the operation of other equipment, nor are susceptible to the effects of unwanted electromagnetic energy from equipment in the same vicinity. Panasonic has various certifications that meet federal requirements for rugged computers. DOWNLOAD MIL-STD-461F REPORTMIL-STD-810GThe Toughpad® FZ-G1 is MIL-STD-810G certified for a range of extreme conditions including 48" drops1, shocks, vibration, humidity, altitude, explosive atmosphere, rain-, dust- and sand-resistance, temperature extremes and thermal shock. Each of the twenty-one MIL-STD-810G tests conducted have been certified by independent lab testing. MIL-STD-810G, which was created in October 2008, supersedes MIL-STD-810F. DOWNLOAD MIL-STD-810G REPORTIngress Protection (IP65)The Toughpad® FZ-G1 is IP65 certified1 according to the IP code defined in the international standard IEC 60529. The products are tested and certified by an independent test lab facility located in the United States. Rather than vaguely describing equipment as "waterproof" or "dustproof", the IP Code uniformly quantifies various levels of resistance to liquids, particulates and solid objects. The numbers following the letters "IP" represent the specific degree of protection provided by electrical enclosures. The first digit (6) indicates the ingress of dust at a level that will not have a harmful effect on the operation of the unit. The second digit (5) indicates that water sprayed from all directions will not compromise the computer's functioning. Higher numbers indicate a higher tolerance to dust and water. For example, a unit with an IP65 rating will withstand both elements better than a unit with an IP54 rating. While IP65-certified Panasonic computers are not completely impervious to the ingress of water or dust, the rating does indicate neither element will cause operational complications while used under conditions commonly encountered by Panasonic rugged computers. DOWNLOAD IP65 REPORTANSIHazardous LocationsAmerican National Standards Institute (ANSI) reviews safety standards, include Hazardous Locations, every 5 years. In July 2012, UL 1604 — Electrical Equipment for Use in Class I and II, Division 2 Hazardous Locations — was withdrawn as the approved ANSI standard for use in the United States. UL1604 was replaced with ISA 12.12.01-2000 which has very similar requirements as UL1604 Hazardous Locations Class 1 Division 2.ANSI 12.12.01-2000 Hazardous Locations certification allows products to be used in potentially explosive environments found in oil and gas, petrochemical, aviation and other industries. Select fully-ruggedToughbook® mobile computers can be configured to provide safe, reliable solutions for spark-free use. ANSI12.12.01-2000 Hazardous Location approved models are available for use in Class I, Division 2, Groups A, B, C andD environments. These are defined as places where flammable gases, vapors and liquids are present during abnormal or accident conditions. DOWNLOAD ANSI 12.12 REPORTENERGY STAR QualificationENERGY STAR, a joint program between the U.S. Environmental Protection Agency and U.S. Department of Energy, offers voluntary qualification for products that are energy efficient. The ENERGY STAR program sets high standards designed to save energy, save money and help protect the environment for future generations. Panasonic is one of nearly 20,000 organizations that have become ENERGY STAR partners, all working to promote, sell, or improve products, homes, and buildings that use less energy and qualify for the ENERGY STAR. Panasonic's commitment to ENERGY STAR initiatives and other environmental programs have resulted in all Toughbook® computers earning the ENERGY STAR.ENERGY STAR for computers raises the efficiency bar dramatically. ENERGY STAR establishes efficiency requirements for all modes of a product's operation, which ensures energy savings when a product is active and running basic applications, as well as in low power modes. Qualifying products must also include an internal power supply that is at least 80 percent efficient. Only the most energy-efficient products, including all Toughbook computers have qualified for the new specification. If all computers sold in the US meet ENERGY STAR requirements, the savings in energy costs will grow to more than $1.5 billion each year, reducing greenhouse gas emissions equivalent to those from 2 million vehicles. READ MOREEPEAT CertificationEPEAT is an easy-to-use, online tool to help purchasers in the public and private sectors evaluate, compare and select products based on their environmental attributes. EPEAT also provides a clear and consistent set of performance criteria for the design of products, and provides an opportunity for manufacturers to secure market recognition for their efforts to reduce the environmental impact of its products.EPEAT evaluates electronic products according to three tiers of environmental performance — Bronze, Silver and Gold. There are 51 total environmental criteria: 23 required criteria and 28 optional criteria. A Bronze-rated product meets all 23 required criteria. A Silver-rated product meets all 23 required criteria plus at least 50% of the optional criteria. A Gold-rated product meets all 23 required criteria and at least 75% of the optional criteria. All Toughbook computer models are either gold- or silver-rated, ensuring the highest level of environmental performance. READ MOREISO CertificationSince 1996, all Panasonic manufacturing plants worldwide—including the factory in Kobe, Japan—have achieved ISO 14001 registration and implemented the ISO 14001 Environmental Management System. The Kobe factory has also been certified for ISO 9001, an international standard for quality management systems that enhance product quality assurance and customer satisfaction.International Organization for Standardization (ISO) is an international federation promoting the development of international manufacturing, trade, and communication standards. ISO 14000, a series of standards, provides the framework for managing the environmental impacts of an organization.The ISO 14001 international standard established a systematic approach that organizations can use to minimize or prevent environmental impacts and risks. This approach, known as an Environmental Management System or EMS, requires the organization to establish an environmental control policy, educate employees about procedures and continually monitor environmental performance.RoHS ComplianceFor manufacturers of electronic equipment, the main impact of RoHS is that only lead-free products can be sold in Europe. Panasonic has therefore shifted to lead-free solder. By selling RoHS-compliant products in all countries, not just Europe, Panasonic helps eliminate hazardous electronic waste materials from landfills and waste dumps around the world. READ MOREVerizonVerizon Wireless delivers high-speed wireless access in 259 major metro areas, covering more than 280 million people. Panasonic Toughbook computers connect to the Verizon Wireless network without the need of a PC card or Wi-Fi hotspot. READ MOREAT&TA United States wireless leader, AT&T has more than 72.9 million subscribers and offers the best coverage of any carrier worldwide1. Panasonic Toughbook mobile computers are designed with embedded wireless technology allowing instant access to AT&T's extensive high-speed network without the need for an external card, additional antenna or other accessories. READ MORETested by national independent third party lab following MIL-STD-810G Method 516.6 Procedure IV for transit drop test and IEC 60529 Sections 13.4, 13.6.2, 14.2.5 and 14.3 for IP65.。
PubMed医学文献检索系统.
PubMed医学文献检索系统PubMed是因特网上重要的免费文献检索系统。
目前全球最著名的医学文献数据库系统是美国国立医学图书馆的MEDLINE，该数据库重数据免费提供给各个检索系统的开发商，因此在因特网上有重多的免费MEDLINE检索系统。
这些系统所涵盖的文献年代、检索结果的输出格式以及检索途径各不相同，但是，目前被医务人员广泛使用的仍然是美国国立医学图书馆的PubMed系统PubMed和NCBI：1．美国国立医学图书馆“NLM”2．早在1879年，编译医学文献的检索刊物IM3．1964年采用计算机进行电子编辑和排版，在此基础上开发了“医学文献分析与检索系统”（即著名的MEDLARS）4．1971年正式建立了钙系统的联机系统，称为“MEDLARS联机检索系统，MEDLARS online,既MEDLINE 系统。
5．PubMed则是NLM的国家生物信息中心（National Center for Biotechnology Information, NCBI）开发的一个以网络为基础的检索系统，自1997年免费提供服务PubMed ――特点：PubMed具有MEDLINE 所具有的各种检索和数据库优势，同时还具有以下特点：⏹连接广泛：包括对外链接和对内链接，对内指与NCBI其它数据库的链接和PubMed文献相似度计算后的相关文献链接，对外连接指出版商提供的文献全文的连接，有免费和需要注册的。
⏹更新速度快：出版商直接把电子版提供给NLM⏹收录文献范围广：三个层次的数据库：MEDLINE数据库、PreMEDLINE数据库和出版商直接提供的文献数据库等PubMed ――收录范围总体包括：⏹收录年限：1966～⏹收录内容：70多个国家和地区的4000余种生物医学期刊的文献和一些非医学内容的文献，主要是MEDLINE。
内容涉及医学、护理、牙科、兽医、健康保健系统、前临床医学等学科，另外有非医学内容的文献，如science 和nature中具有地理学方面的文献。
HADLIMA
HADLIMA®入门指引了解更多关于您的治疗的信息和MSD Harmony™ 给您提供的支持免责声明: 本教育手册仅供澳大利亚接受 HADLIMA 处方治疗的患者使用。
本手册中的信息仅用于教育目的，不用于任何自我诊断目的，也不用于替代您的医生或医疗保健专业人员提供的信息或建议。
如果您对HADLIMA 或您的病情有任何疑问，请务必与您的医生、护士或药剂师联系。
请向您的药剂师索取消费者用药信息的副本。
这本小册子是患者计划的一部分，由 MSD 提供给您。
HADLIMA®（阿达木单抗）是什么HADLIMA 是一种称为生物类似药的生物制剂。
生物制剂是由生物体制成的药物。
生物体的一些例子包括人类细胞、动物细胞和微生物（如酵母和细菌）。
生物制剂不同于其他由化学物质制成的处方药。
生物制剂可分成两种类型：“原研药物” -- 生物制剂的原始版本和“生物类似药” -- 生物制剂的其他版本。
HADLIMA 是原研药物阿达木单抗的生物类似药。
HADLIMA 用于治疗成人和儿童的以下疾病:•类风湿性关节炎•强直性脊柱炎•银屑病关节炎•青少年特发性关节炎•克罗恩病•溃疡性结肠炎•化脓性汗腺炎•银屑病•葡萄膜炎您的医生可能因为其他原因开了 HADLIMA 处方。
如果您对医生为什么为您开 HADLIMA 处方有任何疑问，请咨询您的医生。
23在您开始使用 HADLIMA 之前，与您的医生交谈在您开始使用 HADLIMA 之前，告诉您的医生： •任何其他病症的信息•对其他药物或其他物质的任何过敏•如果您正处于怀孕或哺乳期•如果您将要进行大手术•如果您有或曾经有过感染或感染症状（例如发热、伤口、感到疲倦、牙齿问题）•如果您患有结核病或曾与患有结核病的人密切接触•罹患或曾经患过癌症。
•有任何麻木或刺痛或有影响您（或您的孩子）神经系统的问题，如多发性硬化症。
关于与 HADLIMA 一起服用其他药物，我需要了解什么？告诉您的医生您是否正在服用任何其他药物，包括您在没有处方的情况下从药店、超市或保健食品商店购买的任何药物。
缺失数据统计处理方法的研究进展
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Chinese Journal of Health Statistics， Feb 2013 ， Vol． 30 ， No． 1
④最近距离填补（ nearest neighbor imputation） 最近距离填补法是利用辅助变量， 定义一个测量 单元间距离的函数， 在缺失值临近的回答单元中， 选择 满足所设定距离条件的辅助变量中的单元所对应的变 即在填补类中按匹配变量 量的回答单元作为填补值， 找到与受者记录最接近的供者记录 。用于定义赋值单 位的距离函数可以有很多类型， 马氏距离就是其中一 种。由于距离函数有不同类型， 用最近距离函数得到 的填补值具有伪随机性， 这给考察最近距离填补估计 量的性质带来了挑战。 ⑤热卡填补（ hot deck imputation） 热卡填补中常见的有随机热卡填补法和序贯热卡 填补法。 随机热卡填补是通过对变量 Y 的回答单元 进行有放回的简单随机抽样获得填补值 。这里的填补 值是随机的， 避免了均值填补中方差低估的缺点。 序 贯热卡填补法首先对数据分层， 然后在每层中按照某 种顺序对单元排序， 对于有数据缺失的单元， 用同一层 中最后一个被计算机读取的数据进行填补 。该方法存 在的问题是填补值的选择是由辅助变量决定的 ， 用不 同的变量进行排序， 得到的序列不同， 对某一缺失值来 说可能采用的填补值也就不同。 因此， 应该选择与研 究变量性质高度相关的排序变量， 使得排列位置相邻 〔15 － 16 〕 。 的单位在研究性质上也相近 ⑥冷卡填补（ cold deck imputation） 冷卡填补法是相对于热卡填补而言的， 指填补值 不是从当前的调查， 而是从以往的调查或者其他历史 数据中获得的。 上述单一的填补方法通常可能会扭曲目标变量的 分布， 使填补变量的方差被低估， 还可能歪曲变量与变 〔4 ， 15 〕 。 另外一 量间的关系， 无法得到真实的效应结果 个问题是基于填补的数据推断参数， 无法解释填补的 不确定性。 （ 2 ） 多重填补（ multiple imputation， M I） 〔1 〕 多重填补由 Rubin 在 1978 年提出 ， 它通过某种 方法对每个缺失值都构造 d 个替代值 （ d ≥2 ） ， 以形成 D 个完整的数据集， 对每个数据集均采用相同的针对 完整数据集的统计方法分析， 将得到的结果综合， 产生 M I 能反映 最终的统计推断。与单一的填补方法相比， 由缺失数据带来的不确定性， 增加了估计的效率。 多重填补中最关键的问题是如何进行有效的填 ， 补 从理论上讲缺失值可以从联合后验预测分布中进 行抽取。但在实际中尤其是复杂问题中要做到这点并 不容易， 特别是在多变量数据及涉及非线性关系等情 况下。近十年里， 逐渐形成了两种最常见的对多元数 据进行填补的策略， 分别是联合模型法和全条件定义 法。 JM ） ①联合模型法（ joint modeling ，
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Chanin School Of ArchitectureNew York, NYBArchCornell UniversityCollege of Architecture, Art, and Planning Department of ArchitectureIthaca, NY/arch/BArch; MArchNew York Institute of TechnologySchool of Architecture & DesignOld Westbury, NY/architecture/BArchParsons School of DesignSchool of Constructed EnvironmentsNew York, NY/sceMArchPratt InstituteSchool of ArchitectureBrooklyn, NY/archBArch; MArchRensselaer Polytechnic InstituteSchool of ArchitectureTroy, NYBArch; MArchState University of New York at BuffaloSchool of Architecture and PlanningDepartment of ArchitectureBuffalo, NY/architecture/MArchSyracuse UniversitySchool of ArchitectureSyracuse, NYBArch; MArch5NORTH CAROLINA (2)North Carolina at Charlotte, University ofCollege of Arts + ArchitectureSchool of ArchitectureCharlotte, NCBArch; MArchNorth Carolina State UniversityCollege of DesignSchool of ArchitectureRaleigh, NC/BArch; MArchNORTH DAKOTA (1)North Dakota State UniversityCollege of Engineering and ArchitectureDepartment of Architecture and Landscape Architecture Fargo, ND/MArchOHIO (4)Cincinnati, University ofCollege of Design, Architecture, Art, and Planning School of Architecture & Interior DesignCincinnati, OH/said/MArchKent State UniversityCollege of Architecture & Environmental Design Architecture ProgramKent, OHMArchMiami UniversitySchool of Fine ArtsDepartment of Architecture and Interior Design Oxford, OH/architectureMArchOhio State UniversityKnowlton School of ArchitectureColumbus, OHMArchOKLAHOMA (2)Oklahoma State UniversityCollege of Engineering, Architecture and Technology School of ArchitectureStillwater, OKBArch Oklahoma, University ofCollege of ArchitectureDivision of ArchitectureNorman, OK/BArch; MArchOREGON (2)Oregon, University ofSchool of Architecture and Allied ArtsDepartment of ArchitectureEugene, OR/BArch; MArchPortland State UniversitySchool of Fine and Performing ArtsDepartment of ArchitecturePortland, OR/architecture/MArch - CandidatePENNSYLVANIA (6)Carnegie Mellon UniversitySchool of Fine ArtsSchool of ArchitecturePittsburgh, PA/architectureBArchDrexel UniversityAntoinette Westphal College Media Arts and Design Department of Architecture and Interiors Philadelphia, PA/westphal/architecture/BArchPennsylvania State UniversityCollege of Arts and ArchitectureSchool of Architecture and Landscape Architecture Department of ArchitectureUniversity Park, PABArchPennsylvania, University ofSchool of DesignDepartment of ArchitecturePhiladelphia, PA/gsfa/archMArchPhiladelphia UniversitySchool of ArchitecturePhiladelphia, PA/schools/add/BArch6Temple UniversityTyler School of ArtArchitecture ProgramPhiladelphia, PA/architectureBArch (through 6/30/16)MArch (beginning 1/1/12 as a result of a nomenclature change)PUERTO RICO (2)Polytechnic University of Puerto RicoThe New School of ArchitectureSan Juan, PR/arqpoli/homepage.htmBArchPuerto Rico, Universidad deEscuela De ArquitecturaSan Juan, PR/MArchRHODE ISLAND (2)Rhode Island School of DesignArchitecture + DesignDepartment of ArchitectureProvidence, RIBArch; MArchRoger Williams UniversitySchool of Architecture, Art, and Historic Preservation Bristol, RI/academics/schools/saahp/MArchSOUTH CAROLINA (1)Clemson UniversityCollege of Architecture, Arts and HumanitiesSchool of ArchitectureClemson, SC/caah/architecture/MArchSOUTH DAKOTA - NoneTENNESSEE (2)Memphis, University ofDepartment of ArchitectureMemphis, TNMArch – CandidateTennessee-Knoxville, University ofCollege of Architecture and DesignSchool of ArchitectureKnoxville, TN/BArch; MArch TEXAS (8)Houston, University ofGerald D. Hines College of ArchitectureHouston, TXBArch; MArchPrairie View A&M UniversitySchool of ArchitecturePrairie View, TX/architectureMArchRice UniversitySchool of ArchitectureHouston, TXBArch; MArchTexas A&M UniversityCollege of ArchitectureDepartment of ArchitectureCollege Station, TX/college/MArchTexas at Arlington, University ofArchitecture ProgramArlington, TX/architectureMArchTexas at Austin, University ofSchool of ArchitectureAustin, TX/BArch; MArchTexas at San Antonio, University ofCollege of ArchitectureArchitecture ProgramSan Antonio, TX/architecture/MArchTexas Tech UniversityCollege of ArchitectureLubbock, TX/architectureMArchUTAH (1)Utah, University ofCollege of Architecture and PlanningSchool of ArchitectureSalt Lake City, UTMArch7VERMONT (1)revised March 2011 Norwich UniversitySchool of Architecture and ArtNorthfield, VTMArchVIRGINIA (3)Hampton UniversitySchool of Engineering and TechnologyDepartment of ArchitectureHampton, VA/academics/schools/engineering/MArchVirginia TechCollege of Architecture & Urban StudiesSchool of Architecture + DesignBlacksburg, VA/BArch; MArchVirginia, University ofSchool of ArchitectureCharlottesville, VA/architecture/MArchWASHINGTON (2)Washington, University ofCollege of Architecture and Urban PlanningDepartment of ArchitectureSeattle, WAMArchWashington State UniversityCollege of Architecture and EngineeringSchool of Architecture and Construction ManagementPullman, WAMArchWEST VIRGINIA - NoneWISCONSIN (1)Wisconsin-Milwaukee, University ofSchool of Architecture & Urban PlanningDepartment of ArchitectureMilwaukee, WI/SARUP//architecture/MArchWYOMING - NoneAmerican University of SharjahSchool of Architecture and DesignDepartment of ArchitectureSharjah, United Arab Emirates/arcdes/arc/BArch8。