Weight ratio and corresponding hold-down pressure
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8613",leadTitle:null,fullTitle:"Aerospace Engineering",title:"Aerospace Engineering",subtitle:null,reviewType:"peer-reviewed",abstract:"This book is a collection of reviewed and relevant research chapters, offering a comprehensive overview of recent developments in the field of engineering. The book comprises chapters authored by various researchers and edited by an expert active in the aerospace engineering research area. All chapters are separate but united under a common research study topic. This publication aims at providing a thorough overview of the latest research efforts by international authors on engineering, and opening new possible research paths for further novel developments.",isbn:"978-1-83962-786-6",printIsbn:"978-1-83962-784-2",pdfIsbn:"978-1-83962-787-3",doi:"10.5772/intechopen.79206",price:119,priceEur:129,priceUsd:155,slug:"aerospace-engineering",numberOfPages:228,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"075278075d72ebe02490ff58675119ef",bookSignature:"George Dekoulis",publishedDate:"November 20th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8613.jpg",numberOfDownloads:13193,numberOfWosCitations:5,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:19,numberOfDimensionsCitationsByBook:1,hasAltmetrics:1,numberOfTotalCitations:35,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 10th 2018",dateEndSecondStepPublish:"July 31st 2018",dateEndThirdStepPublish:"September 29th 2018",dateEndFourthStepPublish:"December 18th 2018",dateEndFifthStepPublish:"February 16th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"9833",title:"Prof.",name:"George",middleName:null,surname:"Dekoulis",slug:"george-dekoulis",fullName:"George Dekoulis",profilePictureURL:"https://mts.intechopen.com/storage/users/9833/images/system/9833.jfif",biography:"Prof. George Dekoulis received his Ph.D. in Space Computing and Communications from Lancaster University, UK, in 2007. He was awarded a First Class BEng (Hons) degree in Communications Engineering from De Montfort University, UK, in 2001. He has received several awards from the Science and Technology Facilities Council (STFC), the Engineering and Physical Sciences Research Council (EPSRC), and the Hudswell International Research Scholarship (IET). He is the Founding Dean of the Faculty of Sciences and Technology at the American University of Cyprus (AUCY), Cyprus. He was previously a professor at the Aerospace Engineering Institute (AEI), Cyprus. Founder of the IEEE Aerospace and Electronic Systems Society (AESS), Cyprus. General chair of IEEE Aerospace Engineering Innovations 2019 (IEEE AEI 2019), Limassol, Cyprus. He has worked as a professor in Computer Science & Communications at various departments, such as Space & Planetary Physics, Aeronautical and Space Engineering, Professional Flight, Robotics/Mechatronics & Mechanical Engineering, Computer Science & Engineering, and Electrical and Electronics Engineering. His research focuses on the design of reconfigurable Digital Logic Computer Science and Engineering Systems.",institutionString:"American University of Cyprus (AUCY)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"9",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"111",title:"Aerospace Engineering",slug:"aerospace-engineering"}],chapters:[{id:"65403",title:"Green Comparable Alternatives of Hydrazines-Based Monopropellant and Bipropellant Rocket Systems",doi:"10.5772/intechopen.82676",slug:"green-comparable-alternatives-of-hydrazines-based-monopropellant-and-bipropellant-rocket-systems",totalDownloads:1639,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Concepts are presented for “green” (with reduced hazards) replacements for monopropellant hydrazine propulsion systems and for hypergolic bipropellant systems while maintaining similar performance. At the onset of the “green propulsion” age, “green” alternatives to hydrazine propulsion have been emerging. The introduction rate of these into space systems is very slow due to the conservatism of the space propulsion industry. The concept presented here for monopropellant hydrazine systems offers gradual conversion to “green propellants” by dual capability of conventional hydrazine systems and ammonium dinitramide (ADN)-based systems. An initial risk reduction program has been carried out for materializing the concept. It includes proof of concept of dual use of all propulsion system parts. Materials compatibility and actual operation have been demonstrated. For bipropellants, we present the emerging “green” hypergolic system based on kerosene and peroxide, similar in performance to MMH/N2O4. Results of the proof-of-concept and development model systems are presented. The experimental results of various engine types demonstrate the capability to operate in both pulse and steady-state modes and the ability to produce different thrust levels. The fuel and oxidizer show very robust hypergolicity and short ignition delay times, as well as characteristic velocity efficiency exceeding 98%.",signatures:"Dov Hasan, Dan Grinstein, Alexander Kuznetsov, Benveniste Natan, Zohar Schlagman, Avihay Habibi and Moti Elyashiv",downloadPdfUrl:"/chapter/pdf-download/65403",previewPdfUrl:"/chapter/pdf-preview/65403",authors:[null],corrections:null},{id:"65003",title:"High Strain Rate Characterization of Thermoplastic Fiber-Reinforced Composites under Compressive Loading",doi:"10.5772/intechopen.82215",slug:"high-strain-rate-characterization-of-thermoplastic-fiber-reinforced-composites-under-compressive-loa",totalDownloads:1222,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Experimental study on the mechanical behavior of polyphenylene sulfide (PPS)-based composite laminates reinforced with carbon and glass fibers subjected to different strain rates under compression load is reported. Quasi-static tests have been carried out using an electromechanical universal testing machine at three different strain rates, while dynamic tests were done using a split-Hopkinson pressure bar (SHPB) apparatus at two pressure setups in the gas chamber. High-speed imaging system was used to monitor failure process during dynamic test, and these images were used to measure strain by digital image correlation (DIC) in order to compare the DIC-based measurements performed with the SPHPB strain gauges and quasi-static results. Fractography analysis was also performed to identify the main failure mechanisms induced at different strain rates.",signatures:"Carolina Ramirez, Vitor Reis, Carlos Opelt, Rafael Santiago, Facundo Almeraya, Mauricio V. Donadon, Citlalli Gaona, Rene Croche and Miguel Angel Baltazar",downloadPdfUrl:"/chapter/pdf-download/65003",previewPdfUrl:"/chapter/pdf-preview/65003",authors:[null],corrections:null},{id:"63682",title:"Matrix Converter for More Electric Aircraft",doi:"10.5772/intechopen.81056",slug:"matrix-converter-for-more-electric-aircraft",totalDownloads:1170,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"This proposed chapter discusses three methods that do not allow regenerative power from the matrix converter (MC) motor drive onto the aircraft power supply. According to aerospace power quality specifications, the regenerative power must be dissipated in the drive itself to avoid instability problem in aircraft power supply. These are bidirectional switch (BDS) method, input power clamp (IPC) method, and standard clamp circuit (SCC) method for aerospace applications. To identify regeneration in a matrix converter drive, two novel techniques are proposed. These are power comparison technique (PC) and input voltage reference technique (IVR). In both techniques, output power of MC and direction of speed, these factors are used to detect regeneration in MC drive. The electrical braking is important in many aerospace applications such as surface actuation and air-to-air (in-flight) refueling system. Therefore, the inherent regeneration capability of the matrix converter drive is not desirable for aerospace applications so it has to be avoided. The proposed methods are demonstrated through detailed simulation results and experimental verification. In order to prove the proposed methods with novel techniques, a 7.5-kW matrix converter fed 4-kW induction motor (IM) with inertial load has experimentally implemented. The obtained results using BDS method with PC technique proved avoiding regeneration with a matrix converter is feasible. This chapter is valuable for 150-kVA matrix converter for high-power application.",signatures:"Imayavaramban Munuswamy and Patrick W. Wheeler",downloadPdfUrl:"/chapter/pdf-download/63682",previewPdfUrl:"/chapter/pdf-preview/63682",authors:[null],corrections:null},{id:"64742",title:"Turbine Engine Lubricant and Additive Degradation Mechanisms",doi:"10.5772/intechopen.82398",slug:"turbine-engine-lubricant-and-additive-degradation-mechanisms",totalDownloads:1113,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Modern ester based synthetic lubricants have been used in various formulations with anti-oxidants, phosphorus based anti-wear additives and other additives for many years. The physical and chemical properties of both the basestock and additives are known to change through use. Basestocks are normally thought to degrade through various mechanisms, while additive can either degrade or are used as they react when they complete the function that they are added for. In this chapter, the composition of modern turbine engine lubricants and the mechanisms by which the lubricants degrade over time will be examined. Potential changes in bearing materials being evaluated for future engines and the effects of possible new ionic liquids based additives will be will be discussed as they relate to currently used additives. Also included will be a discussion of effects of degradation on the lubricant properties, how the changes affect turbine engines and how the changes can impact human health. These new materials introduce a number of new possible degradation schemes that must be evaluated before the materials enter wide-spread use.",signatures:"David W. Johnson",downloadPdfUrl:"/chapter/pdf-download/64742",previewPdfUrl:"/chapter/pdf-preview/64742",authors:[{id:"178441",title:"Dr.",name:"David",surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"}],corrections:null},{id:"64957",title:"The Evolution of the Composite Fuselage: A Manufacturing Perspective",doi:"10.5772/intechopen.82353",slug:"the-evolution-of-the-composite-fuselage-a-manufacturing-perspective",totalDownloads:4151,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:1,abstract:"A review of critical technologies and manufacturing advances that have enabled the evolution of the composite fuselage is described. The author’s perspective on several development, military, and production programs that have influenced and affected the current state of commercial fuselage production is presented. The enabling technologies and current approaches being used for wide body aircraft fuselage fabrication and the potential reasons why are addressed. Some questions about the future of composite fuselage are posed based on the lessons learned from today and yesterday.",signatures:"Alan Hiken",downloadPdfUrl:"/chapter/pdf-download/64957",previewPdfUrl:"/chapter/pdf-preview/64957",authors:[null],corrections:null},{id:"64528",title:"Robotic Autonomous Spacecraft Missions: Cassini Mission-To-Saturn Example",doi:"10.5772/intechopen.82161",slug:"robotic-autonomous-spacecraft-missions-cassini-mission-to-saturn-example",totalDownloads:982,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Robotic interplanetary spacecraft sent to the outer planets of our solar system face many challenges: maintaining internal health and functionality of spacecraft subsystems handling material stresses from solar heating close to Earth, the cold of deep space once the destination is reached, solar radiation and bombardment of cosmic rays; maintaining adequate power to support engineering devices and science instruments; handling time-critical onboard faults in the presence of the long round-trip light time; and preserving one-time “crucial event” activities such as moon/planet flybys, deployment of the probe, and selected science targets. As an example, this chapter details the strategy implemented on the Cassini Mission-to-Saturn spacecraft, how its onboard subsystems are protected and maintained, the advantage of automated onboard fault protection monitor/response routines, protocols implemented to preclude human error in uplinked sequences, and updating onboard flight software as new discoveries are uncovered about the adverse flight environment, so that mission objectives are met under the presence of an ever-increasing delay between ground issued commands and the Cassini spacecraft as it approaches the Saturnian system, safeguarding planetary protection constraints as the spacecraft was deposited into the planet in a final fiery plunge.",signatures:"Paula S. Morgan",downloadPdfUrl:"/chapter/pdf-download/64528",previewPdfUrl:"/chapter/pdf-preview/64528",authors:[{id:"110221",title:"Dr.",name:"Paula",surname:"Morgan",slug:"paula-morgan",fullName:"Paula Morgan"}],corrections:null},{id:"64840",title:"Advanced Nonlinear Modeling of Gas Turbine Dynamics",doi:"10.5772/intechopen.82015",slug:"advanced-nonlinear-modeling-of-gas-turbine-dynamics",totalDownloads:1340,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The process of gas turbine development requires different mathematical models. In particular, physics-based nonlinear dynamic models are widely used in the development of control and diagnostic systems. The present chapter firstly reviews known works on nonlinear dynamic engine modeling centering on model applications and developments. As an important development, modeling of heating up engine components is considered. This phenomenon consists in a radial clearance change during transients that influences engine static and dynamic performances. This clearance change is usually computed by a finite element method that is critical to computer resources. The chapter secondly presents a new and more rapid simulation methodology to integrate two dynamic processes, a general engine transient and a clearance change. This allows creating a more accurate and relatively fast engine dynamic model that is easy to use in the design of control and diagnostic systems. Finally, the chapter introduces further methodology enhancement consisting in the consideration of the influence of varying metal temperature on the strains induced by mechanical loads. To validate methodology, it is applied to a particular turbofan engine, and the simulated and real engine dynamic performances are compared.",signatures:"Roman L. Zelenskyi, Sergiy V. Yepifanov and Igor Loboda",downloadPdfUrl:"/chapter/pdf-download/64840",previewPdfUrl:"/chapter/pdf-preview/64840",authors:[null],corrections:null},{id:"63715",title:"Effect of Microstructure on Microhardness and Electrochemical Behavior in Hypereutectic Al-Fe Alloy Processed by Laser Surface Remelting",doi:"10.5772/intechopen.81095",slug:"effect-of-microstructure-on-microhardness-and-electrochemical-behavior-in-hypereutectic-al-fe-alloy-",totalDownloads:740,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"An analysis was made of microstructure of hypereutectic Al-2.0 wt.% Fe alloy treated by laser surface remelting (LSR), microhardness test, and electrochemical behavior test and their numerical simulation was done. Microstructure was analyzed by optical microscopy, field-emission scanning electron microscopy and Vickers microhardness tests. Results obtained in this study indicate in LSR-treatment occurred rapid heating and followed by rapid cooling, resulting in formation of a thin recast layer with a refined microstructure, with dissolution of precipitates and inclusions and formation of metastable phases, however, an overlapping line on consecutive weld fillets was observed. Furthermore, analysis of Vickers hardness were done in the cross-sectional area of treated sample and on the treated sample surface, therefore, result a greater microhardness of the treated region than untreated substrate. Through the electrochemical impedance spectroscopy (EIS) test, laser surface remelting-treated workpiece exhibit higher polarization resistance than untreated, at 11 times higher and capacitive behavior of material is related to aluminum oxide layer properties, then, microstructure characteristic caused by overlapping ratio and multi-track has a strong effect on electrochemical process.",signatures:"Moises Meza Pariona and Katieli Tives Micene",downloadPdfUrl:"/chapter/pdf-download/63715",previewPdfUrl:"/chapter/pdf-preview/63715",authors:[null],corrections:null},{id:"64541",title:"Optimal Control of Fuzzy Systems with Application to Rigid Body Attitude Control",doi:"10.5772/intechopen.82181",slug:"optimal-control-of-fuzzy-systems-with-application-to-rigid-body-attitude-control",totalDownloads:839,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, the author presents a theoretical result on the optimal control of nonlinear dynamic systems. In this theoretical result, the author presents the optimal control problem for nonlinear dynamic systems and shows that this problem can be solved by utilizing the dynamic programming approach and the inverse optimal approach. The author employs the dynamic programming approach to derive the Hamilton-Jacobi-Bellman (H-J-B) equation associated with the optimal control problem for nonlinear dynamic systems. Then, the author presents an analytic way to solve the H-J-B equation with the help of the inverse optimal approach. Based on the theoretical result presented in this chapter, the author establishes an optimal control design for TS-type fuzzy systems that guarantees the global asymptotic stability of an equilibrium point and the optimality with respect to a cost function and provides good convergence rates of state trajectories to an equilibrium point. The author considers the three-axis attitude stabilization problem of a rigid body to illustrate the optimal control design method for TS-type fuzzy systems. The author designs the optimal three-axis attitude stabilizing control law for a rigid body based on this optimal control design method and analyzes its control performance by numerical simulations.",signatures:"Yonmook Park",downloadPdfUrl:"/chapter/pdf-download/64541",previewPdfUrl:"/chapter/pdf-preview/64541",authors:[{id:"2861",title:"Dr.",name:"Yonmook",surname:"Park",slug:"yonmook-park",fullName:"Yonmook Park"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6003",title:"Robotics",subtitle:"Legal, Ethical and Socioeconomic Impacts",isOpenForSubmission:!1,hash:"15ab11f5bb5aac89956dd8b42f261011",slug:"robotics-legal-ethical-and-socioeconomic-impacts",bookSignature:"George Dekoulis",coverURL:"https://cdn.intechopen.com/books/images_new/6003.jpg",editedByType:"Edited 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Through pulse palpation at three locations, i.e. cun, guan and chi, on both wrists, general health condition of a person and a particular organ can be fully recognized. Figure 1 illustrates the locations and their corresponding organs. tcm doctor is used to combine clinical data collected from pulse assessment and other clinical assessments to prescribe treatments to his patient and monitor his prognosis.
Distribution of organs at the six locations (Adapted from [
In view of the increasing popularity of tcm world wide, tcm pulse diagnosis has received much attention from the public concerning its scientific and clinical values. Much research work has been published since 1950s’ to quantify tcm pulse diagnosis which aims at providing scientific base to tcm pulse diagnosis and so substantiating its clinical value. The aim of this review is to provide readers with a complete picture of current progression of tcm pulse quantification.
After reading this chapter, readers should be able to
acquire up-to-date scientific evidence on tcm pulse diagnosis quantification;
analyze strengths and weaknesses of current studies in terms of methodologies and statistical approaches; and
highlight future direction of tcm pulse diagnosis quantification.
The review is divided into five sections. The first three sections discuss and analyze qualification and quantification of tcm pulse diagnosis in ancient and recent literatures. Statistical approaches to quantify tcm pulse diagnosis are discussed. Section four presents a tcm pulse diagnostic framework proposed by the author in 2010 to illustrate the interrelationship of pulse conditions and arterial pulse. The last section highlights limitations of current studies and recommendations are suggested accordingly.
Qualification of tcm pulse diagnosis means the elements that tcm pulse diagnosis should be included in order to have a complete and valid assessment on tcm pulse. Literatures show that there is much confusion about the assessment of pulse in tcm, mainly due to the ambiguous descriptions of pulse condition in Chinese medical texts [1].
Pulse itself is objective, but pulse condition is subjective. It is the quality of pulse as felt by a tcm doctor, and thus represents the subjective judgment of that doctor. More than 30 pulse conditions have been documented in Chinese medical texts. Some of them, e.g. floating, rapid, string-like are single pulse condition which describes one element of a pulse condition. Others describe more than one element of a pulse condition which is called compound pulse condition. For example, replete is the composite of forceful, long, large and stiff [2].
Nei Jing [3] describes over 30 types, e.g. large, small, long, short, slippery, rough, sunken, slow, rapid, strong, tough, soft, moderate, hurried, vacuous, replete, scattered, intermittent, fine, and weak. Mai Jing [4] documents 24 types which are floating, sunken, hollow, large, small, skipping, tight, rapid, stirred, slippery, weak, string-like, faint, soft, dissipated, moderate, slow, bound, drumskin, replete, intermittent, vacuous, rough and hidden. The 28 pulse conditions most commonly used in clinical practice come from Bin Hu Mai Xue [5] and Zhen Jia Zhen Gyan [6]. They are floating, sunken, slow, rapid, surging, fine, vacuous, replete, long, short, slippery, rough, string-like, tight, soggy, moderate, faint, weak, dissipated, hollow, drumskin, firm, hidden, stirred, intermittent, bound, skipping, and racing.
Descriptions of pulse conditions in Chinese medical texts are mostly qualitative, and are often illustrated by similes and poems. For instance, the slippery is compared to “beads rolling” and the string-like is like pressing the string of a musical instrument [5]. A few of the descriptions, such as the rapid, the slow, the floating, and the sunken, are quantitative. The rapid and the slow describe the rate of a pulse, and can be quantified by the number of beats per breath. The floating and the sunken describe the depth of a pulse, and can be quantified by shu, the unit of weight used during the Warring States period (403-221BC) of ancient China, with floating corresponding to three shu and sunken nine shu [7].
Using analogies and poems to describe pulse condition is subject to the interpretation of the tcm doctor. For example, the string-like may be described as like pressing the string of a musical instrument and the tight as like pressing a rope, but the feeling of a string or a rope depends on the sensitivity of one’s fingers. Qualifying words such as “a bit,” “average,” and “very” are used to describe the intensity of a pulse. For example, the difference between the fine and the faint is that the fine is a little bit stronger than the faint. “A little” is countable, but cannot precisely determine how much of this “little” differentiates the fine from the faint.
Descriptions of pulse conditions also overlap [8,9]. Some pulse conditions describe a single dimension of pulse. The floating, for example, describes the depth of a pulse, whereas the rapid describes the rate of a pulse. Others describe two or more dimensions. The firm means string-like, long, replete, surging, and sunken, whereas the drumskin is string-like, large, rapid, and hollow. The number of dimensions that a pulse assessment should encompass is controversial. Floating or sunken and slow or rapid are the two pairs of dimensions suggested in Bin Hu Mai Xue [5]. Nan Jing [7] and Mai Jing [4], in contrast, proposed three dimensions: floating or sunken, slippery or rough, and long or short. Nei Jing [3] described three dimensions: slippery or rough, slow or rapid, and surging or fine, whereas [2] suggested floating or sunken, slow or rapid, and vacuous or replete.
It is suggested that there are two reasons for the obscurity of descriptions of pulse condition. First, tcm doctors are accustomed to assessing pulse by their own perception, rather than on a rational basis [10]. Second, there are no concise and precise standards to guide tcm doctors in the diagnosis of pulse condition. It is likely that these two reasons are the causes of the low inter-rater and intra-rater reliability of pulse diagnosis by tcm doctors found by Craddock (1997) and Krass (1990) (as cited in [11]). As evidence-based practice emphasizes consistency of outcome [12], the low reliability of pulse diagnosis by tcm doctors reported in the literature demonstrates the need to standardize pulse diagnosis in tcm.
Zhou Xuehai’s (1856-1906) early attempt to standardize pulse condition is a milestone in the quantification of tcm pulse diagnosis. He proposed that each pulse condition should have four elements. “Wei Shu Xing Shi Zhe, Zheng Mai Zhi Ti Wang. Qiu Ming Mai Li Zhe, Xu Xian Jiang Wei Shu Xing Shi Jiang De Zhen Qie, Ge Zhong Mai Xiang Liao Ran, Bu Bi Ju Ni Mai Ming” (as cited in [13], p. 31). He explicitly stated that position, frequency, shape, and trend are the four main elements of pulse condition, and that each pulse condition description should contain these four elements.
Various scholars have elaborated on this idea [2,14-18], and have extended the original four elements to eight: depth, rate, regularity, width, length, smoothness, stiffness, and strength. Each pulse condition should contain these eight elements with different intensities [2,15,17,18].
Rate is the number of beats per breath. The definition of regularity is similar to that in modern medicine, it describes rhythm of a pulse condition. Rate and regularity gives information on the nature of a disease, whether heat or cold [19]. Depth is defined as the vertical position of a pulse, and indicates the location of a disease, whether interior or exterior [19]. Width and length describe the shape of a pulse, where width is defined as the intensity of a pulsation and length is defined as the range in which the pulsation can be sensed across the cun, guan, and chi [2]. Smoothness is defined as the slickness of a pulse, stiffness is defined as the sensation of arterial elasticity, and strength is defined as the change in forcefulness of a pulse in response to a change of applied pressure [19]. Width, length, smoothness, stiffness, and strength also describe the interaction of a pathogen and healthy qi in the body [2]. The eight elements thus provide a basis for qualifying pulse condition.
King et al. (2002) [11] developed a measurement scale to standardize tcm pulse diagnosis. However, their scale does not reflect pulse condition adequately for several reasons. First, the six items included in the scale –depth, width, force, relative force, rhythm, and pulse occlusion –are not widely accepted as core items in tcm pulse diagnosis. Appropriate rating scales should include the six locations, as a complete tcm pulse diagnosis must include the eight elements at the six locations. Second, the definitions of the items are abstract. For example, force is defined as the overall intensity of a pulse and relative force is defined as a subtler version with overall force. Third, the scale is an ordinal scale that is anchored with descriptors to measure the items. For example, depth is measured at three levels: superficial, middle, and deep. However, an ordinal scale is not a sufficiently sensitive measure, as there are an insufficient number of available response categories to rate the items [20], and the words used to describe each ordinal level are not universal. Further, as the items have not been well quantified, using an ordinal scale would not reflect the actual sensation perceived by a tcm doctor.
To explore the uniqueness of each of the eight elements in tcm pulse diagnosis, Tang (2010) [21] used principal component analysis to explore the uniqueness of each of the eight elements in tcm pulse diagnosis. The result demonstrated that rate, regularity, width and smoothness represented four unique dimensions while it was not the case for depth, length, stiffness and strength.
The author believes that an appropriate content and rating scale must be chosen to measure pulse condition which should be relevant and should adhere to the fundamental concepts of pulse diagnosis in tcm. Since only a handful of studies have been conducted to qualify pulse condition, a rating scale which can genuinely reflect the sensation of pulse perceived by a tcm doctor should be used to minimize the influence of subjective judgment on a rating scale at a preliminary stage of qualification.
In the qualification of pulse condition, the eight elements are measured unidimensionally. It is hypothesized that the eight elements are related to the arterial pressure waveform and that their intensity is a composite of the physical parameters of the arterial pressure waveform. Relating the eight elements to these physical parameters would thus make them quantitively measurable. Much research has been carried out on the quantification of pulse condition. Measurement of the arterial pressure waveform in the time domain and frequency domain are the two main approaches currently used, but due to the disparity of research aims, methodologies, and statistical approaches, the results of existing studies in this area are incomparable.
The time domain is widely used in cardiovascular research [22] and is also popularly used in the quantification of pulse condition [23]. Time domain analysis looks at the arterial pressure waveform with respect to time, and a time domain graph shows how the arterial pressure waveform changes over time. Figure 2 shows a typical arterial pressure waveform.
A typical arterial pressure waveform (Adapted from [
In time domain, researchers extracted physical parameters from the arterial pressure waveform, such as h1, h3, and generate new parameters from them. Yoon et al. (2000) [24] proposed three parameters to measure depth, width, and strength. Depth was measured by the hold-down pressure with the relatively largest h1 (Pamax). The maximum average h1 (h1) was used to quantify width, and strength was measured by the pressure difference at the 80% maximum average h1 (Δ80%pamax). These three parameters have gained some acceptance as standard parameters for the measurement of depth, width, and strength [2,14].
The advantage of using the time domain for the quantification of pulse condition is that most of the physical parameters related to it have physiological meanings. Exploring their relationship with the eight elements should thus help to understand the elements from a modern medical perspective.
Many studies have demonstrated the association between the physical parameters of the arterial pressure waveform in time domain and the eight elements [2,13,24-31]. Depth has been associated with pamax, rate with t, and regularity with the interval between two individual arterial pressure waveforms and the consistency of the contour of the waveforms. Width has been associated with h4/h1, t1, and h1. The surging has been found to have a smaller h4/h1 and t1 and a larger h1. Length has been associated with h1 at cun, guan, and chi. The short was observed to have small h1, although association with the other physical parameters in the arterial pressure waveform was indiscernible. Smoothness has been related to W/t, h4/h1, t1, h5, and h5/h1. A smaller h4/h1 and a larger h5 have been observed for the slippery, and h3/h1, h4/h1, and h5/h1 are associated with stiffness. A larger h3/h1 and h4/h1, and a smaller h5/h1 have been observed for the string-like. Four types of arterial pressure waveform have been identified for the string-like: lower h1 than h3, h3 equal to h1, h3 higher than h1, and h3 merged with h1. Strength is associated with a Δ80% pamax. Some of these observations have been explained in terms of hemodynamic, For example, the string-like was found to be caused by an increase in arterial stiffness and peripheral resistance, whereas width was determined by blood velocity, cardiac output, peripheral resistance, the diameter of the radial artery, and the spatial movement of the radial artery. Length has been related to the rate of arterial dilatation.
The incongruence of the results of these studies means that their postulations cannot be substantiated. Fei (2003) [2] reported that the superficial and deep levels of depth ranged from 25 to 175g and 100 to 250g, respectively. According to Xu et al. (2003) [27], the range of the superficial, middle, and deep levels was smaller than 100g, 100-200g, and greater than 200g, respectively. In these studies, depth is reported as a unit of force, whereas in other studies report as a unit of pressure [25,26]. Huang and Sun (1995) [26] reported that the superficial, middle, and deep levels ranged from 10 to 40 mmHg, from 50 to 80 mmHg, and 90-120 mmHg respectively, whereas Chen (2008) [25] reported ranges of 89.8 to 157.7 mmHg, 151.9 to 222.9 mmHg, and 279.3 mmHg for the superficial, middle, and deep levels, respectively. In terms of smoothness, Huang and Sun (1995) [26] characterized the slippery as having t1 within the range of 0.07 to 0.09s, h5 larger than 2 mm, obvious h3, and h4/h1 smaller than 0.50, whereas Fei (2003) [2] found that the slippery was characterized as having W/t smaller than 0.20, an h4/h1 smaller than 0.40, and h5/h1larger than 0.10.
There appear to be four reasons for such inconsistency. First, none of the studies reports the surface area of the sensor used. As force varies with the surface area of a sensor with the same hold-down pressure, the lack of this information makes the results incomparable. Second, the characteristics of the subjects in the studies may have affected the results. Age, gender, and weight are all factors that affect pulse condition [2,26], yet these studies report no demographic data on the subjects. Hence, it is not possible to rule out that the incongruence is due to the diversity of the subjects. Third, there is no protocol that standardizes the pulse acquisition procedure, and few of the studies reported the procedure that they used to acquire the waveform. To mimic a tcm pulse assessment, the arterial pressure waveform is acquired with different hold-down pressure applied to the radial artery. Two procedures for pulse acquisition are known. Huang (2007) [13] developed a formula to calculate how much hold-down pressure should be used for the superficial, middle, deep, and hidden levels of depth in women and men. He also proposed that the ratio of actual body weight over ideal body weight is the determinant of the hold-down pressure (Table 1).
Superficial | Middle | Deep | Hidden | |
< 0.8 | 50g | 100g | 200g | 300g |
0.8 – 1.0 | 70g | 130g | 250g | 400g |
1.0 – 1.2 | 100g | 180g | 300g | 450g |
"/> 1.2 | 150g | 230g | 350g | 550g |
Weight ratio and corresponding hold-down pressure
Although several studies have adopted this protocol to acquire the waveform [28,32,33], the rationale for quantifying depth in this way is not explicated, and its credibility is thus suspect. The other procedure is that of Fei (2003) [2], who applied pressure from 0 g to 250 g at 50g intervals for each pulse acquisition. However, the interval of 50 g may be too wide, and does not allow for any change in the waveform within this interval.
Fourth, there is no standard measurement for the eight elements. The majority of the aforementioned studies focused on pulse condition rather than the eight elements. However, as each pulse condition embraces all eight elements with different intensities, even if the other seven elements have the same intensity, variation in one element will lead to a different waveform for the same pulse condition. Moreover, the sensation of a tcm doctor to the eight elements has not been standardized, and variation among the tcm doctors participating in the studies will inevitably have led to different results.
The frequency domain can be used to analyze pulse condition based on the energy distribution of the arterial pressure waveform [34]. A frequency domain graph comprises two parts –amplitude versus frequency and phase versus frequency – and is converted from the time domain of the arterial pressure waveform using a transform, which is a pair of mathematical operators used to carry out a conversion. Fast Fourier transform is an example of a commonly used transform in signal processing. Usually, the amplitude versus frequency graph is examined in studies of pulse condition. A graph showing only the amplitude and frequency is called a power spectrum (Figure 3).
Example of a power spectrum (Adapted from [
The y-axis of a power spectrum graph, which is labelled “amplitude” represents the power of the frequency, whereas the x-axis shows the “frequency” in Hertz (Hz). A harmonic is the frequency component of an arterial pressure waveform.
The majority of the studies that use the frequency domain to analyze the arterial pulse have focused on differentiating diseases [35-37], examining the power spectrum in relation to the meridians [38,39], and investigating the relationship among disease, syndrome, and channels [23,40-43,45]. Only a few studies have explored the characteristics of the power spectrum for different pulse conditions [46,47].
Wang and Xiang (1998) [46] discovered that the power spectrum differed markedly for the normal, the slippery, the string-like, and the slow-intermittent. In general, the power spectrum of all pulse conditions decreased with increasing frequency and the frequency range was within 0 to 40Hz. However, the power spectrum of the normal was smoother than that of the other three pulse conditions. The slippery had more than ten harmonics, whereas the normal had eight harmonics. The string-like and the slow-intermittent had three to five harmonics. The frequency of the normal was distributed within the 25Hz range. The percentage of energy distributed below 10Hz was 99% for the normal and 97% for the string-like, and that distributed below 5Hz was 90.2% for the moderate, 83.7% for the slippery, and 60.9% for the string-like. Forty-five percent of the energy was distributed below 1 Hz for the moderate and 16% for the string-like. These findings suggest that the frequency of the normal falls within the 1 to 5Hz range, and those frequencies below 1 Hz and over 10 Hz may indicate illness. Xu et al. (2002) [47] suggested that counting the number of harmonics in the power spectrum could be used to differentiate pulse conditions. Their study reported that the slippery possessed three main harmonics that were much higher than those of the normal, and the drumskin had two main harmonics. The amplitude of the harmonics in the normal decreased with increasing frequency. The reasons for the different results for the slippery are the same as those proposed for the time domain quantification.
Both the time domain and frequency domain are based on the arterial pressure waveform, but differ in the way in which they interpret it. Although the available evidence supporting the applicability of the frequency domain to quantify pulse condition is weaker than that supporting the use of the time domain, this may simply due be to the lack of studies on the frequency domain. However, the time domain is to a certain extent more advantageous than the frequency domain for quantifying pulse condition because the physical parameters in the time domain have physiological meanings, which means that the physiological implications of the eight elements could be revealed if their relationship with these physical parameters were traced. It is thus more prudent and beneficial to adopt the time domain in the quantification of pulse condition.
Though regression analysis is commonly used in medical research for function approximation and classification [48,49], failure of modelling the relationship of the eight elements and the physical parameters [21] suggested that the relationship is not linear. It has been suggested that more advanced statistical techniques, such as fuzzy inference and artificial neural network (ANN) may be more appropriate for modelling the relationship of the eight elements at the six locations and the physical parameters [50-52].
Fuzzy inference is a modelling technique that is based on fuzzy set theory. Fuzzy set theory deals with the degree of truth in a vaguely defined set, where truth is represented as a value that ranges from 0 to 1. Lee et al. (1993) [53] used fuzzy inference to assess the health state of a subject with renal problems before and after taking herbal medicine. The arterial pressure waveform was acquired at the right chi, and the physical parameters in the time domain were used to construct the fuzzy model. The results showed that the model could successfully predict the prognosis for a patient. The authors thus proposed applying fuzzy inference to assess health status using pulse condition.
ANN is a nonlinear statistical modelling technique commonly used in the modelling of complex nonlinear relationships among independent variables and dependent variables [49,54]. It resembles regression analysis, but has much more flexibility because it is not restricted by any statistical assumptions or prespecified algorithms. In other words, ANN is a self-adaptive and data-driven modelling technique [54,55]. The presence of hidden layers in the network greatly increases its capacity to deal with various complicated relationship. Figure 4 shows the basic architecture of an ANN.
Basic architecture of an ANN (Adapted from [
The architecture shown in Figure 4 is commonly used in the type of ANN known as a multilayer perceptron. This consists of an input layer, a hidden layer, and an output layer. The input layer and output layer also appear in the architecture of linear regression, but the distinguishing characteristic of an ANN is the hidden layer in between the input and output layers. The number of hidden layers can be manipulated by the researcher until a satisfactory result is obtained. The input layer contains input neurons, which represent the number of independent variables in the study. The output neurons in the output layer are the dependent variables. The number of hidden neurons in the hidden layer(s) and the number of hidden layers in the model are determined by trial and error using the sum-squared error in function approximation and the cross entropy function in classification. The cross entropy function can be regarded as analogous to the likelihood function in logistic regression [54]. They are the cost functions that determine when to stop training the model.
Backpropagation is the most popular training algorithm for ANNs. This utilizes the steepest gradient descent in a multilayer perceptron to minimize the sum-squared error. The steepest gradient descent is a mathematical algorithm that locates the local minimum of a function by taking steps proportional to the negative of the gradient of the function at the current point. In backpropagation, the weights of the hidden and input neurons are modified according to the sum-squared error fed back from the output neurons until the mean squared error is minimized.
Wang and Xiang (2001) [57] compared the accuracy of fuzzy inference and ANN in predicting pulse condition. They reported the successful application of ANN in identifying the normal, the string-like, the slippery, and the fine, and showed that ANN had a 87% predictive accuracy, which was 12% higher than that of fuzzy inference. Xu et al. (2007) [58] compared the predictive accuracy of traditional ANN and fuzzy neural network in predicting eight pulse conditions. Three traditional ANNs using backpropagation were developed, each of which had 3 layers: an input layer, a hidden layer, and an output layer. The input neurons were seventeen physical parameters of the arterial pressure waveform in the time domain and the output neurons were the eight pulse conditions, which were, however, not specified. The numbers of hidden neurons used in the three traditional ANNs were 10, 15, and 20. The fuzzy neural network was a composite of four sub-fuzzy neural networks, and was used to model seventeen physical parameters and the four elements (position, frequency, shape and trend) proposed by Zhou Xuehai (1856-1906) (as cited in [13]) separately. The four sub-fuzzy neural networks were then combined to predict the eight pulse conditions. The three traditional ANNs obtained 86-88% accuracy, but the fuzzy neural network outperformed these networks by 4%. They concluded that it was beneficial to combine fuzzy inference and ANN to quantify pulse conditions.
The successful application of these advanced statistical techniques for quantifying pulse conditions is encouraging, and at least indicates that the various pulse conditions have a physiological basis. However, medical research emphasizes the explanatory power of a model, and values statistical techniques with a high explanatory power [59-61]. According to these criteria, ANN can be condemned as black box [49], which means that the internal knowledge of the system cannot be readily known by researchers [59].
A dice model has been formulated by Tang (2010) [21] to explain the interconnection and interrelation between the arterial pulse and the eight elements of pulse condition at the six locations, and between the eight elements at the six locations and health status in tcm. This framework serves as the backbone to quantify tcm pulse diagnosis.
The dice model comprises two levels. Level one includes the arterial pulse and the eight elements at the six locations, and level two covers the eight elements at the six locations and health status in tcm. More specifically, level one deals with the sensation of the arterial pulse as perceived by a tcm doctor, and level two gives an interpretation of the eight elements at the six locations to determine health status. These two concepts are interconnected. The symbolic meaning of a dice and a dice roll with respect to the arterial pulse and the health status in tcm are explicated below.
It is postulated that the eight elements are influenced by the arterial pulse at the six locations (left and right cun, guan, and chi). Depth, rate, regularity, width, length, smoothness, stiffness, and strength are the eight elements of pulse condition at the six locations. The intensity of each element is determined by the sensation of the arterial pulse perceived by a tcm doctor. Thus, the eight elements at the six locations are operationalized as a rating along a continuum with Yin and Yang at the extremes.
Specifically, depth is operationalized as the vertical position of the arterial pulse, and is rated along a continuum with the deepest being Yin and the most floating being Yang. Rate is the number of beats in a minute, with the slowest being Yin and the most rapid being Yang. Regularity is the rhythm of the arterial pulse, which is categorized as either regular or irregular. Width is the intensity of the arterial pulse, with the smallest being Yin and the largest being Yang. Length is the range of the arterial pulse that can be sensed across cun, guan, and chi, with the shortest being Yin and the longest being Yang. Smoothness is the slickness of the arterial pulse, where the roughest is Yin and the smoothest is Yang. Stiffness is the elasticity of the radial artery, with the least stiff being Yin and the stiffest being Yang. Finally, strength is the forcefulness of the arterial pulse relative to the change in pressure applied by a tcm doctor, with the least forceful being Yin and the most forceful being Yang.
In tcm pulse diagnosis, health status is determined by the pulse condition at the six locations, with each location reflecting the health status of a specific organ. Left cun, guan, and chi reflect the health status of the heart, the liver, and the kidneys, whereas right cun, guan, and chi reflect the health status of the lungs, the spleen, and the kidneys (lifegate). The eight elements are the assessment criteria for the health status of the organs. Health status is the outcome measure of tcm pulse diagnosis, and is a composite measure of the health status of the organs.
In the model, a dice is used to embody the intertwining and cascading relationship among the arterial pulse, the eight elements at the six locations, and health status (Figure 5). Figure 5 shows a diagrammatic presentation of the dice model.
The dice model is formulated under three assumptions. The first is that the eight elements carry the same weight in the assessment of overall pulse condition. Second, the mid-point along a continuum indicates the balance of Yin and Yang. Third, the six locations have the same weight in determining health status.
The dice is analogous to the concept of health in tcm. Health is perceived as the balance of Yin and Yang, which in turn relies on the individual functioning and interaction of the organs. The six pyramids that make up a dice are thus analogous to the organs at the six locations.
The inside of the dice represents the blood flow within the organs, the combination of which constitutes the arterial pulse. Hence, any change in the blood flow from any of the organs is reflected in the arterial pulse. By assessing the six pyramids, the health status of the organs and thus overall health status can be revealed.
The dice model
As has been stated, the six pyramids represent the six locations where the pulse is assessed by a tcm doctor. The lungs and the heart, the liver and the spleen, the kidneys and the lifegate are arranged in opposite pyramids according to their role in overall health. This arrangement is based on the notion that left cun, guan, and chi assess the blood, which is Yin in nature, whereas right cun, guan, and chi assess qi, which is Yang in nature. The position of the organs arranged in the dice thus adheres to Yin Yang theory.
Each pyramid is made up of the eight elements. The enlarged square to the lower right of Figure 5 shows the interrelation of the eight elements. Each element is a complementary Yin-Yang pair. According to Yin Yang theory, Yin always represents the inside and Yang the outside. Thus, the black square indicating the Yin nature of the elements is the core of the pyramid, and the white square indicating their Yang nature is the outer part of the pyramid.
The intensity of the eight elements depends on the arterial pulse. The combined intensity of the eight elements thus indicates the health status of the organ denoted by that pyramid.
The dice model of tcm pulse diagnosis is inspired by the Taiji symbol. The dotted line that links the six pyramids together symbolizes the interchanging and dynamic relationship among the organs. In the model, the Yin and Yang of each element, the eight elements in each pyramids, and the six pyramids of the dice are connected with dotted lines, which means that they are Yin and Yang composites and are always interchanging and balancing one another. The solid outline of the dice represents the absolute of health, just as the Taiji circle represents the world. Health is not expandable or reducible: it is only the health status that can be altered, which is determined by the interaction of Yin and Yang in the body.
To further elaborate the dice model, a roll of the dice is taken as analogous to health status. With a balanced or “fair” dice, the probability of rolling each pyramid is equal, because the areas and weights of the pyramids are identical. A “fair” dice is thus analogous to a healthy status, in which the blood flow within the organs is normal, the wave reflection and wave resonance occur in the proper way, the intensity of the eight elements is around the mid-point of the continuum and forms a regular shape in the middle of the pyramid, and the six pyramids are equal and balanced. Yin and Yang are balanced and harmony is attained.
However, if any one of the pyramids is intentionally altered in terms of its area or weight, then the dice is no longer “fair” and can be called a loaded dice. With a loaded dice, the probability of rolling each pyramid is unequal, and varies with the area and weight of the pyramids. A loaded dice is analogous to an unhealthy status, in which the abnormal functioning of any of the organs affects the wave reflection and wave resonance within the circulatory system, blood flow is altered, and thus the weight of the pyramid representing that organ is altered. The arterial pulse changes in accordance with the health status of the organ, and thus the intensity of the eight elements also changes. The pyramid formed by the eight elements is no longer regular, but is smaller or larger and skewed. An imbalance thus occurs in the six pyramids, Yin and Yang are imbalanced, and health is compromised.
Several works have been done to verify the hypotheses of the framework. Tang et al. (2012) [62] conducted a study to validate the content and diagnostic ability of the framework. Content validation index was 0.73 which was acceptable. And the criterion validation was conducted by comparing the accuracy, sensitivity and specificity of the models generated by artificial neural networks. About 80% accuracy was attained among all ANN models. Their specificity and sensitivity carried, ranging from 70% to nearly 90%. It suggested that the tcm pulse diagnostic framework was valid in terms of its content and diagnostic ability.
Tang et al. (2012) [63] reported that the nonlinear relationship of the eight elements at the six locations and the physical parameters in time domain were successfully established by Levenberg-Marquardt algorithm with an r-squared ranged from 0.60-0.86.
The tcm pulse diagnostic framework is a novel direction suggested by Tang (2010) [21] to guide tcm pulse diagnostic quantification. Despite studies [62,63] have been conducted to verify the hypotheses in the framework, the results were preliminary and yet verified the framework fully. Much more effort has to be made in the future. This session highlights limitations of the studies and corresponding recommendations are given.
tcm doctors usually assess pulse at the six locations both individually and simultaneously. However, pulse acquisition device used was usually a single-probe type, as no validated three-sensor pulse acquisition device is available, and the arterial pressure waveforms could only be acquired one at a time. Thus, the simultaneous manipulation of pulse at the six locations carried out in a typical tcm pulse diagnosis could not be examined.
The pulse acquisition process was fairly long at about one hour as reported by [62], [63], which may have provoked motion artifacts in the subjects that affected the quality of the arterial pressure waveforms acquired. Also, the baseline of the arterial pressure waveform fluctuated due to the movement and breathing pattern of the subjects, and the feature extraction program was insufficiently developed to remove this noise from the waveforms. The rescaling of the fluctuating baseline into a horizon would have distorted the arterial pressure waveform and introduced errors into the features extracted. One of the physical parameters, peak-to-peak interval, could not be extracted by the program and thus could not be used in the modelling. Further, the pulse acquisition device limited the hold-down pressure to a maximum of 400 mmHg, but the amplitude of the arterial pressure waveform did not decrease in some of the subjects, and thus ∆80%pamax could not be calculated.
Another limitation is about characteristics of the subject recruited. Those subjects recruitment in [62], [63] were rather stable, the intensity of the eight elements was therefore confined to a narrow range, and such homogeneity in the samples may have lowered the r-squared.
ANN was suggested to verify the relationships in the framework because of their nonlinear nature. There are several limitations with this approach needed to be overcome. First, the sample size required by the ANN was too large to be recruited in a clinical study, and the smaller sample size used may have lowered the effect size of the models. Second, as mentioned before, the low explanatory power of ANN does not allow researchers to fully analyzing the models generated.
In view of the limitations of the studies, five recommendations are made for further studies in this area.
It is suggested that a validated three-sensor pulse acquisition device be developed so that the effect of simultaneous hold-down pressure on the arterial pressure waveforms at cun, guan, and chi can be examined. Also, the feature extraction program requires further enhancement to extract all of the necessary features from the arterial pressure waveform. The development of the feature extraction program is a major part of the study because the physical parameters are calculated based on the features extracted by the program.
A program should be generated that can extract the underlying relationships among the physical parameters and the eight elements at the six locations and the relationships among the eight elements at the six locations and health status. Increasing the explanatory power of the models in this way would provide modern scientific theoretical backing for tcm pulse diagnosis and more evidence to support tcm theories.
Another suggestion is on subject recruitment. More diverse subjects should be recruited to verify the models. The models established are preliminary models that demonstrate the nonlinearity of the physical parameters and the eight elements, but a larger sample is required to validate them fully. As those studies recruited subjects with stable hypertension, the models cannot be extrapolated to patients with severe hypertension or hypotension. It is thus recommended to recruit subjects with severe hypertension or hypotension in future studies to increase the generalizability of the models. In addition, patients with other diseases should also be recruited to examine the models’ ability to differentiate hypertension from other diseases.
Polyvinylpyrrolidone (PVP) is widely employed as a multifunctional material and it was approved by the US Food and Drug Administration as a safe polymer for biological experiments due to its simple processability, biocompatibility, and non-antigenicity [1, 2]. The biomedical and pharmaceutical fields are among the most explored (Figure 1). Recently, PVP is considered as the most promising polymers, not only for the development of new pharmaceutical formulations [3, 4] but also for the optimization of several properties of bioactive glasses [2, 5]. This chapter highlights the link between PVP and some bioactive glasses. The multifunctional roles of PVP in pharmaceutical field were also discussed, focusing on the effect of PVP in terms of physical stabilization and solubility enhancement of various drug formulations in solid state (milling method as example).
Schematic representations of various PVP applications [
PVP was largely employed as a reinforcing material for biocomposites in a variety of applications, including bone tissue engineering, soft implants, biosensors, and artificial cartilage substitutes [2]. PVP can also be used in the fabrication of PVA hydrogels-based composite scaffolds for bone tissue engineering [6].
Cheng et al. have shown that, in the case of bioactive glass ceramics (BG), PVP induced faster apatite deposition and maintained the hybrid structure during electrospinning and pre-oxidation. This led to bioactivity improvement of bioactive glass [5]. For bioactive glass fibers (sol-gel synthesis), Hatcher [7] have demonstrated that PVP facilitated the synthesis process and the control of the rheological properties (more homogeneous fibrous material). PVP acted as a stabilizer by preventing gelation of the sample for 4 months. This was effective for enhancing
Moreover, Xia et al., have also shown that the addition of PVP resulted in sufficient chain entanglement and the formation of smooth bioactive glass nanofibers (electrospinning technique combined with sol-gel processing) [8]. Borate-modified bioactive glass [9] (burning-out method) was successfully achieved thanks to PVP, which greatly improved the blend’s homogeneity. Ali et al. have obtained cerium-doped bioactive glass nanoparticles (scaffold fabrication) [10] by optimization of its mechanical properties using PVP. Table 1 presents a list of published works focusing on bioactive glasses involving PVP.
Bioactive glass | Authors |
---|---|
Bioactive glass-ceramics (BG) | Cheng et al. [5] |
Bioactive glass fibers (sol-gel synthesis) | Hatcher [7] |
Borate-modified bioactive glass (burning-out method) | Abdelghany et al. [9] |
Cerium-doped bioactive glass nanoparticles (scaffold fabrication) | Ali et al. [10] |
The 45S5 Bioglass® (BG) | Yao et al. [11] |
Bioactive glass nanofibers (electrospinning technique combined with sol-gel processing) | Xia et al. [8] |
List of published works on bioactive glasses involving PYP.
Otherwise, PVP was used in some biomaterials for articular cartilage replacement because of its high hydrophilicity, which aids in the lubricating conditions of the resulting hydrogel [12]. PVP-based hydrogel was also obtained by radiation crosslinking and was effective for skin regeneration and wound dressing [13]. Multifunctional chitosan/PVP/45S5 Bioglass® scaffolds were also innovative for bone tissue engineering applications because of their outstanding bioactivity and
PVP (Figure 2) has several advantages in the pharmaceutical fields, and it acted as a stabilizer, a protective agent, a binder, a lubricating, a crystallization inhibitor, and a bioavailability enhancer for several active pharmaceutical ingredients (API) [4, 14]. It is widely known that PVP exhibited a higher solubility in water and polar solvents [15], and it also has a higher glass transition temperature (165 ± 1°C [16]) and was chemically stable in dry conditions [15]. Such physicochemical properties of PVP (Table 2) make it a versatile polymer with effective abilities in pharmaceutical field.
Various pharmaceutical applications of PVP [
Many published works have shown the ability of PVP to enhance complexation, thus influencing drug solubility and stability [17]. Valero et al. have already shown that PVP enhanced the inclusion complex formation in the presence of β-cyclodextrin and naproxen molecules [18]. PVP has been proven to be an effective solubilizer for various β-cyclodextrin complexes [19]. Chemical stability can be also enhanced by PVP in solid state, and the chemical degradation of cilazapril was considerably inhibited by solid dispersion within PVP [20].
On the other hand, PVP was largely used to develop various drug delivery systems, including oral, topical, transdermal, and ophthalmic administration [2, 4, 19]. PVP-based fibers composed of several active substances were successfully achieved [21]. PVP hydrogels [22], oral tablets [23], PVP films [24], composite nanoparticles [25], microcapsules [26], and microspheres [27] were also developed. Table 3 [3, 22, 24, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43] shows a summary of PVP-based drug delivery systems. Gamma irradiation, crosslinking, casting, electrospinning, and grafting were the most used techniques to produce PVP-based hydrogels [22, 31, 32]. PVP-based fibers were prepared by electrospinning, coaxial, and sequential electrospinning [33, 34]. PVP-based tablets were also produced by different techniques: 3D Printing [35, 36], spray drying or ball milling followed by compression, direct or double compression, solvent evaporation or wet granulation followed by compression and supercritical impregnation [3]. Up to now, solution casting was frequently used to obtain PVP-based films [24, 37, 38, 39]. Drug-loaded PVP particles can be prepared by several techniques including spray drying, co-grinding, supercritical-assisted atomization (SAA), supercritical antisolvent (SAS) process, coacervation, freeze drying, and wet chemical method [40, 41, 42].
Regardless of preparation method, PVP-based solid dispersions were widely employed for several poorly soluble drug molecules in order to enhance their dissolution rate, for example, indomethacin (IND), sulfisoxazole, sulfathiazole, phenytoin, chloramphenicol, furosemide, tadalafil, nifedipine, naproxen, carbamazepine, ibuprofen, celecoxib, silymarin, nimodipine, β-lapachone, gliclazide, carvedilol [2, 4, 18, 19, 44, 45, 46, 47]. Actually, solid dispersion technology by milling is one of the most attractive techniques for PVP-drug formulations [48]. Such technique was considered as environmental, scalable, economic, and simpler than other conventional methods [49]. In fact, solubility enhancement and physical stability of amorphous ibuprofen (at RH: 75%/T = 40°C for 6 months) can be achieved by ternary system formation (ibuprofen/β-cyclodextrin/PVP K30) in the ratio (1:1:0.5 w/w) [50]. This led to a 1.5–2-fold increase in the ibuprofen dissolution rate only after 10 min [50]. Such system was obtained by milling the drug in solid state at room temperature (25°C). PVP has undoubtedly reinforced synergy between compounds by establishing intermolecular H-bonds and electrostatic interactions between ibuprofen and β-cyclodextrin molecules [50]. Gupta et al. have shown that the antiplasticizing effect of PVP plays an important role in the stabilization of amorphous celecoxib (CLX) obtained by mechanical grinding, and this effect reduces the molecular mobility of the API and inhibits its recrystallization [51]. It has also been shown that ternary mixtures containing two excipients (PVP/MEG) have a greater CLX-solubilizing effect than that obtained by binary mixtures (PVP/CLX) [52]. Dissolution rate of bicalutamide was also enhanced by physical stabilization of its amorphous state using PVP [53].
Furthermore, several pharmaceutical products are formulated with PVP, for example, Betadine®, Inadine®, Prevail-FX®, ScrubCare®, and DuraPrep® [4]. Various studies have recently reported that PVP-iodine could be explored as a preventive aid against COVID-19 thanks to its antibacterial, antifungal, and antiviral properties [54].
In our recent published work [55], we have studied the solid dispersion of binary system (indomethacin/kaolin) in the presence of PVP K30 by co-milling technique [55]. The milling procedure was carried out in a high-energy planetary ball mill (Pulverisette 7, Fritsch), using the stable γ form of indomethacin (IND, Figure 3). The milling parameters were optimized in order to avoid polymorphic transformations or chemical degradation of drug molecules [55].
Indomethacin molecule.
Main results of characterization techniques are summarized in Table 4 (curves not shown, [55]). According to XRD results [55], the addition of variable amount of PVP to the binary mixture (IND:kaolin, in 1:1 ratio) led to the loss of drug crystallinity. IND particles were totally coated by amorphous films of the polymer as shown by SEM micrographs (Table 4), and this was completely different to that observed in the binary mixture (IND:kaolin, in 1:1 ratio) [55]. Amorphous drug molecules maintain its physical stability even after exposure to stress conditions (RH: 75% and T = 40°C) for 6 months [55]. The stabilization of amorphous Indomethacin dispersed within kaolin was explained by different factors.
Properties | Details |
---|---|
Cas number | 9003-39-8 [15] |
Description | Hygroscopic amorphous white powder [15] |
Formula | (C6 H9 NO)n [15] |
Molecular weight | 2500–30,00,000 D [15] |
IUPAC name | l-ethenylpyirolidin-2-one [15] |
Other names | Povidone, PVP, polyvidone, plasdone, Kollidon, poly [l-(2-oxo-pyrrolidinyl)ethylene], 1-vinyl-2-pyrroli-dinone polymer, 2-pyrrolidinone-l-ethenyl-homopolymer [15] |
Solubility | Soluble in water, polar solvents, acids, and amines. Insoluble in ethers, hydrocarbons, mineral oil, and some esters [15] |
Glass transition temperature | 165 ± 1°C [16] |
Stability | Chemically stable in dry form [15] |
K value | Range 10–120 [15] |
Physicochemical properties of PYP [15].
Drug delivery systems | Active compound involved | Authors |
---|---|---|
Nanoparticles | Ciprofloxacin, paclitaxel, curcumin | [28, 29, 30] |
Hydrogels | Salicylic acid, ketoprofen, amoxicillin | [22, 31, 32] |
Fibers | Indomethacin, emodin, ibuprofen | [3, 33, 34] |
Tablets (3D printing) | Dipyridamole, theophylline, pantoprazole sodium | [3, 35, 36] |
Films | Fentanyl, ibuprofen haloperidol. Diltiazem hydrochloride & indomethacin | [24, 37, 38, 39] |
Microparticles | Andrographolide, celecoxib, cefuroxime axetil, nimesulide | [40, 41, 42, 43] |
Summary of characterization results for binary (BM) and ternary systems (TM) [55].
On the one hand, FTIR results have shown that C=O band (cyclic dimer) of IND shifted toward higher frequencies; however, the C=O (benzoyl) band shifted to lower frequencies and merged with the (C=O) band of PVP [55]. 13C NMR spectroscopy has also indicated an upfield shift of IND carbon peak bound to methoxy groups and carbonyl group (2), which disappeared in the presence of 75% of PVP, while the C=O peak of PVP shifted toward higher values (from 176 ppm to 161 ppm) and merged with indomethacin peak [55]. The same behavior was already reported for IND: SiO2 solid dispersion obtained by co-milling and this is due to intermolecular interactions between siloxane bonds and the oxygen of methoxy or carbonyl groups in IND molecules [56]. Therefore, FTIR and NMR results suggested the establishment of hydrogen bonds between carbonyl group of PVP and carboxylic group of indomethacin [55].
On the other hand, DSC curves have shown the appearance of a single transition event (Tg) that suggests the miscibility of the components in such mixture, and melting event of IND disappeared indicating complete conversion from crystalline to amorphous state [55]. The antiplasticizing effect of PVP has undoubtedly reduced the molecular mobility of amorphous drug molecules leading to its physical stability as shown by the XRD results [55].
According to previous results, the synergy of different factors could explain the stabilization of amorphous IND under stress conditions: hydrogen bonds formation between PVP and drug molecules, antiplasticizing effect of PVP, and hydrophilicity enhancement. This resulted in suppressed recrystallization of amorphous IND by inhibiting its molecular mobility [55].
In the case of binary mixtures (IND:kaolin), drug solubility decreased (Table 5) and this was attributed to kaolin adsorption effect [57]. Such attenuation occurred for many kaolin-based formulations [13], which constitutes an impediment for pharmaceutical use of kaolin [58]. As a result of PVP addition, water solubility of Indomethacin has been considerably improved (Table 5) in ternary systems [55]. By adding 75% of PVP to the binary system (in 1:1 ratio), water solubility increased about 4.5-folds [55].
Samples | Solubility (μg/ml) |
---|---|
IND | 9.33 ± 0.05 |
50% IND + 50% kaolin (BM) | 8.38 ± 0.05 |
25% IND + 75% kaolin | 6.01 ± 0.05 |
BM + 10% PVP | 16.66 ± 0.1 |
BM + 25% PVP | 29.05 ± 0.1 |
BM + 50% PVP | 43.44 ± 0.1 |
BM + 75% PVP | 44.44 ± 0.1 |
Water solubility measurement of indomethacin in binary (BM) and ternary systems [55].
It was already shown that PVP has a potential ability to enhance drug solubility, in many ternary systems [59]. Adding PVP to the binary solid dispersion (sodium lauryl sulfate/ibuprofen) was more efficacious in terms of drug dissolution enhancement [59]. Mahapatra et al. have shown that PVP has better enhanced valsartan solubility than β-cyclodextrin and hydroxypropyl β-cyclodextrin [60]. Dissolution rate enhancement of efavirenz was successfully obtained by ternary solid dispersion using PVP and polyethylene glycol 8000 [61]. In addition to aforesaid, we have recently reported that solubility enhancement of poorly soluble drugs can be achieved by co-milling the drug in the presence of multiple carriers, and this led to the formation of physically stable amorphous system and was more effective than simple binary systems [62].
In summary, the versatility of PVP comes from its multiple utilizations as multifunctional additive in biomedical and pharmaceutical fields. PVP has promoted the actual advances in bioactive glass design (optimizing mechanical properties, enhancing
It is necessary to further investigate on the mechanisms and nature of interactions within bioactive glass materials containing PVP. More attention should be accorded to the role of PVP in drug formulations composed of clay minerals.
The authors thank Pr. Abdessalem Haj Amara (FSB, Tunisia) for his considerable inputs and helpful discussions. On the other hand, the authors confirmed that this research work did not receive any specific funding.
The authors declare that they have no conflict of interest.
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