Comparison of Equations to Predict Creatinine Clearance (CLCR) or Glomerular Filtration Rate (GFR) from Serum Creatinine Concentration
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"5864",leadTitle:null,fullTitle:"Different Types of Field-Effect Transistors - Theory and Applications",title:"Different Types of Field-Effect Transistors",subtitle:"Theory and Applications",reviewType:"peer-reviewed",abstract:'In 1959, Atalla and Kahng at Bell Labs produced the first successful field-effect transistor (FET), which had been long anticipated by other researchers by overcoming the "surface states" that blocked electric fields from penetrating into the semiconductor material. Very quickly, they became the fundamental basis of digital electronic circuits. Up to this point, there are more than 20 different types of field-effect transistors that are incorporated in various applications found in everyday\'s life. Based on this fact, this book was designed to overview some of the concepts regarding FETs that are currently used as well as some concepts that are still being developed.',isbn:"978-953-51-3176-2",printIsbn:"978-953-51-3175-5",pdfIsbn:"978-953-51-4804-3",doi:"10.5772/65626",price:119,priceEur:129,priceUsd:155,slug:"different-types-of-field-effect-transistors-theory-and-applications",numberOfPages:192,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"586a8228e9e9228e77a6a141d8d170bf",bookSignature:"Momcilo M. Pejovic and Milic M. Pejovic",publishedDate:"June 7th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5864.jpg",numberOfDownloads:21895,numberOfWosCitations:20,numberOfCrossrefCitations:28,numberOfCrossrefCitationsByBook:5,numberOfDimensionsCitations:38,numberOfDimensionsCitationsByBook:5,hasAltmetrics:1,numberOfTotalCitations:86,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 13th 2016",dateEndSecondStepPublish:"November 3rd 2016",dateEndThirdStepPublish:"January 30th 2017",dateEndFourthStepPublish:"April 30th 2017",dateEndFifthStepPublish:"June 29th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"147994",title:"Dr.",name:"Momčilo",middleName:"M.",surname:"Pejović",slug:"momcilo-pejovic",fullName:"Momčilo Pejović",profilePictureURL:"https://mts.intechopen.com/storage/users/147994/images/5588_n.jpg",biography:"Momcilo M. Pejovic received his BSc degree in Physics at the University of Belgrade, Serbia, and his MSc and PhD degrees in Electronics at the University of Nis, Serbia, in 1968, 1977, and 1980, respectively. In 1968, he worked at Electronic Industry Nis, Serbia. Between 1973 and 2011, he has worked at the Faculty of Electronic Engineering, University of Nis, as a professor of Physics and is now currently retired. He has authored and coauthored 15 books and more than 250 research papers, among which more than 115 papers have been published in international journals. His research interests include the reliability of field-effect transistors, application of MOSFET dosimeters, characterization of vacuum and gas-filled electrical devices and electrical discharge, and recombination processes in the afterglow periods in gases.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Nis",institutionURL:null,country:{name:"Serbia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"194077",title:"Dr.",name:"Milić M.",middleName:null,surname:"Pejovic",slug:"milic-m.-pejovic",fullName:"Milić M. Pejovic",profilePictureURL:"https://mts.intechopen.com/storage/users/194077/images/5589_n.jpg",biography:"Milic M. Pejovic received his BSc and MSc degrees in Electronics at the University of Nis, Serbia, and PhD degree in Electronics at the University of Belgrade, Serbia, in 1999, 2003, and 2007, respectively. In 2002, he worked for Philips Semiconductor Company, Southampton, UK, in the DVD application sector. In 2007, he worked in Tyndall National Institute as visiting researcher. Currently, he is working as an assistant professor at the Faculty of Electronic Engineering, University of Nis. He has authored or coauthored more than 55 research papers, including 40 papers in international journals and coauthored 2 books. His research interests include process control and measurements as well as the reliability of field-effect transistors and MOSFET dosimeters and electrical characterization of vacuum and gas-filled components.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"739",title:"Electronic Circuits",slug:"electrical-and-electronic-engineering-electronic-circuits"}],chapters:[{id:"54729",title:"Carrier Mobility in Field-Effect Transistors",doi:"10.5772/67885",slug:"carrier-mobility-in-field-effect-transistors",totalDownloads:3320,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Authors investigate the carrier mobility in field-effect transistors mainly when fabricated on Si(110) wafers. They showed that the methods developed to extract the conduction parameters cannot be implemented for Si(110) p-MOSFETs. Authors then developed a more accurate mobility model able to simulate not only the drivability but also the transconductance for these same devices. The study of the relation between the mobility, channel direction and wafer orientation revealed that the channel direction had a significant impact on the mobility for transistors fabricated on Si(110) wafers, the highest electron and hole mobilites being obtained for a channel along the <100> and <110> directions, respectively. No relations were found for Si(100) wafers. The study of the dependence of the scattering mechanism limiting the mobility in Si(110) n-MOSFETs showed that the Coulomb and surface roughness scattering mechanisms were responsible for the degradation of the mobility when compared to the one on Si(100) wafers. Finally, the measurement of the mobility in an accumulation-mode MOSFETs is not straightforward since a bulk contribution, owing to the SOI layer, is adding to channel current. A methodology has been successfully implemented that led to the experimental verification of the universal behaviour of the mobility in an accumulation layer.",signatures:"Philippe Gaubert and Akinobu Teramoto",downloadPdfUrl:"/chapter/pdf-download/54729",previewPdfUrl:"/chapter/pdf-preview/54729",authors:[{id:"181697",title:"Dr.",name:"Philippe",surname:"Gaubert",slug:"philippe-gaubert",fullName:"Philippe Gaubert"},{id:"200442",title:"Dr.",name:"Akinobu",surname:"Teramoto",slug:"akinobu-teramoto",fullName:"Akinobu Teramoto"}],corrections:null},{id:"55540",title:"Resonant Tunneling and Two‐dimensional Gate Transistors",doi:"10.5772/intechopen.69069",slug:"resonant-tunneling-and-two-dimensional-gate-transistors",totalDownloads:1534,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, a new type of field-effect transistors is considered with a gate and a channel on a basis of two-dimensional systems of carriers. The key point of the device is that the systems are different. In particular, they are formed in different quantum wells or valleys of the carriers spectrum. Due to this difference, the coherent tunneling is reduced and inelastic tunneling requires additional excitations with significant momentum and energy. This decreases the tunneling rate significantly. For example, the intervalley tunneling rate is less than intravalley that in 9 orders of magnitude in GaAs/AlAs heterostructures. The two-dimensional character also can decrease the tunnel probability in a wide voltage range. Influence of further miniaturization will be discussed for the new types of the transistors.",signatures:"Vladimir Popov",downloadPdfUrl:"/chapter/pdf-download/55540",previewPdfUrl:"/chapter/pdf-preview/55540",authors:[{id:"198199",title:"Dr.",name:"Vladimir",surname:"Popov",slug:"vladimir-popov",fullName:"Vladimir Popov"}],corrections:null},{id:"54563",title:"High Electron Mobility Transistors: Performance Analysis, Research Trend and Applications",doi:"10.5772/67796",slug:"high-electron-mobility-transistors-performance-analysis-research-trend-and-applications",totalDownloads:3766,totalCrossrefCites:14,totalDimensionsCites:16,hasAltmetrics:0,abstract:"In recent years, high electron mobility transistors (HEMTs) have received extensive attention for their superior electron transport ensuring high speed and high power applications. HEMT devices are competing with and replacing traditional field‐effect transistors (FETs) with excellent performance at high frequency, improved power density and satisfactory efficiency. This chapter provides readers with an overview of the performance of some popular and mostly used HEMT devices. The chapter proceeds with different structures of HEMT followed by working principle with graphical illustrations. Device performance is discussed based on existing literature including both analytical and numerical models. Furthermore, some notable latest research works on HEMT devices have been brought into attention followed by prediction of future trends. Comprehensive knowledge of up‐to‐date results, future directions, and their analysis methodology would be helpful in designing novel HEMT devices.",signatures:"Muhammad Navid Anjum Aadit, Sharadindu Gopal Kirtania,\nFarhana Afrin, Md. Kawsar Alam and Quazi Deen Mohd Khosru",downloadPdfUrl:"/chapter/pdf-download/54563",previewPdfUrl:"/chapter/pdf-preview/54563",authors:[{id:"199691",title:"Dr.",name:"Md. Kawsar",surname:"Alam",slug:"md.-kawsar-alam",fullName:"Md. Kawsar Alam"},{id:"199871",title:"BSc.",name:"Muhammad Navid Anjum",surname:"Aadit",slug:"muhammad-navid-anjum-aadit",fullName:"Muhammad Navid Anjum Aadit"},{id:"199873",title:"BSc.",name:"Sharadindu Gopal",surname:"Kirtania",slug:"sharadindu-gopal-kirtania",fullName:"Sharadindu Gopal Kirtania"},{id:"199874",title:"BSc.",name:"Farhana",surname:"Afrin",slug:"farhana-afrin",fullName:"Farhana Afrin"},{id:"199875",title:"Prof.",name:"Quazi Deen Mohd",surname:"Khosru",slug:"quazi-deen-mohd-khosru",fullName:"Quazi Deen Mohd Khosru"}],corrections:null},{id:"55026",title:"Quantum Confinement in High Electron Mobility Transistors",doi:"10.5772/intechopen.68374",slug:"quantum-confinement-in-high-electron-mobility-transistors",totalDownloads:1839,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Modulation‐doped semiconductor nanostructures exhibit extraordinary electrical and optical properties that are quantum mechanical in nature. The heart of such structures lies in the heterojunction of two epitaxially grown semiconductors with different band gaps. Quantum confinement in this heterojunction is a phenomenon that leads to the quantization of the conduction and the valence band into discrete subbands. The spacing between these quantized bands is a very important parameter that has been perfected over the years into device applications. Most of these devices form low‐dimensional charge carriers that potentially allow optical transitions between the subbands in such nanostructures. The transition energy differences between the quantized bands/levels typically lie in the infrared or the terahertz region of the electromagnetic spectrum and can be designed according to the application in demand. Thus, a proper understanding and a suitable external control of such intersubband transitions (ISTs) are not only important aspects of fundamental research but also a necessity for optoelectronic device applications specifically towards closing the terahertz gap.",signatures:"Shovon Pal, Sascha R. Valentin, Arne Ludwig and Andreas D. Wieck",downloadPdfUrl:"/chapter/pdf-download/55026",previewPdfUrl:"/chapter/pdf-preview/55026",authors:[{id:"198188",title:"Dr.",name:"Shovon",surname:"Pal",slug:"shovon-pal",fullName:"Shovon Pal"},{id:"198391",title:"Dr.",name:"Arne",surname:"Ludwig",slug:"arne-ludwig",fullName:"Arne Ludwig"},{id:"198392",title:"Prof.",name:"Andreas D.",surname:"Wieck",slug:"andreas-d.-wieck",fullName:"Andreas D. Wieck"},{id:"198393",title:"MSc.",name:"Sascha R.",surname:"Valentin",slug:"sascha-r.-valentin",fullName:"Sascha R. Valentin"}],corrections:null},{id:"55007",title:"Group III–V Semiconductor High Electron Mobility Transistor on Si Substrate",doi:"10.5772/intechopen.68181",slug:"group-iii-v-semiconductor-high-electron-mobility-transistor-on-si-substrate",totalDownloads:1567,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"High electron mobility transistor (HEMT) is the futuristic development of the transistor in migration of the nm technology for integration of many devices in a single chip. Moving beyond the silicon‐based devices to reach out the bottlenecks in the scaling and sizing of transistors has become an interesting topic of research. This research area includes the novel approach towards new materials and device structures. Materials focus is on composites made of binary, ternary and quaternary elements. Nanostructures made of two‐dimensional electron gas (2DEG), quantum well and tunnel barrier make the electron transport in devices interesting. A similar approach is adopted in the present work to make the device more suitable for faster device operation with high frequency.",signatures:"Ravindiran Munusami and Shankar Prabhakar",downloadPdfUrl:"/chapter/pdf-download/55007",previewPdfUrl:"/chapter/pdf-preview/55007",authors:[{id:"198942",title:"Dr.",name:"Ravindiran",surname:"Munusami",slug:"ravindiran-munusami",fullName:"Ravindiran Munusami"}],corrections:null},{id:"55277",title:"Metal-Semiconductor Interfaces in Thin-Film Transistors",doi:"10.5772/intechopen.68327",slug:"metal-semiconductor-interfaces-in-thin-film-transistors",totalDownloads:1707,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The metal-semiconductor interface in thin-film transistors (TFTs) is one of the bottlenecks on the development of these devices. Although this interface does not play an active role in the transistor operation, a low-quality interface can be responsible for a low performance operation. In a-Si TFTs, a doped film can be used to improve this interface, however, in other TFT technologies, there is no doped film to be used. In this chapter, some alternatives to improve this interface are analysed. Also, the influence of this interface on the electrical stability of these devices is presented.",signatures:"Miguel Dominguez, Pedro Rosales, Alfonso Torres, Jose A. Luna-\nLopez, Francisco Flores and Mario Moreno",downloadPdfUrl:"/chapter/pdf-download/55277",previewPdfUrl:"/chapter/pdf-preview/55277",authors:[{id:"90640",title:"Dr.",name:"Mario",surname:"Moreno",slug:"mario-moreno",fullName:"Mario Moreno"},{id:"101044",title:"Dr.",name:"Alfonso",surname:"Torres",slug:"alfonso-torres",fullName:"Alfonso Torres"},{id:"106625",title:"Dr.",name:"José Alberto",surname:"Luna López",slug:"jose-alberto-luna-lopez",fullName:"José Alberto Luna López"},{id:"196950",title:"Dr.",name:"Miguel",surname:"Dominguez",slug:"miguel-dominguez",fullName:"Miguel Dominguez"},{id:"197338",title:"Dr.",name:"Francisco",surname:"Flores",slug:"francisco-flores",fullName:"Francisco Flores"},{id:"199898",title:"Dr.",name:"Pedro",surname:"Rosales",slug:"pedro-rosales",fullName:"Pedro Rosales"}],corrections:null},{id:"54885",title:"Organic Field-Effect Transistor: Device Physics, Materials, and Process",doi:"10.5772/intechopen.68215",slug:"organic-field-effect-transistor-device-physics-materials-and-process",totalDownloads:3574,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Organic field-effect transistors have received much attention in the area of low cost, large area, flexible, and printable electronic devices. Lots of efforts have been devoted to achieve comparable device performance with high charge carrier mobility and good air stability. Meanwhile, in order to reduce the fabrication costs, simple fabrication conditions such as the printing techniques have been frequently used. Apart from device optimization, developing novel organic semiconductor materials and using thin-film alignment techniques are other ways to achieve high-performance devices and functional device applications. It is expected that by combining proper organic semiconductor materials and appropriate fabrication techniques, high-performance devices for various applications could be obtained. In this chapter, the organic field-effect transistor in terms of device physics, organic materials, device process, and various thin-film alignment techniques will be discussed.",signatures:"Jingjing Chang, Zhenhua Lin, Chunfu Zhang and Yue Hao",downloadPdfUrl:"/chapter/pdf-download/54885",previewPdfUrl:"/chapter/pdf-preview/54885",authors:[{id:"25754",title:"Prof.",name:"Yue",surname:"Hao",slug:"yue-hao",fullName:"Yue Hao"},{id:"46204",title:"Prof.",name:"Chunfu",surname:"Zhang",slug:"chunfu-zhang",fullName:"Chunfu Zhang"},{id:"198959",title:"Prof.",name:"Jingjing",surname:"Chang",slug:"jingjing-chang",fullName:"Jingjing Chang"},{id:"205064",title:"Dr.",name:"Zhenhua",surname:"Lin",slug:"zhenhua-lin",fullName:"Zhenhua Lin"}],corrections:null},{id:"54938",title:"Field-Effect Transistors for Gas Sensing",doi:"10.5772/intechopen.68481",slug:"field-effect-transistors-for-gas-sensing",totalDownloads:2678,totalCrossrefCites:6,totalDimensionsCites:9,hasAltmetrics:0,abstract:"This chapter reviews gas-sensitive field-effect transistors (FETs) for gas sensing. Although various types of gas sensors have been reported, this review focuses on FET-based sensors such as catalytic-gate FETs, solid electrolyte-based FETs, suspended-gate FETs, and nanomaterial-based FETs. For recognition of analytes in the gas phase, the combination of cross-reactive gas sensor arrays with pattern recognition methods is promising. Cross-reactive sensor arrays consist of gas sensors that have broad and differential sensitivity. Signals from the cross-reactive sensor array are processed using pattern recognition methods. Reports of FET-based sensor arrays combined with pattern recognition methods are briefly reviewed.",signatures:"Toshihiro Yoshizumi and Yuji Miyahara",downloadPdfUrl:"/chapter/pdf-download/54938",previewPdfUrl:"/chapter/pdf-preview/54938",authors:[{id:"198712",title:"Dr.",name:"Toshihiro",surname:"Yoshizumi",slug:"toshihiro-yoshizumi",fullName:"Toshihiro Yoshizumi"},{id:"198731",title:"Prof.",name:"Yuji",surname:"Miyahara",slug:"yuji-miyahara",fullName:"Yuji Miyahara"}],corrections:null},{id:"54564",title:"Transistors as an Emerging Platform for Portable Amplified Biodetection in Preventive Personalized Point‐of‐Care Testing",doi:"10.5772/67794",slug:"transistors-as-an-emerging-platform-for-portable-amplified-biodetection-in-preventive-personalized-p",totalDownloads:1911,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The impressive improvement in biomolecular detection has gone from simple chemical methods to sophisticated high throughput laboratory machines capable of accurately measuring the complex biological components and interactions. In the following chapter, we focus our attention on transistor‐based devices as an emerging platform for easy‐to‐use, portable amplified biodetection for preventive personalized medical applications and point‐of‐care testing. Electronic sensing devices comprise biosensors based on field‐effect transistors (bio‐FETs) and organic electrochemical transistors (OECTs). Transistor sensing devices can transduce electronic and ionic signals thereby creating an effective human‐machine communication channel. In this chapter, we survey the progress done on the development of transistor innovative concepts to examine biological processes, i.e., biosensors integrated with textiles, flexible substrates, and biocompatible materials. Electrochemical and field‐effect transistors can operate at low voltages possibly serving for highly sensitive, selective, and real‐time sensing devices. 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The National Kidney Disease Education Program recommends using either the Cockcroft–Gault creatinine clearance (CLCG) or Modification of Diet in Renal Disease (MDRD) equation when determining dosages of drugs that are primarily eliminated by the kidneys [1]. Both methods attempt to better predict creatinine clearance (CLCR) or glomerular filtration rate (GFR) by taking into account different variables such as age, weight, gender, race, and serum creatinine (SCr), however neither equation captures the key factor of paraplegia. Over time, individuals with paraplegia develop low SCr concentrations relative to their actual CLCR due to significantly reduced muscle mass as a result of chronic immobility and muscle atrophy. Both Cockcroft–Gault (CG) and MDRD formulas have SCr in their denominator inversely proportional to CLCR or GFR, therefore low SCr in paraplegia would result in gross overestimation of their renal function. Based on falsely high CLCR or GFR, clinicians could potentially prescribe renally eliminated medications at dosages higher than recommended, resulting in undesirably high drug concentrations leading to drug toxicity and/or adverse drug reactions (ADRs). For example, supratherapeutic vancomycin and aminoglycosides (AG) serum concentrations, especially if combined with other nephrotoxic and/or ototoxic medications, could drastically increase the risk of nephrotoxicity and/or ototoxicity. This could be devastating to many individuals with paraplegia who have existing renal insufficiency.
In addition to high prevalence of traditional risk factors for CKD such as advanced age, diabetes, hypertension, and cardiovascular disease, individuals with paraplegia have elevated incidence of recurrent and chronic urinary tract infections, neurogenic bladder dysfunction, and nephrolithiasis that put them at risk for developing CKD [2-6]. Fischer et al. conducted cross-sectional analyses of data on 9333 Veterans with spinal cord injury and disorder (SCI/D) and found that the prevalence of CKD in SCI/D was approximately 35%, considerably higher based on the modified MDRD for SCI/D than 10% based on the original MDRD formula [7]. Underrecognition of CKD in paraplegia makes it more crucial to use accurate tools to estimate renal function in this population.
Currently, there is no accepted standard method for determining renal dosing regimens for patients with paraplegia, and data on estimating renal function in such population is scarce. However clearance of drugs primarily eliminated by the kidneys such as vancomycin and AG nearly mirror that of the creatinine, hence could be used to assess renal function in paraplegia.
The aims of this chapter are: (1) to review the current literature on assessing renal function in paraplegia, (2) to evaluate different methods of estimating CLCR or GFR compared with patient-specific vancomycin and AG clearance (CLDRUG) in individuals with paraplegia, (3) to assess whether there is a difference in the estimation of renal function between the two anatomical degrees of SCI/D when compared with CLDRUG, and (4) to present the “Spinal Cord Injury Equation” that more accurately estimates renal function in paraplegia.
Tables 1 and 2 show, respectively, comparison of equations to predict CLCG or GFR from SCr and review of the current literature on assessing renal function in paraplegia. Each equation and study will be discussed in detail below.
\n\t\t\t\t | \n\t\t|
\n\t\t\t | GFR = CLCR (mL/min) = [(140 – age) x IBW in kg] / (72 x SCr); (multiply 0.85 for females) | \n\t\t
\n\t\t\t\t | \n\t\t|
\n\t\t\t | GFR = CLCR (mL/min) = [(140 – age) x IBW in kg] / (72 x SCr); (multiply 0.85 for females) | \n\t\t
\n\t\t\t | SCr rounded to 1 mg/dL for patients with SCr < 1 mg/dL while using the actual SCr for | \n\t\t
\n\t\t\t | patients with SCr ≥ 1 mg/dL | \n\t\t
\n\t\t\t\t | \n\t\t|
\n\t\t\t | GFR (mL/min/1.73 m2) = 175 x standardized SCr-1.154 x age-0.203 x 1.212 (if black) x 0.742 (if female) | \n\t\t
\n\t\t\t\t | \n\t\t|
\n\t\t\t | GFR (mL/min/1.73 m2) = 141 x min (SCr/ | \n\t\t
\n\t\t\t | where | \n\t\t
\n\t\t\t\t | \n\t\t|
\n\t\t\t | GFR = CL24H (mL/min) = [urine creatinine x urine volume (mL)] / [SCr x time (hours) x 60] | \n\t\t
Comparison of Equations to Predict Creatinine Clearance (CLCR) or Glomerular Filtration Rate (GFR) from Serum Creatinine Concentration
*To enable the expression of comparisons among different methods in the same unit (mL/min), GFR values normalized to a BSA of 1.73 m2 need to be converted to uncorrected values.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
36 25 11 --\n\t\t\t | \n\t\t\t58 22 36 22 | \n\t\t\t116 64 52 -- | \n\t\t\t141 52 89 --\n\t\t\t | \n\t\t\t14 --\n\t\t\t\t --\n\t\t\t\t 14 | \n\t\t\t87 54 33 -- | \n\t\t|
38 (24-68) | \n\t\t\tP: 48 ± 17 T: 47 ± 14 | \n\t\t\t63 ± 1 | \n\t\t\t66 ± 11 | \n\t\t\t53 ± 12 | \n\t\t\t65 ± 16 | \n\t\t|
\n\t\t\t\t | \n\t\t\t-- | \n\t\t\tSCI/D: 58 [100] Control: 11 [50] | \n\t\t\t\n\t\t\t | 140 [99] | \n\t\t\t\n\t\t\t | 87 [100] | \n\t\t
-- | \n\t\t\t-- | \n\t\t\t\n\t\t\t | \n\t\t\t | 75 [65] 41 [35] | \n\t\t\t71 [82] 16 [18] | \n\t\t|
\n\t\t\t\t | \n\t\t\t-- | \n\t\t\t-- | \n\t\t\t\n\t\t\t | 25 ± 6 | \n\t\t\t\n\t\t\t | 27 ± 5 | \n\t\t
\n\t\t\t\t | \n\t\t\t\n\t\t\t | P: 82 ± 46 T: 70 ± 23 | \n\t\t\t\n\t\t\t | 91 ± 37 | \n\t\t\t63 ± 26 | \n\t\t\t93 ± 47 | \n\t\t
\n\t\t\t\t | \n\t\t\t-- | \n\t\t\t-- | \n\t\t\t\n\t\t\t | \n\t\t\t | 76 ± 33 | \n\t\t\t\n\t\t |
\n\t\t\t\t | \n\t\t\t-- | \n\t\t\tP: 1 ± 0.4 T: 0.8 ± 0.3 | \n\t\t\t\n\t\t\t | 0.74 ± 0.29 | \n\t\t\tSCI/D: 0.8 ± 0.4 Control: 1.1 ± 0.3 | \n\t\t\t0.88 ± 0.40 | \n\t\t
\n\t\t\t\t | \n\t\t\tCLCG vs. CL24H vs. mea- sured CLCR by 99mTc-DTPA | \n\t\t\tCLCG vs. CL24H \n\t\t\t | \n\t\t\tCLCG vs. CL24H vs. MDRD | \n\t\t\tCLCG vs. CLM vs. CL24H vs. MDRD vs. CKD-EPI | \n\t\t\tSCI/D vs. Non-SCI/D CLVANCO\n\t\t\t | \n\t\t\tCLSCI vs. CLCG vs. CLM vs. CL24H vs. MDRD vs. CKD-EPI | \n\t\t
CL24H more accurate than CLCG\n\t\t\t | \n\t\t\tCorrection factor: 0.8 for paraplegic 0.6 for tetraple-gic | \n\t\t\tCorrection factor: 0.7 for MDRD 0.8 for CLCG\n\t\t\t | \n\t\t\tAll methods over-estimate CLDRUG (P< 0.001). Devel-opment of CLSCI\n\t\t\t | \n\t\t\t↑half-life in SCI/D | \n\t\t\tVerifi-cation of CLSCI: CLSCI un-biased and more precise. | \n\t\t
Review of the Current Literature on Assessing Renal Function in Paraplegia
\n\t\t\t\t
The CG equation was derived from a study of 236 males aged 18-92 years based on their 24-hour creatinine excretion. Since the publication in 1976, it has been exclusively used to estimate CLCR based on SCr to calculate dosing regimens for renally cleared medications including vancomycin and AG. However it may not extrapolate to individuals with paraplegia because the CG study excluded 31 patients with 24-h creatinine excretion < 10 mg/kg, and it didn’t reveal whether the study population included paraplegia and to what extent [8].
The review of current literature reports significant overestimation of renal function by CLCG, thus does not recommend using the original equation in paraplegia [9-10].
Macdiarmid et al. studied 25 paraplegic and 11 tetraplegic patients and sought to compare their CLCG and 24-hour endogenous creatinine clearance (CL24H) to the measured CLCR by 99mTc-DTPA clearance technique [9]. The investigators found that the CG method did not correlate well with that of the CL24H (r=0.426) or 99mTc-DTPA clearance (r=0.366) [9]. The mean difference between CLCG and CL24H was 41.9%, and the difference between CLCG and 99mTc-DTPA clearance 50.7% where CG formula overestimated CLCR [9]. On the other hand, the difference between CL24H and 99mTc-DTPA clearance was 17.7% with good correlation (r=0.71) [9]. The authors concluded that the CG formula significantly overestimates CLCR thus not recommended, however CL24H is an accurate method of determining renal function in paraplegia [9].
A study by Mirahmadi et al. investigated 58 male hospitalized patients with SCI/D and 22 ambulatory subjects, and compared their measured CL24H by autoanalyzer method versus the predicted by CLCG [10]. The authors found that the predicted CLCG and measured CL24H values closely matched in the ambulatory group while the predicted values consistently exceeded the measured values in SCI/D [10]. Between the two anatomical degrees of SCI/D, the paraplegic group had a markedly higher SCr (1.0 ± 0.4 mg/dL) and 24-hour urinary creatinine excretion (16 ± 9 mg/kg) compared to the tetraplegic group where the respective values were 0.8 ± 0.3 mg/dL and 11 ± 4.6 mg/kg [10]. The authors modified the original CG formula using a correction factor of 0.8 for paraplegics and 0.6 for tetraplegics to overcome significant overestimation by CLCG [10]. The correction factors improved the accuracy and precision of the predicted CLCG shown by the difference between the predicted and measured CLCR approaching zero and the slope of a linear correlation between the predicted and measured values approaching one with decreased Y-intercept values (p < 0.01) [10].
4-Variable MDRD:
GFR (mL/min/1.73 m2) = 175 x standardized SCr-1.154 x age-0.203 x 1.212 (if black) x 0.742 (if female)
A more recently developed MDRD has been widely used to estimate GFR in the nephrology arena. It is one of the two equations recommended by The National Kidney Disease Education Program for drug dosing [1].
The MDRD equation was derived from a study of a relatively young non- paraplegic population (mean age 51±13 years) with chronic kidney disease, primarily to stage kidney disease [11-12]. The original 6-variable MDRD formula integrates patient parameters including age, gender, race, blood urea nitrogen (BUN), SCr, and serum albumin [11-12]. The performance of this equation can be limited by variability among clinical laboratories in calibrating SCr assays [13]. Thus, the formula was re-expressed as the 4-variable MDRD equation based on standardized SCr assays as shown above [13]. Despite SCr calibration, the accuracy of the equation remains compromised at levels of GFR >60 mL/min/1.73 m2 [12-14]. Nevertheless, MDRD stands useful for GFR <60 mL/min/1.73 m2 in non- paraplegia and is endorsed by the National Kidney Disease Foundation for estimating GFR in CKD patients [1, 11-12].
Chikkalingaiah et al. compared the performance of the 4-variable MDRD and CG equations with CL24H in 64 patients with chronic paraplegia of greater than 6 months duration and stages II-V CKD [15]. Precision and bias of MDRD and CG formulas were measured by combined root mean square error (CRMSE) calculated as the square root of [(mean difference of estimated GFR and measured CL24H)2 + (SD of the difference)2]. Respective CRMSE values for original MDRD and CG equations were 29 and 19.3 mL/min/1.73m2. In order to improve the performance of the prediction equations, a correction factor of 0.7 for MDRD and 0.8 for CG were applied which resulted in a decrease in their CRMSE values to 11.4 and 13 mL/min/1.73m2, respectively [15]. Accuracy of both prediction equations was evaluated by the percentage of patients who did not deviate >15%, 30%, or 50% from measured CL24H. Respective percentages for MDRD were 12.5, 25, and 48.4 before the correction, and 25, 42, 68 after the correction [15]. Respective percentages for CG were 22, 37.5, and 58 before the correction, and 25, 50, 75 after the correction [15]. On the whole, the CG equation had less bias and was more precise and more accurate than the MDRD equation, however still overestimated GFR in subjects with chronic paraplegia with measured CL24H < 90 mL/min/1.73m2. Application of the correction factors markedly improved in the overall bias, precision, and accuracy of both MDRD and CG equations shown by both decreased CRMSE values and increased percentage of subjects in whom GFR did not deviate >15%, 30%, or 50% from measured CL24H [15].
GFR (mL/min/1.73 m2) = 141 x min (SCr/
where
In order to overcome the known bias of the MDRD equation for GFR values of ≥60 mL/min/1.73 m2, the researchers pooled the data from 26 studies to develop and validate a new equation, the CKD-EPI equation, to define dose modification across the GFR range in patients with and without CKD [14]. The data showed that the CKD-EPI equation was more precise and accurate compared to MDRD, especially at GFR > 60 mL/min/1.73 m2, however it is not frequently used in current clinical practice when determining dosages of drugs that are primarily eliminated by the kidneys due to need for further validation. Furthermore, the sample population used to develop the CKD-EPI formula did not include paraplegia, thus its use in paraplegia may be misleading.
CL24H (mL/min) = [urine creatinine x urine volume (mL)] / [SCr x time (hours) x 60]
Current literature reports that CL24H better predicts renal function compared to CLCG and MDRD in paraplegia, however this method is not routinely utilized for drug dosing due to the impracticability of collecting multiple urine samples as well as the propensity for error from serial collections [8, 16].
Data on the application of methods of estimating renal function compared with patient-specific CLDRUG in paraplegia is scarce.
Lavezo et al. compared the pharmacokinetics of vancomycin in 14 SCI/D and 14 non-SCI/D control patients with their age, weight, pharmacokinetic parameters of total body clearance, volume of distribution, and mean predicted dosages matched. Demographic data between the groups differed only in mean SCr where the values were 0.8 ± 0.4 in the SCI/D group and 1.1 ± 0.3 in the able-bodied control group (p=0.04). The investigators obtained the pharmacokinetic parameters via two steady-state vancomycin serum concentrations by the Sawchuk and Zaske method [17] and found that compared to the control group, mean elimination rate constant was significantly smaller, therefore mean elimination half-life significantly longer in patients with SCI/D [18]. The authors concluded that patients with SCI/D may require longer dosing intervals of vancomycin compared to non-SCI/D [18].
In 2011, Lee and Dang published the results of a retrospective pharmacokinetic analysis of data on 141 patients with long-term SCI/D in the Veterans Affairs (VA) hospital with the largest inpatient SCI center in the VA system. The investigators evaluated frequently employed methods to estimate GFR (CLCG, modified CG, CL24H, MDRD, and CKD-EPI) against patient-specific drug clearance of vancomycin and AG (CLDRUG) [16]. Table 3 shows that all methods overestimate CLDRUG (p <0.001). The mean difference between CLDRUG and MDRD is largest where overestimation by MDRD is more than two-fold. Almost 70% of the patients had overestimation of CLDRUG by greater than 30 mL/min when using MDRD to predict empiric dosing for vancomycin and AG (p < 0.001) [16]. The authors modified the original CG equation by rounding SCr to 1 mg/dL for patients with SCr < 1 mg/dL while using the actual SCr for patients with SCr ≥ 1 mg/dL in attempts to account for low SCr in SCI/D and to overcome gross overestimation of renal function by CLCG [16]. The investigators found that the modified CG equation (CLM) better estimated CLDRUG in SCI/D, compared with other frequently employed methods for predicting GFR. The mean difference between CLDRUG and CLM was smallest among the equations evaluated where overestimation by CLM was approximately 40%. Almost 65% of the patients had prediction of CLDRUG within 30 mL/min when using CLM to estimate empiric dosing for vancomycin and AG (p < 0.001) [16]. Despite pronounced improvement by modification of CG, overestimation may not be clinically acceptable.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t\t | \n\t\t\t49.77 ± 19.97 | \n\t\t\t0 | \n\t\t\t-- | \n\t\t
\n\t\t\t\t | \n\t\t\t119.76 ± 61.49 | \n\t\t\t69.99 | \n\t\t\t<0.001 | \n\t\t
\n\t\t\t\t | \n\t\t\t90.71 ± 27.44 | \n\t\t\t40.94 | \n\t\t\t<0.001 | \n\t\t
\n\t\t\t\t | \n\t\t\t85.16 ± 33.88 | \n\t\t\t35.39 | \n\t\t\t<0.001 | \n\t\t
\n\t\t\t\t | \n\t\t\t91.24 ± 36.90 | \n\t\t\t41.47 | \n\t\t\t<0.001 | \n\t\t
\n\t\t\t\t | \n\t\t\t69.38 ± 13.49 | \n\t\t\t19.61 | \n\t\t\t<0.001 | \n\t\t
Evaluation of Different Methods to Estimate GFR
Abbreviations: GFR, glomerular filtration rate; CLDRUG, actual drug clearance; MDRD, the Modification of Diet in Renal Disease equation; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; CL24H, 24-hour endogenous creatinine clearance; CLCG, the Cockcroft-Gault formula; CLM, modified Cockcroft-Gault formula; S.D., standard deviation. Published with permission of Lee [16].
As previously mentioned, Mirahmadi et al. reported that both SCr and mean urinary creatinine excretion were markedly lower in paraplegics compared with ambulatory subjects [10]. The authors recommended an adjustment of the original CG equation by 20% for paraplegics to correct for reduction of muscle mass relative to the total body weight in such population [10].
Chikkalingaiah et al. found that both prediction equations (MDRD and CG) overestimated GFR in the paraplegic group with an overestimation by MDRD to a higher degree [15]. The fractional prediction error (FPE = (variable 1-variable 2) x 100/variable 1) for MDRD and CG were, respectively, 48.5% and 29.5% for paraplegic subjects, where an FPE greater than 20% was considered to be clinically unacceptable [15]. A correction factor of 0.7 for MDRD and 0.8 for CG proposed by the authors decreased the FPE to 3.9% and 3.6%, respectively, for the paraplegic group [15].
Lee and Dang sought to evaluate various methods to predict CLDRUG for different anatomical degrees of SCI/D (Table 4) [16]. The mean difference between CLSCI and CLDRUG was not statistically significant when separated into paraplegia and tetraplegia [16]. Similar finding was noted for CLM and CL24H [16]. On the other hand, the mean differences between CLCG, CKD-EPI, and MDRD and CLDRUG were statistically significant between the two anatomical degrees of SCI where tetraplegics had a gross overestimation of CLDRUG compared with paraplegics [16]. The investigators stated that such difference may have risen from rounding SCr up to 1 mg/dL for patients with SCr < 1 mg/dL and using a ratio of urine creatinine to SCr done in CLM and CL24H, respectively, contrary to using the actual SCr in the other equations [16].
Individuals with paraplegia have variable functionality and range of mobility and movement depending on the injury levels. Degree of paralysis of lower body and legs and upper body strength could affect muscle mass therefore potentially alter SCr and CLCR or GFR. For example, one with high paraplegia (>T7) may have weaker upper body strength and balance compared to the one with low (T7-T12) paraplegia thus may have lower muscle mass and SCr resulting in a falsely low estimation of renal function compared to the low paraplegia. Unfortunately, there has yet been a study that assesses renal function between different anatomical levels or severity of injury in paraplegia.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t | |||
\n\t\t\t\t | \n\t\t\t-3.11 ± 13.14 | \n\t\t\t-5.39 ± 21.16 | \n\t\t\t0.48 | \n\t\t
\n\t\t\t\t | \n\t\t\t21.04 ± 13.81 | \n\t\t\t18.76 ± 22.26 | \n\t\t\t0.5 | \n\t\t
\n\t\t\t\t | \n\t\t\t32.60 ± 30.78 | \n\t\t\t37.02 ± 35.29 | \n\t\t\t0.45 | \n\t\t
\n\t\t\t\t | \n\t\t\t27.26 ± 20.56 | \n\t\t\t49.76 ± 38.55 | \n\t\t\t<0.001 | \n\t\t
\n\t\t\t\t | \n\t\t\t27.52 ± 25.50 | \n\t\t\t48.77 ± 24.76 | \n\t\t\t<0.001 | \n\t\t
\n\t\t\t\t | \n\t\t\t40.68 ± 40.71 | \n\t\t\t50.64 ± 64.56 | \n\t\t\t<0.001 | \n\t\t
Evaluation of Methods to Predict CLDRUG for Different Anatomical Degrees of SCI/D
Abbreviations: CLDRUG, actual drug clearance; SCI, spinal cord injury; CLSCI, spinal cord injury equation; CLM, modified Cockcroft-Gault formula; CL24H, 24-hour endogenous creatinine clearance; CLCG, the Cockcroft-Gault formula; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; MDRD, the Modification of Diet in Renal Disease equation; S.D., standard deviation. Published with permission of Lee [16].
Gross overestimation of CLDRUG by the frequently employed methods for estimating GFR prompted the authors Lee and Dang to develop an alternative method of estimating CLDRUG in SCI/D, the “spinal cord injury equation” (henceforth referred to as the CLSCI equation):
CLSCI (mL/min) = 2.3 X CLM\n\t\t\t\t0.7
where CLSCI and CLM denote, respectively, clearance values determined via use of the CLSCI equation and the CLM formula [16]. The CLSCI equation yields a value along the
Figures 1 and 2 depict, respectively, plots of actual drug clearance versus modified CG predicted drug clearance and linear regression plots of actual drug clearance versus predicted drug clearance using the CLSCI equation [16]. The slope of a linear correlation between the predicted and measured CLV values approach one, and the Y-intercept of a linear correlation between the predicted and measured CLV values is minimum [16].
The CLSCI equation was tested against other methods through a retrospective analysis of 87 hospitalized patients with long-term SCI/D [19]. The study population had similar baseline characteristics to the previous population by Lee and Dang, exclusively elderly, overweight, males with similar SCr. The authors used the Sheiner and Beal method [20] for determining predictive performance (precision and bias) to evaluate the predictive ability of the CLSCI equation in estimating vancomycin clearance, relative to five alternative methods (CLCG, modified CG, CL24H, MDRD, and CKD-EPI). Compared with other equations, the CLSCI equation was found to be less biased and more precise, with the smallest calculated mean prediction error (ME) and square root of the mean squared prediction error (RMSE) values (p < 0.005) (Table 5) [19]. Predictive performance of the CLSCI relative to each of the other five methods was measured by change in ME (relative bias between two methods) and change in MSE (relative precision) (Table 6). Negative values for changes in ME and MSE indicate an advantage favoring the comparator; a greater negative value signifies a greater magnitude of error. The five alternative equations significantly overestimated CLV, by 45-92% (p < 0.05) (Table 7) [19]. The CLSCI equation underestimated CLV by approximately 6%, however not to a significant degree (p = 0.06) [19]. The results of their finding were consistent with the previous study by Lee and Dang.
Plots of Actual Drug Clearance versus Modified Cockcroft–Gault Predicted Drug Clearance. Published with permission of Lee [
Linear Regression Plots of Actual Drug Clearance versus Predicted Drug Clearance Using the Spinal Cord Injury Equation. The red line, y=x, represents a line with a slope of 1 that indicates a perfectly one-to-one association between the actual and predicted drug clearance. Published with permission of Lee [
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t||||||
\n\t\t\t\t | \n\t\t\t-3.1 | \n\t\t\t21.5 | \n\t\t\t32.5 | \n\t\t\t33.0 | \n\t\t\t44.5 | \n\t\t\t47.5 | \n\t\t
95% CI (mL/min) | \n\t\t\t-6.3 to 0.1 | \n\t\t\t17.8 to 25.1 | \n\t\t\t26.2 to 38.8 | \n\t\t\t27.7 to 38.4 | \n\t\t\t36.2 to 52.7 | \n\t\t\t31.2 to 55.8 | \n\t\t
\n\t\t\t\t | \n\t\t||||||
MSE (mL2/min2) | \n\t\t\t235.2 | \n\t\t\t748.9 | \n\t\t\t1925.2 | \n\t\t\t1712.7 | \n\t\t\t3450.1 | \n\t\t\t3760.3 | \n\t\t
95% CI (mL2/min2) | \n\t\t\t168.9 to 301.4 | \n\t\t\t562.7 to 935.2 | \n\t\t\t1191.2 to 2659.2 | \n\t\t\t1271.6 to 2153.8 | \n\t\t\t2334.8 to 4565.3 | \n\t\t\t2640.1 to 4880.5 | \n\t\t
RMSE (mL/min) | \n\t\t\t15.3 | \n\t\t\t27.4 | \n\t\t\t43.9 | \n\t\t\t41.4 | \n\t\t\t58.7 | \n\t\t\t61.3 | \n\t\t
95% CI (mL/min) | \n\t\t\t13.0 to 17.4 | \n\t\t\t23.7 to 30.6 | \n\t\t\t34.5 to 51.6 | \n\t\t\t35.7 to 46.4 | \n\t\t\t48.3 to 67.6 | \n\t\t\t51.4 to 69.9 | \n\t\t
Absolute Predictive Performance of Vancomycin Clearance
Abbreviations: ME, mean error; CI, confidence interval; MSE, mean squared error; RMSE, root mean squared error; CLSCI, spinal cord injury equation; CLM, modified Cockcroft-Gault formula; CL24H, 24-hour endogenous creatinine clearance; CKD-EPI, Long-term Kidney Disease Epidemiology Collaboration equation; CLCG, the Cockcroft-Gault formula; MDRD, the Modification of Diet in Renal Disease equation. Published with permission of Lee [19].
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t-24.5 (-26.8 TO -22.3) | \n\t\t\t-513.8 (-709.8 to -317.8) | \n\t\t
\n\t\t\t\t | \n\t\t\t-35.5 (-42.6 TO -28.5) | \n\t\t\t-1690.0 (-2436.5 to -943.5) | \n\t\t
\n\t\t\t\t | \n\t\t\t-36.1 (-41.3 TO -30.9) | \n\t\t\t-1477.5 (-1922.8 to -1032.3) | \n\t\t
\n\t\t\t\t | \n\t\t\t-47.5 (-55.9 TO -39.1) | \n\t\t\t-3214.9 (-4331.1 to -2098.7) | \n\t\t
\n\t\t\t\t | \n\t\t\t-50.6 (-59.1 TO -42.1) | \n\t\t\t-3525.1 (-4645.0 to -2405.2) | \n\t\t
Relative Predictive Performance of Vancomycin Clearance
Abbreviations: ΔME, the difference in mean errors; ΔMSE, the difference in mean squared errors; CI, confidence interval; CLSCI, spinal cord injury equation; CLM, modified Cockcroft-Gault formula; CL24H, 24-hour endogenous creatinine clearance; CKD-EPI, Long-term Kidney Disease Epidemiology Collaboration equation; CLCG, the Cockcroft-Gault formula; MDRD, the Modification of Diet in Renal Disease equation. Published with permission of Lee [19].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t\t | \n\t\t\t45.2 ± 9.1 | \n\t\t\t-3.1 | \n\t\t\t0.06 | \n\t\t
\n\t\t\t\t | \n\t\t\t69.7 ± 19.7 | \n\t\t\t21.5 | \n\t\t\t< 0.05 | \n\t\t
\n\t\t\t\t | \n\t\t\t82.8 ± 36.0 | \n\t\t\t34.6 | \n\t\t\t< 0.05 | \n\t\t
\n\t\t\t\t | \n\t\t\t81.2 ± 30.4 | \n\t\t\t33.0 | \n\t\t\t< 0.05 | \n\t\t
\n\t\t\t\t | \n\t\t\t92.7 ± 47.0 | \n\t\t\t44.4 | \n\t\t\t< 0.05 | \n\t\t
\n\t\t\t\t | \n\t\t\t95.7 ± 45.2 | \n\t\t\t47.5 | \n\t\t\t< 0.05 | \n\t\t
Evaluation of Different Methods to Estimate CLV
Abbreviations: CLV, patient-specific vancomycin clearance ; S.D., standard deviation; CLSCI, spinal cord injury equation; CLM, modified Cockcroft-Gault formula; CL24H, 24-hour endogenous creatinine clearance; CKD-EPI, Long-term Kidney Disease Epidemiology Collaboration equation; CLCG, the Cockcroft-Gault formula; MDRD, the Modification of Diet in Renal Disease equation. Published with permission of Lee [19].
SCr determinations are used to estimate the dose of potentially toxic drugs eliminated primarily by the kidneys. Due to immobility and muscle atrophy, individuals with long-duration paraplegia have lower SCr levels relative to their CLCR; this could lead to substantial overestimation of GFR resulting in higher than desired concentrations of medications that increase the risk of toxicity and/or ADRs, especially in persons with existing renal insufficiency. To date, there is no accepted standard method that can reliably predict renal function in paraplegia. Review of the current literature shows that the most widely used CG and MDRD equations overestimate GFR thus not recommended in paraplegia. Although CL24H better predicts renal function compared to CLCG and MDRD in paraplegia, unpracticality of collecting multiple urine samples as well as the propensity for error from serial collections make this method clinically unfeasible. Different authors have recommended different modification of existing methods. Until more studies become available, the following methods can serve as valuable tools in estimating CLDRUG and renal function in individuals with paraplegia: 0.8 CG, 0.7 MDRD, or CLSCI equations.
Supported in full by Grant # 2867 from the PVA Research Foundation.
Orthodontic developments, especially during the last years, have been accompanied by a significant increase in the esthetic demands of the patients [1]. With the significant recent improvements in computer-aided design/computer-aid-ed manufacturing (CAD/CAM) and dental materials, there has been an increase in the demand for plastic systems [2]. Clear aligners provide an esthetic and comfortable treatment experience, facilitate oral hygiene, cause less pain as compared to fixed orthodontic appliances, and reduce the number and duration of appointments [3, 4, 5]. The aligner therapy also involves a lower incidence of demineralization, enamel abrasion, periodontal lesions, and mucosal irritations [6].
The concept of clear aligners was introduced by Kesling in 1946 with a tooth positioner fabricated by thermoplastic material molding technology and designed for minor tooth movements during the finishing stages of orthodontic treatment. In 1993, Sheridan and colleagues developed a technique of giving new clear retainers to the patient at each visit, incorporating interproximal reduction to provide the necessary space for tooth movement [3, 7]. With further advancement in orthodontic technology, Align Technology introduce the clear aligner treatment (CAT) rendering Kesling’s concept a feasible orthodontic treatment option [8]. A series of removable polyurethane aligners were introduced as an esthetic alternative to fixed labial appliances. Scanned images are converted to physical models by using different stereolithography (STL) techniques to fabricate a series of aligners that sequentially reposition the teeth. Each aligner is programmed to move a tooth or a small group of teeth 0.25–0.33 mm every 14 days [9, 10]. Align Technology provides orthodontists with ClinCheck (Align Technology Inc., Santa Clara, Calif) models, which reflect the treatment outcomes. The aligners incrementally shift the teeth into place based on the outcome the orthodontist expects to achieve [11].
The primary focus of the clear aligner system was initially to solve cases of low and moderate crowding and to close small spaces [1]. However, it has continually evolved through the development of new aligner materials, attachments on teeth, as well as new auxiliaries, such as “Precision Cuts” and “Power Ridges” to address a wider range of malocclusions and to enable additional treatment biomechanics [2, 5, 12].
Despite the available body of literature pertaining to aligner technology, only a few investigations have focused on the efficacy of clear aligner therapy in controlling orthodontic tooth movement. Furthermore, the stability after treatment has not been thoroughly investigated.
The purpose of this chapter was to update the knowledge of the available evidence about effectiveness and stability of clear aligners and to answer the following clinical research question: “Are clear aligners effective in controlling the orthodontic movement in non-growing subjects and what about stability of this treatment modality?”
A systematic search in the medical literature produced between January 2015 and January 2021 was performed to identify all peer-reviewed articles potentially relevant to the review’s question.
The following databases have been used: CENTRAL, MEDLINE, MEDLINE in Process, Embase and Cochrane Library databases.
The search strategy comprised use of the following terms: (invisalign OR clear aligners OR aligners OR transparent aligners) AND (effectiveness OR efficacy) AND (dental changes OR treatment outcome) AND (stability).
Additionally, a manual search was conducted in orthodontic journals of interest, such as The Angle Orthodontist, the American Journal of Orthodontics and the European Journal of Orthodontics. Title and abstract screening was performed to select articles for full text retrieval.
The following inclusion and exclusion criteria were used:
Study design: meta-analysis, systematic reviews, randomized and non-randomized clinical trials, prospective and retrospective studies were included.
Participants: non growing patients.
Intervention: articles that studied dental movement of cases treated with clear aligners.
Results: the efficacy of clear aligners in performing dental movements and the stability of treatment, superimposing virtual models or radiographs.
We excluded for our study articles older than 6 years, samples with growing patients, articles written in a language other than English, in-vitro studies, author opinions, letters to the editor, isolated cases, series of cases, surgical cases, or reports of patients with syndromes.
The grading system described by the Swedish Council on Technology Assessment in Health Care (SBU) [13] was used to assess the methodological quality and the level of evidence of the articles (Tables 1 and 2).
Grade A—high value of evidence |
All criteria should be met: |
Randomized clinical study or a prospective study with a well-defined control group |
Defined diagnosis and endpoints |
Diagnostic reliability tests and reproducibility tests described |
Blinded outcome assessment |
Grade B—moderate value of evidence |
All criteria should be met: |
Cohort study or retrospective case series with defined control or reference group |
Defined diagnosis and endpoints |
Diagnostic reliability tests and reproducibility tests described |
Grade C—low value of evidence |
One or more of the conditions below: |
Large attrition |
Unclear diagnosis and endpoints |
Poorly defined patient material |
Swedish Council on Technology Assessment in Health Care (SBU) criteria for grading assessed studies.
Level | Evidence | Definition |
---|---|---|
1 | Strong | At least two studies assessed with level “A” |
2 | Moderate | One study with level “A” and at least two studies with level “B” |
3 | Limited | At least two studies with level “B” |
4 | Inconclusive | Fewer than two studies with level “B” |
Definitions of evidence level.
The selection of articles included in this review is shown in the PRISMA flow chart (Figure 1). Study selection procedure was comprised of title-reading, abstract-reading, and full-text-reading stages. After exclusion of not eligible studies, the full report of publications considered eligible for inclusion by the authors was assessed. Eleven studies were included in the qualitative synthesis.
Flow chart according to the PRISMA statement.
Of the eleven included articles, there were five retrospective studies [6, 14, 15, 16, 17], two prospective studies [7, 11], two randomized controlled trials (RCT) [18, 19], two systematic reviews [2, 20] and one meta-analysis [20]. Most of the included studies evaluated mild to moderate malocclusions except for one [17] that involved first premolar extraction cases. The majority of studies used the Invisalign® system except two studies that used Nuvola® system [15] and F22 aligners [14].
Data collected from each of the included articles are described in Tables 3 and 4. Nine of the covered studies assessed predictability of tooth movements comparing post-treatment patient models to the predicted digital planned tooth movement models [2, 6, 7, 11, 14, 15, 16, 17, 18]. Two studies assessed the stability of the clear aligner therapy [19, 20].
Study | Study design | Participants | Intervention | Results |
---|---|---|---|---|
Buschang et al. 2015 [11] | Prospective clinical trial | 27pts |
|
|
Lombardo et al. 2017 [14] | Retrospective case series | 16 pts. F22 aligners |
|
|
Tepedino et al. 2018 [15] | Retrospective case series | 39 pts. First phase of treatment made of 12 aligners by Nuvola® aligner system |
|
|
Charalampakis et al. 2018 [16] | Retrospective case series | 20 pts. Class I patients treated with Invisalign and needed refinement |
|
|
Lopez et al. 2019 [2] | Systematic review | 20 studies |
|
|
Dai et al. 2019 [17] | Retrospective case series | 30 pts. First premolar extraction treatment with Invisalign |
|
|
Zhou et al. 2020 [7] | Prospective clinical trial | 20 pts. arch expansion with Invisalign aligners |
|
|
Al-Nadawi et al. 2020 [18] | Randomized clinical trial | 80 pts. three aligner wear protocols: 7 day, 10 day, and 14 day. |
|
|
Riede et al. 2021 [6] | Retrospective case series | 30 pts. Aligner treatment (Invisalign®) with the current material (SmartTrack®) |
|
|
Design, participants, type of intervention, and results of studies included in the qualitative analysis.
pts, patients; OGS, Objective Grading System; IPR, interproximal reduction; CBCT, Cone beam computed tomography.
Study | Study design | Participants | Intervention | Results |
---|---|---|---|---|
Zheng et al. 2017 [20] | Systematic review and meta-analysis |
| Scientific evidence |
|
Graf et al. 2021 [19] | Double-center trial | 33pts |
|
|
Studies assessing treatment stability of clear aligners.
pts, patients.
According to the SBU tool (Tables 1 and 2), among the selected studies, the methodological quality was low for four studies [6, 11, 16, 17], moderate for four others [7, 14, 15, 19] and high for one study [18] (Table 5). Thus, conclusions with a moderate level of evidence could be drawn from the review process.
Study (first author, year) | Evidence level |
---|---|
Buschang, 2015 [11] | C |
Lombardo, 2017 [14] | B |
Tepedino, 2018 [15] | B |
Charalampakis, 2018 [16] | C |
Dai, 2019 [17] | C |
Zhou, 2020 [7] | B |
Al-Nadawi, 2020 [18] | A |
Riede, 2021 [6] | C |
Graf, 2021 [19] | B |
Evidence grade according to Swedish Council on Technology Assessment in Health Care.
In this review, we aimed to provide data on the effectiveness and stability of treatment with clear aligners. The level of evidence was moderate as we identified one study with level «A» and four studies with level «B».
The effectiveness of clear aligners was judged by the predictability of tooth movement which varies with the type of tooth and the type of movement. Lopez et al. [2] found that the expression of the programmed movement was not fully accomplished with Invisalign®.
Concerning
Many studies showed that intrusion was the most unpredictable movement especially for the maxillary central and lateral incisors [16, 21]. Invisalign has a bite-block effect, because 2 aligners of 0.38-mm width are interposed between posterior teeth throughout treatment. Unexpected intrusion of the molars would cause the incisors to appear extruded on the posttreatment models after superimposition [16]. In fact, according to Grunheid et al. [22], mandibular incisors tend to be positioned more occlusally than predicted. The bite-block effect may make open bites easier to treat with Invisalign [16].
Concerning
Molar distalization was recorded as the highest accuracy with no need for attachments. Simon et al. [25] also reported a high accuracy (88%) of the bodily movement of upper molars when a distalization movement of at least 1.5 mm was prescribed.
Several studies agreed that derotation of rounded teeth especially canines was difficult to achieve with aligners [16, 22, 26]. An amount of rotation greater than 15° has been identified as a risk factor for decreased accuracy for rotational prediction [25]. Interproximal contacts of rotated canines might also be considered a significant predictor for the diminished efficacy of tooth movement, especially in the absence of interproximal reduction of the enamel (IPR) [26]. The direction of derotation has been also documented to influence the accuracy of the maxillary canine, with distal movement demonstrating less accuracy than mesial [21]. This is possibly due to the actual contact area between canine and premolar and the potential challenges of providing enamel reduction in this area.
It has been recommended to plan overcorrections, especially if rotations exceed 15°, to use attachments, and to reduce staging to less than 1.5° per aligner [8, 16, 25]. However, although various types or shapes of attachment grips or practices of interproximal enamel reduction have been reported as potential prognostic factors for better efficacy of rotational tooth movement, this does not necessarily translate into an identified substantial effect in practice [26].
Concerning
According to Lopez and al. [2], Invisalign® was also able to alter intercanine, interpremolar, and intermolar width in the presence of crowding. Kravitz et al. [23] recommended to treat cases with severe lower crowding mostly by interproximal reduction (IPR) instead of dentoalveolar expansion. This recommendation comes from the finding that retraction is more accurate than dentoalveolar expansion of the lower anterior teeth. The expansion of the mandibular intercanine width also poses the greatest risk of relapse following treatment [29].
Concerning the effectiveness of the occlusal contacts with clear aligners, the study by Izhar et al. [10] found that the software models do not accurately reflect the patient’s final occlusion immediately at the end of active treatment. Kassas et al. [30] also stated that clear aligners were not sufficient for providing ideal occlusal contacts. The deterioration in occlusal contacts was caused by the thickness of aligners, which interferes with the settling of the occlusal plane.
As far as the malocclusion type is concerned, the study by Graf et al. [19] showed that Invisalign® treatments are able to significantly reduce malocclusions in adult patients. The study found that all types of sagittal malocclusion (class I, class II, and class III) were ‘greatly improved’ with a rate of 77.44%. Graf and al. [19] also concluded that conventional attachments and the combination with optimized attachments equally led to treatment effectiveness regarding the total PAR score reduction with equally achieved effectiveness in mild, moderate, and rather severe cases. However, for Class II malocclusion, Patterson et al. [31] reported that there was no significant Class II correction or overjet reduction with elastics for an average of 7-month duration in the adult population. Additional refinements may be necessary to address problems created during treatment mainly posterior open bite.
One study of our review by Dai et al. [17] assessed the effectiveness of Invisalign in first premolar extraction treatment. According to this study, first molar anchorage control and central incisor retraction were not fully achieved as predicted. Only medium anchorage control was achieved as the first molars actually moved mesially. The G6-optimized attachment showed similar control in first molar angulation and mesiodistal translation as did 3- and 5-mm horizontal rectangular attachments. On the other hand, setting a distal tipping of 6.6 mm on the first molars might help clinically maintain the tooth angulation, leading to bodily tooth movement. According to the same study [17], the incisors inclined lingually under the retraction force. Accordingly, the use of power ridges or attachments as well as overcorrection by setting greater buccal crown inclination during the virtual setup should be considered to achieve optimal incisor torque control.
Current evidence does not support the clinical use of aligners as a treatment modality that is equally effective to the gold standard of braces [32]. However, clear aligners have advantage in segmented movement of teeth and shortened treatment duration, but are not as effective as braces in producing adequate occlusal contacts, controlling teeth torque, and retention [5, 33].
Many variables influence the accuracy of dental movements, but very few studies have analyzed these parameters in treatments with clear aligners. According to Tepedino et al. [15], several factors determine successful tooth movement such as the attachment’s shape and position, the aligner’s material and thickness, the amount of activation present in each aligner, and the techniques used for the production of the aligners. Treatment outcomes depend also on the patient’s characteristics, bone density and morphology, crown and root morphology of the teeth, as well as on factors related to the clinician. Orthodontists have to incorporate their expert knowledge in determining proper sequencing of tooth movements, tooth attachment design and placement, and prescribing overcorrection when needed for difficult tooth movements to increase efficiency and achieve better treatment outcomes [22, 34]. Patient compliance is also mandatory to achieve good results by wearing the aligners 22 hours a day or more [28].
One study from this review with a high level of evidence [18] evaluated the impact of wear protocol on the accuracy of clear aligners. It has concluded that fourteen-day changes were statistically significantly more accurate in some posterior movements mainly maxillary intrusion, distal-crown tip and buccal-crown torque, and in mandibular intrusion and extrusion.
As in all types of orthodontic treatment, stability is one of the most important issues to discuss regarding clear aligners. According to the systematic review by Zheng et al. [20], only one study compared the post-retention dental changes between patients treated with Invisalign and those treated with conventional fixed appliances. They found that the change in the total alignment score in the Invisalign group was significantly larger than that for the Braces group. There were significantly larger changes in maxillary anterior alignment in the Invisalign group than in the conventional bracket group. Tamer et al. [5] also reported that maxillary anterior leveling relapsed in the Invisalign group. On average, the posttreatment models lost twice as many points for alignment than the respective ClinCheck models. In other words, a full finishing phase of treatment may be needed to achieve the results indicated in the ClinCheck model [11].
The type and degree of tooth movement, the duration of active treatment and the retention protocol are among major influencing factors of posttreatment stability and relapse. The study by Graf et al. [19] is the first one to assess the stability of clear aligners outcome throughout a retention period of 10 months. The retention protocol involved a mandibular multistrand fixed retainer (0.0155 inch; stainless steel, 24 K gold plated) bonded on each lingual surface from canine to canine and a removable modified Hawley retainer for the upper arch (with mandatory Adams clasps on first molars). The study showed that the treatment outcome can be stable throughout this retention protocol. It has also concluded that treating patients with respect to their physiological boundaries and maintaining their original arch form would be key to treatment stability. Overexpansion of the dental arch, especially in the lower arch and in adult patients, is a potential risk for stable results.
There is current evidence with a moderate level of certainty regarding the effectiveness of clear aligner therapy for certain tooth movements. Clear aligners can safely straighten dental arches in terms of leveling and derotating the teeth, except for canines and premolars. The crown tipping can be easily performed. However, important limitations include arch expansion through bodily tooth movements, extraction space closure, corrections of occlusal contacts, and larger antero-posterior and vertical discrepancies. The use of additional attachments might be more effective for various types of movement, such as bodily expansion of the maxillary posterior teeth, canine and premolar rotational movements, incisors torque control and extrusion of maxillary incisors. Overcorrections might also improve the effectiveness of orthodontic movement. However, overcorrections are not as simple for all movements and need to be made on a case-by-case basis depending on the goal of treatment.
Studies on effectiveness of clear aligners had methodological heterogeneity as they assessed predictability of different types of tooth movements for different teeth by using different materials like Invisalign, F22 aligner and Nuvola system. Retention and stability studies regarding aligners also remain limited in the literature. Therefore, further well-designed and reported researches are required on this subject.
Special thanks to the department of Orthodontics of the Faculty of the dentistry of the University Hassan II of Casablanca. We would also like to acknowledge the support of Professor Farid Bourzgui for the realization of this work and for sharing and discussing the initial idea of the project.
The authors declare no conflict of interest.
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\\n\\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including all published versions, is retained by the Author and any Co-Authors.
\\n\\nSubject to the license granted above, the Author and Co-Authors retain patent, trademark and other intellectual property rights to the Work.
\\n\\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
\\n\\nThe Author, on his/her own behalf and on behalf of the Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from the translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
\\n\\nAUTHOR'S DUTIES
\\n\\nWhen distributing or re-publishing the Work, the Author agrees to credit the Monograph/Compacts as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Monograph/Compacts as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
\\n\\nThe Author agrees to:
\\n\\nThe Author will be held responsible for the payment of the agreed Open Access Publishing Fee before the completion of the project (Monograph/Compacts publication).
\\n\\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
\\n\\nThe Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Work worldwide for the full term of the above licenses, and shall provide to IntechOpen, at its request, the original copies of such consents for inspection or the photocopies of such consents.
\\n\\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\\n\\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\nAUTHOR'S WARRANTY
\\n\\nThe Author and Co-Authors confirm and warrant that the Work does not and will not breach any applicable law or the rights of any third party and, specifically, that the Work contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy.
\\n\\nThe Author and Co-Authors confirm that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement purport to assign, any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\\n\\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\\n\\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\nTERMINATION
\\n\\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\\n\\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\\n\\nIntechOpen’s DUTIES AND RIGHTS
\\n\\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\\n\\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen agrees to provide publishing services which include: managing editing (editorial and publishing process coordination, Author assistance); publishing software technology; language copyediting; typesetting; online publishing; hosting and web management; and abstracting and indexing services.
\\n\\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\\n\\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\nMISCELLANEOUS
\\n\\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\\n\\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\\n\\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\\n\\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\\n\\nPolicy last updated: 2018-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'When submitting a manuscript, the Author is required to accept the Terms and Conditions set out in our Publication Agreement – Monographs/Compacts as follows:
\n\nCORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
\n\nThe Author, on his or her own behalf and on behalf of any of the Co-Authors, reserves the following rights in the Work but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Work as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Author, and any Co-Author, confirms that they are, and will remain, a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including all published versions, is retained by the Author and any Co-Authors.
\n\nSubject to the license granted above, the Author and Co-Authors retain patent, trademark and other intellectual property rights to the Work.
\n\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
\n\nThe Author, on his/her own behalf and on behalf of the Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from the translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
\n\nAUTHOR'S DUTIES
\n\nWhen distributing or re-publishing the Work, the Author agrees to credit the Monograph/Compacts as the source of first publication, as well as IntechOpen. The Author guarantees that Co-Authors will also credit the Monograph/Compacts as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Work.
\n\nThe Author agrees to:
\n\nThe Author will be held responsible for the payment of the agreed Open Access Publishing Fee before the completion of the project (Monograph/Compacts publication).
\n\nAll payments shall be due 30 days from the date of issue of the invoice. The Author or whoever is paying on behalf of the Author and Co-Authors will bear all banking and similar charges incurred.
\n\nThe Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Work worldwide for the full term of the above licenses, and shall provide to IntechOpen, at its request, the original copies of such consents for inspection or the photocopies of such consents.
\n\nThe Author shall obtain written informed consent for publication from those who might recognize themselves or be identified by others, for example from case reports or photographs.
\n\nThe Author shall respect confidentiality during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Author and Co-Authors are confidential and are intended only for the recipients. The contents of any communication may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\nAUTHOR'S WARRANTY
\n\nThe Author and Co-Authors confirm and warrant that the Work does not and will not breach any applicable law or the rights of any third party and, specifically, that the Work contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy.
\n\nThe Author and Co-Authors confirm that: (i) the Work is their original work and is not copied wholly or substantially from any other work or material or any other source; (ii) the Work has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) Authors and any applicable Co-Authors are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) Authors and any applicable Co-Authors have not assigned, and will not during the term of this Publication Agreement purport to assign, any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Author and Co-Authors also confirm and warrant that: (i) he/she has the power to enter into this Publication Agreement on his or her own behalf and on behalf of each Co-Author; and (ii) has the necessary rights and/or title in and to the Work to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licences in this Publication Agreement. If the Work was prepared jointly by the Author and Co-Authors, the Author confirms that: (i) all Co-Authors agree to the submission, license and publication of the Work on the terms of this Publication Agreement; and (ii) the Author has the authority to enter into this biding Publication Agreement on behalf of each Co-Author. The Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each Co-Author.
\n\nThe Author agrees to indemnify IntechOpen harmless against all liabilities, costs, expenses, damages and losses, as well as all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of, or in connection with, any breach of the agreed confirmations and warranties. This indemnity shall not apply in a situation in which a claim results from IntechOpen's negligence or willful misconduct.
\n\nNothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\nTERMINATION
\n\nIntechOpen has the right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Author and/or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Author and/or any Co-Author (being a private individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Author and/or any Co-Author (as a corporate entity) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for, or enters into, any compromise or arrangement with any of its creditors.
\n\nIn the event of termination, IntechOpen will notify the Author of the decision in writing.
\n\nIntechOpen’s DUTIES AND RIGHTS
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen, at its discretion, agrees to publish the Work attributing it to the Author and Co-Authors.
\n\nUnless prevented from doing so by events beyond its reasonable control, IntechOpen agrees to provide publishing services which include: managing editing (editorial and publishing process coordination, Author assistance); publishing software technology; language copyediting; typesetting; online publishing; hosting and web management; and abstracting and indexing services.
\n\nIntechOpen agrees to offer free online access to readers and use reasonable efforts to promote the Publication to relevant audiences.
\n\nIntechOpen is granted the authority to enforce the rights from this Publication Agreement on behalf of the Author and Co-Authors against third parties, for example in cases of plagiarism or copyright infringements. In respect of any such infringement or suspected infringement of the copyright in the Work, IntechOpen shall have absolute discretion in addressing any such infringement that is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\nIntechOpen has the right to include/use the Author and Co-Authors names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Work and has the right to contact the Author and Co-Authors until the Work is publicly available on any platform owned and/or operated by IntechOpen.
\n\nMISCELLANEOUS
\n\nFurther Assurance: The Author shall ensure that any relevant third party, including any Co-Author, shall execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\nThird Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\nEntire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by, or on behalf of, the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (known as the "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of any fraudulent pre-contract misrepresentation or concealment.
\n\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\nVariation: No variation of this Publication Agreement shall have effect unless it is in writing and signed by the parties, or their duly authorized representatives.
\n\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\n\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
\n\nPolicy last updated: 2018-09-11
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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The effects of these two types of factors overlap for the most part. The combined effects of these two aging processes also affect dermal matrix alterations. The main clinical signs of skin aging include wrinkling and irregular pigmentation, which are influenced by a combination of intrinsic and extrinsic (e.g., UV radiation, heat, smoking, and pollutants) factors. Histologically, collagen decreases, and the dermis is replaced by abnormal elastic fibers as a cause of wrinkle formation through the loss of skin elasticity. There have been numerous studies of skin aging performed to elucidate the underlying molecular mechanisms and to develop various antiaging therapeutics and preventive strategies. We summarized the molecular mechanisms and treatments of skin aging. Mainly UV radiation induces ROS formation and DNA damage, leading to increased production of MMPs and decreased production of collagen in keratinocytes and fibroblasts, which reflect the central aspects of skin aging. Besides UV radiation exposure, extrinsic factors including tobacco smoking, exposure to environmental pollutants, infrared radiation, and heat contribute to premature skin aging. Like UV radiation, these factors cause ROS formation and increase expression of MMPs, thus accelerating skin aging by inducing extracellular matrix (ECM) degradation. Accumulated collagen fibrils inhibit the new collagen synthesis and account for the further degradation of the ECM through this positive feedback loop. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. 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