Spinocerebellar functional problems in common SCA types.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
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\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
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\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8909",leadTitle:null,fullTitle:"Slope Engineering",title:"Slope Engineering",subtitle:null,reviewType:"peer-reviewed",abstract:"The field of slope engineering encompasses slope stability analysis and design, movement monitoring, and slope safety management and maintenance. Engineers in this field are concerned with landslides and other gravity-stimulated mass movements. Their job is to frequently evaluate existing and proposed slopes to assess their stability. As such, this book provides information on remote sensing in landslide detection, tunnel face stability, stability analysis and maintenance of cut slopes, design techniques in rock and soil engineering, statistical models for landslide risk mapping, slope stability analysis in open-pit mines, ecological engineering for slope stabilization, and asphalt-stabilized strengthening in open-pit coal mining.",isbn:"978-1-83962-924-2",printIsbn:"978-1-83962-923-5",pdfIsbn:"978-1-83962-946-4",doi:"10.5772/intechopen.82508",price:119,priceEur:129,priceUsd:155,slug:"slope-engineering",numberOfPages:206,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"9be2d5801074590ab1d79845ee5c47e9",bookSignature:"Ali Ismet Kanlı",publishedDate:"March 17th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/8909.jpg",numberOfDownloads:3362,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:2,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:3,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 30th 2020",dateEndSecondStepPublish:"July 21st 2020",dateEndThirdStepPublish:"September 19th 2020",dateEndFourthStepPublish:"December 8th 2020",dateEndFifthStepPublish:"February 6th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"243975",title:"Dr.",name:"Ali Ismet",middleName:null,surname:"Kanlı",slug:"ali-ismet-kanli",fullName:"Ali Ismet Kanlı",profilePictureURL:"https://mts.intechopen.com/storage/users/243975/images/system/243975.jpg",biography:"Prof. Dr. Ali Ismet Kanlı received his undergraduate degree in 1989 from Istanbul University, Faculty of Engineering, Department of Geophysical Engineering. In 1994, he graduated from Istanbul University, Institute of Science with an MSc, and in 1998, he completed his doctorate at the same institute. He began his academic career in 1992 as a research assistant in Istanbul University, Faculty of Engineering, Department of Geophysical Engineering, Division of Applied Geophysics. He became an assistant professor in 2001, an associate professor in 2010, and a full professor in 2016 for the same division. Dr. Kanli is the head of the Applied Geophysics Division of the Geophysical Engineering Department. He has carried out and directed many international and national projects and has several national and international scientific publications to his credit. He is an editorial board member of ten international journals and a reviewer for many international and national journals. He has also been a referee in many international and national projects. Dr. Ali is a member of three national and eight international scientific associations. His areas of scientific interest include applied and near-surface geophysics, engineering and environmental geophysics, engineering seismology, exploration seismology, structural geophysics, earthquake engineering, geotechnical geophysics, borehole geophysics and well logging, alternative energy, and geothermal exploration.",institutionString:"Istanbul University Cerrahpaşa",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Istanbul University Cerrahpaşa",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"708",title:"Geotechnical Engineering",slug:"engineering-civil-engineering-geotechnical-engineering"}],chapters:[{id:"75354",title:"Design and Construction for Tunnel Face Stability: Theoretical and Modeling Approach",doi:"10.5772/intechopen.96277",slug:"design-and-construction-for-tunnel-face-stability-theoretical-and-modeling-approach",totalDownloads:330,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tunneling is considered to be among the most important projects in all countries worldwide. However, interspersed, some tunnels rise to problems of instability during excavation. This chapter is a case study of the tunnel of “Djebel El Kantour” which is part of the East–West Algerian Highway. Face stability is the most critical problems that affect the subject of our research. This study is carried out via analytical and numerical methods based on the instability relationship, characteristics of the ground and the geometry of the tunnel, to draw conclusions and recommendations for overcoming this problem.",signatures:"Adel Aissi, Abdelghani Brikat, Ali Ismet Kanlı, Aissa Benselhoub and Oussama Kessal",downloadPdfUrl:"/chapter/pdf-download/75354",previewPdfUrl:"/chapter/pdf-preview/75354",authors:[{id:"243975",title:"Dr.",name:"Ali Ismet",surname:"Kanlı",slug:"ali-ismet-kanli",fullName:"Ali Ismet Kanlı"},{id:"324217",title:"Ph.D.",name:"Aissa",surname:"Benselhoub",slug:"aissa-benselhoub",fullName:"Aissa Benselhoub"},{id:"339147",title:"Dr.",name:"Adelghani",surname:"Brikat",slug:"adelghani-brikat",fullName:"Adelghani Brikat"},{id:"339149",title:"Dr.",name:"Adel",surname:"Aissi",slug:"adel-aissi",fullName:"Adel Aissi"},{id:"344729",title:"Dr.",name:"Oussama",surname:"Kessal",slug:"oussama-kessal",fullName:"Oussama Kessal"}],corrections:null},{id:"74438",title:"Geoysynthetic Reinforced Embankment Slopes",doi:"10.5772/intechopen.95106",slug:"geoysynthetic-reinforced-embankment-slopes",totalDownloads:526,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Slope failures lead to loss of life and damage to property. Slope instability of natural slope depends on natural and manmade factors such as excessive rainfall, earthquakes, deforestation, unplanned construction activity, etc. Manmade slopes are formed for embankments and cuttings. Steepening of slopes for construction of rail/road embankments or for widening of existing roads is a necessity for development. Use of geosynthetics for steep slope construction considering design and environmental aspects could be a viable alternative to these issues. Methods developed for unreinforced slopes have been extended to analyze geosynthetic reinforced slopes accounting for the presence of reinforcement. Designing geosynthetic reinforced slope with minimum length of geosynthetics leads to economy. This chapter presents review of literature and design methodologies available for reinforced slopes with granular and marginal backfills. Optimization of reinforcement length from face end of the slope and slope - reinforcement interactions are also presented.",signatures:"Akshay Kumar Jha and Madhav Madhira",downloadPdfUrl:"/chapter/pdf-download/74438",previewPdfUrl:"/chapter/pdf-preview/74438",authors:[{id:"327589",title:"Dr.",name:"Akshay Kumar",surname:"Jha",slug:"akshay-kumar-jha",fullName:"Akshay Kumar Jha"},{id:"329058",title:"Prof.",name:"M.R.",surname:"Madhav",slug:"m.r.-madhav",fullName:"M.R. Madhav"}],corrections:null},{id:"75210",title:"Design Techniques in Rock and Soil Engineering",doi:"10.5772/intechopen.90195",slug:"design-techniques-in-rock-and-soil-engineering",totalDownloads:358,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"At the initial stage of tunnel design, the tunnel stability can be assessed by different design techniques which are broadly classified into three categories i.e. Mathematical Analysis, Empirical Methods and Numerical Analysis. Mathematical methods or closed form solutions are more precise methods; however, its use is limited to simple geometries and almost impossible for complex geometries due to complex and tedious calculations involved. In practice, Empirical and Numerical Methods are usually used for stability analysis of tunnels. It should be noted that it is not the replacement of final design. Empirical design methods use information about the structural geology and other rock mass properties as input that can be easily obtained at the initial stage of a project. Numerical Methods commonly require mechanical properties, especially strength and deformation of rocks. Numerical methods are also considered as precise due to provision of allowance for variable inputs and geometry and having ability for sensitivity analysis. It is good practice to evaluate the stability of tunnels using at least two Empirical methods and validated through Numerical methods.",signatures:"Zahid Ur Rehman, Sajjad Hussain, Noor Mohammad, Akhtar Gul and Bushra Nawaz",downloadPdfUrl:"/chapter/pdf-download/75210",previewPdfUrl:"/chapter/pdf-preview/75210",authors:[{id:"280305",title:"Ph.D. Student",name:"Zahid Ur",surname:"Rehman",slug:"zahid-ur-rehman",fullName:"Zahid Ur Rehman"},{id:"314395",title:"Mr.",name:"Sajjad",surname:"Hussain",slug:"sajjad-hussain",fullName:"Sajjad Hussain"},{id:"314396",title:"Ms.",name:"Bushra",surname:"Nawaz",slug:"bushra-nawaz",fullName:"Bushra Nawaz"},{id:"344014",title:"Dr.",name:"Noor",surname:"Mohammad",slug:"noor-mohammad",fullName:"Noor Mohammad"},{id:"344015",title:"Mr.",name:"Akhtar",surname:"Gul",slug:"akhtar-gul",fullName:"Akhtar Gul"}],corrections:null},{id:"73684",title:"Three Dimensional Slope Stability Analysis of Open Pit Mine",doi:"10.5772/intechopen.94088",slug:"three-dimensional-slope-stability-analysis-of-open-pit-mine",totalDownloads:454,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The 3-dimensional slope stability analysis has been developing rapidly since the last decade, and currently a number of geomechanical researchers in the world have put forward ideas for optimization of slope design related to the economics and safety of mining operations. The 3-dimensional slope stability analysis methods has answered the assumption of spatial parameters in determining safety factors and the failure probability, thus the volume of failed material and the location of the most critical slopes can be determined. This chapter discusses two methods of 3-dimensional slope stability analysis, namely the limit equilibrium method (LEM) and finite element method (FEM). LEM 3D requires an assumption of failure type with the variable of analysis are the maximum number of columns, the amount of grid points, increment radius, and type of slip surface. On the other hand, FEM 3D requires an assumption of convergence type, absolute force and energy, with the variable of analysis are mesh type and maximum number of iterations. LEM 3D shows that the cuckoo algorithm is reliable in obtaining position and shape of slip surface. Meanwhile FEM 3D, the optimum iteration number needs to be considered to improve analysis efficiency and preserving accuracy.",signatures:"Masagus Ahmad Azizi, Irfan Marwanza, Muhammad Kemal Ghifari and Afiat Anugrahadi",downloadPdfUrl:"/chapter/pdf-download/73684",previewPdfUrl:"/chapter/pdf-preview/73684",authors:[{id:"326051",title:"Dr.",name:"Masagus Ahmad",surname:"Azizi",slug:"masagus-ahmad-azizi",fullName:"Masagus Ahmad Azizi"},{id:"331111",title:"Dr.",name:"Irfan",surname:"Marwanza",slug:"irfan-marwanza",fullName:"Irfan Marwanza"},{id:"331112",title:"Dr.",name:"Afiat",surname:"Anugrahadi",slug:"afiat-anugrahadi",fullName:"Afiat Anugrahadi"},{id:"331113",title:"Mr.",name:"Muhammad Kemal",surname:"Ghifari",slug:"muhammad-kemal-ghifari",fullName:"Muhammad Kemal Ghifari"}],corrections:null},{id:"74343",title:"Asphalt Fill Strengthening of Free Slip Surfaces of Shale Slopes in Asphaltite Open Quarry: Stability Analysis of Free Sliding Surface for Wet Shale Slopes in Avgamasya Asphaltite Open Quarry No 2. Site",doi:"10.5772/intechopen.94893",slug:"asphalt-fill-strengthening-of-free-slip-surfaces-of-shale-slopes-in-asphaltite-open-quarry-stability",totalDownloads:376,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The stability analysis carried out by GEO5 software and uses free sliding analysis by wet and pore saturated weight charting provided the safety factor of 1.35. The safety precautions were followed by inclinometers and wire extensometer measurements. The other pore saturated asphalt bound shear box and unaxial test compression tests were resulted in the geotechnical and geoseismical data over sliding soil /shale inter surface quality and the characteristics of free rock falling risk and discontinuity distribution, sub crack density and distribution on stereo nets were determined. The research was firstly followed the perched water levels on geoseismical data over causing water burst or explosion of highly free mud and landslides. The hazardous rock falls over saturated soil and uncohesive rock explosions. The proposed study was secondly as strengthening methods such as asphalt mixing as precautious on shear stabilization and other wire mesh barriers anchored. The free sliding cracks was filled by asphalt and compressed for stabilization strengthening known as the characteristics of avoiding shear falls in the future. The unconditional expectations related to this study was also defined for this region such as the influence of the ground water, rock cracks and slope design, explosion exchange dynamics leading to landslide.",signatures:"Yildırım İsmail Tosun",downloadPdfUrl:"/chapter/pdf-download/74343",previewPdfUrl:"/chapter/pdf-preview/74343",authors:[{id:"200229",title:"Dr.",name:"Yıldırım",surname:"İsmail Tosun",slug:"yildirim-ismail-tosun",fullName:"Yıldırım İsmail Tosun"}],corrections:null},{id:"73907",title:"The Potential of Remote Sensing to Assess Conditioning Factors for Landslide Detection at a Regional Scale: The Case in Southeastern Colombia",doi:"10.5772/intechopen.94251",slug:"the-potential-of-remote-sensing-to-assess-conditioning-factors-for-landslide-detection-at-a-regional",totalDownloads:319,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This landslide detection research applied remote sensing techniques. Morphometry to derive both DEM terrain parameters and land use variables. SAR interferometry (InSAR) for showing that InSAR coherence and InSAR displacement obtained with SRTM DEM 30 m resolution were strongly related to landslides. InSAR coherence values from 0.43 to 0.66 had a high association with landslides. PS-InSAR allowed to estimate terrain velocities in the satellite line-of-sight (LOS) in the range − 10 to 10 mm/year concerning extremely slow landslide displacement rates. SAR polarimetry (PolSAR) was used over L-band UAVSAR quad-pol data, obtaining the scattering mechanism of volume and surface retrodispersion more associated with landslides. The optical remote sensing with a multitemporal approach for change detection by multi-year Landsat (5, 7 and 8)-NDVI, showed that NDVI related to landslides had values between 0.42 and 0.72. All the information was combined into a multidimensional grid product and crossed with training data containing a Colombian Geologic Service (CGS) landslide inventory. A detection model was implemented using the Random Forest supervised method relating the training sample of landslides with multidimensional explanatory variables. A test sample with a proportion of 70:30 allowed to find the accuracy of detection of about 70.8% for slides type.",signatures:"Nixon Alexander Correa-Muñoz and Carol Andrea Murillo-Feo",downloadPdfUrl:"/chapter/pdf-download/73907",previewPdfUrl:"/chapter/pdf-preview/73907",authors:[{id:"326644",title:"Prof.",name:"Nixon",surname:"Correa-Munoz",slug:"nixon-correa-munoz",fullName:"Nixon Correa-Munoz"},{id:"326647",title:"Dr.",name:"Carol Andrea",surname:"Murillo-Feo",slug:"carol-andrea-murillo-feo",fullName:"Carol Andrea Murillo-Feo"}],corrections:null},{id:"74242",title:"Comparative Evaluation of Various Statistical Models and Its Accuracy for Landslide Risk Mapping: A Case Study on Part of Himalayan Region, India",doi:"10.5772/intechopen.94347",slug:"comparative-evaluation-of-various-statistical-models-and-its-accuracy-for-landslide-risk-mapping-a-c",totalDownloads:342,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Among other natural hazards, Landslides are the most prominent and frequently occurring natural disaster in the state of Himachal Pradesh with higher socio-economical losses. About 0.42 million sq.kms of area are prone to landslide activities in our country that is excluding the snow covered areas. The current research focuses on estimating the landslide risk zones of the Shimla Tehsil, Himachal Pradesh using various statistical models. Landslide contributing factors as such Landuse Landcover, Elevation, Slope, Lithology, Soil, Geology and Geomorphology has been used to assess the Landslide risk factors. Data obtained from LANDSAT 8 OLI sensors, SRTM DEM, Soil and Land Use Survey of India and SOI Toposheets have been used as sources. Weighted Overlay, Fuzzy logic and Analytical Hierarchical Process models will be used to categorize the Vulnerability and risk Zones of the study area. The causative factors were analyzed and processed in GIS environment. These values will be then being integrated using various studied models to produce individual landslide vulnerability and risk zones. The results reveal that most of the study area falls under Very Low risk category with a total coverage of 67.34%. Low and Moderate area covers about 23% and 9.13% of the study area. Higher risk areas only account for about 0.46%. Higher percent of the study area is mostly covered by settlements. National highways, Metal roads, Slopes and Denser settlements are located along the Moderate and low risk areas. The results retrieved from the WOM model reveals a total of 55% of the area comes under very low category. Low and Moderate category covers about 31.4% and 10.6% of the study area. High and Very High category cover a total of 1.9% together.",signatures:"C. Prakasam, Aravinth R., Varinder S. Kanwar and B. Nagarajan",downloadPdfUrl:"/chapter/pdf-download/74242",previewPdfUrl:"/chapter/pdf-preview/74242",authors:[{id:"327580",title:"Associate Prof.",name:"Dr C",surname:"Prakasam",slug:"dr-c-prakasam",fullName:"Dr C Prakasam"},{id:"334305",title:"Mr.",name:"Aravinth",surname:"R",slug:"aravinth-r",fullName:"Aravinth R"},{id:"334307",title:"Dr.",name:"Varinder",surname:"S Kanwar",slug:"varinder-s-kanwar",fullName:"Varinder S Kanwar"},{id:"334308",title:"Dr.",name:"B",surname:"Nagarajan",slug:"b-nagarajan",fullName:"B Nagarajan"}],corrections:null},{id:"73931",title:"Integrated Analysis Method for Stability Analysis and Maintenance of Cut-Slope in Urban",doi:"10.5772/intechopen.94252",slug:"integrated-analysis-method-for-stability-analysis-and-maintenance-of-cut-slope-in-urban",totalDownloads:257,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the process of constructing roads for the development of the city, cut-slopes are made by excavating mountains. However, these cut-slopes are degraded in strength by time-deterioration phenomenon, and progressive slope failure is caused. This study developed an integrated analysis method for stability analysis and maintenance of cut-slopes in urban. The slope stability analysis was performed using the finite element model, and the progressive slope failure by time-dependent deterioration was quantified by using the strength parameters of soil applying the strength reduction factor (SRF). The displacements until the slope failure by slope stability analysis were quantified by cumulative displacement curve, velocity curve, and inverse velocity curve and, applied to the slope maintenance method. The inverse-velocity curve applied to the prediction of the time of slope failure was regressed to the 1st linear equation in the brittle material and the 3rd polynomial equation in the ductile material. This is consistent with the proposed formula of Fukuzono and also shows similar behavior to the failure case in literature. In the future, integrated analysis method should be improved through additional research. And it should be applied to cut-slope to prevent disasters.",signatures:"Mincheol Park, Heuisoo Han and Yoonhwa Jin",downloadPdfUrl:"/chapter/pdf-download/73931",previewPdfUrl:"/chapter/pdf-preview/73931",authors:[{id:"327494",title:"Dr.",name:"Mincheol",surname:"Park",slug:"mincheol-park",fullName:"Mincheol Park"}],corrections:null},{id:"73557",title:"Ecological Engineering Measures for Ravine Slope Stabilization and Its Sustainable Productive Utilization",doi:"10.5772/intechopen.94136",slug:"ecological-engineering-measures-for-ravine-slope-stabilization-and-its-sustainable-productive-utiliz",totalDownloads:400,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The 120 countries have committed to set the UNCCD sustainable development goal on achieving the land degradation neutrality by 2030 including India. The target has to be accomplished in a synergistic and cost-effective manner in accordance with countries’ specific national contexts and development priorities. Globally, the ravine landscapes are considered among the world’s most degraded ecosystems. Therefore, restoring ravines is considered a high priority item in the natural resource management programs. The vegetation cover augmented with appropriate conservation measures is the most sought restoration strategy. The engineering measures are prerequisite for slope stabilization and sustainable productive utilization in ravine ecosystem. The several methods for slope stabilization are available but only few are applied in ravine land. Therefore, in this chapter, we have covered only those slope stabilization techniques which were successfully applied for the restoration of ravine land.",signatures:"Gaurav Singh, Raj Kumar, Dinesh Jinger and Dinesh Dhakshanamoorthy",downloadPdfUrl:"/chapter/pdf-download/73557",previewPdfUrl:"/chapter/pdf-preview/73557",authors:[{id:"327586",title:"Dr.",name:"Gaurav",surname:"Singh",slug:"gaurav-singh",fullName:"Gaurav Singh"},{id:"327587",title:"Dr.",name:"Raj",surname:"Kumar",slug:"raj-kumar",fullName:"Raj Kumar"},{id:"331673",title:"Dr.",name:"Dinesh",surname:"Jinger",slug:"dinesh-jinger",fullName:"Dinesh Jinger"},{id:"331676",title:"Dr.",name:"Dinesh",surname:"Dhakshanamoorthy",slug:"dinesh-dhakshanamoorthy",fullName:"Dinesh Dhakshanamoorthy"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8361",title:"Applied Geophysics with Case Studies on 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Aging is a biological process that causes a progressive deterioration of structure and function of all organs over the time [1]. According to the United Nation’s report, the number of people aged 60 and over in the world has increased from 8% (200 million) in 1950 to 11% (760 million) in 2005, and it is estimated that this number will further increase to 22% (2 billion) in 2050. It is expected that in the US alone, the aged population of 65 and over will grow rapidly and reach 81 million by 2050 [2,3]. This rapidly increasing aging population will not only cause a decline of productive workforce but also negatively affect the country’s economy. Furthermore, aging is one of the major risk factors for the development of many diseases including cardiovascular diseases [4], stroke [5] and cancer [6]. Moreover, the epidemiological data strongly suggests that more often these diseases are diagnosed in older people compared to younger individuals. In addition to the huge economical impact, these diseases also cause loss of productivity and disability in the elderly population. Therefore, it is extremely important to give high priorities to aging and age-associated disease research in order to develop novel therapies to slow the aging process as well as to prevent and /or treat the age-associated diseases more effectively. It has been found that many factors including genetics [7,8], metabolism [9], diet [10] and stress [11] can in part contribute to the aging process. Similar to other organs, the vascular system, which provides oxygen and nutrients to all the organs in the body, is also affected by the aging process and becomes more vulnerable to disease development in the elders [12,13]. For example, vascular diseases such as coronary artery disease, peripheral arterial disease, stroke and microvascular disease are more often found in the aged population. This is in part due to the structural and functional changes that occur in the vascular system of aged people. In this review, we highlighted (i) the changes that occur in the vascular system, particularly in the endothelium due to aging; (ii) the mechanisms by which the age-associated changes lead to decreased angiogenesis; (iii) how the ubiquitin proteasome system plays important roles in regulating vascular endothelium function; (iv) the mechanisms by which the age-associated increase in oxidative stress might cause endothelial dysfunction; and finally, (iv) how the age-associated changes in the vascular system lead to the development of various vascular diseases such as coronary artery disease, peripheral artery disease and diabetic retinopathy.
Many changes are known to occur due to aging in the entire vascular system that includes heart, coronary arteries, peripheral arteries and small blood vessels known as capillaries (Figure 1). There will be an increase in the overall size of the heart, due to an increase in the heart wall thickness in the aging heart. The heart valves, which control the unidirectional of blood flow, will also become stiffer. There is also deposition of the pigments known as lipofuscin in the aged heart along with possible loss of cardiomyocytes as well as cells present in the sinoatrial node (SA node). Furthermore, there is an increase in the size of cardiomyocytes to compensate for the loss of the heart cells. These changes altogether cause a progressive decline in the physiological functions of the heart in the elderly population. In addition to these changes in the heart, the blood vessels also undergo significant changes. For example, the aorta, the large artery that originates from the heart becomes thicker, stiffer and less flexible. Smaller blood vessels also become thicker and stiffer. These changes are due to alterations that occur in the cells present in the blood vessels and also in the connective tissue of the blood vessel wall. All these changes ultimately lead to hypertrophy of the heart and causes an increase in the blood pressure [14]. There seems to be an interconnection between changes in the blood vessels and changes in the heart. Changes such as thickening of the blood vessels lead to increase in the blood pressure, which further affects the heart function. In that condition, the heart tries to function more efficiently by becoming larger in size (hypertrophy) and by enhancing its pumping capacity.
The vascular endothelium is comprised of a layer of endothelial cells that are positioned in the inner surface of blood vessels. The endothelium forms an interface between circulating blood and vessel wall, hence has a direct contact with circulating blood. In addition to serving as a barrier, endothelial cells participate in many physiological functions. They control vascular homeostasis, regulate blood pressure by vasoconstriction and vasodilatory mechanisms and promote angiogenesis when body requires. They also secrete anti-coagulatory factors to prevent clotting [15]. Importantly, vascular endothelial cells express many important molecules such as vascular endothelial growth factor (VEGF) and its receptors vascular endothelial growth factor receptor-1 (VEGFR1), vascular endothelial growth factor receptor-2 (VEGFR2) and vascular endothelial growth factor receptor-3 (VEGFR3). VEGFR1 and VEGFR2 are expressed exclusively in vascular endothelial cells, whereas VEGFR3 is mainly expressed in the lymphatic endothelial cells [16]. The VEGF/VEGFR2 signaling is critical for vasculogenesis as well as angiogenesis [16]. Disruption or loss of VEGF and VEGFR2 genes is associated with severe vascular abnormalities or embryonic lethality [17]. Furthermore, the endothelial cells produce other growth factors known as angiopoitins (Ang), which are required to remodel and stabilize the immature blood vessels induced by VEGF/VEGFR2. Moreover, molecules such as neuropilines are involved in modulating the binding as well as responses to VEGF receptors [16]. Furthermore, endothelial cells express endothelial nitric oxide synthase (eNOS), which produces nitric oxide (NO). NO has many important physiological functions. For example, NO promotes vasodilation [18], as well as inhibits leukocyte adhesion [19], thrombocyte aggregation [20] and smooth muscle cell proliferation [21]. Under basal conditions eNOS is found inactive, however its activity is increased by many factors including acetyl choline, bradykinin, thrombin and histamine that lead to increased production of NO.
Aging also influences endothelial cells and causes a progressive deterioration of their function. Previous studies have shown that endothelium-mediated vasodilatory function progressively declines with age [22]. This is associated with decreases in eNOS expression and NO production by aging endothelial cells [23,24]. Recently, Yoon et al. have shown that decreased expression of eNOS in aged human umblical vein endothelial cells [24]. However, the precise mechanisms for the age-associated decreases of these molecules remain unknown. Interestingly, it has been observed that the aging endothelial cells produce increased amount of O2-anions [25], which scavenge NO to form peroxinitrite, a potent form of free radical. Peroxinitrite further inactivates eNOS and decreases its activity [26]. These described mechansims in part explain oxidative stress-mediated decrease of eNOS and NO in aging endothelial cells. On the other hand, it has been suggested that the age-associated changes that occur in eNOS regulatory proteins such as caveolin-1, pAkt, and heat shock protein 90 (Hsp90) contribute to the decreased activity of eNOS in aged endothelial cells [24]. In addition to these regulatory mechanisms, several other factors also regulate eNOS activity. For example, shear stress [27], estrogens [28], and growth factors [29] could also positively regulate eNOS expression. However, as their expression levels decrease with advancing in age, these changes might cause a subsequent decrease in eNOS expression. Taken together, these alterations finally lead to both a decreased expression of eNOS and decreased levels of NO in aged endothelial cells. In addition to these changes in endothelial cells, aging also causes several other changes in vascular smooth muscle cells (VSMCs). During the aging process, VSMCs migrate from tunica media to tunica intima and start accumulating there. These cells become less functional and less responsive to growth factors such as transforming growth factor-beta1 [30]. As VSMCs are important regulatory cells that control the vascular wall by vasoconstriction and vasodilatory mechanisms, progressive loss of their physiological functions might lead to changes in vascular endothelium and impaired vascular function in the aged blood vessels.
Angiogenesis, the formation of new blood vessels from pre-existing vessels, is a physiologically an important process during growth, menstrual cycle and wound healing. Several factors are known to influence angiogenesis. The most important one is hypoxia, which activates the transcription factors such as hypoxia-inducible factor-1 alpha (HIF-1 alpha) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) [31]. These transcription factors increase the production of VEGF and other growth factors that promote proliferation and migration of vascular endothelial cells. During angiogenesis, matrix metalloproteinases, the enzymes that degrade the capillary basement membrane and extra-cellular matrix, will be increased in order to facilitate endothelial cell migration. Therefore, angiogenesis is a complex process, and its timely induction is tightly controlled by coordination from multiple factors. Unfortunately, angiogenesis is markedly reduced by aging [32]. In keeping with this notion, wound healing, which is associated with angiogenesis, is also markedly impaired in aged mice [33] and significantly delayed and impaired in aged individuals [34]. Several studies were attempted to find the age-associated changes that might cause impaired angiogenesis. To this end, it has been observed that aging endothelial cells are functionally less angiogenic and less responsive to growth factors [32]. Rivard et al. [32] have found that VEGF levels were markedly reduced in aging mice. During hind limb ischemia, the old mice are unable to produce sufficient VEGF levels compared to younger mice, which are critically necessary for neovascularization and proper wound healing. Furthermore, the T lymphocyte-derived VEGF also markedly reduced in old mice, which compromised the angiogenesis-mediated wound healing process during the hind limb ischemia. This study, therefore, identified loss of VEGF as one of the key factors for the impaired angiogenesis observed in aged mice [32]. Furthermore, Qian et al. found that in addition to VEGF decrease, its key receptor VEGFR2 levels were also significantly decreased in eNOS knockout old mice [35]. Since the VEGF/VEGFR2 signaling is crucial for the survival, proliferation and migration of endothelial cells, a decrease of this pivotal signaling pathway may lead to impaired angiogenesis and delayed wound healing in aged subjects. Even in the eNOS knockout mice, which produce significantly less NO, the angiogenic response was markedly less in older mice due to decreased expression of VEGFR2. This partially explains that VEGFR2 plays an important role in neovascularization even in the absence of eNOS and corresponding NO [35].
Importantly, in addition to the loss of pro-angiogenic molecules, the anti-angiogenic molecules such as thrombospondin-2 (TSP2) levels were also affected by aging. To demonstrate the significance of TSP2 in aging and wound healing process, Agah et al. created full thickness excisional wounds in TSP2 null young and TSP2 null old mice and observed the wound healing process [36]. Consistent with other groups [33], they found that regardless of TSP genetic status, the would healing is delayed in old mice in comparison with young mice. However, interestingly, they found that the wound healing was faster in TSP2 null, old mice compared to wild-type, old mice suggesting that increased TSP2 in older mice might delay the angiogenesis and wound healing process. Correspondingly, there was also impaired expression of matrix metalloproteinase-2 (MMP2) found in TSP2 null old mice. These age-associated increase in expression of TSP2 and impaired MMP2 expression in older mice together might cause impaired angiogenesis and delay the wound healing process [36]. In addition to these changes observed in older mice, there are also changes observed in cell cycle-related molecules, which may affect the proliferation of aged endothelial cells. For example, aged endothelial cells undergo senescence and cease proliferation, which may limit neovascularization. Indeed, after certain passages, human umbilical vein endothelial cells (HUVECs) known to undergo senescence and loose their proliferative capacity [37]. As NO is known to prevent endothelial cell senescence, age associated decreases in eNOS and NO may be in part responsible for the senescence observed in HUVECs. Interestingly, the telomerase reverse transcriptase (TERT), which prevents senescence by counteracting telomere shortening process is active in human endothelial cells. However, after several passages, endothelial cells display a decrease of NO and loss of TERT activity that further lead to endothelial senescence. Indeed, ectopic overexpression of TERT protects from endothelial cells from undergoing senescence and preserve the angiogenic function of endothelial cells [38]. Furthermore, TERT overexpression increased eNOS function and enhanced precursor endothelial cell proliferation and migration that effectively promoted angiogenesis [39,40]. In fact, TERT expression decreased p16 and p21 activities that are significantly increased in senescent endothelial cells. These findings indicate that loss of telomerase-induced senescence also plays a role in affecting angiogenesis in aged endothelial cells. Interestingly, in a separate set of experiments, it has been demonstrated that VEGF-A, a potent pro-angiogenic factor, suppresses both p16 and p21 activities in endothelial cells, suggesting that VEGF-A could serve as an anti-senescence agent [41]. However, it remains unclear whether VEGF-A activates the VEGFR2 kinase to influence hTERT activity to exert this anti-senescence capacity. Taken together, these findings indicate that even though there is a shift between pro-angiogenic and anti-angiogenic molecules in aged endothelial cells, it remains to be determined whether increasing pro-angiogenic factors or inhibiting anti-angiogenic molecules restores angiogenesis and accelerate wound healing process especially by aged endothelial cells. Future research are therefore warranted to thoroughly address these important questions.
Oxidative stress is implicated in causing aging of endothelium and endothelial dysfunctions. In turn, aged endothelium produces increased free radicals, which might further accelerates aging. Based upon biomarkers of oxidant damage, increased levels of nitrotyrosine were observed in human aged vascular endothelial cells [42], Moreover, oxidative stress markers were also observed in the arteries of aged animals [26,43], suggesting that aging is indeed associated with increased formation of reactive oxygen species (ROS). Many different mechanisms are responsible for causing oxidative stress in endothelial cells that includes mitochondria-mediated production of ROS, decreases in free radical scavengers and increased susceptibility of macromolecules to free radical damage. Similar to other cells, oxidative stress damages proteins, lipids and DNA in vascular endothelial cells, thus causing loss of endothelial cell function. One of the major free radicals is super oxide anion (O2-), which is produced by aging mitochondria due to increased mitochondrial DNA damage. It has been demonstrated that NADPH contributes to O2- generation in vascular endothelial cells. Usually, the O2- anions are detoxified to H2O2 by manganese super oxide dismutase (MnSOD), which is present in the mitochondria. However, in the presence of NO, O2- leads to formation of a potent free radical known as peroxinitrite (ONOO-) that further damages macromolecules in the endothelial cells. It has been demonstrated that ONOO- can inactivate both MnSOD and eNOS in the endothelial cells [44]. The switch of eNOS from an NO generating enzyme to an O2- generating enzyme (NO synthase uncoupling) leads to increased production of O2- and enhanced oxidative stress in aged endothelial cells (Figure 2). Taken together, NADPH and eNOS are important contributors for O2- generation in aged endothelial cells, since inhibition of NADPH and eNOS attenuates O2- production in the aorta of aged Wistar-Kyoto rats [25].
The potential role of oxidative stress in vascular endothelium aging is also evident from the experiments carried out with antioxidants. For example, Vitamin C has been shown to decrease telomere shortening and increase the longevity of endothelial cells in culture [45]. N-Acetylcysteine, a potent antioxidant known to decrease endothelial cell senescence by preserving TERT activity and preventing its nuclear export [46]. Interestingly, it has been demonstrated that p66shc deletion protects endothelial cells from aging-associated vascular dysfunction [43] and sirtuins decrease the p66shc expression [47]. Although human clinical trials with antioxidants such as Vitamin C and E have not yielded beneficial effects on improving cardiovascular function [48,49], future studies with other antioxidants such as N-acetylcysteine may yield positive results in improving endothelial dysfunction associated with aging and oxidative stress.
The ubiquitin-proteasome system (UPS) plays important roles in a variety of key cellular functions including cellular protein homeostasis, signal transduction, cell cycle control, immune function, cellular senescence and apoptosis. This system targets specific proteins in the cell for degradation via ubiquitination-mediated destruction mechanism by specific ubiquitin E3 ligases [50,51]. Two major complexes, Skp1-Cul-1-F-box protein complex (SCF) and Anaphase Promoting Complex/Cyclosome (APC/C) are involved in the regulation of cell cycle as well as other key regulatory processes in the cell. Dysfunction of UPS leads to development of many diseases including cancer and cardiovascular disease. Therefore, how UPS regulates endothelial cell function and endothelial cell cycle is crucial in order to understand the underlying mechanisms involved in vascular disease development, and will also provide important insights into developing novel therapies for many vascular diseases associated with aging. Increasing evidence suggests that UPS regulates endothelial function by specifically regulating the key proteins present in endothelial cells. For example, the half-lives of both eNOS and inducible nitric oxide synthase (iNOS) are regulated by proteasome-dependent degradation [52,53]. Furthermore, the von Hippel-Lindau protein (pVHL) regulates HIF-1 alpha, which is a critical factor involved in regulating angiogenesis [54] (Figure 3). Consistent with the key role of UPS in endothelial function, treatment with low doses of proteasome inhibitor increases endothelial cell function [55]. These findings further suggest that UPS could be a potential target to improve the physiological functions of vasculature, hence may be utilized as a valuable drug target to develop novel treatments for aging-associated vascular diseases. However, the specific E3 ligase complexes and the molecular mechanisms that are involved in the regulation of endothelial cell cycle and endothelial cell function remain unknown.
Recent studies indicate that F-box proteins such as SCFFbw7 and SCFβ-TRCP are potentially involved in regulating endothelial cell function. For example, mice lacking Fbw7 die early (embryonic day 10.5) with developmental defects in vascular and haematopoietic system as well as heart chamber maturation [56,57]. As Fbw7 regulates the key cell cycle regulators including Notch, cyclin E, c-Myc and c-Jun, deletion of Fbw7 leads to accumulation of these substrates in the endothelial and /or hematopoitic cells. Indeed, elevated Notch protein levels were observed in Fbw7-deficient embryos that lead to the deregulation of the transcriptional repressor, Hey1, which is an important factor for cardiovascular development [56]. Therefore, these findings suggest that Fbw7 is an important E3 ligase governing the timely destruction of the key substrates involved in cardiovascular development. Furthermore, our laboratory has recently identified SCFβ-TRCP as an E3 ubiquitin ligase that is potentially involved in regulating VEGFR2 protein levels in microvascular endothelial cells [58]. As stated in above sections, VEGFR2 is the major regulator of angiogenesis. Increased angiogenesis is associated with certain cancers, whereas angiogenesis is markedly decreased in aging individuals. Our study, for the first time, revealed that deregulation of β-TRCP leads to stabilization of VEGFR2 and subsequent increases in angiogenesis, whereas increased β-TRCP activity leads to decreased VEGFR2 levels and reduced angiogenesis. Mechanistically, casein kinase-I (CKI)-induced phosphorylation of VEGFR2 at critical phospho-degrons leads to its ubiquitination by β-TRCP, and subsequent degradation of VEGFR2 through the 26S proteasome [58]. However, we are just beginning to understand the critical role of UPS in endothelial function, future studies are therefore warranted to unravel the important role of various E3 ubiquitin ligases in the regulation of vascular system, which may ultimately, help to prevent vascular diseases in the elderly population.
Aging vascular endothelium is susceptible to the development of various vascular diseases including cardiovascular disease (CVD) (coronary artery disease; atherosclerosis and hypertension), peripheral vascular disease (PVD), diabetic retinopathy, renal vascular disease and micro-vascular disease. Importantly, aging-associated changes that occur in the blood vessels are the major cause for the development of these diseases. Therefore, identifying the molecular changes that occur in the aging-endothelium and elucidating the underlying molecular mechanisms responsible for vascular disease development lead to the development of novel therapies to treat various vascular diseases.
Cardiovascular disease (CVD) is the number one cause of human death in the US as well as in the world. CVD mostly occur in the aged population [59], and according to the World Health Organization, an estimated 17.3 million deaths occurred due to CVD in 2008. Coronary artery disease (CAD) is the major form of CVD, which occurs when coronary arteries are blocked due to atherosclerosis. Aging endothelium is very susceptible for plaque formation that leads to progressive blockage of the coronary arteries. This causes reduced blood supply (decreased supply of oxygen and nutrients) to the affected area of the heart. Although partial blockages may cause symptoms such as angina, complete loss of blood supply leads to heart attack, and if not treated immediately, may lead to sudden death. It has been observed that several age-associated changes in the endothelium-derived factors are responsible for plaque formation in the arteries. Importantly, endothelin (ET), a vascular endothelium-derived growth factor was found to be significantly increased in the aged endothelium [60,61,62]. ET mainly acts through its receptors ET-A and ET-B present on endothelial as well as vascular smooth muscle cells (VSMCs). ET-A activation leads to the constriction and proliferation of VSMCs, whereas ET-B activation leads to increased production of NO, which leads to vasodilation and inhibition of platelet aggregation. Studies indicate that ET-A receptor is mainly involved in the development of atherosclerosis, as inhibition of ET-A receptor prevents atherosclerosis in apolipoprotein-E deficient mice [63]. More importantly, endothelin-1 also decreases eNOS in vascular endothelial cells through ET-A receptor activation [64], suggesting that aging-induced increases in ET-1 as well as increased activation of ET-A receptor are potentially involved in causing atherosclerosis. Furthermore, the aging-induced increased expression of various adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) also contribute to the ongoing process of atherosclerosis [65].
Inflammation, another major factor that is also known to increase with aging potentially contribute to the process of atherosclerosis [66]. Consistently, the incidence of atherosclerosis is found much higher in patients with autoimmune diseases such as rheumatoid arthritis [67,68] and systemic lupus erythematosus [69]. Several different immune cells and increased expression of adhesion molecules also play a major role in developing atherosclerotic plaque. For instance, adhesion molecules ICAM-1 and VCAM-1 not only facilitate the binding of immune cells such as monocytes and T-cells, but also help to transport these cells into the arterial wall. Once inside, the monocytes differentiate into macrophages, and ultimately become foam cells by taking up the oxidized LDL. The proteoglycans present in the extra cellular space of the intima bind with the oxidized LDL molecules. Moreover, the activated T-cells secrete several different cytokines that promote inflammation and activate VSMCs to proliferate. Altogether, this ongoing inflammatory process accelerates the process of atherosclerosis and damages the coronary arterial wall [70] (Figure 4).
Atherosclerosis is also occurs in other arteries other than coronary arteries. If atherosclerosis occurs in the peripheral arteries then it is called peripheral vascular disease or peripheral arterial disease (PAD). PAD is also influenced by aging and mostly occurs in elderly population. The prevalence increases with age from 3% under 60 years of age to 20% in aged 70 years and over [71]. Several factors influence the development of PAD that includes smoking, dyslipidemia, hypertension, diabetes and platelet aggregation. Advanced atherosclerosis in coronary arteries leads to angina and heart attack, whereas in cerebral arteries leads to stroke or transient ischemic attacks. If atherosclerosis occurs in peripheral arteries, that will lead to pain during walking or exercising (claudication), and this condition causes defects in the wound healing or ulcers. Preventing or slowing down the age-associated changes that occurs in the vascular system will protect the aged population from developing various vascular diseases.
Diabetes affects approximately 200 million people around the world and almost 20 million in the United States. Diabetic retinopathy (DR) is a microvascular disease of the eye and most commonly seen in elderly population [72]. Type I as well as Type II diabetes lead to the development of DR. Importantly, microvessels of the eye are mostly affected by hyperglycemia. Several changes in the blood vessels have been observed including loss of pericytes, thickening of the basement membrane and increased permeability of blood vessels in DR. Furthermore, as DR progresses from non-proliferative DR to proliferative DR, the new blood vessels start to grow (neovascularization) to compensate for the affected blood vessels. Although the molecular mechanisms by which diabetes affects blood vessels of the eye remain not completely understood, it is evident from several studies that hyperglycemia directly plays a major role in causing DR. The highly elevated blood glucose activates aldose reductase pathway in certain tissues, which converts the sugars into alcohols, mainly sorbitol. The increased formation of sorbitol further affects the intramural pericytes present in the blood vessels of the retina to cause loss of function of pericytes [73]. As pericytes inhibit the endothelial cell function in occular blood vessels, loss of pericytes function leads to the formation of microaneurysms and ultimately lead to neovascularization. This pathological condition is mostly observed at the borders of retina and occurs along the vascular arcades as well as at the optic nerve head. The newly formed blood vessels do not directly affect the retina, however, the blood vessels are susceptible to vitreous traction and lead to hemorrhage into the vitreous cavity or preretinal space. If not treated, this condition may ultimately lead to vision loss. Many studies were attempted to understand the underlying molecular mechanisms by which neovascularization occurs in DR. Like in other pathological conditions described above, it is in part due to aging-associated defects in angiogenesis. Specifically, increased shear stress causes enhanced permeability of the blood vessels. On one hand, the blood vessels constantly remodel to adapt such changes induced by shear stress. On the other hand, the increased shear stress also causes activation, proliferation and migration of endothelial cells that ultimately cause neovascularization [74]. Furthermore, shear stress also known to cause vasodilatory effects by inhibiting endothelin1, a potent vasoconstrictor and increasing the levels of eNOS and prostaglandins which are potent vasodilators. Increased shear stress also increases matrix production by the endothelial cells, which causes basement thickening. Increased secretion of tissue-type plasminogen activator causes thrombosis and affects microcirculation [75]. Once blood vessels are obscured, the hypoxia generated inside will cause increased dilation of nearby vessels and leads to increased production of growth factors that further promote increased neovascularization.
Among the various growth factors, VEGF-A seems to be potentially involved in promoting angiogenesis in DR. In fact, Miller et al. demonstrated that increased VEGF-A levels correlate with enhanced angiogenesis in ocular tissue [76]. Moreover, high affinity receptors for VEGF-A have also been identified in endothelial cells as well as the pericytes of blood vessels located in the eye. This clearly suggests that VEGF-A-induced signaling pathway might play a potential role in promoting angiogenesis in DR. Furthermore, as angiogenesis is precisely regulated both by pro-angiogenic and anti-angiogenic factors, Funatsu et al. conducted studies to evaluate whether the balance between these two types of molecules is critical in causing angiogenesis in DR [77]. They simultaneously measured pro-angiogenic (VEGF-A) as well as anti-angiogenic molecules (endostatin and PF4) in the vitreous and in the plasma samples to correlate with DR. Interestingly, these studies revealed that vitreous VEGF-A and endostatin levels clearly correlate with the severity of DR, however, no correlation was found between DR and plasma levels of VEGF-A and endostatin [77]. Therefore, this study suggested that loss of balance between pro- and anti-angiogenic molecules might be responsible for the neovascularization observed in DR.
Several drugs were investigated to inhibit neovascularization associated with DR. For example, Ruboxistaurin, a protein kinase C inhibitor tested for efficacy. This is based upon the effects of hyperglycemia on diacylglycerol, which is known to be elevated in DR. Diacylglycerol is a potent activator of protein kinase C, and in turn protein kinase C increases VEGF-A secretion. The protein kinase C inhibitors are known to have some beneficial effects on DR. Furthermore, as VEGF-A levels are increased in DR, anti-VEGF-A compounds were also developed to specifically inhibit neovascularization associated with DR [78].
Aging is one of the major risk factors for the development of various vascular diseases such as cardiovascular disease, peripheral vascular disease and vascular diseases of the eye. Although exact molecular mechanisms are not clearly known, several molecules are known to be altered in aged endothelial cells. Importantly, reduced expression of eNOS and decreased production of NO, a potent vasodilator, have been observed. Furthermore, decreased expression of VEGF and VEGF receptors, and conversely, increased expression of TSP2, a potent angiogenesis inhibitor, have been observed in aged endothelial cells as well. The imbalance between the pro-angiogenic and the anti-angiogenic molecules seems to be responsible for the decreased angiogenesis observed in aged endothelial cells. Importantly, it has been also demonstrated that aging-induced oxidative stress is one of the major contributing factors for the loss of endothelial cell function in advanced age. In this regard, novel antioxidants may prevent aging-induced oxidative stress and thereby improve endothelial cell function in aged cells. As most of the pro-angiogenic and the anti-angiogenic molecules are unstable, recent studies have also established a potential role of UPS in regulating endothelial cell function. However, further thorough investigations are required to pinpoint the precise role of UPS in regulating the aging-associated decline of angiogenesis in the endothelial cells. To this end, it is critical to identify the age-associated molecular signature changes in different cells present in the endothelium such as endothelial cells, smooth muscle cells and pericytes in order to understand how these changes ultimately lead to the loss of endothelial function. This critical information will not only help to identify the crucial signaling pathways through which aging process affects the angiogenesis, but also will aid to develop novel therapies to combat various vascular diseases associated with aging.
This work is supported by the grants from National Institutes of Health to Wenyi Wei (GM089763; GM094777). Shavali Shaik and Zhiwei Wang are recipients of Ruth L. Kirschstein National Research Service Award (NRSA) fellowship. Hiroyuki Inuzuka is recipient of K01 award from National Institute on Aging, NIH (AG041218).
Spinocerebellar Ataxia (SCA) is well known to be an autosomal dominant progressive disease that significantly affect quality of life [1]. Despite the many types of SCA based on genetic code variations, which are reflected in varying severity of symptoms, studies have shown that balance problem remained to be the mainstay reason in quality of life reductions [2]. Due to the appearance of all these symptoms, it is still a challenge in prioritizing problems to be managed in order to provide the best impact. One common language that is generally used as a functioning concept in physical medicine and rehabilitation field, is known as the International Classification of Functioning, Disability, and Health (ICF) concept [3]. Several investigations had shown that utilizing this concept in rehabilitation would substantially enhance success due to better prioritization of problems. Although rehabilitation had been demonstrated to be a cornerstone in ataxia therapy, reports about ICF in SCA rehabilitation is still very much lacking [4].
While rehabilitation could alleviate several symptoms of SCA, many concerned if these therapies could match the speed of natural progression in this disease [4, 5]. As a general overview of rehabilitation interventions, it could be majorly divided into technique based rehabilitation exercises, and the utilization of modalities [2, 6, 7]. Exercises are then more specifically classified to each professionals in the rehabilitation team, namely physiotherapist, occupational therapist, and speech therapist. Each of the rehabilitation team play an essential part towards the holistic care of SCA subjects, and hence has to be well apprehended. On the other hand, modern therapy modalities have emerged as adjuncts to conventional therapy [8, 9]. These newer modalities are targeted to improve neuroplasticity in SCA subjects as the residual brain potential towards better functioning [10]. Therefore, this chapter is dedicated to review the comprehensive management of SCA from the physical medicine and rehabilitation point of view.
Over the years there seem to be growing evidence on the language of physical medicine and rehabilitation, especially in defining disability and its impact to both the individual and the society they live. The most recent terminology utilizes the International Classification of Functioning, Disability and Health (ICF) concept [3]. The ICF concept is a supplement of the 10th revision of International Statistical Classification of Diseases and Related Health Problems by World Health Organization (ICD X), that comprehensively describes an individual’s health condition while still accounting their performance in community [3]. This concept could then ease physiatrists in creating both treatment goals and therapy focus which are tailor made for the individual.
Utilizing ICF in the daily practice requires the use of several core sets which are specified for the disease, but this however has been a challenge as not all diseases have their specific core sets published. As SCA have no specific core set yet, it is then recommended for physiatrist to adapt to an existing core set which has similar properties, and chronic stroke core set would seem most fitting to an ongoing central neurological disorder [11]. Aside from utilizing the core set, it is important to focus on some components of the ICF concept that could become the focus of the treatment plan, emphasizing on setting achievable goals by using several measuring tools.
In a glance it could be seen that the ICF concept starts with describing the body structure and body function after stating the diagnosis [3]. Afterwards, activity and participation should be listed as to describe the individuals’ challenges in performing activity of daily living or even in the community level [3]. The next subsection of ICF involves description of environmental factors that would affect the individual, be it from physical environment or the community they are involved in [3]. Last but not least, personal factors should be addressed as well, knowing that adherence and motivation would affect the success of a rehabilitation program.
The focus of body structure in spinocerebellar ataxia is obviously the cerebellum, in the spinocerebellum (center) portion. It is known that the spinocerebellum gathers a large volume of sensory information from the peripheral organs, as well as relaying information from the motor cortex [12, 13]. Etiologically this is caused by autosomal dominant mutation on the SCA gene, and this would disrupt the connection between multiple layers of cerebellum [1]. Prior studies had shown that severity of symptoms would correlate to the cerebellar areas involvement, and differs between various types of SCA [2, 7, 14]. Ultimately these changes result in functional disturbances as well as learning difficulties [15, 16].
One of the main body function disorders in SCA that should be addressed is balance and postural control [9, 17]. Consistently studies had shown that balance is disturbed both during static and dynamic, hence implies difficulty in performing effective gait, and maintaining standing position [9, 18, 19]. Since cerebellum also becomes a relay center for agonist and antagonistic complimentary contractions, it is natural to see that spinocerebellum lesion would affect effective voluntary muscle contractions, which could also present as central hypotonia [4, 6]. As discussed earlier, learning difficulties in SCA would span its impact from impaired conditional skill learning, up until reduced ability in adapting changes from environment [15, 16]. All these errors in cerebellar signaling would also result in poor coordination, as there are several mismatches in relaying sensory information to produce an effective motor response, as well as poor intra-limb coordination in spinocerebellum damage [20, 21]. Limited study are available in exploration of autonomic function disorder, and it was reported that overactive bladder is most commonly seen in SCA 2 [22]. Therefore, despite the local extent of damage in body structure, the functional impact is notoriously destructive.
Having the body function described, it could be inferred that there would be a wide range of activity and participation disorders in SCA patients. One of the most reported problem in activity would be gait efficacy, as the lesion will interfere limb advancing patterns, as well as poor alternative terrain adaptability [8, 19]. Despite the inferior quality of life in motor control, the patients could still communicate as there are supposedly no barrier in this [23]. Even so, several studies revealed that cognitive impairments are found in SCA with varying severity [15, 16]. A number of studies have also reported that difficulty in verbal memory, learning, and fluency are commonly seen [16, 24]. These cognitive disorders would sum into a restriction in several community participation, but motor abilities still remained to inflict the most significant effect to quality of life in SCA [25]. Reports have mentioned the involvement of visuospatial and executive functioning abilities being reduced in SCA3, as it may correlate with reduced cerebellar perfusion [16]. Learning abilities in particular, were consistently shown to be retained in prodromal SCA2, as neural plasticity may still be prominent with Brain Derived Neurotrophic Factor playing its role, and other parts of the brain compensating for the functional deficit [15]. These evidences of preserved learning abilities in progressive disorders, must be recognized in the highest priority, knowing it would be the key to efficient rehabilitation for SCA cases [26, 27, 28].
The main environmental factor issues that was addressed for SCA is the difficulty to walk on varying level terrains [13, 29, 30]. It should be remembered that stable walking in varying level terrains require several functions ranging from cognition, vision, limb control, and balance. Severe fatigue was also seen in 69% of SCA patients, and thus different SCA types would result in different lesion focus and function disorder [31]. Moreover, since learning abilities are also compromised, a combination of these symptoms would ultimately result in terrain adaptation barriers [1, 4]. These should be identified in each patients, and correlated to their living environment in order to formulate an effective intervention.
Depression were consistently reported in several studies on SCA, and this could correlate significantly with quality of life [22, 30]. As mentioned previously that mobility is the main concern, depression levels were also seen lower in those subjects with better mobility [6, 25]. Even when other causes of depression may revolve around memory and learning ability disorders, most SCA subjects would have learning difficulty in limb control, which becomes a vicious cycle and a hazard for them to perform well in mobile activities of daily living [5]. Therefore, early detection of depression is important, especially in the personal factors subsection of ICF.
Although physical medicine and rehabilitation approach to SCA might differ between studies, it’s observable that the main focus is always towards body function, activity and participation. This focus is generally uncommon to be seen in the published studies, since most of these studies would focus on exploring various types of SCA, such as SCA1, SCA2, SCA3, SCA6 and SCA7 that are commonly found in the community [1, 7, 14, 27]. Shortly put, rehabilitative approach to SCA would place its greatest weigh on identifying disorders of body function through physical examination, rather than determining the SCA type through genetic testing [6]. In any case, each individual must receive tailor made interventions even when they are in the same SCA type.
In response to the stated functional problems, various rehabilitation strategies have been implemented and studied over the years [2, 6, 7]. Surely mobility and balance interventions have been one of the main focus in SCA studies, however through time, studies have widened their range of focus into endurance, cognition, and speech [30]. Rehabilitation strategies may be a combination of several mode of interventions, such as exercise, physical modality, and sensory stimulation [9, 14, 27].
Comprehensive examination is required prior to these interventions, as each patients should receive tailormade intervention, and thus not all of these strategies are administered to all patients. Through utilization of ICF conceptual analysis, then clinicians should focus on body function problems identified in SCA patients, as shown on Table 1 that depicts the common functional problems seen in SCA subtypes. This subsection will discuss these strategies in detail to give an overview of what is being studied in the published studies.
No | Function | SCA Type |
---|---|---|
1 | Sensory and Motor Cortex [13] | 6 |
2 | Ataxia & Cognition [15] | 2 |
3 | Falls, Balance Impairment, & Functional Mobility [29] | 1, 2, 3, 6 |
4 | Non-motor & Extracerebellar [22] | 2 |
5 | Cognitive [24] | 6 |
6 | Action perception cerebellar recruitment [26] | 6 |
7 | Dystonia [32] | 1, 2, 3, 6 |
8 | Cognitive & Socio-cognitive [16] | 1, 2, 3, 6, 7 |
9 | Clinical & Genetic of Brain MRI Changes [33] | 1, 2 |
10 | Motor & Cognitive – brain volume [34] | 7 |
11 | Autonomic Function [35] | 2 |
12 | Non ataxic manifestations [36] | 2 |
13 | Dysphagia [37] | 3, 6 |
Spinocerebellar functional problems in common SCA types.
Majority of the published studies have mentioned how physiotherapy plays a big role in mobility interventions of SCA patients, be it through conventional therapy or through exergames and virtual reality [9]. Since physiotherapy intervention is primarily focused on achieving better gait control, it would naturally revolve on improving balance, strength, endurance, and posture simultaneously [18, 27]. This finding has resulted into a more focused exercise sessions in the recent studies, aiming mainly on trunk balance, as these would be positively reflected in significant improvement of Scale for the Assessment and Rating of Ataxia (SARA) score [19, 38].
Although there are no published guidelines on SCA mobility exercise, several published studies from Cuban Centre for the Research and Rehabilitation of Hereditary Ataxia (CIRAH) had effectively shown the benefits of intensive neurorehabilitation as they have conducted [18, 27]. The whole therapy lasted for four hours per day, five days per week, lasting for 12 weeks in total, hence to the authors’ knowledge, this is the longest exercise duration seen per day. Daily tasks include both physiotherapy and occupational therapy interventions, with several breaks in between to restore both energy and training focus. It could be resumed that majority of the exercises given in CIRAH’s daily tasks include static balance improvement, and positional changes, all to improve trunk control and complement daily living tasks being trained by occupational therapists. Another important component that should be noted is the coordination exercises, which trains intra-limb coordination [18, 27]. These sets of exercises had proven to be very effective in improving cerebellar symptoms, as reflected in constant improvement of SARA scores of both SCA subjects in early prodromal stage and SCA2 diagnosed 11 years mean post onset [18, 27].
Other studies had utilized shorter sessions as compared to the CIRAH neurorehabilitation schedule, but all these had shown significant improvement of SARA scores. One such study reported that partial Body Weight Supported Treadmill Training could improve balance significantly, and general positive trend in improving mobility, endurance, and quality of life [19]. It could be possible that these studies alike are more focused on providing intervention in trunk control, which is parallel to the fact that trunk ataxia has better prognosis as compared to limb incoordination in SCA. Another concern lies that there are controversies in the outcome measurement of SARA scores, as they are very sensitive in detecting cerebellar symptoms, but not for extracerebellar symptoms. Despite those controversies, SARA scores could still be utilized as it correlates closely to functional abilities, and thus would pertain to be an effective evaluation tool in SCA studies.
Additionally, consistent evidence revealed that trunk ataxia could have better rehabilitation prognosis as compared to limb ataxia [8, 39]. The main problem persists that the rate of degeneration at every year must be matched with beneficial gains from exercise, and thus effective regimens would be the primary choice as a rehabilitation goal. The natural progression of SARA score in SCA is noted to be 0.6 to 2.5 points per year, whereas it was shown in most studies how training would effectively reduce SARA at least by one point, displaying clinical importance of these interventions [5].
It could be acknowledged that maintaining the provided gains from exercise is of importance in degenerative disorder [2, 6]. Several recent studies had revealed how exergames (exercise games) and immersive virtual reality would be able to fill up this shortfall in conventional therapy [8, 9]. Exergames here are considered adjuvant to the traditional physiotherapy, and could never replace their roles in ataxia rehabilitation [9]. An important feature in exergames that should be highlighted, is the fact that there are rapidly changing environment, thus demands an accurate anticipation from the ataxic cases, providing excellent gains to the sensorimotor system [9]. These anticipation were shown to correlate with real life situations, and could effectively maintain exercise effects throughout longer period [8, 9].
Proper choosing of modalities would benefit SCA subjects in different stages, where early stages could follow high demand competitive sporting exergames such as ping-pong, badminton and squash [8]. These exergames and virtual reality should be performed on elastic carpet, as it’s shown to give additional benefits in improving coordination and postural control through proprioceptive feedback. More severe ataxia would not allow them to play on competitive exergames, and would obtain greater advantage from good postural control. Games such as tightrope walk, which requires the user to maintain a specific position while still advancing forward, had been reported to effectively enhance both static and dynamic balance [8]. On the other hand, mild to moderate stages would benefit from conventional coordinative physiotherapy and severe stages though have no clear guidelines yet [9]. Hence it’s shown how exergames would play its best role in early stages, and also to maintain the gains accrued from conventional physiotherapy. As stated previously that studies had shown how mobility learning mechanisms may still be preserved in SCA cases, these newer therapies would then be targeted to hone these adaptive skills and apply them to their daily situations.
While many studies had shown how trunk control could have many exercise options, improving limb control has been shown as a big challenge in SCA subjects. It was also reported that good intra limb control is best seen in walking analysis, observing their coordination in performing effective transition from single and double leg stance [19]. Several studies had shown that static cycling would be an effective intervention to improve intra limb control [20, 21]. A controlled trial comprising of four week long cycling exercise was reported to restore the ability in modulating H-reflex inhibition, and is also correlated with better functional performances [40]. Although the impact was not as major as their healthy control counterpart, it could be seen that cycling would present itself as a potential exercise option for improving coordination in SCA subjects [40]. Added effects of endurance and strength gains through stationary cycling has also been reported, especially in mobility disorder patients such as cerebral palsy [41].
Postural exercise approach are generally based on “re-learning” strategies of destabilizing responses, that anticipatory movements are trained in various environments, as well as honing of sensorimotor reflexes in the light of preserved plasticity [9, 13]. Postural instability would also lead to chronic low back pain, and thus stretching must also be given in order to alleviate these before and after training sessions [9]. One voxel based study had shown 2 weeks of postural training would lead to improvement of balance, which was maintained for 3 months after training. Additionally, gray matter volume would also increase, and interestingly it is on the non-affected areas, meaning to say that targeted plasticity lies in the cerebral areas to compensate their cerebellar loss [28]. The study had mentioned that dorsal premotor cortex obtained the most compelling change, as they project to primary motor cortex and cerebellum, all of which are involved in movement planning and motor learning. Both patients and controls demonstrated an increase in gray matter volume in temporal association areas, this may be due to the requirement of performing sequential actions, which would in turn stimulates procedural memories in both hippocampus and basal ganglia. Cerebellar changes post exercise are not seen in cerebellar degenerative disorders as expected, but is significantly seen in healthy controls, with parallel increase in visuospatial and temporal inputs. These would then show how interventions towards premotor cortex growth should be the main goal of exercise in SCA subjects in preserving mobility [28].
Besides physiotherapy interventions, occupational therapy is another important modality within the attempts of improving quality of life in SCA subjects [9, 42]. As mentioned previously, occupational therapy is usually incorporated with physiotherapy courses [18]. In the big picture, they should be given after warm up stretches to obtain better postural control during the specific exercises. In the published studies, mainly occupational therapy intervention would have a one hour duration, and this addition have been proven effective in improving both SARA and Functional Independence Measure (FIM) scores. The program itself consists of basic activity of daily living exercises, which are essentially a part of the FIM and Barthel Index Scoring sheet. Some of the examples include dressing activities such as tying shoelaces, buttoning shirts; tabletop instrumental activities for instance inserting sewing needles, drawing, cutting paper figures, using keyboards; and finally communication activities like reading texts out loud, commenting and interpreting verbal and textual information [18].
Despite the promising effects, studies focusing on occupational therapy as an individual therapy is still lacking due to the progressive nature of the disease, thus could only be shown as an additive effect to the proven effective physiotherapy. A study had shown that occupational therapy would improve Hamilton scores for depression in SCA3, and this improvement was independent from its confounders [42]. So far there are no studies yet on occupational therapy being a home program, but it could be speculated that more frequent practices would eventually trigger better quality synapses in the brain, leading to a more superior functional improvement. Therefore, aside from improving the functional abilities, it could also be inferred that occupational therapy would enhance self-confidence, alleviates depressive mood, and thus forecasts better participation [9, 42].
In order to fully complement the comprehensive care of SCA patients, speech and language pathology should be addressed to achieve well-being [23]. However, there are very few studies that discusses this, since only few types of ataxia that has bulbar involvement and thus results in dysphagia due to excess salivation [43]. A study had shown and compared how dysphagia is more severe in SCA3, whereas mild dysphagia is seen in SCA6 [37]. Possible treatment options would depend on related problems, but mostly rehabilitation targets is to increase willingness and independence [23, 43]. At the same time, swallowing exercise would also aim in cueing patients to gain self-recognition in their swallowing process, thus triggering anticipatory self-evaluation [23, 43]. Since cognition is also an identified problem in SCA, this could also be identified by the speech and language pathologist, and self-corrections cueing prove to be effective [23]. In a more severe cases, safe swallowing practice along with appropriate dietary modification may be done in order to prevent aspiration [23]. Despite the scarcity of studies, a Cochrane review on speech disorder treatment for hereditary ataxia revealed that all the rehabilitative interventions have been reported as safe, and hence should be recommended in the comprehensive care [43].
Clinicians should always remember that neuroplasticity plays a big role in alleviating SCA cerebellar signs, as proven in SCA2 subjects [10]. Unfortunately, there are still no reported significant effect on non-ataxia signs [28]. It also appears that SCA2 subjects may have more progressive disorders, and thus 24 weeks of therapy was suggested, whereas for other types such as SCA6 and SCA31, 4 weeks of training may already show better SARA score improvements [27]. Thus, the extent of affected area in the cerebellum would correlate directly to the progressiveness, hence would warrant different sets of rehabilitation strategy. Recognizing the neuroplasticity potential of SCA individuals would assist clinicians in identifying therapy focus, as well as motivating patients and family members to improve exercise adherence.
Although there is no general guideline on this, rehabilitation strategies would adhere to functional disorder basis, that each strategy is given only when the disorder is identified [1, 6, 9]. Due to the progressive nature of the disease though, it is also plausible to administer the intervention even when the disorder have not emerge, knowing the fact that it may alleviate functional deterioration in the future. Two things that should be remembered are that fatigue may be one of the limitation in performing all the available strategies, and secondly, maintenance in quality of life must always be upheld [30]. Despite not many studies focused on quality of life, clinical experiences showed that progressive disease rehabilitation interventions should emphasize on giving life to the rest of the years, rather than adding years to the remaining life.
Aligned with their natural progression of disease, rehabilitation goals in degenerative ataxias would differ significantly from acquired ataxias. It was shown that acquired ataxias such as in stroke cases, would come with focal ischemia, ergo a better prognosis as compared to the diffuse lesion in SCA [1, 44]. Additionally, the degenerative process of SCA is of the highest concern, therefore it must be addressed and evaluated with valid measuring tools. Several subjects that were focused in prior studies include functional abilities, mobility function, balance, endurance, and quality of life [30].
Ataxia specific tools such as SARA and Inventory of Non-Ataxia Symptoms (INAS) are most commonly utilized in many studies [45, 46]. The SARA score is designed to assess cerebellar symptoms semiquantitatively, and exclusively only SCA subjects were tested during the validation process. The SARA score ranges from 0 to 40, higher number showing more severe ataxia, the values then reflect eight physical examination items each with specific numeric scores. Physical examination of gait, stationary standing, and sitting position are observed, with a cut off of maintaining 10 second stationary position without difficulty as sufficient. One common bulbar component of SCA being speech production is also evaluated, and will be scored worst if the subject could only do unintelligible speech during normal conversation. Last but not least, performance of coordination tests namely finger chase, nose to finger test, dysdiadochokinesia, and heel shin test are graded with a score of 4 as the worst performance. As could be seen in these scored items, all of these are included in the general rehabilitation examination of cerebellar symptoms, and therefore this score is very much applicable in daily practice. Consistently it was shown that SARA score would correlate closely to symptom severity, and thus could be practically used to evaluate the efficacy of rehabilitation program [45].
With that being said, the main limitation of SARA would be that other scorings are required in the light of addressing extracerebellar symptoms. Therefore, the same research group had devised INAS score which could quantify the presence and severity of non-ataxia neurological symptoms [46]. The inventory consists of 30 items that is divided into two main section, the first spans widely from addressing cerebellar oculomotor signs, spinal reflexes, upper and lower motor neuron signs through physical examination. The second section on the other hand, lists the possible symptoms that the patient might bring about, such as double vision, dysphagia, urinary dysfunction, cognitive impairment, and other related findings that have not been listed. Similarly, the INAS scoring was also validated by utilizing SCA subjects with varying types, namely SCA1, SCA2, SCA3, and SCA6. Among these SCA types, it was reported that SCA1 and SCA2 presents extracerebellar symptoms along with the baseline ataxia, thus they are good candidates for the INAS, while SCA6 being purely cerebellar would play its role as control. The summation of the score is called INAS count, in which they have concluded that both INAS and INAS count shows good reproducibility, but unsatisfactory responsiveness over extended period due to the wide variation of measurement [46]. However it was clearly shown that INAS is an excellent supplement to the SARA score for SCA subjects.
Other studies had also shown that in very early ataxia stages, both SARA and INAS are ineffective in prodromal stage [18]. Functional test alternatives such as tandem gait for 5 meter test was suggested to be used, as it is very sensitive to changes post rehabilitation [18]. The tandem gait itself is a complex task which may not be performed well by all SCA subjects, therefore traditional balance assessments such as Berg Balance Scale (BBS) [17, 25, 44]. The BBS consist of 14 item list, with an ordinal scale of 0 to 4, higher number meaning better balance function. The main categories in the item list revolves around maintenance of stationary position, transfer, and change of position while performing simple activities. Summation of all the scores for less than 45 would indicate greater risks of falling [47]. In cases that the BBS is not used in total, the components could also be used individually to monitor a specific progression within therapy evaluation.
Another study had also utilized the timed up and go (TUG) test to evaluate balance and function in degenerative ataxia subjects [20, 21]. In several rehabilitation trials, TUG test are well preferred due to their ease of examination, quantification of results in seconds, and finally their best representation to daily living tasks. However in cases of SCA, probably the complete TUG test might not always be performable due to high risk of fall. Several studies had also utilized expanded TUG test, which divides the full TUG test into segments measured by milliseconds, namely sit to stand, gait 1, turning, gait 2, and stand to sit [48, 49]. By separating these components, physiatrists would have a better view on which component are hindering the subject in achieving good TUG performance, and at the same time, would be able to assess improvements more accurately. Although the expanded TUG have not been utilized in SCA studies, it has been commonly used in other chronic neurological cases such as stroke, and hence should be recommended for future studies on degenerative ataxia [48].
Aside from TUG test, a more comprehensive functional test tool such as functional independence measure (FIM) are commonly used in SCA studies [25]. The utilization of FIM had expanded the view on functional activities and illustrate their level of independence in those activities. The FIM tool comprise of several components such as bowel, bladder control, transfer, locomotion, social participation, communication and also self-care activities [50, 51]. These components will then be graded from 1 to 7, when value of 6 and above shows complete dependence, scores 3 to 5 shows moderate dependence, and lastly below 3 shows full dependence. Therefore, this tool would be best used when the subjects are not fully independent, and other individuals such as caregivers are involved. Naturally FIM would have a ceiling effect when the patient is fully independent, and there are no additional scoring for the performance quality.
In SCA subjects it was reported that reduction of 1 point in FIM score would be significantly reflected in 4.49 point decrease in the physical functioning of Short Form 36 (SF-36) score [25]. In the light of SF-36, it is the most commonly used tool to assess quality of life in SCA subjects. As the name implies, this tool has 36 questions which covers eight domains of health, for instance limitations in physical activities, social activities, role function, pain, emotional problem, mental health, fatigue, and finally general health perceptions [52]. Various ordinal options in each questions should firstly be calculated through a formula to obtain domain scores. This finding then reveals how FIM could also be used to assess overtime changes that would complement the changes in other ataxia specific tools, in which better mobility correlates with greater quality of life [25, 53].
In relationship to quality of life, fatigue is pretty much prevalent and thus is essential to note. Aside from SF-36 that touches on the fatigue concept, the fatigue severity scale (FSS) is a specific 9 item scale which measures fatigue in a 1 to 7 scale, 7 being strongly agree with the fatigue item being stated [31]. Accomplishing the FSS requires only 5 minutes, but the questions would not accurately direct the underlying functional disorder beneath, especially in chronic cases where fatigue is evident. Therefore, both cardiovascular and respiratory specific tools must be administered separately in order to evaluate through time. There are a selected number of studies that discuss the changes of cardiorespiratory attributes through evaluation of maximum oxygen consumption (VO2 max), six minute walk test (6MWT), peak expiratory flow (PEF), and maximum inspiratory pressure (MIP) [21, 38, 54].
Evaluation of VO2 max is done by performing ramped ergometer exercise stress testing, while 6MWT could be performed with assistance if the subjects are unable to [21]. With all these limitations, it could be possible that evaluation of cardiovascular function will not be optimal owing to the natural progression of the disease and obstacles in maintaining stationary position. On the contrary, respiratory function has shorter examination time, allowing better examination compliance [54]. A recent study had shown how examination of both PEF and MIP are safe to be performed in SCA2 subjects, when better respiratory function seemed to correlate well with Activity of Daily Living scales, and ataxia specific SARA scales [54]. Additionally, the study had also reported that one third of the subjects complained of dyspnea, with interpretation of restrictive pulmonary disease. It is speculated that the restriction may be caused by the lack of coordination of the respiratory muscles, ultimately resulting in reduced chest expansion [54]. On the other point of view, postural control exercises would be able to improve diaphragmatic excursion, and thus provide attempts in correcting respiratory dysfunction [55, 56, 57]. Therefore, it is only possible that physiotherapy interventions to manage ataxia related symptoms also alleviate respiratory symptoms, thus very mild respiratory dysfunction that could be reported.
Being a progressive degenerative disease, physical medicine and rehabilitation have an important role in alleviating symptoms as well as improving quality of life in Spinocerebellar Ataxia [4]. Initial analysis of SCA begins with identifying the ICF concept, in which body structure being cerebellum, and several body function problems such as postural control and intra-limb control should firstly be addressed [8]. These underlying disorders would lead to below par daily living performance, further leading to restriction in participation, and might also result in depression [25, 30]. Nevertheless it should be remembered that there is a natural progression of functional decline, which is unavoidable in SCA [1]. Therefore, rehabilitation goals are generally focused in maintaining functional capacity, as well as improving social participation and quality of life [4].
Achieving the aforementioned rehabilitation goals could be done through several interventions, but it was shown that physiotherapy exercise sessions focused in improving posture, balance, and gait had proven to be the most effective. Duration of session generally lasts for 1 hour or more, but it should be preceded with stretching to ease pain and provide better proprioceptive feedback [18]. In order to enhance retaining of the exercise gains, proper choices of virtual reality and exergames could be done [8, 9]. Most studies have also incorporated occupational therapy that rehearses daily living activities, and it’s seen to correlate well with quality of life [42]. Simultaneously, speech therapy would also play its role in SCA by managing communication and swallowing disorders that are present in several types of SCA [43]. Several valid outcome measuring tools have been shown effective to monitor changes over time, and it should be remembered that these measures could assess specific components that are being trained [22, 30]. In conclusion, effective rehabilitation approach should comprise of all the previously mentioned components, while always being validated by specific outcome measure tools. In addition to that, further studies should devise a guideline for general rehabilitation of SCA through validated trials.
The authors declare no conflict of interest.
The corresponding author would like to mention a note of thanks to the ever-supporting wife, Gisca Meiviana, for all her constant encouragement during the process of authoring this book chapter, and for being an amazing life partner throughout.
Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.
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As a response to long-term development between BIM and road engineering, this chapter will contribute also by offering innovative and practical solutions for integration of road design and pavement analysis, for a better management and optimization of road pavement maintenance.",book:{id:"9872",slug:"models-and-technologies-for-smart-sustainable-and-safe-transportation-systems",title:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems",fullTitle:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems"},signatures:"Salvatore Antonio Biancardo, Nunzio Viscione, Cristina Oreto and Francesca Russo",authors:[{id:"300972",title:"Dr.",name:"Salvatore Antonio",middleName:null,surname:"Biancardo",slug:"salvatore-antonio-biancardo",fullName:"Salvatore Antonio Biancardo"},{id:"321425",title:"Prof.",name:"Francesca",middleName:null,surname:"Russo",slug:"francesca-russo",fullName:"Francesca Russo"},{id:"327976",title:"Mr.",name:"Nunzio",middleName:null,surname:"Viscione",slug:"nunzio-viscione",fullName:"Nunzio Viscione"},{id:"327977",title:"Ms.",name:"Cristina",middleName:null,surname:"Oreto",slug:"cristina-oreto",fullName:"Cristina Oreto"}]},{id:"64211",doi:"10.5772/intechopen.81159",title:"Contemporary Inspection and Monitoring for High-Speed Rail System",slug:"contemporary-inspection-and-monitoring-for-high-speed-rail-system",totalDownloads:1465,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Non-destructive testing (NDT) techniques have been explored and extensively utilised to help maintaining safety operation and improving ride comfort of the rail system. As an ascension of NDT techniques, the structural health monitoring (SHM) brings a new era of real-time condition assessment of rail system without interrupting train service, which is significantly meaningful to high-speed rail (HSR). This chapter first gives a review of NDT techniques of wheels and rails, followed by the recent applications of SHM on HSR enabled by a combination of advanced sensing technologies using optical fibre, piezoelectric and other smart sensors for on-board and online monitoring of the railway system from vehicles to rail infrastructure. An introduction of research frontier and development direction of SHM on HSR is provided subsequently concerning both sensing accuracy and efficiency, through cutting-edge data-driven analytic studies embracing such as wireless sensing and compressive sensing, which answer for the big data’s call brought by the new age of this transport.",book:{id:"7524",slug:"high-speed-rail",title:"High-Speed Rail",fullTitle:"High-Speed Rail"},signatures:"Lu Zhou, Xiao-Zhou Liu and Yi-Qing Ni",authors:[{id:"253578",title:"Dr.",name:"Lu",middleName:null,surname:"Zhou",slug:"lu-zhou",fullName:"Lu Zhou"},{id:"254448",title:"Prof.",name:"Yi-Qing",middleName:null,surname:"Ni",slug:"yi-qing-ni",fullName:"Yi-Qing Ni"},{id:"270970",title:"Dr.",name:"Xiao-Zhou",middleName:null,surname:"Liu",slug:"xiao-zhou-liu",fullName:"Xiao-Zhou Liu"}]},{id:"63242",doi:"10.5772/intechopen.80302",title:"Main Ways to Improve Cutting Tools for Machine Wheel Tread Profile",slug:"main-ways-to-improve-cutting-tools-for-machine-wheel-tread-profile",totalDownloads:958,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter considers the methods to increase the performance and reliability of the reprofile machining of the wheel tread profile. Proceeding from the fact that both in milling and turning, the cutting tool is a key element to ensure performance and reliability of the manufacturing process, the study considers the methods to increase the performance properties of cutting tools. In particular, the study includes the investigation of the following ways to improve cutting tools (carbide inserts) to machine wheel tread profile: replacement of traditional grades of WC-TiC-Co carbides with more efficient ones based on WC-TiC-TaC-Co; application of special thermally conductive pads, gaskets, and pastes to improve the distribution of heat flows in the cutting zone; and application of modern nanoscale composite multilayer coatings (NMCC). It is noted that even higher performance can be obtained by combining the above three methods, in particular, by combining application of special thermal pads and NMCC.",book:{id:"7524",slug:"high-speed-rail",title:"High-Speed Rail",fullTitle:"High-Speed Rail"},signatures:"Alexey Vereschaka, Popov Alexey, Grigoriev Sergey, Kulikov Mikhail and Sotova Catherine",authors:[{id:"196459",title:"Dr.",name:"Alexey",middleName:null,surname:"Vereschaka",slug:"alexey-vereschaka",fullName:"Alexey Vereschaka"},{id:"264332",title:"Dr.",name:"Alexey",middleName:null,surname:"Popov",slug:"alexey-popov",fullName:"Alexey Popov"},{id:"264333",title:"Prof.",name:"Sergey",middleName:null,surname:"Grigoriev",slug:"sergey-grigoriev",fullName:"Sergey Grigoriev"},{id:"264334",title:"Prof.",name:"Mikhail",middleName:null,surname:"Kulikov",slug:"mikhail-kulikov",fullName:"Mikhail Kulikov"},{id:"264336",title:"Dr.",name:"Catherine",middleName:null,surname:"Sotova",slug:"catherine-sotova",fullName:"Catherine Sotova"}]},{id:"73240",doi:"10.5772/intechopen.93827",title:"Recent Progress in Activity-Based Travel Demand Modeling: Rising Data and Applicability",slug:"recent-progress-in-activity-based-travel-demand-modeling-rising-data-and-applicability",totalDownloads:677,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Over 30 years have passed since activity-based travel demand models (ABMs) emerged to overcome the limitations of the preceding models which have dominated the field for over 50 years. Activity-based models are valuable tools for transportation planning and analysis, detailing the tour and mode-restricted nature of the household and individual travel choices. Nevertheless, no single approach has emerged as a dominant method, and research continues to improve ABM features to make them more accurate, robust, and practical. This paper describes the state of art and practice, including the ongoing ABM research covering both demand and supply considerations. Despite the substantial developments, ABM’s abilities in reflecting behavioral realism are still limited. Possible solutions to address this issue include increasing the inaccuracy of the primary data, improved integrity of ABMs across days of the week, and tackling the uncertainty via integrating demand and supply. Opportunities exist to test, the feasibility of spatial transferability of ABMs to new geographical contexts along with expanding the applicability of ABMs in transportation policy-making.",book:{id:"9872",slug:"models-and-technologies-for-smart-sustainable-and-safe-transportation-systems",title:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems",fullTitle:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems"},signatures:"Atousa Tajaddini, Geoffrey Rose, Kara M. Kockelman and Hai L. Vu",authors:[{id:"321573",title:"Prof.",name:"Hai L.",middleName:null,surname:"Vu",slug:"hai-l.-vu",fullName:"Hai L. Vu"},{id:"327536",title:"Ms.",name:"Atousa",middleName:null,surname:"Tajaddini",slug:"atousa-tajaddini",fullName:"Atousa Tajaddini"},{id:"327537",title:"Prof.",name:"Geoffrey",middleName:null,surname:"Rose",slug:"geoffrey-rose",fullName:"Geoffrey Rose"},{id:"327538",title:"Prof.",name:"Kara M.",middleName:null,surname:"Kockelman",slug:"kara-m.-kockelman",fullName:"Kara M. Kockelman"}]},{id:"73356",doi:"10.5772/intechopen.93892",title:"Optimal Management of Electrified and Cooperative Bus Systems",slug:"optimal-management-of-electrified-and-cooperative-bus-systems",totalDownloads:337,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter presents an integrated management approach exploiting the potentials of the new Cooperative Intelligent Transportation Systems (C-ITS) to meet the requirements of the next generation Public Transport (PT). This approach considers the additional complexity of electrification—for instance electric busses need to periodically recharge during operation using dedicated infrastructure. This not only can impact service level, but also extend operating costs with complex electric charges. We develop new strategies explicitly optimizing the interactions within the PT ecosystem consisting of vehicles, traffic signals, and e-bus charging infrastructure. To achieve these goals, we rely on vehicle control rather than on the use of transit signal priority, which in congested urban scenarios can have negative effects on overall traffic performance. The main research challenges are in formulating and solving complex multi-objective optimization problems and real-time control. The proposed system is tested and evaluated in simulation showing the benefits of electrified and cooperative bus systems.",book:{id:"9872",slug:"models-and-technologies-for-smart-sustainable-and-safe-transportation-systems",title:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems",fullTitle:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems"},signatures:"Francesco Viti, Marco Rinaldi and Georgios Laskaris",authors:[{id:"321907",title:"Dr.",name:"Francesco",middleName:null,surname:"Viti",slug:"francesco-viti",fullName:"Francesco Viti"},{id:"328609",title:"Dr.",name:"Marco",middleName:null,surname:"Rinaldi",slug:"marco-rinaldi",fullName:"Marco Rinaldi"},{id:"328610",title:"Dr.",name:"Georgios",middleName:null,surname:"Laskaris",slug:"georgios-laskaris",fullName:"Georgios Laskaris"}]}],mostDownloadedChaptersLast30Days:[{id:"73624",title:"BIM Approach for Smart Infrastructure Design and Maintenance Operations",slug:"bim-approach-for-smart-infrastructure-design-and-maintenance-operations",totalDownloads:530,totalCrossrefCites:4,totalDimensionsCites:6,abstract:"In the age of the Internet-of-Things and Big Data, Building Information Modeling (BIM) is being expanded into sectors for which it was not originally designed, such as the infrastructure sector, and becomes a necessity for the planning and management of smart cities. The digitization of the urban environment, its building and infrastructural heritage and its services is at the center of the concept of smart city, and this appears strongly linked to the use of BIM on an increasingly extended scale as an enabling tool for planning cities that are increasingly intelligent, sustainable, interconnected and above all liveable. In this chapter a creation process for the digitalization of existing roads, as well-known as reverse engineering method, will be shown as follows: a) modeling 3D digital terrain model; b) creating the horizontal alignment, vertical profiles and editing cross-sections; c) modeling the 3D corridor. As a response to long-term development between BIM and road engineering, this chapter will contribute also by offering innovative and practical solutions for integration of road design and pavement analysis, for a better management and optimization of road pavement maintenance.",book:{id:"9872",slug:"models-and-technologies-for-smart-sustainable-and-safe-transportation-systems",title:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems",fullTitle:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems"},signatures:"Salvatore Antonio Biancardo, Nunzio Viscione, Cristina Oreto and Francesca Russo",authors:[{id:"300972",title:"Dr.",name:"Salvatore Antonio",middleName:null,surname:"Biancardo",slug:"salvatore-antonio-biancardo",fullName:"Salvatore Antonio Biancardo"},{id:"321425",title:"Prof.",name:"Francesca",middleName:null,surname:"Russo",slug:"francesca-russo",fullName:"Francesca Russo"},{id:"327976",title:"Mr.",name:"Nunzio",middleName:null,surname:"Viscione",slug:"nunzio-viscione",fullName:"Nunzio Viscione"},{id:"327977",title:"Ms.",name:"Cristina",middleName:null,surname:"Oreto",slug:"cristina-oreto",fullName:"Cristina Oreto"}]},{id:"73821",title:"Driver Assistance Technologies",slug:"driver-assistance-technologies",totalDownloads:583,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Topic: Driver Assistance Technology is emerging as new driving technology popularly known as ADAS. It is supported with Adaptive Cruise Control, Automatic Emergency Brake, blind spot monitoring, lane change assistance, and forward collision warnings etc. It is an important platform to integrate these multiple applications by using data from multifunction sensors, cameras, radars, lidars etc. and send command to plural actuators, engine, brake, steering etc. ADAS technology can detect some objects, do basic classification, alert the driver of hazardous road conditions, and in some cases, slow or stop the vehicle. The architecture of the electronic control units (ECUs) is responsible for executing advanced driver assistance systems (ADAS) in vehicle which is changing as per its response during the process of driving. Automotive system architecture integrates multiple applications into ADAS ECUs that serve multiple sensors for their functions. Hardware architecture of ADAS and autonomous driving, includes automotive Ethernet, TSN, Ethernet switch and gateway, and domain controller while Software architecture of ADAS and autonomous driving, including AUTOSAR Classic and Adaptive, ROS 2.0 and QNX. This chapter explains the functioning of Assistance Driving Technology with the help of its architecture and various types of sensors.",book:{id:"9872",slug:"models-and-technologies-for-smart-sustainable-and-safe-transportation-systems",title:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems",fullTitle:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems"},signatures:"Pradip Kumar Sarkar",authors:[{id:"321704",title:"Dr.",name:"Pradip Kumar",middleName:null,surname:"Sarkar",slug:"pradip-kumar-sarkar",fullName:"Pradip Kumar Sarkar"}]},{id:"63054",title:"Optimization of Components of Superstructure of High-Speed Rail: The Spanish Experience",slug:"optimization-of-components-of-superstructure-of-high-speed-rail-the-spanish-experience",totalDownloads:906,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The performance of rail transport has increased significantly in recent decades, in particular due to the gradual introduction of high-speed rails worldwide. In 1981, the first high-speed line of the world was inaugurated; nowadays, high-speed is operating in more than 20 countries, the high-speed network covering more than 35,000 kms (with more than 25,000 additional kms under construction). Spain is the second country by total distance of railways installed (only behind China) and the first in terms relative to the population and surface. Since the installation of the first high-speed line in Spain in 1992, the elements of the superstructure have undergone a continuous evolution, in order to improve the performance, the durability of the components and the comfort of the passengers. This evolution rests on an adequate selection of materials based on the characterization of their physical and mechanical properties to ensure the optimum in-service conditions. This chapter includes an overview of the different elements present in the railway superstructure of the high-speed lines in Spain. Throughout the text, the innovations incorporated over time are analyzed, as well as the methods used to validate them. In particular, a description of the mechanical characterization procedures is presented.",book:{id:"7524",slug:"high-speed-rail",title:"High-Speed Rail",fullTitle:"High-Speed Rail"},signatures:"Estela Ruiz, Isidro A. Carrascal, Diego Ferreño, José A. Casado and Soraya Diego",authors:[{id:"38018",title:"Prof.",name:"Diego",middleName:null,surname:"Ferreño",slug:"diego-ferreno",fullName:"Diego Ferreño"},{id:"264427",title:"Dr.",name:"Isidro A.",middleName:null,surname:"Carrascal",slug:"isidro-a.-carrascal",fullName:"Isidro A. Carrascal"},{id:"264428",title:"Prof.",name:"José A.",middleName:null,surname:"Casado",slug:"jose-a.-casado",fullName:"José A. Casado"},{id:"264429",title:"Dr.",name:"Soraya",middleName:null,surname:"Diego",slug:"soraya-diego",fullName:"Soraya Diego"},{id:"268961",title:"Dr.",name:"Estela",middleName:null,surname:"Ruiz",slug:"estela-ruiz",fullName:"Estela Ruiz"}]},{id:"63242",title:"Main Ways to Improve Cutting Tools for Machine Wheel Tread Profile",slug:"main-ways-to-improve-cutting-tools-for-machine-wheel-tread-profile",totalDownloads:958,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter considers the methods to increase the performance and reliability of the reprofile machining of the wheel tread profile. Proceeding from the fact that both in milling and turning, the cutting tool is a key element to ensure performance and reliability of the manufacturing process, the study considers the methods to increase the performance properties of cutting tools. In particular, the study includes the investigation of the following ways to improve cutting tools (carbide inserts) to machine wheel tread profile: replacement of traditional grades of WC-TiC-Co carbides with more efficient ones based on WC-TiC-TaC-Co; application of special thermally conductive pads, gaskets, and pastes to improve the distribution of heat flows in the cutting zone; and application of modern nanoscale composite multilayer coatings (NMCC). It is noted that even higher performance can be obtained by combining the above three methods, in particular, by combining application of special thermal pads and NMCC.",book:{id:"7524",slug:"high-speed-rail",title:"High-Speed Rail",fullTitle:"High-Speed Rail"},signatures:"Alexey Vereschaka, Popov Alexey, Grigoriev Sergey, Kulikov Mikhail and Sotova Catherine",authors:[{id:"196459",title:"Dr.",name:"Alexey",middleName:null,surname:"Vereschaka",slug:"alexey-vereschaka",fullName:"Alexey Vereschaka"},{id:"264332",title:"Dr.",name:"Alexey",middleName:null,surname:"Popov",slug:"alexey-popov",fullName:"Alexey Popov"},{id:"264333",title:"Prof.",name:"Sergey",middleName:null,surname:"Grigoriev",slug:"sergey-grigoriev",fullName:"Sergey Grigoriev"},{id:"264334",title:"Prof.",name:"Mikhail",middleName:null,surname:"Kulikov",slug:"mikhail-kulikov",fullName:"Mikhail Kulikov"},{id:"264336",title:"Dr.",name:"Catherine",middleName:null,surname:"Sotova",slug:"catherine-sotova",fullName:"Catherine Sotova"}]},{id:"74333",title:"Transit Signal Priority in Smart Cities",slug:"transit-signal-priority-in-smart-cities",totalDownloads:427,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Giving priority to public transport vehicles at traffic signals is one of the traffic management strategies deployed at emerging smart cities to increase the quality of service for public transit users. It is a key to breaking the vicious cycle of congestion that threatens to bring cities into gridlock. In that cycle, increasing private traffic makes public transport become slower, less reliable, and less attractive. This results in deteriorated transit speed and reliability and induces more people to leave public transit in favor of the private cars, which create more traffic congestion, generate emissions, and increase energy consumption. Prioritizing public transit would break the vicious cycle and make it a more attractive mode as traffic demand and urban networks grow. A traditional way of protecting public transit from congestion is to move it either underground or above ground, as in the form of a metro/subway or air rail or create a dedicated lane as in the form of bus lane or light rail transit (LRT). However, due to the enormous capital expense involved or the lack of right-of-way, these solutions are often limited to few travel corridors or where money is not an issue. An alternative to prioritizing space to transit is to prioritize transit through time in the form of Transit Signal Priority (TSP). Noteworthy, transit and specifically bus schedules are known to be unstable and can be thrown off their schedule with even small changes in traffic or dwell time. At the same time, transit service reliability is an important factor for passengers and transit agencies. Less variability in transit travel time will need less slack or layover time. Thus, transit schedulers are interested in reducing transit travel time and its variability. One way to reach this goal is through an active intervention like TSP. In this chapter a comprehensive review of transit signal priority models is presented. The studies are classified into different categories which are: signal priority and different control systems, passive versus active priority, predictive transit signal priority, priority with connected vehicles, multi-modal signal priority models, and other practical considerations.",book:{id:"9872",slug:"models-and-technologies-for-smart-sustainable-and-safe-transportation-systems",title:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems",fullTitle:"Models and Technologies for Smart, Sustainable and Safe Transportation Systems"},signatures:"Bahman Moghimi and Camille Kamga",authors:[{id:"321370",title:"Dr.",name:"Bahman",middleName:null,surname:"Moghimi",slug:"bahman-moghimi",fullName:"Bahman Moghimi"},{id:"340958",title:"Prof.",name:"Camille",middleName:null,surname:"Kamga",slug:"camille-kamga",fullName:"Camille Kamga"}]}],onlineFirstChaptersFilter:{topicId:"713",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. 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