10 tallest timber buildings.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5852",leadTitle:null,fullTitle:"Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Development",title:"Peripheral Nerve Regeneration",subtitle:"From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Development",reviewType:"peer-reviewed",abstract:"Peripheral nerve injuries are a high-incidence clinical problem that greatly affects patients' quality of life. Despite continuous refinement of microsurgery techniques, peripheral nerve repair still stands as one of the most challenging tasks in neurosurgery, as functional neuromuscular recovery is rarely satisfactory in these patients. Therefore, the improvement of surgical techniques and the clinical application of innovative therapies have been intensively studied worldwide. Direct nerve repair with epineural end-to-end sutures is still the gold standard treatment for severe neurotmesis injuries but only in cases where well-vascularized tension-free coaptation can be achieved. When peripheral nerve injury originates a significant gap between the nerve stumps, nerve grafts are required, with several associated disadvantages. Therefore, the development of scaffolds by tissue engineering can provide efficient treatment alternatives to stimulate optimum clinical outcome. Nerve conduit tailoring involves reaching ideal wall pores, using electrospinning techniques in their fabrication, surface coating with extracellular matrix materials, and adding of growth factors or cell-based therapies, among other possibilities. Also, intraluminal cues are employed such as the filling with hydrogels, inner surface modification, topographical design, and the introduction of neurotrophic factors, antibiotics, anti-inflammatories and other pharmacological agents. A comprehensive state of the art of surgical techniques, tissue-engineered nerve graft scaffolds, and their application in nerve regeneration, the advances in peripheral nerve repair and future perspectives will be discussed, including surgeons' and researchers' own large experience in this field of knowledge.",isbn:"978-953-51-3166-3",printIsbn:"978-953-51-3165-6",pdfIsbn:"978-953-51-4812-8",doi:"10.5772/65612",price:119,priceEur:129,priceUsd:155,slug:"peripheral-nerve-regeneration-from-surgery-to-new-therapeutic-approaches-including-biomaterials-and-cell-based-therapies-development",numberOfPages:224,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d1cd2e797f008dcee9dd0c1010145eb8",bookSignature:"Ana Colette Mauricio",publishedDate:"May 31st 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5852.jpg",numberOfDownloads:15147,numberOfWosCitations:10,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:21,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:38,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2016",dateEndSecondStepPublish:"November 2nd 2016",dateEndThirdStepPublish:"January 29th 2017",dateEndFourthStepPublish:"April 29th 2017",dateEndFifthStepPublish:"June 28th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"56285",title:"Prof.",name:"Ana Colette",middleName:null,surname:"Maurício",slug:"ana-colette-mauricio",fullName:"Ana Colette Maurício",profilePictureURL:"https://mts.intechopen.com/storage/users/56285/images/system/56285.jpeg",biography:"Ana Colette Pereira de Castro Osório Maurício has a degree on Veterinary Medicine since 1995, a PhD on Veterinary Sciences since 1999 from Faculdade de Medicina Veterinária (FMV) - Universidade de Lisboa (ULisboa) and Habilitation in Veterinary Sciences (ICBAS-UP) since 2011. The PhD experimental work was developed at Instituto Gulbenkian Ciência (IGC) in Oeiras, Portugal, at Freiburg Medicine Faculty in Germany and at Faculdade de Ciências e Tecnologia (FCT) from Universidade Nova de Lisboa (UNL). At the present, she is an Associated Professor with Habilitation, from the Veterinary Clinics Department of Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), she is the vice-President of the Pedagogic Council of ICBAS – UP. She is a Member of the Scientific Council and Member of the Representatives Council of ICBAS-UP. She is the Director of the Veterinary Sciences Doctoral Program at ICBAS – UP. She is the Scientific Coordinator of Regenerative Medicine and Experimental Surgery sub-unit from Centro de Estudos de Ciência Animal (CECA) of Instituto Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA). For the past 12 years she coordinates a multidisciplinary research group of Experimental Surgery and Regenerative Medicine, working with several biomaterials and cellular therapies. She started working with embryonic stem cells obtained by somatic nuclear transfer for therapeutic use; with Ian Wilmut´s group (Dolly’s cloned sheep). Several relevant publications had been produced and conducted to a PhD thesis that she co-supervised together with Ian Wilmut and to the first Portuguese cloned animal (R Ribas, B Oback, W Ritchie, T Chebotareva, J Taylor, AC Maurício, M Sousa, I Wilmut, 2006. Cloning and Stem Cells 8(1): 10; R Ribas, J Taylor, C McCorquodale, AC Maurício, M Sousa, I Wilmut, 2006. Biology of Reproduction 74: 307; R Ribas, B Oback, W Ritchie, T Chebotareva, T Ferrier, C Clarke, J Taylor, E Gallagher, AC Maurício, M Sousa, I Wilmut, 2005. Cloning and Stem Cells 7(2): 126). But ethical issues related to the collection and manipulation of human embryonic stem cells, even for therapeutic use is very controversial and understandable. So, more recently the potential of fetal stem cells derived from extra-embryonic tissues has been deeply investigated by her research group. Therefore, a continued effort to identify and characterize novel stem cell populations appears critical for widespread clinical success. This effort implies in vitro studies, experimental surgery and in vivo testing, before the clinical trials and the compassive treatment in such clinical cases where the traditional and standard treatments failed. Her research groups works exactly in this direction, so she created a multidisciplinary team, including Veterinaries, Engineers, Medical Doctors that through Experimental Surgery have a crucial role in the development of biomaterials and cellular therapies, allowing a close share of knowledge between biomaterials design, development of cellular systems, and surgeons needs when related to specific clinical cases. This group has several recent relevant publications in the research areas of nerve, bone, musculoskeletal and vascular tissue regeneration. In her laboratory have been working several PhD and Post-Doctoral students from various countries who have acquired a high level of competence in the study of tissue regeneration. She is the supervisor of several PhD, Post-Doctoral and Master students (16 PhD thesis already concluded with success and 14 PhD thesis on going), she is the co-author of a large number of scientific articles published in Indexed Journals (she publishes as Maurício AC) and of several scientific book chapters. She was the principal researcher of several national and international scientific projects. Editor of three international scientific books, inventor of three international patents.",institutionString:"University of Porto",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Porto",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1054",title:"Neurobiology",slug:"mental-and-behavioural-disorders-and-diseases-of-the-nervous-system-neurobiology"}],chapters:[{id:"55127",title:"Peripheral Nerve Injury and Current Treatment Strategies",doi:"10.5772/intechopen.68345",slug:"peripheral-nerve-injury-and-current-treatment-strategies",totalDownloads:3003,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:1,abstract:"Neuronal cells are the main fundamental anatomic unit of the system. Nerve injuries are generally divided into three categories as neuropraxia, axonotmesis and neurotmesis. Neurotmesis is the most severe form. Schwann cells are activated within 24 hours of the injury and the healing cascade continued with the cells, which are stimulated by Schwann cells. And neurotrophic factors like nerve growth factor (NGF) have a crucial role in regeneration and degeneration processes. Additionally, Schwann cells upregulate the expression of some proteins, such as fibronectin, which are crucial for axonal regeneration. All this information about nerve healing sheds light on treatment studies. Iatrogenic nerve injury has an important place in peripheral nerve injury. Causes may be direct surgical damage, wrong intraoperative patient positioning, anaesthesia-related reasons or limb tourniquets. Typical symptoms are motor or sensory deficits such as paraesthesia, weakness, paralysis and pain. Many of the traumatic nerve injuries require surgical repair. Direct nerve repair and autologous nerve grafts are still gold-standard treatment options. Additionally, nerve conduits are very successful to provide an ideal peripheral support for neuronal recovery but are still insufficient. In recent years, research efforts have focused on the neurotrophic factors and cell-based therapies to perform better microenvironment for neuronal healing.",signatures:"Aysu Hayriye Tezcan",downloadPdfUrl:"/chapter/pdf-download/55127",previewPdfUrl:"/chapter/pdf-preview/55127",authors:[{id:"205536",title:"Prof.",name:"Aysu",surname:"Hayriye Tezcan",slug:"aysu-hayriye-tezcan",fullName:"Aysu Hayriye Tezcan"}],corrections:null},{id:"54669",title:"Peripheral Nerve Entrapment and their Surgical Treatment",doi:"10.5772/67946",slug:"peripheral-nerve-entrapment-and-their-surgical-treatment",totalDownloads:1760,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Nerves pass from one body area to another through channels made of connective tissue and/or bone. In these narrow passages, they can get trapped due to anatomic abnormalities, ganglion cysts, muscle or connective tissue hypertrophy, tumours, trauma or iatrogenic mishaps. Nearly all nerves can be affected. The clinical presentation is pain, paraesthesia, sensory and motor power loss. The specific clinical features will depend on the affected nerve and on the chronicity, severity, speed and mechanism of compression. Its incidence is higher under some occupations and is some systemic conditions: diabetes mellitus, hypothyroidism, acromegaly, alcoholism, oedema and inflammatory diseases. The diagnosis is suspected with the clinical presentation and provocative clinical test, being confirmed with electrodiagnostic and/or ultrasonographic studies. Magnetic Resonance Studies (MRI) rule out ganglion cysts or tumours. Conservative medical treatment is often sufficient. In refractory ones, surgical decompression should be performed before nerve damage and muscle atrophy are irreversible. The ‘double crash’ syndrome happens when a peripheral nerve is compressed at more than one point along its trajectory. In cases with marked muscle atrophy, a ‘supercharge end‐to‐side’ nerve transfer can be added to the decompression. After decompression in those few cases with refractory pain, a nerve neurostimulator can be applied.",signatures:"Vicente Vanaclocha‐Vanaclocha, Nieves Sáiz‐Sapena, Jose María\nOrtiz‐Criado and Nieves Vanaclocha",downloadPdfUrl:"/chapter/pdf-download/54669",previewPdfUrl:"/chapter/pdf-preview/54669",authors:[{id:"199099",title:"Dr.",name:"Vicente",surname:"Vanaclocha",slug:"vicente-vanaclocha",fullName:"Vicente Vanaclocha"}],corrections:null},{id:"54665",title:"Nerve Transfers in the Treatment of Peripheral Nerve Injuries",doi:"10.5772/67948",slug:"nerve-transfers-in-the-treatment-of-peripheral-nerve-injuries",totalDownloads:2100,totalCrossrefCites:0,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Successful re-innervation of proximal limb peripheral nerve injuries is rare. Axons regenerate at ~1 mm/day, reaching hand muscles by 24 months, finding them atrophied and fibrosed. Peripheral nerve injury repair is often delayed waiting for spontaneous recovery. This waiting time should not be longer than 6 months as after 18 months reinnervation will not achieve effective muscular function. When spontaneous recovery is impossible, referral too late or damage too severe, other options like a transfer from a nearby healthy nerve to the injured one must be considered. They are very successful, and the deficit in the donor site is usually minimal. The most common nerve transfers are a branch of the spinal nerve to the trapezius muscle to the suprascapular nerve, a branch of the long head of the triceps to the axillary nerve, a fascicle of the ulnar nerve to the motor branch of the biceps muscle, two branches of the median nerve to the posterior interosseous nerve and the anterior interosseous nerve to the ulnar nerve. There are many more options that can suit particular cases. Introduced in brachial plexus injury repair, they are now also applied to lower limb, to stroke and to some spinal cord injuries.",signatures:"Vicente Vanaclocha-Vanaclocha, Jose María Ortiz-Criado, Nieves\nSáiz-Sapena and Nieves Vanaclocha",downloadPdfUrl:"/chapter/pdf-download/54665",previewPdfUrl:"/chapter/pdf-preview/54665",authors:[{id:"199099",title:"Dr.",name:"Vicente",surname:"Vanaclocha",slug:"vicente-vanaclocha",fullName:"Vicente Vanaclocha"},{id:"204650",title:"Prof.",name:"Jose María",surname:"Ortiz-Criado",slug:"jose-maria-ortiz-criado",fullName:"Jose María Ortiz-Criado"},{id:"204651",title:"Dr.",name:"Nieves",surname:"Saiz-Sapena",slug:"nieves-saiz-sapena",fullName:"Nieves Saiz-Sapena"},{id:"204652",title:"BSc.",name:"Nieves",surname:"Vanaclocha",slug:"nieves-vanaclocha",fullName:"Nieves Vanaclocha"}],corrections:null},{id:"55030",title:"Surgical Treatment of Brachial Plexus Injury",doi:"10.5772/intechopen.68442",slug:"surgical-treatment-of-brachial-plexus-injury",totalDownloads:1539,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In recent years, brachial plexus injury has been attracting increasing attention, partly because of an increasing incidence arising out of higher survival rates for patients after polytrauma. Brachial plexus injury is one of the hardest and most mutilating injuries. Owing to advances in microsurgical techniques, we can achieve success in restoring motor function for these patients. The purpose of this chapter is to introduce the reader with various microsurgical techniques, including nerve fascicle transfers and end-to-side neurorrhaphy (ETSN), which can be used for brachial plexus reconstruction based on personal experience with 1130 nerve reconstructions performed by the first author (PH) between 1993 and 2017. Another goal of brachial plexus surgery is the resolution of severe intractable pain which can develop in up to 20% of cases. Dorsal root entry zone (DREZ) thermocoagulation is a very effective method for treatment of severe neuropathic pain.",signatures:"Pavel Haninec and Libor Mencl",downloadPdfUrl:"/chapter/pdf-download/55030",previewPdfUrl:"/chapter/pdf-preview/55030",authors:[{id:"200723",title:"Prof.",name:"Pavel",surname:"Haninec",slug:"pavel-haninec",fullName:"Pavel Haninec"},{id:"200895",title:"Dr.",name:"Libor",surname:"Mencl",slug:"libor-mencl",fullName:"Libor Mencl"}],corrections:null},{id:"54772",title:"The Role of Nucleotides in Glial Cells during Peripheral Nerve Trauma and Compressive Disorders",doi:"10.5772/68068",slug:"the-role-of-nucleotides-in-glial-cells-during-peripheral-nerve-trauma-and-compressive-disorders",totalDownloads:2288,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Studies have shown that the administration of drugs containing pyrimidine nucleotides, such as uridine triphosphate (UTP) and cytidine monophosphate (CMP), has been effective in pain-intensity reductions in patients with painful conditions as diabetic neuropathy, back pain, and cervical and trauma-compressive changes. The combination of pyrimidine nucleotides UTP and CMP is part of a peripheral neuro-regenerative process. Its pharmacological properties are stimulation of nerve cells proteins synthesis, nerve cell membranes synthesis, myelin sheaths synthesis, and neurite sprouting through P2Y receptors activation. Herein, chapter will be discussed the combination of UTP and CMP, and in some cases, the inclusion of cobalamin (B12 vitamin) that appears to have analgesic effects in neuropathic pain secondary to spine structural disorders assigned to a complex pharmacodynamic. The mechanisms involved can be both indirect (protein synthesis in nerve cells, myelin synthesis, synthesis of MBP, etc.) and direct (P2Y receptor stimulation).",signatures:"Marina Manhães, Marcelo Cesar, Rayssa Justo, Mauro Geller,\nMendel Suchmacher and Rafael Cisne",downloadPdfUrl:"/chapter/pdf-download/54772",previewPdfUrl:"/chapter/pdf-preview/54772",authors:[{id:"200441",title:"Prof.",name:"Rafael",surname:"Cisne",slug:"rafael-cisne",fullName:"Rafael Cisne"},{id:"200473",title:"MSc.",name:"Marcelo",surname:"Cesar",slug:"marcelo-cesar",fullName:"Marcelo Cesar"},{id:"200474",title:"Ms.",name:"Rayssa",surname:"Justo",slug:"rayssa-justo",fullName:"Rayssa Justo"},{id:"200475",title:"Ms.",name:"Marina",surname:"Manhães",slug:"marina-manhaes",fullName:"Marina Manhães"},{id:"205068",title:"Prof.",name:"Mauro",surname:"Geller",slug:"mauro-geller",fullName:"Mauro Geller"},{id:"205069",title:"MSc.",name:"Mendel",surname:"Suchmacher",slug:"mendel-suchmacher",fullName:"Mendel Suchmacher"}],corrections:null},{id:"55017",title:"The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair",doi:"10.5772/intechopen.68378",slug:"the-role-of-pharmacological-agents-in-nerve-regeneration-after-peripheral-nerve-repair",totalDownloads:1902,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Peripheral nerve injuries are frequent and represent a significant pathology of the peripheral nervous system because, despite operative techniques and successful microsurgical repair, in most cases, the nerve repair is followed by scar formation. Numerous investigations have been carried out with the aim of finding pharmacological substances that can prevent scar formation and speed up the regeneration of repaired nerves. This chapter is dedicated to the efforts of many researchers to find different pharmacological agents with local effects on the improvement of nerve regeneration. Numerous experiments have been carried out in mice and rabbits using hyaluronic acid, tacrolimus, cyclosporin A, melatonin, vitamin B12, methylprednisolone, riluzole and potassium and calcium channel blockers. In the experimental animal studies, topical pharmacological agents were used at the site of peripheral nerve repair. The effect of these substances is most commonly studied in sciatic nerve injury in experimental animals. Their effects were evaluated using a variety of methods, such as morphological, biomechanical, electrophysiological and functional evaluation, and the above‐mentioned substances, have been shown to have neuroprotective and neuroregenerative properties though different mechanisms.",signatures:"Agon Mekaj and Ymer Mekaj",downloadPdfUrl:"/chapter/pdf-download/55017",previewPdfUrl:"/chapter/pdf-preview/55017",authors:[{id:"199721",title:"Prof.",name:"Ymer",surname:"Mekaj",slug:"ymer-mekaj",fullName:"Ymer Mekaj"},{id:"200047",title:"Dr.",name:"Agon",surname:"Mekaj",slug:"agon-mekaj",fullName:"Agon Mekaj"}],corrections:null},{id:"54592",title:"Adult and Reparative Neurogenesis in Fish Brain",doi:"10.5772/67951",slug:"adult-and-reparative-neurogenesis-in-fish-brain",totalDownloads:1220,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The fish brain has a unique feature of vertebrates—it grows with the growth of body over a lifetime. In this regard, fishes are a convenient model for the study of embryonic and postembryonic development of the central nervous system and of the influence of different factors on these processes. Currently, the mechanisms of adult brain morphogenesis of fish, which retain larval stage for a long time, are poorly understood. This is particularly true for participation of radial glia during morphogenesis of the brain, as well as the presence and distribution of the proliferative zone in the adult fish brain. Another interesting and little known aspect is the posttraumatic ability of fish to form active neurogenic niches. Investigation of the structural organizations of neurogenic niches and special conditions of the extracellular environment, as well as the interactions between neighboring cells in a neurogenic niche, is interesting and relevant direction in the study of the neuronal stem cells biology. Injury of fish brain creates special conditions for the implementation of genetic programs aimed at strengthening the proliferation of progenitor cells, as well as the activation and proliferation activity in the neuronal stem cells.",signatures:"Evgeniya V. Pushchina, Anatoly A. Varaksin, Mariya E. Stukaneva\nand Eva I. Zharikova",downloadPdfUrl:"/chapter/pdf-download/54592",previewPdfUrl:"/chapter/pdf-preview/54592",authors:[{id:"169621",title:"Dr.",name:"Evgeniya",surname:"Pushchina",slug:"evgeniya-pushchina",fullName:"Evgeniya Pushchina"}],corrections:null},{id:"54991",title:"Effect of Local Delivery of GDNF Conjugated Iron Oxide Nanoparticles on Nerve Regeneration along Long Chitosan Nerve Guide",doi:"10.5772/intechopen.68526",slug:"effect-of-local-delivery-of-gdnf-conjugated-iron-oxide-nanoparticles-on-nerve-regeneration-along-lon",totalDownloads:1335,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half‐life of few minutes. In previous studies, it was demonstrated that conjugation of various neurotrophic factors to iron oxide nanoparticles (IONP) led to stabilization of the growth factors and to the extension of their biological activity compared to the free factors. In vitro studies performed on organotypic dorsal root ganglion (DRG) cultures seeded in NVR gel (composed mainly of hyaluronic acid and laminin) revealed that the glial cell–derived neurotrophic factor (GDNF) conjugated to IONP‐enhanced early nerve fiber sprouting and accelerated the onset and progression of myelin significantly earlier than the free GDNF and other free and conjugated factors. The present article summarizes results of in vivo study, aimed to test the effect of free versus conjugated GDNF on regeneration of the rat sciatic nerve after a severe segment loss. We confirmed that nerve device enriched with a matrix with GDNF gives more successful results in term of regeneration and functional recovery in respect to the hollow tube; moreover, there are no detectable differences between free versus conjugated GDNF.",signatures:"Federica Fregnan, Michela Morano, Ofra Ziv-Polat, Mira M.\nMandelbaum-Livnat, Moshe Nissan, Tolmasov Michael, Akiva\nKoren, Tali Biran, Yifat Bitan, Evgeniy Reider, Mara Almog, Nicoletta\nViano, Shimon Rochkind, Stefano Geuna and Abraham Shahar",downloadPdfUrl:"/chapter/pdf-download/54991",previewPdfUrl:"/chapter/pdf-preview/54991",authors:[{id:"48118",title:"Prof.",name:"Stefano",surname:"Geuna",slug:"stefano-geuna",fullName:"Stefano Geuna"},{id:"200265",title:"Dr.",name:"Federica",surname:"Fregnan",slug:"federica-fregnan",fullName:"Federica Fregnan"},{id:"205254",title:"Dr.",name:"Michela",surname:"Morano",slug:"michela-morano",fullName:"Michela Morano"},{id:"205256",title:"Dr.",name:"Nicoletta",surname:"Viano",slug:"nicoletta-viano",fullName:"Nicoletta Viano"},{id:"205868",title:"Dr.",name:"Ofra",surname:"Ziv-Polat",slug:"ofra-ziv-polat",fullName:"Ofra Ziv-Polat"},{id:"205869",title:"Dr.",name:"Mira M.",surname:"Mandelbaum-Livnat",slug:"mira-m.-mandelbaum-livnat",fullName:"Mira M. Mandelbaum-Livnat"},{id:"205870",title:"Dr.",name:"Moshe",surname:"Nissan",slug:"moshe-nissan",fullName:"Moshe Nissan"},{id:"205872",title:"Dr.",name:"Michael",surname:"Tolmasov",slug:"michael-tolmasov",fullName:"Michael Tolmasov"},{id:"205873",title:"Mr.",name:"Akiva",surname:"Korn",slug:"akiva-korn",fullName:"Akiva Korn"},{id:"205874",title:"Dr.",name:"Tali",surname:"Biran",slug:"tali-biran",fullName:"Tali Biran"},{id:"205875",title:"Dr.",name:"Yifat",surname:"Bitan",slug:"yifat-bitan",fullName:"Yifat Bitan"},{id:"205876",title:"Dr.",name:"Evgeniy",surname:"Reider",slug:"evgeniy-reider",fullName:"Evgeniy Reider"},{id:"205877",title:"Prof.",name:"Shimon",surname:"Rochkind",slug:"shimon-rochkind",fullName:"Shimon Rochkind"},{id:"205878",title:"Prof.",name:"Abraham",surname:"Shahar",slug:"abraham-shahar",fullName:"Abraham Shahar"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited 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TB is the leading cause of death from a single infectious agent worldwide. The burden of the disease is enormous with an estimated 10.4 million new cases and 1.7 million TB deaths reported in 2016. Furthermore, more than one-fifths of reported deaths occurred among those who were HIV-infected [1]. While TB-mortality rate among HIV-negative people was 17 per 100,000 population, it was 5 per 100,000 among people living with HIV. In addition, 12% of incident cases of TB occurred among HIV-positive people while one in ten of new TB cases occurred among children in the same year [1]. According to WHO, the 30 countries most affected by TB include Angola, Bangladesh, Brazil, Cambodia, China, Congo, Central African Republic, DPR Korea, DR Congo, Ethiopia, India, Indonesia, Kenya, Lesotho, Liberia, Mozambique, Myanmar, Namibia, Nigeria, Pakistan, Papua New Guinea, Philippines, Russian Federation, Sierra Leone, South Africa, Thailand, UR Tanzania, Viet Nam, Zambia, and Zimbabwe [1].
TB mortality burden is continues to pose challenges to socioeconomic development in developing countries as South East Asia, Western Pacific, and African regions accounted for more than 90% of TB-deaths in 2016 [1].
Analysis of cohorts of patients on tuberculosis treatment enables public health programmes to describe the survival of patients and factors associated with mortality experience among patients. While treatment outcomes vary among different cohorts of TB patients, patients with drug resistance TB and those with coexisting debilitating conditions experience worst outcomes. Furthermore, survival of TB patients depends on several medical, demographic and socio-economic factors. This chapter focuses on the epidemiology of TB mortality, and the determinants of survival of TB patients – the factors which represent the most important opportunities for prevention of TB-related deaths in developing countries.
Mycobacterium tuberculosis––the causative organism of TB, is the leading cause of death from a single infectious agent after Human Immunodeficiency Virus (HIV). About 45,000 TB-related deaths occurred in Europe in 2011 and its estimated mortality rate was 5.0 per 100,000 population [2]. While 330 TB-related deaths and an estimated TB-mortality rate of 0.5 per 100,000 population were reported in the United Kingdom, TB-death rates were 0.4, 1.0, 8.9, 15.0, and 16.0 per 100,000 population in Germany, France, Belarus, Russia, and Ukraine respectively [3]. In the United States, more than 50,000 TB-related deaths were reported from 1990 to 2006, accounting for 0.13% of the total number of deaths in the country [4]. While TB was reported as the underlying cause of death in about 40% of the 39,694,210 total deaths that occurred, it was reported as one of the contributing causes of death in more than 60% of the total deaths [1]. The overall mean annual mortality rate was 1.16 per 100,000 person-years during this period [1]. Similarly, 7% of the 301 persons with TB reported to Connecticut TB Control Program from 2007 to 2009 died on account of the disease [5]. Furthermore, 11% of the 40, 125 patients with culture-confirmed TB died on account the disease in California from 1994 to 2008 [3]. In 2014, more than 5% of the 9406 patients with TB in the US died due to the disease [6].
Although TB is a major public health problem worldwide, its mortality in developing countries is alarming. An estimated 2.5 million TB deaths were reported in China from 1990 to 2015 and 2% of these deaths occurred in 2015 [7]. Furthermore, TB-mortality rates were 32 and 44 per 100,000 population in 2016 in India and Pakistan, respectively [1]. While 16% of those who had TB died of the disease in Zimbabwe was in 2013 [8], TB-related mortality rates were estimated at 29, 56, 83, 104, and 222 per 100,000 population in Ethiopia, Ghana, Swaziland, Nigeria, and South Africa respectively in 2016 [1]. In addition, the estimated TB-related mortality rate in in Africa was 72 per 100,000 population while it was 3.4 per 100,000 population in European region and 2.3 per 100,000 population in the WHO Region of the Americas in 2016 [1].
Tuberculosis, often referred to as “consumption,” “phthisis,” or the “white plague,” accounted for the highest number of deaths in Europe and America during the eighteenth and nineteenth centuries. While 70–90% of urban populations of Europe and North America were infected with TB in the late nineteenth century, four-fifths of people infected with TB died of it [9]. Through the knowledge made available by the work of Villemin, Koch, von Pirquet, TB mortality began to decline in the early and mid-nineteenth century [10, 11, 12]. TB Decline in TB mortality in these parts of the world was associated with improvement in socio-economic conditions of the populations.
In the United Kingdom, the rapid decline in TB mortality was cited as one of the most important health gains of the twentieth century [13]. Using all certified causes of death (both underlying cause and elsewhere on certificates), TB-mortality in the Oxford region declined from 39.7 deaths per million population in 1979 to 9.0 in 2008. In England, TB-mortality rates fell from 18.5 per million population in 1995 to 12.2 in 2008 [13].
TB mortality has been dropping rapidly since 1900 in developed countries, especially after the development of new anti-tuberculosis drugs. In the United States, 74,842 TB-related deaths were reported in 1933 [14]. This had declined by 22.9% by 1942 and a further decline was reported in the following decade such that only 25,080 TB-related deaths were reported in 1952 [12]. Furthermore, TB-mortality rates were 59.6, 43.1, and 16.1 per 100, 000 population in 1933, 1942, and 1952 respectively in the United States [12]. While 644 TB-deaths were reported in 2006, the estimated number of TB-related deaths was 610 in 2016 [1]. In essence, TB-mortality declined in the US from 59.6 per 100, 000 in 1933 to 0.19 per 100, 000 in 2016 [1, 12].
Due to poor vital registration systems, records on TB-mortality trends in developing countries are limited. A significant increase in TB mortality was recorded from 1990 and 2000 worldwide. However, the increase was more obvious in developing countries (Figure 1). In 2004, TB-mortality rate in Bangladesh was 51 per 100,000 population, while it was 81 per 100,000 in 2014 [8, 15]. Similarly, TB-death rates in Nigeria and South Africa in 2004 were 82 and 135 per 100,000 population respectively. By 2014, the mortality rates had increased to 170 per 100,000 in Nigeria while it decreased to 24 per 100,000 in South Africa [7, 14]. Furthermore, TB mortality rates declined significantly between 2000 and 2016 (Figure 2).
Global trends in TB mortality from 1990 to 2000. Data source: Global tuberculosis report 2013. WHO/HTM/TB/2013.11. Geneva: WHO; 2013.
Global trends in TB mortality from 2000 to 2016. Data source: WHO. Global Health Observatory data repository. Tuberculosis [Internet]. Geneva: WHO; 2017 Dec 1 [cited 2018 Feb 12]. Available from:
Tuberculosis (TB) is an old disease of mankind from time immemorial. An evidence of TB spine was found in Egyptian mummies of several thousand years BC, while Babylonian and Chinese writings also referred to the disease [16]. TB is an infection caused by the rod-shaped, non-spore-forming bacterium called
TB infection leads to a complex interaction with the immune system of the human host. This interaction is often moderated by a number of factors with influence survival of TB patients.
TB is transmitted from a person with active TB disease to an uninfected person through the air by droplet nuclei––particles measuring 1–5 μm in diameter containing MTBC [19]. These droplet nuclei are produced when persons with pulmonary or laryngeal TB cough, sneeze, speak, or sing. Iatrogenic transmission of TB may also occur during aerosol treatments, sputum induction, bronchoscopy, or during tissue or secretion processing in hospitals or laboratories. Droplet nuclei can remain airborne for long periods of time after expectoration. The transmission of TB depends on a number of factors including the number of tubercle bacilli present in droplets, its virulence and exposure to ultraviolet light, the extent of ventilation, and the immune status of exposed persons. After inhalation of an infectious droplet nucleus, it settles in the respiratory tract and reaches a respiratory bronchiole or alveolus where the tubercle bacilli may establish an infection depending on the bacterial virulence and the inherent mycobactericidal capacity of the alveolar macrophage. With the activation of the host defenses, phagocytosis by alveolar macrophages often initiates a cascade of events resulting in either a successful control of the infection, which is usually followed by latent tuberculosis. The invading mycobacterium may overwhelm host defense mechanisms followed by progression to active disease, known as primary progressive tuberculosis [19]. Within the alveolar macrophage, the tubercle bacillus continues growing slowly and dividing almost every 25–32 h for 2–12 weeks such that they reach 103–104 thereby eliciting a cellular immune response which is often detected by a positive reaction to a tuberculin test. For an immunocompetent person, the formation of granulomas around the invading mycobacterium occurs at this time.
Prior to the development of cellular immunity, tubercle bacilli may be disseminated via the lymphatics to the hilar lymph nodes and the bloodstream. When these bacilli reach more distant sites, they may give rise to extra pulmonary TB infection of the brain meninges, larynx, lymph nodes, spine, and kidney.
Granulomas formed by accumulation of T lymphocytes and microphages limit mycobacterial replication and spread [20]. Although the environment provided by granuloma formation destroys macrophages and produces early solid necrosis at the center of the lesion, tubercle bacilli often adapt to enhance their survival [20]. The formation of caseous necrosis, a soft-cheese structure with low oxygen levels, low pH, and limited nutrients in the following 2–3 weeks creates a condition that limits further mycobacterial growth. Latent tuberculosis is established at this stage. While tuberculous lesions undergo fibrosis and calcification thereby controlling the infection, the tubercle bacilli within the lesions may begin to multiply rapidly if the immune system of the individual deteriorates [21].
For an immunocompromised person, granuloma formation also occurs following infection with MTBC. However, the granulomas formed are unable to contain the infection. Hence, this progresses to primary progressive tuberculosis [21]. The necrotic tissue of the granuloma liquefies and the fibrous wall breaks down. Furthermore, the semiliquid necrotic matter may drain into surrounding structures including the bronchi, and nearby blood vessels leaving an empty, air-filled cavity at the middle of the initial lesion. In addition, discharge of the necrotic material into a vessel may lead to extra pulmonary TB and mortality from TB may be related to this.
The management of patients suspected of TB disease involves clinical assessment and treatment (Figure 3). Of the treatment outcomes, Cured and Completed treatment are considered as successful outcomes while the remaining ones are often referred to as poor treatment outcomes [1, 22].
Clinical assessment and treatment of TB patients.
Although deaths on account of TB disease occur worldwide, developing countries account for more than 90% of TB mortality in recent times. Hence, the focus of this section will be on developing countries. Several factors influence susceptibility of TB infection, its severity as well as mortality.
Factors associated with survival among TB patients in developing countries can be discussed using a framework proposed by the Commission on Social Determinants of Health (CSDH) established by WHO (Figure 4) [23].
Conceptual framework for the social determinants of health and health inequities [
Factors associated with survival among patients with TB disease can be classified into patient and community/social factors. In the context of the CSDH framework, most of the patient factors can be described in terms of the health system while community/social factors are related to the structural determinants of health and health inequities. Patient characteristics include age, sex, alcohol use, cigarette smoking, previous history of TB treatment, HIV co-infection, and comorbid conditions, TB diagnostic methods, and treatment regimens. On the other hand, structural determinants of health associated with TB survival include the presence of education, employment, access to health care and protection from catastrophic expenditure associated with TB morbidity.
Aging affects the immune system at multiple levels including reduced production of B and T cells and diminished function of mature lymphocytes in secondary lymphoid tissues. Furthermore, aging causes a profound alteration in the composition and quality of the mature lymphocyte pool and alters the patterns of gene expression in mature B and T cells. Compared to young people, elderly individuals respond to immune challenge in a less efficient manner [24].
Old age increases the likelihood of death from TB. Evidence for this has been reported in previous studies. While several age cut-points have been used in studies to show vulnerability, TB infection in people over the age of 60 years is associated with increased mortality. A retrospective study among adult patients with clinically and/or bacteriologically diagnosed TB in Argentina reported increased mortality among people who were older than 50 years [22]. A similar study conducted in South Africa reported that patients who were 60 years or older were twice more likely to die from TB than the younger ones [25]. In addition, patients aged 65 years and above were two times more likely to die from TB than other patients in a study in Zimbabwe [26].
Infectious diseases including TB generally affect males more than females. Studies have shown that interactions between sex hormones and the immune system render males more susceptible to infection and disease, with differences in genetic make-up likely playing a role [27, 28].
A recent study in Brazil aimed at examining sex bias in ten major pathogens also reported the characteristic male bias of a male-to-female ratio of almost 2:1 [2]. While tuberculoid leprosy is slightly more common in females (0.85:1), the study reported a ratio of almost 3:1 for the severe lepromatous form. Host immune response to leprosy has been compared to that in tuberculosis and lepromatous leprosy was considered as being analogous to active tuberculosis. Furthermore, tuberculoid leprosy may be seen as analogous to latent TB or cured or TB [29]. Since both diseases are caused by the same pathogen—Mycobacterium, the male bias observed supports the hypothesis that physiological differences may be responsible for the observed differential susceptibility to TB. This physiological hypothesis (PH) has also been found to be relevant in TB disease as a driver of sex differences in disease susceptibility [1, 2]. TB mortality is also in keeping with differential susceptibility between males and females as more than 65% of adult TB deaths in 2016 occurred among males [1]. This is also similar to the twentieth century in New York which showed a male-to-female TB mortality ratio of approximately 2:1 [30].
A consistent finding in literature shows that males are more likely to die from tuberculosis than females. A study in Ethiopia, showed that males are twice more likely to have poor treatment outcome (including death) following TB treatment [31]. In addition, a systematic review and meta-analysis consisting of multidrug resistant-TB (MDR-TB) data from 31 treatment programmes from 21 countries showed that males are less likely to have a successful outcome after treatment [32]. Although there was no association between sex and survival among patients in a study in South Africa, male patients were more likely to have unfavorable TB treatment outcomes [33].
Educational status is an important factor which moderates health care seeking behavior and adherence to prescribed medications. The level of educational achievement may protect against acquiring TB infection through promotion of healthy habits. In addition, education been recognized as a marker of economic status. Hence, low level education may be associated with lack of access to resources, overcrowding and poor hygienic conditions which may also contribute to increased mortality. In a study in Peru, MDR-TB patients who attended formal school for 6 or less years had about threefold increase in TB mortality risk [34]. Similarly, attendance or completion of primary school level was associated with TB treatment failure [35]. While educational status may be a significant factor influencing survival in most health conditions, only a few studies reported it as a determinant of survival among patients with TB in developing countries [32, 34].
Occupations which compromise structural and/or functional integrity of the lungs predispose individuals to the transmission of TB as well as to higher risk of mortality on account of the disease. While exposures to dust inside the mines damage the structure and function of the lungs (e.g., silicosis), associated social conditions outside the mines (e.g., crowding) drive HIV and TB epidemics. This makes mining a strong predictor of TB mortality. Studies in Southern Africa have reported the strong association between mining and TB mortality [36, 37].
Smoking is one of the most important risk factors associated with incidence, morbidity, recurrence and mortality from TB. Smoking has been associated with a fourfold increase in TB mortality risk [38].
Previous TB treatment has been associated with TB mortality. A prospective study among smear positive TB patients with Iranian nationality who had successful TB treatment showed that those who had previous history of TB treatment were almost three times more likely to die [39]. Similarly, patients with a previous history of TB treatment were almost seven times more likely to die than treatment-naive patients in another study in Iran [40]. This may be related to development of resistance following treatment default, failure, or loss to follow up.
Multidrug-resistant tuberculosis (MDR-TB), a form of TB disease resistant to both isoniazid and rifampicin is a global problem. Increasing incidence of this type of TB is a reflection of the health care system of a country. It arises as a result of weak TB treatment programmes coupled with poor adherence to anti-TB therapy. While the extent and burden of the disease varies among countries, it often overwhelms the capacity of the health system in many high burden resource-poor countries.
Studies have consistently shown that MDR-TB is a strong predictor of TB mortality. In 2016, it was responsible for a large percentage of TB mortality worldwide [1]. MDR-TB was associated with almost eightfold increase in mortality risk in a retrospective study in Peru [32]. Other studies have also shown similar findings. Furthermore, MDR-TB associated hazard ratio (HR) estimates in TB mortality increase in previous studies were in the range of 7.8–8.5 [41, 42].
Extensively drug-resistant tuberculosis (XDR-TB), a variant of MDR-TB resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin) in addition to isoniazid and rifampin. XDR-TB has also been associated with high death rates while on treatment.
There are multiple causes for the increased risk of multidrug-resistant TB strains. MDR-TB infection often occur with other co-morbid conditions including HIV infection, diabetes, renal disease, and Substance Use Disorders [43]. In addition, MDR-TB has been associated with high rates of treatment failure and relapse which increases TB mortality. With high toxicity of anti-tuberculosis drugs used in the treatment of MDR-TB and the extended duration of use, an increase in toxicity profile of patients and consequent adverse effects may be related to increased mortality experienced among MDR-TB patients.
Studies have shown that HIV/TB co-infection is associated with increased TB mortality risk before, during, or after TB treatment. In most cases, deaths are usually caused by complications of HIV infection rather than TB disease itself. However, a synergistic interaction occurs between TB and HIV infection which speeds up the progression of illness and increasing mortality risk. HIV infection enhances the reactivation and progression of latent
In Malawi, HIV positive patients were 2.5 times more likely to die from TB infection in a prospective cohort study among TB patients [45]. Another study in Malawi also reported almost fourfold increase in TB mortality among HIV/TB co-infected patients compared to HIV seronegative TB patients [46]. Furthermore, HIV co-infection was associated with almost sixfold increase in TB mortality in a study in Ethiopia [35].
Among patients who were HIV/TB co-infected, being on antiretroviral therapy (ART), initiation of cotrimoxazole prophylactic therapy (CPT), being ambulatory, and having high CD4 counts were factors associated with survival in several studies. Patients who were on ART were 0.35 times less likely to die from TB compared to those who were not on ART [47].
While MDR-TB infection is associated with increased mortality risk for both HIV-seropositive and seronegative patients, HIV/MDR-TB co-infection increases the risk of death. A study in Thailand reported that patients who were HIV positive patients infected with MDR-TB were twice more likely to die compared to HIV seropositive patients who had non-MDR-TB co-infection [48]. Similarly, HIV/TB co-infected patients who delayed initiation of ART 6 or months or more after TB diagnosis were 2.6 times more likely to die compared with those who initiated ART in less than 6 months following TB diagnosis [47].
Although extra pulmonary TB is not as common as pulmonary disease, its occurrence has consistently been shown in literature as a predictor of TB mortality. Patients with extra pulmonary TB including TB meningitis, TB pericarditis, TB peritonitis, bilateral or extensive pleural effusion due to TB, Potts disease, TB of the genitourinary tract, and TB of the intestine were twice more likely to die on account of the disease than patients with pulmonary disease in a study in Brazil [49]. Furthermore, patients who had extra pulmonary TB were three times more likely to die than those who had pulmonary TB [50]. Similarly, miliary TB has also been associated with poor outcomes [51].
Co-morbid conditions including malnutrition, chronic renal disease, chronic liver disease, drug induced immunosuppression, and diabetes mellitus are predictors of mortality among TB patients.
The synergistic interactions between diabetes mellitus and TB are well documented in literature [52]. Diabetes alters host immunity to TB which leads to higher baseline mycobacterial burdens and longer times to achieve culture conversion with treatment. While treatment failure or death was reported in 41% of patients with TB and diabetes in case-control study, these outcomes were only reported in 13% of those with TB alone. Furthermore, seven of the eight patients in the TB and diabetes group died of respiratory failure related to TB [53].
Malnutrition has been cited as a predictor of mortality among TB patients. Malnourished patients were 27 times more likely to have unfavorable TB outcome and death in a study in South Africa [54].
The presence of end stage renal disease requiring dialysis was associated with sevenfold increase in TB mortality risk in a previous study [55].
The presence of drug induced immunosuppression was associated with increased TB mortality risk with adjusted odds ratio of 3.2 [51].
Studies have shown that TB patients with poor adherence to medications are more likely to die compared to other patients. A retrospective study involving patients in 48 clinics in Rwanda among patients treated in 48 clinics in Rwanda showed that poor treatment adherence was associated with more than threefold increase in TB mortality [56].
Neighbourhood factors refer to issues within the society that contribute to TB mortality which are not directly related to a patient’s individual condition but a constellation of factors which affect a patient’s access to care, treatment enablers, emergency services, and attitudes of the general population to health. These include societal norms and values, policy, and governance issues within and outside the health system (Figure 4).
Neighbourhoods play a role in TB morbidity and mortality as good housing may influence air quality and disease transmission. Access to nutritious foods may also be important for immune responses and recovery from TB infection. In addition, Service characteristics of neighbourhoods can create and support employment opportunities which may reinforce socioeconomic disparities in health.
The level of the commitment of health authorities at the local, regional, and national levels towards TB treatment, care and support influences the survival of patients [1]. For instance, the failure of a TB treatment programme to follow up on patients on treatment may contribute to increased mortality. In addition, failure of the health system to screen and test HIV positive patients for TB may also affect their survival.
Social protection is one of the functions of the health system. However, unemployment, low status occupation, low annual income, high cost of travel to the health care facility for TB treatment, poor living conditions, low literacy level, and high out-of-pocket expenditure on TB treatment have been described as factors associated with poor treatment adherence, unfavorable TB treatment outcomes, and death. Furthermore, a strong correlation was reported between TB treatment outcomes and overall health system performance in a study in South Africa where TB treatment centers with higher health system performance rating also had higher percentage of successful treatment outcomes [57].
Studies have shown that seasonal variation in the incidence of TB disease occurs in many developing countries. In India and Hong Kong, TB seasonality was highest among young children. However, seasonality of notified TB cases was more pronounced among males in Mongolia and South Western Cameroon [58]. In Southern Africa, most significant declines in the diagnoses of pulmonary TB occurred in December, followed by April–May. While these may not be unrelated to climatic factors, changes in health-seeking behavior and fluctuations in clinical activities were cited as responsible factors [59]. In China, increased incidence of TB was associated with increased temperature, precipitation, and wind speed [60].
Seasonality of TB disease may be related to differences in TB risk factors at certain seasons. A study in Peru showed the complex interaction of social determinants of TB infection, exposure to infection and increased transmission. Overcrowding, increased indoor time, and poorer ventilation, poorer nutrition, lower immunity, health-seeking behavior, and education interact in a complex way to an increase in TB disease at certain seasons than others. Vitamin D deficiency, more likely to occur in winter, was also associated with TB seasonality [61].
The burden of TB and the mortality on account of the disease has been discussed. While differences in mortality between population groups due to society’s characteristics have been noted, factors associated with reduced survival among TB patients have been highlighted. Furthermore, it is important to note that changes in social and cultural environments of people are associated with changes in their risks of acquiring TB infection, and the risk of dying from the disease. Although associations between social factors and TB morbidity and mortality are well known, there is paucity of studies regarding the underlying processes linking social determinants and TB treatment outcomes and effective ways to intervene. While TB morbidity and mortality have reduced significantly in many parts of the third world in recent times, limited progress achievement are been recorded in other countries. A crucial obstacle in this regard is often the lack of political will. A strategic research agenda on reduction of TB burden should focus on the factors that enhance or impede political will to translate knowledge into effective action.
The utilization of timber in the construction sector has been revived since the mid-1990s [1, 2], and particularly in the last 10 years [3, 4], due to environmental concerns, urbanization challenges, and productivity in the construction industry [5, 6, 7]. Since the end of the twentieth century, the question of how to deal with the increasing scarcity of resources has been at the center and the need for renewable (building) materials has come to the fore, especially in the building construction industry [8]. A potential solution to these challenges is the development of engineered timber products (ETPs) that enable the erection of tall timber buildings [9] as in the case of the 18-story and 85 m high Mjøstårnet (Brumunddal, 2019).
CO2 has been a game-changer since 1970, sparking a revolution in the way buildings are built. With the successful implementation of issues such as efficiency and passive standards in just a few years, there has been an increased emphasis on sustainability during and after the construction site [10]. Furthermore, today, the construction industry accounts for approximately 40% of annual greenhouse gas emissions, 40% of global resource consumption, 40% of energy use, and 50% of global waste, timber is a valuable alternative material [11, 12].
In this sense, the use of timber can enable the construction industry to avoid significant greenhouse gas emissions associated with unsustainable material use, as it is a natural carbon sink [13]. In other words, the fact that it is a renewable building material that can store CO2 compared with steel and concrete, which are traditional building materials, has brought timber to an important point as a construction material [14, 15].
On the other hand, simultaneously, the world population doubled in less than a century, and for the first time in history, more people lived in cities than in the countryside [16]. The overall effect of this high density of people in cities forced buildings to rise. However, combined with the chronically low productivity of the construction sector since the 1990s and the high demand for new buildings in the future [17], there may be other challenges to reducing greenhouse gas emissions. The assessment of a skilled and aging workforce and slow construction time, among other factors, are significant challenges for both established and future companies [18]. Prefabrication is recommended as the best way to improve productivity, and timber is perfectly suited for this as it is light and easy to work with [19, 20].
Latest technical developments in ETPs (e.g., [21]) and systems, as well as regulatory procedures in fire codes, other building codes, and various government regulations initiatives, have allowed timber construction to reach new heights [22]. Multistory construction is a new and promising business with high potential to support the bioeconomy [23] as in the case of the 25-story and 87 m high Ascent (Milwaukee, under construction) (Figure 1). Besides the potential for substantial environmental and economic life cycle advantages can contribute to social sustainability in the processing of materials, as in both primary production and timber-based value chains [24].
Ascent (image courtesy of Jason Korb/Korb + Associates Architects).
In the literature, numerous surveys present the technical features of ETPs, their use in building construction, and diverse technical solutions (e.g., [25, 26, 27, 28]). Several surveys focus on timber as a construction material from the viewpoints of key specialists (e.g., [29, 30, 31, 32]) and users or inhabitants (e.g., [33, 34]); whereas there is a very limited number of comprehensive comparative design studies on architectural and structural parameters of multistory and tall timber buildings (e.g., [35, 36, 37]).
This chapter aims to identify, organize, and combine the data about the tallest timber buildings from the primary architectural and structural aspects to enhance understanding of the design and construction of these towers. To accomplish this goal, data were collected from the 10 tallest timber buildings under construction and completed.
The scope of the chapter is limited to the information available and uses key points to provide a representative understanding of contemporary trends in tallest timber buildings: general information (building name, location, height, number of stories, completion, gross floor area, amount of timber used), architectural and structural design parameters (building form, core type, structural system, and material). It is thought that this study will contribute to aiding and directing architects in the design and construction of future tallest timber towers.
The chapter was mainly conducted through a literature review including peer-reviewed research, official documents and reports, fact sheets, architectural and structural magazines, and other Internet sources. Additionally, case studies were used to identify, gather, and combine the data about the tallest timber buildings to examine the architectural and structural perspectives. The study sample included 10 tallest timber buildings under construction and completed, in a variety of countries (two from Norway, two from Finland, two from Canada, one from Austria, one from the Netherlands, one from the United Kingdom, and one from the United States) as seen in Table 1. In the study, a “tall building” was defined as a building with over eight story [22].
# | Name | City (country) | Height (m) | # of stories | Completion date | Gross floor area | Amount of timber used* |
---|---|---|---|---|---|---|---|
1 | Ascent | Milwaukee (USA) | 87 | 25 | UC | 30,136 m2 | NA |
2 | Mjøstårnet | Brumunddal (Norway) | 85 | 18 | 2019 | 11,300 m2 | 2600 m3/GL (structural timber) |
3 | HoHo | Vienna (Austria) | 84 | 24 | 2020 | 25,000 m2 | 4350 m3 (entire construction) |
4 | HAUT | Amsterdam (Netherlands) | 73 | 22 | 2022 | 14,500 m2 | 2000 m3 (entire timber) |
5 | Brock Commons Tallwood House | Vancouver (Canada) | 58 | 18 | 2017 | 15,115 m2 | 1973 m3/CLT 260 m3/GLPSL |
6 | Treet | Bergen (Norway) | 49 | 14 | 2015 | 7140 m2 | 550 m3/GL 385 m3/CLT |
7 | Lighthouse Joensuu | Joensuu (Finland) | 48 | 14 | 2019 | 5935 m2 | 2000 m3 (entire construction) |
8 | HOAS Tuuliniitty | Tuuliniitty (Finland) | 42 | 13 | 2021 | 7584 m2 | NA |
9 | Origine | Quebec (Canada) | 41 | 13 | 2017 | 13,124 m2 | 3111 m3 (mass timber) |
10 | Trafalgar Place | London (UK) | 36 | 10 | 2015 | 16,661 m2 | 750 m3 (timber volume) |
10 tallest timber buildings.
Different levels and kinds of data for “the amount of timber” e.g. structural timber, entire construction, or only CLT were given by various references.
Note on abbreviation: ‘UC’ indicates under construction; ‘NA’ indicates not available; ‘CLT’ indicates cross-laminated timber; ‘GL’ indicates glue-laminated timber; ‘PSL’ indicates parallel strand lumber.
In terms of functionality, tall buildings can be classified as single-use or mixed-use. In this study, hotel, residence, and office were considered as primary functions, whereas their combinations were considered mixed-use. Taking into account existing literature (e.g., [36, 37, 38, 39, 40, 41, 42, 43]), the classifications based on their structural behavior under lateral loads by Ilgın [44, 45, 46] and Ilgın et al. [47] were used in this paper due to its more comprehensive and clearer structures (see Table 2).
Core | Building form | Structural system | Structural material |
---|---|---|---|
Central core | Prismatic form | Shear-frame system | Steel |
• Central | Setback form | • Shear trussed frame | Reinforced concrete |
• Central split | Tapered form | • Shear walled frame | Composite |
Atrium core | Twisted form | Mega core system | |
• Atrium | Leaning/tilted form | Mega column system | |
• Atrium split | Fee form | Outriggered frame system | |
External core | Tube system | ||
• Attached | • Framed-tube | ||
• Detached | • Trussed-tube | ||
• Partial split | • Bundled tube | ||
• Full split | |||
Peripheral core | |||
• Partial peripheral | |||
• Full peripheral | |||
• Partial split | |||
• Full split |
Core, building form, structural system, and structural material classifications.
As can be seen in Table 3, the case study buildings were designed mostly for residential purposes, and the two mixed-use cases also included residential use. Additionally, central core arrangement was the dominant core typology (only one case with peripheral core). The benefits of a central core are factors, e.g., structural contribution, compactness, making the exterior facade open to light and scenery, and facilitating fire escape, which can aid in the dominant formation of this typology.
# | Name | Function | Core type | Form | Structural system | Structural material | Structural description |
---|---|---|---|---|---|---|---|
1 | Ascent | R | Central | Prismatic | Shear-walled frame | Composite | Core: RC Column: GL |
2 | Mjøstårnet | R/H/O | Central | Prismatic | Trussed-tube | Timber | Nonstructural core: CLT Column: GL exterior brace: GL |
3 | HoHo | R/H/O | Central | Prismatic | Shear-walled frame | Composite | Core: RC Column: GL |
4 | HAUT | R | Central | Free | Shear wall | Composite | Core: RC Shear wall: CLT |
5 | Brock Commons Tallwood House | R | Central | Prismatic | Shear-walled frame | Composite | Core: RC Column: GL and PSL |
6 | Treet | R | Central | Prismatic | Trussed-tube | Timber | Nonstructural core: CLT exterior braces, belt, outrigger: GL |
7 | Lighthouse Joensuu | R | Central | Prismatic | Shear wall | Timber | Core and shear wall: LVL |
8 | HOAS Tuuliniitty | R | Central | Prismatic | Shear wall | Timber | Core and shear wall: CLT |
9 | Origine | R | Central | Free | Shear wall | Timber | Core and shear wall: CLT |
10 | Trafalgar Place | R | Peripheral | Prismatic | Shear wall | Timber | Core and shear wall: CLT |
Tallest timber buildings by function, core type, form, structural system, and structural material.
Note on abbreviations: ‘R’ indicates residential; ‘H’ indicates hotel; ‘O’ indicates office; ‘RC’ indicates reinforced concrete.
Prismatic forms were the most common and occurred in eight case studies including HoHo (Figure 2). The reason why prismatic forms are common may be due to ease of workmanship, practicability, and efficient use of interior space (especially in rectangular floor plans) compared with complicated forms.
HoHo (photo courtesy of DERFRITZ).
The advantages of shear wall systems in buildings up to approximately 35 stories such as construction speed, suitability for prefabrication, and sufficient rigidity to withstand lateral loads may be the reasons behind this occurrence [48] as in the case of the 22-story and 73 m high HAUT (Amsterdam, 2022) (Figure 3) with a concrete core and CLT shear walls. Additionally, Mjøstårnet (Figure 4) and Treet took the advantage of trussed-tube system, in which exterior multistory GL trusses handle the horizontal and gravity loads to ensure the required rigidity of the structure and the CLT core has a nonstructural function [49, 50].
HAUT (photo courtesy of Jannes Linders).
Mjøstårnet (photo courtesy of Voll Arkitekter AS + Ricardo Foto).
On the other hand, the interstory drift between adjacent floors of upper stories in shear wall systems and the interstory drift between adjacent floors of lower stories in rigid frame systems are problematic issues, but shear frame systems (namely shear trussed frame and shear-walled frame systems) offer a solution where both systems compensate for each other’s disadvantages as in the case of the 18-story and 58 m high Brock Commons Tallwood House (Vancouver, 2017) (Figure 5).
Brock Commons Tallwood House (photo by Michael Elkan and courtesy of Acton Ostry Architects).
In terms of structural material, CLT was the structural material commonly used in 10 selected cases (Table 3). In the buildings where composite/hybrid systems were employed, concrete was utilized in all four cases. Additionally, in all case studies, the ground floor or podium was made of concrete and had a reinforced concrete core. Moreover, among them, in Ascent, mass timber residential floors were built over 5-story-concrete parking. Concrete podium construction has many advantages, including ground-level housing facilities and services, offering high clearances in public areas and large openings, and creating fireproof zones for primary mechanical and electrical components [51]. Furthermore, the reason for employing concrete core: (i) to provide the lateral rigidity and strength of the structure to a great extent; (ii) to take advantage of the natural resistance of concrete against fire; (iii) to benefit from its advantage in damping wind-induced building sway, which is one of the commonly confronted issues in high-rise buildings [52].
Driven predominantly by decarbonization, forest management, and timber life cycle, urbanization and intensification, and productivity in the construction industry, tall timber buildings have been at the forefront of construction practices in the global urban context for over one decade with an ever-increasing trend of height. It is thought that the analysis of the key architectural and structural design concerns of the 10 tallest buildings (one is under construction) will contribute to the planning of future timber buildings that will push the height limits.
The tallest timber buildings were mostly designed as residential. Central core arrangement was the dominant core typology. Prismatic forms were most widely used. Shear wall systems were preferred in five cases. In terms of structural material, six cases used pure wood, mostly CLT, while others opted for composite, usually concrete.
Rules, expectations, requirements, and typologies for tall wooden buildings, whose design dynamics are associated with technological developments and new construction techniques, have not yet been clarified. The diversity in the design and construction methods of these structures is still evolving to meet various building codes, market demands, contexts, and environments. This chapter has given the most up-to-date information on this pioneer building typology.
This report also has its limitations, since the empirical data presented in this chapter were limited to 10 buildings, it seems difficult to generalize about timber tall buildings of the future. On the other hand, given the increase in the number of tall timber buildings erected, further research can be conducted with larger sample groups to obtain broader generalizations and new information.
Additionally, the increase in global environmental awareness strengthens the attractiveness of timber construction, which leads the search for innovative and environmentally friendly engineered timber product solutions such as the DoMWoB project (Dovetailed Massive Wood Board Elements for Multi-Story Buildings); see Acknowledgments and Funding (Figure 6) [53] in the future. Although for example, the uptake of dovetail massive timber elements for industrial applications is very limited at the moment, with new research projects to be developed, these elements can be used more in multistory and even tall building construction.
(a) Dovetail massive wood board prototype manufactured at Vocational College Lapland (Ammattiopisto Lappia), Kemi, Finland; (b) Fire test specimens mounted to supporting construction made of aerated concrete blocks at Tampere University Fire Laboratory, Tampere, Finland (photos by Hüseyin Emre Ilgın).
This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No [101024593].
This project has also received funding (60,000 EUR) from the Marjatta and Eino Kolli Foundation for funding the technical performance tests including fire safety, structural, moisture transfer resistance and air-tightness, and sound insulation.
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