Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis? Incorporating presentations on scoliogeny at the 2012 IRSSD and SRS meetings

Scoliosis

Jack CY Cheng⁴  Theodoros B Grivas⁵  Alan Moulton³  Peter H Dangerfield¹  R Geoffrey Burwell² 

[1] Royal Liverpool Children’s Hospital, Eaton Road, Liverpool L12 2AP, UK;Centre for Spinal Studies and Surgery, Nottingham University Hospitals Trust, Queen’s Medical Centre Campus, Derby Road, Nottingham NG7 2UH, UK;Department of Orthopaedic Surgery, King’s Mill Hospital, Sutton Road, Mansfield NG17 4JL, UK;Department of Orthopaedics & Traumatology, The Joint Scoliosis Research Centre of the Chinese University and Nanjing University, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, China;Department of Trauma and Orthopaedics, “Tzanio” General Hospital, Tzani and Afendouli 1 st, Piraeus 18536, Greece

关键词: Epigenetics;    Scoliogeny;    Pathogenesis;    Etiology;    Scoliosis;   

Others  :  791361
DOI  :  10.1186/1748-7161-8-4

 received in 2012-11-29, accepted in 2013-02-09,  发布年份 2013

【 摘 要 】

This paper aims to integrate into current understanding of AIS causation, etiopathogenetic information presented at two Meetings during 2012 namely, the International Research Society of Spinal Deformities (IRSSD) and the Scoliosis Research Society (SRS). The ultimate hope is to prevent the occurrence or progression of the spinal deformity of AIS with non-invasive treatment, possibly medical. This might be attained by personalised polymechanistic preventive therapy targeting the appropriate etiology and/or etiopathogenetic pathways, to avoid fusion and maintain spinal mobility. Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

【 授权许可】

   
2013 Burwell et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Burwell RG, Dangerfield PH: Whither the etiopathogenesis (and scoliogeny) of adolescent idiopathic scoliosis? Stud Health Technol Inform 2012, 176:3-19.
• [2]Sevastik J: Animal experiments in scoliosis. A critical review. Eur J Exper Musculoskel Res 1993, 2:51-60.
• [3]Cheung KM, Wang T, Qiu GX, Luk KD: Recent advances in the aetiology of adolescent idiopathic scoliosis. Int Orthop 2008, 32(6):729-734.
• [4]Burwell RG, Dangerfield PH, Freeman BJC: Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis. Stud Health Technol Inform 2008, 135:3-52.
• [5]Wang WJ, Yeung HY, Chu WC, Tang NL, Lee KM, Qiu Y, Burwell RG, Cheng JC: Top theories for the etiopathogenesis of adolescent idiopathic scoliosis. J Pediatr Orthop 2011, 31:S14-S27.
• [6]Wise CA, Gao X, Shoemaker S, Gordon D, Herring JA: Understanding genetic factors in idiopathic scoliosis, a complex disease of childhood. Curr Genomics. 2008, 9(1):51-59.
• [7]Burwell RG, Aujla RK, Grevitt MP, Dangerfield PH, Moulton A, Randell TL, Anderson SI: Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy. Scoliosis 2009, 4:24.
• [8]Burwell RG, Dangerfield PH: Adolescent idiopathic scoliosis: hypotheses of causation. In Etiology of Adolescent Idiopathic Scoliosis: Current Trends and Relevance to New Treatment Approaches, State of the Art Reviews: Spine. Edited by Burwell RG, Dangerfield PH, Lowe TG, Margulies JY. Philadelphia: Hanley & Belfus Inc; 2000. 14(2):319–333
• [9]Lowe TG, Edgar M, Margulies JY, Miller NH, Raso VJ, Reinker KA, Rivard C-H: Current concepts review: etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 2000, 82-A:1157-1168.
• [10]Acaroglu E, Bobe R, Enouf J, Marcucio R, Moldovan F, Moreau A: The metabolic basis of adolescent idiopathic scoliosis, report of the “metabolic” workgroup of the Fondation Yves Cotrel. Eur Spine J 2011, 21(6):1033-1042.
• [11]Hochberg Z, Feil R, Constancia M, Fraga M, Junien C, Carel JC, Boileau P, Le Bouc Y, Deal CL, Lillycrop K, Scharfmann R, Sheppard A, Skinner M, Szyf M, Waterland RA, Waxman DJ, Whitelaw E, Ong K, Albertsson-Wikland K: Child health, developmental plasticity, and epigenetic programming. Endocr Rev 2011, 32(2):159-224.
• [12]Rappaport SM, Smith MT: Epidemiology: Environment and disease risks. Science 2010, 330(6003):460-461.
• [13]Feinberg AP: Epigenetics at the epicenter of modern medicine. JAMA 2008, 299(11):1345-1350.
• [14]Carey N: The epigenetics revolution. London: Icon Books; 2011:339.
• [15]Francis RC: Epigenetics, the ultimate mystery of inheritance. New York: WW Norton & Company; 2011:234.
• [16]Feil R, Fraga MF: Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 2012, 13(2):97-109.
• [17]Mazzio EA, Soliman KF: Basic concepts of epigenetics: Impact of environmental signals on gene expression. Epigenetics 2012, 7(2):119-130.
• [18]Burwell RG, Dangerfield PH, Moulton A, Grivas TB: Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy. Scoliosis 2011, 6(1):26.
• [19]Guo X, Chau W-W, Chan YL, Cheng J-C-Y, Burwell RG, Dangerfield PH: Relative anterior spinal overgrowth in adolescent idiopathic scoliosis - result of disproportionate endochondral-membranous bone growth? Summary of an electronic focus group debate of the IBSE. Eur Spine J 2005, 14:862-873.
• [20]Janssen MMA, Vincken EL, Van R, Vrtovec T, Kemp B, Viergever MA, Bartels LW, Castelein RM: Sagittal spinal profile and spinopelvic balance in parents of scoliotic children, as compared to normal controls. Stud Health Technol Inform 2012, 176:463.
• [21]Janssen MMA, Vincken KL, Vrtovec T, Kemp B, Viergever MA, Bartels LW, Castelein RM: Sagittal spinal profile and spinopelvic balance in parents of scoliotic children, as compared to normal controls. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 145.
• [22]Van Loon PJ: Ever-present factors in healthy children that can deform their spines, Opposition to Dickson’s paradigm on lordosis. Stud Health Technol Inform 2012, 176:63-67.
• [23]Van Loon PJ, Roukens M, Thunnissen FB, Munneke J: A similar approach in bracing of adolescent scoliosis and kyphosis with the use of growth itself in Thoracolumbar Lordotic Intervention (TLI). Stud Health Technol Inform 2012, 176:68-72.
• [24]Janssen MMA, Vrtovec T, Pernus F, Oner FC, Veereecke EE, Channon AJ, Viergever MA, Vincken KL, Castelein RM: The pelvic lordosis: an essential adaptation in human evolution, and a determinant of spinopelvic alignment. Stud Health Technol Inform 2012, 176:462.
• [25]Chu WCW, Lam WWM, Ng BKW, Lam T-p, Lee K-m, Guo X, Cheng JCY, Burwell RG, Dangerfield PH, Jaspan T: Relative shortening and functional tethering of spinal cord in adolescent scoliosis – Result of asynchronous neuro-osseous growth? Summary of an electronic focus group debate of the IBSE. Scoliosis 2008, 3:8:48-7161-3.
• [26]Lao LF, Shen JX, Chen ZG, Wang YP, Wen XS, Qiu GX: Uncoupled neuro-osseous growth in adolescent idiopathic scoliosis? A preliminary study of 90 adolescents with whole-spine three-dimensional magnetic resonance imaging. Eur Spine J 2011, 20(7):1081-1086.
• [27]Dudin M, Pinchuk D: Typical and atypical AIS, Pathogenesis. Stud Health Technol Inform 2012, 176:139-145.
• [28]Sevastik J, Burwell RG, Dangerfield PH: A new concept for the etiopathogenesis of the thoracospinal deformity of idiopathic scoliosis: summary of an electronic focus group debate of the IBSE. Eur Spine J 2003, 12:440-450.
• [29]Janssen MM, Kouwenhoven JW, Castelein RM: The role of posteriorly directed shear loads acting on a pre-rotated growing spine: a hypothesis on the pathogenesis of idiopathic scoliosis. Stud Health Technol Inform 2010, 158:112-117.
• [30]Castelein RM: Pre-existent rotation of the normal spine at different ages and its consequences for the scoliotic mechanism. Stud Health Technol Inform 2012, 176:20-25.
• [31]Schlosser T, Janssen M, Attrach H, Viergever M, Vincken K, Castelein R: Systematic analysis of of the neurocentral junction (NCJ) in the normal infantile, juvenile and adolescent spine. Stud Health Technol Inform 2012, 176:482.
• [32]Karnezis IA: Flexural-torsional buckling initiates idiopathic scoliosis. Med Hypotheses 2011, 77(5):924-926.
• [33]Stokes IAF, Burwell RG, Dangerfield PH: Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the ‘vicious cycle’ pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE. Scoliosis 2006, 1:16:-7161-1-16.
• [34]Bettany-Saltikov J, Cole L: The effect of frontpacks, shoulder bags and handheld bags on 3D back shape and posture in young university students: an ISIS2 study. Stud Health Technol Inform 2012, 176:117-121.
• [35]Raison M, Ballaz L, Detrembleur C, Mahaudens P, Lebleu J, Fisette P, Mousny M: Lombo-sacral joint efforts during gait: comparison between healthy and scoliotic subjects. Stud Health Technol Inform 2012, 176:113-116.
• [36]Menard A-L, Valteau B, Londono I, Moldovan F, Gromard G, Villemure I: Influence of dynamic loading parameters on bone growth modulation. Stud Health Technol Inform 2012, 176:469.
• [37]Rizza R, Liu XC, Thometz J: The in-vivo effect of torque on growth in caudal vertebrae. Stud Health Technol Inform 2012, 176:209-212.
• [38]Moldovan F, Villemure I, Fendri K, Grimard G, Zaouter C, Parent S, Moreau A, Labelle H, Patten SA: Adolescent idiopathic scoliosis(AIS): metabolic factors, biomechanical stress and estrogen impact. Stud Health Technol Inform 2012, 176:452.
• [39]Karski T: The etiology of the so-called idiopathic scoliosis. New classification (2001-2004-6). The new rehabilitation treatment. Lublin: Prophylaxis; 2011.
• [40]Karski T: Present day explanation of the clinical signs in the biomechanical aetiology of the so-called idiopathic scoliosis (1995–2011). The relationship between the “model of hips movement” and the character of scoliosis; three groups and four types. The causative role of “gait” and “standing ”at ease“ on the right leg”. Stud Health Technol Inform 2012, 176:133-138.
• [41]Taylor TFK, Melrose J: The role of the intervertebral disc in adolescent idiopathic scoliosis. In Etiology of Adolescent Idiopathic Scoliosis: Current Trends and Relevance to New Treatment Approaches, State of the Art Reviews: Spine. Edited by Burwell RG, Dangerfield PH, Lowe TG, Margulies JY. Philadelphia: Hanley & Belfus Inc; 2000. 14(2):359–369
• [42]Antoniou J, Arlet V, Goswami T, Aebi M, Alini M: Elevated synthetic activity in the convex side of scoliotic intervertebral discs and endplates compared with normal tissues. Spine 2001, 26(10):E198-E206.
• [43]Yu J, Fairbank JC, Roberts S, Urban JP: The elastic fiber network of the annulus fibrosus of the normal and scoliotic human intervertebral disc. Spine 2005, 30(16):1815-1820.
• [44]Bertram H, Steck E, Zimmerman G, Chen B, Carstens C, Nerlich A, Richter W: Accelerated intervertebral disc degeneration in scoliosis versus physiological ageing develops against a background of enhanced anabolic gene expression. Biochem Biophys Res Commun 2006, 342(3):963-972.
• [45]Grivas TB, Vasiliadis E, Malakasis M, Mouzakis V, Segos D: Intervertebral disc biomechanics in the pathogenesis of idiopathic scoliosis. Stud Health Technol Inform 2006, 123:80-83.
• [46]Will RE, Stokes IA, Qiu X, Walker MR, Sanders JO: Cobb angle progression in adolescent scoliosis begins at the intervertebral disc. Spine (Phila Pa 1976). 2009, 34(25):2782-2786.
• [47]Hristova GI, Jarzem P, Ouellet JA, Roughley PJ, Epure LM, Antoniou J, Mwale F: Calcification in human intervertebral disc degeneration and scoliosis. J Orthop Res 2011, 29(12):1888-1895.
• [48]Grivas TB, Vasiliadis ES, Triantafyllopolous G, Kaspiris A: A comprehensive model of idiopathic scoliosis (IS) progression, based on the patho-biomechanics of the deforming “three joint complex”. Scoliosis 2009, 4:Suppl 2.
• [49]Herman R, Mixon J, Fisher A, Maulucci R, Stuyck J: Idiopathic scoliosis and the central nervous system: a motor control problem. The Harrington Lecture, 1983. Scoliosis Research Society. Spine 1985, 10(1):1-14.
• [50]Doménech J, Tormos JM, Barrios C, Pascual-Leone A: Motor cortical hyperexcitability in idiopathic scoliosis: could focal dystonia be a subclinical etiological factor? Eur Spine J 2010, 19(2):223-230.
• [51]Domenech J, García-Martí G, Martí-Bonmatí L, Barrios C, Tormos JM, Pascual-Leone A: Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI. Eur Spine J 2011, 20(7):1069-1078.
• [52]Yu WS, Chan KY, Yu FWP, Yeung HY, Lee KM, Ng KW, Qiu Y, Lam TP, Cheng JCY: Lower handgrip strength ingirls with adolescent idiopathic scoliosis (AIS) a case control study. Stud Health Technol Inform 2012, 176:475.
• [53]Dalleau G, Damavandi M, Leroyer P, Verkindt C, Rivard CH, Allard P: Horizontal body and trunk center of mass offset and standing balance in scoliotic girls. Eur Spine J 2011, 20(1):123-128.
• [54]Beaulieu M, Toulotte C, Gatto L, Rivard CH, Teasdale N, Simoneau M, Allard P: Postural imbalance in non-treated adolescent idiopathic scoliosis at different periods of progression. Eur Spine J 2009, 18(1):38-44.
• [55]Shi L, Wang D, Chu WC, Burwell RG, Wong TT, Heng PA, Cheng JC: Automatic MRI segmentation and morphoanatomy analysis of the vestibular system in adolescent idiopathic scoliosis. Neuroimage 2011, 54(Suppl 1):S180-S188.
• [56]Chu WCW, Shi L, Wang D, Cheng JCY: Computational morphometry of semicircular canals in adolescent idiopathic scoliosis (AIS) based on high- resolution MR images. Stud Health Technol Inform 2012, 176:480.
• [57]Veldhuizen AG, Wever DJ, Webb PJ: The aetiology of idiopathic scoliosis: biomechanical and neuromuscular factors. Eur Spine J 2000, 9(3):178-184.
• [58]Burwell RG, Freeman BJC, Dangerfield PH, Aujla RK, Cole AA, Kirby AS, Polak F, Pratt RK, Webb JK, Moulton A: Etiologic theories of idiopathic scoliosis: neurodevelopmental concept of maturational delay of the CNS body schema (“body-in-the-brain”). Stud Health Technol Inform 2006, 123:72-79.
• [59]Lowe TG, Burwell RG, Dangerfield PH: Platelet calmodulin levels in adolescent idiopathic scoliosis: can they predict curve progression and severity? Summary of an electronic focus group debate of the IBSE. Eur Spine J 2004, 13:257-265.
• [60]Burwell RG, Dangerfield PH: Pathogenesis of progressive adolescent idiopathic scoliosis. Platelet activation and vascular biology in immature vertebrae: an alternative molecular hypothesis. Acta Orthop Belg 2006, 72:247-260.
• [61]Machida M, Dubousset J, Imamura Y, Miyashita Y, Yamada T, Kimura J: Melatonin: A possible role in pathogenesis of adolescent idiopathic scoliosis. Spine 1996, 21(10):1147-1152.
• [62]Machida M: Cause of idiopathic scoliosis. Spine 1999, 24(24):2576-2583.
• [63]Dubousset J, Machida M: Possible role of the pineal gland in pathogenesis of idiopathic scoliosis: experimental and clinical studies. Bull de l’Acad Nat de Méd 2010, 185:593-602. discussion 602–604 (French)
• [64]Girardo M, Bettini N, Dema E, Cervellati S: The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS). Eur Spine J 2011, Suppl 1:S68-S74.
• [65]Yim APY, Sun GQ, Yeung HY, Lee KM, Ng KW, Lam TP, Qiu Y, Cheng JCY: Abnormally lower expression of melatonin receptor in osteoblasts of adolescent idiopathic scoliosis girls. Stud Health Technol Inform 2012, 176:447.
• [66]Moreau A, Wang DS, Forget S, Azeddine B, Angeloni D, Fraschini F, Labelle H, Poitras B, Rivard C-H, Grimard G: Melatonin signaling dysfunction in adolescent idiopathic scoliosis. Spine 2004, 29(16):1772-1781.
• [67]Azeddine B, Letellier K, Wang da S, Moldovan F, Moreau A: Molecular determinants of melatonin signaling dysfunction in adolescent idiopathic scoliosis. Clin Orthop Relat Res 2007, 462:45-52.
• [68]Azeddine B, Franco A, Rompré PH, Roy-Gagnon M-H, Turgeon I, Boiro MS, Blain S, Boulanger H, Wang DS, Bagnall KM, Poitras B, Labelle HLL, Rivard C-H, Grimard G, Ouellet J, Parent S, Moreau A: High circulating levels of osteopontin are associated with idiopathic scoliosis onset and spinal deformity progression [abstract]. In Proceedings of Pediatric Orthopaedic Society of North America 25th Anniversary 2009 Annual Meeting Boston, Massachusetts, April 30-May 2. Boston: Marriott Copley Place; 2009:128.
• [69]Moreau A, Franco A, Azeddine B, Rompré PH, Roy-Gagnon M-H, Bagnall KM, Poitras B, Labelle HLL Rivard C-H, Grimard G, Ouellet J, Parent S: High circulating levels of osteopontin are associated with idiopathic scoliosis onset and spinal deformity progression [abstract]. Scoliosis Research Society 44th Annual Meeting and Course, San Antonio, Texas, USA, September 23–26 2009, 109.
• [70]Moreau A, Akoumé-Ndong MY, Azeddine B, Franco A, Rompré PH, Roy-Gagnon MH, Turgeon I, Wang D, Bagnall KM, Poitras B, Labelle H, Rivard CH, Grimard G, Ouellet J, Parent S, Moldovan F: Molecular and genetic aspects of idiopathic scoliosis, Blood test for idiopathic scoliosis. Orthopade 2009, 38(2):114-116. 118–21
• [71]Akoume MY, Azeddine B, Turgeon I, Franco A, Labelle H, Poitras B, Rivard CH, Grimard G, Ouellet J, Parent S, Moreau A: Cell-based screening test for idiopathic scoliosis using cellular dielectric spectroscopy. Spine (Phila Pa 1976). 2010, 35(13):E601-E608.
• [72]Moreau A: Interview with Dr A Moreau, creator of Scoliosis blood test. http://www.scoliosis.org/forum/showthread.php?10705-Interview-with-Dr-Alain-Moreau-creator-of-Scoliosis-blood-test webcite. (Accessed 20 April 2012)
• [73]Sun GQ, Lam TP, Bobby NG, Yim PY, Lee KM, Moreau A, Qiu YY, Cheng JCY: High osteopontin plasma level associated with abnormal cortical bone mineral density in girls with adolescent idiopathic scoliosis. Stud Health Technol Inform 2012, 176:457.
• [74]Elbakry M, Taheri M, Bouhank S, Akoume M, Moreau A: Identification of key disease-modifying factors in adolescent idiopathic scoliosis. Stud Health Technol Inform 2012, 176:449.
• [75]Leboeuf D, Letellier K, Alos N, Edery P, Moldovan F: Do estrogens impact adolescent idiopathic scoliosis? Trends Endocrinol Metab 2009, 20(4):147-152.
• [76]Lombardi G, Akoume MY, Colombini A, Moreau A, Banfi G: Biochemistry of adolescent idiopathic scoliosis. Adv Clin Chem 2011, 54:165-182.
• [77]Rusin B, Kotwicki T, Głodek A, Andrusiewicz M, Urbaniak P, Kotwicka M: Estrogen receptor 2 expression in back muscles of girls with idiopathic scoliosis - relation to radiological parameters. Stud Health Technol Inform 2012, 176:59-62.
• [78]Qiu Y, Sun X, Qiu X, Li W, Zhu Z, Zhu F, Wang B, Yu Y, Qian B: Decreased circulating leptin level and its association with body and bone mass in girls with adolescent idiopathic scoliosis. Spine 2007, 32(24):2703-2710.
• [79]Liu Z, Tam EM, Sun GQ, Lam TP, Zhu ZZ, Sun X, Lee KM, Ng TB, Qiu Y, Cheng JC, HY Yn: Abnormal leptin bioavailability in adolescent idiopathic scoliosis - an important new finding. Spine (Phila Pa 1976). 2012, 37(7):599-604.
• [80]Tam EMS, Yu FWP, Liu Z, Lam TP, Ng BKW, Lee KM, Yong Q, Cheng JCY: Association of low volumetric bone mineral density with leptin and soluble leptin receptor in girls with adolescent idiopathic scoliosis. Stud Health Technol Inform 2012, 176:470.
• [81]Tam EMS, Yu FWP, Hung VWY, Liu Z, Lam TP, Ng BKW, Lee KM, Yong Q, Cheng JC: Are volumetric bone mineral density and bone micro-architecture in adolescent idiopathic scoliosis associated with leptin and soluble leptin receptor? Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 91-92.
• [82]Tam EMS, Yeung HY, Liu Z, Lam TP, Ting T, Lok JYF, Ng BKW, Lee KM, Yong Q, Cheng JCY: Elevated soluble leptin receptor level and association with body composition in girls with adolescent idiopathic scoliosis. Stud Health Technol Inform 2012, 176:472.
• [83]Wu T, Sun X, Zhu Z, Zheng X, Qian B, Zhu F, Cheng JC, Qiu Y: Role of high central leptin activity in a scoliosis model created in bipedal amputated mice. Stud Health Technol Inform 2012, 176:31-35.
• [84]de Gouzy S, Gennero I, Accobled H, Salles J-P: Ghrelin levels in adolescent idiopathic scoliosis. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 110-111.
• [85]Khaymina T, Avaliani T, Dudin M, Pinchuk D: Neurohumoral regulation in children with idiopathic scoliosis. Stud Health Technol Inform 2012, 176:168-173.
• [86]Hung VWY, Qin L, Cheung CSK, Lam TP, Ng BKW, Tse YK, Go X, Lee KM, Cheng JCY: Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg Am 2005, 87-A:2709-2716.
• [87]Szalay EA, Bosch P, Schwend RM, Buggie B, Tandberg D, Sherman F: Adolescents with idiopathic scoliosis are not osteoporotic. Spine 2008, 33(7):802-806.
• [88]Park WW, Suh KT, Kim JI, Kim SJ, Lee JS: Decreased osteogenic differentiation of mesenchymal stem cells and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 2009, 18(12):1920-1926.
• [89]Sun GQ, Lam TP, Bobby NG, Yim PY, Lee KM, Qiu Y, Cheng JCY: Abnormal bone matrix mineralization in patients with adolescent idiopathic scoliosis. Stud Health Technol Inform 2012, 176:458.
• [90]Yu WS, Chan KY, Yu FWP, Yeung HY, Lee KM, Ng KW, Lok KW, Qiu Y, Lam TP, Cheng JCY: Bone quality in adolescent idiopathic scoliosis girls – a case control study. Stud Health Technol Inform 2012, 176:471.
• [91]Yu WS, Chan KY, Yu FWP, Lee KM, Ng BKW, Liu KL, Lam TP, Cheng JC, Zhu Z, Tam EMS: Abnormal bone quality in osteopenic adolescent idiopathic scoliosis girls – a case control study. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 127.
• [92]Goldberg CJ, Dowling FE, Fogarty EE, Moore DP: Adolescent idiopathic scoliosis as developmental instability. Genetica 1995, 96(3):247-255.
• [93]Goldberg CJ, Fogarty EE, Moore DP, Dowling FE: Scoliosis and developmental theory: adolescent idiopathic scoliosis. Spine 1997, 22(19):2228-2237.
• [94]Burwell RG, Grevitt MP, Randell TL, Dangerfield PH, Ranjit RK, Cole AA, Pratt RK, Webb JK, Moulton A, Anderson SI: Abnormal bilateral skeletal asymmetries and their putative genetic and epigenetic origins in enantiomorphic growth plates of girls with adolescent idiopathic scoliosis (AIS)(abstract). Clin Anat 2012, 25(2):267.
• [95]Burwell RG, Aujla RK, Randell TL, Dangerfield PH, Moulton A, Anderson SI: Regional skeletal sizes of healthy girls relative to size attained at 10 years as the comparator: percentage size trajectories reveal effects of differential growth consistent with intrinsic growth-plate programs involving time-tally patterning, genetically- and epigenetically-determined (abstract). Clin Anat 2012, 25(2):268.
• [96]Grivas TB, Burwell RG, Mihas C, Vasiliadis ES, Triandaffylopoulos G, Kaspiris A: Relatively lower body mass index is associated with an excess of severe truncal asymmetry in healthy adolescents. Do body fat, leptin, hypothalamus and sympathetic nervous system influence truncal growth asymmetry? Scoliosis 2009, 4(1):13.
• [97]Burwell RG, Cole AA, Cook TA, Grivas TB, Kiel AW, Moulton A, Thirlwall AS, Upadhyay SS, Webb JK, Wemyss-Holden SA, et al.: Pathogenesis of idiopathic scoliosis. The Nottingham concept. Acta Orthop Belg 1992, 58(Suppl 1):33-58.
• [98]de Sèze M, Cugy E: Pathogenesis of idiopathic scoliosis: A review. Ann Phys Rehabil Med 2012. [Epub ahead of print] (French)
• [99]de Mauroy JC, Ginoux JM: Is AIS under 20–30 degrees a chaotic dynamical system? Stud Health Technol Inform 2012, 176:473.
• [100]Burwell RG: Aetiology of idiopathic scoliosis: current concepts. Pediatr Rehabil 2003, 6(3–4):137-70.
• [101]Sanders JO, Browne RH, McConnell SJ, Margraf SA, Cooney TE, Finegold DN: Maturity assessment and curve progression in girls with idiopathic scoliosis. J Bone Joint Surg Am 2007, 89(1):64-73.
• [102]Xiong B, Sevastik B, Sevastik J, Hedlund R: Early three dimensional radiographic changes in scoliosis. In International Symposium on 3-D Scoliotic Deformities joined with the VIIth International Symposium on Spinal Deformity and Surface Topography. de l’Ēcole Polytechnique de Montrēal edition. Edited by Dansereau J. Stuttgart, Germany: Gustav Fischer Verlag; 1992:498-504.
• [103]Liu Z, Zhu Z, Guo J, Mao S, Wang W, Qian B, Zhu F, Chu W, Cheng JC, Qiu Y: Analysis of body growth parameters in girls with adolescent idiopathic scoliosis: single thoracic idiopathic scoliosis versus single lumbar idiopathic scoliosis. Stud Health Technol Inform 2012, 176:195-201.
• [104]Yim APY Yeung HY, Wang WJ, Hung VWY, Qin L, Lee KM, Lam TP, Qiu Y, Cheng JCY: Abnormal skeletal growth patterns in adolescent idiopathic scoliosis--a longitudinal study till skeletal maturity. Stud Health Technol Inform 2012, 176:474. and Spine (Phila Pa 1976). 2012 Aug 15;37(18):E1148-54
• [105]Chazono M, Soshi S, Kida Y, Hashimoto K, Inoue T, Nakamura Y, Shinohara A, Marumo K, Kono K, Suzuki N: Height velocity curves in female patients with idiopathic scoliosis. Stud Health Technol Inform 2012, 176:202-5.
• [106]Burwell RG, James NJ, Johnson F, Webb JK, Wilson YG: Standardised trunk asymmetry scores; a study of back contour in healthy school children. J Bone Joint Surg Br 1983, 65(4):452-63.
• [107]Nissinen M, Heliövaara M, Seitsamo J, Poussa M: Trunk asymmetry, posture, growth, and risk of scoliosis, A three-year follow-up of Finnish prepubertal school children. Spine 1993, 18(1):8-13.
• [108]Janssen MM, Kouwenhoven JW, Schlösser TP, Viergever MA, Bartels LW, Castelein RM, Vincken KL: Analysis of preexistent vertebral rotation in the normal infantile, juvenile, and adolescent spine. Spine (Phila Pa 1976). 2011, 36(7):E486-91.
• [109]Sarnadskiy VN: The structure of postural disorders and spinal deformities in age and gender according to computer optical topography. Stud Health Technol Inform 2012, 176:77-82.
• [110]Sarnadskiy VN: Classification of postural disorders and spinal deformities in the three dimensions according to computer optical topography. Stud Health Technol Inform 2012, 176:159-63.
• [111]Pecherskiy V, Lihacheva L, Chicherin A, Dudin M, Pinchuk D: The evolution of state of vertebral column in three planes. Stud Health Technol Inform 2012, 176:164-7.
• [112]Kluszczynski M, Czernicki J: Analysis of changes in selected body characteristics in many years of observation of children and adolescents with faulty body posture. Stud Health Technol Inform 2012, 176:465.
• [113]Stolinski L, Kotwicki T: Trunk asymmetry in one thousand school children aged 7–10 years. Stud Health Technol Inform 2012, 176:259-63.
• [114]Stolinski L, Kotwicki T, Czaprowski D, Chowanska J, Suzuki N: Analysis of the Anterior Trunk Symmetry Index (ATSI), Preliminary report. Stud Health Technol Inform 2012, 176:242-6.
• [115]Burwell RG, Aujla RK, Grevitt MP, Randell TL, Dangerfield PH, Cole AA, Kirby AS, Polak FJ, Pratt RK, Webb JK, Moulton A: Upper arm length model suggest transient bilateral asymmetry is associated with right thoracic adolescent idiopathic scoliosis (RT-AIS) with implications for pathogenesis and estimation of linear growth. Stud Health Technol Inform 2012, 176:188-94.
• [116]D’Amico M, Roncoletta P, Di Felice F, Porto D, Bellomo R, Saggini R: Leg length discrepancy in scoliotic patients. Stud Health Technol Inform 2012, 176:146-50.
• [117]Shi L, Wang D, Chu WC, Burwell RG, Freeman BJ, Heng PA, Cheng JC: Volume-based morphometry of brain MR images in adolescent idiopathic scoliosis and healthy control subjects. AJNR Am J Neuroradiol 2009, 30(7):1302-7.
• [118]Bardin J: Neuroscience: Making connections. Nature 2012, 483(7390):394-6.
• [119]Wang D, Shi L, Chu WC, Burwell RG, Cheng JC, Ahuja AT: Abnormal cerebral cortical thinning pattern in adolescent girls with idiopathic scoliosis. Neuroimage 2012, 59(2):935-42.
• [120]Benoist M: The Michel Benoist and Robert Mulholland yearly European Spine Journal review: a survey of the “medical” articles in the European Spine Journal, 2011. Eur Spine J 2012, 21(2):185-94.
• [121]Freeman BJ: Reviewer’s comment concerning “Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI”. Eur Spine J 2011, 20(7):1079-80. by J. Domenech et al
• [122]Huber J, Rogala P: Etiopathogenesis of the adolescent idiopathic scoliosis basing on neuroimaging and neurophysiological examinations with the special emphazing of motor evoked potentials (MEP). Stud Health Technol Inform 2012, 176:446.
• [123]Pinchuk D, Dudin M, Bekshayev S, Pinchuk O: Peculiarities of brain functioning in children with adolescence idiopathic scoliosis (AIS) according to EEG studies. Stud Health Technol Inform 2012, 176:87-90.
• [124]Chu WC, Shi L, Wang D, Cheng JCY: Statistical difference in cerebral cortical thickness in patients with adolescent idiopathic scoliosis and normal controls using computational techniques – the updated data. Stud Health Technol Inform 2012, 176:481.
• [125]Wiernicka M, Lochynski D, Kotwicki T, Michalowski L, Kaminska E, Lewandowski J, Hurnik E: Static and dynamic postural control in girls with idiopathic scoliosis. Stud Health Technol Inform 2012, 176:460.
• [126]Syngayevskaya I, Bumakova S, Pinchuk D, Dudin M: Integrated assessment of back muscles bioelectrical activity and H-reflex research in AIS. Stud Health Technol Inform 2012, 176:83-6.
• [127]Waldrop MM: Computer modelling: Brain in a box. Nature 2012, 482(7386):456-8.
• [128]Koch C, Reid RC: Neuroscience: Observatories of the mind. Nature 2012, 483(7390):397-8.
• [129]Barabasi AL, Gulbahce N, Loscalzo J: Network medicine: a network-based approach to human disease. Nat Rev Genet 2011, 12(1):56-68.
• [130]Shi L, Wang D, Driscoll M, Villemure I, Chu WC, Cheng JC, Aubin CE: Biomechanical analysis and modeling of different vertebral growth patterns in adolescent idiopathic scoliosis and healthy subjects. Scoliosis 2011, 6:11.
• [131]Ledford H: Life-changing experiments: The biological Higgs. Nature 2012, 483(7391):528-30.
• [132]Kirkwood TB, Melov S: On the programmed/non-programmed nature of ageing within the life history. Curr Biol 2011, 21(18):R701-7.
• [133]Tang NL, Yeung HY, Hung VW, Liao CD, Lam TP, Yeung HM, Lee KM, Ng BK, Cheng JC: Genetic epidemiology and heritability of AIS: A study of 415 Chinese female patients. J Orthop Res 2012.
• [134]Sharma S, Gao X, Londono D, Devroy SE, Mauldin KN, Frankel JT, Brandon JM, Zhang D, Li QZ, Dobbs MB, Gurnett CA, Grant SF, Hakonarson H, Dormans JP, Herring JA, Gordon D, Wise CA: Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet 2011, 20(7):1456-62.
• [135]Wise C, Herring JA, Guo X, Zhong D, Sharma S: Idiopathic scoliosis mutations in VANGL1 on axial development gene. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 90-1.
• [136]Takahashi Y, Matsumoto M, Kono K, Kawakani M, Ito M, Uno K, Minani S, Yanagida H, Taneichi H, Watanabe K, Tsuji T, Sudo H, Suzuki T, Toyama Y, Ikegawa S: A genome wide association study identified a new susceptibility locus for adolescent idiopathic soliosis. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 90.
• [137]Gorman KF, Julien C, Yuan Q, Franco A, Wang DS, Bouhanik S, Larouche G, Lacroix G, Moreau A: The identification of unique gene expression, profiles associated with cellular and biochemical endophenotypes of idiopathic scoliosis. Stud Health Technol Inform 2012, 176:450.
• [138]Janusz P, Kotwicki T, Kotwicka M, Andrusiewicz M: Association of CHD7 polymorphism with susceptibility to and severity of idiopathic scoliosis in central European population: preliminary study. Stud Health Technol Inform 2012, 176:448.
• [139]Zhou S, Zhu Z, Qiu X, Wu W, Wang W, Liu Z, Lv F, Qiu Y: Association study of IL-17RC, CHL1, DSCAM and CNTNAP2 genes polymorphisms with adolescent idiopathic scoliosis susceptibility in a Chinese Han population. Stud Health Technol Inform 2012, 176:47-51.
• [140]Harasymczuk P, Janusz P, Kotwick IT: Genetic association studies in idiopathic scoliosis – who was really tested? Stud Health Technol Inform 2012, 176:451.
• [141]Moldovan F, Patten SA, Fendri K, Girard S, Zaouter C, Edery P: Exome sequencing identifies novel candidate nutations in idiopathic scoliosis. Stud Health Technol Inform 2012, 176:453.
• [142]Ward K, Ogilvie JW, Singleton MV, Chettier R, Engler G, Nelson LM: Validation of DNA-based prognostic testing to predict spinal curve progression in adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2010, 35(25):E1455-64.
• [143]Ogilvie JW: Update on prognostic genetic testing in adolescent idiopathic scoliosis (AIS). J Pediatr Orthop 2011, 31(1 Suppl):S46-8.
• [144]Cahill KS, Wang MY: DNA-based prediction of scoliosis curve progression. World Neurosurg 2011, 76(5):371.
• [145]Carlson B: Scoliscore AIS prognostic test personalizes treatment for children with spinal curve. Biotechnol Healthc 2011, 8(2):30-31.
• [146]Ward K, Nelson LM, Chettier R, Ogilvie JW: The clinical value of an intermediate risk score with AIS prognostic testing. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 98.
• [147]Nelson LM, Ogilvie JW, Ward K: AIS Prognostic Test (AIS-PT) testing of patients with advanced Cobb angles provides further validation of the Test algorithm. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 154-5.
• [148]Ward K: Comparing apples and oranges: pathogenesis of adolescent idiopathic scoliosis varies by patient ancestry. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 90.
• [149]Ogilvie JW, Chettier R, Nelson LM, Ward K: DNA-based prognostic test scores are higher in patients who fail orthotic treatment for adolescent idiopathic scoliosis. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 159.
• [150]Nault M-L, Mac-Thiong J-M, Roy-Beaudry M, Turgeon I, Labelle H, de Guise J, Parent S: The use of 3D spinal parameters to differentiate between progressive and non-progressive AIS curves at he first visit. Scoliosis Research Society 47rd Annual Meeting and Course, Chicago, Illinois, USA, September 5-8th 2012, 62.
• [151]Butcher LM, Beck S: Future impact of integrated high-throughput methylome analyses on human health and disease. J Genet Genomics 2008, 35(7):391-401.
• [152]Bjornsson HT, Fallin MD, Feinberg AP: An integrated epigenetic and genetic approach to common human disease. Trends Genet 2004, 20(8):350-8.
• [153]Nelissen EC, van Montfoort AP, Dumoulin JC, Evers JL: Epigenetics and the placenta. Hum Reprod Update 2011, 17(3):397-417.
• [154]Silahtaroglu A, Stenvang J: MicroRNAs, epigenetics and disease. Essays Biochem 2010, 48(1):165-85.
• [155]Talens RP, Boomsma DI, Tobi EW, Kremer D, Jukema JW, Willemsen G, Putter H, Slagboom PE, Heijmans BT: Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J 2010, 24(9):3135-44.
• [156]Grivas TB, Mihas C, Mazioti C, Zisis N, Sakellaropoulou S, Akriotis A, Burwell RG: Maternal age at birth: does it dictate the epigenotypic expression of the trunkal asymmetry of a child? Stud Health Technol Inform 2012, 176:36-42.
• [157]Burwell RG, Dangerfield PH, Vernon CL: Anthropometry and scoliosis. In Scoliosis, Proceedings of a Fifth Symposium, Edited by Zorab PA. London: Academic; 1977:123-163.
• [158]Burwell RG, Dangerfield PH, James NJ, Johnson F, Webb JK, Wilson YG: Anthropometric studies of normal and scoliotic children: axial and appendicular skeletal asymmetry, sexual dimorphisms and age-related changes. In Pathogenesis of idiopathic scoliosis. Proceedings of an international conference. Edited by Jacobs RR. Chicago: Scoliosis Research Society; 1984:27-44.
• [159]McMaster M, Lee AJ, Burwell RG: Physical activities of patients with adolescent idiopathic scoliosis (AIS) compared with a control group: implications for etiology and possible prevention. In International Research Society of Spinal Deformities Symposium. Edited by Sawatzky BJ. Vancouver: University of British Columbia; 2004:68-71.
• [160]McMaster M, Lee AJ, Burwell RG: Indoor heated swimming pools: vulnerability of some infants to develop spinal asymmetries years later. Stud Health Technol Inform 2006, 123:151-155.
• [161]McMaster ME: Heated indoor swimming pools, infants, and the pathogenesis of adolescent idiopathic scoliosis: a neurogenic hypothesis. Environ Health 2011, 10:86.
• [162]Herring JA: Scoliosis: Chapter 11. In Tachdjian’s Pediatric Orthopaedics, Volume 1. Third Edition edition. Philadelphia: WB Saunders; 2002:215.
• [163]Burwell RG, Grevitt MP, Randell TL, Dangerfield PH, Cole AA, Pratt RK, Webb JK, Moulton A, Anderson SI: Several phenotypic features of girls with adolescent idiopathic scoliosis (AIS) are explained by postulating hypothalamic alterations in two successive normal life-history phase transitions (abstract). Clin Anat 2012, 24(6):800.
• [164]Matusik E, Durmała J, Matusik P, Malecka-Tendera E: Nutritional status of children and adolescents with idiopathic scoliosis preliminary results. Stud Health Technol Inform 2012, 176:476. and in Ortop Traumatol Rehabil. 2012 14(4):351–62. doi: 10.5604/15093492.1005093
• [165]Taubes G: Unravelling the obesity-cancer connection. Science 2012, 335(6064):28-32.
• [166]Reardon S: A world of chronic disease. Science 2011, 333(6042):558-9.
• [167]Reardon S: U.N. Summit on non-communicable diseases. Meeting brings attention but little action on chronic diseases. Science 2011, 333(6049):1561.
• [168]Garber K: Autophagy, Explaining exercise. Science 2012, 335(6066):281.
• [169]Gluckman P, Hanson M: Fat fate & disease. Oxford, UK: Oxford University Press; 2012:288.
• [170]Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA: Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 2011, 60(5):1528-34.
• [171]Davey RC, Cochrane T, Dangerfield PH, Chockalingam N, Dorgan JC: Anthropometry and body composition in females with adolescent idiopathic scoliosis, International Research Society of Spinal Deformities Symposium. Vancouver: Edited by Bonita J Sawatzky; 2004:323-6.
• [172]Barrios C, Cortés S, Pérez-Encinas C, Escrivá MD, Benet I, Burgos J, Hevia E, Pizá G, Domenech P: Anthropometry and body composition profile of girls with nonsurgically treated adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2011, 36(18):1470-7.
• [173]Iwaniec UT, Boghossian S, Lapke PD, Turner RT, Kalra SP: Central leptin gene therapy corrects skeletal abnormalities in leptin-deficient ob/ob mice. Peptides 2007, 28(5):1012-9.
• [174]Iwaniec UT, Wong CP, Lindenmaier LB, Philbrick KA, Olson DA, Turner RT: Reduced peripheral leptin signaling drastically reduces bone formation. In Proceedings of ASBMR Annual Meeting, September 16–20. San Diego, California, USA; 2011.
• [175]Burwell RG, Aujla RK, Grevitt MP, Dangerfield PH, Cole AA, Kirby AS, Polak FJ, Pratt RK, Moulton A, Webb JK, Anderson SI: Leptin, asymmetric bone growth, pathogenesis of adolescent idiopathic scoliosis (AIS), and hormesis: Lower spine scoliosis (Abstract). Clin Anat 2009, 22(3):411.
• [176]Burwell RG, Aujla RK, Grevitt MP, Dangerfield PH, Moulton A, Randell TL, Anderson SI: Pathogenesis of adolescent idiopathic scoliosis (AIS) in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy. Stud Health Technol Inform 2010, 158:212.
• [177]Zuo T, Tycko B, Liu TM, Lin JJ, Huang TH: Methods in DNA methylation profiling. Epigenomics 2009, 1(2):331-45.
• [178]Lin SY, Lee CN, Hung CC, Tsai WY, Lin SP, Li NC, Hsieh WS, Tung YC, Niu DM, Hsu WM, Chen LY, Fang MY, Tu MP, Kuo PW, Lin CY, Su YN, Ho HN: Epigenetic profiling of the H19 differentially methylated region and comprehensive whole genome array-based analysis in Silver-Russell syndrome. Am J Med Genet A 2010, 152A(10):2521-8.
• [179]Bruce S, Hannula-Jouppi K, Peltonen J, Kere J, Lipsanen-Nyman M: Clinically distinct epigenetic subgroups in Silver-Russell syndrome: the degree of H19 hypomethylation associates with pheotype severity and genital and skeletal anomalies. J Clin Endocrinol Metab 2009, 94(2):579-87.
• [180]Adams J: Collaborations: The rise of research networks. Nature 2012, 490(7420):335-6.
• [181]Abbott A, Schiermeier Q: Research prize boost for Europe. Nature 2013, 493(7434):585-6.
• [182]Markoff J: Obama seeking to boost study of human brain. New York: The New York Times; 2013:A1.
• [183]Underwood E, Kaiser J: Brain project draws Presidential interest. Scienceinsider; 2013.