{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:36:10Z","timestamp":1789140970106,"version":"build-2803163510"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T00:00:00Z","timestamp":1472601600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T00:00:00Z","timestamp":1472601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p\u2009=\u20090.005 and p\u2009=\u20090.002, respectively), average 24-h BP values (all p\u2009&lt;\u20090.001), plasma glucose (p\u2009=\u20090.008), TG (p\u2009=\u20090.003), TG: HDL-C ratio (p\u2009=\u20090.010), and vWF levels (p\u2009=\u20090.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p\u2009=\u20090.039) and baseline-corrected flicker (bFR) responses (p\u2009=\u20090.022), as well as, prolonged dilation reaction time (RT, p\u2009=\u20090.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in <jats:underline>all<\/jats:underline> individuals with adiposity above normal range.<\/jats:p>","DOI":"10.1038\/srep32282","type":"journal-article","created":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T16:47:22Z","timestamp":1472662042000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk"],"prefix":"10.1038","volume":"6","author":[{"given":"Sunni R.","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Bellary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Karimzad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doina","family":"Gherghel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,31]]},"reference":[{"key":"BFsrep32282_CR1","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1161\/01.CIR.0000145546.97738.1E","volume":"110","author":"S Klein","year":"2004","unstructured":"Klein, S. et al. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 110, 2952\u20132967 (2004).","journal-title":"Circulation"},{"key":"BFsrep32282_CR2","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/sj.ijo.0802877","volume":"29","author":"K Nanchahal","year":"2005","unstructured":"Nanchahal, K., Morris, J. N., Sullivan, L. M. & Wilson, P. W. Coronary heart disease risk in men and the epidemic of overweight and obesity. International journal of obesity 29, 317\u2013323 (2005).","journal-title":"International journal of obesity"},{"key":"BFsrep32282_CR3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1136\/jech.2003.015651","volume":"59","author":"SG Wannamethee","year":"2005","unstructured":"Wannamethee, S. G., Shaper, A. G. & Walker, M. Overweight and obesity and weight change in middle aged men: impact on cardiovascular disease and diabetes. Journal of epidemiology and community health 59, 134\u2013139 (2005).","journal-title":"Journal of epidemiology and community health"},{"key":"BFsrep32282_CR4","first-page":"147","volume":"103","author":"PT Katzmarzyk","year":"2012","unstructured":"Katzmarzyk, P. T. et al. Body mass index and risk of cardiovascular disease, cancer and all-cause mortality. Canadian journal of public health\u2009=\u2009Revue canadienne de sante publique 103, 147\u2013151 (2012).","journal-title":"Canadian journal of public health\u2009=\u2009Revue canadienne de sante publique"},{"key":"BFsrep32282_CR5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.pathophys.2008.04.007","volume":"15","author":"PA Stapleton","year":"2008","unstructured":"Stapleton, P. A., James, M. E., Goodwill, A. G. & Frisbee, J. C. Obesity and vascular dysfunction. Pathophysiology: the official journal of the International Society for Pathophysiology\/ISP 15, 79\u201389 (2008).","journal-title":"Pathophysiology: the official journal of the International Society for Pathophysiology\/ISP"},{"key":"BFsrep32282_CR6","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1161\/HYPERTENSIONAHA.108.111427","volume":"52","author":"GL Pierce","year":"2008","unstructured":"Pierce, G. L. et al. Weight loss alone improves conduit and resistance artery endothelial function in young and older overweight\/obese adults. Hypertension 52, 72\u201379 (2008).","journal-title":"Hypertension"},{"key":"BFsrep32282_CR7","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.jpeds.2004.08.004","volume":"145","author":"AS Kelly","year":"2004","unstructured":"Kelly, A. S. et al. Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise. The Journal of pediatrics 145, 731\u2013736 (2004).","journal-title":"The Journal of pediatrics"},{"key":"BFsrep32282_CR8","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1007\/s12350-011-9370-3","volume":"18","author":"K Yoshinaga","year":"2011","unstructured":"Yoshinaga, K., Manabe, O. & Tamaki, N. Assessment of coronary endothelial function using PET. Journal of nuclear cardiology: official publication of the American Society of Nuclear Cardiology 18, 486\u2013500 (2011).","journal-title":"Journal of nuclear cardiology: official publication of the American Society of Nuclear Cardiology"},{"key":"BFsrep32282_CR9","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1113\/expphysiol.2008.043349","volume":"94","author":"PE Gates","year":"2009","unstructured":"Gates, P. E., Strain, W. D. & Shore, A. C. Human endothelial function and microvascular ageing. Experimental physiology 94, 311\u2013316 (2009).","journal-title":"Experimental physiology"},{"key":"BFsrep32282_CR10","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1159\/000226220","volume":"46","author":"AJ Krentz","year":"2009","unstructured":"Krentz, A. J., Clough, G. & Byrne, C. D. Vascular disease in the metabolic syndrome: do we need to target the microcirculation to treat large vessel disease? Journal of vascular research 46, 515\u2013526 (2009).","journal-title":"Journal of vascular research"},{"key":"BFsrep32282_CR11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.mvr.2010.11.007","volume":"81","author":"KE Kotliar","year":"2011","unstructured":"Kotliar, K. E. et al. Dynamic retinal vessel response to flicker in obesity: A methodological approach. Microvascular research 81, 123\u2013128 (2011).","journal-title":"Microvascular research"},{"key":"BFsrep32282_CR12","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1378\/chest.127.6.2254","volume":"127","author":"AL Moens","year":"2005","unstructured":"Moens, A. L., Goovaerts, I., Claeys, M. J. & Vrints, C. J. Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 127, 2254\u20132263 (2005).","journal-title":"Chest"},{"key":"BFsrep32282_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1758-5996-2-11","volume":"2","author":"MC Bertoluci","year":"2010","unstructured":"Bertoluci, M. C., Quadros, A. S., Sarmento-Leite, R. & Schaan, B. D. Insulin resistance and triglyceride\/HDLc index are associated with coronary artery disease. Diabetology & metabolic syndrome 2, 11 (2010).","journal-title":"Diabetology & metabolic syndrome"},{"key":"BFsrep32282_CR14","first-page":"311","volume":"57","author":"S Tewari","year":"2005","unstructured":"Tewari, S. et al. Premature coronary artery disease in North India: an angiography study of 1971 patients. Indian heart journal 57, 311\u2013318 (2005).","journal-title":"Indian heart journal"},{"key":"BFsrep32282_CR15","first-page":"141","volume":"49","author":"AD Blann","year":"1992","unstructured":"Blann, A. D. von Willebrand factor antigen: a radial immunodiffusion method evaluated and compared with an ELISA method. Medical laboratory sciences 49, 141\u2013143 (1992).","journal-title":"Medical laboratory sciences"},{"key":"BFsrep32282_CR16","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0301-5629(91)90043-V","volume":"17","author":"R Salonen","year":"1991","unstructured":"Salonen, R., Haapanen, A. & Salonen, J. T. Measurement of intima-media thickness of common carotid arteries with high-resolution B-mode ultrasonography: inter- and intra-observer variability. Ultrasound in medicine & biology 17, 225\u2013230 (1991).","journal-title":"Ultrasound in medicine & biology"},{"key":"BFsrep32282_CR17","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1111\/j.1755-3768.2009.01587.x","volume":"88","author":"G Garhofer","year":"2010","unstructured":"Garhofer, G. et al. Use of the retinal vessel analyzer in ocular blood flow research. Acta ophthalmologica 88, 717\u2013722 (2010).","journal-title":"Acta ophthalmologica"},{"key":"BFsrep32282_CR18","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1167\/iovs.03-0667","volume":"45","author":"E Nagel","year":"2004","unstructured":"Nagel, E., Vilser, W. & Lanzl, I. Age, blood pressure, and vessel diameter as factors influencing the arterial retinal flicker response. Investigative ophthalmology & visual science 45, 1486\u20131492 (2004).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep32282_CR19","doi-asserted-by":"publisher","first-page":"5833","DOI":"10.1167\/iovs.09-5136","volume":"51","author":"R Heitmar","year":"2010","unstructured":"Heitmar, R., Blann, A. D., Cubbidge, R. P., Lip, G. Y. & Gherghel, D. Continuous retinal vessel diameter measurements: the future in retinal vessel assessment? Investigative ophthalmology & visual science 51, 5833\u20135839 (2010).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep32282_CR20","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S0735-1097(01)01746-6","volume":"39","author":"MC Corretti","year":"2002","unstructured":"Corretti, M. C. et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. Journal of the American College of Cardiology 39, 257\u2013265 (2002).","journal-title":"Journal of the American College of Cardiology"},{"key":"BFsrep32282_CR21","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.2337\/diacare.27.10.2506","volume":"27","author":"A Iannuzzi","year":"2004","unstructured":"Iannuzzi, A. et al. Increased carotid intima-media thickness and stiffness in obese children. Diabetes care 27, 2506\u20132508 (2004).","journal-title":"Diabetes care"},{"key":"BFsrep32282_CR22","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/0021-9150(92)90027-E","volume":"95","author":"B Hennig","year":"1992","unstructured":"Hennig, B., Chung, B. H., Watkins, B. A. & Alvarado, A. Disruption of endothelial barrier function by lipolytic remnants of triglyceride-rich lipoproteins. Atherosclerosis 95, 235\u2013247 (1992).","journal-title":"Atherosclerosis"},{"key":"BFsrep32282_CR23","doi-asserted-by":"publisher","first-page":"e1082","DOI":"10.1542\/peds.2012-1726","volume":"131","author":"EM Urbina","year":"2013","unstructured":"Urbina, E. M. et al. Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults. Pediatrics 131, e1082\u20131090 (2013).","journal-title":"Pediatrics"},{"key":"BFsrep32282_CR24","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1475-2840-7-4","volume":"7","author":"C Li","year":"2008","unstructured":"Li, C., Ford, E. S., Meng, Y. X., Mokdad, A. H. & Reaven, G. M. Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race\/ethnicity? Cardiovascular diabetology 7, 4 (2008).","journal-title":"Cardiovascular diabetology"},{"key":"BFsrep32282_CR25","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.cmet.2010.03.013","volume":"11","author":"C Rask-Madsen","year":"2010","unstructured":"Rask-Madsen, C. et al. Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice. Cell metabolism 11, 379\u2013389 (2010).","journal-title":"Cell metabolism"},{"key":"BFsrep32282_CR26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/00004872-200202000-00001","volume":"20","author":"A Simon","year":"2002","unstructured":"Simon, A., Gariepy, J., Chironi, G., Megnien, J. L. & Levenson, J. Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular risk. Journal of hypertension 20, 159\u2013169 (2002).","journal-title":"Journal of hypertension"},{"key":"BFsrep32282_CR27","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1177\/1741826711414623","volume":"19","author":"SE Elias-Smale","year":"2012","unstructured":"Elias-Smale, S. E. et al. Common carotid intima-media thickness in cardiovascular risk stratification of older people: the Rotterdam Study. European journal of preventive cardiology 19, 698\u2013705 (2012).","journal-title":"European journal of preventive cardiology"},{"key":"BFsrep32282_CR28","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1161\/01.CIR.0000112565.60887.1E","volume":"109","author":"EJ Benjamin","year":"2004","unstructured":"Benjamin, E. J. et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation 109, 613\u2013619 (2004).","journal-title":"Circulation"},{"key":"BFsrep32282_CR29","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.ijcard.2010.07.020","volume":"152","author":"V Palmieri","year":"2011","unstructured":"Palmieri, V., Russo, C., Pezzullo, S., Di Minno, M. N. & Celentano, A. Relation of flow-mediated dilation to global arterial load: impact of hypertension and additional cardiovascular risk factors. International journal of cardiology 152, 225\u2013230 (2011).","journal-title":"International journal of cardiology"},{"key":"BFsrep32282_CR30","doi-asserted-by":"publisher","first-page":"413","DOI":"10.9734\/BJMMR\/2012\/1479","volume":"2","author":"AK Gupta","year":"2012","unstructured":"Gupta, A. K. et al. Endothelial Dysfunction: An Early Cardiovascular Risk Marker in Asymptomatic Obese Individuals with Prediabetes. British journal of medicine and medical research 2, 413\u2013423 (2012).","journal-title":"British journal of medicine and medical research"},{"key":"BFsrep32282_CR31","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1549-8719.2011.00130.x","volume":"19","author":"MP De Boer","year":"2012","unstructured":"De Boer, M. P. et al. Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. Microcirculation (New York, N.Y.: 1994) 19, 5\u201318 (2012).","journal-title":"Microcirculation (New York, N.Y.: 1994)"},{"key":"BFsrep32282_CR32","doi-asserted-by":"publisher","first-page":"e52708","DOI":"10.1371\/journal.pone.0052708","volume":"8","author":"A Boillot","year":"2013","unstructured":"Boillot, A. et al. Obesity and the microvasculature: a systematic review and meta-analysis. PloS one 8, e52708 (2013).","journal-title":"PloS one"},{"key":"BFsrep32282_CR33","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.diabres.2008.11.001","volume":"83","author":"R Schiel","year":"2009","unstructured":"Schiel, R. et al. Retinal vessel response to flicker light in children and adolescents with type 1 diabetes mellitus and overweight or obesity. Diabetes Res Clin Pract 83, 358\u2013364 (2009).","journal-title":"Diabetes Res Clin Pract"},{"key":"BFsrep32282_CR34","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1136\/bjo.2010.201665","volume":"95","author":"SR Patel","year":"2011","unstructured":"Patel, S. R. et al. Abnormal retinal vascular function and lipid levels in a sample of healthy UK South Asians. The British journal of ophthalmology 95, 1573\u20131576 (2011).","journal-title":"The British journal of ophthalmology"},{"key":"BFsrep32282_CR35","doi-asserted-by":"publisher","first-page":"H2537","DOI":"10.1152\/ajpheart.01081.2006","volume":"293","author":"DW Stepp","year":"2007","unstructured":"Stepp, D. W. et al. Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat. American journal of physiology. Heart and circulatory physiology 293, H2537\u20132542 (2007).","journal-title":"American journal of physiology. Heart and circulatory physiology"},{"key":"BFsrep32282_CR36","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.amjcard.2007.07.055","volume":"101","author":"JM Arkin","year":"2008","unstructured":"Arkin, J. M. et al. Relation of cumulative weight burden to vascular endothelial dysfunction in obesity. Am J Cardiol 101, 98\u2013101 (2008).","journal-title":"Am J Cardiol"},{"key":"BFsrep32282_CR37","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1007\/s11695-008-9504-0","volume":"18","author":"J Faintuch","year":"2008","unstructured":"Faintuch, J., Marques, P. C., Bortolotto, L. A., Faintuch, J. J. & Cecconello, I. Systemic inflammation and cardiovascular risk factors: are morbidly obese subjects different? Obes Surg 18, 854\u2013862 (2008).","journal-title":"Obes Surg"},{"key":"BFsrep32282_CR38","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.amjmed.2010.02.016","volume":"123","author":"LM Biasucci","year":"2010","unstructured":"Biasucci, L. M. et al. Paradoxical preservation of vascular function in severe obesity. Am J Med 123, 727\u2013734 (2010).","journal-title":"Am J Med"},{"key":"BFsrep32282_CR39","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s00059-014-4140-z","volume":"40","author":"A Temiz","year":"2015","unstructured":"Temiz, A. et al. Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and carotid intima-media thickness: Associations in rheumatoid arthritis patients. Herz 40 Suppl 3, 217\u2013224 (2015).","journal-title":"Herz"},{"key":"BFsrep32282_CR40","doi-asserted-by":"publisher","first-page":"402053","DOI":"10.1155\/2013\/402053","volume":"2013","author":"MS Fernandez-Alfonso","year":"2013","unstructured":"Fernandez-Alfonso, M. S. et al. Mechanisms of perivascular adipose tissue dysfunction in obesity. International journal of endocrinology 2013, 402053 (2013).","journal-title":"International journal of endocrinology"},{"key":"BFsrep32282_CR41","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ejphar.2015.09.012","volume":"766","author":"G Ozen","year":"2015","unstructured":"Ozen, G., Daci, A., Norel, X. & Topal, G. Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling. Eur J Pharmacol 766, 16\u201324 (2015).","journal-title":"Eur J Pharmacol"},{"key":"BFsrep32282_CR42","doi-asserted-by":"publisher","first-page":"S51","DOI":"10.1007\/s11739-013-0910-5","volume":"8","author":"A Koller","year":"2013","unstructured":"Koller, A., Balasko, M. & Bagi, Z. Endothelial regulation of coronary microcirculation in health and cardiometabolic diseases. Internal and emergency medicine 8 Suppl 1, S51\u201354 (2013).","journal-title":"Internal and emergency medicine"},{"key":"BFsrep32282_CR43","doi-asserted-by":"publisher","first-page":"453","DOI":"10.2174\/1570161112666140423221843","volume":"12","author":"Z Bagi","year":"2014","unstructured":"Bagi, Z., Broskova, Z. & Feher, A. Obesity and coronary microvascular disease - implications for adipose tissue-mediated remote inflammatory response. Current vascular pharmacology 12, 453\u2013461 (2014).","journal-title":"Current vascular pharmacology"},{"key":"BFsrep32282_CR44","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/HJH.0b013e328333d1fc","volume":"28","author":"S Czernichow","year":"2010","unstructured":"Czernichow, S. et al. Microvascular dysfunction in healthy insulin-sensitive overweight individuals. Journal of hypertension 28, 325\u2013332 (2010).","journal-title":"Journal of hypertension"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep32282.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32282","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32282.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:02:38Z","timestamp":1672898558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep32282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,31]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,8,31]]}},"alternative-id":["BFsrep32282"],"URL":"https:\/\/doi.org\/10.1038\/srep32282","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,31]]},"assertion":[{"value":"30 April 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32282"}}