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Chapter 4 in: Regulation of Tissue Oxygenation. San Rafael (CA): Morgan &amp; Claypool Life Sciences. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK54103\" xlink:type=\"simple\">http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK54103<\/ext-link>. Accessed 2014 Feb 10."},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"West JB (1998) High Life: a history of high altitude medicine and physiology. Am Physiol Soc and Oxford Univ Press, New York Oxford, 1998.ISBN 978-0-1951219-4-0","DOI":"10.1007\/978-1-4614-7573-6"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa0801581","article-title":"Arterial blood gases and oxygen content in climbers on Mount Everest","volume":"360","author":"MP Grocott","year":"2009","journal-title":"N Engl J Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1152\/jappl.1998.84.4.1242","article-title":"Polycythaemic responses to hypoxia: molecular and genetic mechanisms of chronic mountain sickness","volume":"84","author":"LC Ou","year":"1998","journal-title":"J Appl Physiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1096\/fj.11-197772","article-title":"Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest","volume":"26","author":"DZ Levett","year":"2012","journal-title":"FASEB"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/0735-1097(95)00007-Q","article-title":"Endothelium-derived relaxing factor is important in mediating the high output state in chronic severe anemia","volume":"25","author":"IS Anand","year":"1995","journal-title":"J Am Coll Cardiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1161\/01.CIR.8.1.111","article-title":"The Heart in Anemia","volume":"8","author":"WB Porter","year":"1953","journal-title":"Circulation"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ccc.2004.01.001","article-title":"Physiologic aspects of anemia","volume":"20","author":"PC H\u00e9bert","year":"2004","journal-title":"Crit Care Clin"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1017\/S1368980008002401","article-title":"Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005","volume":"12","author":"E McLean","year":"2009","journal-title":"Public Health Nutr"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1152\/japplphysiol.01204.2010","article-title":"Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease","volume":"110","author":"L Boyer","year":"2011","journal-title":"J Appl Physiol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/ACO.0b013e3283421201","article-title":"Hypoxic pulmonary vasoconstriction: mechanisms of oxygen-sensing","volume":"24","author":"AM Evans","year":"2011","journal-title":"Curr Opin Anaesthesiol"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Shovlin CL, Jackson JE (2010) Pulmonary arteriovenous malformations and other vascular abnormalities. In: Mason RJ, Broaddus VC, Martin T, <etal>et al<\/etal>.. editors. Murray and Nadel&apos;s Textbook of Respiratory Medicine. 5th Edn. Philadelphia, Elsevier-Saunders. pp. 1261\u20131282.","DOI":"10.1016\/B978-1-4160-4710-0.00054-7"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/thx.49.4.327","article-title":"Oxygen and 99mTc-MAA shunt estimations in patients with pulmonary arteriovenous malformations: effects of changes in posture and lung volume","volume":"49","author":"T Ueki","year":"1994","journal-title":"Thorax"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1152\/jappl.1993.75.1.321","article-title":"Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts","volume":"75","author":"MK Whyte","year":"1993","journal-title":"J Appl Physiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1056\/NEJM198305193082005","article-title":"Pulmonary arteriovenous malformations. Physiologic observations and results of therapeutic balloon embolization","volume":"308","author":"PB Terry","year":"1983","journal-title":"N Engl J Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0009-9260(88)80065-5","article-title":"Quantification of right to left shunt through pulmonary arteriovenous malformations using 99Tcm albumin microspheres","volume":"39","author":"ER Chilvers","year":"1989","journal-title":"Clin Radiol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.2214\/ajr.165.5.7572487","article-title":"Pulmonary arteriovenous malformations: results of treatment with coil embolization in 53 patients","volume":"165","author":"JA Dutton","year":"1995","journal-title":"AJR Am J Roentgenol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1164\/ajrccm\/145.5.1047","article-title":"Treatment of pulmonary arteriovenous malformations by therapeutic embolization","volume":"145","author":"D Pennington","year":"1992","journal-title":"Am Rev Resp Dis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1136\/thx.47.10.790","article-title":"Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations","volume":"47","author":"MK Whyte","year":"1992","journal-title":"Thorax"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1378\/chest.115.1.109","article-title":"Sensitivity and specificity of radioisotope right-left shunt measurements and pulse oximetry for the early detection of pulmonary arteriovenous malformations","volume":"115","author":"RD Thompson","year":"1999","journal-title":"Chest"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2214\/ajr.179.2.1790347","article-title":"Pulmonary arteriovenous malformations: effect of embolization on right-to-left shunt, hypoxemia and exercise tolerance in 66 patients","volume":"179","author":"P Gupta","year":"2002","journal-title":"AJR Am J Roentgenol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1042\/cs1020127","article-title":"Quantification of right-to-left shunt with (99m)Tc-labelled albumin macroaggregates and 100% oxygen in patients with hereditary haemorrhagic telangiectasia","volume":"102","author":"JJ Mager","year":"2002","journal-title":"Clin Sci (Lond)"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1136\/thx.2007.087452","article-title":"Primary determinants of ischaemic stroke\/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia","volume":"63","author":"CL Shovlin","year":"2008","journal-title":"Thorax"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Shovlin CL, Chamali B, Santhirapala V, Livesey JA, Angus G, et al. (2014) Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets. PLOS ONE 2014 Feb 19;9(2):e88812","DOI":"10.1371\/journal.pone.0088812"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MD.0b013e31802f8da1","article-title":"Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients","volume":"86","author":"V Cottin","year":"2007","journal-title":"Medicine (Baltimore)"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF02552883","article-title":"Cerebral embolism-first manifestation of pulmonary arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia","volume":"8","author":"RC Hewes","year":"1985","journal-title":"Cardiovasc Intervent Radiol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1212\/WNL.55.7.959","article-title":"Pulmonary arteriovenous malformations: cerebral ischemia and neurologic manifestations","volume":"55","author":"M Moussouttas","year":"2000","journal-title":"Neurology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1136\/jmg.2009.069013","article-title":"International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia","volume":"48","author":"ME Faughnan","year":"2011","journal-title":"J Med Genet"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.blre.2010.07.001","article-title":"Hereditary haemorrhagic telangiectasia: Pathogenesis, diagnosis and treatment","volume":"24","author":"CL Shovlin","year":"2010","journal-title":"Blood Rev"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e76516","DOI":"10.1371\/journal.pone.0076516","article-title":"Hemorrhage-adjusted iron requirements, hematinics and hepcidin define hereditary haemorrhagic telangiectasia as a model of hemorrhagic iron deficiency","volume":"8(10)","author":"H Finnamore","year":"2013","journal-title":"PLoS ONE"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1572-0241.2000.01792.x","article-title":"Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia","volume":"95","author":"AD Kjeldsen","year":"2000","journal-title":"Am J Gastroenterol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/lary.23893","article-title":"A questionnaire-based study suggests lifestyle and dietary factors influencing nosebleed severity in hereditary hemorrhagic telangiectasia (HHT)","volume":"123","author":"BM Silva","year":"2013","journal-title":"Laryngoscope"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/thoraxjnl-2011-201076","article-title":"Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli\/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia","volume":"67","author":"JA Livesey","year":"2012","journal-title":"Thorax"},{"key":"ref34","unstructured":"British Thoracic Society Standards of Care Committee (2006) Clinical component for the home oxygen service in England and Wales. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.brit-thoracic.org.uk\/Portals\/0\/Clinical%20Information\/Home%20Oxygen%20Service\/clinical%20adultoxygenjan06.pdf\" xlink:type=\"simple\">https:\/\/www.brit-thoracic.org.uk\/Portals\/0\/Clinical%20Information\/Home%20Oxygen%20Service\/clinical%20adultoxygenjan06.pdf<\/ext-link>. Accessed 2014 Feb 10."},{"key":"ref35","doi-asserted-by":"crossref","first-page":"vi1","DOI":"10.1136\/thx.2008.102947","article-title":"BTS guideline for emergency oxygen use in adult patients. British Thoracic Society","volume":"63","author":"BR O'Driscoll","year":"2008","journal-title":"Thorax"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/j.1365-2141.2005.05535.x","article-title":"Guidelines for the diagnosis, investigation and management of polycythaemia\/erythrocytosis","volume":"130","author":"MF McMullin","year":"2005","journal-title":"Br J Haematol"},{"key":"ref37","first-page":"218","article-title":"Pulmonary arteriovenous malformations and other pulmonary aspects of hereditary haemorrhagic telangiectasia","volume":"54","author":"P Shovlin CL Wilmshurst","year":"2011","journal-title":"Eur Respir Mon"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P","article-title":"Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)","volume":"91","author":"CL Shovlin","year":"2000","journal-title":"Am J Med Genet"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/ajmg.a.35715","article-title":"Hereditary hemorrhagic telangiectasia: how accurate are the clinical criteria?","volume":"161A","author":"MW van Gent","year":"2013","journal-title":"Am J Med Genet A"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1183\/09031936.00126207","article-title":"Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure","volume":"32","author":"CL Shovlin","year":"2008","journal-title":"Eur Resp J"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1007\/s00330-010-1851-2","article-title":"Embolization of pulmonary arteriovenous malformations using the Amplatzer vascular plug: successful treatment of 69 consecutive patients","volume":"20","author":"JL Hart","year":"2010","journal-title":"Eur J Radiology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1183\/09059180.00011102","article-title":"Management of pulmonary arteriovenous malformations in pulmonary hypertensive patients: a pressure to embolise?","volume":"18","author":"CL Shovlin","year":"2009","journal-title":"Eur Respir Rev"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1160\/TH07-01-0064","article-title":"Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism","volume":"98","author":"CL Shovlin","year":"2007","journal-title":"Thromb Haemost"},{"key":"ref44","unstructured":"Santhirapala V, Tighe HC, Springett JT, Wolfenden H, Hughes JMB, <etal>et al<\/etal>.. (2011) When hypoxaemia is not the predominant cause of dyspnea. Lessons from a single-centre 2005-2010 cohort of patients with pulmonary arteriovenous malformations. Chest 140: 681A, 10.1378\/chest.1114540"},{"key":"ref45","first-page":"1665","article-title":"Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC Committee on the aetiology of chronic bronchitis (MRC breathlessness score)","volume":"2","author":"CM Fletcher","year":"1960","journal-title":"BMJ"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1136\/jcp.200X.033944","article-title":"Best practice in primary care pathology: review 3","volume":"59","author":"WS Smellie","year":"2006","journal-title":"J Clin Pathol"},{"key":"ref47","unstructured":"NICE Clinical Knowledge Summaries: Interpreting ferritin levels. Available <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/cks.nice.org.uk\/anaemia-iron-deficiency#!diagnosisadditional:1\/A-487719_1\" xlink:type=\"simple\">http:\/\/cks.nice.org.uk\/anaemia-iron-deficiency#!diagnosisadditional:1\/A-487719_1<\/ext-link>. Accessed 2014 Feb 10"},{"key":"ref48","first-page":"1240","article-title":"Plasma ferritin concentrations: their clinical significance and relevance to patient care","volume":"122","author":"LS Valberg","year":"1980","journal-title":"Can Med Assoc J"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000335620","article-title":"Effects of exercise training on red blood cell production: implications for anemia","volume":"127","author":"M Hu","year":"2012","journal-title":"Acta Haematol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1681\/ASN.2009020213","article-title":"Reassessment of albumin as a nutritional marker in kidney disease","volume":"21","author":"AN Friedman","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1536\/ihj.16.629","article-title":"Correlation between pulmonary vascular resistance and pulmonary arterial diastolic pressure in congenital heart diseases with left to right shunt","volume":"16","author":"S Honda","year":"1975","journal-title":"Jpn Heart J"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"e1003389","DOI":"10.1371\/journal.pgen.1003389","article-title":"Molecular networks of human muscle adaptation to exercise and age","volume":"9","author":"BE Phillips","year":"2013","journal-title":"PLoS Genet"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1542\/peds.67.5.667","article-title":"Phlebotomy with iron therapy to correct the microcytic polycythaemia of chronic hypoxia","volume":"67","author":"PM Sondel","year":"1981","journal-title":"Pediatrics"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1365-2141.1986.tb05562.x","article-title":"Whole blood viscosity in polycythaemia: the effect of iron deficiency at a range of haemoglobin and packed cell volumes","volume":"63","author":"JE Van de Pette","year":"1986","journal-title":"Br J Haematol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1136\/thoraxjnl-2011-201027","article-title":"Flight-related complications are infrequent with hereditary haemorrhagic telangiectasia\/pulmonary arteriovenous malformations, despite low oxygen saturations and anaemia","volume":"67","author":"CG Mason","year":"2012","journal-title":"Thorax"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0090777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T22:02:17Z","timestamp":1648591337000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0090777"}},"subtitle":[],"editor":[{"given":"Tracey","family":"Rouault","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,3,17]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,3,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0090777","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,17]]}}}