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Current Rheumatology Reports
Published in: Current Rheumatology Reports 5/2013

01-05-2013 | ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Inhibition of Nitric Oxide and Antiphospholipid Antibody-Mediated Thrombosis

Author: Chieko Mineo

Published in: Current Rheumatology Reports | Issue 5/2013

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Abstract

The antiphospholipid syndrome (APS) is characterized by recurrent vascular thrombosis, thrombocytopenia, and fetal loss occurring in the presence of antiphospholipid antibodies (aPL). Along with arterial and venous thrombosis and pregnancy complications, patients with APS have an increased risk of myocardial infarction, stroke, and coronary artery disease, resulting from vascular cell dysfunction induced by aPL. Accumulating evidence to date indicates that interactions between circulating aPL and cell surface molecules of target cells, primarily endothelial cells and platelets, underlie the vascular disease phenotypes of APS. However, the molecular basis of APS is poorly understood. Nitric oxide produced by endothelial cells is a key determinant of vascular health that regulates several physiologic processes, including thrombosis, endothelial-leukocyte interaction, vascular cell migration, and the modulation of vascular tone. This review will discuss recent findings that indicate a novel mechanism by which aPL antagonize endothelial cell production of nitric oxide and thereby promote thrombosis.
Literature
1.
Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.PubMedCrossRef
2.
Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997;314:253–7.PubMedCrossRef
3.
Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996;174:1584–9.PubMedCrossRef
4.
Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ. 2005;330:565.PubMedCrossRef
5.
6.
Soltesz P, Szekanecz Z, Kiss E, Shoenfeld Y. Cardiac manifestations in antiphospholipid syndrome. Autoimmun Rev. 2007;6:379–86.PubMedCrossRef
7.
8.
Freedman JE, Sauter R, Battinelli EM, et al. Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res. 1999;84:1416–21.PubMedCrossRef
9.
Freedman JE, Loscalzo J, Barnard MR, et al. Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Investig. 1997;100:350–6.PubMedCrossRef
10.
Mehta JL, Chen LY, Kone BC, et al. Identification of constitutive and inducible forms of nitric oxide synthase in human platelets. J Lab Clin Med. 1995;125:370–7.PubMed
11.
Sase K, Michel T. Expression of constitutive endothelial nitric oxide synthase in human blood platelets. Life Sci. 1995;57:2049–55.PubMedCrossRef
12.
Stagliano NE, Zhao W, Prado R, et al. The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab. 1997;17:1182–90.PubMedCrossRef
13.
Shultz PJ, Raij L. Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis. J Clin Investig. 1992;90:1718–25.PubMedCrossRef
14.
Waddington S, Cook HT, Reaveley D, et al. L-arginine depletion inhibits glomerular nitric oxide synthesis and exacerbates rat nephrotoxic nephritis. Kidney Int. 1996;49:1090–6.PubMedCrossRef
15.
Yao SK, Ober JC, Krishnaswami A, et al. Endogenous nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries. Circulation. 1992;86:1302–9.PubMedCrossRef
16.
Broeders MA, Tangelder GJ, Slaaf DW, et al. Endogenous nitric oxide protects against thromboembolism in venules but not in arterioles. Arterioscler Thromb Vasc Biol. 1998;18:139–45.PubMedCrossRef
17.
Atochin DN, Huang PL. Endothelial nitric oxide synthase transgenic models of endothelial dysfunction. Pflugers Arch. 2010;460:965–74.PubMedCrossRef
18.
Lefer DJ, Jones SP, Girod WG, et al. Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice. Am J Physiol. 1999;276:H1943–50.PubMed
19.
Huang Z, Huang PL, Ma J, et al. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab. 1996;16:981–7.PubMedCrossRef
20.
Atochin DN, Wang A, Liu VW, et al. The phosphorylation state of eNOS modulates vascular reactivity and outcome of cerebral ischemia in vivo. J Clin Invest. 2007;117:1961–7.PubMedCrossRef
21.
Kuhlencordt PJ, Rosel E, Gerszten RE, et al. Role of endothelial nitric oxide synthase in endothelial activation: insights from eNOS knockout endothelial cells. Am J Physiol Cell Physiol. 2004;286:C1195–202.PubMedCrossRef
22.
Michelson AD, Benoit SE, Furman MI, et al. Effects of nitric oxide/EDRF on platelet surface glycoproteins. Am J Physiol. 1996;270:H1640–8.PubMed
23.
Folts JD, Stamler J, Loscalzo J. Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries. Circulation. 1991;83:2122–7.PubMedCrossRef
24.
Mergia E, Friebe A, Dangel O, et al. Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system. J Clin Investig. 2006;116:1731–7.PubMedCrossRef
25.
Radomski MW, Moncada S. Regulation of vascular homeostasis by nitric oxide. Thromb Haemost. 1993;70:36–41.PubMed
26.
Radomski MW, Moncada S. The biological and pharmacological role of nitric oxide in platelet function. Adv Exp Med Biol. 1993;344:251–64.PubMedCrossRef
27.
Negrescu EV, Sazonova LN, Baldenkov GN, et al. Relationship between the inhibition of receptor-induced increase in cytosolic free calcium concentration and the vasodilator effects of nitrates in patients with congestive heart failure. Int J Cardiol. 1990;26:175–84.PubMedCrossRef
28.
Lowenstein CJ. Nitric oxide regulation of protein trafficking in the cardiovascular system. Cardiovasc Res. 2007;75:240–6.PubMedCrossRef
29.
Matsushita K, Morrell CN, Cambien B, et al. Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell. 2003;115:139–50.PubMedCrossRef
30.
Freedman JE, Loscalzo J. Nitric oxide and its relationship to thrombotic disorders. J Thromb Haemost. 2003;1:1183–8.PubMedCrossRef
31.
32.
DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med. 1980;303:897–902.PubMedCrossRef
33.
Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation. 1985;71:699–708.PubMedCrossRef
34.
Langford EJ, Wainwright RJ, Martin JF. Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors. Arterioscler Thromb Vasc Biol. 1996;16:51–5.PubMedCrossRef
35.
Freedman JE, Ting B, Hankin B, et al. Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes. Circulation. 1998;98:1481–6.PubMedCrossRef
36.
Minamino T, Kitakaze M, Sato H, et al. Plasma levels of nitrite/nitrate and platelet cGMP levels are decreased in patients with atrial fibrillation. Arterioscler Thromb Vasc Biol. 1997;17:3191–5.PubMedCrossRef
37.
Clark BA, Ludmir J, Epstein FH, et al. Urinary cyclic GMP, endothelin, and prostaglandin E2 in normal pregnancy and preeclampsia. Am J Perinatol. 1997;14:559–62.PubMedCrossRef
38.
Lacolley P, Gautier S, Poirier O, et al. Nitric oxide synthase gene polymorphisms, blood pressure and aortic stiffness in normotensive and hypertensive subjects. J Hypertens. 1998;16:31–5.PubMedCrossRef
39.
Elbaz A, Poirier O, Moulin T, et al. Association between the Glu298Asp polymorphism in the endothelial constitutive nitric oxide synthase gene and brain infarction. The GENIC Investigators. Stroke. 2000;31:1634–9.PubMedCrossRef
40.
Hingorani AD, Liang CF, Fatibene J, et al. A common variant of the endothelial nitric oxide synthase (Glu298 Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999;100:1515–20.PubMedCrossRef
41.
Shimasaki Y, Yasue H, Yoshimura M, et al. Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. J Am Coll Cardiol. 1998;31:1506–10.PubMedCrossRef
42.
Wang XL, Sim AS, Badenhop RF, et al. A smoking-dependent risk of coronary artery disease associated with a polymorphism of the endothelial nitric oxide synthase gene. Nat Med. 1996;2:41–5.PubMedCrossRef
43.
Tanus-Santos JE, Desai M, Deak LR, et al. Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol. Pharmacogenetics. 2002;12:407–13.PubMedCrossRef
44.
Pierangeli SS, Chen PP, Raschi E, et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost. 2008;34:236–50.PubMedCrossRef
45.
Pierangeli SS, Gharavi AE, Harris EN. Experimental thrombosis and antiphospholipid antibodies: new insights. J Autoimmun. 2000;15:241–7.PubMedCrossRef
46.
Oku K, Amengual O, Atsumi T. Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome. Eur J Clin Investig. 2012;42:1126–35.CrossRef
47.
Jankowski M, Vreys I, Wittevrongel C, et al. Thrombogenicity of beta 2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood. 2003;101:157–62.PubMedCrossRef
48.
Pierangeli SS, Colden-Stanfield M, Liu X, et al. Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation. 1999;99:1997–2002.PubMedCrossRef
49.
Espinola RG, Liu X, Colden-Stanfield M, et al. E-Selectin mediates pathogenic effects of antiphospholipid antibodies. J Thromb Haemost. 2003;1:843–8.PubMedCrossRef
50.
Romay-Penabad Z, Montiel-Manzano MG, Shilagard T, et al. Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood. 2009;114:3074–83.PubMedCrossRef
51.
Vega-Ostertag ME, Ferrara DE, Romay-Penabad Z, et al. Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation. J Thromb Haemost. 2007;5:1828–34.PubMedCrossRef
52.
Vega-Ostertag M, Liu X, Kwan-Ki H, et al. A human monoclonal antiprothrombin antibody is thrombogenic in vivo and upregulates expression of tissue factor and E-selectin on endothelial cells. Br J Haematol. 2006;135:214–9.PubMedCrossRef
53.
Pierangeli SS, Espinola RG, Liu X, Harris EN. Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and P-selectin. Circ Res. 2001;88:245–50.PubMedCrossRef
54.
Branch DW, Rodgers GM. Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: a possible mechanism of thrombosis. Am J Obstet Gynecol. 1993;168:206–10.PubMed
55.
Atsumi T, Khamashta MA, Haworth RS, et al. Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1. Arthritis Rheum. 1998;41:800–7.PubMedCrossRef
56.
Dunoyer-Geindre S, de Moerloose P, Galve-de RB, et al. NFkappaB is an essential intermediate in the activation of endothelial cells by anti-beta(2)-glycoprotein 1 antibodies. Thromb Haemost. 2002;88:851–7.PubMed
57.
Lopez-Pedrera C, Buendia P, Cuadrado MJ, et al. Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-kappaB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-1/ERK pathway. Arthritis Rheum. 2006;54:301–11.PubMedCrossRef
58.
Simoncini S, Sapet C, Camoin-Jau L, et al. Role of reactive oxygen species and p38 MAPK in the induction of the pro-adhesive endothelial state mediated by IgG from patients with anti-phospholipid syndrome. Int Immunol. 2005;17:489–500.PubMedCrossRef
59.
Vega-Ostertag M, Casper K, Swerlick R, et al. Involvement of p38 MAPK in the up-regulation of tissue factor on endothelial cells by antiphospholipid antibodies. Arthritis Rheum. 2005;52:1545–54.PubMedCrossRef
60.
Belizna C, Lartigue A, Favre J, et al. Antiphospholipid antibodies induce vascular functional changes in mice: a mechanism of vascular lesions in antiphospholipid syndrome? Lupus. 2008;17:185–94.PubMedCrossRef
61.
Delgado AJ, Mason LJ, Ames PR, et al. Antiphospholipid antibodies are associated with enhanced oxidative stress, decreased plasma nitric oxide and paraoxonase activity in an experimental mouse model. Rheumatology (Oxford). 2005;44:1238–44.CrossRef
62.
Ames PR, Tommasino C, Alves J, et al. Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study. Lupus. 2000;9:688–95.PubMedCrossRef
63.
• Ames PR, Batuca JR, Ciampa A, et al. Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome. J Rheumatol. 2010;37:2523–30. This is one of the series of studies published by the group that provide the link between nitric oxide and APS in humans. PubMedCrossRef
64.
•• Ramesh S, Morrell CN, Tarango C, et al. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via beta2GPI and apoER2. J Clin Invest. 2011;121:120–31. This work demonstrates for the first time that aPL antagonism of eNOS plays an important role in the abnormal vascular phenotypes in APS.PubMedCrossRef
65.
Mineo C, Shaul PW. New Insights into the Molecular Basis of the Antiphospholipid Syndrome. Drug Discov Today Dis Mech. 2011;8:e47–52.PubMedCrossRef
66.
Mineo C, Gormley AK, Yuhanna IS, et al. FcgammaRIIB mediates C-reactive protein inhibition of endothelial NO synthase. Circ Res. 2005;97:1124–31.PubMedCrossRef
67.
Loscalzo J. Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res. 2001;88:756–62.PubMedCrossRef
68.
Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003;102:2717–23.PubMedCrossRef
69.
Miyakis S, Giannakopoulos B, Krilis SA. Beta 2 glycoprotein I–function in health and disease. Thromb Res. 2004;114:335–46.PubMedCrossRef
70.
Ninivaggi M, Kelchtermans H, Lindhout T, de Laat B. Conformation of beta2glycoprotein I and its effect on coagulation. Thromb Res. 2012;130(1):S33–6.PubMedCrossRef
71.
de Groot PG, van Lummel M, Pennings M, et al. Beta2-glycoprotein I and LDL-receptor family members. Thromb Res. 2004;114:455–9.PubMedCrossRef
72.
Urbanus RT, Derksen RH, de Groot PG. Platelets and the antiphospholipid syndrome. Lupus. 2008;17:888–94.PubMedCrossRef
73.
Pierangeli SS, Vega-Ostertag M, Harris EN. Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: a pathway to targeted therapies. Thromb Res. 2004;114:467–76.PubMedCrossRef
74.
de Laat B, de Groot PG. Autoantibodies directed against domain I of beta2-glycoprotein I. Curr Rheumatol Rep. 2011;13:70–6.PubMedCrossRef
75.
de Laat B, Derksen RH, Urbanus RT, de Groot PG. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood. 2005;105:1540–5.PubMedCrossRef
76.
de Laat B, Pengo V, Pabinger I, et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost. 2009;7:1767–73.PubMedCrossRef
77.
Del Papa N, Guidali L, Sala A, et al. Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-beta 2-glycoprotein I antibodies react in vitro with endothelial cells through adherent beta 2-glycoprotein I and induce endothelial activation. Arthritis Rheum. 1997;40:551–61.PubMedCrossRef
78.
Del Papa N, Guidali L, Spatola L, et al. Relationship between anti-phospholipid and anti-endothelial cell antibodies III: beta 2 glycoprotein I mediates the antibody binding to endothelial membranes and induces the expression of adhesion molecules. Clin Exp Rheumatol. 1995;13:179–85.PubMed
79.
He J, Luster TA, Thorpe PE. Radiation-enhanced vascular targeting of human lung cancers in mice with a monoclonal antibody that binds anionic phospholipids. Clin Cancer Res. 2007;13:5211–8.PubMedCrossRef
80.
Ran S, He J, Huang X, et al. Antitumor effects of a monoclonal antibody that binds anionic phospholipids on the surface of tumor blood vessels in mice. Clin Cancer Res. 2005;11:1551–62.PubMedCrossRef
81.
Herz J, Chen Y. Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev Neurosci. 2006;7:850–9.PubMedCrossRef
82.
Pennings MT, van Lummel M, Derksen RH, et al. Interaction of beta2-glycoprotein I with members of the low density lipoprotein receptor family. J Thromb Haemost. 2006;4:1680–90.PubMedCrossRef
83.
Urbanus RT, Pennings MT, Derksen RH, de Groot PG. Platelet activation by dimeric beta2-glycoprotein I requires signaling via both glycoprotein Ibalpha and apolipoprotein E receptor 2'. J Thromb Haemost. 2008;6:1405–12.PubMedCrossRef
84.
Pennings MT, Derksen RH, Urbanus RT, et al. Platelets express three different splice variants of ApoER2 that are all involved in signaling. J Thromb Haemost. 2007;5:1538–44.PubMedCrossRef
85.
Herz J, Goldstein JL, Strickland DK, et al. 39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. J Biol Chem. 1991;266:21232–8.PubMed
86.
•• Romay-Penabad Z, Guilar-Valenzuela R, Urbanus RT, et al. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome. Blood. 2011;117:1408–14. The paper provides concrete evidence that apoER2 is required for aPL-induced thrombus formation in vivo. PubMedCrossRef
87.
Fulton D, Gratton JP, Sessa WC. Post-translational control of endothelial nitric oxide synthase: why isn't calcium/calmodulin enough? J Pharmacol Exp Ther. 2001;299:818–24.PubMed
88.
Shaul PW. Regulation of endothelial nitric oxide synthase: location, location, location. Annu Rev Physiol. 2002;64:749–74.PubMedCrossRef
89.
Greif DM, Kou R, Michel T. Site-specific dephosphorylation of endothelial nitric oxide synthase by protein phosphatase 2A: evidence for crosstalk between phosphorylation sites. Biochemistry (Mosc). 2002;41:15845–53.CrossRef
90.
Michell BJ, Chen Z, Tiganis T, et al. Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem. 2001;276:17625–8.PubMedCrossRef
91.
Mumby MC, Walter G. Protein serine/threonine phosphatases: structure, regulation, and functions in cell growth. Physiol Rev. 1993;73:673–99.PubMed
92.
Leidi M, Mariotti M, Maier JA. EDF-1 contributes to the regulation of nitric oxide release in VEGF-treated human endothelial cells. Eur J Cell Biol. 2010;89:654–60.PubMedCrossRef
93.
Urbich C, Reissner A, Chavakis E, et al. Dephosphorylation of endothelial nitric oxide synthase contributes to the anti-angiogenic effects of endostatin. FASEB J. 2002;16:706–8.PubMed
94.
Wu F, Wilson JX. Peroxynitrite-dependent activation of protein phosphatase type 2A mediates microvascular endothelial barrier dysfunction. Cardiovasc Res. 2009;81:38–45.PubMedCrossRef
95.
Meroni PL, Raschi E, Testoni C, et al. Innate immunity in the antiphospholipid syndrome: role of toll-like receptors in endothelial cell activation by antiphospholipid antibodies. Autoimmun Rev. 2004;3:510–5.PubMedCrossRef
96.
Fischetti F, Durigutto P, Pellis V, et al. Thrombus formation induced by antibodies to beta2-glycoprotein I is complement dependent and requires a priming factor. Blood. 2005;106:2340–6.PubMedCrossRef
97.
Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet? Lupus. 2010;19:475–85.PubMedCrossRef
98.
Erkan D, Harrison MJ, Levy R, et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum. 2007;56:2382–91.PubMedCrossRef
99.
Finazzi G, Marchioli R, Brancaccio V, et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J Thromb Haemost. 2005;3:848–53.PubMedCrossRef
100.
Garcia DA, Khamashta MA, Crowther MA. How we diagnose and treat thrombotic manifestations of the antiphospholipid syndrome: a case-based review. Blood. 2007;110:3122–7.PubMedCrossRef
Metadata
Title
Inhibition of Nitric Oxide and Antiphospholipid Antibody-Mediated Thrombosis
Author
Chieko Mineo
Publication date
01-05-2013
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 5/2013
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-013-0324-4

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