1. Marijon E, Le Heuzey JY, Connolly S, Yang S, Pogue J, Brueckmann M, et al. Causes of death and influencing factors in patients with atrial fibrillation: a competing-risk analysis from the randomized evaluation of long-term anticoagulant therapy study. Circulation. 2013; 128:2192–201.
2. Camm AJ, Amarenco P, Haas S, Hess S, Kirchhof P, Kuhls S, et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2016; 37:1145–53.
3. Kim D, Yang PS, Jang E, Yu HT, Kim TH, Uhm JS, et al. Increasing trends in hospital care burden of atrial fibrillation in Korea, 2006 through 2015. Heart. 2018; 104:2010–7.
4. Bunch TJ. Atrial fibrillation and dementia. Circulation. 2020; 142:618–20.
5. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC guideline for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021; 42:373–498.
6. Giannone ME, Filippini T, Whelton PK, Chiari A, Vitolo M, Boriani G, et al. Atrial fibrillation and the risk of early-onset dementia: a systematic review and meta-analysis. J Am Heart Assoc. 2022; 11:e025653.
7. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008; 358:2667–77.
8. Opolski G, Torbicki A, Kosior DA, Szulc M, Wozakowska-Kaplon B, Kolodziej P, et al. Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Chest. 2004; 126:476–86.
9. Singh SN, Singh BN, Reda DJ, Fye CL, Ezekowitz MD, Fletcher RD, et al. Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]). Am J Cardiol. 2003; 92:468–72.
10. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002; 347:1825–33.
11. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002; 347:1834–40.
12. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation: Pharmacological Intervention in Atrial Fibrillation (PIAF). A randomised trial. Lancet. 2000; 356:1789–94.
13. Kim D, Yang PS, You SC, Sung JH, Jang E, Yu HT, et al. Treatment timing and the effects of rhythm control strategy in patients with atrial fibrillation: nationwide cohort study. BMJ. 2021; 373:n991.
14. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, et al. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 2020; 383:1305–16.
15. Kalman JM, Al-Kaisey AM, Parameswaran R, Hawson J, Anderson RD, Lim M, et al. Impact of early vs. delayed atrial fibrillation catheter ablation on atrial arrhythmia recurrences. Eur Heart J. 2023; 44:2447–54.
16. Bunch TJ, May HT, Bair TL, Johnson DL, Weiss JP, Crandall BG, et al. Increasing time between first diagnosis of atrial fibrillation and catheter ablation adversely affects long-term outcomes. Heart Rhythm. 2013; 10:1257–62.
17. De Greef Y, Schwagten B, Chierchia GB, de Asmundis C, Stockman D, Buysschaert I. Diagnosis-to-ablation time as a predictor of success: early choice for pulmonary vein isolation and long-term outcome in atrial fibrillation: results from the Middelheim-PVI Registry. Europace. 2018; 20:589–95.
18. Yu HT, Kim IS, Kim TH, Uhm JS, Kim JY, Joung B, et al. Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation. J Cardiovasc Electrophysiol. 2020; 31:457–64.
19. De Greef Y, Bogaerts K, Sofianos D, Buysschaert I. Impact of diagnosis-to-ablation time on AF recurrence: pronounced the first 3 years, irrelevant thereafter. JACC Clin Electrophysiol. 2023; 9:2263–72.
20. Turakhia MP, Guo JD, Keshishian A, Delinger R, Sun X, Ferri M, et al. Contemporary prevalence estimates of undiagnosed and diagnosed atrial fibrillation in the United States. Clin Cardiol. 2023; 46:484–93.
21. Tsao CW, Aday AW, Almarzooq ZI, Anderson CA, Arora P, Avery CL, et al. Heart disease and stroke statistics: 2023 update. A report from the American Heart Association. Circulation. 2023; 147:e93–621.
22. Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014; 129:837–47.
23. Kim D, Yang PS, Jang E, Yu HT, Kim TH, Uhm JS, et al. 10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population. Am Heart J. 2018; 202:20–6.
24. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004; 110:1042–6.
25. Gorenek B, Pelliccia A, Benjamin EJ, Boriani G, Crijns HJ, Fogel RI, et al. European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS). Europace. 2017; 19:190–225.
26. Miller JD, Aronis KN, Chrispin J, Patil KD, Marine JE, Martin SS, et al. Obesity, exercise, obstructive sleep apnea, and modifiable atherosclerotic cardiovascular disease risk factors in atrial fibrillation. J Am Coll Cardiol. 2015; 66:2899–906.
27. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014; 64:e1–76.
28. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010; 31:2369–429.
29. Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994; 271:840–4.
30. Cox JL, Schuessler RB, D’Agostino HJ, Stone CM, Chang BC, Cain ME, et al. The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. J Thorac Cardiovasc Surg. 1991; 101:569–83.
31. Prasad SM, Maniar HS, Camillo CJ, Schuessler RB, Boineau JP, Sundt TM, et al. The Cox maze III procedure for atrial fibrillation: long-term efficacy in patients undergoing lone versus concomitant procedures. J Thorac Cardiovasc Surg. 2003; 126:1822–8.
32. Gaynor SL, Schuessler RB, Bailey MS, Ishii Y, Boineau JP, Gleva MJ, et al. Surgical treatment of atrial fibrillation: predictors of late recurrence. J Thorac Cardiovasc Surg. 2005; 129:104–11.
33. Johansson BI, Väärt O, Edvardsson N, Nyström B, Scherstén H, Karlsson T, et al. Low mortality and low rate of perceived and documented arrhythmias after Cox maze III surgery for atrial fibrillation. Pacing Clin Electrophysiol. 2014; 37:147–56.
34. Haïssaguerre M, Shah DC, Jaïs P, Hocini M, Yamane T, Deisenhofer I, et al. Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation. 2000; 102:2463–5.
35. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998; 339:659–66.
36. Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, et al. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation. 2001; 104:2539–44.
37. Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, et al. Circumferential radiofrequency ablation of pulmonary vein ostia: a new anatomic approach for curing atrial fibrillation. Circulation. 2000; 102:2619–28.
38. Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015; 372:1812–22.
39. He X, Zhou Y, Chen Y, Wu L, Huang Y, He J. Left atrial posterior wall isolation reduces the recurrence of atrial fibrillation: a meta-analysis. J Interv Card Electrophysiol. 2016; 46:267–74.
40. Scott PA, Silberbauer J, Murgatroyd FD. The impact of adjunctive complex fractionated atrial electrogram ablation and linear lesions on outcomes in persistent atrial fibrillation: a meta-analysis. Europace. 2016; 18:359–67.
41. Lee JM, Shim J, Park J, Yu HT, Kim TH, Park JK, et al. The electrical isolation of the left atrial posterior wall in catheter ablation of persistent atrial fibrillation. JACC Clin Electrophysiol. 2019; 5:1253–61.
42. Kistler PM, Chieng D, Sugumar H, Ling LH, Segan L, Azzopardi S, et al. Effect of catheter ablation using pulmonary vein isolation with vs without posterior left atrial wall isolation on atrial arrhythmia recurrence in patients with persistent atrial fibrillation: the CAPLA randomized clinical trial. JAMA. 2023; 329:127–35.
43. Writing Committee Members, Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024; 83:109–279.
44. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2017; 14:e275–444.
45. Morady F, Scheinman MM. Transvenous catheter ablation of a posteroseptal accessory pathway in a patient with the Wolff-Parkinson-White syndrome. N Engl J Med. 1984; 310:705–7.
46. Houmsse M, Daoud EG. Biophysics and clinical utility of irrigated-tip radiofrequency catheter ablation. Expert Rev Med Devices. 2012; 9:59–70.
47. Natale A, Reddy VY, Monir G, Wilber DJ, Lindsay BD, McElderry HT, et al. Paroxysmal AF catheter ablation with a contact force sensing catheter: results of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol. 2014; 64:647–56.
48. Reddy VY, Pollak S, Lindsay BD, McElderry HT, Natale A, Kantipudi C, et al. Relationship between catheter stability and 12-month success after pulmonary vein isolation: a subanalysis of the SMART-AF trial. JACC Clin Electrophysiol. 2016; 2:691–9.
49. Macle L, Frame D, Gache LM, Monir G, Pollak SJ, Boo LM. Atrial fibrillation ablation with a spring sensor-irrigated contact force-sensing catheter compared with other ablation catheters: systematic literature review and meta-analysis. BMJ Open. 2019; 9:e023775.
50. Duytschaever M, Vijgen J, De Potter T, Scherr D, Van Herendael H, Knecht S, et al. Standardized pulmonary vein isolation workflow to enclose veins with contiguous lesions: the multicentre VISTAX trial. Europace. 2020; 22:1645–52.
51. Natale A, Monir G, Patel AM, Fishel RS, Marchlinski FE, Delaughter MC, et al. Long-term safety and effectiveness of paroxysmal atrial fibrillation ablation using a porous tip contact force-sensing catheter from the SMART SF trial. J Interv Card Electrophysiol. 2021; 61:63–9.
52. Habibi M, Berger RD, Calkins H. Radiofrequency ablation: technological trends, challenges, and opportunities. Europace. 2021; 23:511–9.
53. Suga K, Kato H, Akita S, Sakurai T, Ota R, Okada T, et al. Optimal ablation settings of TactiFlex SE laser-cut irrigated-tip catheter: comparison with ThermoCool SmartTouch SurroundFlow porous irrigated-tip catheter. J Interv Card Electrophysiol. 2024 Apr 4 [Epub].
https://doi.org/10.1007/s10840-024-01797-9.
54. Naniwadekar A, Dukkipati SR. High-power short-duration ablation of atrial fibrillation: a contemporary review. Pacing Clin Electrophysiol. 2021; 44:528–40.
55. Leshem E, Zilberman I, Tschabrunn CM, Barkagan M, Contreras-Valdes FM, Govari A, et al. High-power and short-duration ablation for pulmonary vein isolation: biophysical characterization. JACC Clin Electrophysiol. 2018; 4:467–79.
56. Baher A, Kheirkhahan M, Rechenmacher SJ, Marashly Q, Kholmovski EG, Siebermair J, et al. High-power radiofrequency catheter ablation of atrial fibrillation: using late gadolinium enhancement magnetic resonance imaging as a novel index of esophageal injury. JACC Clin Electrophysiol. 2018; 4:1583–94.
57. Ravi V, Poudyal A, Abid QU, Larsen T, Krishnan K, Sharma PS, et al. High-power short duration vs. conventional radiofrequency ablation of atrial fibrillation: a systematic review and meta-analysis. Europace. 2021; 23:710–21.
58. Osorio J, Hussein AA, Delaughter MC, Monir G, Natale A, Dukkipati S, et al. Very high-power short-duration, temperature-controlled radiofrequency ablation in paroxysmal atrial fibrillation: the prospective multicenter Q-FFICIENCY trial. JACC Clin Electrophysiol. 2023; 9:468–80.
59. Hussein AA, Delaughter MC, Monir G, Natale A, Dukkipati S, Oza S, et al. Paroxysmal atrial fibrillation ablation with a novel temperature-controlled CF-sensing catheter: Q-FFICIENCY clinical and healthcare utilization benefits. J Cardiovasc Electrophysiol. 2023; 34:2493–503.
60. Andrade JG, Khairy P, Dubuc M. Catheter cryoablation: biology and clinical uses. Circ Arrhythm Electrophysiol. 2013; 6:218–27.
61. Avitall B, Kalinski A. Cryotherapy of cardiac arrhythmia: from basic science to the bedside. Heart Rhythm. 2015; 12:2195–203.
62. Kuck KH, Brugada J, Fürnkranz A, Metzner A, Ouyang F, Chun KR, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med. 2016; 374:2235–45.
63. Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, et al. Cryoballoon ablation as initial therapy for atrial fibrillation. N Engl J Med. 2021; 384:316–24.
64. Straube F, Pongratz J, Kosmalla A, Brueck B, Riess L, Hartl S, et al. Cryoballoon ablation strategy in persistent atrial fibrillation. Front Cardiovasc Med. 2021; 8:758408.
65. Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, et al. Cryoablation or drug therapy for initial treatment of atrial fibrillation. N Engl J Med. 2021; 384:305–15.
66. Su WW, Reddy VY, Bhasin K, Champagne J, Sangrigoli RM, Braegelmann KM, et al. Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: results from the multicenter STOP Persistent AF trial. Heart Rhythm. 2020; 17:1841–7.
67. Metzner A, Rausch P, Lemes C, Reissmann B, Bardyszewski A, Tilz R, et al. The incidence of phrenic nerve injury during pulmonary vein isolation using the second-generation 28 mm cryoballoon. J Cardiovasc Electrophysiol. 2014; 25:466–70.
68. Fürnkranz A, Bordignon S, Schmidt B, Perrotta L, Dugo D, De Lazzari M, et al. Incidence and characteristics of phrenic nerve palsy following pulmonary vein isolation with the second-generation as compared with the first-generation cryoballoon in 360 consecutive patients. Europace. 2015; 17:574–8.
69. Abugattas JP, de Asmundis C, Iacopino S, Salghetti F, Takarada K, Coutiño HE, et al. Phrenic nerve injury during right inferior pulmonary vein ablation with the second-generation cryoballoon: clinical, procedural, and anatomical characteristics. Europace. 2018; 20:e156–63.
70. Hoffmann E, Straube F, Wegscheider K, Kuniss M, Andresen D, Wu LQ, et al. Outcomes of cryoballoon or radiofrequency ablation in symptomatic paroxysmal or persistent atrial fibrillation. Europace. 2019; 21:1313–24.
71. Dukkipati SR, Cuoco F, Kutinsky I, Aryana A, Bahnson TD, Lakkireddy D, et al. Pulmonary vein isolation using the visually guided laser balloon: a prospective, multicenter, and randomized comparison to standard radiofrequency ablation. J Am Coll Cardiol. 2015; 66:1350–60.
72. Bordignon S, Chun KR, Gunawardene M, Urban V, Kulikoglu M, Miehm K, et al. Energy titration strategies with the endoscopic ablation system: lessons from the high-dose vs. low-dose laser ablation study. Europace. 2013; 15:685–9.
73. Reynolds MR, Zheng Q, Doros G. Laser balloon ablation for AF: a systematic review and meta-analysis. J Cardiovasc Electrophysiol. 2018; 29:1363–70.
74. Weber S, Höher M, Schultes D. First results and follow-up of a second-generation circular mapping and ablation catheter. J Interv Card Electrophysiol. 2016; 47:213–9.
75. Mönnig G, Eckardt L. Multielectrode Pulmonary Vein Ablation Catheter (PVAC(®)): current data on results and risks. Herzschrittmacherther Elektrophysiol. 2014; 25:236–40.
76. Gaita F, Leclercq JF, Schumacher B, Scaglione M, Toso E, Halimi F, et al. Incidence of silent cerebral thromboembolic lesions after atrial fibrillation ablation may change according to technology used: comparison of irrigated radiofrequency, multipolar nonirrigated catheter and cryoballoon. J Cardiovasc Electrophysiol. 2011; 22:961–8.
77. Bulava A, Haniš J, Sitek D, Ošmera O, Karpianus D, Snorek M, et al. Catheter ablation for paroxysmal atrial fibrillation: a randomized comparison between multielectrode catheter and point-by-point ablation. Pacing Clin Electrophysiol. 2010; 33:1039–46.
78. Vurma M, Dang L, Brunner-La Rocca HP, Sütsch G, Attenhofer-Jost CH, Duru F, et al. Safety and efficacy of the nMARQ catheter for paroxysmal and persistent atrial fibrillation. Europace. 2016; 18:1164–9.
79. Mahida S, Hooks DA, Nentwich K, Ng GA, Grimaldi M, Shin DI, et al. nMARQ ablation for atrial fibrillation: results from a multicenter study. J Cardiovasc Electrophysiol. 2015; 26:724–9.
80. Shin DI, Kirmanoglou K, Eickholt C, Schmidt J, Clasen L, Butzbach B, et al. Initial results of using a novel irrigated multielectrode mapping and ablation catheter for pulmonary vein isolation. Heart Rhythm. 2014; 11:375–83.
81. Reddy VY, Al-Ahmad A, Aidietis A, Daly M, Melton I, Hu Y, et al. A novel visually guided radiofrequency balloon ablation catheter for pulmonary vein isolation: one-year outcomes of the multicenter AF-FICIENT I trial. Circ Arrhythm Electrophysiol. 2021; 14:e009308.
82. Dhillon GS, Honarbakhsh S, Di Monaco A, Coling AE, Lenka K, Pizzamiglio F, et al. Use of a multi-electrode radiofrequency balloon catheter to achieve pulmonary vein isolation in patients with paroxysmal atrial fibrillation: 12-month outcomes of the RADIANCE study. J Cardiovasc Electrophysiol. 2020; 31:1259–69.
83. Boersma L. New energy sources and technologies for atrial fibrillation catheter ablation. Europace. 2022; 24(Suppl 2):ii44–51.
84. Maor E, Sugrue A, Witt C, Vaidya VR, DeSimone CV, Asirvatham SJ, et al. Pulsed electric fields for cardiac ablation and beyond: a state-of-the-art review. Heart Rhythm. 2019; 16:1112–20.
85. Neven K, van Es R, van Driel V, van Wessel H, Fidder H, Vink A, et al. Acute and long-term effects of full-power electroporation ablation directly on the porcine esophagus. Circ Arrhythm Electrophysiol. 2017; 10:e004672.
86. van Driel VJ, Neven K, van Wessel H, Vink A, Doevendans PA, Wittkampf FH. Low vulnerability of the right phrenic nerve to electroporation ablation. Heart Rhythm. 2015; 12:1838–44.
87. du Pré BC, van Driel VJ, van Wessel H, Loh P, Doevendans PA, Goldschmeding R, et al. Minimal coronary artery damage by myocardial electroporation ablation. Europace. 2013; 15:144–9.
88. Ekanem E, Reddy VY, Schmidt B, Reichlin T, Neven K, Metzner A, et al. Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF). Europace. 2022; 24:1256–66.
89. Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, et al. Pulsed field ablation for pulmonary vein isolation in atrial fibrillation. J Am Coll Cardiol. 2019; 74:315–26.
90. Reddy VY, Gerstenfeld EP, Natale A, Whang W, Cuoco FA, Patel C, et al. Pulsed field or conventional thermal ablation for paroxysmal atrial fibrillation. N Engl J Med. 2023; 389:1660–71.
91. Duytschaever M, De Potter T, Grimaldi M, Anic A, Vijgen J, Neuzil P, et al. Paroxysmal atrial fibrillation ablation using a novel variable-loop biphasic pulsed field ablation catheter integrated with a 3-dimensional mapping system: 1-year outcomes of the multicenter inspIRE study. Circ Arrhythm Electrophysiol. 2023; 16:e011780.
92. Di Biase L, Marazzato J, Govari A, Altman A, Beeckler C, Keyes J, et al. Pulsed field ablation index-guided ablation for lesion formation: impact of contact force and number of applications in the ventricular model. Circ Arrhythm Electrophysiol. 2024; 17:e012717.
93. Di Biase L, Marazzato J, Zou F, Lin A, Grupposo V, Chowdhuri N, et al. Point-by-point pulsed field ablation using a multimodality generator and a contact force-sensing ablation catheter: comparison with radiofrequency ablation in a remapped chronic swine heart. Circ Arrhythm Electrophysiol. 2023; 16:663–71.