CINXE.COM

<!DOCTYPE html><html lang="en-US"><head><title>Just a moment...</title><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta http-equiv="X-UA-Compatible" content="IE=Edge"><meta name="robots" content="noindex,nofollow"><meta name="viewport" content="width=device-width,initial-scale=1"><style>*{box-sizing:border-box;margin:0;padding:0}html{line-height:1.15;-webkit-text-size-adjust:100%;color:#313131;font-family:system-ui,-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Helvetica Neue,Arial,Noto Sans,sans-serif,Apple Color Emoji,Segoe UI Emoji,Segoe UI Symbol,Noto Color Emoji}body{display:flex;flex-direction:column;height:100vh;min-height:100vh}.main-content{margin:8rem auto;max-width:60rem;padding-left:1.5rem}@media (width <= 720px){.main-content{margin-top:4rem}}.h2{font-size:1.5rem;font-weight:500;line-height:2.25rem}@media (width <= 720px){.h2{font-size:1.25rem;line-height:1.5rem}}#challenge-error-text{background-image:url(data:image/svg+xml;base64,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);background-repeat:no-repeat;background-size:contain;padding-left:34px}@media (prefers-color-scheme:dark){body{background-color:#222;color:#d9d9d9}}</style><meta http-equiv="refresh" content="390"></head><body class="no-js"><div class="main-wrapper" role="main"><div class="main-content"><noscript><div class="h2"><span id="challenge-error-text">Enable JavaScript and cookies to continue</span></div></noscript></div></div><script>(function(){window._cf_chl_opt={cvId: '3',cZone: "www.acpjournals.org",cType: 'managed',cRay: '913fa8b5cba9ce09',cH: 'BY5pa_.QTGLudG2baP4LX7PcioNPAqRqEeS.CWD5luM-1739898924-1.2.1.1-DixfNzMFF1apI4QLfMYUJASbXTQ69fr9.4DCWDX2cBEP7Jn6iIhYTdb_Z_T7jn2N',cUPMDTk: "\/doi\/10.7326\/M20-3012?__cf_chl_tk=7Cye1WvoQ9CVkyZ4asK1mOhP.XIQ47jGUTO0btua9do-1739898924-1.0.1.1-vLrdYhEmUJqJy1_UcnromvH9O.vYE.UEJFrR4x7Of.E",cFPWv: 'g',cITimeS: '1739898924',cTTimeMs: '1000',cMTimeMs: '390000',cTplC: 0,cTplV: 5,cTplB: 'cf',cK: "unsupported-browser",fa: "\/doi\/10.7326\/M20-3012?__cf_chl_f_tk=7Cye1WvoQ9CVkyZ4asK1mOhP.XIQ47jGUTO0btua9do-1739898924-1.0.1.1-vLrdYhEmUJqJy1_UcnromvH9O.vYE.UEJFrR4x7Of.E",md: "LfFts.C0yuQYQauuOzunMu_hBpe95RVhJC.OVSDjtbs-1739898924-1.2.1.1-LrOEx13VwquJs1Dw9vLdf5cAHYWqaHa2Q3M0.hk81RaDXT4avfX5w1AJfUz3qHbR32grMglXV.PLWRzBPtpIzddGfJqeDb9diSDv5Qd01uWZeqBwbrYR4vcJy8n6UDPOaxxRrj1_ILI1WhCc4LQSQhRTVkcoBQB_gN3A__ZpXLFzSC_NuAB.nKWMJhGOwBB6FlhQNfqqa.JfHOVwkxTQo9fg.rK.MO5SIeLxXPMtn7H8BqmYUAfUTAhIgEtfKekLX_YJCWQ.HQkLMQnqbmA41A8TA9Z.tpEdzIKAtB0WJh51jNlxJd5nFwMRh37C7udnut6DYGXMBSPfF93R.GAvfA6vNRcWDdJzkpTl82RB.6c0RWnMtzh4wM5Y6aCSbxHx768qS0v2JeOx7O_k8djjEorUKywKFH8oPnU6A3kM1KGMV6hqMeTTe29oYqPbFqLCkcn7eY3FkHV8BEA9L_DYR7al5BHwHGEL15BTjQPL7CZjhWZpDJlFegilWl.YzgmOOaySBxVM6c6S2zD_bReN4LZxwkFiUDYVyfxHDx7Y2yscPWaOgAbdi7HGBUdJAg7an2tEcrrqnPWELml..HnuIT10ffK4xQ.U4h8ldOu_mInjNEkolxd77WCD5A3AiTFOT5jTjbGN8xKsQcppxN71qAtgipNP2qm074M54mObSeXeccLk9Nq7KOEvhut5X5hiWr1urz30JJHCmXhk8_4Alnc2DMvfyJe1UsGRhiSIhtOf8FYr3vD1KBPjeCW0ohNKLCc4e1teXgAun2GQhTZG0uiEljk194AQq8HF87ZPHa9K19fLfom1d68Ub85qRgG_keluHCiehl.DvgX1rnLQ8VzksG8KaxCRHhB.AE8y8V39Yfb6OsiGS7v6h4glHpoEQ3EvAiDAro9XRYOE9hK_P6ufwlzUVkTq_LRt0lMjsPbaIFQElrBLD0nSzKoRUh5v7cIESXkcj1Mz7smVlb1iF2Tm59Jw2KZBRm2BcLfT7ohNnYVgJ_r79sHtZ35qDGIsl_nJ6GNV5E0ol2gqW4nnBCPlXbcsmpsZR7SINlC91jo._szmeS.YBHoWEmNLEUH7rLBmvQPpBV6IZAvdygHt2Z4o6l_9i54SVIE5j7OIcCJWh.QGqRLW2lRDFvMT3hiiW2lIXsccF_ZC_vD9dazr_3gDHHMxxd__jFKzs6d6g0RydFpWdR.S0Ar8RiIvau1.0FKWr406LYC2MUQo3J2gFeoSnc7dAkx8WKsYRieB7YUlp3zMzBSy730eVZ91kzOYcw5nJYjD0wVXIxA4wcyq9uB7h4GuvDRgnoS1YdXMVoIl.6MPlOqobb30sSWwHsjoB0m0FbpBRxgBcpRvNaz2NobMhLYAM7B.SkUTYl6GsZ61lblIbSYyrS.r7JtEsp6Y3lKQK4JX6jL6K1cTgwalnjAhhK16R6nNVYMDXnNLzvVCJvX6DYcV2ROCvJmv4ZP1lHHFs7Zvh9DqG6fnM6Ojnbozw.YF4hM3ogvNXsBnsnI22cZLzJ1rBcVus.OjkSB_Ly0c6k6LRTVXEV0t.zURDsEunxXnMbyrE5EM6QqIjODc19kz2nN6MkO41mForPN6WuAZ21MysxGixF65kztHMuEe27C_BjdytKGBc7mBIeBcNZq332nCAVmXoE71gyZFqDMeSR8DtO_cC675r4kgyvN.PuP_0HFLXncSFMIJ8TL.U0LtLsUpvKuv7cmKwterRbSOB.IHuwX6eKkfzgQeslkqOPwoORAd2On3YiZnte6ZCWqJzIf_kbJ6eh7L4f1.uudieI4DSHyPsu8QK3ugDHbzkjxCzKzzQ5sqi7hJ68RMgMhCbIuC5XJCObWRhQuGeqnTuxJY7wSN4l101RQV51amv95JUR4xJci9H3GegMeWFXOWN2uB.OYrUFcK9PrP0uNr5E6pjqH9oF235.0gkQuheDnUdlAn9el01WbotNg18Z3BfJNIHpkIrMZ_L7.hpcxJnkFBsNnrXqnIRDMekOsyTR3.DCaaqHRWfRA6vt_TOOB45WXlrLF4tYfOicJUjBAGiST0iHmLb0tsoMGNjUQ6g1NYkPL45c3dQvwnZ8oUbYmLBSlPddaD0P45uuF0wny8jmcprJK_wlTrkCHwwrDKts_II93r.R1hBkH476ygKgTXDhc7yAnZ960fHwWu6raEmtzAjUayByRtp71eBWfT_4pOkbznx56ZVv0tJm65Qt784_CxI_RIO.KfBvwAaSsSjN5vghkjQtGwsJlOckNTU4yiG5qx62CPJm1R9uhRqQAmqyaDxzL9zv3mX.bn1gqrl8n10W.CD172b4V4JChc8hQN7biFzwMMXKSEHZcy1a7tyTDF5yftSIlTivMKLG8LzxFdrWybA4STyDyperp4uHMnJeHqbvPdBQEXbwIqbTZI2b7GkDpzDpvix57M7XlUWcdBmefx4ZH1QO8E8X6UM.HMSYMG7cEKvbNI3UHKuCy4.V_76Z_Gl_8j8kk6FOMvXdnmw3rohSbMgQXpC_pDfgLVOPpebZjk1b9w0_MGK.k8RfDcMmC6CvYtdrVnQWse5eFymjB514Pjqj3VTQ",mdrd: "VZzxmdMz_lmOAh.QDduTP1QV6BYQnPhmo0Dsw6G8hwc-1739898924-1.2.1.1-HzjnV7u0XAz1TJUZbqCRjviZDm9ytibBiR10TCUrfg5VIOKP_Z7YpWMBu2L.HjkN7e2OLQvS39BK7y0OVuJ8OP7pTedXnWQD2V3LiM1xz71rWsMrehF4Vc0qQFgSeVEkIn2PjXVzU1LprTHz8ruL5uJMPcTHdgECG6SrJn48roor47UKWZV7Z1Hx9YsG5aJF99oX52pnPn_19cgklokDZY_UDkm15jVIPvhGDMKglMInFaqpALlU_KaUZFPax7Nivd6CsPS6RApHLUz0WVG5L0yWN09NxlYTMTCC_c_kYAunTx6c3QERe4jir6aD4.qXIyxtRjiCrbWL4FrGu8j5JVHGjIny.T7DIARzG824c6ZQ_Y9tnquwY2mkyveQwFg3RkBhh2KqDFNJhQLhT8H6iZ3vVkeLeqKbE1vpsZKddWnp33OOV58aVJQb7V1rGPsiNq7hmfPK4UWSS9qmu9x4L87wE..YaOAKZVnkJ7hmCKONnRQfB4hrMmZg4k5TzGQdD2OwhHz66tqBch.Xzg0KZWmQSk.wTUNJLlShXfTg0W0TbcUS9tavZSLLT3cOmnbhNjPunz.3OVw8LBLaaTaNX3i8yX0tXIubxiLF221oaAeAwGInBwid1UTbIiXyNQ.ubSuOEAHqdrpUTdaqf_GXu0QduIS4cOjyhbHNeJbk_9lYx8DqNYBd72.kysvVfdcGzhhW5S8OU_H5QQOLi1KIlpqS1cgCZE00PLnUtGE7XB4OLjClnnOQ7s3iMYbycgaMUQVO19uDfGfEqwyQwdcjOBnGz1CN5ufLgWaYFV.e7wGRhTI46yvyANNk5l4az83eWM2sA3aIGnV.qbhPeeKBMGbJHe0vH2bbJKqHPWM4l9Atk3dylWCl4KDbEKkdeN.eEkcAOMi329r2uwsFKGNJAkUmc6SHZNf5qKVE0zOY_A7P7bIsiTaqYWumqNzNlWQY5KXMfb9rgKMpyY7tAjSWL9bTNyYhAqqfaWwiTEnoCc5JRkLD4x8M507N2Z_cXycoHD3Uah975n7P6IjogLJwnUowU4hUeauwtY3QmXp6ZH0dgLy6brt2lMU3K.7uPevn3IZQK4Z2qU1AVGKeFPokB.uPg6FPEZQOMQOe9XJQN8oC_ctcoZZ1WTg8Ha1R8FBIg79G_r9MYgvbX40s88e7lVN0g1UHz1kp8jAMzizA3R4pYFaXm2dhqbF0ZGbXp.zjw4DJxvHMBHRgd.fBSEn.eR2zYny3L4kTb6ACjdd4gwSEeJjlMbqMEXLYxUbudj3pBf1IVYZTI0ni2UBrz3I9bKgROt4._egZIZARKABVQPwFy7_WeQFYBUkO8lQeKCsRI2xcC6Ul9h3u5UdfgxIfVh5XQoGCXgjz4ygnMxtSkKgkHEASjVlYONQzzEoYy5Hyk6sN5QYhh8ShlUNIgJ6ru5ghZXpBTUykOmwVbOm_.ueg0at4iCajk0wNyszRl8oXK4cLExAAfrH63aXjqfaIuB68bN6.BpxlMCw3.80be4Wqpk0bIVGrOMiLLqs1rjckjiPcC.bajBEQXwx59b0Buc9RnglL4eJf3OJyvrYuCanznDD7X2K_Nm6ohRThbC3a1vj91pmPQcPzi1bF23WzY2QKgCABtyrcpupY1Z1v7n3BkkCUk7lnSzlmfCsvZOrFpeqft3oERvYbXWpt7EqHXi1jbiWN7zexblvGwmsDfQLv7U2.6lHZjHwqRz9Gf8PWQWL.WK.pt7ORNEAZlv1hep7iCtsAbjnFeYPqtiXi4sTv.KoVBqyjkT79DW7v7i_jLHQZ27SZJ10mT21B42YGeDeKPwOFW6y0hGi74rK58SnZPNBITwlCg6kRvaS_B2MeY1hjUjAP5Q5_Cp1BGmYj1wS93EzXTRllTBDNEeOdPbVGXtghqPk5rsnoBlmw69Fzt22rowg18TaLtR4Re8H8GIVjHjhOsf_X0mcxMzBbLv4"};var cpo = document.createElement('script');cpo.src = '/cdn-cgi/challenge-platform/h/g/orchestrate/chl_page/v1?ray=913fa8b5cba9ce09';window._cf_chl_opt.cOgUHash = location.hash === '' && location.href.indexOf('#') !== -1 ? '#' : location.hash;window._cf_chl_opt.cOgUQuery = location.search === '' && location.href.slice(0, location.href.length - window._cf_chl_opt.cOgUHash.length).indexOf('?') !== -1 ? '?' : location.search;if (window.history && window.history.replaceState) {var ogU = location.pathname + window._cf_chl_opt.cOgUQuery + window._cf_chl_opt.cOgUHash;history.replaceState(null, null, "\/doi\/10.7326\/M20-3012?__cf_chl_rt_tk=7Cye1WvoQ9CVkyZ4asK1mOhP.XIQ47jGUTO0btua9do-1739898924-1.0.1.1-vLrdYhEmUJqJy1_UcnromvH9O.vYE.UEJFrR4x7Of.E" + window._cf_chl_opt.cOgUHash);cpo.onload = function() {history.replaceState(null, null, ogU);}}document.getElementsByTagName('head')[0].appendChild(cpo);}());</script></body></html>