{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:01:17Z","timestamp":1792785677587,"version":"4.5.0"},"reference-count":47,"publisher":"IOP Publishing","issue":"20","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"}],"funder":[{"name":"Division of Cancer Prevention, National Cancer Institute","award":["R01CA271330"],"award-info":[{"award-number":["R01CA271330"]}]},{"name":"University of Wisconsin Carbone Cancer Center","award":["P30CA014520"],"award-info":[{"award-number":["P30CA014520"]}],"id":[{"id":"https:\/\/ror.org\/01e4byj08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Norris Cotton Cancer Center","award":["P30CA023108"],"award-info":[{"award-number":["P30CA023108"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Phys. Med. Biol."],"published-print":{"date-parts":[[2026,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Ultra-high dose-rate (UHDR) irradiation reduces normal-tissue toxicity as compared conventional dose-rate irradiation, known as the FLASH effect, yet the underlying radiochemical mechanisms remain poorly understood. Direct measurements rely upon longer lived water-radiolysis species such as aqueous electrons (e\n                    <jats:sub>aq<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) and oxygen, to infer behaviors of toxic species leading to tissue damage. This study uses kinetic modeling to identify which chemical pathways exhibit dose-rate-dependent behavior and can be used to correlate experiments.\n                    <jats:italic>Approach.<\/jats:italic>\n                    A comprehensive physicochemical model of water radiolysis was developed, incorporating 16 molecular species and 56 coupled reaction rate equations, with pulsed-beam structures matched to published UHDR electron irradiation experiments. Simulations were performed across a range of oxygen tensions (0.1%\u201310% O\n                    <jats:sub>2<\/jats:sub>\n                    ) and dose-rate conditions (0.3\u2013300 Gy s\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). Model predictions were validated against experimental measurements of e\n                    <jats:sub>aq<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    transients, and oxygen-consumption\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . They also were compared to prior computational models.\n                    <jats:italic>Main results.<\/jats:italic>\n                    Modeled lifetimes of e\n                    <jats:sub>aq<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    matched experiments across O\n                    <jats:sub>2<\/jats:sub>\n                    concentrations and showed that &gt;90% of scavenging occurs via O\n                    <jats:sub>2<\/jats:sub>\n                    and reactions with proteins, with radical\u2013radical recombination contributing &lt;5% even at 300 Gy s\n                    <jats:sup>\u22121<\/jats:sup>\n                    . The lifetimes of OH\u00b7 radicals were similarly dominated by protein scavenging, with recombination pathways remaining minor (&lt;5%) with UHDR. Modeled oxygen consumption matched the magnitude and dose-rate dependence observed in published experiments. The results indicated a primary dose-rate sensitive pathway, the reaction between hydroperoxyl radical (HO\n                    <jats:sub>2<\/jats:sub>\n                    \u00b7) and superoxide (O\n                    <jats:sub>2<\/jats:sub>\n                    \u00b7\n                    <jats:sup>\u2212<\/jats:sup>\n                    ). Peroxyl-radical formation decreased at UHDR within oxygen tensions (\u22485\u201320 mmHg) corresponding to the experimentally observed FLASH oxygen-window.\n                    <jats:italic>Significance.<\/jats:italic>\n                    This work identifies specific radiochemical pathways that exhibit true dose-rate sensitivity and clarifies which proposed FLASH mechanisms are unsupported by homogeneous-phase radical kinetics. Radical\u2013radical recombination contributes too little (&lt;5%) to account for known FLASH sparing at UHDR, whereas peroxyl-radical and HO\n                    <jats:sub>2<\/jats:sub>\n                    \u00b7\/O\n                    <jats:sub>2<\/jats:sub>\n                    \u00b7\n                    <jats:sup>\u2212<\/jats:sup>\n                    chemistry shows dose-rate-dependent behavior within physiologic oxygen tensions associated with FLASH. Although constrained by simplified aqueous conditions lacking scavengers and tissue heterogeneity, the model provides mechanistic insight into the radiochemical regimes dominating the homogeneous phase chemistry.\n                  <\/jats:p>","DOI":"10.1088\/1361-6560\/aeabe5","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:53:23Z","timestamp":1790204003000},"page":"205012","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Physicochemical modeling of electron FLASH to identify the roles of oxygen, aqueous electrons and causal radical recombination effects underlying them"],"prefix":"10.1088","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9829-1794","authenticated-orcid":true,"given":"William S","family":"Thomas","sequence":"first","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8749-1716","authenticated-orcid":false,"given":"Xu","family":"Cao","sequence":"additional","affiliation":[{"name":"Thayer School of Engineering at Dartmouth"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-0297","authenticated-orcid":true,"given":"David J","family":"Gladstone","sequence":"additional","affiliation":[{"name":"Thayer School of Engineering at Dartmouth"},{"name":"Geisel School of Medicine at Dartmouth"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold M","family":"Swartz","sequence":"additional","affiliation":[{"name":"Thayer School of Engineering at Dartmouth"},{"name":"Geisel School of Medicine at Dartmouth"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-670X","authenticated-orcid":false,"given":"Brian W","family":"Pogue","sequence":"additional","affiliation":[{"name":"University of Wisconsin School of Medicine and Public Health"},{"name":"Thayer School of Engineering at Dartmouth"},{"name":"Geisel School of Medicine at Dartmouth"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"pmbaeabe5bib1","doi-asserted-by":"publisher","DOI":"10.1002\/mp.17972","type":"journal-article","article-title":"A Monte Carlo simulation framework for investigating the effect of inter-track coupling on H2O2 productions at ultra-high dose rates","volume":"52","author":"Abolfath","year":"2025","journal-title":"Med. 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