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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cortical Responsiveness to Nociceptive Stimuli in Patients with Chronic Disorders of Consciousness: Do C-Fiber Laser Evoked Potentials Have a Role?</title><author><name sortKey="Naro, Antonino" sort="Naro, Antonino" uniqKey="Naro A" first="Antonino" last="Naro">Antonino Naro</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Russo, Margherita" sort="Russo, Margherita" uniqKey="Russo M" first="Margherita" last="Russo">Margherita Russo</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Leo, Antonino" sort="Leo, Antonino" uniqKey="Leo A" first="Antonino" last="Leo">Antonino Leo</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Rifici, Carmela" sort="Rifici, Carmela" uniqKey="Rifici C" first="Carmela" last="Rifici">Carmela Rifici</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Pollicino, Patrizia" sort="Pollicino, Patrizia" uniqKey="Pollicino P" first="Patrizia" last="Pollicino">Patrizia Pollicino</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Bramanti, Placido" sort="Bramanti, Placido" uniqKey="Bramanti P" first="Placido" last="Bramanti">Placido Bramanti</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Calabr, Rocco Salvatore" sort="Calabr, Rocco Salvatore" uniqKey="Calabr R" first="Rocco Salvatore" last="Calabr">Rocco Salvatore Calabr</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26674634</idno><idno type="pmc">4684218</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684218</idno><idno type="RBID">PMC:4684218</idno><idno type="doi">10.1371/journal.pone.0144713</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000041</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000041</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cortical Responsiveness to Nociceptive Stimuli in Patients with Chronic Disorders of Consciousness: Do C-Fiber Laser Evoked Potentials Have a Role?</title><author><name sortKey="Naro, Antonino" sort="Naro, Antonino" uniqKey="Naro A" first="Antonino" last="Naro">Antonino Naro</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Russo, Margherita" sort="Russo, Margherita" uniqKey="Russo M" first="Margherita" last="Russo">Margherita Russo</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Leo, Antonino" sort="Leo, Antonino" uniqKey="Leo A" first="Antonino" last="Leo">Antonino Leo</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Rifici, Carmela" sort="Rifici, Carmela" uniqKey="Rifici C" first="Carmela" last="Rifici">Carmela Rifici</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Pollicino, Patrizia" sort="Pollicino, Patrizia" uniqKey="Pollicino P" first="Patrizia" last="Pollicino">Patrizia Pollicino</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Bramanti, Placido" sort="Bramanti, Placido" uniqKey="Bramanti P" first="Placido" last="Bramanti">Placido Bramanti</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author><author><name sortKey="Calabr, Rocco Salvatore" sort="Calabr, Rocco Salvatore" uniqKey="Calabr R" first="Rocco Salvatore" last="Calabr">Rocco Salvatore Calabr</name><affiliation><nlm:aff id="aff001"></nlm:aff></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>It has been shown that the presence of Aδ-fiber laser evoked potentials (Aδ-LEP) in patients suffering from chronic disorders of consciousness (DOC), such as vegetative state (VS) and minimally conscious state (MCS), may be the expression of a residual cortical pain arousal. Interestingly, the study of C-fiber LEP (C-LEP) could be useful in the assessment of cortical pain arousal in the DOC individuals who lack of Aδ-LEP. To this end, we enrolled 38 DOC patients following post-anoxic or post-traumatic brain injury, who met the international criteria for VS and MCS diagnosis. Each subject was clinically evaluated, through the coma recovery scale-revised (CRS-R) and the nociceptive coma scale-revised (NCS-R), and electrophysiologically tested by means of a solid-state laser for Aδ-LEP and C-LEP. VS individuals showed increased latencies and reduced amplitudes of both the Aδ-LEP and C-LEP components in comparison to MCS patients. Although nearly all of the patients had both the LEP components, some VS individuals showed only the C-LEP ones. Notably, such patients had a similar NCS-R score to those having both the LEP components. Hence, we could hypothesize that C-LEP generators may be rearranged or partially spared in order to still guarantee cortical pain arousal when Aδ-LEP generators are damaged. Therefore, the residual presence of C-LEP should be assessed when Aδ-LEP are missing, since a potential pain experience should be still present in some patients, so to properly initiate, or adapt, the most appropriate pain treatment.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Giacino, J" uniqKey="Giacino J">J Giacino</name></author><author><name sortKey="Ashwal, S" uniqKey="Ashwal S">S Ashwal</name></author><author><name sortKey="Childs, N" uniqKey="Childs N">N Childs</name></author><author><name sortKey="Cranford, R" uniqKey="Cranford R">R Cranford</name></author><author><name sortKey="Jennett, B" uniqKey="Jennett B">B Jennett</name></author><author><name sortKey="Katz, Di" uniqKey="Katz D">DI Katz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kassubek, J" uniqKey="Kassubek J">J Kassubek</name></author><author><name sortKey="Juengling, Fd" uniqKey="Juengling 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26674634</article-id><article-id pub-id-type="pmc">4684218</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0144713</article-id><article-id pub-id-type="publisher-id">PONE-D-15-25743</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Cortical Responsiveness to Nociceptive Stimuli in Patients with Chronic Disorders of Consciousness: Do C-Fiber Laser Evoked Potentials Have a Role?</article-title><alt-title alt-title-type="running-head">CLEP in DOC Diagnosis</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Naro</surname><given-names>Antonino</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Russo</surname><given-names>Margherita</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Leo</surname><given-names>Antonino</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Rifici</surname><given-names>Carmela</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Pollicino</surname><given-names>Patrizia</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Bramanti</surname><given-names>Placido</given-names></name><xref ref-type="aff" rid="aff001"></xref></contrib><contrib contrib-type="author"><name><surname>Calabrò</surname><given-names>Rocco Salvatore</given-names></name><xref rid="cor001" ref-type="corresp">*</xref><xref ref-type="aff" rid="aff001"></xref></contrib></contrib-group><aff id="aff001"><addr-line>IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Ward</surname><given-names>Lawrence M</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of British Columbia, CANADA</addr-line></aff><author-notes><fn fn-type="conflict" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: AN MR RSC. Performed the experiments: AN MR AL CR PP. Analyzed the data: AN. Contributed reagents/materials/analysis tools: CR PP AL PB. Wrote the paper: AN RSC PB.</p></fn><corresp id="cor001">* E-mail: <email>salbro77@tiscali.it</email></corresp></author-notes><pub-date pub-type="epub"><day>16</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>10</volume><issue>12</issue><elocation-id>e0144713</elocation-id><history><date date-type="received"><day>12</day><month>6</month><year>2015</year></date><date date-type="accepted"><day>23</day><month>11</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 Naro et al</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Naro et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0144713.pdf"></self-uri><abstract><p>It has been shown that the presence of Aδ-fiber laser evoked potentials (Aδ-LEP) in patients suffering from chronic disorders of consciousness (DOC), such as vegetative state (VS) and minimally conscious state (MCS), may be the expression of a residual cortical pain arousal. Interestingly, the study of C-fiber LEP (C-LEP) could be useful in the assessment of cortical pain arousal in the DOC individuals who lack of Aδ-LEP. To this end, we enrolled 38 DOC patients following post-anoxic or post-traumatic brain injury, who met the international criteria for VS and MCS diagnosis. Each subject was clinically evaluated, through the coma recovery scale-revised (CRS-R) and the nociceptive coma scale-revised (NCS-R), and electrophysiologically tested by means of a solid-state laser for Aδ-LEP and C-LEP. VS individuals showed increased latencies and reduced amplitudes of both the Aδ-LEP and C-LEP components in comparison to MCS patients. Although nearly all of the patients had both the LEP components, some VS individuals showed only the C-LEP ones. Notably, such patients had a similar NCS-R score to those having both the LEP components. Hence, we could hypothesize that C-LEP generators may be rearranged or partially spared in order to still guarantee cortical pain arousal when Aδ-LEP generators are damaged. Therefore, the residual presence of C-LEP should be assessed when Aδ-LEP are missing, since a potential pain experience should be still present in some patients, so to properly initiate, or adapt, the most appropriate pain treatment.</p></abstract><funding-group><funding-statement>The authors received no specific funding for this work.</funding-statement></funding-group><counts><fig-count count="1"></fig-count><table-count count="2"></table-count><page-count count="12"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the paper.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the paper.</p></notes></front><body><sec sec-type="intro" id="sec001"><title>Introduction</title><p>In contrast to comatose patients, who lack of both wakefulness and awareness, individuals suffering from Vegetative State (VS) are awake but unaware of the environment and cannot purposefully respond to stimuli, whilst patients affected by Minimally Conscious State (MCS) are awake but limitedly aware and may show some purposeful behaviors [<xref rid="pone.0144713.ref001" ref-type="bibr">1</xref>–<xref rid="pone.0144713.ref002" ref-type="bibr">2</xref>].</p><p>Pain perception in chronic disorder of consciousness (DOC) represents a controversial issue, since there is growing evidence concerning the presence of residual pain experience even in some VS individuals [<xref rid="pone.0144713.ref003" ref-type="bibr">3</xref>–<xref rid="pone.0144713.ref006" ref-type="bibr">6</xref>]. Taking into account that such patients have a strongly limited repertoire of communication, and that the inability to communicate could not exclude a possible pain experience, the issues of nociception and pain in such individuals are of ethic and clinical importance, especially concerning a proper diagnosis and an adequate pain treatment.</p><p>Laser evoked potentials (LEP) are extensively used in pain study, since the laser stimulation can selectively activate the nociceptive pathways [<xref rid="pone.0144713.ref007" ref-type="bibr">7</xref>]. Laser stimulation typically evokes several LEP components, reflecting the activity of multiple cortical assemblies within different cortical areas (including primary and secondary somatosensory cortices, insula, and anterior cingulate cortex) that process either nociceptive or non-nociceptive inputs [<xref rid="pone.0144713.ref008" ref-type="bibr">8</xref>–<xref rid="pone.0144713.ref009" ref-type="bibr">9</xref>]. The N1P1 complex reflects an early stage of sensory processing at unaware level, whereas the N2P2 wave is related to the stimulus saliency, independently from the nociceptive nature of the incoming stimulus [<xref rid="pone.0144713.ref008" ref-type="bibr">8</xref>,<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref012" ref-type="bibr">12</xref>].</p><p>Although the Aδ-fiber LEP (Aδ-LEP) amplitudes and latencies have been put in relation with the intensity of nociceptive pain [<xref rid="pone.0144713.ref012" ref-type="bibr">12</xref>], it has been shown that LEP depend on non-specific neural pathways within the so-called pain-matrix, so that LEP characteristics cannot be considered as a marker of pain-related cognitive processes [<xref rid="pone.0144713.ref008" ref-type="bibr">8</xref>,<xref rid="pone.0144713.ref013" ref-type="bibr">13</xref>–<xref rid="pone.0144713.ref014" ref-type="bibr">14</xref>], but only a sign of a relevant-stimulus dependent arousal [<xref rid="pone.0144713.ref008" ref-type="bibr">8</xref>–<xref rid="pone.0144713.ref015" ref-type="bibr">15</xref>].</p><p>Interestingly, recent LEP studies have shown reliable cortical responses following nociceptive stimuli in VS and MCS individuals [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>], regardless of the preservation of non-nociceptive somatosensory evoked potentials. Such issues may suggest that “the cortical awareness toward pain stimulus may be a basal function for survival in state of vegetative autonomy, despite the absence of evident motor reaction to nociceptive inputs”. Therefore, nociceptive stimuli may be processed even in severe DOC patients [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>].</p><p>Nevertheless, whereas Aδ-LEP have been studied in DOC patients [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>], the assessment of C-fiber LEP (C-LEP) has not been yet performed in DOC individuals. C-LEP have been shown to be generated by C-fiber activation through laser stimuli with specific characteristics, but they probably share common cortical generators with Aδ-LEP [<xref rid="pone.0144713.ref016" ref-type="bibr">16</xref>–<xref rid="pone.0144713.ref018" ref-type="bibr">18</xref>].</p><p>We hypothesized that the VS patients who lack of Aδ-LEP could show a cortical pain arousal, as demonstrated by C-LEP preservation, and they therefore might experience pain. Therefore, we tested this hypothesis by assessing the presence and the characteristics of C-LEP elicited by means of a solid-state laser device in a sample of DOC patients lacking of Aδ-LEP.</p></sec><sec sec-type="materials|methods" id="sec002"><title>Materials and Methods</title><p>The study was conducted in accordance with the Declaration of Helsinki and was approved by Ethic Committee of IRCCS Centro Neurolesi “Bonino-Pulejo” all the HC subjects and the legal guardian of the DOC patients gave written informed consent before any study-related procedures were performed. Moreover, the families of the patients gave written informed consent to publish the potentially identifying case details.</p><sec id="sec003"><title>Subjects</title><p>We enrolled 38 DOC subjects affected by anoxic or traumatic brain injury, who met the international criteria for VS and MCS diagnosis [<xref rid="pone.0144713.ref001" ref-type="bibr">1</xref>–<xref rid="pone.0144713.ref002" ref-type="bibr">2</xref>]. The exclusion criteria were: cutaneous or systemic disease contraindicating LEP execution; critical conditions (e.g. mechanical ventilation, hemodynamic instability); peripheral nervous system damage; brainstem lesions. As control group, we enrolled 15 healthy age-matched individuals (HC). We summarized the detailed clinic and demographic characteristics of DOC patients in <xref rid="pone.0144713.t001" ref-type="table">Table 1</xref>. All of the patients and the HC had previously performed an Aδ-LEP study, according to the standard procedures of Cruccu and coworkers [<xref rid="pone.0144713.ref019" ref-type="bibr">19</xref>–<xref rid="pone.0144713.ref020" ref-type="bibr">20</xref>].</p><table-wrap id="pone.0144713.t001" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0144713.t001</object-id><label>Table 1</label><caption><title>Shows the clinic-demographic characteristics and the Aδ-LEP and C- LEP amplitude and latency values (individual mean of each laser stimulation run ±SD, SD of the two laser stimulation runs, and <italic>group averages±SD</italic>).</title><p>Patients showing only the N2P2 CLEP are marked in bold.</p></caption><alternatives><graphic id="pone.0144713.t001g" xlink:href="pone.0144713.t001"></graphic><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col></colgroup><thead><tr><th rowspan="2" align="center" colspan="1">et</th><th rowspan="2" align="center" colspan="1">age</th><th rowspan="2" align="center" colspan="1">gen</th><th rowspan="2" align="center" colspan="1">dd</th><th rowspan="2" align="center" colspan="1">CRS</th><th rowspan="2" align="center" colspan="1">NCS</th><th colspan="12" align="center" rowspan="1">Aδ-LEP</th><th colspan="12" align="center" rowspan="1">C-LEP</th></tr><tr><th colspan="2" align="center" rowspan="1">N1(ms)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N1(μV)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N2(ms)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N2(μV)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N1(ms)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N1(μV)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N2(ms)</th><th align="center" rowspan="1" colspan="1">SD</th><th colspan="2" align="center" rowspan="1">N2(μV)</th><th align="center" rowspan="1" colspan="1">SD</th></tr></thead><tbody><tr><td colspan="30" align="center" rowspan="1"><bold>MCS (n = 15)</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">64</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">14</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">127±16</td><td align="center" rowspan="1" colspan="1">130±12</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">0.005</td><td align="center" rowspan="1" colspan="1">172±22</td><td align="center" rowspan="1" colspan="1">170±12</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">0.7</td><td align="center" rowspan="1" colspan="1">213±27</td><td align="center" rowspan="1" colspan="1">222±16</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">3.4±0.5</td><td align="center" rowspan="1" colspan="1">0.03</td><td align="center" rowspan="1" colspan="1">306±40</td><td align="center" rowspan="1" colspan="1">314±49</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">6.6±1</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">0.4</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">58</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">13</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">138±18</td><td align="center" rowspan="1" colspan="1">137±11</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">188±24</td><td align="center" rowspan="1" colspan="1">185±16</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">6.1±1</td><td align="center" rowspan="1" colspan="1">6.4±1</td><td align="center" rowspan="1" colspan="1">0.3</td><td align="center" rowspan="1" colspan="1">213±27</td><td align="center" rowspan="1" colspan="1">210±21</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">5.4±0.5</td><td align="center" rowspan="1" colspan="1">5.7±0.5</td><td align="center" rowspan="1" colspan="1">0.2</td><td align="center" rowspan="1" colspan="1">365±47</td><td align="center" rowspan="1" colspan="1">361±28</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">4.3±0.5</td><td align="center" rowspan="1" colspan="1">4.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">60</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">13</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">168±22</td><td align="center" rowspan="1" colspan="1">165±11</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">6.4±0.5</td><td align="center" rowspan="1" colspan="1">6.6±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">185±24</td><td align="center" rowspan="1" colspan="1">192±12</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">5.4±1</td><td align="center" rowspan="1" colspan="1">5.2±1</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">181±23</td><td align="center" rowspan="1" colspan="1">177±28</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">4.5±0.5</td><td align="center" rowspan="1" colspan="1">4.7±0.5</td><td align="center" rowspan="1" colspan="1">0.2</td><td align="center" rowspan="1" colspan="1">275±36</td><td align="center" rowspan="1" colspan="1">264±48</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">48</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">33</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">141±18</td><td align="center" rowspan="1" colspan="1">145±18</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1.1±0.5</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">231±30</td><td align="center" rowspan="1" colspan="1">237±13</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">5.4±1</td><td align="center" rowspan="1" colspan="1">5.4±1</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">216±28</td><td align="center" rowspan="1" colspan="1">207±36</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">3.4±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">347±44</td><td align="center" rowspan="1" colspan="1">343±60</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">37</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">26</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">152±20</td><td align="center" rowspan="1" colspan="1">148±18</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">190±25</td><td align="center" rowspan="1" colspan="1">194±16</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">1.1±1</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">226±29</td><td align="center" rowspan="1" colspan="1">234±15</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">5.5±0.5</td><td align="center" rowspan="1" colspan="1">5.4±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">275±36</td><td align="center" rowspan="1" colspan="1">279±28</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">0.2</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">66</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">23</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">178±23</td><td align="center" rowspan="1" colspan="1">171±14</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">183±24</td><td align="center" rowspan="1" colspan="1">182±14</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2.1±1</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">247±32</td><td align="center" rowspan="1" colspan="1">247±14</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">6.7±0.5</td><td align="center" rowspan="1" colspan="1">6.1±0.5</td><td align="center" rowspan="1" colspan="1">0.4</td><td align="center" rowspan="1" colspan="1">308±39</td><td align="center" rowspan="1" colspan="1">301±22</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">62</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">30</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">127±16</td><td align="center" rowspan="1" colspan="1">125±10</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">5.2±0.5</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">164±21</td><td align="center" rowspan="1" colspan="1">167±19</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">7.3±1</td><td align="center" rowspan="1" colspan="1">7.6±1</td><td align="center" rowspan="1" colspan="1">0.2</td><td align="center" rowspan="1" colspan="1">181±23</td><td align="center" rowspan="1" colspan="1">179±14</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">3.6±0.5</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">0.4</td><td align="center" rowspan="1" colspan="1">291±38</td><td align="center" rowspan="1" colspan="1">296±53</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">61</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">18</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">131±17</td><td align="center" rowspan="1" colspan="1">135±13</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">1.1±0.5</td><td align="center" rowspan="1" colspan="1">0.003</td><td align="center" rowspan="1" colspan="1">200±26</td><td align="center" rowspan="1" colspan="1">201±15</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">17±1</td><td align="center" rowspan="1" colspan="1">14±1</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">209±27</td><td align="center" rowspan="1" colspan="1">220±17</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">4.4±0.5</td><td align="center" rowspan="1" colspan="1">4.4±0.5</td><td align="center" rowspan="1" colspan="1">0.04</td><td align="center" rowspan="1" colspan="1">241±31</td><td align="center" rowspan="1" colspan="1">244±19</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">1.4±0.5</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">1.3</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">75</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">24</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">114±15</td><td align="center" rowspan="1" colspan="1">118±14</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">1.2±0.5</td><td align="center" rowspan="1" colspan="1">0.05</td><td align="center" rowspan="1" colspan="1">159±21</td><td align="center" rowspan="1" colspan="1">152±15</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">6.4±1</td><td align="center" rowspan="1" colspan="1">6.4±1</td><td align="center" rowspan="1" colspan="1">0.001</td><td align="center" rowspan="1" colspan="1">276±36</td><td align="center" rowspan="1" colspan="1">275±17</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">312±40</td><td align="center" rowspan="1" colspan="1">302±15</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">4±1</td><td align="center" rowspan="1" colspan="1">0.03</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">60</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">32</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">122±16</td><td align="center" rowspan="1" colspan="1">124±18</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">131±17</td><td align="center" rowspan="1" colspan="1">134±19</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">7.6±1</td><td align="center" rowspan="1" colspan="1">7.7±1</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">315±41</td><td align="center" rowspan="1" colspan="1">309±25</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">3.4±0.5</td><td align="center" rowspan="1" colspan="1">3.4±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">275±36</td><td align="center" rowspan="1" colspan="1">225±15</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">5.3±1</td><td align="center" rowspan="1" colspan="1">5.5±1</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">57</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">33</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">133±17</td><td align="center" rowspan="1" colspan="1">132±18</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.4±0.5</td><td align="center" rowspan="1" colspan="1">4.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">179±23</td><td align="center" rowspan="1" colspan="1">180±13</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">14±2</td><td align="center" rowspan="1" colspan="1">13±1</td><td align="center" rowspan="1" colspan="1">0.7</td><td align="center" rowspan="1" colspan="1">218±28</td><td align="center" rowspan="1" colspan="1">207±17</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">5.8±0.5</td><td align="center" rowspan="1" colspan="1">5.7±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">347±45</td><td align="center" rowspan="1" colspan="1">346±20</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">68</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">116±15</td><td align="center" rowspan="1" colspan="1">119±14</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">0.04</td><td align="center" rowspan="1" colspan="1">185±24</td><td align="center" rowspan="1" colspan="1">185±14</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">10±2</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">0.2</td><td align="center" rowspan="1" colspan="1">227±28</td><td align="center" rowspan="1" colspan="1">237±12</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">3.0±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">278±36</td><td align="center" rowspan="1" colspan="1">286±49</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">5.3±0.5</td><td align="center" rowspan="1" colspan="1">5.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">59</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">113±15</td><td align="center" rowspan="1" colspan="1">115±13</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">5.4±0.5</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">149±19</td><td align="center" rowspan="1" colspan="1">145±12</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">218±28</td><td align="center" rowspan="1" colspan="1">208±12</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">5.4±0.5</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">237±31</td><td align="center" rowspan="1" colspan="1">227±21</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">66</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">29</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">109±14</td><td align="center" rowspan="1" colspan="1">106±19</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">185±24</td><td align="center" rowspan="1" colspan="1">191±16</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">0.4</td><td align="center" rowspan="1" colspan="1">253±33</td><td align="center" rowspan="1" colspan="1">253±14</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">5.9±0.5</td><td align="center" rowspan="1" colspan="1">5.8±0.5</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">255±33</td><td align="center" rowspan="1" colspan="1">262±42</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">57</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">32</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">128±17</td><td align="center" rowspan="1" colspan="1">131±11</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">188±24</td><td align="center" rowspan="1" colspan="1">188±14</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">8.2±1</td><td align="center" rowspan="1" colspan="1">7.5±1</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">237±31</td><td align="center" rowspan="1" colspan="1">224±19</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">4.3±0.5</td><td align="center" rowspan="1" colspan="1">4.3±0.5</td><td align="center" rowspan="1" colspan="1">0.04</td><td align="center" rowspan="1" colspan="1">324±42</td><td align="center" rowspan="1" colspan="1">328±60</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">4.4±1</td><td align="center" rowspan="1" colspan="1">4.4±0.5</td><td align="center" rowspan="1" colspan="1">0.02</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"><italic>60±9</italic></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"><italic>23±8</italic></td><td align="center" rowspan="1" colspan="1"><italic>16±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>7±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>130±19</italic></td><td align="center" rowspan="1" colspan="1"><italic>131±17</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>2</italic>.<italic>9±1</italic>.<italic>8</italic></td><td align="center" rowspan="1" colspan="1"><italic>2</italic>.<italic>8±1</italic>.<italic>8</italic></td><td align="center" rowspan="1" colspan="1"><italic>0</italic>.<italic>03±0</italic>.<italic>05</italic></td><td align="center" rowspan="1" colspan="1"><italic>178±25</italic></td><td align="center" rowspan="1" colspan="1"><italic>179±27</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>7</italic>.<italic>6±4</italic>.<italic>1</italic></td><td align="center" rowspan="1" colspan="1"><italic>7</italic>.<italic>4±3</italic>.<italic>7</italic></td><td align="center" rowspan="1" colspan="1"><italic>0</italic>.<italic>1</italic></td><td align="center" rowspan="1" colspan="1"><italic>235±34</italic></td><td align="center" rowspan="1" colspan="1"><italic>233±35</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±3</italic></td><td align="center" rowspan="1" colspan="1"><italic>4</italic>.<italic>6±1</italic>.<italic>2</italic></td><td align="center" rowspan="1" colspan="1"><italic>4</italic>.<italic>5±1</italic>.<italic>2</italic></td><td align="center" rowspan="1" colspan="1"><italic>0</italic>.<italic>1</italic></td><td align="center" rowspan="1" colspan="1"><italic>290±36</italic></td><td align="center" rowspan="1" colspan="1"><italic>291±40</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>3±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>0</italic>.<italic>2±0</italic>.<italic>3</italic></td></tr><tr><td colspan="30" align="center" rowspan="1"><bold>VS (n = 23)</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">62</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">167±30</td><td align="center" rowspan="1" colspan="1">166±12</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.4±0.5</td><td align="center" rowspan="1" colspan="1">4.1±0.6</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">231±42</td><td align="center" rowspan="1" colspan="1">230±25</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">13±2</td><td align="center" rowspan="1" colspan="1">11±0.6</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">344±63</td><td align="center" rowspan="1" colspan="1">348±44</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.05</td><td align="center" rowspan="1" colspan="1">448±82</td><td align="center" rowspan="1" colspan="1">446±54</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">3±1</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">64</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">25</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">170±31</td><td align="center" rowspan="1" colspan="1">165±11</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">215±39</td><td align="center" rowspan="1" colspan="1">216±10</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">9±2</td><td align="center" rowspan="1" colspan="1">13±0.5</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">314±57</td><td align="center" rowspan="1" colspan="1">316±41</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.8</td><td align="center" rowspan="1" colspan="1">410±75</td><td align="center" rowspan="1" colspan="1">405±44</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">3±1</td><td align="center" rowspan="1" colspan="1">3.5±0.5</td><td align="center" rowspan="1" colspan="1">0.4</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">62</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">19</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">129±24</td><td align="center" rowspan="1" colspan="1">125±19</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">179±33</td><td align="center" rowspan="1" colspan="1">189±11</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">8±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">442±81</td><td align="center" rowspan="1" colspan="1">344±35</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">1.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1"><italic>596±109</italic></td><td align="center" rowspan="1" colspan="1">592±56</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">7±1</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">3</td></tr><tr><td align="center" rowspan="1" colspan="1"><bold>T</bold></td><td align="center" rowspan="1" colspan="1"><bold>50</bold></td><td align="center" rowspan="1" colspan="1"><bold>M</bold></td><td align="center" rowspan="1" colspan="1"><bold>11</bold></td><td align="center" rowspan="1" colspan="1"><bold>7</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>157±29</bold></td><td align="center" rowspan="1" colspan="1"><bold>159±17</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>5±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>2±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>423±77</bold></td><td align="center" rowspan="1" colspan="1"><bold>326±32</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>1.1±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>1±0.5</bold></td><td align="center" rowspan="1" colspan="1">0.04</td><td align="center" rowspan="1" colspan="1"><bold>531±97</bold></td><td align="center" rowspan="1" colspan="1"><bold>532±73</bold></td><td align="center" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" rowspan="1" colspan="1"><bold>6±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>6.6±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.4</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">67</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">147±27</td><td align="center" rowspan="1" colspan="1">143±11</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">4±1</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">217±40</td><td align="center" rowspan="1" colspan="1">213±19</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">6.3±1</td><td align="center" rowspan="1" colspan="1">6.5±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">461±66</td><td align="center" rowspan="1" colspan="1">463±35</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">1.1±0.5</td><td align="center" rowspan="1" colspan="1">1.4</td><td align="center" rowspan="1" colspan="1">382±70</td><td align="center" rowspan="1" colspan="1">405±18</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">7±1</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"><bold>A</bold></td><td align="center" rowspan="1" colspan="1"><bold>59</bold></td><td align="center" rowspan="1" colspan="1"><bold>M</bold></td><td align="center" rowspan="1" colspan="1"><bold>32</bold></td><td align="center" rowspan="1" colspan="1"><bold>6</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>133±24</bold></td><td align="center" rowspan="1" colspan="1"><bold>136±13</bold></td><td align="center" rowspan="1" colspan="1"><bold>3</bold></td><td align="center" rowspan="1" colspan="1"><bold>5±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>4±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>314±57</bold></td><td align="center" rowspan="1" colspan="1"><bold>319±29</bold></td><td align="center" rowspan="1" colspan="1"><bold>3</bold></td><td align="center" rowspan="1" colspan="1"><bold>1±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>3.2±0.5</bold></td><td align="center" rowspan="1" colspan="1">1.5</td><td align="center" rowspan="1" colspan="1"><bold>398±73</bold></td><td align="center" rowspan="1" colspan="1"><bold>408±32</bold></td><td align="center" rowspan="1" colspan="1"><bold>7</bold></td><td align="center" rowspan="1" colspan="1"><bold>2±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>8±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>4</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">58</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">158±29</td><td align="center" rowspan="1" colspan="1">155±11</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">4±1</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">266±59</td><td align="center" rowspan="1" colspan="1">267±35</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">7±1</td><td align="center" rowspan="1" colspan="1">9±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">397±72</td><td align="center" rowspan="1" colspan="1">393±34</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">1.1±0.5</td><td align="center" rowspan="1" colspan="1">0.7</td><td align="center" rowspan="1" colspan="1">446±81</td><td align="center" rowspan="1" colspan="1">442±16</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">3±1</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">80</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">18</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">155±28</td><td align="center" rowspan="1" colspan="1">153±18</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">249±38</td><td align="center" rowspan="1" colspan="1">247±13</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">10±2</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">485±59</td><td align="center" rowspan="1" colspan="1">492±56</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">0.03</td><td align="center" rowspan="1" colspan="1">382±80</td><td align="center" rowspan="1" colspan="1">387±55</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">2</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">70</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">29</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">140±26</td><td align="center" rowspan="1" colspan="1">143±11</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">4±1</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">345±63</td><td align="center" rowspan="1" colspan="1">343±20</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">2±0.5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1"><bold>T</bold></td><td align="center" rowspan="1" colspan="1"><bold>59</bold></td><td align="center" rowspan="1" colspan="1"><bold>F</bold></td><td align="center" rowspan="1" colspan="1"><bold>27</bold></td><td align="center" rowspan="1" colspan="1"><bold>5</bold></td><td align="center" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" rowspan="1" colspan="1"><bold>158±29</bold></td><td align="center" rowspan="1" colspan="1"><bold>154±13</bold></td><td align="center" rowspan="1" colspan="1"><bold>3</bold></td><td align="center" rowspan="1" colspan="1"><bold>5±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>4±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>323±55</bold></td><td align="center" rowspan="1" colspan="1"><bold>338±49</bold></td><td align="center" rowspan="1" colspan="1"><bold>4</bold></td><td align="center" rowspan="1" colspan="1"><bold>2.2±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>2.1±0.5</bold></td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1"><bold>361±66</bold></td><td align="center" rowspan="1" colspan="1"><bold>363±66</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>5±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>6±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.1</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">64</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">116±21</td><td align="center" rowspan="1" colspan="1">119±18</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">472±59</td><td align="center" rowspan="1" colspan="1">464±27</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">63</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">24</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">179±33</td><td align="center" rowspan="1" colspan="1">180±14</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5±1</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">400±73</td><td align="center" rowspan="1" colspan="1">404±19</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">28</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">16</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">145±26</td><td align="center" rowspan="1" colspan="1">145±10</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">466±81</td><td align="center" rowspan="1" colspan="1">470±59</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">0.8</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">48</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">32</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">169±31</td><td align="center" rowspan="1" colspan="1">169±11</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">4±1</td><td align="center" rowspan="1" colspan="1">7±0.5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">177±32</td><td align="center" rowspan="1" colspan="1">182±14</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">7±1</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">443±81</td><td align="center" rowspan="1" colspan="1">434±55</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">3.3±0.5</td><td align="center" rowspan="1" colspan="1">0.2</td><td align="center" rowspan="1" colspan="1">555±61</td><td align="center" rowspan="1" colspan="1">557±63</td><td align="center" rowspan="1" colspan="1">1.4</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">8.2±1</td><td align="center" rowspan="1" colspan="1">0.1</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">45</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">17</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">148±27</td><td align="center" rowspan="1" colspan="1">149±17</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">456±83</td><td align="center" rowspan="1" colspan="1">467±53</td><td align="center" rowspan="1" colspan="1">8</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">43</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">20</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">161±29</td><td align="center" rowspan="1" colspan="1">162±13</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">5±1</td><td align="center" rowspan="1" colspan="1">1±0.5</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">358±65</td><td align="center" rowspan="1" colspan="1">371±10</td><td align="center" rowspan="1" colspan="1">9</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">3.1±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">58</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">33</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">159±29</td><td align="center" rowspan="1" colspan="1">160±15</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4±1</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">406±74</td><td align="center" rowspan="1" colspan="1">398±28</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">3.2±0.5</td><td align="center" rowspan="1" colspan="1">0.8</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">48</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">26</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">155±28</td><td align="center" rowspan="1" colspan="1">154±18</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">409±78</td><td align="center" rowspan="1" colspan="1">405±21</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">3.1±1</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.7</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="center" rowspan="1" colspan="1">A</td><td align="center" rowspan="1" colspan="1">47</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1">26</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">155±28</td><td align="center" rowspan="1" colspan="1">158±19</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">4.1±1</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">130±24</td><td align="center" rowspan="1" colspan="1">135±13</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">2.2±0.5</td><td align="center" rowspan="1" colspan="1">2.1±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">453±79</td><td align="center" rowspan="1" colspan="1">457±19</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">3±1</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">382±70</td><td align="center" rowspan="1" colspan="1">408±10</td><td align="center" rowspan="1" colspan="1">18</td><td align="center" rowspan="1" colspan="1">5.3±1</td><td align="center" rowspan="1" colspan="1">5.1±0.5</td><td align="center" rowspan="1" colspan="1">0.13</td></tr><tr><td align="center" rowspan="1" colspan="1"><bold>T</bold></td><td align="center" rowspan="1" colspan="1"><bold>46</bold></td><td align="center" rowspan="1" colspan="1"><bold>M</bold></td><td align="center" rowspan="1" colspan="1"><bold>15</bold></td><td align="center" rowspan="1" colspan="1"><bold>5</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>155±30</bold></td><td align="center" rowspan="1" colspan="1"><bold>158±12</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>4±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>4±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>406±80</bold></td><td align="center" rowspan="1" colspan="1"><bold>408±17</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>3.3±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>3.3±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.01</bold></td><td align="center" rowspan="1" colspan="1"><bold>370±68</bold></td><td align="center" rowspan="1" colspan="1"><bold>371±43</bold></td><td align="center" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" rowspan="1" colspan="1"><bold>5.4±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>5±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.3</bold></td></tr><tr><td align="center" rowspan="1" colspan="1"><bold>T</bold></td><td align="center" rowspan="1" colspan="1"><bold>66</bold></td><td align="center" rowspan="1" colspan="1"><bold>M</bold></td><td align="center" rowspan="1" colspan="1"><bold>7</bold></td><td align="center" rowspan="1" colspan="1"><bold>5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0</bold></td><td align="center" rowspan="1" colspan="1"><bold>155±27</bold></td><td align="center" rowspan="1" colspan="1"><bold>161±14</bold></td><td align="center" rowspan="1" colspan="1"><bold>4</bold></td><td align="center" rowspan="1" colspan="1"><bold>4.4±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>4.1±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.1</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>440±80</bold></td><td align="center" rowspan="1" colspan="1"><bold>449±66</bold></td><td align="center" rowspan="1" colspan="1"><bold>6</bold></td><td align="center" rowspan="1" colspan="1"><bold>3±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>3.3±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.2</bold></td><td align="center" rowspan="1" colspan="1"><bold>358±65</bold></td><td align="center" rowspan="1" colspan="1"><bold>362±56</bold></td><td align="center" rowspan="1" colspan="1"><bold>3</bold></td><td align="center" rowspan="1" colspan="1"><bold>5.5±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>5.5±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.03</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">T</td><td align="center" rowspan="1" colspan="1">44</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1">11</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">0</td><td align="center" rowspan="1" colspan="1">156±21</td><td align="center" rowspan="1" colspan="1">154±11</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">4.3±0.5</td><td align="center" rowspan="1" colspan="1">4.3±0.5</td><td align="center" rowspan="1" colspan="1">0.04</td><td align="center" rowspan="1" colspan="1">227±40</td><td align="center" rowspan="1" colspan="1">131±17</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">444±81</td><td align="center" rowspan="1" colspan="1">444±72</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">3.3±1</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">0.2</td><td align="center" rowspan="1" colspan="1">345±63</td><td align="center" rowspan="1" colspan="1">343±11</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">5.4±1</td><td align="center" rowspan="1" colspan="1">5.4±0.5</td><td align="center" rowspan="1" colspan="1">0.01</td></tr><tr><td align="center" rowspan="1" colspan="1"><bold>A</bold></td><td align="center" rowspan="1" colspan="1"><bold>48</bold></td><td align="center" rowspan="1" colspan="1"><bold>M</bold></td><td align="center" rowspan="1" colspan="1"><bold>13</bold></td><td align="center" rowspan="1" colspan="1"><bold>6</bold></td><td align="center" rowspan="1" colspan="1"><bold>2</bold></td><td align="center" rowspan="1" colspan="1"><bold>156±26</bold></td><td align="center" rowspan="1" colspan="1"><bold>160±10</bold></td><td align="center" rowspan="1" colspan="1"><bold>3</bold></td><td align="center" rowspan="1" colspan="1"><bold>4.3±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>4.3±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.04</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>NA</bold></td><td align="center" rowspan="1" colspan="1"><bold>448±82</bold></td><td align="center" rowspan="1" colspan="1"><bold>447±70</bold></td><td align="center" rowspan="1" colspan="1"><bold>1</bold></td><td align="center" rowspan="1" colspan="1"><bold>3±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>3.2±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.1</bold></td><td align="center" rowspan="1" colspan="1"><bold>333±61</bold></td><td align="center" rowspan="1" colspan="1"><bold>348±21</bold></td><td align="center" rowspan="1" colspan="1"><bold>10</bold></td><td align="center" rowspan="1" colspan="1"><bold>5±1</bold></td><td align="center" rowspan="1" colspan="1"><bold>5.4±0.5</bold></td><td align="center" rowspan="1" colspan="1"><bold>0.3</bold></td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"><italic>55±11</italic></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"><italic>20±7</italic></td><td align="center" rowspan="1" colspan="1"><italic>5±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>1±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>153±13</italic></td><td align="center" rowspan="1" colspan="1"><italic>152±13</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>0</italic>.<italic>1±0</italic>.<italic>8</italic></td><td align="center" rowspan="1" colspan="1"><italic>207±41</italic></td><td align="center" rowspan="1" colspan="1"><italic>199±45</italic></td><td align="center" rowspan="1" colspan="1"><italic>3±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>7±3</italic></td><td align="center" rowspan="1" colspan="1"><italic>8±3</italic></td><td align="center" rowspan="1" colspan="1"><italic>1±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>415±51</italic></td><td align="center" rowspan="1" colspan="1"><italic>406±54</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>2</italic>.<italic>2±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>0</italic>.<italic>1</italic></td><td align="center" rowspan="1" colspan="1"><italic>418±80</italic></td><td align="center" rowspan="1" colspan="1"><italic>422±77</italic></td><td align="center" rowspan="1" colspan="1"><italic>5±5</italic></td><td align="center" rowspan="1" colspan="1"><italic>5±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>5±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>1</italic>.<italic>1±1</italic>.<italic>3</italic></td></tr><tr><td colspan="30" align="center" rowspan="1"><bold>HC (n = 15)</bold></td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">65</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">118±11</td><td align="center" rowspan="1" colspan="1">119±11</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">13±1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">171±16</td><td align="center" rowspan="1" colspan="1">166±15</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">9±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">232±21</td><td align="center" rowspan="1" colspan="1">242±29</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">26±0.5</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">255±23</td><td align="center" rowspan="1" colspan="1">248±18</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">13±2</td><td align="center" rowspan="1" colspan="1">2</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">60</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">152±17</td><td align="center" rowspan="1" colspan="1">153±17</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">223±22</td><td align="center" rowspan="1" colspan="1">129±14</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">12±05</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">187±17</td><td align="center" rowspan="1" colspan="1">187±17</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">312±28</td><td align="center" rowspan="1" colspan="1">313±28</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">16±1</td><td align="center" rowspan="1" colspan="1">17±1</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">61</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">136±13</td><td align="center" rowspan="1" colspan="1">138±10</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">165±15</td><td align="center" rowspan="1" colspan="1">166±13</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">11±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">234±21</td><td align="center" rowspan="1" colspan="1">238±11</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">266±21</td><td align="center" rowspan="1" colspan="1">270±11</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">19±2</td><td align="center" rowspan="1" colspan="1">10±0.5</td><td align="center" rowspan="1" colspan="1">6</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">55</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">158±24</td><td align="center" rowspan="1" colspan="1">159±15</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">187±17</td><td align="center" rowspan="1" colspan="1">288±13</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">11±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">182±16</td><td align="center" rowspan="1" colspan="1">191±10</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">8±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">291±27</td><td align="center" rowspan="1" colspan="1">293±14</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">18±2</td><td align="center" rowspan="1" colspan="1">16±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">61</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">122±11</td><td align="center" rowspan="1" colspan="1">135±17</td><td align="center" rowspan="1" colspan="1">10</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">126±12</td><td align="center" rowspan="1" colspan="1">128±14</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">14±1</td><td align="center" rowspan="1" colspan="1">9±0.5</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">251±21</td><td align="center" rowspan="1" colspan="1">254±15</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">304±28</td><td align="center" rowspan="1" colspan="1">309±12</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">19±0.5</td><td align="center" rowspan="1" colspan="1">5</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">65</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">145±13</td><td align="center" rowspan="1" colspan="1">150±15</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">248±23</td><td align="center" rowspan="1" colspan="1">241±12</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">14±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">224±20</td><td align="center" rowspan="1" colspan="1">226±23</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">298±18</td><td align="center" rowspan="1" colspan="1">300±63</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">17±2</td><td align="center" rowspan="1" colspan="1">19±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">61</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">119±11</td><td align="center" rowspan="1" colspan="1">126±12</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">212±19</td><td align="center" rowspan="1" colspan="1">215±17</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">13±0.5</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">139±13</td><td align="center" rowspan="1" colspan="1">135±10</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">229±21</td><td align="center" rowspan="1" colspan="1">222±12</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">11±5</td><td align="center" rowspan="1" colspan="1">11±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">63</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">150±12</td><td align="center" rowspan="1" colspan="1">152±15</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">164±15</td><td align="center" rowspan="1" colspan="1">168±17</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">30±3</td><td align="center" rowspan="1" colspan="1">12±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">201±18</td><td align="center" rowspan="1" colspan="1">208±10</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">7±1</td><td align="center" rowspan="1" colspan="1">5±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">350±32</td><td align="center" rowspan="1" colspan="1">352±28</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">16±0.5</td><td align="center" rowspan="1" colspan="1">6</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">55</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">130±15</td><td align="center" rowspan="1" colspan="1">126±15</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">176±16</td><td align="center" rowspan="1" colspan="1">177±13</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">9±0.5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">162±15</td><td align="center" rowspan="1" colspan="1">159±17</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">9±0.5</td><td align="center" rowspan="1" colspan="1">0.1</td><td align="center" rowspan="1" colspan="1">354±32</td><td align="center" rowspan="1" colspan="1">355±28</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">11±0.5</td><td align="center" rowspan="1" colspan="1">4</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">56</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">110±10</td><td align="center" rowspan="1" colspan="1">119±17</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">168±15</td><td align="center" rowspan="1" colspan="1">163±17</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">18±2</td><td align="center" rowspan="1" colspan="1">28±0.5</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">171±15</td><td align="center" rowspan="1" colspan="1">168±15</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">7±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">245±22</td><td align="center" rowspan="1" colspan="1">250±14</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">16±1</td><td align="center" rowspan="1" colspan="1">8±0.5</td><td align="center" rowspan="1" colspan="1">6</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">65</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">131±12</td><td align="center" rowspan="1" colspan="1">132±17</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">202±18</td><td align="center" rowspan="1" colspan="1">205±16</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">29±3</td><td align="center" rowspan="1" colspan="1">13±0.5</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">147±13</td><td align="center" rowspan="1" colspan="1">150±17</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">9±0.5</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">355±32</td><td align="center" rowspan="1" colspan="1">351±16</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">4</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">56</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">119±10</td><td align="center" rowspan="1" colspan="1">119±16</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">152±14</td><td align="center" rowspan="1" colspan="1">159±17</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">23±2</td><td align="center" rowspan="1" colspan="1">19±0.5</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">158±14</td><td align="center" rowspan="1" colspan="1">167±11</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">253±20</td><td align="center" rowspan="1" colspan="1">252±49</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">15±0.5</td><td align="center" rowspan="1" colspan="1">3</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">59</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">162±15</td><td align="center" rowspan="1" colspan="1">160±17</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">206±19</td><td align="center" rowspan="1" colspan="1">210±15</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">33±3</td><td align="center" rowspan="1" colspan="1">28±0.5</td><td align="center" rowspan="1" colspan="1">11</td><td align="center" rowspan="1" colspan="1">183±17</td><td align="center" rowspan="1" colspan="1">181±17</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">3±0.5</td><td align="center" rowspan="1" colspan="1">2</td><td align="center" rowspan="1" colspan="1">217±29</td><td align="center" rowspan="1" colspan="1">218±12</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">12±1</td><td align="center" rowspan="1" colspan="1">10±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">55</td><td align="center" rowspan="1" colspan="1">M</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">143±13</td><td align="center" rowspan="1" colspan="1">143±12</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">3</td><td align="center" rowspan="1" colspan="1">187±17</td><td align="center" rowspan="1" colspan="1">181±17</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">11±1</td><td align="center" rowspan="1" colspan="1">21±0.5</td><td align="center" rowspan="1" colspan="1">7</td><td align="center" rowspan="1" colspan="1">227±21</td><td align="center" rowspan="1" colspan="1">229±17</td><td align="center" rowspan="1" colspan="1">4</td><td align="center" rowspan="1" colspan="1">6±1</td><td align="center" rowspan="1" colspan="1">4±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">317±23</td><td align="center" rowspan="1" colspan="1">313±17</td><td align="center" rowspan="1" colspan="1">5</td><td align="center" rowspan="1" colspan="1">8±1</td><td align="center" rowspan="1" colspan="1">11±0.5</td><td align="center" rowspan="1" colspan="1">2</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">65</td><td align="center" rowspan="1" colspan="1">F</td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1">134±12</td><td align="center" rowspan="1" colspan="1">133±17</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">9±1</td><td align="center" rowspan="1" colspan="1">10±1</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">167±15</td><td align="center" rowspan="1" colspan="1">167±17</td><td align="center" rowspan="1" colspan="1">0.5</td><td align="center" rowspan="1" colspan="1">21±2</td><td align="center" rowspan="1" colspan="1">33±0.5</td><td align="center" rowspan="1" colspan="1">15</td><td align="center" rowspan="1" colspan="1">169±15</td><td align="center" rowspan="1" colspan="1">178±13</td><td align="center" rowspan="1" colspan="1">6</td><td align="center" rowspan="1" colspan="1">4±0.6</td><td align="center" rowspan="1" colspan="1">6±0.5</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">253±23</td><td align="center" rowspan="1" colspan="1">252±10</td><td align="center" rowspan="1" colspan="1">1</td><td align="center" rowspan="1" colspan="1">13±1</td><td align="center" rowspan="1" colspan="1">11±0.5</td><td align="center" rowspan="1" colspan="1">1</td></tr><tr><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"><italic>60±4</italic></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"></td><td align="center" rowspan="1" colspan="1"><italic>132±16</italic></td><td align="center" rowspan="1" colspan="1"><italic>137±14</italic></td><td align="center" rowspan="1" colspan="1"><italic>5±5</italic></td><td align="center" rowspan="1" colspan="1"><italic>9±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>9±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>178±30</italic></td><td align="center" rowspan="1" colspan="1"><italic>176±35</italic></td><td align="center" rowspan="1" colspan="1"><italic>3±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>17±8</italic></td><td align="center" rowspan="1" colspan="1"><italic>16±8</italic></td><td align="center" rowspan="1" colspan="1"><italic>4±4</italic></td><td align="center" rowspan="1" colspan="1"><italic>182±30</italic></td><td align="center" rowspan="1" colspan="1"><italic>177±34</italic></td><td align="center" rowspan="1" colspan="1"><italic>6±5</italic></td><td align="center" rowspan="1" colspan="1"><italic>6±2</italic></td><td align="center" rowspan="1" colspan="1"><italic>7±5</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±4</italic></td><td align="center" rowspan="1" colspan="1"><italic>276±65</italic></td><td align="center" rowspan="1" colspan="1"><italic>258±85</italic></td><td align="center" rowspan="1" colspan="1"><italic>2±1</italic></td><td align="center" rowspan="1" colspan="1"><italic>13±4</italic></td><td align="center" rowspan="1" colspan="1"><italic>13±4</italic></td><td align="center" rowspan="1" colspan="1"><italic>3±2</italic></td></tr></tbody></table></alternatives><table-wrap-foot><fn id="t001fn001"><p><italic>Legend</italic>: <underline>A</underline>: post-anoxic brain-injury; <underline>age</underline> in years; <underline>CRS-R</underline>: coma recovery scale-revised; <underline>dd</underline>: disease duration in months; <underline>et</underline>: etiology; <underline>gen</underline>: gender; <underline>MCS</underline>: minimally conscious state; <underline>NCS-R</underline>: nociception coma scale-revised; <underline>sd</underline>: standard deviation; <underline>T</underline>: post-traumatic brain-injury; <underline>VS</underline>: vegetative state.</p></fn></table-wrap-foot></table-wrap></sec><sec id="sec004"><title>Clinical assessment</title><p>DOC individuals (23 VS and 15 MCS) were clinically evaluated by two neurologists, skilled in DOC diagnosis, through the JFK Coma Recovery Scale-Revised (CRS-R). This scale is a reliable and standardized tool, which integrates neuropsychological and clinical assessment, and includes the current diagnostic criteria for coma, VS and MCS, allowing the clinician to assign the patient to the most appropriate diagnostic category. Thus, the CRS-R is considered as an appropriate measure for characterizing level of consciousness and for monitoring neurobehavioral function recovery [<xref rid="pone.0144713.ref021" ref-type="bibr">21</xref>].</p><p>Pain perception was specifically evaluated by means of the Nociception Coma Scale-Revised (NCS-R) [<xref rid="pone.0144713.ref022" ref-type="bibr">22</xref>] that has been developed for assessing pain in severely brain-injured patients, and allows a better specification of the conscious behavioral patterns linked to pain experience in MCS and VS. This tool consists in the observation of motor, verbal, and facial responses to painful stimulation. The total score ranges from zero to 9. A cut-off of 4 has been proposed to suggest an aware pain perception.</p></sec><sec id="sec005"><title>Laser stimulation set-up</title><p>LEP were recorded at bed and over a reclining armchair in a quiet and mild-lighted room in DOC patients and HC individuals, respectively. All measures concerning laser-safety were observed (protective goggles, earplugs). Aδ-LEP were previously recorded in either HC or DOC patients. We used a Neodymium:Yttrium-Aluminium-Perovskite laser (Nd:YAP) (wavelength 1.34μm, pulse duration 2-20ms, maximum energy 7J, 4mm beam diameter) with fiber-optic guidance (Electronic Engineering, Florence, Italy). A red helium–neon (He–Ne) laser, confocal with the infrared beam, was used to visually indicate the irradiated skin area of the right trigeminal maxillary branch region, close to the nasus-genius sulcus. In each individual, we employed a laser stimulation intensity of 60-80mJ/mm<sup>2</sup> that induced a Visual Analogic Score of at least 4/10 in the HC. Such intensity produced clear and stable evoked components in all of the HC individuals, and was therefore used throughout the entire experimental procedure. The mean stimulation intensity employed in HC individuals was used to evoke LEP in the DOC sample. We delivered two trains of 30 laser pulses, with a 5-minute inter-train interval. In order to avoid habituation phenomena and skin overheating and damage, the delivery frequency was 0.1±0.025Hz and the stimulator, whose handle was held perpendicularly to skin surface, was slightly shifted over the skin. During the stimulation, HC did not perform any mental task (neutral condition) [<xref rid="pone.0144713.ref016" ref-type="bibr">16</xref>], whereas DOC patients practiced the CRS-R arousal protocol [<xref rid="pone.0144713.ref023" ref-type="bibr">23</xref>] before the LEP session.</p><p>In order to record C-LEP, the laser stimulation was carried out according to Bragard and co-workers protocol [<xref rid="pone.0144713.ref024" ref-type="bibr">24</xref>] that obtained the direct isolation of C-LEP from tiny cutaneous surfaces by means of a CO<sub>2</sub> laser. The laser stimuli (wavelength 1.34μm, pulse duration 10ms, 4mm beam diameter) were directed to the skin area of the right trigeminal maxillary branch region, close to the nasus-genius sulcus, but a thin aluminium disk, drilled with calibrated holes (~0.15mm<sup>2</sup>) was interposed just above the skin surface [<xref rid="pone.0144713.ref024" ref-type="bibr">24</xref>]. Stimulus intensity was individually adapted in the HC individuals, so that sensations reported ranged from “barely detectable” to “slight pain”. Such intensity produced clear and stable evoked components in all of the HC individuals, and was, therefore, used throughout the entire experimental procedure. The mean stimulation intensity applied in HC individuals was employed to evoke C-LEP in the DOC sample.</p></sec><sec id="sec006"><title>LEP recording</title><p>LEP were recorded from three Ag-AgCl scalp-surface electrodes (put on Fp2, Cz, and T3). The reference electrode was put on the nose and the ground on Fpz. Eye movements and blinks were monitored by an electrode above the right eyebrow. Electrode impedance was kept ≤5kΩ. The time-analysis was set at 2s, with a pre-analysis period of 100ms. Signals were filtered at 0.3-70Hz, sampled at 250Hz through a Synergy-Medelec System (Tecnomed, Pescara, Italy), and stored on a PC for off-line analysis. Trials contaminated by ocular or muscle artifacts were automatically excluded from the analysis through an artifact-rejection system that excluded all runs containing transient signals exceeding ±65μV in any recording channel (including the electro-oculogram) from the average. In the HC group, we identified three LEP components, defined in terms of estimated topography and latency values, i.e the N2P2 (Cz-nose), the N1 (T3-nose), and the P1 (Fp2-nose). The time-windows were determined after having analyzed the grand-average of all the LEP, and then applied in each individual analysis. Thus, we measured the baseline-peak amplitude (μV) of N1 and N2 waves, and the latency (ms) of N2 and N1 (in addition, we calculated the N1P1 by computing an offline bipolar montage T3-Fp2, where phase reversal is evident) [<xref rid="pone.0144713.ref017" ref-type="bibr">17</xref>,<xref rid="pone.0144713.ref025" ref-type="bibr">25</xref>], in either the single runs or the average of the two runs. Latencies were determined by using a modified box-plot method known as the median rule [<xref rid="pone.0144713.ref026" ref-type="bibr">26</xref>].</p></sec><sec id="sec007"><title>Statistical analysis</title><p>Latencies and amplitudes of the LEP components were analyzed at their scalp sites through a one-way analysis of variance (ANOVA), with <italic>group</italic> (three levels: HC, VS, and MCS) as between-subject factor. Cases without LEP were labeled as missing data. The Greenhouse-Geisser method was used if necessary to correct the degrees of freedom [<xref rid="pone.0144713.ref027" ref-type="bibr">27</xref>]. A p-value <0.05 after correction was accepted as statistically significant. Conditional on a significant F-value, <italic>post-hoc</italic> analysis (Tukey's honestly significant difference -THSD) was performed to explore the strength of the main effects and the patterns of interaction between experimental factors. All data are given as means± standard deviation (SD). We also calculated a two-tailed bivariate Pearson’s correlation coefficient between the clinical (CRS-R and NCS-R) and electrophysiological parameters (latencies and amplitudes of Aδ-LEP and C-LEP components).</p></sec></sec><sec sec-type="results" id="sec008"><title>Results</title><p>We did not report any side effects during and after the stimulation protocol. In <xref rid="pone.0144713.t001" ref-type="table">Table 1</xref>, we summarize the single-subject values of LEP latencies and amplitudes in the two runs of laser stimulation, the standard deviation of LEP amplitude and latencies between the two laser stimulation runs for each subject, the group values of LEP latencies and amplitudes, and the clinical and demographic characteristics of HC and DOC patients. In <xref rid="pone.0144713.g001" ref-type="fig">Fig 1</xref>, we reported the two averaged waveforms at each electrode in the two groups of DOC patients, concerning either Aδ-LEP or C-LEP.</p><fig id="pone.0144713.g001" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0144713.g001</object-id><label>Fig 1</label><caption><title>Shows the grand averages in the time-domain (the two thick waveforms represent the two pulse-train–runs, the shady areas express the inter-subject variability) of Aδ-LEP and C-LEP at electrode Cz (N2P2), T3 (N1) and Fp2 (P1).</title><p>Amplitude negative values are plotted up. The vertical and horizontal black lines indicate the time point of the laser stimulation and the zero line, respectively. The vertical and horizontal red bars refer to the standard deviation concerning LEP latency and amplitude, respectively.</p></caption><graphic xlink:href="pone.0144713.g001"></graphic></fig><p>The Aδ-LEP stimulation set up induced both the N1P1 and N2P2 components, as well as the C-LEP paradigm produced the ultra-late LEP waves. Either the HC or the DOC patients showed reliable evoked responses, since the LEP waveforms were track-by-track stable within each laser stimulation run, and the two consecutive averaged waveforms were almost superimposable at either individual or group level (<xref rid="pone.0144713.g001" ref-type="fig">Fig 1</xref>). Similarly, the individual LEP values showed a run-by-run low variability (i.e. no more than 3 times the mean run-by-run SD) (<xref rid="pone.0144713.t001" ref-type="table">Table 1</xref>).</p><p>All of the participants showed the N1P1 component of both Aδ-LEP and C-LEP. All of the HC and the MCS patients showed the Aδ-LEP N2P2 component, whereas this was missing in 13 VS individuals (<xref rid="pone.0144713.t001" ref-type="table">Table 1</xref>). Interestingly, six out of these patients showed the C-LEP N2P2 component. Hence, the VS individuals showed three distinct N2P2 LEP patterns: i) both the Aδ-LEP N2P2 and C-LEP (10 individuals); ii) only the C-LEP N2P2 (6 individuals); and iii) neither the Aδ-LEP N2P2 nor the C-LEP N2P2 (7 individuals). Notably, none of the patients showed the Aδ-LEP N2P2 without the C-LEP N2P2.</p><p>We found higher LEP amplitudes and less delayed LEP latencies in HC than DOC patients. On the other hand, LEP latencies were significantly higher in VS than MCS individuals, whereas LEP amplitudes were almost superimposable. The statistically significant inter-group differences are summarized in <xref rid="pone.0144713.t002" ref-type="table">Table 2</xref>. The other parameters (age, disease duration, etiology, and gender) were not significantly different among the three groups, and the LEP parameters did not correlate with the clinical scale scores.</p><table-wrap id="pone.0144713.t002" orientation="portrait" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0144713.t002</object-id><label>Table 2</label><caption><title>Resumes the one-way ANOVA findings (<italic>group</italic> effect) and the <italic>post-hoc</italic> THSD data concerning LEP parameters.</title><p>NS stands for non-significant.</p></caption><alternatives><graphic id="pone.0144713.t002g" xlink:href="pone.0144713.t002"></graphic><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col><col align="left" valign="middle" span="1"></col></colgroup><thead><tr><th align="center" rowspan="1" colspan="1"></th><th colspan="2" align="center" rowspan="1">one-way ANOVA</th><th colspan="3" align="center" rowspan="1"><italic>post-hoc</italic> THSD</th></tr><tr><th align="center" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">F<sub>(2,100)</sub></th><th align="center" rowspan="1" colspan="1">p</th><th align="center" rowspan="1" colspan="1">HC/MCS</th><th align="center" rowspan="1" colspan="1">HC/VS</th><th align="center" rowspan="1" colspan="1">MCS/VS</th></tr></thead><tbody><tr><td colspan="6" align="center" rowspan="1"><bold>Aδ-LEP</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">N1 latency</td><td align="center" rowspan="1" colspan="1">4.9</td><td align="char" char="." rowspan="1" colspan="1">0.01</td><td align="center" rowspan="1" colspan="1">NS</td><td align="char" char="." rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">0.01</td></tr><tr><td align="center" rowspan="1" colspan="1">N1 amplitude</td><td align="center" rowspan="1" colspan="1">75</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1"><0.001</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1">NS</td></tr><tr><td align="center" rowspan="1" colspan="1">N2 latency</td><td align="center" rowspan="1" colspan="1">3.9</td><td align="char" char="." rowspan="1" colspan="1">0.03</td><td align="center" rowspan="1" colspan="1">NS</td><td align="char" char="." rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">0.01</td></tr><tr><td align="center" rowspan="1" colspan="1">N2 amplitude</td><td align="center" rowspan="1" colspan="1">11</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1"><0.001</td><td align="char" char="." rowspan="1" colspan="1">0.003</td><td align="center" rowspan="1" colspan="1">NS</td></tr><tr><td colspan="6" align="center" rowspan="1"><bold>C-LEP</bold></td></tr><tr><td align="center" rowspan="1" colspan="1">N1 latency</td><td align="center" rowspan="1" colspan="1">67</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1">0.01</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="center" rowspan="1" colspan="1">N1 amplitude</td><td align="center" rowspan="1" colspan="1">19</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1">0.001</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1">0.002</td></tr><tr><td align="center" rowspan="1" colspan="1">N2 latency</td><td align="center" rowspan="1" colspan="1">29</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1">NS</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1"><0.001</td></tr><tr><td align="center" rowspan="1" colspan="1">N2 amplitude</td><td align="center" rowspan="1" colspan="1">42</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1"><0.001</td><td align="char" char="." rowspan="1" colspan="1"><0.001</td><td align="center" rowspan="1" colspan="1">NS</td></tr></tbody></table></alternatives></table-wrap></sec><sec sec-type="conclusions" id="sec009"><title>Discussion</title><p>To the best of our knowledge, this is the first study investigating C-LEP in DOC patients. Our findings agree with previous reports showing an increased latency of Aδ-LEP in DOC patients (more in VS than MCS individuals) without any significant amplitude inter-group difference [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>]. The preservation of N2P2 Aδ-LEP may suggest a residual nociceptive cortical processing in severe brain-injured patients, even when other sensory evoked potentials are missing [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>]. Therefore, a potential pain experience should be taken into account in such patients.</p><p>It is worthy to note that it is not so easy to record C-LEP, as reported by the international guidelines [<xref rid="pone.0144713.ref028" ref-type="bibr">28</xref>–<xref rid="pone.0144713.ref029" ref-type="bibr">29</xref>]. Therefore, a first critical question is whether the evoked responses we obtained may or not reliably represent C-LEP. Indeed, there are two main problems in C-LEP recording: i) the preceding Aδ-LEP may hinder the following C-LEP; and ii) the extremely low range of conduction speed of the unmyelinated fibers limits the necessary synchronization of the input to produce a clear signal from the scalp (in fact, C-LEP have been mainly investigated in facial territories). There are two main methods to record C-LEP: i) Bragard et al. [<xref rid="pone.0144713.ref024" ref-type="bibr">24</xref>] and Opsommer et al. [<xref rid="pone.0144713.ref030" ref-type="bibr">30</xref>] employed a laser beam passing through a grid with micro-spots, without any substantial Aδ-LEP interference; and ii) Iannetti et al. [<xref rid="pone.0144713.ref013" ref-type="bibr">13</xref>] and Cruccu et al. [<xref rid="pone.0144713.ref031" ref-type="bibr">31</xref>] used very large and low-energy laser beams, directly focused on skin, thus stimulating warmth receptors of the skin overlying the spine.</p><p>We used the Bragard’s approach (i.e. the micro-spot technique) [<xref rid="pone.0144713.ref024" ref-type="bibr">24</xref>], since mechano/heat-sensitive A-fiber nociceptors (AMHs) are less numerous than mechano/heat-sensitive C-fiber nociceptors (CMHs), and therefore the micro-spot technique reduces the probability of activating AMHs. Instead, the large-beam and low-intensity method [<xref rid="pone.0144713.ref013" ref-type="bibr">13</xref>,<xref rid="pone.0144713.ref031" ref-type="bibr">31</xref>] allows a selective activation of the warmth C-fiber receptors, which have a lower threshold than AMHs and CMHs. Nevertheless, AMHs are more sparse on face but have larger receptive fields than CMHs and warmth C-fiber receptors. Hence, the probability of activating AMHs could be the same with or without the spatial restriction provided by the grid [<xref rid="pone.0144713.ref032" ref-type="bibr">32</xref>]. However, in the present study we used a solid-state laser, which has well-known different properties in comparison to the gas one, with the former showing a shorter wavelength and a deeper penetration power [<xref rid="pone.0144713.ref014" ref-type="bibr">14</xref>,<xref rid="pone.0144713.ref033" ref-type="bibr">33</xref>]. Instead, gas laser has a greater energy dissipation [<xref rid="pone.0144713.ref034" ref-type="bibr">34</xref>–<xref rid="pone.0144713.ref035" ref-type="bibr">35</xref>] when has to activate the deep nociceptors (i.e. at the dermo-epidermal junction, approximately 100–500μm). Moreover, the short pulse duration of solid-state laser reduces the time for CMHs activation and generates a more synchronous afferent volley [<xref rid="pone.0144713.ref036" ref-type="bibr">36</xref>], leading to more synchronized brain evoked potentials [<xref rid="pone.0144713.ref037" ref-type="bibr">37</xref>]. In addition, AMHs in glabrous skin respond with a long latency of several seconds to sustained heat stimulus and can be sensitized dramatically, whereas CMHs innervating glabrous skin do not share these properties [<xref rid="pone.0144713.ref038" ref-type="bibr">38</xref>–<xref rid="pone.0144713.ref039" ref-type="bibr">39</xref>]. Hence, there is a bulk of data attesting to the suitability of solid-state lasers in activating CMHs [<xref rid="pone.0144713.ref031" ref-type="bibr">31</xref>,<xref rid="pone.0144713.ref040" ref-type="bibr">40</xref>].</p><p>In our study, we at first registered C-LEP in HC individuals, identifying clear and stable LEP components, with a significantly low intra-subject and inter-subject variability. In addition, the two averaged trains of stimuli were overimposable. In DOC patients, the evoked responses were more delayed in latency and smaller in amplitude in comparison to HC, but they still showed a low intra-subject variability, and a similar inter-train superimposability. Therefore, taking into account the aforementioned methodological discussion, we believe that the responses we obtained reliably expressed the C-LEP. Moreover, although several hundred stimuli were necessary in order to record C-LEP in a previous study [<xref rid="pone.0144713.ref024" ref-type="bibr">24</xref>], we could use a smaller number of laser stimuli because of differences in our methodology, including the laser type employed (solid-state vs. gas) and the site of stimulation (face vs. hand).</p><p>Notably, 13 VS patients did not show any Aδ-LEP N2P2 response, whereas previous studies reported a high-level of Aδ-LEP preservation [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>]. Such discrepancy between our findings and de Tommaso’s data [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>] may depend on either the larger sample we studied, or the aforementioned methodological issues.</p><p>By a quantitative point of view, C-LEP latencies were significantly higher in the VS than the MCS individuals, whereas there were no significant inter-group differences concerning C-LEP N2P2 amplitude. Nonetheless, our LEP patterns did not significantly correlate with the clinical assessment, without any relation between pain arousal and the awareness level, according to previous works [<xref rid="pone.0144713.ref010" ref-type="bibr">10</xref>–<xref rid="pone.0144713.ref011" ref-type="bibr">11</xref>]. Moreover, some VS patients showed very small LEP amplitude, even for the C-LEP amplitude range. This may depend on the variability of P2 waveforms we observed, which could have somehow influenced the baseline-peak amplitude values of N2 waves.</p><p>Interestingly, six out of the 13 VS patients lacking of Aδ-LEP N2P2 component showed clear C-LEP N2P2 waves. Moreover, such patients had a clinical picture, NCS-R and CRS-R score, similar to the VS patients showing both the Aδ-LEP and C-LEP N2P2 components. Hence, we may argue that the cortical arousal towards nociceptive stimuli could be guaranteed in those patients lacking of Aδ-LEP by a reshuffle or a residual preservation of cortical C-LEP generators. In our opinion, such findings raise an important question concerning the functional role of the C-LEP generators, since we did not observe any patients showing only Aδ-LEP N2P2 without C-LEP N2P2 waves. Although previous source analysis studies have shown that Aδ-LEP and C-LEP cortical generators may share similar circuits (even if related to different Aδ/C-fiber activation) [<xref rid="pone.0144713.ref009" ref-type="bibr">9</xref>], they independently process (either in series or in parallel) [<xref rid="pone.0144713.ref031" ref-type="bibr">31</xref>] some features of the afferent inputs (e.g. abrupt vs. slow-changing stimuli) [<xref rid="pone.0144713.ref041" ref-type="bibr">41</xref>]. Taking into account the functional differentiation of LEP generators, a substitute role of C-LEP N2P2 generators could be due to an over-activation of the slow-conducting medial pain-system (that oversees the nociceptive-related reflexive and affective responses) [<xref rid="pone.0144713.ref041" ref-type="bibr">41</xref>–<xref rid="pone.0144713.ref042" ref-type="bibr">42</xref>], which in turn depends on a brain injury-induced limbic and subcortical hyperconnectivity [<xref rid="pone.0144713.ref043" ref-type="bibr">43</xref>]. In addition, a selective modulation of the regional cortical excitability, an enlargement of the receptive fields, and the effects of cortical deafferentation could be taken into account in an attempt to explain a C-LEP generator preservation or reorganization [<xref rid="pone.0144713.ref044" ref-type="bibr">44</xref>–<xref rid="pone.0144713.ref047" ref-type="bibr">47</xref>]. Moreover, we could speculate about a strong C-LEP network stability in reason of an older phylogenetic origin [<xref rid="pone.0144713.ref048" ref-type="bibr">48</xref>], and a functional switch to a fixed “in-parallel” or “in-series” processing of nociceptive inputs [<xref rid="pone.0144713.ref049" ref-type="bibr">49</xref>].</p><p>The main limitations in our study are to be considered the small number of EEG channels we employed (since we were not able to use a full-EEG cap), and the non-homogeneous gender and age matching of our sample.</p><p>In conclusion, our work suggests that DOC patients may somehow show a residual cortical responsiveness to nociceptive stimuli. Indeed, C-LEP preservation could indicate the presence of a residual pain arousal even in the VS patients who do not show Aδ-LEP. 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