CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma
Identifieur interne : 00A738 ( Main/Exploration ); précédent : 00A737; suivant : 00A739CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma
Auteurs : Robert Marcus [Royaume-Uni, Canada, Espagne, Australie, France, Belgique, Pologne, Portugal] ; Kevin Imrie ; Andrew Belch ; David Cunningham ; Eduardo Flores ; John Catalano ; Philippe Solal-Celigny ; Fritz Offner ; Jan Walewski ; Jo O Raposo ; Andrew Jack ; Paul SmithSource :
- Blood [ 0006-4971 ] ; 2005.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal antibody against CD20, is active in follicular lymphoma, both as monotherapy and in combination with chemotherapy. Previously untreated patients with stages III to IV follicular lymphoma were randomly assigned to receive either 8 cycles of CVP plus rituximab (R-CVP; n = 162) or CVP (n = 159). Overall and complete response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP arm, respectively (P <.0001). At a median follow-up of 30 months, patients treated with R-CVP had a very significantly prolonged time to progression (median 32 months versus 15 months for CVP; P <.0001). Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months In the CVP arm (P <.0001). Rituximab did not add significantly to the toxicity of CVP. The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma, without increased toxicity.
Affiliations:
- Australie, Belgique, Canada, Espagne, France, Pologne, Portugal, Royaume-Uni
- Angleterre, Communauté de Madrid, Grand Londres, Pays de la Loire
- Le Mans, Londres, Madrid
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 004729
- to stream PascalFrancis, to step Curation: 001974
- to stream PascalFrancis, to step Checkpoint: 004726
- to stream Main, to step Merge: 00B376
- to stream Main, to step Curation: 00A738
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma</title>
<author><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Addenbrooke's Hospital</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Addenbrooke's Hospital</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Toronto-Sunnybrook Regional Cancer Center</s1>
<s2>Toronto, ON</s2>
<s3>CAN</s3>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Toronto-Sunnybrook Regional Cancer Center</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Cross Cancer Institute</s1>
<s2>Edmonton, AB</s2>
<s3>CAN</s3>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Cross Cancer Institute</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Royal Marsden Hospital</s1>
<s2>Surrey</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Royal Marsden Hospital</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Hospital Qregorio Marañón</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
</inist:fA14>
<country>Espagne</country>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Monash Medical Centre</s1>
<s2>Clayton</s2>
<s3>AUS</s3>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Monash Medical Centre</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Clinique Victor Hugo</s1>
<s2>Le Mans</s2>
<s3>FRA</s3>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Le Mans</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Dienst Hematologie</s1>
<s2>UZ Gent</s2>
<s3>BEL</s3>
</inist:fA14>
<country>Belgique</country>
<wicri:noRegion>Dienst Hematologie</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>M. Sklodowska- Curie Memorial Institute</s1>
<s2>Warszawa</s2>
<s3>POL</s3>
</inist:fA14>
<country>Pologne</country>
<wicri:noRegion>M. Sklodowska- Curie Memorial Institute</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Hospital Santa Maria</s1>
<s2>Usboa</s2>
<s3>PRT</s3>
</inist:fA14>
<country>Portugal</country>
<wicri:noRegion>Hospital Santa Maria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Leeds General Infirmary</s1>
<s2>Leeds</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Leeds General Infirmary</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Cancer Research UK and University College London (UCL) Cancer Trials Centre</s1>
<s2>London</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Imrie, Kevin" sort="Imrie, Kevin" uniqKey="Imrie K" first="Kevin" last="Imrie">Kevin Imrie</name>
</author>
<author><name sortKey="Belch, Andrew" sort="Belch, Andrew" uniqKey="Belch A" first="Andrew" last="Belch">Andrew Belch</name>
</author>
<author><name sortKey="Cunningham, David" sort="Cunningham, David" uniqKey="Cunningham D" first="David" last="Cunningham">David Cunningham</name>
</author>
<author><name sortKey="Flores, Eduardo" sort="Flores, Eduardo" uniqKey="Flores E" first="Eduardo" last="Flores">Eduardo Flores</name>
</author>
<author><name sortKey="Catalano, John" sort="Catalano, John" uniqKey="Catalano J" first="John" last="Catalano">John Catalano</name>
</author>
<author><name sortKey="Solal Celigny, Philippe" sort="Solal Celigny, Philippe" uniqKey="Solal Celigny P" first="Philippe" last="Solal-Celigny">Philippe Solal-Celigny</name>
</author>
<author><name sortKey="Offner, Fritz" sort="Offner, Fritz" uniqKey="Offner F" first="Fritz" last="Offner">Fritz Offner</name>
</author>
<author><name sortKey="Walewski, Jan" sort="Walewski, Jan" uniqKey="Walewski J" first="Jan" last="Walewski">Jan Walewski</name>
</author>
<author><name sortKey="Raposo, Jo O" sort="Raposo, Jo O" uniqKey="Raposo J" first="Jo O" last="Raposo">Jo O Raposo</name>
</author>
<author><name sortKey="Jack, Andrew" sort="Jack, Andrew" uniqKey="Jack A" first="Andrew" last="Jack">Andrew Jack</name>
</author>
<author><name sortKey="Smith, Paul" sort="Smith, Paul" uniqKey="Smith P" first="Paul" last="Smith">Paul Smith</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">05-0446726</idno>
<date when="2005">2005</date>
<idno type="stanalyst">PASCAL 05-0446726 INIST</idno>
<idno type="RBID">Pascal:05-0446726</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">004729</idno>
<idno type="wicri:Area/PascalFrancis/Curation">001974</idno>
<idno type="wicri:Area/PascalFrancis/Checkpoint">004726</idno>
<idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">004726</idno>
<idno type="wicri:doubleKey">0006-4971:2005:Marcus R:cvp:chemotherapy:plus</idno>
<idno type="wicri:Area/Main/Merge">00B376</idno>
<idno type="wicri:Area/Main/Curation">00A738</idno>
<idno type="wicri:Area/Main/Exploration">00A738</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma</title>
<author><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Addenbrooke's Hospital</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Addenbrooke's Hospital</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Toronto-Sunnybrook Regional Cancer Center</s1>
<s2>Toronto, ON</s2>
<s3>CAN</s3>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Toronto-Sunnybrook Regional Cancer Center</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Cross Cancer Institute</s1>
<s2>Edmonton, AB</s2>
<s3>CAN</s3>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Cross Cancer Institute</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Royal Marsden Hospital</s1>
<s2>Surrey</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Royal Marsden Hospital</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Hospital Qregorio Marañón</s1>
<s2>Madrid</s2>
<s3>ESP</s3>
</inist:fA14>
<country>Espagne</country>
<placeName><settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Monash Medical Centre</s1>
<s2>Clayton</s2>
<s3>AUS</s3>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Monash Medical Centre</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Clinique Victor Hugo</s1>
<s2>Le Mans</s2>
<s3>FRA</s3>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Le Mans</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Dienst Hematologie</s1>
<s2>UZ Gent</s2>
<s3>BEL</s3>
</inist:fA14>
<country>Belgique</country>
<wicri:noRegion>Dienst Hematologie</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>M. Sklodowska- Curie Memorial Institute</s1>
<s2>Warszawa</s2>
<s3>POL</s3>
</inist:fA14>
<country>Pologne</country>
<wicri:noRegion>M. Sklodowska- Curie Memorial Institute</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Hospital Santa Maria</s1>
<s2>Usboa</s2>
<s3>PRT</s3>
</inist:fA14>
<country>Portugal</country>
<wicri:noRegion>Hospital Santa Maria</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Leeds General Infirmary</s1>
<s2>Leeds</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Leeds General Infirmary</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Cancer Research UK and University College London (UCL) Cancer Trials Centre</s1>
<s2>London</s2>
<s3>GBR</s3>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Imrie, Kevin" sort="Imrie, Kevin" uniqKey="Imrie K" first="Kevin" last="Imrie">Kevin Imrie</name>
</author>
<author><name sortKey="Belch, Andrew" sort="Belch, Andrew" uniqKey="Belch A" first="Andrew" last="Belch">Andrew Belch</name>
</author>
<author><name sortKey="Cunningham, David" sort="Cunningham, David" uniqKey="Cunningham D" first="David" last="Cunningham">David Cunningham</name>
</author>
<author><name sortKey="Flores, Eduardo" sort="Flores, Eduardo" uniqKey="Flores E" first="Eduardo" last="Flores">Eduardo Flores</name>
</author>
<author><name sortKey="Catalano, John" sort="Catalano, John" uniqKey="Catalano J" first="John" last="Catalano">John Catalano</name>
</author>
<author><name sortKey="Solal Celigny, Philippe" sort="Solal Celigny, Philippe" uniqKey="Solal Celigny P" first="Philippe" last="Solal-Celigny">Philippe Solal-Celigny</name>
</author>
<author><name sortKey="Offner, Fritz" sort="Offner, Fritz" uniqKey="Offner F" first="Fritz" last="Offner">Fritz Offner</name>
</author>
<author><name sortKey="Walewski, Jan" sort="Walewski, Jan" uniqKey="Walewski J" first="Jan" last="Walewski">Jan Walewski</name>
</author>
<author><name sortKey="Raposo, Jo O" sort="Raposo, Jo O" uniqKey="Raposo J" first="Jo O" last="Raposo">Jo O Raposo</name>
</author>
<author><name sortKey="Jack, Andrew" sort="Jack, Andrew" uniqKey="Jack A" first="Andrew" last="Jack">Andrew Jack</name>
</author>
<author><name sortKey="Smith, Paul" sort="Smith, Paul" uniqKey="Smith P" first="Paul" last="Smith">Paul Smith</name>
</author>
</analytic>
<series><title level="j" type="main">Blood</title>
<title level="j" type="abbreviated">Blood</title>
<idno type="ISSN">0006-4971</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Blood</title>
<title level="j" type="abbreviated">Blood</title>
<idno type="ISSN">0006-4971</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Advanced stage</term>
<term>Antineoplastic agent</term>
<term>Chemotherapy</term>
<term>Cyclophosphamide</term>
<term>Drug combination</term>
<term>First line treatment</term>
<term>Follicular lymphoma</term>
<term>Human</term>
<term>Immunotherapy</term>
<term>Monoclonal antibody</term>
<term>Prednisone</term>
<term>Rituximab</term>
<term>Therapeutic protocol</term>
<term>Treatment</term>
<term>Vincristine</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Chimiothérapie</term>
<term>Anticancéreux</term>
<term>Anticorps monoclonal</term>
<term>Rituximab</term>
<term>Stade avancé</term>
<term>Vincristine</term>
<term>Immunothérapie</term>
<term>Prednisone</term>
<term>Association médicamenteuse</term>
<term>Lymphome folliculaire</term>
<term>Protocole thérapeutique</term>
<term>Traitement</term>
<term>Cyclophosphamide</term>
<term>Homme</term>
<term>Antigène CD20</term>
<term>Traitement première intention</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal antibody against CD20, is active in follicular lymphoma, both as monotherapy and in combination with chemotherapy. Previously untreated patients with stages III to IV follicular lymphoma were randomly assigned to receive either 8 cycles of CVP plus rituximab (R-CVP; n = 162) or CVP (n = 159). Overall and complete response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP arm, respectively (P <.0001). At a median follow-up of 30 months, patients treated with R-CVP had a very significantly prolonged time to progression (median 32 months versus 15 months for CVP; P <.0001). Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months In the CVP arm (P <.0001). Rituximab did not add significantly to the toxicity of CVP. The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma, without increased toxicity.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Belgique</li>
<li>Canada</li>
<li>Espagne</li>
<li>France</li>
<li>Pologne</li>
<li>Portugal</li>
<li>Royaume-Uni</li>
</country>
<region><li>Angleterre</li>
<li>Communauté de Madrid</li>
<li>Grand Londres</li>
<li>Pays de la Loire</li>
</region>
<settlement><li>Le Mans</li>
<li>Londres</li>
<li>Madrid</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Belch, Andrew" sort="Belch, Andrew" uniqKey="Belch A" first="Andrew" last="Belch">Andrew Belch</name>
<name sortKey="Catalano, John" sort="Catalano, John" uniqKey="Catalano J" first="John" last="Catalano">John Catalano</name>
<name sortKey="Cunningham, David" sort="Cunningham, David" uniqKey="Cunningham D" first="David" last="Cunningham">David Cunningham</name>
<name sortKey="Flores, Eduardo" sort="Flores, Eduardo" uniqKey="Flores E" first="Eduardo" last="Flores">Eduardo Flores</name>
<name sortKey="Imrie, Kevin" sort="Imrie, Kevin" uniqKey="Imrie K" first="Kevin" last="Imrie">Kevin Imrie</name>
<name sortKey="Jack, Andrew" sort="Jack, Andrew" uniqKey="Jack A" first="Andrew" last="Jack">Andrew Jack</name>
<name sortKey="Offner, Fritz" sort="Offner, Fritz" uniqKey="Offner F" first="Fritz" last="Offner">Fritz Offner</name>
<name sortKey="Raposo, Jo O" sort="Raposo, Jo O" uniqKey="Raposo J" first="Jo O" last="Raposo">Jo O Raposo</name>
<name sortKey="Smith, Paul" sort="Smith, Paul" uniqKey="Smith P" first="Paul" last="Smith">Paul Smith</name>
<name sortKey="Solal Celigny, Philippe" sort="Solal Celigny, Philippe" uniqKey="Solal Celigny P" first="Philippe" last="Solal-Celigny">Philippe Solal-Celigny</name>
<name sortKey="Walewski, Jan" sort="Walewski, Jan" uniqKey="Walewski J" first="Jan" last="Walewski">Jan Walewski</name>
</noCountry>
<country name="Royaume-Uni"><noRegion><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</noRegion>
<name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
<name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
<name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</country>
<country name="Canada"><noRegion><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</noRegion>
<name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</country>
<country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</region>
</country>
<country name="Australie"><noRegion><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</noRegion>
</country>
<country name="France"><region name="Pays de la Loire"><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</region>
</country>
<country name="Belgique"><noRegion><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</noRegion>
</country>
<country name="Pologne"><noRegion><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</noRegion>
</country>
<country name="Portugal"><noRegion><name sortKey="Marcus, Robert" sort="Marcus, Robert" uniqKey="Marcus R" first="Robert" last="Marcus">Robert Marcus</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 00A738 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 00A738 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Main |étape= Exploration |type= RBID |clé= Pascal:05-0446726 |texte= CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma }}
This area was generated with Dilib version V0.6.33. |