Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.
Identifieur interne : 000748 ( Main/Exploration ); précédent : 000747; suivant : 000749Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.
Auteurs : Mariano Serrao [Italie] ; Alberto Ranavolo [Italie] ; Carmela Conte [Italie] ; Chiara Davassi [Italie] ; Silvia Mari [Italie] ; Alfonso Fasano [Canada] ; Giorgia Chini [Italie] ; Gianluca Coppola [Italie] ; Francesco Draicchio [Italie] ; Francesco Pierelli [Italie]Source :
- Journal of neurology [ 1432-1459 ] ; 2015.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Biomechanical Phenomena, Dopamine Agonists (administration & dosage), Dopamine Agonists (pharmacology), Female, Gait Disorders, Neurologic (diagnosis), Gait Disorders, Neurologic (drug therapy), Gait Disorders, Neurologic (etiology), Humans, Locomotion (drug effects), Male, Middle Aged, Outcome Assessment (Health Care), Parkinson Disease (complications), Parkinson Disease (drug therapy), Tetrahydronaphthalenes (administration & dosage), Tetrahydronaphthalenes (pharmacology), Thiophenes (administration & dosage), Thiophenes (pharmacology).
- MESH :
- chemical , administration & dosage : Dopamine Agonists, Tetrahydronaphthalenes, Thiophenes.
- chemical , pharmacology : Dopamine Agonists, Tetrahydronaphthalenes, Thiophenes.
- complications : Parkinson Disease.
- diagnosis : Gait Disorders, Neurologic.
- drug effects : Locomotion.
- drug therapy : Gait Disorders, Neurologic, Parkinson Disease.
- etiology : Gait Disorders, Neurologic.
- Aged, Aged, 80 and over, Biomechanical Phenomena, Female, Humans, Male, Middle Aged, Outcome Assessment (Health Care).
Abstract
The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.
DOI: 10.1007/s00415-015-7883-4
PubMed: 26303834
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000379
- to stream PubMed, to step Curation: 000379
- to stream PubMed, to step Checkpoint: 000379
- to stream Ncbi, to step Merge: 001C88
- to stream Ncbi, to step Curation: 001C88
- to stream Ncbi, to step Checkpoint: 001C88
- to stream Main, to step Merge: 000749
- to stream Main, to step Curation: 000748
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.</title><author><name sortKey="Serrao, Mariano" sort="Serrao, Mariano" uniqKey="Serrao M" first="Mariano" last="Serrao">Mariano Serrao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy. mariano.serrao@uniroma1.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina</wicri:regionArea><wicri:noRegion>Latina</wicri:noRegion></affiliation></author><author><name sortKey="Ranavolo, Alberto" sort="Ranavolo, Alberto" uniqKey="Ranavolo A" first="Alberto" last="Ranavolo">Alberto Ranavolo</name><affiliation wicri:level="3"><nlm:affiliation>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Conte, Carmela" sort="Conte, Carmela" uniqKey="Conte C" first="Carmela" last="Conte">Carmela Conte</name><affiliation wicri:level="3"><nlm:affiliation>Fondazione Don Gnocchi, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Fondazione Don Gnocchi, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Davassi, Chiara" sort="Davassi, Chiara" uniqKey="Davassi C" first="Chiara" last="Davassi">Chiara Davassi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina</wicri:regionArea><wicri:noRegion>Latina</wicri:noRegion></affiliation></author><author><name sortKey="Mari, Silvia" sort="Mari, Silvia" uniqKey="Mari S" first="Silvia" last="Mari">Silvia Mari</name><affiliation wicri:level="3"><nlm:affiliation>Fondazione Don Gnocchi, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Fondazione Don Gnocchi, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Fasano, Alfonso" sort="Fasano, Alfonso" uniqKey="Fasano A" first="Alfonso" last="Fasano">Alfonso Fasano</name><affiliation wicri:level="4"><nlm:affiliation>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Chini, Giorgia" sort="Chini, Giorgia" uniqKey="Chini G" first="Giorgia" last="Chini">Giorgia Chini</name><affiliation wicri:level="3"><nlm:affiliation>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Coppola, Gianluca" sort="Coppola, Gianluca" uniqKey="Coppola G" first="Gianluca" last="Coppola">Gianluca Coppola</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti Foundation-IRCCS, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti Foundation-IRCCS, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Draicchio, Francesco" sort="Draicchio, Francesco" uniqKey="Draicchio F" first="Francesco" last="Draicchio">Francesco Draicchio</name><affiliation wicri:level="3"><nlm:affiliation>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Pierelli, Francesco" sort="Pierelli, Francesco" uniqKey="Pierelli F" first="Francesco" last="Pierelli">Francesco Pierelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina</wicri:regionArea><wicri:noRegion>Latina</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26303834</idno><idno type="pmid">26303834</idno><idno type="doi">10.1007/s00415-015-7883-4</idno><idno type="wicri:Area/PubMed/Corpus">000379</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000379</idno><idno type="wicri:Area/PubMed/Curation">000379</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000379</idno><idno type="wicri:Area/PubMed/Checkpoint">000379</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000379</idno><idno type="wicri:Area/Ncbi/Merge">001C88</idno><idno type="wicri:Area/Ncbi/Curation">001C88</idno><idno type="wicri:Area/Ncbi/Checkpoint">001C88</idno><idno type="wicri:Area/Main/Merge">000749</idno><idno type="wicri:Area/Main/Curation">000748</idno><idno type="wicri:Area/Main/Exploration">000748</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.</title><author><name sortKey="Serrao, Mariano" sort="Serrao, Mariano" uniqKey="Serrao M" first="Mariano" last="Serrao">Mariano Serrao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy. mariano.serrao@uniroma1.it.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina</wicri:regionArea><wicri:noRegion>Latina</wicri:noRegion></affiliation></author><author><name sortKey="Ranavolo, Alberto" sort="Ranavolo, Alberto" uniqKey="Ranavolo A" first="Alberto" last="Ranavolo">Alberto Ranavolo</name><affiliation wicri:level="3"><nlm:affiliation>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Conte, Carmela" sort="Conte, Carmela" uniqKey="Conte C" first="Carmela" last="Conte">Carmela Conte</name><affiliation wicri:level="3"><nlm:affiliation>Fondazione Don Gnocchi, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Fondazione Don Gnocchi, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Davassi, Chiara" sort="Davassi, Chiara" uniqKey="Davassi C" first="Chiara" last="Davassi">Chiara Davassi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina</wicri:regionArea><wicri:noRegion>Latina</wicri:noRegion></affiliation></author><author><name sortKey="Mari, Silvia" sort="Mari, Silvia" uniqKey="Mari S" first="Silvia" last="Mari">Silvia Mari</name><affiliation wicri:level="3"><nlm:affiliation>Fondazione Don Gnocchi, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Fondazione Don Gnocchi, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Fasano, Alfonso" sort="Fasano, Alfonso" uniqKey="Fasano A" first="Alfonso" last="Fasano">Alfonso Fasano</name><affiliation wicri:level="4"><nlm:affiliation>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, ON</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Chini, Giorgia" sort="Chini, Giorgia" uniqKey="Chini G" first="Giorgia" last="Chini">Giorgia Chini</name><affiliation wicri:level="3"><nlm:affiliation>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Coppola, Gianluca" sort="Coppola, Gianluca" uniqKey="Coppola G" first="Gianluca" last="Coppola">Gianluca Coppola</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti Foundation-IRCCS, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti Foundation-IRCCS, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Draicchio, Francesco" sort="Draicchio, Francesco" uniqKey="Draicchio F" first="Francesco" last="Draicchio">Francesco Draicchio</name><affiliation wicri:level="3"><nlm:affiliation>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Pierelli, Francesco" sort="Pierelli, Francesco" uniqKey="Pierelli F" first="Francesco" last="Pierelli">Francesco Pierelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina</wicri:regionArea><wicri:noRegion>Latina</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of neurology</title><idno type="eISSN">1432-1459</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Biomechanical Phenomena</term><term>Dopamine Agonists (administration & dosage)</term><term>Dopamine Agonists (pharmacology)</term><term>Female</term><term>Gait Disorders, Neurologic (diagnosis)</term><term>Gait Disorders, Neurologic (drug therapy)</term><term>Gait Disorders, Neurologic (etiology)</term><term>Humans</term><term>Locomotion (drug effects)</term><term>Male</term><term>Middle Aged</term><term>Outcome Assessment (Health Care)</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (drug therapy)</term><term>Tetrahydronaphthalenes (administration & dosage)</term><term>Tetrahydronaphthalenes (pharmacology)</term><term>Thiophenes (administration & dosage)</term><term>Thiophenes (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Dopamine Agonists</term><term>Tetrahydronaphthalenes</term><term>Thiophenes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Dopamine Agonists</term><term>Tetrahydronaphthalenes</term><term>Thiophenes</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Gait Disorders, Neurologic</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Locomotion</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Gait Disorders, Neurologic</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Gait Disorders, Neurologic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Biomechanical Phenomena</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Outcome Assessment (Health Care)</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The aim of this study was to investigate the effect of a rotigotine transdermal patch on stationary and non-stationary locomotion in de novo Parkinson disease (PD) patients in an open-label uncontrolled study. A 3-D gait analysis system was used to investigate four different locomotor tasks: steady-state linear walking, gait initiation, gait termination and 180°-turning. A series of gait variables were measured for each locomotor task. PD patients who received rotigotine treatment (4-8 mg) displayed: (1) increased step length, gait speed, cadence and arm oscillations, and reduced double support duration and step asymmetry during steady-state linear gait; (2) increased initial step length during gait initiation; (3) increased final step length and gait speed, and decreased stability index during gait termination; (4) decreased duration of turning and head-pelvis delays during 180°-turning. The main finding that emerges from the present study is that the dopamine agonist rotigotine can improve various aspects of gait in de novo PD patients.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Italie</li></country><region><li>Latium</li><li>Lombardie</li><li>Ontario</li></region><settlement><li>Milan</li><li>Rome</li><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Italie"><noRegion><name sortKey="Serrao, Mariano" sort="Serrao, Mariano" uniqKey="Serrao M" first="Mariano" last="Serrao">Mariano Serrao</name></noRegion><name sortKey="Chini, Giorgia" sort="Chini, Giorgia" uniqKey="Chini G" first="Giorgia" last="Chini">Giorgia Chini</name><name sortKey="Conte, Carmela" sort="Conte, Carmela" uniqKey="Conte C" first="Carmela" last="Conte">Carmela Conte</name><name sortKey="Coppola, Gianluca" sort="Coppola, Gianluca" uniqKey="Coppola G" first="Gianluca" last="Coppola">Gianluca Coppola</name><name sortKey="Davassi, Chiara" sort="Davassi, Chiara" uniqKey="Davassi C" first="Chiara" last="Davassi">Chiara Davassi</name><name sortKey="Draicchio, Francesco" sort="Draicchio, Francesco" uniqKey="Draicchio F" first="Francesco" last="Draicchio">Francesco Draicchio</name><name sortKey="Mari, Silvia" sort="Mari, Silvia" uniqKey="Mari S" first="Silvia" last="Mari">Silvia Mari</name><name sortKey="Pierelli, Francesco" sort="Pierelli, Francesco" uniqKey="Pierelli F" first="Francesco" last="Pierelli">Francesco Pierelli</name><name sortKey="Ranavolo, Alberto" sort="Ranavolo, Alberto" uniqKey="Ranavolo A" first="Alberto" last="Ranavolo">Alberto Ranavolo</name></country><country name="Canada"><region name="Ontario"><name sortKey="Fasano, Alfonso" sort="Fasano, Alfonso" uniqKey="Fasano A" first="Alfonso" last="Fasano">Alfonso Fasano</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000748 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000748 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:26303834
|texte= Effect of 24-h continuous rotigotine treatment on stationary and non-stationary locomotion in de novo patients with Parkinson disease in an open-label uncontrolled study.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:26303834" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |