Extract text from PDF.ipynb

{
 "metadata": {
  "name": "",
  "signature": "sha256:b7930b6172472b720517f0a39345cf049ab9aafbb963771cb5bebed93ab9b4bc"
 },
 "nbformat": 3,
 "nbformat_minor": 0,
 "worksheets": [
  {
   "cells": [
    {
     "cell_type": "code",
     "collapsed": false,
     "input": [
      "# importing required modules \n",
      "import PyPDF2 \n",
      "\n",
      "# creating a pdf file object \n",
      "pdfFileObj = open('/Users/phuong/Downloads/AAAI_Data/Kwan_1999_9987702.pdf', 'rb') \n",
      "\n",
      "# creating a pdf reader object \n",
      "pdfReader = PyPDF2.PdfFileReader(pdfFileObj) \n",
      "\n",
      "# printing number of pages in pdf file \n",
      "print(pdfReader.numPages) \n",
      "\n",
      "# creating a page object\n",
      "for i in xrange(pdfReader.numPages):\n",
      "    pageObj = pdfReader.getPage(0) \n",
      "\n",
      "    # extracting text from page \n",
      "    print(pageObj.extractText()) \n",
      "\n",
      "# closing the pdf file object \n",
      "pdfFileObj.close() "
     ],
     "language": "python",
     "metadata": {},
     "outputs": [
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "8\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n",
        "DRUGINTERACTIONSTheEffectsofAcetaminophenonPharmacokineticsandPharmacodynamicsofWarfarinDeboraKwan,BScPhm,MSc,WilliamR.Bartle,PharmD,andScottE.Walker,MScPhmTheoralanticoagulantwarfarinisclinicallyadministeredasaracemicmixtureoftwoenantiomers,(R)and(S).Manyrele-vantdruginteractionswithwarfarinhavebeenattributedtothespecificmetabolicinhibitionoftheeliminationofthemorepharmacologicallyactive(S)-enantiomer.Toinvestigatereportsthatacetaminophencanpotentiatetheanticoagulanteffectofwarfarin,20healthymalevolunteerswereeachgivensingleoral20mgdosesofracemicwarfarinonthreeseparateoccasions:(1)alone,(2)after1dayofacetaminophen(4gld),and(3)after2weeksofcicetaminophen(4g/d).TheurinaryINTRODUCTIONTheoralanticoagulantwarfarinhasbeenshowntointeractwithnumerousdrugs,frequentlyresultinginthemostseriousandcommonconsequenceofantico-agulanttherapy,hemorrhage.Manyclinicallysignifi-cantwarfarindruginteractionshavebeenattributedtothespecificinhibitionofthemetabolismofthemorepharmacologicallyactive(S)-enantiomer.'Thewidelyusednonprescriptionanalgesic/antipy-retic,acetaminophen,isoftenrecommendedtoantico-agulatedpatientsasanalternativetoacetylsalicylicacid(aspirin)becauseitlackstheeffectsofthelatteronthegastricmucosaandplatelets.However,casereportsandcontrolledstudiesintheliteraturehavesuggestedthatthehypoprothrombinemicresponsetowarfarincanbepotentiatedbyconcomitantacetaminophenFromtheDepartmentsofPharmacy,SunnybrookHealthScienceCentre,NorthYork,Ontario,andtheTorontoRehabilitationInstitute.SubmittedforpublicationApril30,1998;revisedversionacceptedAugust17,1998.Addressforreprints:Dr.WilliamR.Bartle,DepartmentofPhormacy,Sunny-brookHealthScienceCentre,2075BayviewAve.,NorthYork,Ontario,CanadaM5N3M5.excretionpatternofacetaminophenanditsmetaboliteswasnotsignificantlyalteredoveritscourseofadministration.The(R)-and(S)-enantiomersofwarfarinexhibitedsignificantlydifferentpharmacokineticproperties.However,acetamino-phendidnotalterthedispositionofeither(R)-or(S)-warfarin.Allsubjectsexhibitedapharmacodynamicresponsetorace-micw6irJarin.Theresponsewasnotsignificantlyalteredinthepresenceofacuteorchronicacetaminophendosing,asassessedbyprothrombintimeandfactorVIIconcentrations.JournalofClinicalPharmacology,1999;39:68-75(\u00a91999theAmericanCollegeofClinicalPharmacologyadministration.2'-Todate,theinformationavailableremainsinconclusive.Theobjectivesofthisstudy,usinghealthymalevolunteers,were(1)toassessthepharmacodynamiceffect(viaprothrombintimeandfactorVIIconcentrations)ofsingledosesofracemicwarfarinwhengivenaloneandconcomitantlywithacutelyandchronicallyadministeredacetaminophen,(2)todetermineifacuteand/orchronicacetaminophendosingaltersthestereoselectivedispositionandmetabolismofthe(R)-and/or(S)-enantiomersofwar-farin,and(3)tostudytheurinaryexcretionprofileofacetaminophenanditsmetabolitesoveritscourseofadministrationtodetermineapossiblemechanismforanypotentialinteraction.METHODSThestudywascarriedoutusingatwo-phaserandomizedcrossoverdesign.Acuteandchronicacetaminophendosingwasincorporatedintoonearm;thecontrolphasewastheotherarm.Thestudywasapprovedbytheinstitution'sresearchethicscommittee.Twentynonsmokingmales68*JClinPharmacol1999;39:68-75"
       ]
      },
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "\n"
       ]
      }
     ],
     "prompt_number": 2
    },
    {
     "cell_type": "code",
     "collapsed": false,
     "input": [
      "from pdfminer.pdfinterp import PDFResourceManager, PDFPageInterpreter\n",
      "from pdfminer.converter import TextConverter\n",
      "from pdfminer.layout import LAParams\n",
      "from pdfminer.pdfpage import PDFPage\n",
      "from io import BytesIO as StringIO\n",
      "import re\n",
      "import sys\n",
      "\n",
      "def convert_pdf_to_txt(path):\n",
      "    rsrcmgr = PDFResourceManager()\n",
      "    retstr = StringIO()\n",
      "    codec = 'utf-8'\n",
      "    laparams = LAParams()\n",
      "    device = TextConverter(rsrcmgr, retstr, codec=codec, laparams=laparams)\n",
      "    fp = open(path, 'rb')\n",
      "    interpreter = PDFPageInterpreter(rsrcmgr, device)\n",
      "    password = \"\"\n",
      "    maxpages = 0\n",
      "    caching = True\n",
      "    pagenos=set()\n",
      "\n",
      "    for page in PDFPage.get_pages(fp, pagenos, maxpages=maxpages, password=password,caching=caching, check_extractable=True):\n",
      "        interpreter.process_page(page)\n",
      "\n",
      "    text = retstr.getvalue()\n",
      "\n",
      "    fp.close()\n",
      "    device.close()\n",
      "    retstr.close()\n",
      "    return text\n",
      "\n",
      "text = convert_pdf_to_txt('/Users/phuong/Downloads/AAAI_Data/Kwan_1999_9987702.pdf')\n",
      "article_plaintext = open('/Users/phuong/Downloads/AAAI_Data/Kwan_1999_9987702.txt','w')  \n",
      "article_plaintext.write(text) \n",
      "article_plaintext.close()\n",
      "\n",
      "#Get the text between Methods & Results section: \n",
      "article_plaintext_file = open('/Users/phuong/Downloads/AAAI_Data/Kwan_1999_9987702.txt','r')          \n",
      "text_between_Methods_Results = []\n",
      "recording = False\n",
      "start_pattern = \"METHODS\"\n",
      "stop_pattern = \"RESULTS\"\n",
      "output_section = []\n",
      "for line in article_plaintext_file:\n",
      "    if recording is False:\n",
      "        #If the line contains \"METHODS\" header, start record the text, change the flag to \"TRUE\"\n",
      "        if re.search(start_pattern, line) is not None:\n",
      "            recording = True\n",
      "            output_section.append(line.strip())\n",
      "    elif recording is True:\n",
      "        #If the line contains \"METHODS\" header, start record the text, change the flag to \"FALSE\"\n",
      "        if re.search(stop_pattern, line) is not None:\n",
      "            recording = False\n",
      "        else:\n",
      "            output_section.append(line.strip())\n",
      "print '\\n'.join(output_section)   "
     ],
     "language": "python",
     "metadata": {},
     "outputs": [
      {
       "output_type": "stream",
       "stream": "stdout",
       "text": [
        "METHODS\n",
        "The study was carried out using a two-phase randomized\n",
        "crossover design. Acute and chronic acetaminophen\n",
        "dosing was incorporated into one arm; the control\n",
        "phase was the other arm.\n",
        "The study was approved by the institution's\n",
        "research ethics committee. Twenty nonsmoking males\n",
        "\n",
        "68 *\n",
        "\n",
        "J Clin Pharmacol 1999;39:68-75\n",
        "\n",
        "EFFECTS OFACETAMINOPHEN ON WARFARIN\n",
        "\n",
        "between the ages of 18 and 47, judged to be healthy\n",
        "based on a medical examination, including biochemi-\n",
        "cal and haematological profile, were recruited. Each\n",
        "volunteer gave written informed consent.\n",
        "In the first phase, each subject received a single 20\n",
        "mg dose of racemic warfarin orally, supplied as Cou-\n",
        "madin\u00ae 5 mg tablets (Du Pont Pharmaceuticals, Can-\n",
        "ada). This was referred to as treatment 1 (warfarin con-\n",
        "trol). In the second phase, each subject received a\n",
        "22-day regimen ofacetaminophen, 1 g four times a day,\n",
        "administered orally at 0700, 1200, 1800, and 2300 hr,\n",
        "supplied as Tylenol\u00ae 500 mg tablets (McNeil Consumer\n",
        "Products, Canada). On day 2 (representing acute dos-\n",
        "ing) and day 16 (representing chronic dosing) of this\n",
        "regimen, a single oral 20 mg dose of racemic warfarin\n",
        "was also administered. These were referred to as treat-\n",
        "ment 2 (warfarin and acute acetaminophen) and treat-\n",
        "ment 3 (warfarin and chronic acetaminophen), respec-\n",
        "tively. The order of phase one and two was assigned\n",
        "randomly with a 14-day washout period in between.\n",
        "Warfarin was administered with 240 mL of water and,\n",
        "in the second phase, was taken 1 hr after acetamino-\n",
        "phen administration.\n",
        "Blood samples (10 mL each) were collected at 0.5, 1,\n",
        "2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hr after warfarin\n",
        "administration. The samples were centrifuged and the\n",
        "serum removed and stored in red-top Vacutainer tubes\n",
        "(Becton-Dickinson) and then frozen (-200C) until the\n",
        "time of assay.\n",
        "Urine samples werecollected by the subjects, in bot-\n",
        "tles provided, at 24-hr intervals for 7 consecutive days\n",
        "after each dose of warfarin was administered. A urine\n",
        "sample was also collected just prior to administration\n",
        "of the warfarin dose. The volume of urine collected per\n",
        "24 hr was recorded and an aliquot frozen (-20\u00b0C) until\n",
        "the time of assay.\n",
        "\n",
        "Parameters Monitored\n",
        "\n",
        "Liver function tests, aspartate aminotransferase (AST)\n",
        "and alanine aminotransferase (ALT), were performed\n",
        "twice per week during treatments 2 and 3. It was\n",
        "decided that in the interest of subject safety, aceta-\n",
        "minophen would be discontinued if values increased\n",
        "to greater than four times normal (normal AST & ALT =\n",
        "30 IU/L).\n",
        "Subjects were asked about any adverse effects or\n",
        "protocol violations (e.g., missed urine collections,\n",
        "missed acetaminophen doses), and these were also\n",
        "recorded by the investigator in the diary.\n",
        "Upon completion of the study, blood samples were\n",
        "drawn, and the biochemical/haematological blood\n",
        "\n",
        "DRUG INTERACTIONS\n",
        "\n",
        "screen was repeated for each subject to ensure that val-\n",
        "ues were within normal limits.\n",
        "ANALYTICAL METHODS\n",
        "Warfarin Enantiomer Analysis\n",
        "The concentration of the (R)- and (S)-enantiomers of\n",
        "warfarin in the serum was determined using solid-\n",
        "phase extraction, normal-phase chiral liquid chroma-\n",
        "tography, and UV detection. Solid-phase extraction\n",
        "(Sep-Pak\u00ae C,8 3 mL cartridges; Waters Scientific, Mis-\n",
        "sissauga, Ontario) was used to prepare serum samples\n",
        "for analysis. Following conditioning with methanol\n",
        "and dilute phosphoric acid (H3PO4), 1 mL of serum\n",
        "mixed with 4 mL 0.5 M H3PO4 was introduced onto the\n",
        "cartridge. The column was washed with 15 mL of ace-\n",
        "tonitrile/0.5 M H3PO4 (30:70, v/v), and the drug was\n",
        "eluted from the column with 2.5 mL methanol. The\n",
        "sample was evaporated under nitrogen at 70\u00b0C. The\n",
        "residue was reconstituted with 300 .tL of mobile phase\n",
        "(ethyl alcohol/hexane, 2:1, v/v) and 50 .tL injected onto\n",
        "the column for analysis.\n",
        "The mobile phase was pumped at 0.5 mL/min\n",
        "(Waters 510, Waters Scientific, Mississauga, Ontario)\n",
        "through a 25 cm x 4.6 mm cellulose tris(phenyl carba-\n",
        "mate) 10.tm column (Chiralcel\u00ae OC, Chiral Technolo-\n",
        "gies Inc, Exton, PA) with a silica 1.5 cm guard cartridge\n",
        "(Brownlee Aquapore Silica, Applied Biosystems, CA).\n",
        "The column effluent was monitored with a variable\n",
        "wavelength ultraviolet detector at 280 nm (Spectro-\n",
        "flow 783, Kratos, Westwood, NJ). Chromatograms were\n",
        "recorded and integrated on a chromatographic integra-\n",
        "tor (ChromJet, Spectra Physics Analytical, CA).\n",
        "A pure (S)-warfarin standard was prepared from\n",
        "racemic warfarin by the method of West et al.8 Briefly,\n",
        "this method produces quinidine-(S)-warfarin as an\n",
        "intermediate that can then be hydrolyzed to yield\n",
        "(S)-warfarin. Confirmation ofthe identity ofquinidine-\n",
        "(S)-warfarin and (S)-warfarin was carried out by measur-\n",
        "ing optical rotations and melting points and comparing\n",
        "the observed results with published reference stan-\n",
        "dards.8 The pure standard of (S)-warfarin was used\n",
        "to confirm that (R)-warfarin eluted at 9.3 min and\n",
        "(S)-warfarin eluted at 12.5 min.\n",
        "Calibration curves were linear over the range of 0 to\n",
        "1.75 Rtg/mL. Mean recovery was 90.6% for (R)-warfarin\n",
        "and 91.4% for (S)-warfarin, and the limit of quantita-\n",
        "tion was 0.05 ,ug/mL for each enantiomer. Intra-assay\n",
        "coefficients of variation (CV) were less than 2.5% at\n",
        "0.25 .tg/mL and less than 1.5% at 1.0 Hig/mL for both\n",
        "(R)- and (S)-warfarin.\n",
        "\n",
        "69L\n",
        "\n",
        "KWAN ETAL\n",
        "\n",
        "Acetaminophen and Metabolites in Urine\n",
        "The concentration of acetaminophen and its metabo-\n",
        "lites in urine was determined using a reverse-phase C,8\n",
        "5 gm column (25 cm x 4.6 mm, 5 Ht ODS Ultrasphere,\n",
        "Beckman, Ontario), linear gradient mobile phase (5%\n",
        "to 30% acetonitrile over 50 min), and UV detection at\n",
        "246 nm (Spectroflow 783 programmable absorbance\n",
        "detector, Kratos, NJ). One microliter ofeach urine sam-\n",
        "ple was injected directly onto the column. The liquid\n",
        "chromatographic system comprised of a tertiary gradi-\n",
        "ent solvent pump (Waters 600E system controller, Mil-\n",
        "lipore, Ontario), which pumped the mobile phase at 1\n",
        "mL/min. Chromatograms were recorded and integrated\n",
        "on a chromatographic integrator (ChromJet, Spectra\n",
        "Physics Analytical, CA). The assay was linear over\n",
        "the range of0 to 6000 mg/L acetaminophen. The limit of\n",
        "quantitation was 10 mg/L acetaminophen. All metabo-\n",
        "lites of acetaminophen-sulfate, glucuronide,\n",
        "3-cysteinylacetaminophen, 3-methylthioacetaminophen,\n",
        "acetaminophen-3-mercapturate, 3-hydroxya-\n",
        "cetaminophen, and 3-methoxyacetaminophen- were\n",
        "kindly provided by Dr. S. D. Nelson of the University of\n",
        "Washington. The quantity of acetaminophen and\n",
        "metabolites was expressed as a percentage of the total\n",
        "amount recovered per.24 hr of urine collection (e.g., %\n",
        "glucuronide). Metabolites formed via the cytochrome\n",
        "P450 pathway (3-cysteinyl- acetaminophen, methyl-\n",
        "thioacetaminophen, and acetaminophen-3-\n",
        "mercapturate) were grouped together and expressed as\n",
        "one percentage (%oP450).\n",
        "DATA ANALYSIS\n",
        "Warfarin\n",
        "Pharmacokinetic analysis was carried out to describe\n",
        "the disposition of the (R)- and (S)-enantiomers of war-\n",
        "farin in the absence and presence of acute and chronic\n",
        "acetaminophen administration. For each enantiomer,\n",
        "the following parameters were calculated: the maxi-\n",
        "mum serum concentration and time to maximum\n",
        "serum concentration, obtained from each subject's\n",
        "serum concentration-time profile by direct observa-\n",
        "tion. Using the serum concentration-time curve, the\n",
        "elimination rate constant was determined by linear\n",
        "least squares regression of the slope of the terminal log\n",
        "serum concentration-time profile. Elimination half-\n",
        "life, the area under the serum concentration-time\n",
        "curve, and the total apparent oral clearance were calcu-\n",
        "lated using standard methods.,' Each pharmacokinetic\n",
        "\n",
        "parameter was reported as the mean \u00b1 standard\n",
        "deviation.\n",
        "Pharmacodynamic Data:\n",
        "Assessment of Anticoagulation\n",
        "The degree of anticoagulation was assessed by\n",
        "prothrombin time (PT) and factor VII concentrations\n",
        "(FVII) and reflects the pharmacodynamic effects of\n",
        "racemic warfarin. Since warfarin was administered as\n",
        "a racemic mixture, the anticoagulant effects of the\n",
        "enantiomers could not be measured separately.\n",
        "After each dose of warfarin, 4.5 mL blood samples\n",
        "were collected in tubes containing 0.5 mL of buffered\n",
        "sodium citrate (3.8%) at the following times: 0, 4, 8, 12,\n",
        "24, 48, 72, and 96 hr for PT and 0, 12, 24, and 96 hr for\n",
        "FVII. Each subject's PT and FVII had to return to within\n",
        "baseline limits before the subject could proceed to the\n",
        "next treatment. Times chosen reflect those at which\n",
        "significant changes in PT and FVII should be\n",
        "detected.\",2\n",
        "The PT, in seconds, was determined by the one-stage\n",
        "prothrombin time test using the Simplastin\u00ae auto-\n",
        "mated thromboplastin reagent derived from rabbit\n",
        "brain and lung. For FVII concentrations, a range ofdilu-\n",
        "tions of sample and standard plasmas using Factor VII\n",
        "Deficient Plasma was prepared and clotting times per-\n",
        "formed for each dilution.\n",
        "PT and FVII values were reported as the change in\n",
        "PT and the percentage reduction in FVII, rather than\n",
        "absolute values. This would allow a comparison of the\n",
        "relative changes between subjects and treatments. A\n",
        "significant change in PT was predefined as a change of\n",
        "greater than 2 sec. A reduction in FVII of at least 50%\n",
        "was considered to be a significant change.-3\n",
        "Parameters used to assess the degree of anticoagula-\n",
        "tion were mean time to maximum effect, maximum\n",
        "change in PT, maximum percentage reduction in FVII,\n",
        "and area under the curve for change in PT versus time.\n",
        "The reductions in FVII were compared between treat-\n",
        "ments at each corresponding time point measured (i.e.,\n",
        "12, 24, and 96 hr).\n",
        "STATISTICAL ANALYSIS\n",
        "Three-way analysis of variance (ANOVA) was carried\n",
        "out for each pharmacokinetic and pharmacodynamic\n",
        "parameter blocking for subject, treatment, and order of\n",
        "exposure to warfarin. Fisher's protected least signifi-\n",
        "cant difference multiple-range test was used to identify\n",
        "significant differences between treatments and order.\n",
        "\n",
        "70 *\n",
        "\n",
        "J Clin Pharmacol 1999;39:68-75\n",
        "\n",
        "EFFECTS OF ACETAMINOPHEN ON WARFARIN\n",
        "\n",
        "For each of acetaminophen and its metabolites, fac-\n",
        "torial analysis of variance was performed to compare\n",
        "values between each day of urine collection during the\n",
        "acetaminophen regimen. The pattern of urinary excre-\n",
        "tion during acute versus chronic acetaminophen dos-\n",
        "ing was also compared.\n",
        "The 5% level was used as the limit of statistical\n",
        "significance.\n"
       ]
      }
     ],
     "prompt_number": 1
    },
    {
     "cell_type": "code",
     "collapsed": false,
     "input": [],
     "language": "python",
     "metadata": {},
     "outputs": []
    }
   ],
   "metadata": {}
  }
 ]
}