University of Groningen

Acute metabolic changes in critical care and cardiac careHoekstra, Miriam

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Publication date:2016

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Citation for published version (APA):Hoekstra, M. (2016). Acute metabolic changes in critical care and cardiac care: Role of potassium, glucoseand lactate. [Groningen]: University of Groningen.

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)nh.mias— fmocac— rnshtdMdn0— 1aslmlrnshtdMpofp— .nitllomh— unrisnd— tyiasutscotu— lmsfas,T— rn— oh.tui— nr— tisotdyowsoddtionr—ns—tisotd—ydmiias

b

–na-list—Av—–alladl—Jv—Goarlist—Av—Yap—Jv—qmca—Jtrlor-—5v—Vnfadxtrf—Av—1tr—cas–nsli—C)v—Atsotro—A5v—ca—9hai—5Av—9ism,l—AAv—Zo/dlist—Uv—jo/liar—A%g

American Heart Journal, accepted for publication.

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Abstract

IntroductionRpol—limc,—0tl—calofrac—in—caiashora—ipa—ayyaui—ny—i0n—coyyasari—.nitllomh—safmdtionr—listiafoal—0oipcoyyasari—itsfail—30oipor—ipa—sayasarua—strfa(—nr—5UW5UJ—or—t—unpnsi—ny—oriarlo1a—utsa—mroi—3C)N(—.tioariltyias—utscotu—lmsfas,g

MethodsRpa—DGC7M)qA7599—limc,—0tl—t—.snl.auio1a—cnmwdaMwdorcac—orias1arionrtd—limc,—or—8bI—.tioaril—tyiasutscotu—lmsfas,—3unsnrts,—tsias,—w,.tll—fstyiorf—trcWns—1td1mdts—lmsfas,(g—7tioaril—0asa—tllofrac—in—aoipasipa—rnshtdMdn0—.nitllomh—itsfai—3rJ7—fsnm.v—kgI—hhndWJ(—ns—ipa—rnshtdMpofp—.nitllomh—itsfai—3r–7—fsnm.vkgP—hhndWJ( or—tdiasrtiorf—wdnu-l—ny—PI—.tioarilg—7nitllomh— da1adl—0asa—safmdtiac—mlorf—t—1tdoctiacunh.miasMtlloliac—.nitllomh—sa.dtuahari—.sninund—3DGC7MCC(g—Rpa—.sohts,—arc.nori—0tl—ipa—oruocaruany—5UW5UJ—nr—t—b Mdatc—z)D—cmsorf—ipa—yosli—.nlin.astio1a—0aa-g

Resultsqy—ipa—8bI—.tioarilv—kk6—0asa—tllofrac—in—ipa—rJ7—fsnm.—trc—kS4—in—ipa—r–7—fsnm.v—0oip—rn—wtladoracoyyasarual—wai0aar—ipa—i0n—fsnm.lg—Rpa—hatr—ctod,Mtchoroliasac—cnla—ny—.nitllomh—0tl—4I± 4—hhnd3rJ7(— 1aslml— P ± 6—hhnd— 3r–7(— 37OgIIb(v—0poup— salmdiac— or—hatr— C)N—.nitllomh—unruaristionr—nysal.auio1ad,—kg ±g4S—hhndWJ—trc—kg44±g4k—hhndWJ—37OgIIb(g—Rpa—oruocarua—ny—5UW5UJ—tyias—utscotulmsfas,—coc—rni—coyyasT—4:;—or—ipa—rJ7—fsnm.—trc—kb;—or—ipa—r–7—fsnm.g—5dln—or—la1astd—lmwfsnm.l—3agfg.tioaril—rni—-rn0r—0oip—.sons—5UW5UJ—ns—0oip—1td1a—lmsfas,(v—ipasa—0asa—rn—coyyasarualg

Conclusions Rpasa—0asa—rn—coyyasarual—or—oruocarua—ny—5UW5UJ—0oip—i0n—.nitllomh—safmdtionr—listiafoal—0oip—coyyasari.nitllomh—itsfail—trc—coyyasari—thnmril—ny—.nitllomh—tchoroliasac—or—.tioaril—tyias—utscotu—lmsfas,g

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Introduction

5isotd—yowsoddtionr—35U(—ns—tisotd—ydmiias—35UJ(—nuumsl—ysa marid,—or—.tioaril—tchoiiac—in—ipa—oriarlo1a—utsa—mroi3C)N(—tyias—utscotu—lmsfas,—trc—ol—tllnuotiac—0oip—orusatlac—hnswocoi,—trc—hnsitdoi,—bv— g—Rpa—mrcasd,orfhauptrolhl—tsa—hmdioMytuinsotd—trc—utr—wa—co1ocac—orin—.tioariMsadtiac—ytuinsl—3lismuimstd—patsi—colatlavndcas—tfa(—trc—tumia—lmsfas,Msadtiac—ytuinsl—3hoistd—1td1a—lmsfas,v—utscon.mdhnrts,—w,.tll(g—5csarasfoutuio1tionr—sadtiac—in—lmsfoutd—lisall—trc—orydthhtionr—.dt,l—tr—oh.nsitri—snda—4v—kg—5rnipas—.nllowda—sol-ytuins—yns—ipa—ca1adn.hari—yns—5UW5UJ—unmdc—wa—.nitllomh—castrfaharil—lorua—ipa,—tsa—tllnuotiac—0oiplm.st1arisoumdts— tssp,iphot— kLSg— %paipas— iofpi— .nitllomh— safmdtionr— unmdc— sacmua— ipa— oruocarua— ny.nlin.astio1a—5UW5UJ—ol—mr-rn0rg—Cr—t—farastd—utscon1tlumdts—.n.mdtionrv—t—rnshtdMpofp—.nitllomh—da1adol—tllnuotiac—0oip—.nloio1a—nmiunha—6g—%a—p,.nipaloxac—ipti—t—rnshtdMpofp—.nitllomh—itsfai—cmsorf—C)Ntchollonr—hofpi—tdln—wa—warayouotd—or—ipa—.sa1arionr—ny—.nlin.astio1a—5U—trc—5UJ—tyias—utscotu—lmsfas,—6v:g—Cr—ipa—.salari—lorfda—uariasv—.snl.auio1ad,—unrisnddac—isotdv—0a—unh.tsac—t—unh.mias—fmocac—rnshtdMdn0—.nitllomh—unrisnd—listiaf,—0oip—t—rnshtdMpofp—.nitllomh—unrisnd—listiaf,—nr—ipa—nuumssarua—ny5UW5UJ—or—.tioaril—tyias—utscotu—lmsfas,g

Methods

Study designRpa— unh.miasMcso1ar— Ddmunla— trc— .nitllomh— Gafmdtionr— .snfsth— or— Criarlo1a— utsa— 7tioaril— 0oip)qA.tsolnr—ny—7ni599omh—itsfail—0oipor—rnshn-tdahou—strfa—3DGC7M)qA7599(—isotd—0tl—t—.snl.auio1acnmwdaMwdorcac—orias1arionrtd—limc,—unh.tsorf—i0n—.nitllomh—unrisnd—listiafoal—trc—ipa—ayyaui—nr—5Utrc—5UJ—tyias—utscotu—lmsfas,g—Crudmlonr—litsiac—Bmra— II8—trc—arcac—quinwas— IbIg—Rpa—limc,—calofrptl—waar—calusowac—.sa1onmld,—:g—9imc,—t..sn1td—0tl—nwitorac—ysnh—ipa— orlioimionrtd—hacoutd—aipoulunhhoiiaa—3AzRu— II8WI8S(—trc—ipa—limc,—.sninund—0tl—safoliasac—ti—)doroutdRsotdlgfn1—3j)R—IbI:PI6b(gCrynshac—unrlari—0tl—0to1ac—w,—ipa—orlioimionrtd—hacoutd—aipoul—unhhoiiaa—lorua—or—wnip—limc,—tshl—ipa.nitllomh—safmdtionr—.sninund—ol—litrctsc—utsa—or—nms—orlioimionrv—0oip—ipa—nrd,—coyyasarua—ipti—ipa—i0ntshl—tohac—ti—i0n—l.auoyou—da1adl—ipti—0asa—wnip—0oipor—ipa—rnshtd—strfa—orliatc—ny—/mli—tr,—da1ad—0oiporipa—rnshtd—strfag

Rpa—limc,—0tl—.asynshac—or—t—b4Mwac—utsconipnstuou—C)N—or—ipa—jaipasdtrcl—ipti—ol—.tsi—ny—t—dtsfas—kPMwac—tcmdi—C)N—ny—ipa—Nro1asloi,—Aacoutd—)arias—Dsnrorfarg—5dd—tcmdi—.tioaril—tchoiiac—cmsorf—ipa—limc,.asonc—0asa—unrlocasac—adofowda— yns— orudmlonrg— Crudmlonr—usoiasot—0tl—tchollonr—tyias—utscotu—lmsfas,3unsnrts,—tsias,—w,.tll—fstyiorf—[)5ED]—trcWns—1td1a—lmsfas,(g—zFudmlonr—usoiasot—0asa—ipa—twlarua—ny—tuaristd—1arnml— dora—ns—tr—ariastd— yaacorf— imwav—tl— ipnla—0asa—htrctins,— yns— ipa—unh.miasMtlloliac.nitllomh—unrisnd—tl—.asynshac—w,—DGC7MCC—3fdmunla—trc—.nitllomh—safmdtionr—or—oriarlo1a—utsa—.tioaril(or—ipol—orlioimionrg—5yias—orudmlonrv—ipa—.tioaril—0asa—tddnutiac—in—ipa—rnshtdMdn0—.nitllomh—3rJ7(—itsfai3kgI—hhndWJ(—ns—rnshtdMpofp—.nitllomh—3r–7(—itsfai—3kgP—hhndWJ(—or—tdiasrtiorf—wdnu-l—ny—PI—unrlaumio1a.tioarilg—7tioaril—sahtorac—or—ipol—isatihari—listiaf,—mriod—C)N—coluptsfag

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Computer-assisted potassium regulation5yias—orudmlonr—ohhacotiad,—ynddn0orf—C)N—tchollonrv—.nitllomh—0tl—safmdtiac—tuunscorf—in—ipa—tddnutiac.nitllomh—itsfai—ny—kgI—hhndWJ—ns—kgP—hhndWJv—w,—ipa—unh.miasMtlloliac—.nitllomh—safmdtionr—.sninundutddac—DGC7MCC—8Lbbg—Rpa—.p,louotrlv—rmslal—trc—.tioaril—0asa—mrt0tsa—yns—ipa—tddnutiac—isatihari—listiaf,gDGC7MCC—ol—t—rmslaMwtlac—oriafstiac—.nitllomh—trc—fdmunla—safmdtionr—.snfsth—ipti—.asoncoutdd,—.sn1ocaltc1oual—nr—ipa—calosac—.nitllomh—trc—orlmdor—orymlonr—stial—tl—0add—tl—ipa—raFi—lth.dorf—iohag—7nitllomhol—tchoroliasac—unriormnmld,—w,—t—l,sorfa—.mh.—or—t—b—hhndWhd—unruaristionr—n1as—t—uaristd—1arnmlutipaias—ns—ariastdd,—n1as—t—ftlisouv—cmncartd—ns—/a/mrtd—imwag—Uns—ipa—.nitllomh—tdfnsoiphv—ipa—tc1olac.mh.—stia—ol—wtlac—nr—wnip—ipa—.nitllomh—isarc—n1as—ioha—trc—l.auoyou—.tioari—uptstuiasolioul—do-a—-ocra,ymruionrg— Cr— tccoionr— in— ipa— safmdtionr— tdfnsoiphv— oi— tdln— tuil— tl— t—0tsrorf— l,liah— yns— nmiMnyMstrfa.nitllomh—trc—fdmunla—da1adlg—Ednnc—lth.dal—yns—.nitllomh—hatlmsaharil—0asa—it-ar—ysnh—ipa—tsiasotddora—or—doipomhMpa.tsor—trioMuntfmdtiac—l,sorfal—37C)qv—Gtconhaiasv—)n.arptfar(—trc—trtd,lac—w,—t—.noriMnyMutsa— 37q)(— wdnnc— ftl— trtd,las— .salari— ti— ipa— C)N— 35EJ— Gtconhaias— :II— lasoalv— Gtconhaiasv)n.arptfarv—Harhts-(g—5yias—C)NMcoluptsfa—.nitllomh—safmdtionr—0tl—.p,louotrMwtlacv—0oipnmi—ipapad.—ny—t—l.auoyou—tdfnsoiph—trc—tdln—0oipnmi—t—l.auoyou—itsfaig—Hmsorf—C)N—tchollonr—ipa—litrctsc—orymlonrydmoc—yns—ipa—wtltd—ctod,—sa mosahari—0tl—ltdora—gkP;—0oip—fdmunla— gP;g—)tscotu—.tioaril—0asa—litsiacnr—unriormnml—htfralomh—lmdytia—lm..daharitionr—ny—4I—hhndWct,—m.nr—tsso1td—ti—ipa—C)Ng

Study endpoints7sohts,—arc.nori—0tl—ipa—oruocarua—ny—5UW5UJ—or—ipa—yosli—6—ct,l—tyias—utscotu—lmsfas,—3)5ED—trc—ns1td1a—lmsfas,(—0oip—ns—0oipnmi—ipa—mla—ny—utscon.mdhnrts,—w,.tllg—Rpa—.salarua—ny—5UW5UJ—ptc—in—waunryoshac—0oip—t—b Mdatc—adauisnutsconfsth—3z)D(v—0oip—ipa—tssp,iphot—.salari—yns—ipa—ariosa—safolistionr3bI—lau(g—9aunrcts,—arc.noril—0asa—ipa—da1ad—ny—.nitllomh—unrisnd—3hatr—.nitllomh—1tdmalv—hatr—ctod,thnmri—ny—tchoroliasac—.nitllomhv—oruocarua—ny—p,.nM—trc—p,.as-tdahot(g—Rasiots,—arc.noril—0asa—darfipMnyMlit,—3C)N—trc—pnl.oitd(v—tumia—h,nutscotd—orytsuionrv—uasawstd—1tlumdts—tuuocaril—3)V5(v—-ocra,—ytodmsasa mosorf—sartd—sa.dtuahari—ipast.,—trc—hnsitdoi,—3ti—C)Nv—pnl.oitdv—8I—ct,lv—trc—nraM,ats(g

Figure 1 Udn0uptsi—ny—ipa—DGC7M)qA7599—limc,g5i—C)N—tchollonrv—.tioaril—tyias—utscotu—lmsfas,—0asa—tllofrac—in—aoipas—ipa—rnshtdMdn0—.nitllomh—itsfai—3rJ7(—ns—iparnshtdMpofp—.nitllomh—itsfai—3r–7(—or—wdnu-l—ny—PI—.tioarilg

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Data collection7tioari—cahnfst.poul—0asa—unddauiac—ti—C)N—tchollonrg—Cr—tccoionrv—yns—.tioaril—tchoiiac—tyias—utscotulmsfas,v—ctit—saftscorf—ipa—oristMn.astio1a—.asonc—0asa—saisoa1ac—ysnh—ipa—tralipaiou—sa.nsig—5—utlaMsa.nsiynsh—3)GU(—0tl—yoddac—nmi—yns—a1as,—orudmcac—.tioari—trc—unddauiac—ti—pnl.oitd—coluptsfag—Ealoca—tuunscorfin— ipa— tddnutiac— itsfaig— 5dd— hacoutd— .snuacmsalv— orudmcorf— unh.miasoxac— .nitllomh— unrisndv— z)Dhnroinsorf—trc— dtwnstins,—hatlmsaharil—0asa—.tsi—ny— snmiora—udoroutd—utsag—5dd— dtwnstins,—ctit—0tlsaisoa1ac—ysnh—ipa—pnl.oitd— orynshtionr—l,liahg—Htit—saftscorf—.nitllomh—trc—fdmunla—unrisnd—0asasaisoa1ac—ysnh—ipa—DGC7MCC—adauisnrou—ctitwtlag—Rpa—zmsn9)qGz—CC—hncad—trc—ipa—575)–z—CC—lunsa—0asamlac—in—utdumdtia—ipa—hnsitdoi,—sol-—or—.tioaril—mrcasfnorf—utscotu—lmsfas,—b v—b4g—JnrfMiash—hnsitdoi,—ynddn0Mm.—0tl—.asynshac—ipsnmfp—unm.dorf—ny—hmrouo.td—hnsitdoi,—saunscl—0oip—unh.daia—ynddn0Mm.—yns—4—,atslg5dd—.tioari—ctit—0asa—htrtfac—trnr,hnmld,g

5—b Mdatc—z)D—0tl—htca—ti—C)N—tchollonrv—ctod,—yns—ipa—yosli—P—C)N—ct,lv—ti—pnl.oitd—coluptsfav—0par—tsp,iph—colnscas—0tl—nwlas1ac—nr—ipa—hnroins—ns—0par—ipa—.tioari—0tl—pt1orf—unh.dtorilg—Hmsorf—C)Ntchollonr—tdd—.tioaril—0asa—hnroinsac—unriormnmld,—0oip—t—b Mdatc—z)D—0oip—sp,iph—saunfroionr—trc—9Rlafhari—hnroinsorfg—%par—t—.tioari—0tl—unrlocasac—ti—sol-—in—ca1adn.—la1asa—tssp,iphotlv—unriormnmlhnroinsorf—w,—iadahais,—0tl—unriormac—ti—ipa—farastd—0tscg—Uns—ipa—.sohts,—arc.noriv—ipa—nuumssarua—ny5UW5UJ—0tl—cayorac—tl—tisotd—yowsoddtionr—ns—tisotd—ydmiias—unryoshac—w,—t—linsac—b Mdatc—z)D—3cmsorf—ipaariosa—bI—launrcl—ny—safolistionr(v—sa1oa0ac—w,—tr—orca.arcari—trc— mtdoyoac—utscondnfoliv—wdorcac—yns—ipaisatihari— tddnutionrg— 7tioaril— 0pn— ca1adn.ac— 5UW5UJ— 0asa— isatiac— tuunscorf— in— dnutd— fmocadoralg5riountfmdtionr—0tl—litsiac—0par—5UW5UJ—0tl—.salari—yns—n1as— k—pnmslg—5dd—.tioaril—0pn—coac—cmsorfpnl.oitd—tchollonr—0asa—udnlad,—sa1oa0ac—oy—twrnshtd—.nitllomh—da1adl—unmdc—pt1a—tiisowmiac—in—ipa—utmlany—catipg

Statistical analysisUns—ipa—.sohts,—arc.noriv—t—.n0as—trtd,lol—0tl—.asynshac—wtlac—nr—t—.sa1onml—4Mhnrip—nwlas1tionr—ornms—orlioimionr—ipti—ny—ipa—.tioaril—tyias—utscotu—lmsfas,—t..snFohtiad,—PI;—ca1adn.ac—5UW5UJ—cmsorfpnl.oitd—tchollonrg—%oip—t— Mlocac—da1ad—ny—lofroyoutrua—ny—P;—trc—t—.n0as—ny—:I;v—:II—utscotu—lmsfas,.tioaril—lpnmdc—wa—orudmcac—in—caiaui—t—bI;—sacmuionr—or—ipa—oruocarua—ny—5UW5UJg—5l—orcoutiac—waynsavtdd—.tioaril—tchoiiac—in—ipa—C)N—sauao1ac—.nitllomh—unrisnd—0oip—DGC7MCCg—5llmhorf—ipti—t..snFohtiad,6P;—ny—ipa—tchoiiac—.tioaril—0nmdc—mrcasfn—utscotu—lmsfas,—trc—30oip—t—bI;—htsfor(—0a—tsso1ac—ti—titsfai—rmhwas—ny—b II—unrlaumio1a—.tioarilg

Rn—unh.tsa—fsnm.lv—ipa—9imcari’l—iMialiv—ipa—AtrrM%poira,—NMiali—ns—Uolpas’l—aFtui—iali—0tl—mlac—0part..sn.sotiag 9aunrcts,—trtd,lal—0asa—.asynshac—or—.sacayorac—lmwfsnm.l—:g—5—dnfMstr-—iali—0tl—mlac—inunh.tsa—<t.dtrMAaoas—ums1alg—Amdio1tsotia—trtd,lal—0asa—.asynshac—in—caiashora—.sacouinsl—yns—.nliMn.astio1a—5UW5UJ—or—utscotu—lmsfas,g—5—i0nMlocac—7M1tdma—ny—OgIP—0tl—unrlocasac—lofroyoutrig—5dd—ctit0tl—trtd,lac—mlorf—ipa—oriarionr—in—isati—.soruo.dag 9799—1aslonr— IgI—0tl—mlac—yns—tdd—litiolioutd—trtd,lalg

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Hmsorf—ipa—limc,—.asonc—b P4—unrlaumio1a—.tioaril—0asa—unrlocasac—adofowdag—qy—ipnla—.tioarilv— :—0asaaFudmcac—wtlac—nr—ipa—aFudmlonr—usoiasot—3Uofmsa—b(g—qy—ipa—sahtororf—.tioarilv—8bI—.tioaril—0asa—tchoiiactyias—utscotu—lmsfas,g—Rpnla—.tioaril—0asa—tddnutiac— in—aoipas— ipa—rJ7—ns—r–7—.nitllomh— isatiharilistiaf,g—Uns—ipol—fsnm.—ipa—hatr—±—9H—tfa—0tl—SS±b4—,atsl—trc—S6;—0tl—htdag—Rpa—ht/nsoi,—ny—.tioaril0asa—tchoiiac—tyias—1td1a—lmsfas,—ns—nyyM.mh.—)5EDg—kk6—.tioaril—0asa—tddnutiac—in—ipa—rJ7—fsnm.—trckS4— .tioaril— 0asa— tddnutiac— in— ipa— r–7— fsnm.g— Hahnfst.pouv— wtladora— trc— oristMn.astio1a— .tioariuptstuiasolioul— tsa— cahnrlistiac— or— Rtwda— bg— Rpasa— 0asa— rn— litiolioutd— coyyasarual— or— wtladorauptstuiasolioul—wai0aar—ipa—i0n—fsnm.lg

Hmsorf—C)N—tchollonr—ipa—hatr—thnmri—ny—tchoroliasac—.nitllomh—0tl—4I± 4—hhndWct,—yns—ipa—rJ7fsnm.—trc—P ± 6—hhndWct,—yns—ipa—r–7—fsnm.—37OgIIbv—itwda— (g—Rpol—salmdiac—or—hatr—C)N—.nitllomhunruaristionr—ny—sal.auio1ad,—kg ±g4S—hhndWJ—trc—kg44±g4k—hhndWJ—37OgIIb(g—9aa—Uofmsal— —trc—4—ynsipa—isarcl—n1as—ioha—or—.nitllomh—tchorolistionr—trc—.nitllomh—1tdmal—cmsorf—C)N—tchollonrg—5yiastchollonr— ipa—hatr—.nitllomh—1tdmal— litsi— in— coyyas— tyias— S— pnmslg— Rpasa—0tl— rn—coyyasarua— or— ipanuumssarua—ny—la1asa—p,.nM—trc—p,.as-tdahot—3O gP—hhndWJ—trc—>SgP—hhndWJ(—wai0aar—ipa—i0n—fsnm.l3itwda— (g—Aatr—htfralomh—da1adl—cmsorf—C)N—lit,—0asa—a mtd—yns—wnip—fsnm.l—3rJ7—bgIk±gb:—trc—r–7bgIk±g (g

Uns—ipa—.sohts,—arc.noriv—ipasa—0tl—rn—litiolioutd—coyyasarua—tl—ipa—oruocarua—yns—5UW5UJ—tyias—utscotulmsfas,—0tl—b6 Wkk6—34:;(—yns—ipa—rJ7—fsnm.—trc—b::WkS4—3kb;(—yns—ipa—r–7—fsnm.g—<t.dtrMAaoas—ioha

Figure 2 7nitllomh—unruaristionr—cmsorf—ipa—yosli—6 p—tyias—C)N—tchollonrgAatr—.nitllomh—unruaristionr—cmsorf—6 —pnmsl—tyias—C)N—tchollonr—yns—wnip—ipa—rJ7—trc—r–7—fsnm.lg

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in—a1ari—ums1al—yns—ipa—i0n—fsnm.l—0asa—rni—coyyasari—3Uofmsa—k(g—qy—ipa—.tioaril—0pn—ca1adn.ac—5UW5UJv6P;—.salariac—0oipor—ipa—yosli—4—ct,l—tyias—lmsfas,v—0oip—ipa—pofpali—oruocarua—nr—ipa—launrc—ct,g—5dlnor—la1astd—.saMcayorac—fsnm.l—3orudmcorf—.tioaril—0oipnmi—t—polins,—ny—5UW5UJ(—rn—coyyasarual—0asa—ynmrcyns—ipa—.sohts,—arc.nori—3Uofmsa—P(g—Cr—hmdio1tsotia—trtd,lolv—orca.arcari—.sacouinsl—yns—.nlin.astio1a—5Uns—5UJ—0asa—ndcas—tfav—.sons—5UW5UJ—trc—1td1a—lmsfas,—37OgIIb(g—Jarfip—ny—lit,—yns—ipa—C)N—trc—initdpnl.oitdoxtionr—0asa—unh.tstwda—yns—ipa—i0n—fsnm.l—3Rtwda— (g—5dln—ipasa—0asa—rn—litiolioutdd,—lofroyoutricoyyasarual—or—ipa—oruocarua—ny—uasawstd—1tlumdts—tuuocarilv—tumia—h,nutscotd—orytsuionrv—ipa—raac—yns—sartdsa.dtuahari—ipast.,—trc—hnsitdoi,g

7tioaril—0pn—ca1adn.ac—5UW5UJ—0asa—hnsa—do-ad,—in—ca1adn.—t—)V5—3bgS;—1aslml—Pg:;v—7=gIIb(—ns—in—coacmsorf—pnl.oitdoxtionr—3 g8;—1aslml—Sgb;v—7=gI4(g—Rpasa—0asa—rn—orMpnl.oitd—catipl—ipti—or—saisnl.auio1atrtd,lol—unmdc—wa—sadtiac—in—p,.nM—ns—p,.as-tdahou—a1aril—tl—ipa—utmla—ny—catipg

Table 1 Hahnfst.poulv—udoroutd—trc—lmsfoutd—uptstuiasolioulg

CharacteristicsnLP Group

n= 447nHP Group

n=4635fav—hatr—±—9Hv—, SS±b SS±b4Atda 4II—3S6( 4bb—3S6(Enc,—Atll—CrcaFv—hatr—±—9Hv—-fWh 6±k 6±k–olins,—nyT–,.asiarlonr b8I—3k4( b88—3k4(Hotwaial—Aaddoimlv—rnr—orlmdor—ca.arcari P8—3b4( 6P—3bS(Hotwaial—Aaddoimlv—orlmdor—ca.arcari kI—38( 4I—3S(7mdhnrts,—colatla P4—3b ( PS—3b ()psnrou—sartd—c,lymruionr kI—38( 46—3:(5isotd—yowsoddtionr—trcWns—tisotd—ydmiias :P—3b8( : —3b:()asawsn1tlumdts—tuuocari k:—3bb( PP—3b (

)tscotu—litiml—3dayi—1arisoumdts—ymruionr(tAncastia 8b—3 I( :S—3b8(7nns 6I—3bS( 66—3b6(

zmsn9unsaMCCv—hatr—±—9H 4gP±SgI 4g ±kg:575)–zMCCv—hatr—±—9H k4±b6 kk±b6Gauari—h,nutscotd—orytsuionr—3O8I—ct,l( :6—3b8( 6S—3bS(R,.a—ny—lmsfas,TVtd1a—lmsfas, bP6—34P( bP6—34k(9orfda—5nsiou—1td1a 8b—3 I( bI4—3 (9orfda—Aoistd—1td1a 4I—36( 4b—36()nhwortionr—W—nipas 4S—3:( 4—3P(

)5ED—3nyyM.mh.( bk6—344( bS8—346()5ED—3nrM.mh.( SP—3bP( SP—3bk()5ED—.dml—1td1a 6:—3b6( 6 —3bS(

Ga.ati—lmsfas, S—3S( 8—3S(Hmstionr—ny—.snuacmsav—hatr—±—9Hv—hor kS±:8 kI±8Hmstionr—ny—aFistuns.nsatd—uosumdtionrv—hatr—±—9Hv—hor bP4±6b bk8±6PHmstionr—ny—tnsiou—usnllMudth.orfv—hatr—±—9Hv—hor bIS±PI bI4±k8Htit—ol—.salariac—tl—jn—3;(v—mrdall—nipas0ola—l.auoyoacgtAncastia—dayi—1arisoumdts—ymruionrT—a/auionr—ystuionr—4ILPI;v—7nns—dayi—1arisoumdts—ymruionrT—a/auionr—ystuionr—O4I;5wwsa1otionrl—mlac—or—itwdaT—rJ7—rnshtd—dn0—.nitllomhK—r–7—pofpMrnsrtd—.nitllomhK—9H—litrctsc—ca1otionrK—)5EDunsnrts,—tsias,—w,.tll—fstyiorfg

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Discussion

Cr—ipol—.snl.auio1a—isotd—nr—.tioaril—tyias—n.ar—patsi—lmsfas,—rn—coyyasarua—0tl—nwlas1ac—wai0aar—i0ncoyyasari—.nitllomh—safmdtionr—listiafoal—0oip—t—rnshtdMdn0—trc—rnshtdMpofp—.nitllomh—itsfai—yns—ipaosayyaui—nr—ipa—oruocarua—ny—5UW5UJg

Rpa—tupoa1ac—.nitllomh—strfal—yns—ipa—rJ7—trc—r–7—fsnm.l—0asa—udnlas—in—atup—nipas—iptr—ipa—.sacayoracitsfailv—cal.oia—t—hts-acd,—3+64;(—pofpas—.nitllomh—orymlonr—stia—or—ipa—r–7—fsnm.g—Rpol—.snFohoi,—nyipa—tupoa1ac—rJ7—trc—r–7—strfal—0tl—mraF.auiac—trc—.nllowd,— orcoutial—tr— orisorlou— iarcaru,—ny.nitllomh—da1adl—in—laiida—rats—kg —hhndWJg—%oip—saftsc—in—ipa—ltyai,—ny—DGC7MCC—tdfnsoiphv—0a—nwlas1ac1as,—ya0—aFisaha—.nitllomh—castrfaharil—or—wnip—ipa—itsfai—fsnm.lg—Rpol—ol—or—tuunsctrua—0oip—nmsaF.asoarual—0oip—ipa—t..snFohtiad,—bIvIII—.tioaril—ti—nms—C)N—ipti—pt1a—waar—.nitllomh—htrtfac—w,DGC7MCC—lorua— IIS—8v—bkg

5dipnmfp—.nitllomh—safmdtionr—ti—ipa—C)N—ol—unrlocasac—oh.nsitriv—ya0—limcoal—calusowa—listiafoal—insafmdtia—.nitllomh—or—ipa—usoioutdd,—odd—.tioarig—z1ar—ipnmfp—or—sadtiac—.tioari—fsnm.l—twrnshtd—.nitllomhda1adl—tsa—tllnuotiac—0oip—tc1asla—nmiunha—bPLb6v— in—nms—-rn0dacfa—ipasa—tsa—rn—limcoal—unh.tsorfcoyyasari—.nitllomhMwtlac—isatihari—listiafoal—ti—ipa—C)N—trc—nmiunhag—7nitllomh—tl—.tsi—ny—t—fdmunlaMorlmdorM.nitllomh—3DC<(—safoha—0tl—limcoac—hnsa—aFiarlo1ad,—or—tumia—h,nutscotd—orytsuionr—trc—cmsorfutscotu—lmsfas,—b:g

Table 2 7nitllomh—safmdtionr—trc—nmiunha—tyias—utscotu—lmsfas,gnLP Group

n= 447nHP Group

n=463P-value

Criarlo1a—utsa—mroi—3C)N(5chollonr—.nitllomhv—hhndWJ—3hatr—±—9H( 4g8S±gk8 4g86±gPb g6I7nitllomhv—hhndWJ—3hatr—±—9H( kg ±g4S kg44±g4k OgIIbjmhwas—ny—hatlmsaharil :Pkk :8P67nitllomh—tchorolistionrv—hhndWct,—3hatr—±—9H( 4I± 4 P ± 6 OgIIb9a1asa—p,.n-tdahot—3O gP—hhndWJ(v—rn—.tioaril—3;( —3gk( b—3g ( gS9a1asa—p,.as-tdahot—3>SgP—hhndWJ(v—rn—.tioaril—3;( :—3bg:( bS—3 gk( gSP

5yias—C)N—coluptsfav—ti—ipa—farastd—0tsc7nitllomhv—hhndWJ—3hatr—±—9H( kg ±gk kg ±gk g6:jmhwas—ny—hatlmsaharil 4P S 4k6I9a1asa—p,.n-tdahot—3O gP—hhndWJ(v—rn—.tioaril—3;( IWkk4—3I( 4WkP4—3gS( g P9a1asa—p,.as-tdahot—3>SgP—hhndWJ(v—rn—.tioaril—3;( 4Wkk4—3g6( 4WkP4—3gS( b

C)N—JarfipMnyMlit,v—hacotr—3CQG(v—ct,l g8—3g:Lbgb( g8—3g:Lbg6( gS–nl.oitd—darfipMnyMlit,v—hacotr—3CQG(v—ct,l bIgb—36g4LbPg4( bIg —36g4LbPg4( g4SA,nutscotd—Crytsuionr 8—3 gI( 4—3gS( gI8<ocra,—Utodmsa—3sartd—sa.dtuahari—ipast.,—ti—C)N( :—3bg:( bk—34gI( g :)V5 bk—34gb( bS—34gP( g:P

RstrlymlonrlGac—wdnnc—uaddlv—rn—.tioaril—3;( bP6—34P( bP8—34k( g:kUsalp—ysnxar—.dtlhtv—rn—.tioaril—3;( 44—36( 4I—3S( gSIRpsnhwnu,ialv—rn—.tioaril—3;( 4P—3:( P —3bb( gI8

C)N—hnsitdoi, :—3bg:( bP—34g ( g b–nl.oitd—hnsitdoi,— bk—34gb( P—3Pgk( gbI8IMct,l—hnsitdoi, I—3kgP( 4 —3Sg8( gbqraM,ats—hnsitdoi,— P—3PgS( 48—3:gk( gbHtit—ol—.salariac—tl—jn—3;(v—mrdall—nipas0ola—l.auoyoacg5wwsa1otionrl—mlac—or—itwdaT—rJ7—rnshtd—dn0—.nitllomhK—r–7—pofpMrnsrtd—.nitllomhK—C)N—oriarlo1a—utsa—mroiK—9H—litrctscca1otionrK—CQG—orias mtsioda—strfaK—DGC7—fdmunla—trc—.nitllomh—safmdtionr—or—oriarlo1a—utsa—.tioarilK—)V5—uasawstd1tlumdts—tuuocarig

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Aaipncndnfoutdd,v—0a—wadoa1a—nms—isotd—unritorl—i0n—rn1ad—adaharilg—Uosli—oi—unh.tsac—i0n—itsfai—da1adlipti—wnip—0asa—0oipor—ipa—.p,londnfoutd—strfag—9aunrcv—ipa—i0n—mrcasd,orf—.nitllomh—orymlonr—listiafoal3rJ7—trc—r–7(—0asa—oh.dahariac—ipsnmfp—unh.mias—lm..nsig—Rpa—DGC7M.nitllomh—unrisnd—l,liah—0tltwda—in—ayyauio1ad,—safmdtia—.nitllomhv—orcoutiorf—ipti—oriafstiac—fdmunla—trc—.nitllomh—unrisnd—or—ipaC)N—ol—rni—nrd,—.nllowda—wmi—mlaymd—tl—0addg—Cr—ipa—cnhtor—ny—fdmunla—unrisndv—ipa—unh.tsolnr—ny—i0n—tidatli—.tsiotdd,—unh.miasMfmocac—.sninundl—coc—cahnrlistia—ipa—lm.asonsoi,—ny—t—pofpas—fdmunla—itsfai—n1ast—dn0as—itsfai—b8g—5c1truac—unrisnd—tdfnsoiphl—lmup—tl—DGC7MCC—unmdc—tdln—wa—t..doac—in—nipas—.tsthaiasllmup—tl—htfralomhv—utduomh—ns—lncomh—ipti—tsa—coyyoumdi—ns—iohaMunrlmhorf—yns—pmhtrl—in—utsaymdd,safmdtiag

Rpa—i0n—isatihari—listiafoal—ipti—0a—limcoac—coc—rni—lpn0—coyyasari—nmiunhal—or—iashl—ny—ipa—oruocaruany—5UW5UJg—Rpol—ht,—wa—ipa—salmdi—ny—ipa—itsfail—waorf—unh.tstio1ad,—udnlav—trc—ipa—tuimtdd,—tupoa1acda1adl—a1ar—udnlasg—Rpml—oi—ol—unruao1twda—ipti—hnsa—la.tstia—.nitllomh—itsfail—ht,—.sncmua—coyyasarinmiunhalg—5l—yts—tl—ptl—waar—lmffaliac—w,—nipas—tmipnslv—hnli—limcoal—.noriac—in0tscl—t—.sniauio1aayyaui—ny—pofpas—.nitllomh—da1adl—or—utscon1tlumdts—.tioaril—6g—%a—ynmrc—rn—coyyasarual—or—ipa—oruocarua—ny5UW5UJv—tdln—rni—or—ipa—.saMl.auoyoac—lmwfsnm.lg—qms—salmdil—cn—rni—a1ar—orcoutia—t—isarc—in0tscl—twarayouotd—ayyaui—ny—pofpas—.nitllomh—nr—5UW5UJg

qms—limc,—ptl—oh.nsitri—dohoitionrlg—5dipnmfp—nms—isotd—0tl—dtsfas—iptr—hnli—limcoal—ipti—unh.tsac—ipaayyaui—ny—orias1arionrl—nr—5U—ns—5UJ— Iv—oi—ht,—rni—pt1a—waar—lmyyouoarid,—dtsfa—in—caiaui—t—coyyasaruag—5dlnv

Figure 3 7nitllomh—tchorolistionr—cmsorf—C)N—tchollonrgRpol—yofmsa—cahnrlistial—ipa—umhmdtio1a—thnmri—ny—.nitllomh—tchoroliasac—yni—wnip—ipa—rJ7—trc—r–7—fsnm.l—cmsorfipa—yosli—6 —pnmsl—tyias—C)N—tchollonrg

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Figure 4 5isotd—yowsoddtionr—ns—tisotd—ydmiias—tyias—utscotu—lmsfas,g7asuaritfa—ny—.tioaril—0pn—ca1adn.ac—5UW5UJ—yns—ipa—yosli—6—.nlin.astio1a—ct,l—tyias—utscotu—lmsfas,g—qy—ipnla—.tioarilipa—ht/nsoi,—.salariac—0oip—ca—rn1n—5UW5UJ—0oipor—ipa—yosli—4—.nlin.astio1a—ct,lg—Rpa—dnfMstr-Miali—lpn0ac—rn—lofroyoutricoyyasarua—or—ipa—oruocarua—ny—5UW5UJ—wai0aar—ipa—r–7—trc—rJ7—fsnm.lg

Figure 5 9mwfsnm.—trtd,lolgCr—la1astd—lmwfsnm.lv—ipasa—0asa—rn—litiolioutd—coyyasarual—or—ipa—oruocarua—ny—.nlin.astio1a—5UW5UJg

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ipa—oruocarua—ny—5UW5UJ—0tl—dn0as—or—ipa—limc,—.n.mdtionr—iptr—ipa—lml.auiac—oruocarua—mlac—yns—ipa.n0as—trtd,lolg— Jo-a0olav—nms—.tioaril—0asa—rni— strcnhoxac—nra—w,—nrav—wmi—0asa— isatiac—0oip—trtdiasrtiorf—itsfai—ny—dn0—ns—pofp—rnshtd—.nitllomhg—Rpa—ctit—lpn0—ipti—ipa—rJ7—trc—r–7—fsnm.l—0asa0add—wtdtruac—ti—wtladora—trc—0a—wadoa1a—ipti—ipa—tdiasrtiorf—itsfai—calofr—coc—rni—orisncmua—mrcma—wotlg

Cr—tccoionrv—ipa—C)N—lit,—0tl—sadtio1ad,—lpnsiv—dohoiorf—ipa—coyyasariotd—ayyaui—ny—ipa—isatihari—tshlg—–n0a1asvtdln—or—.tioaril—tchoiiac—in—ipa—C)N—yns—t—dnrfas—.asonc—ny—iohav—ipasa—0asa—rn—coyyasarual—or—ipa—nuumssaruany—5UW5UJg

5dipnmfp—oi—unmdc—rn0—wa—tsfmac—ipti—hnsa—0ocad,—l.tuac—itsfail—lpnmdc—pt1a—waar—unh.tsacv—nms—salmdillmffali— ipti— a1ar—pofpas—.nitllomh—tchorolistionr— stial— in—tupoa1a—pofpas— itsfail—pt1a—rn—warayoiunh.tsac—in—t—dn0Mrnshtd—.nitllomh—itsfai—ny—kgI—hhndWJg—Hal.oia—udatsd,—coyyasari—unh.mias—itsfailtrc—unrunhoitrid,—udatsd,—pofpas—.nitllomh—tchorolistionr—stialv—ipa—da1adl—tupoa1ac—or—ipa—.tioariliarcac—in—wa—hnsa—lohodts—iptr—0a—aF.auiacg—Rpol—ht,—saydaui—ipa—orpasari—litwodoi,—ny—ipa—.nitllomh—da1ador—htr,—.tioaril—trc—ipa—orusatlac—sartd—dnll—ny—.nitllomh—or—ipa—r–7—fsnm.g—Hal.oia—t—64;—orusatla—or.nitllomh—tchorolistionr—oi—salmdiac—or—nrd,—t— gS;—orusatla—ny—uosumdtiorf—.nitllomh—ny—kg —in—kg44hhndWJg—%a—wadoa1a—ipol—orcoutial—iptiv—mrdo-a—yns—aFth.da—fdmunla—da1adlv—oi—ht,—rni—wa—.nllowda—in—hncoy,.nitllomh—da1adl—ti—0oddg—9mwla mari—trtd,lol—ny—.tioaril—0pn—0asa—isatiac—yns—.sndnrfac—.asoncl—or—ipaC)N—lmffalil—ipti—orusatlac—.nitllomh—tchorolistionr—coc—rni—orusatla—ipa—oristuaddmdts—1ndmha—in—tcaiauitwda—cafsaa— bg—Rpml—ipa—tccoionrtd—.nitllomh—ol—rni—saitorac—wmi—aFusaiac—w,—ipa—-ocra,l— v— 4g

Conclusions

Cr—unrudmlonrv—i0n—coyyasari—unh.miasMtlloliac—.nitllomh—safmdtionr—listiafoal—0oip—wnip—itsfail—0oiporipa—rnshtd—strfa—lpn0ac—rn—coyyasarua—or—ipa—oruocarua—ny—5UW5UJ—tyias—utscotu—lmsfas,g

Acknowledgements: Hs— Bnso-— Gg— Rohhas— 3orca.arcari— utscondnfoliv— Cltdt— <doroa-v— Z0nddav— ipajaipasdtrcl(g

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References

bg Atsolutdun—Dv—<dasl,—)v—Ztrnworo—Av—Etrtup—Av—Uasstsala—9v—Ensltro—7v—)trinsa—)v—Eofdondo—7v—9tdt5T— 5isotd— yowsoddtionr— tyias— olndtiac— unsnrts,— lmsfas,— tyyauil— dtia— lms1o1tdg— )osumdtionr— II:vb:3bS(TbSb LbSb:g

g zdM)ptho—AUv—<odfn—7v—Rpnmstro—Vv—Jtiinmy—qAv—Hadmsfon—HEv—Dm,inr—G5v—Janr—5Gv—7ml-tl—BHTja0—nrlai—tisotd—yowsoddtionr—.sacouil—dnrfMiash—hnsitdoi,—tyias—unsnrts,—tsias,—w,.tll—fstyig—B—5h)ndd—)tscond— IbIv—PP3b4(Tb46ILb46Sg

4g Atalar—Ev—jo/l—Bv—Atallar—Bv—5ddalloa—Av—9upniiar—NT—7nliMn.astio1a—tisotd—yowsoddtionrT—t—htxa—nyhauptrolhlg—zmsn.tua— Ib v—bk3 (TbP8Lb6kg

kg Atipa0—B7v—Unrial—AJv—Rmcns—C)v—Gthlt,—Bv—Hm-a—7v—Atxas—)Hv—Etstlp—7Dv—–lm—7–v—AtrftrnHRv— Cr1alioftinsl—ny—ipa—Clupahot—Galatsup—trc—zcmutionr—UnmrctionrK—Amdiouarias—9imc,—ny7ason.astio1a—Clupahot—Galatsup—Dsnm.T—5—Amdiouarias—sol-—orcaF—yns—tisotd—yowsoddtionr—tyias—utscotulmsfas,g—B5A5— IIkv— 8b3bk(Tb6 ILb6 8g

Pg Etlpnms—Rv—–lm—dv—Dsnyor-ad—–Bv—%ou-sthala-tstr—Gv—Gonl—B)T—5ison1ariso1umdts—trc—orist1arisoumdtsunrcmuionr—or—p,.as-tdahotg—5h—B—utscond—b86Pv—4P3 (Tb88L I4g—

Sg 5dynrxn— 5Vv— Cldal— )v— Daccal— )v— Haofptr— )T— 7nitllomh— colnscasl— L— udoroutd— l.auismh— trcahasfarua—htrtfaharig—Galmluoitionr— IISv—6I3b(TbIL Pg

6g AtuHnrtdc— Bzv—9ismipasl—5HT—%pti— ol— ipa—n.iohtd— lasmh—.nitllomh— da1ad— or— utscon1tlumdts.tioarilg—B—5h—)ndd—)tscond— IIkv—k43 (TbPPLbSbg

:g –na-list—Av—Vnfadxtrf—Av—1tr—cas—–nsli—C)v—Jtrlor-—5qv—1tr—cas—Attiar—BAv—Clhtad—Uv—Zo/dlist—Uvjo/liar—A%T—Rsotd—calofrT—)nh.mias—fmocac—rnshtdMdn0—1aslml—rnshtdMpofp—.nitllomh—unrisnd—orusoiutdd,—odd—.tioarilT—Gtionrtda—ny—ipa—DGC7M)qA7599—limc,g—EA)—5ralipalond— IbIv—bIT 4g

8g –na-list—Av—Vnfadxtrf—Av—Hsnli—BRv—Btrla—Av—Jnay—EDv—1tr—cas—–nsli—C)v—Zo/dlist—Uv—jo/liar—A%gCh.daharitionr—trc—a1tdmtionr—ny—t—rmslaMuariasac—unh.miasoxac—.nitllomh—safmdtionr—.sninundor—ipa—oriarloua—utsa—mroi—L—t—waynsa—trc—tyias—trtd,lolg—EA)—Aac—Crynsh—Hauol—At-— IbIv—bITPg

bIg Vnfadxtrf—Av—Jnay—EDv—Gafioar—BDv— 1tr—cas—–nsli— C)v— 1tr—5llar—–v—Zo/dlist—Uv—jo/liar—A%g)nh.miasMtlloliac—fdmunla—unrisnd—or—usoioutdd,—odd—.tioarilg—Criarlo1a—)tsa—Aac— II:v—4k3:(Tbk bLbk 6g

bbg Vnfadxtrf—Av—Zo/dlist—Uv—jo/liar—A%T—Halofr—trc—oh.daharitionr—ny—DGC7T—t—unh.miasoxac—fdmunlaunrisnd—l,liah—ti—t—lmsfoutd—oriarlo1a—utsa—mroig—EA)—Aac—Crynsh—Hauol—At-— IIPv—PT4:g

b g jtlpay— 95v— Gnfmal— Uv— 9pts.dal— JHv— jodllnr— Bv— 9hoip— )v— Dndclinra— 5Gv— Jnupn0trci— NTzmsn9)qGz—CCg—zms—B—)tsconipnstu—9msf— Ib v—kb3k(T64kL6kPg

b4g <rtml—%5v—Hst.as—z5v—%tfras—H7v—Zohhashtr—BzT—575)–z—CCT—t—la1asoi,—ny—colatla—udtlloyoutionrl,liahg—)soi—)tsa—Aac—b8:Pv—b43bI(T:b:L: 8g

bkg –alladl—Jv—–na-list—Av—Ao/xar—zBv—ai—tdT—Rpa—sadtionrlpo.—wai0aar—.nitllomh—castrfaharil—trcorMpnl.oitd—hnsitdoi,—trc—ipa—orydmarua—ny—oh.dahariorf—t—unh.miasMtlloliac—.nitllomh—safmdtionrtdfnsoiphg—z9C)A—unrfsall— Ib4v—twlistui—I8b6g

bPg Dn,td— 5v— 9.asiml— B5v—Dnlup—<T— 9asmh—.nitllomh— da1adl— trc—hnsitdoi,— or— tumia—h,nutscotdorytsuionrg—B5A5— Ib v—4I63 (TbP6LbSkg

bSg %tps—Bv—7ts-l—Gv—Enol1asi—Hv—)nhmrtda—Av—Utwotr—Bv—Gthlt,—Bv—Atrftrn—HRT—7san.astio1a—lasmh.nitllomh— da1adl— trc— .ason.astio1a— nmiunhal— or— utscotu— lmsfas,— .tioarilg— B5A5— b888v:b3 4(T I4L bIg

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b6g AuAtpnr—DAv—Aarcm—AJv—Dowwnrl—U<v—)psolin.pas—<ET—5llnuotionr—wai0aar—p,.as-tdahot—tiusoioutd—utsa—oroiotionr—trc—hnsitdoi,g—Criarlo1a—)tsa—Aac— Ib v—4:3bb(Tb:4kLb:k g

b:g Utr— Yv— Zptrf— 5Av— Xotn— YEv— –aixas— GT— DdmunlaMorlmdorM.nitllomh— ipast.,— or— tcmdi— .tioarilmrcasfnorf—utscotu—lmsfas,T—t—haitMtrtd,lolg—zms—B—)tsconipnstu—9msf— Ibbv—kI3b(Tb8 Lb88g

b8g jC)zM9ND5G— 9imc,— Cr1alioftinslv— Uoryas— 9v— )poiinu-— HGv— 9m— 9Yv— ai— tdT— Criarlo1a— 1aslmlunr1arionrtd—fdmunla—unrisnd—or—usoioutdd,—odd—.tioarilg—j—zrfd—B—Aac— II8v—4SI3b4(Tb :4L86g

Ig 5slartmdi—<5v—Ymlmy—5Av—)s,litd—zv—–atda,—B9v—Ansoddn—)5v—jtos—DAv—%poidnu-—G7T—Crias1arionrlyns—.sa1ariorf—.nliMn.astio1a—tisotd—yowsoddtionr—or—.tioaril—mrcasfnorf—patsi—lmsfas,g—)nupstraHtitwtla—9,li—Ga1— Ib4v—bT)HII4Sbbv—cnoT—bIgbII WbkSPb:P:g

bg –alladl—Jv—–na-list—Av—Yap—Jv—jo/liar—A%T—Rpa—orydmarua—ny—i0n—.nitllomh—itsfai—da1adl—nr—ipaydmoc—wtdtrua—or—usoioutdd,—odd—.tioarilg—z9C)A—unrfsall— Ib v—twlistui—I6bbg

g –na-list—Av—Yap—Jv—Jtrlor-—5qv—Vnfadxtrf—Av—9iafahtr—)5v—Gncfasl—ADv—1tr—cas—–nsli—C)v%oaitlup—Dv—Zo/dlist—Uv—jo/liar—A%T—Haiashortril—ny—sartd—.nitllomh—aFusaionr— or—usoioutdd,— odd.tioarilT—Rpa—snda—ny—orlmdor—ipast.,g—)soi—)tsa—Aac— Ib v—kI34(T6S L6SPg

4g –alladl—Jv—–na-list—Av—qmca—Jtrlor-—5qv—jo/liar—A%T—Holisowmionr—ny—orist1arnml—ydmocl—n1as—ipaaFistuaddmdts—trc—oristuaddmdts—unh.tsiharil—or—.nlin.astio1a—utsconipnstuou—.tioaril—isatiac—tiipa—C)Ng—Raliorf—ipa—litrctsc—hncad—nr—0tias—trc—adauisnd,ia—colisowmionr—0oip—.nitllomh—wtdtruatrtd,lolg—z9C)A—unrfsall— Ibk

20151129_quarkx manuscript.qxp_proefschrift M Hoekstra 29/11/15 21:41 Page 183

20151129_quarkx manuscript.qxp_proefschrift M Hoekstra 29/11/15 21:41 Page 184