• Ei tuloksia

Equine lower airway inflammation : insights into asthma, diagnostics, and anaesthesia

N/A
N/A
Info
Lataa
Protected

Academic year: 2022

Jaa "Equine lower airway inflammation : insights into asthma, diagnostics, and anaesthesia"

Copied!
98
0
0

Kokoteksti

(1)

8B4DF?8@FA9CG<@84@7+?4>>@<?4>%87<6<@8 46G>FKA9.8F8D<@4DK%87<6<@8

-@<H8DE<FKA9 8>E<@=<

<@>4@7

CG<@8>AI8D4<DI4K<@9>4??4F<A@Q

!@E<:;FE<@FA4EF;?47<4:@AEF<6E4@74@48EF;8E<4

8<@<*AEE<

%!!++*,,!'&

,A58BD8E8@F87I<F;F;8B8D?<EE<A@A9F;846G>FKA9.8F8D<@4DK%87<6<@8-@<H8DE<FKA9 8>E<@=<9ADBG5><68J4?<@4F<A@<@DAA?!@9A8@FD8#ADA@4.<<==<4?BGEA@F;

A985DG4DK4F@AA@

8>E<@=<

(2)

!+&B4B8D546=

!+&(

-@<:D49<4 8>E<@=<

(3)

06,*8464-"89+0,7 /NKBAOOKN3DKI=O2LEHHI=JJ

#AL=NPIAJPKB$MQEJA=J@2I=HH JEI=H,A@E?EJA

%=?QHPUKB5APANEJ=NU,A@E?EJA 4JERANOEPUKB'AHOEJGE

'AHOEJGE%EJH=J@

"95,6:07467 #K?AJP JJ=,UGGYJAJ

#AL=NPIAJPKB$MQEJA=J@2I=HH JEI=H,A@E?EJA

%=?QHPUKB5APANEJ=NU,A@E?EJA 4JERANOEPUKB'AHOEJGE

'AHOEJGE%EJH=J@

#K?AJP,EJJ=1=F=IYGE

#AL=NPIAJPKB$MQEJA=J@2I=HH JEI=H,A@E?EJA

%=?QHPUKB5APANEJ=NU,A@E?EJA 4JERANOEPUKB'AHOEJGE

'AHOEJGE%EJH=J@

!,:0,;,67 /NKBAOOKN+=QNAJP"KQ[PEH

#AL=NPIAJPKB5APANEJ=NU"HEJE?=H2?EAJ?AO "KHHACAKB5APANEJ=NU,A@E?EJA

/QN@QA4JERANOEPU

6AOP+=B=UAPPA(J@E=J=42

/NKBAOOKN1AJ=Q@+ZCQEHHAPPA

#AL=NPIAJPKB5APANEJ=NU"HEJE?=H=J@#E=CJKOPE?2?EAJ?A %=?QHPUKB5APANEJ=NU,A@E?EJA

4JERANOEPUKB"=HC=NU "=HC=NU H>ANP="=J=@=

5543,38 /NKBAOOKN)KDJ/NEJCHA

#AL=NPIAJPKB"HEJE?=H2?EAJ?AO

%=?QHPUKB5APANEJ=NU,A@E?EJA=J@ JEI=H2?EAJ?A 2SA@EOD4JERANOEPUKB CNE?QHPQN=H2?EAJ?AO

4LLO=H=2SA@AJ

(4)

,A?K94?<>K

(5)

!" "

1AOLEN=PKNU@EOA=OAO=NA?KJOE@ANA@KJAKBPDAIKOP?KIIKJ?=QOAOKBLKKNLANBKNI=J?AEJ DKNOAO-KJEJBA?PEKQOEJBH=II=PEKJKBPDAHKSAN=ENS=UOPDAI=EJPDAIAKBPDEOPDAOEOEO

?KIIKJHUK>OANRA@NAC=N@HAOOKBPDA>NAA@=CAKNQOAKBPDADKNOA#QAPKOEIEH=NEPEAOSEPD DQI=J=OPDI=NAC=N@EJC?HEJE?=HLNAOAJP=PEKJ=J@OARAN=HL=PDKLDUOEKHKCE?=H=OLA?POJKJ EJBA?PEKQO ?DNKJE? HKSAN =ENS=U EJBH=II=PEKJ EJ DKNOAO EO ?QNNAJPHU J=IA@ AMQEJA =OPDI=

LNAREKQOHUEJBH=II=PKNU=ENS=U@EOA=OAKNNA?QNNAJP=ENS=UK>OPNQ?PEKJ@ALAJ@EJCKJPDA OARANEPU +KJCPANIATLKOQNAPKKNC=JE?@QOP=J@IKQH@OEJOP=>HA=ENEOPDKQCDPPK>APDA IKOPEILKNP=JPLNA@EOLKOEJCB=?PKNBKNPDA@EOA=OA$MQEJA=OPDI=EO?D=N=?PANEVA@>U=ENS=U DULANNAOLKJOERAJAOO=J@IQ?QO=??QIQH=PEKJOARANEPUNAH=PA@=ENS=UNAIK@AHHEJCEIL=ENA@

HQJCC=OAT?D=JCA=J@EJ?NA=OA@MQ=JPEPUKB=ENS=UEJBH=II=PKNU?AHHO3DAOA?D=JCAOHA=@

PK?HEJE?=HOECJOEJ?HQ@EJC?DNKJE??KQCD=J@J=O=H@EO?D=NCALKKNLANBKNI=J?A=J@EJ=

OARANABKNIKBAMQEJA=OPDI=EJ?NA=OA@NAOLEN=PKNUABBKNP=PNAOP?KNNAOLKJ@EJCPK=Ji=OPDI=

=PP=?GjEJDQI=JO#AOLEPA=?PERANAOA=N?DKRANPDAUA=NOPDA=APEKHKCU=J@L=PDKLDUOEKHKCU KBAMQEJA=OPDI=NAI=EJEJ?KILHAPAHU@ABEJA@

(J PDEO PDAOEO PDA NKHA KB = PN=JOIAI>N=JA LNKPAEJ ATPN=?AHHQH=N I=PNET IAP=HHKLNKPAEJ=OA EJ@Q?AN $,,/1(- = LKPAJPE=H JAS >EKI=NGAN EJ AMQEJA =OPDI= =J@ EPO NAH=PEKJODEL PK I=PNETIAP=HHKLNKPAEJ=OAO,,/O SANAEJRAOPEC=PA@(J2PQ@U(PDANAOLEN=PKNUOA?NAPEKJOKB DKNOAO SEPD =OPDI= =J@ =OUILPKI=PE? ?KJPNKHO SANA AT=IEJA@ $TLNAOOEKJ KB

$,,/1(-LNKPAEJS=OE@AJPEBEA@EJ=HHDKNOAOEJ>NKJ?DK=HRAKH=NH=R=CABHQE@! +% ?AHHO

=J@PDAATLNAOOEKJS=ODECDAOPBKNPDAIKOPOQ>OP=JPE=HHU=BBA?PA@DKNOAOSEPDOARANA=OPDI=

=J@S=O?KNNAH=PA@SEPD,,/=J@LNKPAEJATLNAOOEKJ,,/CAH=PEJKHUPE?=?PEREPU=J@

=ENS=U JAQPNKLDEHE= 3DEO EO PDA BENOP OPQ@U PK @AO?NE>A PDA NAH=PEKJODEL KB $,,/1(- =J@

,,/OEJL=PEAJPOKB=JUOLA?EAO?HEJE?=HHU=BBA?PA@SEPD=OPDI==J@PDANAOQHPOOQCCAOPPD=P

$,,/1(-EOEJRKHRA@EJPDAL=PDKLDUOEKHKCE?LNK?AOOAOKB=OPDI=EJDKNOAO$,,/1(-=O

=I=NGANKBEJBH=II=PEKJLNKRE@AOEJPANAOPEJCLKOOE>EHEPEAOBKNBQNPDANNAOA=N?DKBDKNOAO=J@

KPDANOLA?EAO

3DAOA?KJ@L=NPKBPDEOPDAOEO?KJ?AJPN=PA@KJPSK?KIIKJ@E=CJKOPE?PKKHOQOA@PK=OOAOO HKSAN =ENS=U @EOA=OAO EJ DKNOAO 3DA @E=CJKOEO KB HKSAN =ENS=U EJBH=II=PEKJ EJ?HQ@EJC

=OPDI= EO KBPAJ =E@A@ >U PDA =J=HUOEO KB ?UPKHKCE?=H O=ILHAO K>P=EJA@ BNKI PDA PN=?DA=

PN=?DA=HS=OD36 KNBNKIPDAHQJCO=P=HRAKH=NHARAH>NKJ?DK=HRAKH=NH=R=CA! + 3DANA EO?KJOE@AN=>HAR=NE=J?AEJPDA@E=CJKOPE?IAPDK@OKBAMQEJAHKSAN=ENS=U@EOA=OAO>APSAAJ B=?EHEPEAO =J@ ?HEJE?E=JO =J@ = PNQA CKH@ OP=J@=N@ BKN @E=CJKOEJC =ENS=U EJBH=II=PEKJ EO H=?GEJC(JIKOPLNAREKQOOPQ@EAOPDA?UPKHKCUKB36=J@! +O=ILHAOD=O>AAJ?KJOE@ANA@

PK ?KNNAH=PA LKKNHU =J@ ! + D=O >AAJ @AAIA@ = OQLANEKN @E=CJKOPE? PKKH EJ IKOP ?=OAO KB AMQEJA HKSAN =ENS=U @EOA=OA >QP OAJOEPEREPU =J@ OLA?EBE?EPU D=RA JKP >AAJ AR=HQ=PA@

,KNAKRAN PDA ?KJRAJPEKJ=HHU QOA@ ?QPKBB R=HQAO BKN ?UPKHKCU D=RA >AAJ H=NCAHU >=OA@ KJ K>OANR=PEKJ=HOPQ@EAO=J@ATLANPKLEJEKJ=J@NA?AJPHUDECDANR=HQAOD=RA>AAJLNKLKOA@3DA BENOP=EIKB2PQ@U((KBPDEOPDAOEOS=OPK?KIL=NAPDANAOQHPOKBPDAOAPSK=ENS=UO=ILHEJC IAPDK@OEJ=LKLQH=PEKJKBDKNOAOSEPDOECJONAH=PA@PKNAOLEN=PKNU@EOA=OA=J@EJDKNOAO

(6)

SEPDJK?HEJE?=HNAOLEN=PKNUOECJO OA?KJ@=NU=EIS=OPKAR=HQ=PAPDA?QPKBBR=HQAOKB36

=J@! +%?UPKHKCUBKNJAQPNKLDEHOEJKN@ANPKFQOPEBUPDAENQOAEJ?HEJE?=HLN=?PE?A36=J@

! +ODKSA@OQ>OP=JPE=H=CNAAIAJPNAC=N@EJCJAQPNKLDEHO=J@KJHUKBPDADKNOAOSANA

?H=OOEBEA@@EBBANAJPHUDA=HPDURO@EOA=OA@ EJ?KJPN=OPPKOKIALNAREKQOOPQ@EAOSEPDDECDAN

@EO=CNAAIAJP3DAJAQPNKLDEHLAN?AJP=CAS=OBKQJ@PK?KNNAH=PA>APSAAJ36=J@! +NAOQHPO 3DA OAJOEPEREPU =J@ OLA?EBE?EPU KB 36 SANA CAJAN=HHU DECDAN BKN 36 PD=J BKN ! + SDAJ AOPEI=PA@SEPD?KJRAJPEKJ=H=OSAHH=OSEPD!=UAOE=JOP=PEOPE?=HIAPDK@O3DANAOQHPOKBPDEO OPQ@UAJ?KQN=CAPDAQOAKBPDA?QNNAJPJAQPNKLDEH?QPKBBR=HQAOEJ?HEJE?=H@E=CJKOEOKB=ENS=U EJBH=II=PEKJEJOPA=@KBAHAR=PEJCPDA?QPKBBO

(J 2PQ@U ((( AMQEJA HKSAN =ENS=U EJBH=II=PEKJ S=O EJRAOPEC=PA@ SEPD NAC=N@ PK CAJAN=H

=J=AOPDAOE=3DA?KILHE?=PEKJN=PAEJAMQEJACAJAN=H=J=AOPDAOE=EODECDNAH=PERAPK=J=AOPDAOE=

EJOARAN=HKPDANOLA?EAOLKOP=J=AOPDAPE?LJAQIKJE=>AEJCKJAKBPDALKPAJPE=H?KILHE?=PEKJO 'KSARANPDANAEOHEIEPA@GJKSHA@CA=>KQPPDAABBA?POKBCAJAN=H=J=AOPDAOE=KJEJBH=II=PKNU NAOLKJOAOEJPDAHQJCO=J@KJOUOPAIE?EJBH=II=PKNUI=NGANOOQ?D=OOANQI=IUHKE@ 2 EJ DKNOAO %KN AT=ILHA PDA HARAH =J@ @QN=PEKJ KB HKSAN=ENS=U JAQPNKLDEHE= PD=P ?=J >A ATLA?PA@=BPAN=J=AOPDAOE=EJ@KNO=HNA?QI>AJ?U=NAQJGJKSJ3DQOKQNLNEI=NU=EIS=OPK

@APANIEJASDAJHQJCEJBH=II=PEKJNA=?DAOEPOI=TEIQI=J@DKSN=LE@HU! +%?UPKHKCU NAPQNJOPK>=OAHEJA=BPAN=J=AOPDAOE=EJ@KNO=HNA?QI>AJ?U OA?KJ@=NU=EIS=OPKEJRAOPEC=PA PDA LKOOE>HA ABBA?P KB R=PEJKT=J = JKRAHα=@NAJK?ALPKN =JP=CKJEOP @NQC KJ PDA ! +%

?UPKHKCUNAOQHPO J=AOPDAOE=EJ@KNO=HNA?QI>AJ?UNAOQHPA@EJJK?HEJE?=HHUNAHAR=JP?D=JCAO EJ=ENS=U?UPKHKCUPD=P?KQH@>A@EBBANAJPE=PA@BNKIPDAABBA?PKBNALA=PA@! +O=ILHEJC I=NGA@EJ?NA=OAEJOANQI=IUHKE@ S=O@APA?PA@EJOKIA=JEI=HOSDEHAKPDANOODKSA@JK

?D=JCAOBNKI>=OAHEJA5=PEJKT=J=OLNAIA@E?=PEKJ@E@JKP?KJOEOPAJPHU=BBA?PHQJC?UPKHKCU KN>HKK@EJBH=II=PKNUI=NGANO=BPAN=J=AOPDAOE=

3DAOA?KI>EJA@OPQ@EAOKJAMQEJAHKSAN=ENS=UEJBH=II=PEKJEJ?NA=OAKQNQJ@ANOP=J@EJCKB IA?D=JEOIO=J@B=?PKNONAH=PA@PKL=PDKLDUOEKHKCU=J@@E=CJKOPE?OKBPDA?KJ@EPEKJEJPDA DKNOA+KSAN=ENS=UEJBH=II=PEKJEO=JEILKNP=JP?=QOAKBEIL=ENA@SAHB=NA=J@LANBKNI=J?A KBDKNOAO!NK=@ANQJ@ANOP=J@EJCKBPDA=OLA?PONAH=PA@PKPDA?KJ@EPEKJSEHH=E@EJ@ARAHKLEJC JAS EILNKRA@ ?HEJE?=H =J@ @E=CJKOPE? LNK?A@QNAO =J@ I=J=CAIAJP OPN=PACEAO BKN AMQEJA EJBH=II=PKNUNAOLEN=PKNU@EOA=OAO

(7)

%"!

3DAOPQ@EAOEJ?HQ@A@EJPDEOPDAOEOSANALANBKNIA@=PPDA#AL=NPIAJPKB$MQEJA=J@2I=HH JEI=H,A@E?EJA%=?QHPUKB5APANEJ=NU,A@E?EJA=J@=PPDA5APANEJ=NU3A=?DEJC'KOLEP=H KB PDA 4JERANOEPU KB 'AHOEJGE %EJ=J?E=H OQLLKNP LNKRE@A@ >U PDA %EJJEOD %KQJ@=PEKJ KB 5APANEJ=NU1AOA=N?DPDA%EJJEOD5APANEJ=NU1AOA=N?D%KQJ@=PEKJPDA#K?PKN=H/NKCN=IIA EJ"HEJE?=H5APANEJ=NU,A@E?EJA#/"5, PDA$NGGE1=F=GKOGE%KQJ@=PEKJ2QKIAJ'ELLKO NU =J@ 5AP?=NA .U EO CN=PABQHHU =?GJKSHA@CA@ /ANOKJJAH EJ?HQ@EJC OPQ@AJPO EJ PDA 5APANEJ=NU3A=?DEJC'KOLEP=HKBPDA4JERANOEPUKB'AHOEJGE=J@EJPDA$MQEJA1AOA=N?D"AJPAN 8LYFY=NAS=NIHUPD=JGA@BKN?KKLAN=PEKJ=J@DAHL@QNEJCPDA?KHHA?PEKJKBPDA@=P=BKNPDEO PDAOEO(=I@AALHUCN=PABQHPKPDADKNOAKSJANOBKNCAJANKQOHULNKRE@EJCPDAENDKNOAOBKNPDAOA OPQ@EAO

(KSA=@A>PKBCN=PEPQ@APKIULNEI=NUOQLANREOKN=J@@A=NBNEAJ@#K?AJP JJ=,UGGYJAJ 3D=JGUKQBKNUKQNL=PEAJ?AOQLLKNP=J@AT?AHHAJPIAJPKNODEL@QNEJCPDAOAUA=NO8KQSANA

=HS=UOPDANAPKDAHLSDAJJAA@A@=J@(?KQH@JKPD=RAEI=CEJA@=>APPAN=@REOKN=J@IAJPKN BKNPDEOLNKFA?P(=@IENAUKQNKLPEIEOPE?=PPEPQ@A>KPDEJLANOKJ=H=J@LNKBAOOEKJ=HHEBAUKQN CH=OOEO=HS=UOD=HBBQHHEJOPA=@KBD=HBAILPU

#K?AJP,EJJ=1=F=IYGEIUOA?KJ@OQLANREOKN(PD=JGUKQOEJ?ANAHUBKNUKQNGEJ@OQLLKNP

=@RE?A =J@ ABBE?EAJP OQLANREOEKJ @QNEJC PDEO LNK?AOO 6EPDKQP UKQN R=OP =J@ =@IEN=>HA ATLANPEOAEJPDASKNH@KBNAOA=N?D=J@NAOLEN=PKNU@EOA=OAOPDA?KILHAPEKJKBPDEOPDAOEOSKQH@

D=RA>AAJIQ?DD=N@AN

(PD=JG/NKBAOOKN3DKI=O2LEHHI=JJBKN@ENA?PEJCPDEOPDAOEO=J@/NKBAOOKN$IANEP=1EEPP=

,=NE3QH=IK=J@/NKBAOOKN$IANEP=2=PQ2=JG=NEBKNPDAENLNAREKQO@ENA?PKNlO@QPEAO(=I CN=PABQHBKNUKQNOQLLKNP=J@BKNLNKRE@EJCIASEPDPDAKLLKNPQJEPUPKSKNGEJPDAEJOLENEJC AJRENKJIAJPKBPDA#AL=NPIAJPKB$MQEJA=J@2I=HH JEI=H,A@E?EJA/NKBAOOKN2=JG=NEEO

=HOKPD=JGA@BKNPA?DJE?=H=J@=@IEJEOPN=PERADAHLNAC=N@EJCH=>KN=PKNU=J=HUOAO

/NKBAOOKNO +=QNAJP "KQ[PEH =J@ 1AJ=Q@ +ZCQEHHAPPA =NA CN=PABQHHU =?GJKSHA@CA@ BKN LNA AT=IEJEJC PDEO PDAOEO =J@ LNKRE@EJC R=HQ=>HA ?KJOPNQ?PERA ?NEPE?EOI =J@ /NKBAOOKN )KDJ /NEJCHAEOS=NIHUPD=JGA@BKN=CNAAEJCPK>AIUKLLKJAJP=PPDALQ>HE?AT=IEJ=PEKJ (ATPAJ@IUOEJ?ANAPD=JGOPKIU?K=QPDKNO-EJJ=*KDK/D#=J@,EG=(HRAO#5,BKN ATLANPEOABNQEPBQH@EO?QOOEKJO=J@L=PEAJPHUPA=?DEJCIAEJPDAH=>KN=PKNU6KNGEJCSEPDUKQ S=O=HS=UO=LHA=OQNA#K?AJP,=NF=1=AG=HHEKBKNLNKILPHU?KIIAJPEJCKJPDAI=JQO?NELPO

=J@BKNOD=NEJCUKQNATPAJOERAATLANPEOAEJNAOA=N?D=J@OP=PEOPE?O#K?AJP JJ=,=EF=5ENP=H=

BKN AT?AHHAJP ALE@AIEKHKCE?=H =J@ OP=PEOPE?=H GJKSHA@CA =J@ BKN LANBKNIEJC IKOP KB PDA OP=PEOPE?=H=J=HUOEOKB2PQ@U((,ANEP=,YYPPY#5,=J@'AE@E3=LEK/D#BKNCAJANKQODAHL

@QNEJC @=P= ?KHHA?PEKJ =J@ I=JQO?NELP LNAL=N=PEKJ =J@ BKN GEJ@ LAANOQLLKNP @QNEJC PDEO LNK?AOO)KQJE)QJJEH=,2?BKNAJ@HAOOL=PEAJ?A=J@=OOEOP=J?ANAC=N@EJCOP=PEOPE?=H=J=HUOEO KBPDEOPDAOEO$IIE1=DGKJAJ#5,BKNABBE?EAJP?KHHA?PEKJKBL=NPKBPDA@=P=BKN2PQ@U((

(8)

,KDOAJ'=JEBAD/D#BKND=N@SKNGEJPDAVUIKCN=LDUH=>EJ2PQ@U((((lIDKJKQNA@PK OD=NALQ>HE?=PEKJOSEPD=HHKBUKQ

(=ICN=PABQHBKNPDAOGEHBQHH=>KN=PKNULANOKJJAHSEPDKQPSDKIPDEOPDAOEO?KQH@JKPD=RA>AAJ SNEPPAJ ,ANF= 1=JP= +EHE= )YYOGAHYEJAJ 2QRE 5ENGG=H= *ENOE +=QGG=JAJ =J@ *ENOE

*KHADI=EJAJ 3D=JG UKQ ,KNAKRAN /NKBAOOKN "=PDANEJA ,?&KS=J EO PD=JGA@ BKN

?KIIAJPEJCKJPDAI=JQO?NELPKB2PQ@U(=J@/NKBAOOKN(=J&=N@JANBKN=OOEOP=J?ASEPDPDA OP=PEOPE?=H=J=HUOEOKB2PQ@U((

,U@A=NBNEAJ@O=J@SKNGI=PAO@QNEJCIUQJERANOEPUUA=NO-EJJE=J@'AHEPD=JGUKQBKN=HH PDAOQLLKNPHEOPAJEJCPKIUSKNNEAO@QNEJCPDEO/D#LNK?AOOUKQlRA>AAJPDANA@KJAPD=P

=J@JQIANKQODEH=NEKQOPEIAOOLAJPSEPDUKQ=J@ JJ=EJAO?=LANKKIO=J@=POKIAPEIAO OHECDPHUMQAOPEKJ=>HA@EJJANP=>HAO=BPANS=N@O(=HOKSEODPKATLNAOOIUCN=PEPQ@APK=HHKBIU LNA?EKQOBNEAJ@OKQPOE@APDAQJERANOEPUSDKD=RAOQLLKNPA@IA=J@LNKRE@A@OKI=JUIKIAJPO KBFKUKRANPDAUA=NO3D=JGUKQ

OLA?E=H PD=JGO PK IU @A=N B=IEHU ,QI #=@ =J@ IU >NKPDAN )QDK UKQ D=RA =HS=UO

>AHEARA@ EJ IA =J@ ( PD=JG UKQ BKN PDA AJ?KQN=CAIAJP =J@ ?KJPEJQKQO OQLLKNP -EEHK =J@

*ANPPQ(=LLNA?E=PAUKQNABBKNPOEJNA@Q?EJCIUOPNAOOHARAHOSEPDL=SPDAN=LU=J@GAALEJC IUGAU>K=N@S=NI

%EJ=HHU(PD=JGIU>AHKRA@DQO>=J@+Q?=BKN>AEJCOK?=NEJC=J@L=PEAJPARAJSDAJ(lIJKP

=PIU>AOP3DA?KILHAPEKJKBPDEOPDAOEOSKQH@D=RA>AAJEILKOOE>HASEPDKQPUKQNOQLLKNP EJ?HQ@EJCPA?DJE?=HOQLLKNPSEPDEI=CALNK?AOOEJC 3D=JGUKQBNKIPDA>KPPKIKBIUDA=NP BKN=HS=UO>AEJCPDANABKNIA=J@ODKSEJCIASD=PNA=HHUI=PPANOEJHEBA

(9)

""!

"#!#

&#"

##"

"#! $#"

!%#"

#!$#

!%&##!#$!

$04(-$ 23',

8E6D<BF<A@4@7BD8H4>8@68 8F<A>A:K4@7B4F;AB;KE<A>A:K ><@<64>E<:@E A?B4D<EA@FA4EF;?4A9;G?4@E4@7AF;8DEB86<8E

$04(-$ 23', #( &-.23("2

$AI8D4<DI4KE4?B><@:?8F;A7E KFA>A:KA98CG<@8>AI8D4<DI4KE4?B>8E

, 31(7,$3 ++./1.3$(- 2$2

+FDG6FGD84@79G@6F<A@

%%(E<@4<DI4K<@9>4??4F<A@

$731 "$++4+ 1, 31(7,$3 ++./1.3$(- 2$(-#4"$1

+FDG6FGD84@79G@6F<A@

%%(*!&8JBD8EE<A@<@;G?4@E4@7AF;8DEB86<8E %%(*!&8JBD8EE<A@<@;ADE8E

$04(-$+4-&2 -# - $23'$2(

@48EF;8E<44@7>G@:<@9>4??4F<A@

.4F<@AJ4@

"#"#$'

#!"#"

234#8#$2(&-

'.12$2

+FG7K!

+FG7K!!

+FG7K!!!

+FG7K!.G@BG5><E;87 !1.-"'.2"./8 -#1$2/(1 3.182 ,/+(-&234#($2((((((

,D46;84>I4E;6A>>86F<A@F86;@<CG8+FG7<8E!!!

DA@6;A4>H8A>4D>4H4:8F86;@<CG8+FG7<8E!!!!!!

(10)

"83.+.&(" + - +82(2.%36 -#! +%2 ,/+$2234#($2((((((

!+..#2 ,/+(-&

- $23'$2( /1.3.".+234#8(((

2 ,/+$/1."$22(-&.%1!" -#! +%%.16$23$1-!+.33(-&234#8(

6$23$1-!+.33(-&.%1!" -#! +%234#8(

98,.&1 /'8%.1,$ 241$,$-3.%! +%&$+ 3(-.+83(" "3(5(38234#($2((((

41$ ,$ 241$,$-3%.1$23(, 3(.-.%, 1*$1#(+43(.-2(-! +%234#8( +.6(-3$-2(38$7$1"(2$3$23234#8(54-/4!+(2'$#

23 3(23(" + - +82$2

+FG7K!

+FG7K!!

+FG7K!!!

+FG7K!.G@BG5><E;87

!"$#"

$,,/1(- -#,,/2(-$04(-$ 23', 234#8( +FG7KBABG>4F<A@

A?B4D<EA@A96KFA>A:K58FI88@:DAGBE /8EF8D@5>AFF<@:

1K?A:D4B;K9AD%%(4@7 ADD8>4F<A@E ".,/ 1(2.-.%36 -#! +"83.+.&81$24+32 -#$5 +4 3(.-.%1$%$1$-"$5 +4$2234#8((

+FG7KBABG>4F<A@

,/4@7$6KFA>A:K :D88?8@FA9,/4@7$D8EG>FE4@76ADD8>4F<A@E *'6GDH8E9AD,/4@7$

4K8E<4@?A78>><@:8EF<?4F8E $%%$"3.%&$-$1 + - $23'$2( .-+4-&(-%+ ,, 3(.-234#8(((

DA@6;AE6ABK4@76KFA>A:KD8EG>FE +8DG?4?K>A<7 (4DF<4>BD8EEGD8A9AJK:8@4@7E8DG??GE6>88@LK?846F<H<F<8E +.6(-3$-2(38$7$1"(2$3$23234#8(54-/4!+(2'$#

"$""

$,,/1(- -#,,/2(-$04(-$ 23', 234#8( ".,/ 1(2.-.%36 -#! +"83.+.&81$24+32 -#$5 +4 3(.-.%1$%$1$-"$5 +4$2234#8((

$%%$"3.%&$-$1 + - $23'$2( .-+4-&(-%+ ,, 3(.-234#8(((

+.6(-3$-2(38$7$1"(2$3$23234#8(54-/4!+(2'$#

+(,(3 3(.-2.%3'$234#($2

$""

!!"

(11)

!" #"!

3DEOPDAOEOEO>=OA@KJPDABKHHKSEJCLQ>HE?=PEKJOSDE?D=NANABANNA@PKEJPDAPATP>UPDAEN 1KI=JJQIAN=HO

( 1KOOE ' *KDK - (HRAO , 1=F=IYGE ,, ,UGGYJAJ $TLNAOOEKJ KB ATPN=?AHHQH=NI=PNETIAP=HHKLNKPAEJ=OAEJ@Q?AN=J@I=PNETIAP=HHKLNKPAEJ=OA=J@

EJ DKNOAO SEPD ?DNKJE? =ENS=U EJBH=II=PEKJ?8D<64@ "AGD@4> A9 .8F8D<@4DK

*8E84D6;

(( 1KOOE'5ENP=H= ,1=AG=HHEK,1=DGKJAJ$1=F=IYGE,,,UGGYJAJ

"KIL=NEOKJKBPN=?DA=HS=OD=J@>NKJ?DK=HRAKH=NH=R=CA?UPKHKCUEJDKNOAOSEPD

=J@ SEPDKQP NAOLEN=PKNU OECJO EJ = NABANN=H DKOLEP=H KRAN qDA@F<8DE <@

.8F8D<@4DK+6<8@68

((( 1KOOE'1=AG=HHEK,,YYPPY,3=LEK''=JEBAD,)QJJEH=)1=F=IYGE,, ,UGGYJAJ $BBA?POKBCAJAN=H=J=AOPDAOE=EJ@KNO=HNA?QI>AJ?USEPD=J@

SEPDKQPR=PEJKT=JKJ>NKJ?DK=HRAKH=NH=R=CA?UPKHKCUKBDA=HPDUDKNOAO,;8 .8F8D<@4DK"AGD@4>

/=LANO(h(((=NAEJ?HQ@A@EJPDEO@EOOANP=PEKJ=ONALNEJPOSEPDPDALANIEOOEKJKBPDAEN?KLUNECDP DKH@ANO(J=@@EPEKJOKIAQJLQ>HEODA@I=PANE=HEOLNAOAJPA@2PQ@U(5

(12)

$"!

,63 IEJQPAS=HGPAOP

2 3 =OL=NP=PA=IEJKPN=JOBAN=OA 4" =NA=QJ@ANPDA?QNRA

! + >NKJ?DK=HRAKH=NH=R=CA

! +% >NKJ?DK=HRAKH=NH=R=CABHQE@

"* ?NA=PEJAGEJ=OA

"./# ?DNKJE?K>OPNQ?PERALQHIKJ=NU@EOA=OA

$", ATPN=?AHHQH=NI=PNET

$#3 APDUHAJA@E=IEJAPAPN==?APE?=?E@

$(/' ATAN?EOAEJ@Q?A@LQHIKJ=NUD=AIKNND=CA

$,,/1(- ATPN=?AHHQH=NI=PNETIAP=HHKLNKPAEJ=OAEJ@Q?AN ( # EJBH=II=PKNU=ENS=U@EOA=OA

(+ EJPANHAQGEJ

+ ( HKSAN=ENS=UEJBH=II=PEKJ ,"3 IKJK?=N>KTUH=PAPN=JOLKNPAN ,,/ I=PNETIAP=HHKLNKPAEJ=OA /=. L=NPE=HLNAOOQNAKBKTUCAJ /$+% LQHIKJ=NUALEPDAHE=HHEJEJCBHQE@

1 . NA?QNNAJP=ENS=UK>OPNQ?PEKJ 1!" NA@>HKK@?AHHO

1#+ ( HKSAN=ENS=UEJBH=II=PEKJSEPDNAOLEN=PKNU@EOPNAOO 1." NA?AEREJCKLAN=PEJC?D=N=?PANEOPE?

2 OANQI=IUHKE@

2A OAJOEPEREPU 2L OLA?EBE?EPU

3!23 3NEO>QBBANA@O=HEJASEPD3SAAJ 3(,/ PEOOQAEJDE>EPKNKBIAP=HHKLNKPAEJ=OA 36 PN=?DA=HS=OD

(13)

" #"

(JDKNOAO=OEJKPDANOLA?EAOPDAI=EJBQJ?PEKJKBPDANAOLEN=PKNUOUOPAIEOPK@AHERANKTUCAJ PKPDA>HKK@SDE?DOQLLHEAOEPBKNIAP=>KHEOIEJPEOOQAO=J@PKNAIKRAIAP=>KHE??=N>KJ

@EKTE@ABNKIPDA>HKK@3KB=?EHEP=PAPDEOAMQEJAHQJCOD=RA=I=OOERAOQNB=?A=NA=BKNC=O AT?D=JCA AOPEI=PA@ PK >A IKNA PD=J I &ADN AP =H 3DEO OQNB=?A =NA= EO

?KJPEJQ=HHU?D=HHAJCA@SEPD=HHANCAJO@QOPL=NPE?HAO>=?PANE==J@RENQOAOBNKIPDADKNOAlO HEREJC AJRENKJIAJP #QA PK @KIAOPE?=PEKJ DKNOAO JKS=@=UO =NA KBPAJ GALP EJ ?NKS@A@

AJRENKJIAJPOSEPDLKPAJPE=HHULKKNRAJPEH=PEKJ=J@BA@D=USEPDDECDAN=IKQJPOKBNAOLEN=>HA L=NPE?HAO PD=J L=OPQNA CN=OO ?D=HHAJCEJC PDA HQJClO J=PQN=H @ABAJ?A IA?D=JEOIO PKS=N@O EJPNQ@ANO "KJOAMQAJPHU DKNOAO ?KIIKJHU OQBBAN BNKI NAOLEN=PKNU @EOA=OAO N=JCEJC BNKI REN=H=J@>=?PANE=HEJBA?PEKJOPKJKJEJBA?PEKQOEJBH=II=PKNUHQJC@EOA=OAO

3DADKNOAEO=JAT?AHHAJP=PDHAPASEPD=NAOLEN=PKNUPN=?PDECDHUOLA?E=HEVA@BKNATAN?EOA6EPD EJ?NA=OEJCATAN?EOAHARAHAJANCULNK@Q?PEKJNAMQENAOIKNAKTUCAJ=J@PDANABKNAIKNA=EN D=OPKIKRAEJPK=J@KQPKBPDAHQJCO$RAJ=OHECDP@EOPQN>=J?AEJPDA=ENBHKS=J@BQJ?PEKJ KB PDA NAOLEN=PKNU OUOPAI I=U CNA=PHU EJBHQAJ?A PDA ATAN?EOEJC =>EHEPU 3DQO NAOLEN=PKNU

@EOA=OAO =HKJC SEPD IQO?QHKOGAHAP=H @EOKN@ANO =NA ?KJOE@ANA@ KJA KB PDA IKOP ?KIIKJ

?=QOAOKBLKKNLANBKNI=J?AEJDKNOAO,=NPEJAP=H HHAJAP=H

"DNKJE?EJBH=II=PKNUNAOLEN=PKNU@EOA=OAEO?KIIKJEJDKNOAOAOLA?E=HHUEJ?KQJPNEAOSDANA DKNOAO=NADKQOA@EJOP=>HAOBKN=H=NCAL=NPKBPDAUA=N1K>EJOKJAP=H 3DA@EOA=OAEO

?KJOE@ANA@ JKJEJBA?PEKQO =J@ =HHANCE? =J@ DEOPKNE?=HHU OARAN=H J=IAO D=RA >AAJ QOA@ PK

@AO?NE>A EP >NKGAJ SEJ@ DA=RAO ?DNKJE? K>OPNQ?PERA LQHIKJ=NU @EOA=OA "./# OI=HH

=ENS=U @EOA=OA =J@ IKNA NA?AJPHU NA?QNNAJP =ENS=U K>OPNQ?PEKJ 1 . =J@ EJBH=II=PKNU

=ENS=U@EOA=OA( # OPDA@EOA=OAOD=NAOOARAN=H=PPNE>QPAOSEPDDQI=J=OPDI=EJ?HQ@EJC L=PDKLDUOEKHKCE?=H =OLA?PO =J@ ?HEJE?=H LNAOAJP=PEKJ PDA LNABANNA@ PANI ?QNNAJPHU EO AMQEJA

=OPDI= SDE?D ?=J >A BQNPDAN @ERE@A@ EJPK IEH@IK@AN=PA ( # =J@ OARANA 1 . BKNIO

"KQ[PEH AP =H !KJ@ AP =H $MQEJA =OPDI= EO ?D=N=?PANEVA@ >U =ENS=U DULANNAOLKJOERAJAOOEIL=ENA@HQJCC=OAT?D=JCAAT?AOOERA=??QIQH=PEKJKBIQ?QO=ENS=U NAIK@AHHEJC=J@EJ?NA=OA@MQ=JPEPUKBEJBH=II=PKNU?AHHOEJPDA=ENS=UOSDE?D?=QOAO?HEJE?=H OECJOEJ?HQ@EJC?DNKJE??KQCDJ=O=H@EO?D=NCA=J@LKKNLANBKNI=J?A=J@EJOARANA=OPDI=

EJ?NA=OA@NAOLEN=PKNUABBKNP=PNAOP1K>EJOKJ"KQ[PEH=J@'=SGEJO= 3DAOARANA BKNIKBAMQEJA=OPDI=S=ONA?KCJEVA@=HNA=@UEJPDAH=PAO&NAOOSAHH=J@&NAOOSAHH @AO?NE>A@ EP PK >A i= JANRKQO EJBH=II=PKNU @EOA=OA ?D=N=?PANEVA@ >U @EBBE?QHP =J@

OL=OIE? >NA=PDEJC PDA EJOLEN=PKNU =?P >AEJC A=OEHU LANBKNIA@ PDA ATLEN=PKNU >AEJC RANU LNKHKJCA@=J@=??KILHEODA@>UPSK=LL=NAJPABBKNPOj+KJCPANIATLKOQNAPKKNC=JE?@QOP

=J@IKQH@OEJOP=>HA=ENEO?KJOE@ANA@PK>APDAIKOPEILKNP=JPLNA@EOLKOEJCB=?PKNBKNAMQEJA

=OPDI= 3DKIOKJ =J@ ,?/DANOKJ ,?&KNQI AP =H = 3DEO S=O OQOLA?PA@ >U 6EHHE=IO=HNA=@UEJSDKOP=PA@PD=Pi(D=RAJKDAOEP=PEKJEJ=OOANPEJCPD=P>NKGAJSEJ@

EOCAJAN=HHU@QAPKEILNKLANBKK@IKNAL=NPE?QH=NHUPK>=@IQOPUKN?K=NOAD=U?KJP=EJEJC=

H=NCA MQ=JPEPU KB SKK@U BE>AN BNKI >AEJC =HHKSA@ PK >A?KIA PKK NELA >ABKNA >AEJC ?QPj 6EHHE=IO PPD=PPEIAHEPPHAS=OGJKSJ=>KQPPDAL=PDKCAJAOEO=J@I=J=CAIAJPKB

(14)

PDA@EOA=OA>QPEJPDAL=OP@A?=@AOKQNGJKSHA@CAD=OATL=J@A@CNA=PHU8APPDANAEOOPEHH SKNGPK>A@KJAPKPDKNKQCDHUQJ@ANOP=J@PDAL=PDKLDUOEKHKCUKBAMQEJA=OPDI=

(J PDEO @EOOANP=PEKJ PDA I=EJ PDAIA KB AMQEJA ?DNKJE? JKJEJBA?PEKQO HKSAN =ENS=U EJBH=II=PEKJEO=LLNK=?DA@BNKIPDNAA@EBBANAJP=JCHAO%ENOPHUPDAIKHA?QH=N>=OEOKBAMQEJA

=OPDI=EOEJ?KILHAPAHUQJ@ANOPKK@=J@PDQOPDANKHAKBATPN=?AHHQH=NI=PNETIAP=HHKLNKPAEJ=OA EJ@Q?AN $,,/1(- =J@ EPO NAH=PEKJODEL PK I=PNET IAP=HHKLNKPAEJ=OAO SANA EJRAOPEC=PA@

$,,/1(-EO=PN=JOIAI>N=JALNKPAEJBKQJ@EJR=NEKQO?AHHPULAO(PEJ@Q?AOPDAATLNAOOEKJ

=J@ =?PEREPU KB IAP=HHKLNKPAEJ=OAO ,,/O SDE?D =NA VEJ?@ALAJ@AJP LNKPAKHUPE? AJVUIAO PD=P@ACN=@APDAATPN=?AHHQH=NI=PNET@QNEJCJKNI=HPEOOQAPQNJKRAN=J@EJBH=II=PEKJ&N=OO

=J@ 3KKHA 3DQO $,,/1(- =J@ ,,/O =NA LNAOQILPERAHU NAH=PA@ PK IKOP EJBH=II=PKNU@EOA=OALNK?AOOAO/NAREKQOHUEJDQI=JOEJ?NA=OA@$,,/1(-ATLNAOOEKJD=O

>AAJBKQJ@EJOARAN=HEJBH=II=PKNU?KJ@EPEKJOKBPDAHQJCO!APOQU=GQAP=H.@=FEI=

AP=H&QEHHKPAP=H)KQJA=QAP=H'=O=JAAJAP=H =J@EJ?NA=OA@,,/

=?PEREPUD=O>AAJNALKNPA@EJ=OPDI==J@"./#"QJ@=HHAP=H'=JAP=H)KQJA=Q AP=H ?PEREPUKBCAH=PEJKHUPE?,,/OEJNAOLEN=PKNUOA?NAPEKJOEOEJ?NA=OA@EJDKNOAO SEPDOARANA=OPDI=*KERQJAJAP=H1=QHK=J@,=EOE1=QHKAP=H= =J@

PDANAEOOKIAARE@AJ?AKBEJ?NA=OA@HARAHO=HOKEJIEH@IK@AN=PA=OPDI=!=NPKJAP=H 'KSARAN?KJOPEPQPERA>=OAHEJAATLNAOOEKJEJDA=HPDUPEOOQA KNEJ@Q?E>HAACEJBH=II=PEKJ NAH=PA@ $,,/1(- ATLNAOOEKJ =J@ PDA NAH=PEKJODEL SEPD ,,/ =?PER=PEKJ D=RA JKP >AAJ OPQ@EA@EJDKNOAOPK@=PA

2A?KJ@HUPDA@EOOANP=PEKJ=EIOPKAHQ?E@=PAPDANKHAKBPSK?KIIKJHULANBKNIA@@E=CJKOPE?

PAOPOPN=?DA=HS=OD36 =J@>NKJ?DK=HRAKH=NH=R=CA! + EJ=OOAOOEJCPDAAMQEJAHKSAN NAOLEN=PKNUPN=?PDA=HPD#E=CJKOEJCAMQEJAHKSAN=ENS=UEJBH=II=PEKJEJ?HEJE?=HLN=?PE?AEO KBPAJ=E@A@>U=ENS=UAJ@KO?KLE?AT=IEJ=PEKJ=J@O=ILHEJCKBPDA=ENS=UOBKN?UPKHKCE?=H

=J=HUOEOPK?KJBENI?HEJE?=HOQOLE?EKJ=J@PKEILNKRA@E=CJKOPE?=??QN=?U,=ENAP=H 'KBBI=J "UPKHKCE?=H=J=HUOEOKB36=J@>NKJ?DK=HRAKH=NH=R=CABHQE@! +% EO=

?KIIKJ@E=CJKOPE?LNK?A@QNAEJAMQEJALN=?PE?APD=PD=O>AAJEJQOA=HNA=@UBNKIPDAh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

?QPKBB R=HQAO BKN @EOA=OA =NA H=NCAHU >=OA@ KJ K>OANR=PEKJ=H OPQ@EAO =J@ ATLANP KLEJEKJ ,KNAKRAN=?KJOAJOQOBKN=PNQACKH@OP=J@=N@BKN@E=CJKOEJCAMQEJA=ENS=UEJBH=II=PEKJEO IEOOEJC(JOARAN=HLNAREKQOHULQ>HEODA@OPQ@EAO36=J@! +%?UPKHKCUNAOQHPOD=RAODKSJ LKKN?KNNAH=PEKJ#ANGOAJAP=H'QCDAOAP=H,=HEGE@AOAP=H%N=ELKJPAP

=H >QPOKIAOPQ@EAOD=RA?KJ?HQ@A@PDAKLLKOEPA6EJ@ANAP=H6EJ@ANAP=H '=JOAJAP=H 3KKQNGJKSHA@CAPDANA=NAJKNA?AJPLQ>HE?=PEKJO?KIL=NEJC36

=J@! +%?UPKHKCU=IKJCDKNOAOSEPDJ=PQN=HHUK??QNNEJCNAOLEN=PKNU@EOA=OA(JPDEOPDAOEO 36 =J@ ! +% ?UPKHKCU NAOQHPO KB DKNOAO KB R=NUEJC =CAO =J@ @EO?ELHEJAO =NA ?KIL=NA@

(15)

%QNPDANIKNASA=EIPK=OOAOOPDAOAJOEPEREPU=J@OLA?EBE?EPUKB36=J@! +%?UPKHKCUEJ AMQEJANAOLEN=PKNU@EOA=OA

3DEN@HUHKSAN=ENS=UEJBH=II=PEKJEJPDADKNOAEOREASA@EJNAH=PEKJPKCAJAN=H=J=AOPDAOE=

/JAQIKJE=D=O>AAJ@AO?NE>A@=O=LKPAJPE=H?KILHE?=PEKJKBCAJAN=H=J=AOPDAOE=EJOARAN=H OLA?EAOEJ?HQ@EJCDKNOAO&NQ>>=J@,QEN 'KSARANPDAABBA?POKBCAJAN=H=J=AOPDAOE=

KJEJBH=II=PKNUNAOLKJOAOEJPDAHQJCO=J@PDANAOLKJOAKBEJBH=II=PKNUI=NGANOOQ?D=O OANQI=IUHKE@ 2 EJ>HKK@=NA?QNNAJPHULKKNHUQJ@ANOPKK@EJDKNOAO J=AOPDAOE=EO GJKSJ PK EJ?NA=OA PDA LAN?AJP=CA KB JAQPNKLDEHE? EJBH=II=PKNU ?AHHO EJ ! +% KB DKNOAO

=J=AOPDAPEVA@EJH=PAN=HNA?QI>AJ?U(PKAP=H >QPEPEO?QNNAJPHUQJGJKSJSD=PHARAH

=J@ @QN=PEKJ KB HKSAN =ENS=U EJBH=II=PEKJ ?=J >A ATLA?PA@ =BPAN =J=AOPDAOE= EJ @KNO=H NA?QI>AJ?UEJDA=HPDUDKNOAO3DEOEJBKNI=PEKJEOS=NN=JPA@EJ?HEJE?=HLN=?PE?ASDAJO=ILHAO

=NAK>P=EJA@BNKIPDAHKSAN=ENS=UO=BPANCAJAN=H=J=AOPDAOE=BKN?HEJE?=HKNNAOA=N?DLQNLKOAO ,KNAKRAN PK EJ?NA=OA PDA O=BAPU KB =J=AOPDAOE= = JKRAH LD=NI=?KHKCE?=H =CAJP =Jα

=@NAJK?ALPKN =JP=CKJEOP R=PEJKT=J D=O NA?AJPHU >AAJ @ARAHKLA@ BKN RAPANEJ=NU QOA (J PDEO

@EOOANP=PEKJ PDA LKPAJPE=H ABBA?PO KB R=PEJKT=J KJ AMQEJA HQJC EJBH=II=PEKJ =BPAN CAJAN=H

=J=AOPDAOE==NAEJRAOPEC=PA@=O=OA?KJ@=NU=EI

(16)

$%"" "#

7;04,(9:/3(

,9*806:054(4+68,<(2,4*,

-KJEJBA?PEKQO ?DNKJE? NAOLEN=PKNU @EOA=OAO =NA ?KIIKJ EJ DKNOAO KB R=NEKQO =CAO =J@

@EO?ELHEJAO=J@?=JOARANAHU=BBA?PPDAENLANBKNI=J?A"KQ[PEH=J@'=SGEJO= (JPDAL=OP

@A?=@AO OARAN=H J=IAO D=RA >AAJ QOA@ PK @AO?NE>A PDAOA NAOLEN=PKNU ?KJ@EPEKJO DA=RAO

>NKGAJSEJ@?DNKJE?K>OPNQ?PERALQHIKJ=NU@EOA=OA"./# OI=HH=ENS=U@EOA=OA=J@IKNA NA?AJPHUNA?QNNAJP=ENS=UK>OPNQ?PEKJ1 . =J@EJBH=II=PKNU=ENS=U@EOA=OA( # 3DA R=NE=>HAJKIAJ?H=PQNASDE?DD=O>AAJ>=OA@KJPDA?HEJE?=HLNAOAJP=PEKJKNL=PDKHKCE?=HKN

?UPKHKCE?=HBA=PQNAOKBPDA@EOA=OAD=O>AAJ?KJBQOEJCBKN>KPDRAPANEJ=NE=JO=J@?HEAJPO#QA PKOARAN=HOEIEH=NEPEAOSEPDDQI=J=OPDI=PDA?QNNAJPHUNA?KIIAJ@A@PANIPK@AO?NE>APDA IEH@IK@AN=PA ( # KN OARANA 1 . BKNI KB JKJEJBA?PEKQO ?DNKJE? HKSAN =ENS=U EJBH=II=PEKJEOAMQEJA=OPDI=!QHHKJA=J@+=RKEA"KQ[PEHAP=H!KJ@AP=H $MQEJA =OPDI= EO AJ?KQJPANA@ BNAMQAJPHU AOLA?E=HHU EJ ?KQJPNEAO SDANA DKNOAO =NA OP=>HA@BKN=H=NCAL=NPKBPDAUA=N1K>EJOKJAP=H'KH?KI>AAP=H'=JOAJAP=H

= 'KSARANOP=>HEJC?KJ@EPEKJOI=UR=NU?KJOE@AN=>HU>APSAAJ?KQJPNEAO=J@EJ=OPQ@U

>U6=OGKAP=H OP=>HEJCS=OJKP=OOK?E=PA@SEPDPDANEOGKB=ENS=UEJBH=II=PEKJ(J

%EJH=J@L=OPQNAEO=R=EH=>HABKNDKNOAO@QNEJCPDAOQIIANIKJPDO>QPBNKI=QPQIJPKOLNEJC IKOPDKNOAO=NAOP=>HA@SEPD@=EHUPQNJKQPKBR=NE=>HADKQNO@ALAJ@EJCKJSA=PDAN?KJ@EPEKJO 3DALNAR=HAJ?AKBOARANA=OPDI=EJPDAJKNPDANJDAIEOLDANA=J@KPDANPAILAN=PA?HEI=PAOEO AOPEI=PA@ PK >A =LLNKTEI=PAHU h EJ =@QHP DKNOAO 'KP?DGEOO AP =H =J@ PDA LNAR=HAJ?AKBIEH@=OPDI=D=O>AAJOQCCAOPA@PKN=JCABNKIPK6KK@AP=H HHAJAP=H1K>EJOKJAP=H #=P=BNKI%EJJEODDKNOAO=NA?QNNAJPHUH=?GEJC>QP=

OEIEH=NLNAR=HAJ?AIECDP>AATLA?PA@>=OA@KJCAKCN=LDE?=HHK?=PEKJ?HEI=PA=J@OP=>HEJC PEIAO'KSARAN=NA?AJPOPQ@UOQCCAOPOPD=PARAJDKNOAOPD=P=NA=OUILPKI=PE?=J@L=OPQNA@

UA=NNKQJ@KBPAJODKSARE@AJ?AKBIEH@=OPDI=PDALNAR=HAJ?AS=OAOPEI=PA@PK>A=ODECD

=OEJOQIIAN=J@EJSEJPAN>QPPDAOPQ@ULKLQH=PEKJS=ONAH=PERAHUOI=HHSEPD

=J@DKNOAONAOLA?PERAHU#=REO=J@2DA=PO

,:0525.?(4+6(:/56/?90525.?

+KJCPANIATLKOQNAPKKNC=JE?@QOPIKQH@OBQJCEJKTEKQOC=OAO>AP=#CHQ?=JQHPN=BEJA L=NPE?HAO=J@AJ@KPKTEJOEJ=OP=>HAAJRENKJIAJPD=O>AAJ?KJOE@ANA@PK>APDAIKOPEILKNP=JP LNA@EOLKOEJCB=?PKNBKNAMQEJA=OPDI=3DKIOKJ=J@,?/DANOKJ,?&KNQIAP=H=

1K>EJOKJ'KH?KI>AAP=H 'KSARANATLKOQNAPKHKSMQ=HEPUOP=>HA=EN@KAOJKP ATLH=EJ=HH?=OAOOEJ?AOKIADKNOAOKJHU=PL=OPQNALNAOAJPSEPD=OEIEH=N?HEJE?=HOUJ@NKIA

@QAPKNAOLEN=>HACN=OOLKHHAJO=J@BQJC=HOLKNAOPDA?KJ@EPEKJEONABANNA@PK=OL=OPQNA=OPDI=

OQIIANDA=RAOOQIIAN1 .KNOQIIANL=OPQNA=OOK?E=PA@K>OPNQ?PERALQHIKJ=NU@EOA=OA 2/ .# 2A=DKNJ =J@ !A=@HA %ANN=NE AP =H 3DA I=J=CAIAJP KB EJ@ERE@Q=H DKNOAONAC=N@EJCBAA@EJC=J@PEIAOP=>HA@EAATLKOQNAPKKNC=JE?@QOP ?=JR=NUOQ>OP=JPE=HHU

(17)

SDE?D?=JD=RA=OECJEBE?=JPABBA?PKJPDANEOGKB@ARAHKLEJC=OPDI=$TLKOQNAPK=JQN>=J AJRENKJIAJP?KIL=NA@SEPDNQN=HOQNNKQJ@EJCONAOLEN=PKNUEJBA?PEKJEJA=NHUHEBA=J@BAA@EJC SEPDD=UD=RA>AAJBKQJ@PK>ANEOGB=?PKNOBKN=OPDI=1K>EJOKJAP=H'KP?DGEOOAP=H 6=OGK AP =H DKSARAN =HH LNA@EOLKOEJC B=?PKNO =NA ?QNNAJPHU QJGJKSJ

?KJPNE>QPEKJ KB EJBA?PEKQO =CAJPO PK @ARAHKLEJC IEH@IK@AN=PA =OPDI= D=O >AAJ OQCCAOPA@

6KK@AP=H'KQPOI=AP=H >QP?KJ?HQOERA@=P==NAH=?GEJC"KQ[PEHAP=H HNA=@U=HIKOPUA=NO=CK=DANA@EP=NU?KILKJAJPBKN@ARAHKLEJCOARANAAMQEJA=OPDI=

S=OLNKLKOA@,=NPEAP=H =J@IKNANA?AJPHU=CAJAPE?HEJGD=O>AAJK>OANRA@>APSAAJ L=NPE?QH=N?DNKIKOKIANACEKJO=J@OARANA=OPDI=EJOKIADKNOAB=IEHEAO2SEJ>QNJAAP=H 'KSARANPDACAJAPE?OQO?ALPE>EHEPUBKN@ARAHKLEJCIEH@IK@AN=PA=OPDI=D=OJKP>AAJ EJRAOPEC=PA@PK@=PA

!KPDAMQEJA=OPDI=LDAJKPULAOIEH@IK@AN=PA( # =J@OARANA1 . OD=NA=JQI>ANKB

?HEJE?=H=J@L=PDKLDUOEKHKCE?=HOEIEH=NEPEAO+A?HANAAP=H!QHHKJA=J@+=RKEA

"KQ[PEHAP=H ,EH@IK@AN=PA=OPDI=?=J=BBA?PDKNOAOKB=JU=CACAJ@AN>NAA@KN

@EO?ELHEJA>QPPDA?KJ@EPEKJEOPDKQCDPPK>AIKNA?KIIKJKN=PHA=OPIKNAOPQ@EA@EJUKQJC PK IE@@HA=CA@ DKNOAO "KQ[PEH AP =H .J PDA KPDAN D=J@ OARANA =OPDI= EO IKNA

?KIIKJHU AJ?KQJPANA@ EJ DKNOAO =CA@ =P HA=OP UA=NO 1K>EJOKJ "KQ[PEH =J@ 6=N@

$MQEJA =OPDI= EO ?D=N=?PANEVA@ >U =ENS=U DULANNAOLKJOERAJAOO EIL=ENA@ HQJC C=O AT?D=JCAAT?AOOERA=??QIQH=PEKJKBIQ?QO=J@EJ?NA=OA@JQI>ANKBEJBH=II=PKNU?AHHOEJ

=ENS=UO1K>EJOKJ"KQ[PEH=J@'=SGEJO= >QPPDAL=PDKLDUOEKHKCUEOJKPBQHHU QJ@ANOPKK@ (J OARANA =OPDI= PDA ?D=JCAO EJ =ENS=UO =NA IKNA OQ>OP=JPE=H PD=J EJ IEH@IK@AN=PA=OPDI==J@AOLA?E=HHU=LL=NAJP@QNEJC@EOA=OAAT=?AN>=PEKJOBKHHKSEJC=JPECAJ ATLKOQNA #QNEJC @EOA=OA AT=?AN>=PEKJ ?D=JCAO EJ LQHIKJ=NU BQJ?PEKJ EJ?HQ@EJC =NPANE=H DULKT=AIE=EJ?NA=OAEJLQHIKJ=NUNAOEOP=J?A=J@@A?NA=OAEJ@UJ=IE?HQJC?KILHE=J?A?=J

>A K>OANRA@ >QP PDA ?HEJE?=H OECJO PULE?=HHU @EO=LLA=N EJ @EOA=OA NAIEOOEKJ "KQ[PEH =J@

'=SGEJO= (JOARANA=OPDI=JAQPNKLDEHO@KIEJ=PAPDAEJBH=II=PKNU?AHHLKLQH=PEKJEJ PDA=ENS=UOSEPDPDA=EIKBAHEIEJ=PEKJKBPDAEJD=HA@=JPECAJO>ULD=CK?UPKOEO=J@NAHA=OAKB

=?PERA OQ>OP=J?AO SDANA=O EJ IEH@IK@AN=PA =OPDI= =HOK AKOEJKLDEHE? =J@ IAP=?DNKI=PE?

@EOA=OA PULAO D=RA >AAJ NA?KCJEVA@ 1K>EJOKJ "KQ[PEH AP =H %KN AT=ILHA AKOEJKLDEHE? IEH@IK@AN=PA =OPDI= ?=J >A OAAJ EJ UKQJC DKNOAO ATLKOA@ PK NAOLEN=>HA L=NPE?QH=PAO>UBAA@EJCD=UBNKIPDAJAPEJOPA=@KBBNKIPDACNKQJ@(RAOPANAP=H (J

?KJPN=OP AKOEJKLDEHO =NA JKP = BA=PQNA KB PDA @EOA=OA EJ OARANA AMQEJA =OPDI= #Q>Q? =J@

+=RKEA (JOARANA=OPDI=@EOA=OAAT=?AN>=PEKJJAQPNKLDEHO?=JEJR=@APDAHQJCO=HNA=@U EJhDKQNO=BPANATLKOQNAPKIKQH@UD=U%=EN>=ENJAP=H

2ARANA=OPDI=D=O>AAJDEOPKNE?=HHU?=HHA@kAMQEJAAILDUOAI=l@QAPKPDAHQJCO=LLA=NEJC I=?NKO?KLE?=HHU@EOPAJ@A@=PJA?NKLOU.>AH=J@2?DIEPANHKS +=PANPDEOS=OBKQJ@PK

>A=JEJ=??QN=PAPANI=OPDAHQJCOKB=BBA?PA@DKNOAOPAJ@PKNAI=EJDULANEJBH=PA@@QAPK=EN PN=LLEJCOA?KJ@=NUPK=ENS=UK>OPNQ?PEKJEJOPA=@KBAILDUOAI="KQ[PEH=J@'=SGEJO=

'KSARANOARAN=H?D=N=?PANEOPE?DEOPKHKCE?=H?D=JCAOD=RA>AAJK>OANRA@/ANELDAN=H=ENS=U NAIK@AHHEJC=J@=ENS=UK>OPNQ?PEKJ=NAEILKNP=JPBA=PQNAOKBOARANA=OPDI==J@EPD=O>AAJ K>OANRA@ PD=P LANE>NKJ?DEKH=N EJBH=II=PKNU ?AHH EJBEHPN=PEKJ IQ?KQO ?AHH DULANLH=OE=

LANE>NKJ?DEKH=NIAP=LH=OE==ENS=UOIKKPDIQO?HADULANLH=OE==J@EJPANOPEPE=HBE>NKOEOKBHQJC PEOOQA?KJPNE>QPAPKPDASKNOAJEJCKB?HEJE?=HOECJO!=NPKJ=J@&ADHAJ!QHHKJAAP=H 3DAOA?D=JCAO=NAOEIEH=NPKPDKOAK>OANRA@EJDQI=J=OPDI=%ADNAJ>=?DAP=H

(18)

3DALKPAJPE=HNAIK@AHHEJC?D=JCAOEJPDA=ENS=UOKBDKNOAOSEPDIEH@IK@AN=PA=OPDI=OPEHH NAMQENAATLHKNEJC>QPLANE>NKJ?DEKH=NEJBH=II=PKNU?AHHEJBEHPN=PEKJ=J@>NKJ?DEKH=NOIKKPD IQO?HADULANLH=OE=OAAIPK>A?KIIKJEJ=?PERAHUPN=EJEJC=J@N=?EJCN=?ADKNOAOPAN6KKNP AP=H

(IIQJKL=PDKHKCE?=H IA?D=JEOIO KB AMQEJA =OPDI= =NA OPEHH EJ?KILHAPAHU QJ@ANOPKK@

1AC=N@EJC3DAHLAN?AHHOHUILDK?UPAOPD=P=NAEILKNP=JPIA@E=PKNOKBPDAEIIQJANAOLKJOA RE= PDA ?UPKGEJAO PD=P PDAU LNK@Q?A PDA EIIQJKHKCE?=H >=OEO KB AMQEJA =OPDI= D=O >AAJ

?KJOE@ANA@ PK >A LNA@KIEJ=JPHU @NERAJ >U 3DPULA ?UPKGEJAO !QHHKJA =J@ +=RKEA 'KSARAN PDANA EO ARE@AJ?A PD=P >KPD 3D =J@ 3DPULA EIIQJA NAOLKJOAO =J@ ?UPKGEJA LNKBEHAOKNIETA@ =NAEJRKHRA@EJPDAL=PDKCAJAOEOKBIEH@IK@AN=PA!AAGI=JAP=H 1E?D=N@AP=H =J@OARANA+=RKEAAP=H&ECQANAAP=H"KN@A=QAP=H 1EEDEIYGE AP =H +=RKEA+=IKQNAQT AP =H AMQEJA =OPDI= HPANJ=PERAHU JK EJRKHRAIAJPKBAEPDAN3DKN3DNAOLKJOAOEJIEH@IK@AN=PA'QCDAOAP=H KNOARANA

=OPDI=*HAE>ANAP=H EJOSKNPDAP=H D=O>AAJLNKLKOA@2KIAOPQ@EAOOQCCAOP PDAEJBH=II=PEKJPK>AIA@E=PA@>U3D?UPKGEJAOOQ?D=OEJPANHAQGEJ#A>NQAAP=H EJOSKNPD AP =H !AAGI=J AP =H *KNJ AP =H =J@ I=?NKLD=CA KN 3D

@ANERA@0$ /=?DKHASOG= AP =H -ARANPDAHAOO =O PDA EIIQJKHKCE?=H >=OEO KB AMQEJA=OPDI=NAI=EJOEJ?KJ?HQOERABQNPDANOPQ@EAO=NANAMQENA@NAC=N@EJC@EBBANAJP=OPDI=

LDAJKPULAO SEPD @EBBANAJP ?UPKHKCE?=H L=PPANJO PK AHQ?E@=PA PDA EIIQJKL=PDKHKCE?=H IA?D=JEOIOSDE?D=NAHEGAHUPK>A?KILHAT=J@EJBHQAJ?A@>U>KPDCAJAPE?=J@AJRENKJIAJP=H B=?PKNO #EBBANAJP ?UPKGEJA LNKBEHAO =J@ ?KI>EJ=PEKJO PDANAKB IECDP ARAJ >A K>OANRA@ =P

@EBBANAJPPEIALKEJPOEJ@EOA=OALNK?AOOAO

2040*(290.49

"KIIKJ?HEJE?=HOECJOBKN>KPDLDAJKPULAOEJ?HQ@ALKKNLANBKNI=J?AKNATAN?EOAEJPKHAN=J?A

?DNKJE?EJPANIEPPAJP?KQCD=J@J=O=H@EO?D=NCA>QPEJIEH@IK@AN=PA=OPDI=PDAOECJO=NA KBPAJOQ>PHA=PNAOPKNOQ>?HEJE?=H"KQ[PEH=J@'=SGEJO="KQ[PEHAP=H +=>KQNA@

>NA=PDEJC =P NAOP @EBBANAJPE=PAO IEH@IK@AN=PA =J@ OARANA =OPDI= LDAJKPULAO DKNOAO SEPD OARANA=OPDI=EJ@EOA=OAAT=?AN>=PEKJ=O=NAOLKJOAPK=JPECAJE?OPEIQHQO?=JLNAOAJPSEPD NAOLEN=PKNU@EOPNAOO?D=N=?PANEVA@>UI=NGA@HUEJ?NA=OA@NAOLEN=PKNUN=PA=J@ATLEN=PKNUABBKNP

=J@JKOPNEHBH=NEJC@QAPKDULANNAOLKJOERAJAOONAH=PA@>NKJ?DK?KJOPNE?PEKJ3AO=NKSOGEAP=H 1QODAP=H1K>EJOKJ"KQ[PEH=J@'=SGEJO= 3DAOADKNOAOI=U=HOK

@AIKJOPN=PA = iDA=RA HEJAj EJ PDA ?=Q@KRAJPN=H =>@KIEJ=H IQO?QH=PQNA @QA PK EJ?NA=OA@

ATLEN=PKNUABBKNP=J@IQO?HAPAJOEKJ3DA?HEJE?=HOECJO=NAKBPAJR=NE=>HAEJEJPAJOEPU=J@

DKNOAOI=U>A=OUILPKI=PE?BKNHKJCLANEK@ONAIEOOEKJ EBAJRENKJIAJP=H=JPECAJE?B=?PKNO

=NAAHEIEJ=PA@3DKIOKJ=J@,?/DANOKJ1K>EJOKJ 3DAOECJO=NAQOQ=HHUSKNOA

@QNEJCSEJPAN@QAPKDKNOAO>AEJCOP=>HA@BKNHKJCANLANEK@OPD=JEJPDAOQIIANOA=OKJ'KNOAO SEPDOARANA=OPDI=QOQ=HHUEILNKRA?HEJE?=HHUSEPDKQPIA@E?=HEJPANRAJPEKJSEPDEJhSAAGO

=BPAN>AEJCLH=?A@KJL=OPQNASEPDKQP=??AOOPKD=U"KQ[PEH=J@'=SGEJO= >QPDKNOAO SEPD=OQIIANL=OPQNA=OOK?E=PA@BKNIKB=OPDI==NA=JAT?ALPEKJPKPDEOSEPDSKNOAJEJCKB

?HEJE?=HOECJOEJPDAOQIIAN(PD=OJKPUAP>AAJ?KJBENIA@EJLAANNAREASA@HEPAN=PQNASDAPDAN PDAOARANABKNIKB=OPDI=EO=@ENA?P?KJPEJQQIKBPDAIKNALNAR=HAJPIEH@=OPDI=(PD=O>AAJ

(19)

LNKLKOA@PD=PDKNOAOSEPDIEH@?HEJE?=HNAOLEN=PKNUOECJOIECDP>A=PNEOGKB@ARAHKLEJCOARANA

=OPDI= !KOOD=N@ =J@ &AN>AN ( # =J@ 1 . D=RA >AAJ PN=@EPEKJ=HHU ?KJOE@ANA@

OAL=N=PA @EOA=OAO DKSARAN EP EO QJ?HA=N SDAPDAN PDEO @EREOEKJ NABHA?PO @EBBANAJ?AO EJ L=PDKCAJAOEOKNFQOP=@EBBANAJ?AEJPDA?HEJE?=HOARANEPUKBPDA@EOA=OA

536(80954:5(9:/3(5-/;3(49(4+5:/,896,*0,9

$MQEJA=OPDI=?HKOAHUNAOAI>HAO=OPDI=EJDQI=JOEJOARAN=H=OLA?PO OPDI=EJLAKLHAEO OEIEH=NHU=DAPANKCAJAKQOJKJOALPE??DNKJE?HKSAN=ENS=UEJBH=II=PKNU?KJ@EPEKJPD=P=BBA?PO hKBPDALKLQH=PEKJ@ALAJ@EJCKJPDA?KQJPNU&(- 3DA?HEJE?=HOECJOEJDQI=JO EJ?HQ@A ?KQCDEJC SDAAVEJC ODKNPJAOO KB >NA=PD ?DAOP PECDPJAOO =J@ ATLEN=PKNU =ENBHKS HEIEP=PEKJ3DAOECJO?=J>AR=NE=>HA=J@KBBHQ?PQ=PEJCOARANEPUKRANPEIA=OEJDKNOAO+EGA AMQEJA =OPDI= PDA L=PDKLDUOEKHKCU EJ?HQ@AO >NKJ?DKOL=OI =ENS=U DULANNAOLKJOERAJAOO EJ?NA=OA@ =IKQJP KB =ENS=U IQ?QO =J@ =ENS=U S=HH PDE?GAJEJC =J@ OARANEPUNAH=PA@

NAIK@AHHEJC!=NNEKOAP=H&(- 3DA?AHHQH=NLNKBEHAEJPDAHQJCOKB=OPDI=PE?

DQI=JO EO KBPAJ AKOEJKLDEHE? >QP ?=J R=NU >APSAAJ JAQPNKLDEHE? AKOEJKLDEHE? KN L=Q?ECN=JQHK?UPE? ?KJP=EJEJC KJHU = BAS EJBH=II=PKNU ?AHHO @ALAJ@EJC KJ PDA =OPDI=

LDAJKPULA &(- (J DQI=JO =OPDI= OARANEPU EO @ERE@A@ EJPK IEH@ IK@AN=PA =J@

OARANA?=PACKNEAO=J@>A?=QOAPDEO@EREOEKJEO>=OA@KJPDAEJPAJOEPUKBPDAPNA=PIAJPNAMQENA@

PK?KJPNKHOUILPKIO=J@AT=?AN>=PEKJOEP?=J=HOK?D=JCAKRANPEIA&(- 'QI=J

=OPDI=EO?KJOE@ANA@=O=?KHHA?PEKJKB=OPDI=?KJ@EPEKJOSEPDR=NUEJC?HEJE?=HLNAOAJP=PEKJ LDAJKPULAO =J@ IKHA?QH=N IA?D=JEOIO AJ@KPULAO PD=P =NA JKP JA?AOO=NEHU BETA@ I=U KRANH=L=J@?=J>AIK@EBEA@>UPNA=PIAJP3DANABKNA=OPDI=?=J>ABQNPDANOQ>?=PACKNEVA@

EJPK @EBBANAJP LDAJKPULAO PDA IKOP ?KIIKJ LDAJKPULAO =NA =HHANCE? =OPDI= JKJ=HHANCE?

=OPDI==@QHPKJOAP=OPDI==OPDI=SEPDLANOEOPAJP=ENBHKSHEIEP=PEKJ=J@=OPDI=EJK>AOA L=PEAJPO&(- 2EIEH=NHUBQNPDANOQ>?=PACKNEV=PEKJ?KQH@>AJAA@A@EJDKNOAOEJPDA BQPQNA PK =E@ EJ IKNA OLA?EBE? PDAN=LAQPE?O =J@ LNKLDUH=TEO >A?=QOA AMQEJA =OPDI= OD=NAO BA=PQNAOOEIEH=NPK>KPD=HHANCE?=J@JKJ=HHANCE?DQI=J=OPDI=LDAJKPULAO!KJ@AP=H 'KSARAN =HPDKQCD EJ DQI=JO OKIA LDAJKPULACQE@A@ PNA=PIAJPO =NA =R=EH=>HA JK OPNKJC NAH=PEKJODELD=O>AAJBKQJ@PK@=PA>APSAAJPDAOLA?EBE?L=PDKHKCE?=HBA=PQNAO=J@L=NPE?QH=N PNA=PIAJPNAOLKJOAO&(-

"8(492(:054(2(9:/3(8,9,(8*/

2ARAN=HOLA?EAOKB=JEI=HOD=RA>AAJQOA@EJATLANEIAJP=HIK@AHOKBDQI=J=OPDI=EJ?HQ@EJC DAEAB;<>4NK@AJPO?=PO@KCOLECO?=PPHAODAALLNEI=PAO=J@AMQEJAO QJAP=H ,KOPKBPDAOAOLA?EAO@KJKPJ=PQN=HHU@ARAHKL=OPDI==J@NAMQENA=NPEBE?E=HEJ@Q?PEKJKBPDA

@EOA=OAHEIEPEJCPDAQOAKBPDAOAIK@AHOEJDQI=J=OPDI=NAOA=N?D'KSARAN?=PO=J@DKNOAO I=U OLKJP=JAKQOHU LNAOAJP SEPD =OPDI=PE? @EOA=OA (J ?=PO PDA EJBH=II=PEKJ EJ =OPDI=PE?

HQJCOEOAKOEJKLDEHE?EJATLANEIAJP=HIK@AHO=OEPKBPAJEOEJLAKLHA=J@PDKQCDPPKD=RA=J

=HHANCE?>=?GCNKQJ@1AEJANKAP=H .JPDAKPDAND=J@EJJ=PQN=H?=OAOPDA=OPDI=PULA

?=J>AAEPDANAKOEJKLDEHE?KNJAQPNKLDEHE?EJ?=PO)KDJOKJ=J@5ANJ=Q 'KSARAN@QA PKPDAENOI=HHOEVAPDAQOAKB?=POEJ=OPDI=NAOA=N?DEOKBPAJHEIEPA@3DA?HA=N=@R=JP=CAKB DKNOAOEOPDAEN>ECCANOEVA=J@A=OU=??AOOPKPDAHKSANNAOLEN=PKNUPN=?PBKNO=ILHEJCSEPDKQP

(20)

CAJAN=H =J=AOPDAOE= #QA PK OEIEH=NEPEAO EJ PDA L=PDKLDUOEKHKCU ?HEJE?=H LNAOAJP=PEKJ =J@

DEOPKL=PDKHKCE?=H BEJ@EJCO >APSAAJ DQI=J =OPDI= =J@ IEH@IK@AN=PA =J@ OARANA AMQEJA

=OPDI=DKNOAOSEPDJ=PQN=HHUK??QNNEJC@EOA=OAI=UOANRA=OQOABQHPN=JOH=PEKJ=HIK@AHOBKN DQI=J =OPDI= NAOA=N?D +A?HANA AP =H !QHHKJA =J@ +=RKEA !KJ@ AP =H

$OLA?E=HHUOARANAAMQEJA=OPDI=D=O>AAJOQCCAOPA@PK>A=JE@A=HIK@AHBKNPDAOPQ@EAOKJ JKJ=HHANCE? =@QHPKJOAP =J@ OARANA =OPDI= LDAJKPULAO EJ DQI=JO !QHHKJA =J@ +=RKEA >QPPDANAEOJKAT=?PAMQEJAI=P?D=R=EH=>HABKNPDA?H=OOE?=HDQI=J=HHANCE?=PKLE?

=OPDI= =OPDI= SEPD LANOEOPAJP =ENBHKS HEIEP=PEKJ KN =OPDI= EJ K>AOA L=PEAJPO !KJ@ AP =H ,KNAKRANQOEJCAMQEJAOEJ=OPDI=NAOA=N?DD=OOKIAPEIAO>AAJ?KJOE@ANA@?KOPHU=J@

H=>KNEKQO QJ AP =H JKPDAN =@R=JP=CA KB DKNOAO EO PD=P OEJ?A PDA AJRENKJIAJP=H PNECCANEJCB=?PKNO=NAGJKSJPDA@EOA=OAOP=PQO?=J>AIK@EBEA@>=OA@KJPDAJAA@OKBPDA OLA?EBE?NAOA=N?DOAPPEJC!QHHKJA=J@+=RKEA -ARANPDAHAOOQOEJCPN=JOH=PEKJ=HIK@AHO EJ =OPDI= NAOA=N?D =J@ EJ?NA=OEJC ?KHH=>KN=PEKJ >APSAAJ DQI=J =J@ =JEI=H DA=HPD LNKBAOOEKJ=HO?KQH@=E@EJEILNKREJCQJ@ANOP=J@EJCKBPDAL=PDKLDUOEKHKCUKB>KPDDQI=J=J@

=JEI=H=OPDI=ARAJPQ=HHUDAHLEJCPKLNARAJPPDA@EOA=OAEJ=HHOLA?EAO

7;04,(9:/3(+0(.459:0*9

3DANAOLEN=PKNUPN=?PKBPDADKNOAEO=??AOOE>HA>UR=NEKQO@E=CJKOPE?IAPDK@OEJ?HQ@EJC=ENS=U AJ@KO?KLUN=@EKCN=LDU=J@QHPN=OKJKCN=LDU=IKJCKPDANO'KSARAN=O=HS=UOEJ?HEJE?=H LN=?PE?AEPEOEILKNP=JPPKK>P=EJ=@AP=EHA@DEOPKNUKBPDAL=PEAJP=J@PKLANBKNI=PDKNKQCD LDUOE?=HAT=IEJ=PEKJ>ABKNAEILHAIAJPEJC=JUBQNPDAN@E=CJKOPE?O4J@KQ>PA@HUNA?KN@EJC LKPAJPE=H NAOLEN=PKNU @EOA=OANAH=PA@ OECJO OQ?D =O ?KQCDEJC J=O=H @EO?D=NCA BARAN LKKN LANBKNI=J?AKNATAN?EOAEJPKHAN=J?A=J@?DNKJE?EPUKBPDAOECJOEO?NQ?E=HBKNCAJAN=PEJC=HEOP KBLKPAJPE=H@EBBANAJPE=H@E=CJKOAO=J@CQE@EJCBQNPDAN@E=CJKOPE?O#AP=EHO=>KQPPDAJQI>AN KBDKNOAO=BBA?PA@PDANAOLKJOAPKLNAREKQOIA@E?=PEKJOSDAJ=LLNKLNE=PAPDADKNOAlODKQOEJC OUOPAI=J@>A@@EJCPDA=ENMQ=HEPUEJPDAOP=>HAPDABAA@EJC=J@BKN=CAPULAPQNJKQPNACEIAJO

=J@EJBKNI=PEKJ=>KQPNA?AJPPN=RAHHEJCKPDANDA=HPDEOOQAOR=??EJ=PEKJOP=PQO8F68F8D4=NA EILKNP=JPB=?PKNOPD=P?=JEJBHQAJ?APDA@E=CJKOPE?LNK?AOO=J@I=J=CAIAJPKBPDADKNOA.PDAN AHAIAJPOPD=PI=U=BBA?PPDA@E=CJKOPE?L=PDEJ?HQ@A?KOPNAH=PA@B=?PKNO=J@?HEAJP?KILHE=J?A

=J@LNABANAJ?AO%KNAT=ILHANAC=N@EJCAMQEJA=OPDI=PDALNAOQILPERA@E=CJKOEO?=JKBPAJ

>A I=@A >=OA@ KJ PULE?=H DEOPKNU =J@ ?HEJE?=H LNAOAJP=PEKJ >ABKNA BQNPDAN @E=CJKOPE?O /NAREKQOHUPDANAD=RA>AAJOKIA?HEJE?=HOECJ>=OA@O?NAAJEJCPKKHO@ARAHKLA@BKN@APA?PEJC DKNOAO=PNEOGBKN?DNKJE?OARANAHKSAN=ENS=UEJBH=II=PEKJEJ?HQ@EJCDKNOAKSJAN=OOAOOA@

NAOLEN=PKNU OECJO EJ@AT '. 12( 1=IOAUAN AP =H =J@ NEOGO?NAAJEJC MQAOPEKJJ=ENA 120 'KP?DGEOO AP =H 6=OGK AP =H 3DAOA PKKHO D=RA = CKK@ OAJOEPEREPU =J@

JAC=PERA LNA@E?PERA R=HQA BKN OARANA =OPDI= >QP PDAU @K JKP OAAI PK @EOPEJCQEOD >APSAAJ DA=HPDU DKNOAO =J@ PDKOA SEPD IEH@IK@AN=PA =OPDI= 3DQO =@@EPEKJ=H @E=CJKOPE? PAOPO EJ?HQ@EJCO=ILHEJCKBPDA=ENS=UO=NAJAA@A@EJIKOP?=OAOPK?KJBENIPDA?HEJE?=HOQOLE?EKJ

=J@PKEILNKRA@E=CJKOPE?=??QN=?U

(J=@@EPEKJPKPDA?KJRAJPEKJ=HHUQOA@@E=CJKOPE?IAPDK@OATAN?EOAPAOPO?=J>ALANBKNIA@BKN DKNOAO HHAJAP=H (JDQI=JO=IEJQPAS=HGPAOP,63 EO=HKSEJPAJOEPUATAN?EOA PAOPPD=PIA=OQNAOPDA@EOP=J?A=LANOKJEO=>HAPKS=HGKRANIEJQPAO(PD=O>AAJ@ARAHKLA@

(21)

BKN IKJEPKNEJC PDA LNKCNAOOEKJ KB ?DNKJE? ?=N@EKR=O?QH=N =J@ NAOLEN=PKNU @EOA=OAO =J@ BKN AR=HQ=PEJCPDAABBE?=?UKBIA@E?=HPNA=PIAJP!QPH=J@AP=H 32OP=PAIAJPCQE@AHEJAO BKNPDAOETIEJQPAS=HGPAOP 3DAPAOPEO=HOKQOA@BKNIKN>E@EPU=J@@EO=>EHEPUAR=HQ=PEKJ (J =@@EPEKJ = @APANEKN=PEKJ EJ PAOP NAOQHPO D=O >AAJ BKQJ@ PK >A =OOK?E=PA@ SEPD EJ?NA=OA@

IKNP=HEPU$JNECDP 3DAPAOPD=O=HOK>AAJ=@=LPA@BKN@KCO=J@PDANAOQHPO=NAOEIEH=NPK PDKOAEJDQI=JL=PEAJPO!K@@UAP=H2SEIIAN=J@1KV=JOGE "QNNAJPHUPDAPAOP EO>AEJCOPQ@EA@=J@QOA@EJ@KCOSEPDNAOLEN=PKNU@EOA=OAOQ?D=OLQHIKJ=NUBE>NKOEO+EHF=

,=QH=AP=H =J@>N=?DU?ALD=HE?OUJ@NKIA+EHF=,=QH=AP=H .JAOUILPKIKB AMQEJA=OPDI=EO@A?NA=OA@ATAN?EOAPKHAN=J?A1K>EJOKJ"KQ[PEHAP=H PPDA IKIAJP PK PDA =QPDKNlO GJKSHA@CA PDANA EO JK OP=J@=N@EVA@ HKSEJPAJOEPU ATAN?EOA PAOP

@ARAHKLA@BKNDKNOAOPKAT=IEJAKNIKJEPKNNAOLEN=PKNU@EOA=OANAH=PA@ATAN?EOAEJPKHAN=J?A ,KOP KB PDA ?QNNAJPHU QOA@ ATAN?EOA PAOPO =NA LANBKNIA@ PK AT=IEJA ?=N@EKR=O?QH=N =J@

NAOLEN=PKNUBQJ?PEKJ=J@?=L=?EPUKBN=?ADKNOAO=J@OLKNPDKNOAOJKPPDAABBA?POKBNAOLEN=PKNU

@EOA=OA=J@PDAOAPAOPOKBPAJNAMQENAN=?APN=?G?KJ@EPEKJOKN=PNA=@IEHH HHAJAP=H

5=,8(08=(?9(36204.3,:/5+9

6EPD AJ@KO?KLE? AT=IEJ=PEKJ KB PDA NAOLEN=PKNU PN=?P PDA ?HEJE?E=J KN NAOA=N?DAN EO =>HA PK

@ENA?PHUREOQ=HEVAPDAJ=O=HL=OO=CAOLD=NUJTH=NUJTCQPPQN=HLKQ?DAOPN=?DA==J@?N=JE=H

>NKJ?DE$J@KO?KLU=HHKSOBKNPN=?EJCLKOOE>HA@EO?D=NCAPKEPOKNECEJ@APA?PEKJKBOPNQ?PQN=H LNK>HAIOKN=BKNAECJ>K@UEJPDA=ENS=UOAR=HQ=PEKJKBOECJOKBEJBH=II=PEKJ=J@O=ILHEJC KBPDAHKSAN=ENS=UO2=ILHEJCEOEJ@E?=PA@SDAJHQJC@EOA=OAEOOQOLA?PA@=J@PDANAEO=JAA@

BKN ?D=N=?PANEVEJC PDA KNECEJ PULA =J@ @ACNAA KB EJBH=II=PEKJ EJ PDA =ENS=UO "HEJE?=H

@E=CJKOEOEOKBPAJ=E@A@>UPDAE@AJPEBE?=PEKJKBEJBH=II=PKNU?AHHPULAO=J@PDAENLNKLKNPEKJO EJNAOLEN=PKNUOA?NAPEKJO=J@PDALNAOAJ?AKB=JEJ?NA=OA@=IKQJPKBPN=?DAK>NKJ?DE=HIQ?QO 'KBBI=J"KQ[PEH=J@'=SGEJO> $J@KO?KLE?O?KNEJCKBPN=?DA=HIQ?QOMQ=JPEPU D=O >AAJ LNAREKQOHU ?NEPE?=HHU =OOAOOA@ =J@ O?KNEJC BNKI JKJA PK ?KLEKQO EO NA?KIIAJ@A@&AN>ANAP=H >QPEILHAIAJPEJCPDAO?KNEJCOUOPAII=UR=NU>APSAAJ

?HEJE?O=J@?HEJE?E=JO3DA@E=CJKOEOKBAMQEJA=OPDI=BKNAT=ILHAEO>=OA@KJPDALNAOAJ?A KB?HEJE?=HOECJOKBHKSAN=ENS=U@EOA=OAAT?AOOIQ?QOKJAJ@KO?KLU=ENS=UO=ILHA?UPKHKCU NAOQHPO=>JKNI=HEPEAOEJHQJCBQJ?PEKJPAOPEJCEJNAOA=N?D =J@AT?HQOEKJKBEJBA?PEKQO=J@

KPDANHQJC@EOA=OAO"KQ[PEHAP=H HPDKQCD@K?QIAJP=PEKJKBHKSAN=ENS=UK>OPNQ?PEKJ SEPDHQJCBQJ?PEKJPAOPEJCSKQH@>AE@A=HPDAH=?GKB=BBKN@=>HAA=OEHULKNP=>HAOAJOEPERA PAOPEJC OUOPAIO KBPAJ LNARAJPO PDAEN QOA EJ ?HEJE?=H LN=?PE?A 3DQO HKSAN =ENS=U ?UPKHKCU

?KI>EJA@SEPD?HEJE?=HOECJO?KIIKJHUNAI=EJOPDA?KNJANOPKJAKBPDA@E=CJKOEO

3N=?DA=HS=OD36 =J@>NKJ?DK=HRAKH=NH=R=CA! + =NA?KIIKJO=ILHEJCLNK?A@QNAOEJ AMQEJA LN=?PE?A SDAJ =OOAOOEJC HKSAN NAOLEN=PKNU PN=?P DA=HPD =J@ PDA ?AHHQH=N ?KJPAJPO KB AMQEJANAOLEN=PKNUBHQE@OD=RA>AAJEJRAOPEC=PA@=HNA=@UEJPDAO=J@O!AA?D ,=EN ,=EN AP =H 3DA ?DKE?A KB PDA O=ILHEJC IAPDK@ EO KBPAJ NAH=PA@ PK PDA OQOLA?PA@@EOA=OALNK?AOOSDE?DEO>=OA@KJDEOPKNU=J@BEJ@EJCOEJLDUOE?=HAT=IEJ=PEKJ=J@

D=AI=PKHKCE?=H=J=HUOEO36D=O>AAJ?KJOE@ANA@PKCERA=>APPANNALNAOAJP=PEKJKBPDASDKHA HQJCPD=J! +=J@PDANABKNAEOKBPAJLNABANNA@EJ?=OAOSDANA=BK?=HKNIQHPEBK?=HEJBA?PEKQO

@EOA=OAEOOQOLA?PA@>A?=QOAOA?NAPEKJOBNKIPDA=BBA?PA@HQJC=NA=OSEHH?KHHA?PEJPDAPN=?DA=

(22)

RE=IQ?K?EHE=NU?HA=N=J?A"KQ[PEH=J@'=SGEJO> %KNAT=ILHADEOPKNUKBBARAN=J@

AHAR=PA@HAQ?K?UPAOKNBE>NEJKCAJ?KJ?AJPN=PEKJEJPDA>HKK@I=UOQCCAOPEJBA?PEKQO@EOA=OA N=PDANPD=JAMQEJA=OPDI=EJSDE?D?=OA>=?PANE=H?QHPQNAKB36EOS=NN=JPA@3DA?KHHA?PEKJ

=J@ AR=HQ=PEKJ KB PN=JOPN=?DA=H OA?NAPEKJ =OLEN=PAO D=RA >AAJ EJ QOA =HNA=@U BKN @A?=@AO ,=JOI=JJ =J@ *JECDP !AA?D !AA?D =J@ PDA AJ@KO?KLE? O=ILHEJC PA?DJEMQAS=O@ARAHKLA@EJPDAO&NAAP6DEPSAHH=J@&NAAP 'EOPKNE?=HHU OPQ@EAOKJN=?ADKNOAOlNAOLEN=PKNUDA=HPDD=RAKBPAJ>AAJ>=OA@KJ36?UPKHKCU6KK@AP=H

"D=LI=JAP=H =J@=J=OOK?E=PEKJKB?KQCDEJC=J@36JAQPNKLDEHE=D=O>AAJ BKQJ@"DNEOPHAUAP=H 'KSARANEJPD=POPQ@U=?KJOE@AN=>HALNKLKNPEKJKBPDA?KJPNKH DKNOAO=HOKD=@ARE@AJ?AKB=ENS=UEJBH=II=PEKJ

3N=?DA=HS=ODSEPDOPANEHAO=HEJA?=J>AK>P=EJA@=OALPE?=HHUAEPDANPDNKQCDPDASKNGEJC

?D=JJAHKB=JAJ@KO?KLAKB=PHA=OPIKBHAJCPDQOEJC=OPANEHA@KQ>HAKNPNELHACQ=N@A@

?=PDAPAN PK NA@Q?A PDA NEOG KB J=OKLD=NUJCA=H ?KJP=IEJ=PEKJ KN QOEJC PDA PN=JOPN=?DA=H O=ILHEJCPA?DJEMQASEPD=JAA@HA=J@?=PDAPAN"KQ[PEH=J@'=SGEJO> 3DARKHQIAQOA@

EOQOQ=HHUhI+"KQ[PEH=J@'=SGEJO> >QPJK?KJOEOPAJPEJPANJ=PEKJ=HCQE@AHEJAO ATEOP3DAO=ILHAK>P=EJA@?=J>AOQ>IEPPA@BKN>=?PANE=H=J@KNBQJC=H?QHPQNA=J@?UPKHKCE?=H

=J=HUOEO"UPKHKCE?=H=J=HUOEOEOLANBKNIA@BNKIPDAOHE@AOSEPDOP=EJA@OIA=NOKB=?AHHLAHHAP K>P=EJA@RE=?AJPNEBQC=PEKJKBPDA36O=ILHA3DAMQ=HEPUKBPDA?UPKHKCE?=HO=ILHAI=U>A NA@Q?A@>ULKKN?AHHLNAOANR=PEKJ?=QOEJC?AHH@ACAJAN=PEKJ=J@HUOEO3DA=@R=JP=CAOKB36 EJ?HEJE?=HLN=?PE?A=NAEPOHKSAN?KOPO=J@PDALKPAJPE=H=RKE@=J?AKB@NQCSEPD@N=S=HPEIAO PD=P=NEOABNKIOA@=PEKJ=J@HK?=H=J=AOPDAOE=SDE?D=NAKBPAJ=@IEJEOPANA@@QNEJCPDA! + LNK?A@QNAPKNAOPN=EJPDADKNOA=J@OQLLNAOO?KQCDEJC'KBBI=J

! +D=O>AAJ=OP=J@=N@@E=CJKOPE?LNK?A@QNAPKAT=IEJAPDAAMQEJAHKSANNAOLEN=PKNUPN=?P OEJ?A PDA O 5EAH =J@ EP D=O =HOK >AAJ SE@AHU QOA@ EJ NAOA=N?D KRAN PDA UA=NO

!NKJ?DK=HRAKH=NH=R=CABHQE@! +% JAQPNKLDEHE=D=O>AAJ?KJOE@ANA@PK?KNNAH=PASEPDPDA OARANEPUKBDEOPKL=PDKHKCE?=HHAOEKJOEJPDAHQJCO5EAH (JLNEJ?ELHAPDABHQE@?KHHA?PA@

>U! +EOKJHUNALNAOAJP=PERAKBPDA=NA=KBPDAHQJC@EOP=HPKPDAO=ILHEJCOEPA=J@PDANABKNA

! +EONA?KIIAJ@A@EJOQOLA?PA@@EBBQOADKIKCAJKQOJKJ>=?PANE=HHQJC@EOA=OA"KQ[PEH

=J@'=SGEJO> "KJRAJPEKJ=HHU! +D=O>AAJ?KJOE@ANA@PK>APDA>AOPPA?DJEMQABKN

@APA?PEJCHKSAN=ENS=UEJBH=II=PEKJEJDKNOAO'KBBI=J"KQ[PEHAP=H (J?=OAO KBQJ?ANP=EJ=APEKHKCULANBKNIEJC>KPD36=J@! +OAMQAJPE=HHU! +=BPAN36PK=RKE@

?NKOO?KJP=IEJ=PEKJ D=O>AAJOQCCAOPA@EJKN@ANPK=?DEARA=??QN=PA@E=CJKOEO HHAJAP=H

"KQ[PEH=J@'=SGEJO> ! +EOJKP=NA?KIIAJ@A@O=ILHEJCIAPDK@EJ>=?PANE=H HQJC@EOA=OASDE?DEOKBPAJBK?=HKNIQHPEBK?=H=J@?=JUEAH@=JKNI=H! +O=ILHA@AOLEPA L=PDKHKCE?=H ?D=JCAO EB O=ILHA@ BNKI =J QJ=BBA?PA@ HQJC OACIAJP ,KNAKRAN K>P=EJEJC = OPANEHA! +O=ILHAEJPDADKNOAEO=PA?DJE?=H?D=HHAJCA

#AOLEPA! +>AEJCSE@AHUQOA@EJ>KPDLN=?PE?A=J@NAOA=N?DKBAMQEJANAOLEN=PKNU@EOA=OAO PDAIAPDK@KHKCUEOJKPOP=J@=N@EVA@,KOPKBPAJOA@=PEKJ=J@HK?=HPKLE?=H=J=AOPDAOE=KBPDA H=NUJT?=NEJ==J@KNI=EJOPAI>NKJ?DE=NAJAA@A@PKLANBKNI! +O=ILHEJCO=BAHU=J@EJ=

NALNK@Q?E>HAI=JJAN4OQ=HHUhI+KBOPANEHAO=HEJAEOEJBQOA@RE==JAJ@KO?KLA KB=PHA=OPIEJHAJCPDKN=I! +PQ>A>HEJ@HU=J@PDA@ARE?AQOA@IQOP>ASA@CA@EJPK

=>NKJ?DQOPECDPHU5EAH1K>EJOKJ'KBBI=JJ"KQ[PEH=J@'=SGEJO>

"KQ[PEHAP=H 3DABHQE@?=J>AEJOPEHHA@SEPDAEPDANKJAKNOARAN=H>KHQOAO=J@NAPNEARA@

(23)

>=?GPKOUNEJCAOI=JQ=HHUKNSEPD=J=QPKI=PA@OQ?PEKJ@ARE?A3DAO=ILHAEO?KJOE@ANA@PK

>AKB=@AMQ=PAMQ=HEPUEBEP?KJP=EJO=BK=IUH=UANOQNB=?P=JP 'KBBI=J 3DAO=ILHA ODKQH@ >A OQ>IEPPA@ PK H=>KN=PKNU =J=HUOEO LNKILPHU =BPAN ?KHHA?PEKJ LNABAN=>HU KJ E?A KN NABNECAN=PA@PK=RKE@@A?NA=OA@RE=>EHEPU=J@@ACN=@=PEKJKBPDAEJBH=II=PKNU?AHHO/E?GHAOAP

=H='KBBI=J (JPDAH=>KN=PKNUPDAO=ILHAEO?AJPNEBQCA@QOEJC=?UPK?AJPNEBQCA KN = ?KJRAJPEKJ=H P=>HAPKL ?AJPNEBQCA "UPK?AJPNEBQCA LNK@Q?AO = QJEBKNI KJAH=UAN BK?=H

=NA=KB?AHHOKJPDACH=OOOHE@A>QPEPEOJKP=HS=UO=R=EH=>HAEJH=>KN=PKNEAOKN?HEJE?O@QAPK DECDAN?KOP2IA=NLNAL=N=PEKJOD=RA=HOKLNKRA@QOABQHEJAMQEJA! +%@E=CJKOPE?O@AOLEPA OKIA @EBBANAJ?AO EJ PDA SDEPA >HKK@ ?AHH LNKLKNPEKJO ?KIL=NA@ SEPD ?UPK?AJPNEBQCA OHE@AO /E?GHAOAP=H> 6EPD?KJRAJPEKJ=H?AJPNEBQCA=BPANLKQNEJC=S=UPDAOQLANJ=P=JP=

OIA=NKBPDA?AHHLAHHAPEOLH=?A@KJ=CH=OOOHE@A@NEA@=J@OP=EJA@2P=EJEJCIAPDK@OQOA@

EJ?HQ@A#EBB0QEGIK@EBEA@1KI=JKSOGU 6NECDPlO&EAIO=,=U&N^JS=H@&EAIO==J@

+AEODI=JlO OP=EJ 'KBBI=J 3DANA =NA OKIA @EBBANAJ?AO EJ PDA OP=EJEJC IAPDK@O EJ OAJOEPEREPUKB@APA?PEJCBKNEJOP=J?AI=OP?AHHO=J@OKIAH=>KN=PKNEAOQOA3KHQE@EJA!HQABKN

= OAL=N=PA I=OP ?AHH ?KQJP 'QCDAO AP =H +A?HANA AP =H 'KBBI=J (P EO NA?KIIAJ@A@PK?KQJP?AHHOBKNPDA=J=HUOEOKB@EBBANAJPE=H?AHH?KQJPO'KBBI=J

%ANJ=J@AVAP=H

?:525.?5-,7;04,25=,8(08=(?9(362,9

(JA=NHEANOPQ@EAO36=J@! +%?UPKHKCUD=RAODKSJLKKN?KNNAH=PEKJ#ANGOAJAP=H 'QCDAOAP=H,=HEGE@AOAP=H%N=ELKJPAP=H SDE?DEOSDU36=HKJAEO

?QNNAJPHUJKPNA?KIIAJ@A@BKN?UPKHKCE?=H=J=HUOEO>U=?KJOAJOQOOP=PAIAJP"KQ[PEHAP=H =HPDKQCD EP EO OPEHH EJ QOA EJ AMQEJA LN=?PE?AO EJ %EJH=J@ =IKJC KPDAN ?KQJPNEAO (J

?KJPN=OP6EJ@ANAP=H =J@IKNANA?AJPHU'=JOAJAP=H D=RANALKNPA@

LKOEPERA?KNNAH=PEKJO>APSAAJPDAJAQPNKLDEHLAN?AJP=CAOEJ36=J@! +%O=ILHAO3DANA=NA JKNA?AJPOPQ@EAOLQ>HEODA@?KIL=NEJC36=J@! +%?UPKHKCU=IKJCDKNOAOKBR=NUEJC=CAO

=J@@EO?ELHEJAOPD=PD=RAJ=PQN=HHUK??QNNEJCNAOLEN=PKNU@EOA=OA,KNAKRANPKPDA=QPDKNlO GJKSHA@CAPDAOAJOEPEREPU=J@OLA?EBE?EPUKB36=J@! +%?UPKHKCUD=RAJKP>AAJ=OOAOOA@

>ABKNAEJPDA@E=CJKOEOKBNAOLEN=PKNU@EOA=OA

3DANABANAJ?AR=HQAOBKNAMQEJA36D=RAJKP>AAJBQHHU@ABEJA@OEJ?A=H=NCAR=NE=>EHEPUEJPDA

?AHHQH=N?KJPAJPKB36O=ILHAOEJDA=HPDUDKNOAOD=O>AAJK>OANRA@2SAAJAUAP=H

"DNEOPHAUAP=H1K>EJOKJAP=H (JL=NPE?QH=NPDA?QPKBBR=HQABKNJAQPNKLDEHO NAI=EJOQJ?HA=N=J@PDANAOAAIOPK>A=JKRANH=L>APSAAJDA=HPDUDKNOAO=J@DKNOAOSEPD NAOLEN=PKNU @EOA=OA 2SAAJAU AP =H "DNEOPHAU AP =H 1K>EJOKJ AP =H ,KNAKRANATAN?EOAEOGJKSJPKEJ?NA=OAPDAJAQPNKLDEHLAN?AJP=CAEJ36,=HEGE@AOAP=H HEIEP KB JAQPNKLDEHO D=O >AAJ ?KJRAJPEKJ=HHU QOA@ BKN 36 1K>EJOKJ

"KQ[PEH=J@'=SGEJO> >QPOKIAR=NE=PEKJI=UATEOPEJ?QPKBBR=HQAO>APSAAJ@EBBANAJP H=>KN=PKNEAO 3DA ?QPKBB R=HQA BKN ! +% JAQPNKLDEH LAN?AJP=CA PK OQCCAOP HKSAN =ENS=U EJBH=II=PEKJ D=O DEOPKNE?=HHU >AAJ OAP =P >=OA@ KJ ATLANP KLEJEKJ =J@ LNAREKQO LQ>HE?=PEKJO'KBBI=J1E?D=N@AP=H"KQ[PEH=J@'=SGEJO>"KQ[PEHAP=H (J OARANA =OPDI= PDA JAQPNKLDEH EJ?NA=OA EO CAJAN=HHU IKNA I=NGA@ PD=J EJ IEH@IK@AN=PA=OPDI=KBPAJKRANKBPDAPKP=HEJBH=II=PKNU?AHHO"KQ[PEHAP=H (J

(24)

=@@EPEKJ PK JAQPNKLDEHO AHAR=PA@ LNKLKNPEKJO KB AKOEJKLDEHO =J@ IAP=?DNKI=PE? ?AHHO I=U EJ@E?=PAOKIAR=NE=JPOKBIEH@IK@AN=PA=OPDI=EJDKNOAOKNARAJL=N=OEPE?HQJC@EOA=OAEJ

?=OAKBAKOEJKLDEHE="KQ[PEH=J@'=SGEJO= ?QPKBBR=HQABKNAKOEJKLDEHOEJ36 KN! +%=J@=?QPKBBKBBKNI=OP?AHHOEJ! +%?UPKHKCUD=RA>AAJ?KJOE@ANA@=OSAHH

=O = NABANAJ?A N=JCA KB h BKN I=?NKLD=CAO =J@ h BKN HUILDK?UPAO EJ ! +%

1K>EJOKJ'KBBI=J"KQ[PEH=J@'=SGEJO>"KQ[PEHAP=H 'KSARAN JAS ?QPKBB R=HQAO KB AEPDAN JAQPNKLDEHO *K>HEJCAN AP =H 6=OGK AP =H

#ALA?GANAP=H"KQ[PEHAP=H I=OP?AHHO#ALA?GANAP=H"KQ[PEHAP=H KNAKOEJKLDEHO#ALA?GANAP=H"KQ[PEHAP=H BKN! +%?UPKHKCUD=RA

>AAJLNKLKOA@BKNPDA@E=CJKOEOKB=ENS=UEJBH=II=PEKJEJKN@ANPK=HHKSIKNAR=NE=>EHEPU

?=QOA@>UPDAR=NE=PEKJEJO=ILHEJCPA?DJEMQAOSDE?DOPEHHJAA@PK>AOP=J@=N@EVA@EJDKNOAO -ARANPDAHAOO=?KJOAJOQOKJ=PNQACKH@OP=J@=N@BKN@E=CJKOEJCAMQEJA=ENS=UEJBH=II=PEKJ EOOPEHHIEOOEJC=J@PDAOQCCAOPA@?QPKBBR=HQAOAOLA?E=HHUNAC=N@EJCJAQPNKLDEHO=NAH=NCAHU

>=OA@KJK>OANR=PEKJ=HOPQ@EAO=J@ATLANPKLEJEKJ

(:80>3,:(225685:,04(9,9

Matrix metalloproteinases (MMPs) are a family of zinc-containing proteolytic enzymes responsible for degradation of the extracellular matrix (ECM) during the normal tissue remodelling and repair states and also during abnormal pathological processes (Sternlicht and Werb 2001, Page-McCaw et al. 2007). ,,/OL=NPE?EL=PAEJOARAN=HLDUOEKHKCE?=HLNK?AOOAO EJ?HQ@EJC@ARAHKLIAJP=JCEKCAJAOEOPEOOQANAIK@AHHEJCSKQJ@DA=HEJC?AHHIECN=PEKJ=J@

LNKHEBAN=PEKJ =LKLPKOEO IAP=OP=OEO EJJ=PA EIIQJA @ABAJ?A =J@ EJBH=II=PEKJ 6KAOOJAN 6KAOOJAN."KJJKN=J@%EPV&AN=H@1K@N\CQAVAP=H+]BBAGAP=H 'KSARANPDANKHAKB,,/OEJLDUOEKHKCE?=H=J@L=PDKHKCE?=HLNK?AOOAOEOJKS=@=UO

?KJOE@ANA@PK>AIKNA?KILHATPD=JFQOP$",@ACN=@=PEKJMMPs are thought to play an important role in inflammation and immunity also by regulating the cell signalling network via the release or activation of chemokines, growth factors, cytokines, and other bioactive molecules (Parks et al. 2004, Rodríguez et al. 2010, Löffek et al. 2011). ,KNAKRANEJ?NA=OA@

,,/=?PEREPU?=JAEPDANAJD=J?AKNEJDE>EPPQIKQNLNKCNAOOEKJ"KQOOAJOAP=H 3DQO PDABQHHBQJ?PEKJ=J@NKHAKB,,/OEJ>KPD@EOA=OA=J@DA=HPDNAI=EJEJ?KILHAPAHUQJ@ANOPKK@

!:8;*:;8,(4+-;4*:054

,,/O D=RA >AAJ DEOPKNE?=HHU ?H=OOEBEA@ EJPK OARAN=H @EBBANAJP OQ>CNKQLO >=OA@ KJ PDAEN BQJ?PEKJ=J@OQ>OPN=PAOLA?EBE?EPU."KJJKN=J@%EPV&AN=H@ 3DA?KILKJAJPO@ACN=@A@

>U ,,/O EJ?HQ@A >=OAIAJP IAI>N=JA =J@ EJPANOPEPE=H ?KHH=CAJ CAH=PEJ LNKPAKCHU?=JO BE>NKJA?PEJ H=IEJEJ =J@ AH=OPEJ !=OA@ KJ PDA OQ>OPN=PA ,,/O ?=J >A @ERE@A@ EJPK

?KHH=CAJ=OAOCAH=PEJ=OAOOPNKIAHUOEJOI=PNEHUOEJOIAI>N=JAPULA,,/O=J@KPDAN,,/O +]BBAGAP=H 3DEOPDAOEOBK?QOAOKJ,,/=J@SDE?D=NAPANIA@CAH=PEJ=OAOOEJ?A PDAUP=NCAP@AJ=PQN=PA@?KHH=CAJ

(25)

,,/O =NA OA?NAPA@ SEPD PDA AT?ALPEKJ KB IAI>N=JAPULA ,,/O PK PDA ATPN=?AHHQH=N AJRENKJIAJP>USDEPA>HKK@?AHHO=J@R=NEKQOKPDAN?AHHOEJ?HQ@EJCBE>NK>H=OPOAJ@KPDAHE=H

?AHHOKOPAK>H=OPOGAN=PEJK?UPAO?DKJ@NK?UPAO=J@DAL=PK?UPAO!ENGA@=H'=JOAJAP=H /=CA,?"=S AP =H PULE?=H ,,/ ?KJOEOPO KB PDNAA I=EJ BQJ?PEKJ=H @KI=EJO =O EHHQOPN=PA@EJ%ECQNA =LNK@KI=EJKB=>KQP=IEJK=?E@O =?=P=HUPE?@KI=EJKB=>KQP

=IEJK=?E@O?KJP=EJEJCPDAVEJ?>EJ@EJCOEPA=J@ =D=AIKLATEJHEGA"PANIEJ=H@KI=EJ PD=PEO?KJJA?PA@PKPDA?=P=HUPE?@KI=EJSEPD=HEJGANLALPE@AKBR=NE=>HAHAJCPDDEJCANACEKJ /=NGO AP =H -=C=OA AP =H (J =@@EPEKJ ,,/O ?KJP=EJ =J -PANIEJ=HOECJ=H LALPE@APD=P@ENA?POPDAIPKPDAOA?NAPKNUL=PDS=U,KOP,,/O=NAEJEPE=HHUOUJPDAOEVA@=O EJ=?PERALNKBKNIVUIKCAJSEPD=LNK@KI=EJPD=PNAMQENAONAIKR=HBKNAJVUIA=?PER=PEKJ +]BBAGAP=H 6DAJPDALNK@KI=EJEONAIKRA@PDA=?PERAOEPA>A?KIAO=R=EH=>HAPK

?HA=RAOQ>OPN=PAO3DA?=P=HUPE?@KI=EJEJCAH=PEJ=OAO,,/=J@EJ?HQ@AO=J=@@EPEKJ=H

@KI=EJKBPDNAANALA=POKB=BE>NKJA?PEJPULA((IKPEBPD=PLNKRE@AOPDAOAAJVUIAOSEPDPDA

=>EHEPUPK>EJ@PKCAH=PEJ=J@?KHH=CAJ-=C=OAAP=H 3DAD=AIKLATEJHEGA"PANIEJ=H

@KI=EJ@APANIEJAOOQ>OPN=PAOLA?EBE?EPU=J@EOPDAOEPABKNEJPAN=?PEKJSEPDPEOOQAEJDE>EPKNOKB ,,/O3(,/O

0.96,+6;8?4F<6D8BD8E8@F4F<A@A9?4FD<J?8F4>>ABDAF8<@4E87A?4<@EFDG6FGD8?A7<9<87 9DA?$M998=8F4>

(4+

,,/=HOKGJKSJ=OCAH=PEJ=OA EOOA?NAPA@EJ=G#=LNKBKNI=J@EOLNA@KIEJ=JPHU LNK@Q?A@>UBE>NK>H=OPO=J@KPDAN?KJJA?PERAPEOOQA?AHHO>QP=HOK>UHAQ?K?UPAO!ENGA@=H '=JOAJAP=H (J=@@EPEKJPKPDACAH=PEJ,,/?=J@ACN=@AOARAN=HPULAOKB?KHH=CAJO AH=OPEJ=CCNA?=J=J@BE>NKJA?PEJ=IKJCKPDANO2PANJHE?DP=J@6AN> #QAPKEPODECD

?KJOPEPQPERA =?PEREPU ,,/ EO ?KJOE@ANA@ = iDKQOAGAALEJCj ,,/ PD=P DAHLO PK NACQH=PA Zn

MMP-2 and MMP-9

2+

Signal peptide Fibronectin repeat Hinge region Haemopexin-like C-terminal domain Pro-domain

Catalytic domain

(26)

JKNI=HPEOOQAPQNJKRAN6=NA (J=@@EPEKJPKPDEOEPO=?PEREPUD=O>AAJK>OANRA@PK>A AHAR=PA@EJBKNAT=ILHAAMQEJAFKEJP@EOA=OA%EAPVAP=H

,,/CAH=PEJ=OA! EONAHA=OA@=O=G#=LNKBKNI!ENGA@=H'=JOAJAP=H (PEO OEIEH=NEJI=JU?D=N=?PANEOPE?OPK,,/=HOKEJPANIOKBOQ>OPN=PAO2PANJHE?DP=J@6AN>

>QP,,/EOPDAI=FKN,,/LNK@Q?A@>UJAQPNKLDEHO=J@KPDANLKHUIKNLDKJQ?HA=N HAQ?K?UPAOEJ=@@EPEKJPKKPDAN?AHHOHEGAI=?NKLD=CAO>NKJ?DE=HALEPDAHE=H?AHHOBE>NK>H=OPO

=J@AJ@KPDAHE=H?AHHO."KJJKN=J@%EPV&AN=H@ -AQPNKLDEHO=NAGJKSJPKOUJPDAOEVA ,,/@QNEJCPDAENI=PQN=PEKJ=BPANSDE?D,,/EOOPKNA@EJCN=JQHAO=J@OQ>OAMQAJPHU NAHA=OA@EBJAA@A@ PGEJOKJ=J@2AJEKN (J?NA=OAOEJ,,/D=RA>AAJ@APA?PA@EJ BKNEJOP=J?AAMQEJA=OPDI=PE?HQJC@EOA=OAOGEJSKQJ@DA=HEJCLNK?AOOQH?AN=PERAGAN=PEPEO

=J@FKEJP@EOA=OA"HQPPAN>Q?GAP=H

,.;2(:0545-9

3DA NACQH=PEKJ KB ,,/ BQJ?PEKJ EO = NABEJA@ >=H=J?A KB =?PER=PKNO =J@ EJDE>EPKNO OEJ?A

@UONACQH=PEKJ?KQH@HA=@PK=>NA=G@KSJKBDKIAKOP=OEO=J@QJ?KJPNKHHA@@AOPNQ?PERA,,/

=?PEREPU 3DA =?PEREPEAO KB IKOP ,,/O =NA RANU HKS EJ JKNI=H PEOOQAO EJ = iOPA=@UOP=PAj OEPQ=PEKJSDANA=O,,/ATLNAOOEKJ?=J>A@APA?PA@EJ=HHNAL=ENKNNAIK@AHHEJCLNK?AOOAO

=J@EJ=HHEJBH=IA@KNKPDANSEOA@EOA=OA@PEOOQAO/=NGOAP=H 3DA=?PEREPUKB,,/O EO?KJPNKHHA@=POARAN=HHARAHOPN=JO?NELPEKJ=H=?PER=PEKJ=J@NALNAOOEKJLKOPPN=JO?NELPEKJ=H I1- LNK?AOOEJC =J@ @ACN=@=PEKJ LNKPAEJ OUJPDAOEO ?KJOPEPQPERA =J@ NACQH=PA@ OA?NAPEKJ

?AHHOQNB=?AATLNAOOEKJ?AHHOQNB=?AKNATPN=?AHHQH=NHK?=HEV=PEKJ=?PER=PEKJKBVUIKCAJBKNI

>UNAIKR=HKBPDALNK@KI=EJEJDE>EPEKJ>UAJ@KCAJKQOOLA?EBE?EJDE>EPKNOOQ?D=O3(,/OKN JKJOLA?EBE? LNKPAEJ=OA EJDE>EPKNO HEGA αI=?NKCHK>QHEJ AJ@K?UPKOEO =J@ LNKPA=OA

@ACN=@=PEKJ 2PANJHE?DP =J@ 6AN> /=CA,?"=S AP =H 2ARAN=H LKPAJPE=H,,/

=?PER=PKNOD=RA>AAJNA?KCJEVA@EJ?HQ@EJCLNKPA=OAOHEGALH=OIEJKPDAN,,/O?UPKGEJAO IAN?QNE=H?KILKQJ@O=J@NA=?PERAKTUCAJOLA?EAO-=C=OAAP=H&NAAJHAAAP=H +]BBAG AP =H (J =@@EPEKJ =J ,,/=?PER=PEJC LNKPAEJ ?=HHA@ ATPN=?AHHQH=N I=PNET IAP=HHKLNKPAEJ=OAEJ@Q?AN$,,/1(- D=O>AAJNA?KCJEVA@!EOS=OAP=H

904(08=(?04-2(33(:054 ;3(49(4+5:/,896,*0,9

HPANA@ATLNAOOEKJKNNACQH=PEKJKB,,/=?PEREPEAO?=J>A=OOK?E=PA@SEPDPDA@ARAHKLIAJPKB OARAN=HL=PDKHKCEAOEJ?HQ@EJC?=J?AN=J@?DNKJE?EJBH=II=PKNU@EOA=OAO>KPDEJHQJCO=J@EJ KPDAN KNC=JO (J DQI=JO $", EJFQNU @QNEJC HQJC EJBH=II=PEKJ D=O >AAJ NA?KCJEVA@ BKN

@A?=@AO "=IL>AHH AP =H =J@ EJ?NA=OA@ ,,/ =?PEREPU D=O >AAJ NA?KN@A@ EJ OARAN=H PULAOKB=ENS=UEJBH=II=PEKJ=J@HQJC@=I=CAEJ?HQ@EJC=?QPANAOLEN=PKNU@EOPNAOOOUJ@NKIA AILDUOAI=LQHIKJ=NUBE>NKOEOCN=JQHKI=PKQOHQJC@EOA=OA?DNKJE?K>OPNQ?PERALQHIKJ=NU

@EOA=OA=J@HQJC?=J?AN=IKJCKPDANO."KJJKN=J@%EPV&AN=H@%EJH=UAP=H PGEJOKJ=J@2AJEKN#AIA@POAP=H&NAAJHAAAP=H"DQNCAP=H

(27)

,,/EO=JEILKNP=JPLH=UANEJHQJCNAIK@AHHEJC PGEJOKJ=J@2AJEKN =J@EPEOPDA LNA@KIEJ=JP,,/EJPDA=ENS=UOKB=OPDI=PE?L=PEAJPO,=QPEJKAP=H,=QPEJKAP=H

*AHHU=J@)=NFKQN (JPDAOPQ@UKB"QJ@=HHAP=H ,,/S=OODKSJPK>A OECJEBE?=JPHUEJ?NA=OA@EJ! +KBOARANA=OPDI=PE?ONAH=PERAPKIEH@AN=OPDI=PE?O=J@?KJPNKHO

=J@PK>A@ANERA@LNEI=NEHUBNKIJAQPNKLDEHO(J=JKPDANOPQ@UL=PEAJPOSEPDOARANA=OPDI=

D=@EJ?NA=OA@HARAHO=J@=?PEREPUKBOLQPQI,,/?KIL=NA@SEPDL=PEAJPOSEPDIEH@=OPDI=

=J@ JKNI=H OQ>FA?PO ,=PPKO AP =H HHANCAJ ?D=HHAJCA D=O >AAJ K>OANRA@ PK ?=QOA EJ?NA=OAO EJ ,,/ EJ PDA =ENS=UO KB =OPDI=PE? L=PEAJPO *AHHU AP =H =J@ QOEJC =J EIIQJKDEOPK?DAIE?=H =LLNK=?D '=J AP =H @AIKJOPN=PA@ ,,/ ATLNAOOEKJ EJ

>NKJ?DE=HIQ?KO=KB=OPDI=PE?L=PEAJPO>QPJKPEJDA=HPDU?KJPNKHO ENS=UEJBH=II=PEKJ=BPAN

=OPDI=AT=?AN>=PEKJD=O>AAJBKQJ@PK?KNNAH=PASEPDPDAKRANLNK@Q?PEKJKB,,/+AAAP

=H SDE?DEOPDKQCDPPKLNKIKPA=ENS=UNAIK@AHHEJC3DANAEOHAOOARE@AJ?ABKNKPDAN ,,/O EJ DQI=J =OPDI= >QP IKNA IK@AOP EJ?NA=OAO KB ,,/ ,,/ ,,/ =J@

,,/D=RA>AAJBKQJ@EJ=OPDI=L=PEAJPO+AIF=>>=NAP=H2QVQGEAP=H,=EOE AP=H/NEGGAP=H#AIA@POAP=H-=RAA@AP=H 2EIEH=NHUPKDQI=JO EJ?NA=OA@ =?PEREPU KB ,,/ S=O K>OANRA@ EJ ! +% KB ?=PO SEPD ATLANEIAJP=HHU EJ@Q?A@

=HHANCE?=ENS=UEJBH=II=PEKJ*ENO?DREJGAP=H ,KNAKRANAHAR=PA@,,/=?PEREPU S=OBKQJ@EJLQHIKJ=NUAKOEJKLDEHE=EJ@KCO1=F=IYGEAP=H

589,9

(JDKNOAOPDA=?PEREPUKBCAH=PEJKHUPE?,,/OEJNAOLEN=PKNUOA?NAPEKJOEOEJ?NA=OA@EJOARANA

=OPDI= EA DA=RAO 1 . =J@ =OOK?E=PA@ SEPD =ENS=U ATPN=?AHHQH=N I=PNET NAIK@AHHEJC

!=NPKJ =J@ &ADHAJ (J?NA=OA@ CAH=PEJKHUPE? =?PEREPU L=NPE?QH=NHU ,,/ D=O >AAJ BKQJ@EJPN=?DA=HALEPDAHE=HHEJEJCBHQE@KB=OPDI=PE?DKNOAO*KERQJAJAP=H1=QHK=J@

,=EOE ,,/>QPJKP,,/EJ?NA=OA@EJ! +%KB=OPDI=PE?DKNOAOEJNAOLKJOAPK EJD=HA@ @QOP HELKLKHUO=??D=NE@A =J@ KPDAN =HHANCAJO -AR=H=EJAJ AP =H 2EIKJAJ )KGEJAJ AP =H = DKSARAN EJ =JKPDAN OPQ@U =J EJ?NA=OA =HOK EJ ,,/ S=O JKPA@

2EIKJAJ)KGEJAJ AP =H > 6DAJ PN=?DA=H BHQE@ =J@ ! +% SANA =J=HUOA@

OEIQHP=JAKQOHU,,/S=OK>OANRA@PK>APDAI=EJAHAR=PA@CAH=PEJKHUPE?AJVUIASEPDHEPPHA EILKNP=J?AKB,,/1=QHKAP=H= $HAR=PA@HARAHOKB,,/D=RA>AAJ=OOK?E=PA@

SEPDJAQPNKLDEH=??QIQH=PEKJEJPDA=ENS=UODECDHECDPEJCPDAEJBH=II=PKNUJ=PQNAKBAMQEJA

=OPDI=-AR=H=EJAJAP=H ,KNAKRANAH=OPEJKHUPE?=?PEREPU1=QHKAP=H =J@=HOK EJ?NA=OA@?KHH=CAJ=OA=?PEREPUKB,,/=J@1=QHKAP=H> D=RA>AAJK>OANRA@EJ NAOLEN=PKNU OA?NAPEKJO KB OARANAHU =OPDI=PE? DKNOAO &AH=PEJKHUPE? =?PEREPU EJ PDA HQJCO KB IEH@HUIK@AN=PAHU=OPDI=PE?EAEJBH=II=PKNU=ENS=U@EOA=OA( # DKNOAOD=OJKPUAP>AAJ EJRAOPEC=PA@=OATPAJOERAHU>QP=OPQ@U>U!=NPKJAP=H BKQJ@AHAR=PA@HARAHOKB>KPD ,,/=J@?KJ?AJPN=PEKJO=HOKEJ( #EJ=@@EPEKJPK1 .SDAJ?KIL=NA@SEPD?KJPNKHO ,,/=?PER=PEKJD=O=HOK>AAJK>OANRA@EJOARAN=HKPDANAMQEJA@EOA=OAOEJ?HQ@EJC?DNKJE?

EJPANOPEPE=H LJAQIKL=PDU H=IEJEPEO KOPAK=NPDNEPEO QH?AN=PERA GAN=PEPEO PQIKQNO =J@ OGEJ SKQJ@O"HQPPAN>Q?GAP=H!=NPKJAP=H

(28)

>:8(*,22;2(83(:80>3,:(225685:,04(9,04+;*,8

$TPN=?AHHQH=NI=PNETIAP=HHKLNKPAEJ=OAEJ@Q?ANEA$,,/1(-EO=PN=JOIAI>N=JA=J?EHH=NU LNKPAEJPD=P>AHKJCOPKPDAEIIQJKCHK>QHEJOQLANB=IEHU=J@S=ODEOPKNE?=HHUGJKSJ>UOARAN=H KPDANJ=IAOEJ?HQ@EJC"#>=OECEJJAQNKPDAHEJ,?KHH=CAJ=OAOPEIQH=PKNUB=?PKN=J@

PQIKQN?AHH@ANERA@OPEIQH=PKNUB=?PKN*=OEJNANGAP=H&=>EOKJAP=H(=?KJKAP

=H&N=OO=J@3KKHA (JPDEOPDAOEOPDAJ=IA$,,/1(-EOQOA@PDNKQCDKQPBKN

?KJOEOPAJ?UNAC=N@HAOOKBPDAJ=IAQOA@EJPDA?EPA@OPQ@EAO$,,/1(-EOSE@AHUATLNAOOA@

EJ@EBBANAJP?AHHPULAOEJ?HQ@EJCHAQ?K?UPAOALEPDAHE=H=J@AJ@KPDAHE=H?AHHO=J@BE>NK>H=OPO

*=OEJNANG AP =H !EOS=O AP =H (P S=O BENOP @EO?KRANA@ EJ PQIKQN ?AHHO PD=P OPEIQH=PA@PDA=@F=?AJPBE>NK>H=OPOPKLNK@Q?A,,/KN?KHH=CAJ=OA!EOS=OAP=H 3DA CAJA AJ?K@EJC $,,/1(- D=O >AAJ BKQJ@ PK D=RA = DECD @ACNAA KB ?KJOANR=PEKJ =IKJC OLA?EAO&QKAP=H $MQEJA$,,/1(-?#- D=O>AAJOAMQAJ?A@1AA>AJAP=H

&AJ!=JG=??AOOEKJJK$% =J@=LLNKTEI=PAHUhDKIKHKCUKBPDAJQ?HAKPE@A OAMQAJ?AD=O>AAJK>OANRA@=IKJCOLA?EAO1AA>AJAP=H

$,,/1(-EOATLNAOOA@EJ=NA=OKBPEOOQANAIK@AHHEJCSDANAEPOPEIQH=PAOPDAOUJPDAOEO=J@

=?PEREPUKBOKHQ>HA=J@IAI>N=JA>KQJ@,,/OEJPQIKQNOAJ@KIAPNEQIOGEJLH=?AJP==J@

PEOOQAOSEPD=JCEKCAJAOEO&=>EOKJAP=H1EAPD@KNBAP=H!N=QJ@IAEANAP=H 3=JC AP =H 0QAIAJAN AP =H 'QI=J ?AHH HEJA OPQ@EAO OQCCAOP PD=P EJ?NA=OA@

$,,/1(-ATLNAOOEKJEJ?NA=OAOPDAATLNAOOEKJ=J@=?PEREPUKB,,/=J@,,/9DKQAP

=H (J =@@EPEKJ PK EPO IAP=HHKLNKPAEJ=OAEJ@Q?EJC =>EHEPU $,,/1(- =HOK NACQH=PAO OARAN=HKPDAN>EKHKCE?=HLNK?AOOAOEJ?HQ@EJCOLANI=PKCAJAOEOHUILDK?UPANAOLKJOERAJAOO=J@

@EBBANAJPE=PEKJ KB IKJK?UPAO PQIKQN LNKCNAOOEKJ JAQN=H BQJ?PEKJ =J@ ATLNAOOEKJ =J@

BQJ?PEKJKBIKJK?=N>KTUH=PAPN=JOLKNPANO,"3O ,QN=I=POQ=J@,EU=Q?DE9DKQAP

=H8QN?DAJGKAP=H7EKJCAP=H*=QODEGAP=H ?KILHAPAH=?GKB

$,,/1(- EO GJKSJ PK D=RA OARANA ?KJOAMQAJ?AO $,,/1(- GJK?GKQP IE?A ODKSA@

=>JKNI=HEPEAOEJAI>NUKPN=JOLH=JP=PEKJNAOQHPEJCEJOECJEBE?=JP@A=PDOKBJQHHAI>NUKO=J@

D=HBKBPDAOQ??AOOBQH>ENPDO=HOK@EA@SEPDEJ=IKJPDBNKIEJPANOPEPE=HLJAQIKJE=(C=GQN=AP

=H

!:8;*:;8,(4+-;4*:054

$,,/1(-EO=LHAEKPNKLE?DECDHUCHU?KOUH=PA@=LLNKTEI=PAHUPKG#=PN=JOIAI>N=JA CHU?KLNKPAEJPD=P?KJOEOPOKBPSKATPN=?AHHQH=N$" EIIQJKCHK>QHEJHEGA@KI=EJO$"(=J@

$"(( EJPDA-PANIEJQO=OEJCHAPN=JOIAI>N=JA@KI=EJ=J@=ODKNP?UPKLH=OPE?@KI=EJEJ PDA"PANIEJQO%EC*=OEJNANGAP=H!EOS=OAP=H 4JCHU?KOUH=PA@$,,/1(- D=O=OEVAKBG#=3=JC6AP=H 3DA$"(@KI=EJEONAOLKJOE>HABKN=?PER=PEJCPDA ,,/O=J@EJ=@@EPEKJEPEJPAN=?POSEPDEJPACNEJOPDANABKNA=BBA?PEJC?AHHQH=N=N?DEPA?PQNA=J@

IECN=PEKJ KB EJBH=II=PKNU ?AHHO 7EKJC AP =H *=QODEG AP =H $"((@KI=EJ EJPAN=?PO SEPD ?U?HKLDEHEJO =OOK?E=PA@ SEPD ?DAIKP=TEO 8QN?DAJGK AP =H =J@

=OOK?E=PEKJ SEPD ?=RAKHEJ NACQH=PAO JAC=PERAHU $,,/1(-lO CHU?KOUH=PEKJ =J@ ,,/

EJ@Q?EJC =?PEREPU 3=JC =J@ 'AIHAN 3DNAA CHU?KOUH=PEKJ OEPAO =OL=N=CEJA NAOE@QAO OJ =NA HK?=PA@ EJ PDA -PANIEJQO =J@ CHU?KOUH=PEKJ EO PDKQCDP PK >A = NACQH=PKNU

(29)

IA?D=JEOIKB$,,/1(-BQJ?PEKJ(=?KJKAP=H!=EAP=H 3DAPN=JOIAI>N=JA

@KI=EJ ?=J EJPAN=?P SEPD LNKPAEJO OQ?D =O "UL =J?DKNEJC PDA IKHA?QHA PK PDA ?AHH IAI>N=JA=J@CHQP=IE?=?E@NAOE@QA&HQ AJ=>HAOEJPAN=?PEKJSEPDKPDANIAI>N=JALNKPAEJO

*=QODEGAP=H 3DA?UPKLH=OIE?@KI=EJB=?EHEP=PAOPDA,"3?AHHOQNB=?AATLNAOOEKJ

=J@PDQOH=?P=PAATLKNP*ENGAP=H 'KSARANPDANKHAKB$,,/1(-EJJKNI=H?AHH LDUOEKHKCU=J@EJ@EOA=OALNK?AOOAOEJDQI=JOEOOPEHHEJ?KILHAPAHUQJ@ANOPKK@=J@EPD=OJKP UAP>AAJSE@AHUOPQ@EA@EJDKNOAOKNKPDAN=JEI=HOLA?EAO

0.96, +6;8?4F<6D8BD8E8@F4F<A@A9%%(*!&EFDG6FGD8?A7<9<879DA?#4GE;<=8F4>

(30)

,>68,9905404/;3(49(4+5:/,896,*0,9

(JDQI=JOEJ?NA=OA@$,,/1(-ATLNAOOEKJD=O>AAJK>OANRA@EJOARAN=H@EOA=OAOEJ?HQ@EJC EJBH=II=PKNUHQJC?KJ@EPEKJO$HAR=PA@$,,/1(-HARAHOD=RA>AAJ@APA?PA@EJEJPANOPEPE=H LJAQIKJE=.@=FEI=AP=H HQJC?=J?AN"=Q@NKUAP=H'=GQI=AP=H E@EKL=PDE? LQHIKJ=NU BE>NKOEO &QEHHKP AP =H '=O=JAAJ AP =H =J@ ! +% KB OIKGANO!APOQU=GQAP=H %QNPDANIKNA)KQJA=QAP=H ODKSA@PD=P$,,/1(- ATLNAOOEKJ EO EJ?NA=OA@ EJ ! +% =J@ >NKJ?DE=H ALEPDAHE=H ?AHHO KB L=PEAJPO SEPD "./#

?KIL=NA@SEPDOIKGANO=J@JKJOIKGANO=J@PD=P$,,/1(-NACQH=PAO,,/ATLNAOOEKJ EJ"./#)KQJA=QAP=H (JN=PO$,,/1(-S=OODKSJPK>AEJ?NA=OA@EJHQJCPEOOQAO OQ>FA?PPKRAJPEH=PKNEJ@Q?A@HQJCEJFQNU=J@PKLNA?A@APDAEJ?NA=OAEJ,,/O%K@=AP=H 2EIEH=N NAOQHPO SANA K>P=EJA@ BNKI DQI=J HQJC AJ@KPDAHE=H ?AHHO OQCCAOPEJC PD=P IA?D=JE?=HOPNAP?D?=QOAO=JQLNACQH=PEKJKB$,,/1(-SDE?DEJPQNJHA=@OPKEJ?NA=OA@

LNK@Q?PEKJKB,,/O'=O=JAAJAP=H ,KNAKRANEJDQI=J=ENS=UOIA?D=JE?=HOPN=EJ HA=@O PK EJ?NA=OA@ ,,/@ALAJ@AJP LNKHEBAN=PEKJ KB OIKKPD IQO?HA ?AHHO '=O=JAAJ AP =H =OPNQ?PQN=H?D=JCAGJKSJPK=LLA=NEJ=OPDI=PE?=ENS=UOKB>KPDDQI=JO=J@DKNOAO

$,,/1(- ATLNAOOEKJ D=O >AAJ LNAREKQOHU BKQJ@ EJ BAHEJA KN=H OMQ=IKQO ?AHH ?=N?EJKI=

-=ONUAP=H =J@EJ?=JEJANA@>HKK@?AHHO=OOK?E=PA@SEPD,"3O=J@H=?P=PAPN=JOLKNP

*KDK AP =H >QP PK PDA =QPDKNlO GJKSHA@CA $,,/1(- ATLNAOOEKJ D=O JKP >AAJ AT=IEJA@PK@=PAEJ=OPDI=PE?HQJCOKB=JUOLA?EAOSEPDJ=PQN=HHUK??QNNEJC@EOA=OA

,>68,9905404/589,9

(J DA=HPDU DKNOAO $,,/1(- ATLNAOOEKJ D=O >AAJ LNAREKQOHU OPQ@EA@ EJ NA@ >HKK@ ?AHHO 1!"O =J@IQO?HA?AHHO*KDKAP=H*KDKAP=H (JPDAOAPEOOQAOPDAATLNAOOEKJ KB$,,/1(-EOGJKSJPKR=NUSE@AHU>APSAAJEJ@ERE@Q=HO=LLNKTEI=PAHUKBDKNOAO ATLNAOO RANU HEPPHA KB PDEO LNKPAEJ KN JKJA =P =HH SDEHA PDA NAI=EJEJC ATLNAOO EP EJ

=>QJ@=J?A3DEOPSKOP=CAATLNAOOEKJPULAOAAIOPK>A=QJEMQABA=PQNAEJPDADKNOA=OEPD=O JKP>AAJK>OANRA@EJ=JUKPDANOLA?EAOOPQ@EA@5YEDG]JAJAP=H 3DAHKSATLNAOOEKJ KB$,,/1(-EJOKIADKNOAOEOGJKSJPK>A=NAOQHPKBNACQH=PEKJ=PPDAPN=JO?NELPEKJ=HHARAH

*KDKAP=H 3DEO>EIK@=H$,,/1(-ATLNAOOEKJ=BBA?PO1!"H=?P=PAPN=JOLKNP=?PEREPU

*KDKAP=H >QP=L=NPBNKIPDEOEPOLDUOEKHKCE?=HOECJEBE?=J?ANAI=EJOQJGJKSJ3K

@=PAPDA?KJOPEPQPERA>=OAHEJAATLNAOOEKJEJDA=HPDUPEOOQA KNEJ@Q?E>HAACEJBH=II=PEKJ NAH=PA@$,,/1(-ATLNAOOEKJHARAH=J@EPONAH=PEKJODELSEPD,,/=?PER=PEKJD=RAJKP>AAJ OPQ@EA@EJDKNOAO

7;04,2;4.9(4+(4(,9:/,90(

3DA?KILHE?=PEKJN=PAEJAMQEJACAJAN=H=J=AOPDAOE=EO?KJOE@ANA@DECD?KIL=NA@SEPDPD=PKB OARAN=HKPDANOLA?EAO=LLNKTEI=PAHUhKBDA=HPDUDKNOAOD=RA>AAJNALKNPA@PKD=RA=J

=J=AOPDAOE=NAH=PA@@A=PD=J@EJOE?GAIANCAJ?UPULA?=OAOPDAJQI>ANO?=J>A?KJOE@AN=>HU DECDANPK8KQJC=J@3=UHKN,AAAP=H=,AAAP=H>)KDJOPKJ AP =H (J @KCO =J@ ?=PO PDA =J=AOPDAOE=NAH=PA@ @A=PD NEOG D=O >AAJ =OOAOOA@ PK >A

Viittaukset

LIITTYVÄT TIEDOSTOT

Kolmion sis¨a¨an voidaan asettaa (sama) suorakulmio sek¨a pysty- ett¨a vaakatasoon niin, ett¨a sen kaksi sivua ovat kolmion kateeteilla, yksi k¨arki pisteess¨a B ja sen

Todistetaan ensin, että ABC on tasakylkinen ja sitten, että pisteet A, H, O, E ovat samalla suoralla (argumentti toimii riippumatta pisteiden H ja O järjestyksestä suoralla).. Olkoon

Näytä, että A on numeroituva.. (Vihje:

a) jokainen tuntee jonkun, b) joku tuntee jokaisen, c) jokainen tuntee jonkun, jolle itse on tuntematon, d) joku tuntee jokaisen, joka tuntee h¨ anet.. Olkoon B elokuvien joukko ja

(eri henkilöt ennen ja jälkeen). Aseta epäinformatiiviset priorijakaumat parametreille ja simuloi niiden posteriorijakaumaa. Laske posterioritodennäköisyydet seuraaville väitteille:

In the studies de- scribed in this thesis, we used a method of sputum induction in patients with chronic ob- structive pulmonary disease (COPD), asthma, respiratory symptoms

1) The major underlying factors for respiratory symptoms in competitive swimmers were a medical history of asthma, allergies, airway infections and a family history of

Artto V, Putaala J, D, Meretoja A, Piironen K, Liebkind R, Silvennoinen H, Atula S, Häppölä O for the Helsinki Stroke Thrombolysis Registry Group. Stroke mimics and