Partial least squares Cox regression on genomic data handling additional covariates

(1)

% &'()(* #+,-'*./+01!243

5 %% 276.8.6.9:<;.8 => "* ?> 6.6.9

@BADCFEHG AIJIKLANMOEPM QSRTACOKMVUXWZY[C\K]/COKM^M G'W`_aW`_[]bK_cW`deG'f

g AhE,AjiTAD_ g I'G'_k]lA gkg G1E GW`_TAI7fZWZmADC\G ALE KM

nOo prqtscuwvOxyprz{

|L}'~4}'ZHc.&}'S'}&SN

/ c<b ¡¢}O£Z¤)¥N£<¦

}¤§S©¨ª.«¬¬®¯ °F¬«±²§³y´.µ0²t®µ

¶

z·¹¸ q»ºN¼/½Fzxy¾4·

|L}'~4}'ZHc.&}'S'}&SN

/ c<b ¡¢}O£Z¤)¥N£<¦

}¤§S©¨^¿µ<ÀÁ¢¬®¯ °F¬«±²§³y´.µ0²t®µ

ÂÃqtsÅÄbÆ^zÇtÈ'o Çt¾r·ÊÉÇ©· xËÌz{ s

|L}'~-&b}\Í)Î&'}& wN-

/ cÏb ¡¢}O£Z¤)¥N£<¦

}'¤tS t¨µÐ¯4´.Ñ4´^²§³y´µ²§®µ

Ò sxFsÅÉZsÇ»o sÅnOoÓFzÔr½Fqt{

|h}~}'\Í)¢Î<S.&'h}'1wHN

(/ c<Ïb,¡¢}'&¹£¤§<¥SN 4£&¦

}¤§ t¨^±ÐÁÐ¢ª.«¢¯4´.Ñr´^²t³y´µ0²©®µ

ÕwÖ ×Ø'Ù.ÚÛØ

Ü}} }'-OS}&¢¡yÎ<O-Ý .~&}¡¢$& <LÎ&BÞ¢¤)¡¢b} <

(2)

¢¡¢}'<¦Z&`-<}0¡¢b} <}¡¢Ý$& <}-S.N&}1åÝ} æ<}~-&

}<&å<Ý4&}çÎ0è^éê$ë<H0è\é/ HHá <Ý^.¦ì ,Ý¡/á4}~~ }¡

&/&}!â, w¡}'t¡í¡¢ îr}}Z~~&<<1}, }Nár}'}'ÃÝÞÞ<}-}¡¹ Ü}

~r}'&~4Z<-}á }D<}Hæãïðñ.ò\ç©óóê$Ý-}S&}Î</Ý

4&}Dâ, b æ} ¢¡!&! &-<!~r}h æ<}' ¢¡y}}á/}'á Þ!}-¤

& S.& <ôáS }'1.& <}'}¦,} Þ<<&}¡~-&F }-&å<Ý4&}0ÎÞ}'}'1 ä}¡

}D¢¡¢}'Sõö}S~&}}'íb¢¡¢ ÷}¡ö<}'1-ö}}&¢¡T æ

ï'ðñò(¹ç©ó<ó<ê$¦Z1ø}& S}&}Dá}'}L4ä&¡ø¡ô}NÞ<}'}D}'îr}$&

ø}'~&}N&}'~,LÝ~~&<<1w<0&}D¡¢.1Þ}0O}¡ Þ/b0è^é

¡¢&}$& <O 4 }0<}}á}áÞ'<}~&}1.& <' ~&.¡¢¤

Þ}-S.}Z -Ý y~&áá }ÎZ}'¦ù~.& }<14¡ô}áÞS

/Ý1Å4¡k }L}'&¤§¡}'S¡ Þô}-c~¢}¡¢Ý&}LÍ)ö¡¡¢& <

<ÝH}¡S .¦^Î0 '&~4<&/y .¦}'¤)¡¢ }-4¢¤§Þ}

.&á}\ æ}Z¡¢}}Þ1¡¢}¡!Ý< 1æ}&'^ú~~ ÞDÝ }&¢¡

&¦L¡¢ îr}}^&<&1 Þ}}0}'~} <á&}-^'}'^¡.1L}1' }

¦Z Å<¡¡¢ O<¢¤§Þ}'!..&}'.¦LÝh}&¢¡kÞ}

L}-LÞ¢¡k~&}¡¢$& <L<&}}¡Å0Hæûï'ðhñ.ò(çtóóêr¡

&.}'&}LZ!&bár}DÞ< }¡wáwÝ¡¢ÞÞ}}N}¢~&}&-0<Þ}'}

¦Z í}` 'y.&á }'

ü,ýþ/ÿ "!$# %'&(*) +'-, .!0/1&/$3245$6

! /87!0/1&/$:9;/8<&=/87>7"/8&4?-#0/8A@B# C-C/87(, ! %'&

D EFHG4IJLKNMNO3GQPBJRF

STVU0WX<Y ZX\[^]_Z`aUcbed^ZVY0befgUhb(iHjkWX<lVU:jelVUgm4jelBU0Wnbe[n];U [abefgU$op+X<W^UqWaj(ZBjrX<l.j([nX\f.o

s

beTZBj([tZuj

s^s^v

X<Y:j(ZX<be[kb(iwfxX<Y TVb;j(TTBj0ylzj([aWrbeZ`aU TR`^X\]>`oZ`^TVbed^]>`

s

d^ZzlVbed^TVY0U0l:{}|H[aU

s

j(TZX<Y d

v

j(T}X\[alZBj([aY0UHb(i~Z`^X<l

s

TVbem

v

U flVU0U lZVb

v

X\[^.];U [abefgU$op+X<W^UHfgb

v

U0Y d

v

j(T

s

TVb(o

v

U0lb(iRZd^fgbeTVlNZVbrZ`aUcZX\fgUb(ilBbefgUcWX<lVU:jelVUl

s

U0Y X YcU ;U [ZxldaYB`jelNW^U:j(Z`beT

TVU0Y d^TTVU [aY0U+b(i4WX<lVU:jelVU>(iTVU0daU [tZ

v

yTVU$i'U TTVU0WZVbHmyZ`aU}ZVU0YV`^[^X<Y:j

v

ZVU Tfij(X

v

d^TVUZX\fgU

beT}ld^TX\ej

v

ZX\fgU>{Y

v

jelVlVX<Y:j

v

lZBj(ZX<lZX<Y:j

v

fgbtW^U

v

i'beTld^TX\>j

v

Waj(ZBjzZ`4j(Z`4jelmU0U [

U$

s^v

beTVU0WcTVU0Y0U [Z

v

yxX\[gZ`^X<l}Y0be[ZVU$Zmy.fd

v

ZX

s^v

Uuj(d^Z`abeTVlX<lZ`aUHb:

s

TVb

s

beTZX<be[4j

v

`4j(Aj(TVW^lRfgbW^U

v {

"[kY0be[e1d^[aY ZX<be[p+X\Z`rZ`aU];U [abefxX<YWaj(ZBjaX\[i'beTfcj(ZX<be[be[kW^U fgbe]>TBj

s

`^X<YNj([aW

Y v X\[^X<Y:j

v

>j(TXj(m

v

U0lj(TVUrb(iZVU [j:ej(X

v

j(m

v

U>{ulVld^fgUhZ`4j(ZcpUq`4j0;UZ"pbnY0bAej(TXj(ZVU

;U0Y ZVbeTVl3 :¡0¢0¢0¢¡t£¤"¥¦j([aW¨§©ª; :¡0¢0¢0¢:¡VªA«:¤"¥}3Z`aU TVlZY0beTTVU0l

s

be[aWX\[^]ZVb

];U [abefgU$op+X<W^UWaj(ZBj¬ldaYB`jel.fxX<Y TVb;j(TTBj0y®];U [aUqU$

s

TVU0lBlX<be[¯fgU:jeld^TVU fgU [ZVlAj([aW

Z`aUlBU0Y0be[aWY0beTTVU0l

s

be[aWX\[^]¬ZVb_jeW^WX\ZX<be[4j

v

W^U fgbe]>TBj

s

`^X<Yrj([aW®Y

v

X\[^X<Y:j

v

ej(TXj(m

v

U0l

°

U>{]a{^ldaYV`jel+lVU$~aj(];U>aj([aWhZd^fgbeT+Z`^X<YV[aU0lVl-±}Z`4j(Zj(TVUui'U pX\[q[d^fmU THj([aWh[abeZ

(3)

v v

Z`4j(Z

v

X\[^lRZ`aUY0bAej(TXj(ZVU;U0Y ZVbeTVlRnj([aWk§gp+X\Z`kZ`aU

s

j(ZX<U [ZVli'j(X

v

d^TVUZX\fgU0l:4be[aU

jelVld^fgU0luZ`4j(ZHZ`aUN`4j(Aj(TVWTBj(ZVU>X{U>{4Z`aUNX\[alZBj([tZVU [abedalzTX<lb(iij(X

v

d^TVUxj(ZHZX\fgU´

ZBj(;U0lRZ`aUzi'beTf µ

´¶(·³¡V¸3¤

µ ¹

´^¤8ºA»;¼½^¾¿(¼tÀ3¢

° ß ±

ÁHU TVU.ÂÃÄÅ3 :¡0¢0¢0¢A¡Å£¤ ¥ j([aWkÆÇ4 :¡0¢0¢0¢¡8Ç«0¤¥ j(TVU.;U0Y ZVbeTVlb(i³TVU ]>TVU0lVlX<be[ÈY0b(o

U$ÉcY X<U [ZVluWÛ0lVY TX\m^X\[^]gZàULU$Ê~U0Y ZVlRb(i*ZàU];U [aULU$

s

TVU0lVlVX<be[alj([aWqZ`aUz[abe[o];U [abefxX<Y

Y0b:>j(TXj(ZVU0l:TVU0l

s

U0Y ZX\;U

v

y;j([aW µ ¹

´a¤X<lxjrm4jelVU

v

X\[aU`4j(Aj(TVW®Y0befxfgbe[¯ZVb¬j

v\vs jo

ZX<U [ZVl:{Ë³`aU¬m4jelVU

v

X\[aU¬`4j(Aj(TVWX<lrjelVld^fgU0W¦ZVbmÌU¬j([Íj(Tm^X\ZTBj(Ty¦[abe[Î[aU ]j(ZX\;U

id^[aY ZX<be[3~j([aWkX\ZHY0beTTVU0l

s

be[aW^luZVbgZ`aU`4j(Aj(TVWTBj(ZVUNb(i}j([kX\[aWX\X<Wd4j

v

p+X\Z`¬j

v\v

Ï

j([aWrª Ï U0d4j

v

ZVb.:U TVb^{

ÐHlVd4j

v\v

y;3Z`aU.[d^fmU TNb(i];U [aUxU$

s

TVU0lVlX<be[al+ÑÈX\[

° ß

±Hp+X

v\v

mykij(TU$Y0U0U0W_Z`aU

[d^fmÌU TuÒ¨b(i

s

j(ZX<U [tZVlHX\[Z`aUlZdaWy

°

ÑqÓÔÒÕ±${³ÖbefgULi'beTf×b(iWX\fgU [alX<be[TVU0WdaY$o

ZX<be[3beTwTVU ]>d

v

j(TX\Aj(ZX<be[3X<lwZ`aU [xTVU0td^X\TVU0W.ZVbLbem^ZBj(X\[xdalVU$id

vs

j(TBj(fgU ZVU TU0lZX\fcj(ZVU0l:{

ØabeTLZ`aU.Y

v

jelVlX<Y:j

v

Y:jelVU.b(i}beTVWX\[4j(Ty

v

X\[aU:j(TLTVU ]>TVU0lBlX<be[3Ìfcj([yfgU Z`abtW^lLU$X<lZHibeT

Z`^X<l

s

d^T

s

b>lVU>QX\[aY

v

daWX\[^]fgU Z`abW^lZ`4j(ZulVU

v

U0Y Zujcld^malVU Zb(iZ`aUY0b:>j(TXj(ZVU0lZVbcmU

dalVU0WhX\[qZ`aUzTVU ]>TVU0lVlX<be[3

s

TX\[aY X

s j v Y0bef

s

be[aU [tZVlRTVU ]>TVU0lVlX<be[

°

SÙu±$

s

j(TZXj

v3v U:jelZ

lVd4j(TVU0l

°

SÚÕÖ^±$*TX<W];UTVU ]>TVU0lVlX<be[¯j([aWÈZ`aU

v

jelVlVb^lBU0UcU>{]a{*ÁujelZX<U¬Û ÜÝeÞß{

°

²>à>àFß ±

ibeTj_TVU tX<U p{áj([ty®b(iLZ`aU0lVUrfgU Z`abtW^lc`4j0;UrmÌU0U [j

s^s^v

X<U0WâZVbb0~ãlgTVU ]>TVU0l8o

lX<be[fgbW^U

v ° ß ±.ibeTZàUY:jelVUp+àU TVUZàU TVUj(TVU[abjeW^WX\ZX<be[4j

v

Y0bAej(TXj(ZVU0l

°

X{U>{

p+`aU TVUg¸åä±${xæ+j(X\Tj([aW_Ë³X\mal`^X\TBj([^X

°

²>à>à(ç ±Lj([aW_æ+j(X\TÛ ÜuÝeÞè{

°

²>à>à>é ± s TVb

s

b>lVU0W

ê ld

s

U TX<lVU0WS}Ù ê }jrfgU Z`abWZ`4j(ZNdalBU0lNSÙëbe[¯jkld^malVU Z.b(iZ`aU];U [aU0libeT

p+`^X<YV`ìZ`aU¨b0lVY0beTVU0lhU$Y0U0U0WìjY0U TZBj(X\[Z`^TVU0l`ab

v

W~p+`^X

v

U>j([¦ÁubedpU

v

X\[^];U [

Û ÜÝeÞ<í

°

²>à>à>é ±Nl`abAp}U0W¯`abApTX<W];UhTVU ]>TVU0lBlX<be[¯Y:j([¯mUhjeW^b

s

ZVU0W®ZVb¨b0~ãlxfgbtW^U

v

dalX\[^]Èj

s

U [4j

v

X\:U0W

v

X\;U

v

X\`abbWâj

s^s

TVb;jeYV`3{¯îH]>d^y;U [j([aW¯ÙbYV;U

°

²>à>à>²

±xj

s^s^v X<U0W

SÚÕÖZVbÈb:®TVU ]>TVU0lBlX<be[¯my¯ld^malZX\Zd^ZX\[^]_Z`aUbeTX\]>X\[4j

v

;U0Y ZVbeTcb(iH];U [aUU$

s

TVU0l8o

lX<be[alX\[

° ß ±zmy¨j

v

b:pU T8o"WX\fgU [alX<be[4j

v

;U0Y ZVbeTbem^ZBj(X\[aU0W¨Z`^TVbed^]>`nm^X\ej(TXj(ZVUSÚÕÖ

TVU ]>TVU0lVlX<be[®b(i³Z`aUY0U [alVbeTVU0WÈi'j(X

v

d^TVUcZX\fgU0lNj([aWnZ`aUcY0U [alBbeTX\[^]kX\[aWX<Y:j(ZVbeTVl.be[Èï{

Øab

v\v

b:p+X\[^]hð¦`^X\ZVU `aU:jeW

°

ß:ñ>ò>à ±$S*j(TnÛ Ü+ÝeÞß{

°

²>à>à>² ±RU$

s

TVU0lVlBU0WrZ`aU

v

X\;U

v

X\`abbtWribeT

Z`aUkb0®fgbtW^U

v

jelcj¬SÕbeX<lBlVbe[âZ"y

s U v X\;U

v

X\`abtbW~Z`aU TVU mtyâU [4j(m

v

X\[^]nj

s^s^v X<Y:j(ZX<be[

b(iHZ`aUhX\ZVU TBj(ZX\;UqTVU pU X\]>`aU0W

s

j(TZXj

v+v

U:jelZglVtd4j(TVU0l

°

ÙHSÚÕÖ^±.j

v

];beTX\Z`^f

°

á¬j(T8Ì

ß:ñ>ñ>é ±$X\[p+`^X<YV`¯Z`aUp}U X\]>`tZVU0W

v

U:jelZ.lVd4j(TVU0l.lZVU

s

X\[Z`aUX\ZVU TBj(ZX\;UhTVU p}U X\]>`aU0W

v

U:jelZRlVtd4j(TVU0l

°

ÙHÚÕÖ^±j

v

];beTX\Z`^f

°

ákYA}d

v\v

j(]>`j([aWqîHU

v

W^U T ß:ñ>ò>ñ ±}X<l³TVU

s^v jeY0U0Wqmty

p}U X\]>`ZVU0W

s

j(TZXj

v3v

U:jelZHlVd4j(TVU0lA{

îHU X\ZàU TNb(iRZàUxfgU [ZX<be[aU0W®WX\fgU [alX<be[nTVU0WdaY ZX<be[nfgU ZàbW^lNU$

s^v X<Y X\Z

v

y¨lZBj(ZVU

`ab:póU0lZX\fcj(ZX<be[_l`abed

v

WmÌU

s

U T8ibeTfgU0WX\[¬Z`aU

s

TVU0lBU [aY0UNb(i}Z`aU.jeW^WX\ZX<be[4j

v

[abe[o

];U [abefxX<YxY0b:>j(TXj(ZVU0lL¸*Ìm^d^Zui'beTHfgb>lVZub(iZ`aU fij(X\T

v

yklZTBj(X\]>`tZ8ibeTp³j(TVW¨lVb

v

d^ZX<be[al

U$X<lZ:{.ØabeTld^malVU ZlVU

v

U0Y ZX<be[Èj[4j(Zd^TBj

v j s^s

TVb;jeYB`nY0bed

v

W_mÌUNZVbrlZBj(TZbed^ZLmtyU0l8o

ZX\fcj(ZX\[^]kZàUU$ÊÌU0Y ZNb(i³ZàUc[abe[o];U [abefxX<YY0bAej(TXj(ZVU0l.¸wwj([aW¨ZàU [¯jeW^WX\ZX<be[4j

v\v

y

(4)

v s

b s ZX\fcj

v\v ynX\f

s

TVbA;U0W~{Ø4beTgS}Ùõbe[aUqY0bed

v

W¯W^U TX\;UhZ`aU

s

TX\[aY X

s j v Y0bef

s

be[aU [ZVl

m4jelVU0W¨be[

°j

v\v

beTNjhld^malVU Zb(i$±HZ`aUx];U [abefxX<YY0b:>j(TXj(ZVU0l:ÕmU$i'beTVU

s

U T8i'beTfxX\[^]j([

beTVWX\[4j(Tygb:NTVU ]>TVU0lBlX<be[cbe[xZ`aU0lVU+Y0bef

s

be[aU [ZVlZVbe];U Z`aU Tp+X\Z`gZ`aU³[abe[o];U [abefxX<Y

Y0b:>j(TXj(ZVU0l:{Ë³`aUN[4j(Zd^TBj

v

U$ZVU [alX<be[ibeTzTX<W];Ugb0¬TVU ]>TVU0lVlX<be[¬pbed

v

W¬mUNZVb

s

U$o

[4j

v

X\:UgZ`aUgU0lZX\fcj(ZX<be[b(i}ÂÃX\[

° ß

±$m^d^Z[abeZZ`4j(Zb(iÆH{gØ4beTSÚÕÖ3`ab:p}U ;U T:wX\Z

X<l³[abeZRlVb.bemX<bedal+`ab:pöZ`aULjeW^WX\ZX<be[4j

v

Y0bAej(TXj(ZVU0lH¸klV`abed

v

WhmUuZTVU:j(ZVU0W~4j(Z

v

U:jelZ

[abeZHX\[ZàUiTBj(fgU p}beTb(iZàUU$X<lZX\[^]fgU ZàbtW^lA{ÃlyfxfgU ZTX<Y:j

v

ZTVU:j(ZfgU [ZLb(i

Z`aUY0bAej(TXj(ZVU0lx·÷j([aWn¸wwp}bed

vW v

U:jeWZVbSÚ*ÖÈY0bef

s

be[aU [ZVl.mÌU X\[^]fxXßZd^TVU0l.b(i

];U [abefxX<Ycj([aW_[abe[o];U [abefxX<YgY0bAej(TXj(ZVU0l:p+`^X<YV`¨pbed

vW v

jeYV¬X\[tZVU T

s

TVU ZBj(ZX<be[3*j([aW

s

TVU0ld^fcj(m

v

yrj

v

lVbxTVU0ld

v

Z+X\[

s

bbeT

s

TVU0WX<Y ZX<be[3{

"[Z`^X<l

s j s

U T:}];U [aU TBj

v

X\0X\[^]nZ`aUrpbeT®b(iSwj(TÍÛ ÜNÝ>Þè{

°

²>à>à>²

±$pUld^]>];U0lZ

jh;U TVlX<be[Èb(i+SÚÕÖki'beTb0~ãlfgbW^U

v

p+`^X<YB`¨X\f

s

b>lBU0lWX\fgU [alX<be[¨TVU0WdaY ZX<be[be[

vy

be[kZ`aU];U [aUU$

s

TVU0lVlX<be[al:{R[Swj(TÛ Ü+ÝeÞß{

°

²>à>à>² ±$U ;U [Z`aUm4jelVU

v

X\[aU`4j(Aj(TVWX\[o

Y TVU fgU [ZVlj(TVUZTVU:j(ZVU0W_be[¬j([¬U0td4j

v

i'bbeZX\[^]p+X\Z`¬Z`aU];U [abefxX<Y.ej(TXj(m

v

U0l:p+`^X

vU

bed^TRfgU Z`abtWr;U0U

s

lRZ`aULU0lZX\fcj(ZX<be[b(i*Z`aULm4jelBU

v

X\[aUL`4j(Aj(TVW~4jel+pU

v\v

jel+Z`aUz[abe[o

];U [abefxX<Yc>j(TXj(m

v

U0lXßij0>j(X

v

j(m

v

U>wbed^ZVlX<WÛxZàUWX\fgU [alX<be[ÈTVU0WdaY ZX<be[®b(iZàUSÚÕÖ

U0lZX\fcj(ZX<be[3{Ë³`^X<lX<lX\f

s

beTZBj([tZ:tlX\[aY0URX\Z}j

v\v

b:pRl}dalZVb

s

TVU0WX<Y Zld^TtX\>j

vas TVbem4j(m^X

vo

X\ZX<U0lzibeTz]>X\;U [¨>j

v

daU0lLb(i³Z`aU.];U [aUxU$

s

TVU0lVlVX<be[alj([aW¬Z`aUcjeW^WX\ZX<be[4j

v

Y0b:>j(TXj(ZVU0l:{

[abeZ`aU TRjeW>j([ZBj(];ULb(iÕbed^TRj

s^s

TVb;jeYV`qX<lZ`4j(Z³p}UzY:j([hdalVUHZ`aUzbeTX\]>X\[4j

v

Waj(ZBjfcjo

ZTXßqjel³X\[

s

d^Z³i'beTRU0lZX\fcj(ZX<be[qX\[alZVU:jeWrb(ij([rU$ZVU [aW^U0Whfcj(ZTXßhp+`^X<YV`X<l³TVU0d^X\TVU0W

ibeT+Z`aUzfgU Z`abWqb(iwSwj(T¨Û ÜÝ>Þè{

°

²>à>à>² ±$^Z`tdalRX\[aY TVU:jelX\[^]xZ`aULl

s

U0U0Wrj([aWqW^U0Y TVU:jel8o

X\[^]qZ`aUNY0bef

s

d^ZVU TLfgU fgbeTy¬W^U fcj([aW~~p+`^X<YB`ÈY:j([¬mU.Y TdaY Xj

v

i'beTHZ`aU0lVU.X\[aW^lzb(i

Waj(ZBj{

Ë³`aUbed^Z

v

X\[aURb(i~Z`aU

s j s

U TX<ljelib

v\v

bApRl:{"[ÖU0Y ZX<be[ ² p}UHl`ab:pâ`abApX\ZVU TBj(ZX\;U

TVU p}U X\]>`ZVU0W

v

U:jelZglVtd4j(TVU0lxY:j([¯mUqj

s^s^v

X<U0W¯ZVb¬U0lZX\fcj(ZVUrTVU ]>TVU0lVlX<be[âY0bU$ÉcY X<U [ZVl

ibeThZ`aUZ"pb¯lVU ZVlhb(iY0b:>j(TXj(ZVU0lrj([aW¦Z`aUkm4jelBU

v

X\[aUk`4j(Aj(TVWX\[Z`aU¨b0¦fgbtW^U

v

° ß ±${Ë³àU [âX\[¦ÖU0Y ZX<be[ ô p}UrlVàb:põàbAp×ZàU

v

U:jelZglBd4j(TVU0llZVU

s

X\[âZ`^X<lg1ÙÚÕÖ

j v

];beTX\Z`^føY:j([¯mUhTVU

s^v

jeY0U0WâmynSÚÕÖ]>X\X\[^]Èj([âÙHSÚÕÖ®j

v

];beTX\Z`^følX\fxX

v

j(TxZVb

Z`aUbe[aUb(iáj(T8

°

ß:ñ>ñ>é ±$am^d^ZfgbtWX U0WklVb.Z`4j(ZZ`aULm4jelBU

v

X\[aUL`4j(Aj(TVWkjel+pU

v\v jel

[abe[o];U [abefxX<Yc>j(TXj(m

v

U0lj(TVUx`aU

v

WÈbed^ZVlX<WÛgZàUgSÚÕÖTVU ]>TVU0lVlX<be[be[¨ZàUx];U [abefxX<Y

Y0b:>j(TXj(ZVU0l:{ù"[ìÖU0Y ZX<be[ ç p}UkdalVUkZ"p}b®WXßÊ~U TVU [ZfxX<Y TVb;j(TTBj0y¦];U [aUkU$

s

TVU0lVlX<be[

m^TVU:jelZ}Y:j([aY0U TWaj(ZBjlVU ZVl:;be[aUp+X\Z`jeW^WX\ZX<be[4j

v

Y0bAej(TXj(ZVU0lAZVbLfcj(;UHY0bef

s

j(TX<lVbe[al

mU Zp}U0U [Z`aU

s

U T8ibeTfcj([aY0Ub(i

°

X±Rbed^THj([aWSwj(TãlfgU Z`abtWj([aW

°

X\X±+bed^TfgU Z`abtW

p+X\Z`j([aWqp+X\Z`abed^ZH];U [aUU$

s

TVU0lVlX<be[Y0bAej(TXj(ZVU0lHX\[aY

v

daWÛ0WrX\[kZàULfgbtWÛ

v

{Ø*X\[4j

v\v

y

p}UWX<lVY dalBl+Z`aULfgU Z`abWj([aWrY0be[aY

v

daW^ULX\[ÖU0Y ZX<be[ú{

(5)

HlVlVd^fgULZ`4j(ZHpU`4j:;UY0U [alVbeTVU0Wkld^TX\ej

v

Waj(ZBjw´1¡1¡8¡V§"¤$e¡0¢0¢0¢A¡ÒaibeT

ÒX\[aWX\X<Wd4j

v

l:{rÁuU TVUg´+X<lZ`aUcbemalVU T;U0WbeTY0U [alVbeTVU0WÈij(X

v

d^TVUgZX\fgUcibeTZ`aUZ`

X\[aWX\tX<Wd4j

v

~X<lj([cX\[aWX<Y:j(ZVbeTibeTp+àU ZàU TZàU³ij(X

v

d^TVURZX\fgU+X<l}bemalVU T;U0W

°

A±

beTNY0U [alVbeTVU0W

°

uõä±$j([aWÈH 0¡0¢0¢0¢A¡ £¤ ¥ j([aWÈ§!u ª" :¡0¢0¢0¢:¡Vª#\«:¤ ¥ j(TVU

Z"p}bc;U0Y ZVbeTVlb(iY0b:>j(TXj(ZVU0l:{

Ë³`aUzid

v\v~v X\;U

v

X\àbtbWhi'beT+ZàUb0qfgbWÛ

v

X\[

° ß ±fcj0yhmÌUzp+TX\ZZVU [

$ %

&

('Õ )+*

µ ¹

´'¤8º »;¼,½^¾¿(¼,aÀ-".

,0/213

*546

¹

´¤8º »;¼,t½^¾¿(¼,aÀ-87 ¡

p+`aU TVU

6 ¹

´^¤LX<lZ`aUgY d^fd

v

j(ZX\;Um4jelVU

v

X\[aUc`4j(Aj(TVW~{qØ4beTZ`aUj(malBb

v

d^ZVU

v

y¨Y0be[ZX\[o

dabedalNY:jelBUcZ`aU

v

X\;U

v

X\`abtbWY:j([nmÌUgfcjeW^Uhj(Tm^X\ZTBj(TX

vy v j(T];Umy

v

U ZZX\[^]

µ ¹

´^¤mU

:U TVbU$^Y0U

s

ZiTVbefÔY

v

b>lVUZVbZ`aUbemalVU T;U0Wni'j(X

v

d^TVUZX\fgU0l:wp+`aU TVUp}U

v

U ZNX\Z

s

U:j(

`^X\]>àU Tj([aW¬`^X\]>àU T:{Áub:pU ;U T:3myY0be[alX<WÛ TX\[^]kj([_U$ZVU [aWÛ0W¬fgbtWÛ

v

~p+`aU TVU.Z`aU

Y d^fd

v

j(ZX\;UNm4jelVU

v

X\[aU`4j(Aj(TVW

6 ¹

´a¤³fcj:yqmUj([yq[abe[o[aU ]j(ZX\;U>[abe[o"W^U0Y TVU:jelX\[^]

id^[aY ZX<be[3Z`aU+id

v\vav X\;U

v

X\`abbtWcX<lfcjX\fxX\:U0WgXßiÕj

v\vQs TVbem4j(m^X

v

X\Z"ygfcjelBlX<l

s

d^Zj(ZZ`aU

WX<lZX\[aY ZbemalVU T;U0W¨i'j(X

v

d^TVUcZX\fgU0l:9- <;=9?>@;BA8A8AC;=9ED

°GF

be`4j([alVU [ ß:ñ>ò>ô ±${hðX\Z`

Z`^X<lU$ZVU [alX<be[

6 ¹

´¤IH

Ï8JKML8NPO

,!Q

6 ¹

+9Ï ¤$p+`aU TVU

Q 6 ¹

+9 Ï ¤X<lZ`aUX\[aY TVU fgU [tZRb(i

Z`aUNY d^fd

v

j(ZX\;U.m4jelVU

v

X\[aUN`4j(Aj(TVW_j(ZuZX\fgU9'Ï>~j([aWZ`aUid

v\vÕv X\;U

v

X\`abbWkZBj(;U0lzZ`aU

ibeTf

$ %

&

('Õ R)S*

Q 6 ¹

´¤8º:» ¼, ½a¾¿ ¼, À - . , /21T3

*546

¹

´"¤8º:» ¼, ½a¾¿ ¼, À -87 ¢ ° ² ±

Ë³`aUX\[aY TVU fgU [tZVl

Q 6 ¹

+9Ï ¤b(iaZ`aU}m4jelVU

v

X\[aU³Y d^fd

v

j(ZX\;U`4j(Aj(TVWxj([aWZ`aU}TVU ]>TVU0lVlX<be[

Y0btU$ÉcY X<U [tZ;U0Y ZVbeTVl+Âöj([aWÆ¦j(TVULU0lZX\fcj(ZVU0WmyfcjX\fxX\0X\[^]Z`aU

v

X\;U

v

X\`abbtW

° ²

±${

ØabeT³]>X\;U [hej

v

daU0l³b(i3Â¦j([aWcÆ®Z`aUH>j

v

daU0l³b(iZ`aUHm4jelVU

v

X\[aUu`4j(Aj(TVWX\[aY TVU fgU [tZVl

Z`4j(ZRfcjX\fxX\:UZ`aU

v

X\;U

v

X\`abtbWj(TVUL]>X\;U [my

QVU

6 ¹

+9'Ï¶"Âu¡1Æ³¤ W Ï

H JO

,GX KML

º » ¼, ½a¾¿ ¼, À ¡ ° ô ±

p+`aU TVU

W Ï H JO ,' KML

X<lZ`aU[td^fmÌU Tgb(iRX\[aWX\tX<Wd4j

v

lNij(X

v

X\[^]¨j(ZY9 Ï {¬"i

°ô

±LX<l

X\[alVU TZVU0WrX\[

°²

±+be[aUL];U ZVlHj

s

TVb vU v X\;U

v

X\`abtbWhi'beT+Âöj([aWhÆZ`4j(ZRX<l

s

TVb

s

beTZX<be[4j

v

ZVbgæTVU0l

v

b:pãlfgbtWX

Y:j(ZX<be[b(ib:Ìãl³ij(fgbedal

s

j(TZXj

vv X\;U

v

X\`abtbW

Z:[8Âz¡1Æ³¤

D

&

Ï 'Õ

&

JO ,' KML \

º » ¼, ½a¾¿ ¼, À

H^]

JO_

X

KML º » ¼_

½a¾¿ ¼_ Àa`

., ¢ ° ç ±

Ë³`dalfcjX\fxX\Aj(ZX<be[ìb(iZ`aU

v

X\;U

v

X\`abtbW

° ² ±xfcj0yâmÌU

s

U T8i'beTfgU0WâX\[¦Z"p}blZVU

s

l#b

TVlZLZ`aU

v

be]j(TX\Z`^f b(i

°ç

±HX<lzfcjX\fxX\:U0W¬p{T:{Z:{Âùj([aWkÆödalX\[^]qlVbefgU.X\ZVU TBj(ZX\;U

(6)

fcjX\fxX\Aj(ZX<be[¯j

v

];beTX\Z`^f U>{]a{3îuU p+ZVbe[o"ÙHj

s

àlBbe[Q±$*j([aW_ZàU [nZàU0lVU.fcjX\fd^f

v

X\;U

v

X\`abtbW¯U0lZX\fcj(ZVU0lgj(TVUX\[alVU TZVU0WX\[

° ô

±ZVb¬bem^ZBj(X\[¯Z`aUfcjX\fd^f

v

X\;U

v

X\`abbtW

U0lZX\fcj(ZVU0lxi'beTxZ`aUhX\[aY TVU fgU [ZVlb(iHZ`aUqm4jelBU

v

X\[aUh`4j(Aj(TVW~{âË³`^X<lxX<l.Z`aUrY0befxfgbe[

j

s^s

TVb;jeYV`kibeTRU0lZX\fcj(ZX<be[X\[b0~ãl+TVU ]>TVU0lVlX<be[fgbtW^U

v {

ØabeTbed^T

s

d^T

s

b>lBU>p+`^X<YB`nX<lZVblVU ZZ`aUlVY0U [aU.i'beTZ`aU

s

j(TZXj

vv

U:jelZlBd4j(TVU0l

fgU Z`abtWkb(iÖU0Y ZX<be[

ô

^X\ZHX<lR`ab:pU ;U THfgbeTVUNj

s^s TVb

s

TXj(ZVUNZVbxfcjX\fxX\:UZ`aU

v

X\;U

v

Xßo

`abtbWhlX\fd

v

ZBj([aU0bedal

v

yp+X\Z`qTVU ]j(TVWZVbZ`aUum4jelVU

v

X\[aUu`4j(Aj(TVWX\[aY TVU fgU [ZVl

Q 6 ¹

+9Ï ¤

j([aWâZ`aUq;U0Y ZVbeTVlb(iuTVU ]>TVU0lBlX<be[Y0bU$ÉcY X<U [ZVlcÂ×j([aWÆH{Ë³`^X<lY:j([âmUkjeYV`^X<U ;U0W

my TVlZulVU ZZX\[^]X\[^X\ZXj

v

>j

v

daU0lb(iZ`aU;U0Y ZVbeTVlzb(iTVU ]>TVU0lVlX<be[¬Y0bU$ÉcY X{]a{4mty

v

U ZZX\[^]

U

Âdc

¹e

gfj([aW

U

Æc

¹e

hf3³j([aW®Z`aU [âX\ZVU TBj(ZX\[^]¨Z`aUi'b

v\v

b:p+X\[^]lZVU

s

lNibeT

i ä¡#e¡j¡0¢0¢0¢^d^[ZX

v

ZàURZàUHYV`4j([^];U0lX\[cZàU

v

be]j(TX\Z`^fb(i~Z`aU

v

X\;U

v

X\`abbW

°² ±j(TVU

lfcj

v\v

b

kml U Zd

s

Waj(ZVU0W¦U0lVZX\fcj(ZVU0l

Q U6 con

e

¹

+9Ï ¤b(iZ`aUm4jelVU

v

X\[aU`4j(Aj(TVWX\[aY TVU fgU [tZVl

dalX\[^]

°ô ±³p+X\Z`

s

j(TBj(fgU ZVU T;U0Y ZVbeTU0lVZX\fcj(ZVU0l

U

Â cpn

e

j([aW

UÆ con e {

kml U Zcd

s

Waj(ZVU0W¦U0lZX\fcj(ZVU0l

U

Âdcon

¾ e j([aW

U

Æcon

¾ e

b(iLÂ×j([aW®Æ m4jelBU0Wbe[Z`aU

Y d^TTVU [tZ³U0lVZX\fcj(ZVU0l+b(i3Z`aUm4jelVU

v

X\[aUu`4j(Aj(TVWX\[aY TVU fgU [ZVlHj([aWcZ`aUHTVU ]>TVU0lVlX<be[

s

j(TBj(fgU ZVU TR;U0Y ZVbeTVlA{

ð¨UudalVUuZ`aUH1ÙÚÕÖj

v

];beTX\Z`^fëZVbd

s

Waj(ZVUuZ`aUuZ"pb.;U0Y ZVbeTVl+b(iTVU ]>TVU0lVlX<be[qY0bU$io

Y X<U [ZVl:{³Ö

s

U0Y X Y:j

v\v

y;^]>X\;U [kY d^TTVU [ZHU0lVZX\fcj(ZVU0l

Q U

6

cpn

e

¹

+9 Ï ¤$

U

Â cpn

e

j([aW

UÆ con

e

b(i*Z`aU

m4jelVU

v

X\[aUR`4j(Aj(TVWcX\[aY TVU fgU [ZVl+j([aWxZ`aURTVU ]>TVU0lBlX<be[

s

j(TBj(fgU ZVU T;U0Y ZVbeTVl:;pURp+X

v\v ];U Z

d s

Waj(ZVU0WU0lZX\fcj(ZVU0lb(i~Âj([aW.ÆnX\[Z"p}b.lZVU

s

l"bÕØ*X\TVlZ}p}UHdalVURZ`aUHÙHÚÕÖxj

v

];beTX\Z`^f

ZVb¬];U Zcj([âd

s

Waj(ZVU0W¯U0lVZX\fcj(ZVUrb(iÂ ZTVU:j(ZX\[^]¨Z`aUqY d^TTVU [ZU0lZX\fcj(ZVU0l

Q U

6

cpn

e

¹

+9Ï ¤

j([aW

U

Æcon

e

b(i3Z`aUHm4jelVU

v

X\[aU`4j(Aj(TVWX\[aY TVU fgU [ZVlHj([aWgZ`aUH;U0Y ZVbeTb(i3TVU ]>TVU0lVlVX<be[Y0bU$io

Y X<U [ZVl³Æjel

^U0Whd4j([tZX\ZX<U0l

°

b(Ê~lVU ZVl-±X\[qZ`aUuTVU ]>TVU0lVlX<be[3{Ë³`aU [qpULd

s

Waj(ZVUzZ`aU

U0lZX\fcj(ZVUb(i3ÆZTVU:j(ZX\[^]

Q U6 con

e

¹

+9Ï ¤³j([aW

U

Â con

e

jelRb(Ê~lVU ZVl:{Ë³`aUzfgbeZX\>j(ZX<be[qibeTRW^b(o

X\[^]Z`^X<l}X\[gZ"pblZVU

s

lÎNp+`^X<YB`ci'beTZ`aUbeTVWX\[4j(Tyg1ÙÚ*Öxj

v

];beTX\Z`^f pbed

v

WcmÌURW^be[aU

X\[be[aUlVX\[^]

v

UlZVU

s

Î.X<lZ`4j(Z}p}URX\[qÖU0Y ZX<be[

ô

p+X

v\v

ld^malZX\Zd^ZVUZ`aU1ÙÚÕÖ.d

s

Waj(ZX\[^]

lZVU

s

b(iZ`aU.`^X\]>`o"WX\fgU [alVX<be[4j

v

Y0bU$ÉcY X<U [Z;U0Y ZVbeTLÂùp+X\Z`¨SÚÕÖ_U0lZX\fcj(ZX<be[3m^d^Z

lZX

v\v TVU

v

yhbe[ÙHÚÕÖcZVbxd

s

Waj(ZVULZ`aU

v

b:p³o"WX\fgU [alVX<be[4j

v

Y0bU$ÉcY X<U [Z;U0Y ZVbeTRÆH{

Ëb¬WÛ0lVY TX\mÌUcàbAp ZàU1ÙÚÕÖ¨d

s

Waj(ZX\[^]lZVU

s

li'beTZ`aU;U0Y ZVbeTVl.b(iRTVU ]>TVU0lVlX<be[

Y0btU$ÉcY X<U [tZVlRÂöj([aWÆj(TVU

s

U T8ibeTfgU0W~^pUL[aU0U0WrlVbefgU[abeZBj(ZX<be[3{Ø*X\TVlZRp}Up+TX\ZVU

Uq

con

e

U6

cpn

e

¹

´¤8º

»;¼,r½ sMt?u¾¿(¼,

r

À sMtvu

°

ú;±

ibeT}Z`aUHY d^fd

v

j(ZX\;UH`4j(Aj(TVWci'beTX\[aWX\X<Wd4j

v ° U >j

v

d4j(ZVU0Wj(Z}X\ZVl}Y0U [alVbeTVU0Wld^TX\ej

v

ZX\fgU´±+d^[aWÛ TuZàUNY d^TTVU [ZLU0lZX\fcj(ZVU0lzb(iZàUm4jelBU

v

X\[aU`4j(Aj(TVWkX\[aY TVU fgU [ZVlj([aW

Z`aU.TVU ]>TVU0lVlX<be[

s

j(TBj(fgU ZVU T;U0Y ZVbeTVl:{Ë³`aU [_p}U.X\[tZTVbtWdaY0UxZ`aU ê s

lBU daW^bqbemalVU Tejo

(7)

U

w

cpn

e

·

¥ U

Â

cpn e x

Uq

con

e

S

4 Uq cpn

e

¤-¡

° é ±

j([aW

Uy

con

e

¸

¥

U

Æ

con

e x

Uq

cpn

e

S

4 U

q

con

e

¤-¢

°{z

±

"[kZ`aUj

s^s

U [aWXßÌQp}UNl`ab:p÷Z`4j(ZZ`aUN1ÙÚÕÖqd

s

Waj(ZX\[^]b(iÂöX<l

s

U T8ibeTfgU0WmyrTVU$o

]>TVU0lVlX\[^]gZ`aU ê s

lBU daW^bgbemalVU T>j(ZX<be[al ê U

w

cpn

e

be[qZ`aUY0b:>j(TXj(ZVU0lH· dalX\[^]gpU X\]>`ZVU0W

v

U:jelZlVtd4j(TVU0lp+X\Z`¨pU X\]>`ZVl

Uq

cpn

e

{hÖtX\fxX

v

j(T

v

y¬Z`aUcU0lZX\fcj(ZVUgb(iÆÍX<lLd

s

Waj(ZVU0W¨mty

p}U X\]>`ZVU0W

v

X\[aU:j(TTVU ]>TVU0lVlX<be[nb(i+Z`aU ê s

lVU daW^brbemalVU T>j(ZX<be[al ê U y

cpn

e

be[¨Z`aUcY0bAej(TXßo

j(ZVU0l¸ {

"[_beTVWÛ TzZVbhWÛ0lVY TX\mÌUZàU.1ÙÚÕÖd

s

Waj(ZX\[^]qlZVU

s

lzX\[¬fgbeTVUNW^U ZBj(X

v

lAÌX\ZuX<lzY0be[o

;U [^X<U [ZcZVbdalVUh;U0Y ZVbeTcj([aW®fcj(ZTXß®[abeZBj(ZX<be[3{¯Ëb¬Z`^X<lcU [aW®p}UhX\[ZTVbWdaY0UrZ`aU

;U0Y ZVbeT:|kõS ¡0¢0¢0¢:¡

% ¤ ¥ b(i}i'j(X

v

d^TVUNX\[aWX<Y:j(ZVbeTVlzi'beTzZ`aUX\[aWX\X<Wd4j

v

l:~Z`aUN;U0Y ZVbeT

U

}

con

e

å

Uq

cpn

e

¡0¢0¢0¢

U

q

cpn

e

%

¤"¥4j([aWZ`aUWXj(];be[4j

v

fcj(ZTXß~con

e

IP(Q

U

}

cpn

e

¤Z`4j(Z`4jel

Z`aUgU0lZX\fcj(ZVU0WÈY d^fd

v

j(ZX\;Uc`4j(Aj(TVW^l

°

ú;±zbe[¨Z`aUgWXj(];be[4j

v

{Ë³`aU [ÈZ`aUg;U0Y ZVbeTb(i

ê s

lVU daW^bgbemalVU T>j(ZX<be[al ê °é ±ZBj(;U0lZ`aUuibeTf

U

cpn

e

^

U

Â

cpn e x

U

~

cpn eS

| 4 U

}

cpn e{

¡ ° ò ±

p+`^X

v

ULZ`aUL;U0Y ZVbeTb(i ê s

lVU daW^bgbemalVU T>j(ZX<be[al ê

°{z

±³fcj0yhmUzp+TX\ZZVU [

U

con

e

U

Æ

cpn e x

U

~

cpn

e | 4 U

}

cpn

e ¢ ° ñ ±

ÁHU TVU X<l³Z`aUzÒNÑrfcj(ZTXßp+X\Z`qTVbApRl· ¥

p+`^X

v

UåX<l³Z`aUzÒfcj(ZTXßp+X\Z`

TVb:pRl¸Q¥

{Ë³`aUÙHÚÕÖd

s

Waj(ZX\[^]lZVU

s

i'beT+Z`aUL;U0Y ZVbeTb(iwTVU ]>TVU0lVlX<be[Y0bU$ÉcY X<U [ZVlÂ

fcj0yhZ`aU [rmÌUz]>X\;U [rmy

°

Y$i{Z`aUj

s^s

U [aWXß4±b

U

Â con ¾ e ¥ U

~ cpn

e ¥ U

~ cpn e U

cpn

e ¢ °

ß:à

±

"[jxlVX\fxX

v

j(T+fcj([^[aU TZ`aU1ÙÚÕÖd

s

Waj(ZX\[^]clZVU

s

i'beTÆX<l+]>X\;U [rmty

UÆ

con

¾ e ¥ U

~

cpn

e ¥ U

~ cKeU

con

e ¢ °

ß¢ß

±

Ë³`aUqY0bef

s^v

U ZVUhfgbtWX U0W¯1ÙÚ*Önj

v

];beTX\Z`^fÔi'beTxlX\fd

v

ZBj([aU0bedalcU0lZX\fcj(ZX<be[âb(i

Z`aUq;U0Y ZVbeTcb(izTVU ]>TVU0lVlX<be[âY0bU$ÉcY X<U [ZVlhj([aW®Z`aUqm4jelVU

v

X\[aUh`4j(Aj(TVWâX\[aY TVU fgU [tZVlgX<l

ld^fxfcj(TX\:U0WX\[kËÕj(m

vU ß {}ØabeTlX\f s^v

X<Y X\Zy;4pU`4j:;UbefxX\ZZVU0WrZàUX\[aWÛ$ i ibeTRZàU

X\ZVU TBj(ZX<be[[d^fmU THX\[qZ`^X<lld^fxfcj(Ty;{

(8)

ËÕj(m

vU ß b*Ötd^fxfcj(Ty.b(i4Z`aUfgbWX U0WxÙHÚÕÖLfgU Z`abWibeTlX\fd

v

ZBj([aU0bedalU0lZX\fcj(ZX<be[

b(i*TVU ]>TVU0lVlVX<be[Y0btU$ÉcY X<U [tZVluj([aWrm4jelVU

v

X\[aUL`4j(Aj(TVWqX\[kb:ÌãlTVU ]>TVU0lVlX<be[rfgbW^U

v{

êöé} ¹. Ý}\}~&}}}<&áw}-& Þ ¡

óêcÍ§}&}DÝy}`1Þ<}ø&}Þ< O&} æ<}' ¢¡ãç©ó<ê,}S©¨

ç©<êTé}C ¢¡+£¤ ¦¥ £2§©¨ª¬«?®S¯±°¬²³´µ

®¶

·±¸º¹

µ

® ¶»

çÎá4êöè¹}'

¼

á4}D&}}$&¦Z&Ã}'}'}'&

½ ª

¾¨

£ «°¬²E¿T?®

ÀÁ(¡+£¤{³ ´µ

®¶

·±¸º¹

µ

® ¶

»

ç©êTé} Â ÃÄoÅ#Æ

½ Ç#ÈÉÉÊÉ ½PË

¤ É

ç»¡êTé} Ì=ÎÍ Ï ÂVÐ

Ç

ÒÑVÓ

¼

¤ h¡ Ý~r¡.}Å}T}-S.&}Å Ý Þ

¦,} Þ<}¡ø}-åÝ}}Þ&}&-¹¨ ÍÔ Â Í ¤ Ð Ç

ÍÔ Â Ì

ç»}êTé}

Õ

×Ö

Ï ÂVÐ

Ç

+ÑPÓ

¼

¤

.¡DÝ~r¡}0},}-}

Ý4-Þ¦}'Þ}¡

}-åÝ},&}'Þ<}¹¨

Ö Ô Â Ö ¤ Ð Ç Ö Ô

Â

Õ

Ø Ù¯ÿÚÛJ0 I+I4PBJRF

"ZHX<lujgTVU0d^X\TVU fgU [tZHi'beTZ`aUfgbtWX

U0W1ÙÚÕÖj

v

];beTX\Z`^f©b(iZ`aU

s

TVU tX<bedalulVU0Y ZX<be[

Z`4j(ZZ`aUx[td^fmÌU TNb(ii'j(X

v

d^TVUcZX\fgU0lU$^Y0U0U0W_Z`aUg[td^fmÌU Tb(iRY0b:>j(TXj(ZVU0l:{ØabeT];U$o

[abefxX<YWaj(ZBj.Z`^X<l+X<lHlVU

v

W^befõZ`aULY:jelVU>a`ab:p}U ;U T:Ìj([aWrlVbefgUWX\fgU [alX<be[rTVU0WdaY ZX<be[

ZVU0YV`^[^X<tdaU+X<lY:j

v\v

U0WNibeT:{Õð¨U³p+X

v\v ib

v\v

bAp¯Z`aURj

s^s

TVb;jeYV`cb(iÌáj(T8

°

ß:ñ>ñ>é ±wj([aW.fgbtWo

Xßiy_Z`aUÙHÚÕÖ¨j

v

];beTX\Z`^f b(iËÕj(m

vU ß mty_TVU s^v

jeY X\[^]¬Z`aUcpU X\]>`ZVU0W

v

U:jelZlBd4j(TVU0l

TVU ]>TVU0lVlX<be[_U0lZX\fcj(ZX<be[¨b(iCÜX\[¬lVZVU

s °

W4±p+X\Z`¨jp}U X\]>`ZVU0W

s

j(TZXj

vv

U:jelZulBd4j(TVU0l

°

SÚÕÖ^±³TVU ]>TVU0lBlX<be[3{

îHbeZVUZ`4j(ZqZ`aU_j

v

];beTX\Z`^f b(iË*j(m

vU ß d s

Waj(ZVU0lhZ`aUTVU ]>TVU0lVlX<be[ìY0bU$ÉcY X<U [Z

;U0Y ZVbeTVlzÂùj([aWÆÍj([aW¬Z`aUm4jelBU

v

X\[aU.`4j(Aj(TVW¬X\[Z`^TVU0UxlBU

s

j(TBj(ZVUxlZVU

s

l:p+`^X<YV`nj

vo

v

b:pRlzdaluZVbqj

s^s^v

ySÚÕÖbe[

v

yrZVbhU0lZX\fcj(ZVUÂLÌbeTuZ`aU;U0Y ZVbeTb(i

v

X\[aU:j(T

s

TVU0WX<Y ZVbeTVl

+Ý ¡0¢0¢0¢A¡EÝ

%

¤"¥ÃÞÜÃßâÂLp+`^X<YB`âX<l.Z`aUqtd4j([ZX\Z"ydalVU0W®X\[¯Z`aUhá¬j(T8Ìãlgj

v

];b(o

TX\Z`^fr{Ë³`^X<l.j

s^s

TVb;jeYV`¯X<ldalVU$id

v

lVX\[aY0Uc`^X\]>`o"WX\fgU [alX<be[4j

v

];U [abefxX<YWaj(ZBjb(iZVU [

U$X<lZ³X\[rY0be[e8d^[aY ZX<be[rp+X\Z`h[abe[o];U [abefxX<YWaj(ZBj.b(i

v

b:p}U THWX\fgU [alX<be[34j([aWp}U [aW

X\ZTVU:jelVbe[4j(m

v

UZVb

v

U:j:;UZ`aUNU0lZX\fcj(ZX<be[¬b(iwZ`aU

v

j(ZZVU Tubed^ZVlVX<W^UZ`aUNWX\fgU [alX<be[kTVU$o

WdaY ZX<be[

s

TVbAtX<W^U0WmygSÚÕÖ{Ø^d^TZ`aU TàÜ¨j([aWxÆ®bed^]>`tZ}ZVbmUHU0lZX\fcj(ZVU0WlBU

s

j(TBj(ZVU

vy

iTVbefõZ`aUzm4jelBU

v

X\[aUL`4j(Aj(TVW~ap+`^X<YB`X<l³y;U ZHj([abeZ`aU TuWX<lZX\[aY Ztd4j([ZX\Z"y;{

|Hd^TxX\ZVU TBj(ZX\;U

v

ynTVU pU X\]>`ZVU0W

s

j(TZXj

v+v

U:jelZxlVd4j(TVU0l

°

1ÙSÚÕÖ^±.j

v

];beTX\Z`^fÔibeT

b0TVU ]>TVU0lVlVX<be[X<llVd^fxfcj(TX\:U0WX\[ËÕj(m

vU ² {+ÁHU TVU

° W ß ±"o

°

Waú;±j(TVUZ`aUSÚÕÖlZVU

s l

Z`4j(Z3TVU

s^v jeY0UlZVU

s °

W4±ÌX\[Z`aUj

v

];beTX\Z`^fb(i^ËÕj(m

vU ß {*ÖtZVU

s l °W ²

±"o

°W ç

±3j(TVUpU X\]>`ZVU0W

;U TVlX<be[alzb(iZ`aUlZVU

s

luX\[kZ`aUY

v

jelVlVX<Y:j

v

SÚ*Ökj

v

];beTX\Z`^f

°

U>{]a{uáj(TZVU [alzj([aWîâá³l

ß:ñ>ò>ñ ;Ø^TBj(fgU ô {ç ±$;U$^Y0U

s

ZwZ`4j(Z*pU+be[

v

yW^bLj

s

j(TZXj

v d s

Waj(ZVU+b(i

U

ÜX\[xlZVU

s °W ç ±ÕZVb

j0;beX<WY0be[;U T];U [aY0U

s

TVbem

v

U fgl:{ËbW^U ZVU TfxX\[aUdãä¦X\[lZVU

s °W ç

±p}U

s

U T8i'beTf j v X\[aU

(9)

v v s vv v

TX\Z`^fëibeTzb0~ãl+TVU ]>TVU0lVlX<be[rfgbW^U

v {

NÍ) ä}Náí-}'-Þ

å

¾ ¡

ó¢Dë<0æ èç

ÈÊÉÉÉÈvé

¦Z}}êæ Z}!Ý!ár}'LH0è^é¤§'~r}<1 }&}`Ý&

}`14Þ<}

¼

}S©¨

ç©<êTé}C

¢¡£ ¤ ¦¥ £ § ¨ª¬«?®S¯±°¬² ³ ¶ë ®

¸º¹

µ

® ¶

»

çÎá4êöè¹}'

¼

á4}D&}}$&¦Z&Ã}'}'}'&

½ ª ¨ £ «°¬²E¿T?®

ÀÁ(¡+£¤{³

¶

ë ®

¸P¹

µ

® ¶

»

ç©êTé} Â ÃÄoÅ#Æ

½ Ç#ÈÉÉÊÉ ½PË

¤ É

ç©¡yêTé} Ì

å Ï ÂìÐ

Ç

ÒÑâÓ

¼

¤

ç©¡óêTé} í îÍ Ó×ï

ð

Ô ¦Z}'&}

ð

ÍÔ Â ï¤ñ§!{ï Ô Â ï¤ !}í}$&!

¦,} Þ<}¡í }&Þ} \}`'Ý Í Ý-Þ¦}'ÞZ& Âö

ç©¡<êöë<aò óç

È?ôÈÉÊÉÉÈ æö}¨

t

õ÷ö

í Ôö Ð Ç Â Ì ö Ð Ç

t

ø ö í ö Ð Ç õö

t

ù ö ÌÔ

ö Ð Ç Â ø ö

¤v§

ø Ôö Â ø ö ¤

F

Ì ö

Ì ö Ð Ç Ó ø ö ù ö

F

úö

í Ô

ö Ð Ç Â ø ö

¤ñ§

ø Ôö Â ø ö ¤

t í ö í ö Ð Ç Ó ø ö

úö

ç©¡ûêö~F¡.&}

å

á

å

¦üý

þ÷ÿ ý

ÿ

ý

Ï ç Ó üý ¤

å

<¦Z}'&} þ÷ÿ ý

ø

Ç#ÈÉÊÉÉÈ

ø ý ê

¡

ÿ

ý

ù2Ç2ÈÊÉÉÉÊÈ ù ý ¤ Ô

¡

üý

È

ç

b¦}'ÞZ¢ ä'Þ}

æ} ¢¡yÎÝ¡íáô~4}-Î<ÞS/}`-}11öç©-}}L&}ZÎ¡}& 1ê$

ç©¡êTé}

å

å Ó Ç

Ë ¨ Ë ª

Ç ª

ç»}êTé}

Õ

=Ö

Ï

ÂìÐ

Ç

+ÑâÓ

¼

¤

,¡ Ý~r¡}ô}í}-S.}ø&}ô<}

y&}'Þ&}& <'}w}'&

Ý-Þ&}h¦}'Þ&}¡}-,&åÝ&}H&}'Þ<}

ç<ê$

(10)

v vv v

° ² ± °

p+X\Z`· ¥ ÂìTVU

s^v

jeY0U0Wqmy@Ý±${}Ö

s

U0Y X Y:j

v\v

yqp}UW^bxZ`^X<lRmyhfcj(tX\[^]jNd^[^XßibeTf

]>TX<Wrb(i ß:à >j

v

daU0l³mU Zp}U0U [ à j([aW ß j([aW

[aWX\[^]cZ`aUzej

v

daULb(i ãHZ`4j(Z+fcjX\fxX\:U0l

Z`aUZVbeZBj

v³v X\;U

v

X\àbbtW~{¬ðÜZàU [®fcj(;Uqj [aU T.Zd^[^X\[^]_mty¨TVU

s

U:j(ZX\[^]¬Z`^X<lNi'beT.j

[aU pd^[^Xßi'beTf×]>TX<Wkp+X\Z`ú à ej

v

daU0l

v

btY:j

v\v

yj(TVbed^[aWkZ`aUãzibed^[aWX\[Z`aU TVlZ

v

X\[aU

lVU:j(TVYV`3{qîubeZVUxZ`4j(Zbe[nY0be[;U T];U [aY0U

U

ÜBãÊä

U

cä e U

cä e x

?

4

ãäz¤

U

ÜÕX\f

s^v ytX\[^]

Z`4j(ZRp}ULZ`aU [`4j0;U

U

Ü_

U

cä e U

cä e

^Y0beTTVU0l

s

be[aWX\[^]cZVbgjid

v\v d s

Waj(ZVU>{

ÖbefgUNid^TZ`aU TzY0befxfgU [ZVlbe[Z`aUxj

v

];beTX\Z`^f b(i}Ë*j(m

vU ² Ìj([aW_jY0bef

s

j(TX<lVbe[

p+X\Z`xZ`aUSÚÕÖoj

v

];beTX\Z`^f b(iQá¬j(T8

°

ß:ñ>ñ>é

s j(];U

ô

zz

±i'beT*];U [aU TBj

v

X\:U0W

v

X\[aU:j(TfgbtWo

U v

l:4j(TVULX\[beTVW^U T:{[áj(T8~ãlj

v

];beTX\Z`^f©j

v\v

SÚÕÖo"WX\TVU0Y ZX<be[alj(TVULdalBU0Wj(Z TVlZRZVb

[aWâj([U0lZX\fcj(ZVUqb(iâÜ}mÌU$i'beTVUcX\ZVU TBj(ZX\[^]Èbe[Z`^X<lxU0lZX\fcj(ZVUhd^[tZX

v

Y0be[t;U T];U [aY0U>{

ÖtX\[aY0Uhp}U;U0U

s

Z`aUU0lVZX\fcj(ZX<be[®b(iuZ`aUcm4jelBU

v

X\[aUh`4j(Aj(TVW®j([aWZ`aU[abe[o];U [abefxX<Y

ej(TXj(m

v

U0lbed^ZVlVX<W^UZ`aUxSÚÕÖkTVU ]>TVU0lVlX<be[3~X\ZzX<lzfgbeTVUxY0be[t;U [^X<U [ZLi'beTLbed^T

s

d^T

s

b>lVU

ZVbLlZBj(TZwp+X\Z`cjzlX\[^]

v

U³SÚÕÖo"WX\TVU0Y ZX<be[3X\ZVU TBj(ZVU+be[xZ`aURÜ}Ænj([aW.Z`aUm4jelVU

v

X\[aU³`4j( o

j(TVW

6 ¹

U0lZX\fcj(ZVU0ld^[tZX

v

Y0be[t;U T];U [aY0URi'beTZ`^X<l}WX\TVU0Y ZX<be[3j([aWcZ`aU [cY:j(TTygbe[gp+X\Z`

ZàUNbeZàU TSÚÕÖo"WX\TVU0Y ZX<be[alX\[¬ZàU.lBj(fgUNpj:y

°

Y$i{ÌlZVU

s ² X\[_ËÕj(m

vU ² ±${ØabeTU:jeYV`

X\[aY TVU:jelVUgX\[n[d^fmÌU Tb(iRSÚ*Öo"WX\TVU0Y ZX<be[al.p}UcY:j(TTy¬p+X\Z`ndalZ`aUcU0lVZX\fcj(ZVU0lb(iÜ}

Æìj([aW

6 ¹

{Ë³`^X<lufgbWX Y:j(ZX<be[_b(iáj(T8~ãl

s

TVbY0U0Wd^TVUX<lfcj(X\[

v

ykj

v

];beTX\Z`^fxX<Y:j

v\v

y

fgbeZX\ej(ZVU0W~{HÖtX\[aY0UZ`aU

TVlVZRi'U pÍSÚÕÖo"WX\TVU0Y ZX<be[alb(iZVU [p+X

v\v

U$ZTBjeY ZHfgb>lZHb(iZ`aU

X\[ibeTfcj(ZX<be[ÈiTVbef Z`aUgWaj(ZBjÕbed^Tj

s^s

TVb;jeYV`np+X

v\v

fgbeTVUxTBj

s

X<W

vy [aW_TVU:jelVbe[4j(m vU

U0lZX\fcj(ZVU0l}b(iÌZ`aURm4jelBU

v

X\[aU+`4j(Aj(TVWj([aWcZ`aU

v

X\[aU:j(T

s

TVU0WX<Y ZVbeTVl:j([aWgZ`aU TVU$i'beTVU+]>X\;U

i'jelZVU TRY0be[t;U T];U [aY0U>{

iup}U

v

bbej(ZxZ`aUid

v\v

b0

v

X\;U

v

X\`abtbW

° ² ±p+X\Z`· ¥

ÂTVU

s^v

jeY0U0W¯my×Ý1p}U

lVU0UrZ`4j(ZhjeW^WX\[^]jŸ0be[alVZBj([ZZVb¨ZàU Ýlj([aWld^m^ZTBjeY ZX\[^]ZàUlBj(fgUkY0be[alZBj([Z

iTVbef Z`aU

v

be]m4jelVU

v

X\[aU`4j(Aj(TVWnX\[aY TVU fgU [ZVl:

v

be]

Q 6 ¹

+9'Ï¤$

v

U:j:;U0lZ`aU

v

X\;U

v

X\`abbtW

d^[aYV`4j([^];U0W~{Ë³`^X<lfgU:j([al³ZàU TVUHX<l+j([X\[aWÛ ZVU TfxX\[4jeY yX\[ZàUuU0lZX\fcj(ZX<be[qb(iZàU0lVU

Z"p}btd4j([ZX\ZX<U0l:Õp+`^X<YV`np}UgTVU0lBb

v

;Ugmy¬Z`aUgY0U [tZVU TX\[^]kX\[nlZVU

s °

Waú;±zb(i+Z`aUcj

v

];b(o

TX\Z`^fr{cË³`^X<lY0U [tZVU TX\[^]kfcj(;U0l H %

¬'Õ

U

Ý+ ä^Y0beTTVU0l

s

be[aWX\[^]ZVbqZ`aUxY0be[alVZTBj(X\[Z

H %

('Õ

U

Â ¥ · ÷äcX\f

s

b>lVU0Wbe[Z`aU

v

X\[aU:j(T

s

TVU0WX<Y ZVbeTVlzb(i}j([¬beTVWX\[4j(Ty¬b:fgbtW^U

v

p+X\Z`Y0U [ZVU TVU0WkY0b:>j(TXj(ZVU0l:{

ØabeTcfgbW^U

v

U >j

v

d4j(ZX<be[3p+`^X<YV`p+X

v\v

mUqW^U0lVY TX\mÌU0W¯X\[âZ`aUr[aU$ZclBU0Y ZX<be[3³j([

U0lZX\fcj(ZVUhb(iRÂzwZVbe];U Z`aU T.p+X\Z`

U

ÆwX<lN[aU0U0W^U0W~{_ÐHlX\[^]Z`aUcibeTfd

vj s

TVbAtX<W^U0W®X\[

ÁHU

v\v j([aW

°

ß:ñ>ò>ò

±$4p}Ubem^ZBj(X\[Z`^X<l+my

U

Ââø

U

¥

¤ U

¡

p+`aU TVU ×

U

¡0¢0¢0¢¡

U

äu¤$

U

×

U

0¡0¢0¢0¢¡

U

äu¤zj([aW

U

×

U

e 0¡0¢0¢0¢¡

U

8äu¤"¥~dalX\[^]

Z`aU

[4j

v

U0lZX\fcj(ZVU0lHb(i*Z`aU0lVULtd4j([ZX\ZX<U0lA{

iwZ`aU TVUj(TVUz[abcj:ej(X

v

j(m

v

UNjeW^WX\ZX<be[4j

v

Y0bAej(TXj(ZVU0l÷ j0>j(X

v

j(m

v

U>4jxl

s

U0Y Xj

v

Y:jelVU

b(i*Z`aUj

v

];beTX\Z`^fÄX<lj

s^s^v

X<U0Wqp+`^X<YB`klX\f

s^v

yhbefxX\ZVlRZ`aU

°

UA±³lVZVU

s

X\[ËÕj(m

vU ² {

(11)

"[¯Z`^X<llVU0Y ZX<be[âp}Ukj

s^s^v

y®bed^TSÚÕÖâb:®fgU Z`abW¯ZVb_Zp}bÈm^TVU:jelZcY:j([aY0U TcWaj(ZBj

lVU ZVl:+be[aUkp+X\Z`¦be[

v

yâ];U [aUkU$

s

TVU0lBlX<be[fgU:jelVd^TVU fgU [ZVlhX\[ìjeW^WX\ZX<be[ZVbnZ`aU

s

jo

ZXj

v

ZX\fgU0l

°

p+X\Z`¯Y0U [alVbeTX\[^]¬X\[i'beTfcj(ZX<be[Q±$j([aW®be[aUp+X\Z` é W^U fgb(o

]>TBj

s

`^X<Y(Y

v

X\[^X<Y:j

v

>j(TXj(m

v

U0lX\[xY0be[e1d^[aY ZX<be[cp+X\Z`gZ`aU³];U [abefxX<Yj([aWxld^TX\ej

v

Waj(ZBj{

Ë³`aU0lVULWaj(ZBjNlVU ZVlRj(TVUudalVU0WZVbxY0bef

s

j(TVULbed^TfgU Z`abWhp+X\Z`qZ`aUzbeTX\]>X\[4j

v

SÚÕÖqb:

fgU Z`abtWhb(iSwj(TÛ ÜÝeÞß{

°

²>à>à>² ±${Ë³`aU

v

j(ZZVU T+Waj(ZBjlVU ZX<l+j

v

lVbNj

s^s^v X<U0WZVbX

v\v dalZTBj(ZVU

`ab:p¯bed^TwfgU Z`abtWNY:j([.mUdalVU0WZVbuX\[aY

v

daW^U+jeW^WX\ZX<be[4j

v

[abe[o];U [abefxX<Y³ej(TXj(m

v

U0lj([aW

ZVbU0lZX\fcj(ZVUld^TtX\>j

vs TVbem4j(m^X

v

X\ZX<U0l:{qæ³U$i'beTVUxp}Ul`ab:p j([aWÈWX<lVY dalVlZ`aUgTVU0ld

v

ZVl:

p}UL]>X\;Ujxm^TX<U$iwW^U0lVY TX

s

ZX<be[b(i*Z`aUzZp}bWaj(ZBjxlVU ZVl:{

! #"%$'&)(+*,.-/"0"21435&6,7&987"0,;:

Ë³`aU TVlVZRWaj(ZBj.lVU ZRY0be[alX<lZVl+b(iQÑh=<0>7>.];U [aU

U$

s

TVU0lVlVX<be[_fgU:jeld^TVU fgU [ZVlNj

v

be[^]rp+X\Z`¨ld^TX\ej

v

ZX\fgU0lj([aW¨Y0U [alBbeTX\[^]qX\[ibeTfcjo

ZX<be[iTVbefÄÒ¨j;>;?gpbefgU [¬p+X\Z`km^TVU:jelZzY:j([aY0U T:{Ë³`aUNWaj(ZBjc`4j0;UmU0U [kdalVU0Wmty

ej([ÁHbedtp}U

v

X\[^];U [Û Ü+ÝeÞ<í

°

²>à>à>é

±+ZVbcX

v\v

dalZTBj(ZVUTX<W];UTVU ]>TVU0lVlVX<be[ri'beTzb0~ãlufgbtW^U

v

° ß ±$tj([aW.X\ZY0be[ZBj(X\[aljzld^malVU Zb(iZ`aU*Ñq j@<0A;A;?z];U [aURU$

s

TVU0lVlX<be[alwX\[xZ`aU+beTX\]>X\[4j

v

°

²>à>à>² ±${Ë³`aU.Waj(ZBjhlVU ZzX\[¬ej([¬W^U.BHX8;U TgÛ ÜÝeÞ<í

°

²>à>à>²

±zX<lj([¨U$ZVU [alX<be[Èb(i³Z`aUgWaj(ZBjqlVU ZLp+X\Z`ÈÒâÎD

s

j(ZX<U [ZVlX\[Èej([3ãZ/BU0U T

Û ÜÝ>Þè{

°

²>à>à>²

±$4p+`ab>lVUL[4j(fgULp+X

v\v

mÌUzdalVU0Wjel+TVU$i'U TVU [aY0Uzi'beT+Z`aUWaj(ZBjxlVU Z:{

! #"9EGFH1JILKM"N3#&6,7&O8"P,;: Ë³`^X<lRWaj(ZBjxlBU ZRbeTX\]>X\[4j(ZVU0lRiTVbefÄÖRQeT

v

X<UÛ Ü³ÝeÞ<í

°

²>à>à>ô ±

j([aWY0be[ZBj(X\[al];U [aUkU$

s

TVU0lVlVX<be[fgU:jeld^TVU fgU [tZVlciTVbef

ß¢ß

ú_p}befgU [¦p+X\Z`m^TVU:jelZ

Y:j([aY0U T:{ð¨UkdalVUZ`aU

v

X<lVZb(iú>ú ß X\[ZTX\[alX<Yk];U [aU0lX\[ZTVbWdaY0U0WX\[ìÖRQeT

v

X<U¯Û ÜxÝeÞ<í

°

²>à>à>ô ±${Ë³`aUWaj(ZBjlBU Zj

v

lVbLX\[aY

v

daW^U é W^U fgbe]>TBj

s

`^X<Y(Y

v

X\[^X<Y:j

v

>j(TXj(m

v

U0lp+`^X<YB`hj(TVU

Y0bef

s^v

U ZVULi'beT ß:à>ò b(i*Z`aU

s

j(ZX<U [ZVl:{

SUTWV X4Y[Z=\+]_^0`ba@Y[cedf`hgPijg;i+kmlonqprX4YtsuZ=k'gPiUYwvuYyxzl.]_^P{jk'gN]G|T

ð¨Up³j([ZZVbhY0bef

s

j(TVU.Z`aU

s

U T8ibeTfcj([aY0U.b(ibed^TzfgbWX U0W¬SÚÕÖ_b0fgU Z`abtW¬ZVb

Z`aUubeTX\]>X\[4j

v

be[aUzb(iwS*j(T_Û Ü}ÝeÞß{

°

²>à>à>²

±${HlX\[aWX<Y:j(ZVU0WhX\[ÖU0Y ZX<be[

ß

^j([aWid^TZ`aU T

WX<lVY dalVlVU0WX\[ölVU0Y ZX<be[ÍúumÌbeZ`ìfgU Z`abtW^lrdalVUZ`aU_X\ZVU TBj(ZVU0WTVU p}U X\]>`tZVU0W

s

j(TZXj

v

U:jelZ}lVtd4j(TVU0l

°

1ÙSÚÕÖ^±j

s^s

TVb;jeYB`ZVbbem^ZBj(X\[c];U [aUY0bU$ÉcY X<U [Z³U0lZX\fcj(ZVU0l:tm^d^Z}bed^T

fgbtWX U0WÈ;U TVlX<be[nj

v\v

b:pRlibeTlVU

s

j(TBj(ZVUgU0lZX\fcj(ZX<be[b(iZ`aUxm4jelBU

v

X\[aUg`4j(Aj(TVW_TBj(ZVU

jel+p}U

v\v

jelRY0btU$ÉcY Xj(TXj(m

v

U0lÎXßij0>j(X

v

j(m

v

U>{

HlZ`aULfgU Z`abWrb(iS*j(TnÛ Ü³ÝeÞß{

°

²>à>à>² ±+W^bU0l+[abeZHj

v\v

bApöi'beTRX\[aY

v

dalX<be[b(i*[abe[o

];U [abefxX<YWaj(ZBjtp}URp+X

v\v be[

v

yNdalBU+Z`aU+];U [aURU$

s

TVU0lVlX<be[g>j(TXj(m

v

U0l}X\[gZ`^X<lY0bef

s

j(TXßo

lVbe[3{ÕË³`^X<l*fgU:j([alwZ`4j(Z*p}Up+X

v\v

j

s^s^v yZ`aUl

s

U0Y Xj

v

Y:jelVUb(iQbed^T*fgU Z`abtWNp+X<YV`xbefxX\ZVl

Z`aUÆ_U0lZX\fcj(ZX<be[xlZVU

s

X\[

°

UA±b(iQbed^Tj

v

];beTX\Z`^f

°

ËÕj(m

vU ² ±${Õð¨U TVlZ*WX\X<W^U³jWaj(ZBj

lVU ZzX\[ZVbhZ"pb

s

j(TZVl:3be[aUhÜL}ÝJ~MH~M20Û Üwb(i³j(mÌbed^Z ² ô b(i}Z`aU.Waj(ZBjcibeTLU0lZX\fcj(ZX<be[

j([aWbe[aUNÜ"Û Ü50Û Üb(iZ`aUHTVU0lZb(iÕZ`aUHWaj(ZBji'beT}U >j

v

d4j(ZX<be[hbeTZVU0lZX\[^]xb(i3Z`aUufgbtW^U

v

ZZVU0Wnbe[Z`aUgZTBj(X\[^X\[^]_Waj(ZBj{Ë³`aU [p}Uhj

s^s^v y ß:à o'i'b

v

WnY TVb>lVloej

v

X<Waj(ZX<be[ZVbZ`aU

(12)

s v

ÁHbedtp}U

v

X\[^];U [

°

ß:ñ>ñ>ô

±$ãlHY TVb>lBl8oej

v

X<Waj(ZVU0W

s

j(TZXj

vv be]eo

v

X\;U

v

X\`abbW

°

Y

s^v

±³Y TX\ZVU TX\d^fr

X{U>{

Y

s^v

k¤

¹

n

'Õ Ñ [

U

Â c n e

ä ¤ 4

Ñ [ c n e U

Â c n e

ä

¤W¢

ÁHU TVUwÑ [8Â¤wW^U [abeZVU0lZ`aU

v

be]b(i~Z`aU

s

j(TZXj

vav X\;U

v

X\`abbtW

°ç ±Õi'beTZ`aU+p+`ab

v

URZTBj(X\[^X\[^]

lVU Zj([aWÑ [ñc

n e

Â¤ZàUulBj(fgUm^d^Z}p+X\Z`ZàU i oZìb

vW v

U$iZ³bed^Z:tp+`^X

vU U Â c n e

ä

X<lZ`aU

U0lZX\fcj(ZVUb(iÌÂ¯dalX\[^]z×SÚÕÖxWX\TVU0Y ZX<be[al

v

U:j0X\[^]Z`aU i oZ`gi'b

v

Wgbed^Z:{

l

X\;U [cZ`aU

fcjX\fxX\0X\[^]Y

s^v

k¤$pUU0lZX\fcj(ZVUzÂ¦iTVbefëZ`aUzp+`ab

v

UlVU ZRb(iÕZTBj(X\[^X\[^]

s

j(ZX<U [ZVl:

j([aWrW^U [abeZVULZ`^X<lU0lVZX\fcj(ZVU

U

ÂwML{

ðÜLZàU [jelVlVU0lBl³àb:pìp}U

v\v

U

ÂwMLX<lRj(m

v

UzZVb

s

TVU0WX<Y ZRZ`aULbed^ZVY0befgUb(i*Z`aUzZVU0lZ

Waj(ZBj{Ë³`^X<lRp+X

v\v

mÌULW^be[aULX\[qZVU TfglHb(i*Zp}bgY TX\ZVU TXj{

ß ±+H 1@&)([,7"087,;: "[Z`aUlZdaWyâb(iY:j([aY0U Thbe[aUkfcj0y¯mÌUrX\[ZVU TVU0lVZVU0WX\[

jelVlX\]>[^X\[^]Z`aU

s

j(ZXTVbed

s

lm4jelBU0Wkbe[kZ`aU X\T

s

TVbe]>[ab>lX<l:{HÁHU TVUZ`^X<lHY:j([kmU

W^be[aULmyqY:j

v

Y d

v

j(ZX\[^]cZ`aU

s

TVbe]>[ab>lZX<YLX\[aW^U$

°

S±b

U

Ý·

¥ U

Âw

°

ß:² ±

ibeTU:jeYB`ZVU0lZ

s

j(ZX[^X\[^]HZ`aU

s

j(ZXTVbed

s

lÕjeY0Y0beTVWX\[^]

ZVbxZ`aUTBj([^lRb(iZ`aU X\T

s

TVbe]>[ab>lZX<YX\[aWX<Y0U0l:{Ë³`aUNj(m^X

v

X\Z"yrb(iwZ`aUfgbW^U

v

ZVb

s

TVU0WX<Y Z

ZàUbed^ZVY0befgUhb(iRZàUZVU0lZNWaj(ZBjX<lZàU [®U >j

v

d4j(ZVU0Wnmy¨Z`aUìZ×>j

v

daUciTVbef j v be]

TBj([^¯ZVU0lZxi'beTgZTVU [aWj(fgbe[^]Èibed^TcU0td4j

v

lVX\:U0Wâld^m^]>TVbed

s

l:+lVU0UU>{]a{+

v

U X\[j([aW

ákbU0lVYV`tmU T];U T

°

²>à>à>ô s j(];U ²Fß

z

±}i'beT+Z`aUl

s

U0Y X Yui'beTfd

v

jxdalBU0W~{

²

±q

"P$[K&)(#P"):

H[abeZ`aU Tp³j0y_b(i³U >j

v

d4j(ZX\[^]r`abApóp}U

v\v

Z`aU.ZTBj(X\[^X\[^]klVU ZU0l8o

ZX\fcj(ZVU0lNj(TVUcj(m

v

UgZVb

s

TVU0WX<Y ZZ`aUgbed^ZVY0befgU0lNb(i³Z`aUxZVU0lZWaj(ZBjhX<lZVb

v

btbe¨j(ZZ`aU

WXßÊÌU TVU [aY0UX\[rW^U tXj([aY0UziTVbefõZ`aUz[td

v\v fgbW^U

v

b(i*Z`aULZVU0lVZRWaj(ZBj.dalX\[^]

4 j * Ñ [

c

MM

e U

ÂwML¤

4

Ñ [

c

e

Sf¤ - ¢ °

ß:ô ±

ÁHU TVUwÑ [ c

MM

e U

ÂwML¤wj([aWzÑ [ c

e

Sf¤j(TVU+Z`aU

v

be]b(ib0

s

j(TZXj

v4v X\;U

v

X\`abbW

°ç ±ibeT

Z`aUzZVU0lZ+Waj(ZBj.U ej

v

d4j(ZVU0Wj(Z

U

Âwxj([aWf3{Ë³`aU

s

TVU0WX<Y ZX<be[rX<l³];bbtWp+`aU [

°

ß:ô ±}X<l

lfcj

v\v

{

ð`aU TVU:jel}Z`aU TVlVZ}Y TX\ZVU TX\d^f1dalZ}U ej

v

d4j(ZVU0l}Z`aUY0beTTVU0Y Z]>TVbed

s

jelVlVX\]>[^fgU [ZVl:

m^d^ZHWX<lTVU ]j(TVW^lZ`aULTBj([^tX\[^]p+X\Z`^X\[Z`aUL]>TVbed

s

lAaZ`aUlVU0Y0be[aWbe[aULdalVU0lRZ`aU

Zb(i

U ;U TyrlX\[^]

v

ULX\[aWX\X<Wd4j

v

lfgbeTVUWX\TVU0Y Z

v

y;{³Ë³àU TVlZY TX\ZVU TX\d^f×fcj:yrbe[rZàUbeZàU T

`4j([aWqmUzfgbeTVUTVU

v

U ej([tZRi'beTj.Y

v

X\[^X<Y:j

v j s^s^v

X<Y:j(ZX<be[kb(iwZ`aUzfgU Z`abW^l:{

RiZVU T*`4j0X\[^]zlVZdaWX<U0WZ`aUTVU0ld

v

ZX\[^]zY TX\ZVU TXju>j

v

daU0liTVbefÃjY0bed

s^v

U³b(i4TBj([aW^bef

² bß ZTBj(X\[^X\[^]2ZVU0lZwl

s^v

X\ZVl:(p}Uibed^[aWZ`4j(ZZ`aUTVU0ld

v

ZVlpU TVU}td^X\ZVUW^U

s

U [aW^U [Zbe[Z`aU

s

j(TZX<Y d

v

j(Tl

s^v

X\Z:{wË³`aU TVU$i'beTVURpU

s

U T8ibeTfgU0Wú à WXßÊÌU TVU [tZZTBj(X\[^X\[^]2ZVU0lZ

s

j(TZX\ZX<be[al

ibeTRU:jeYB`kb(iwZ`aULZ"pbgWaj(ZBjxlVU ZVl:{

(13)

New PLS Cox Park´s PLS Cox

−4

−3.5

−3

−2.5

−2

−1.5

−1

−0.5 0

log10 p−value

Log rank test

p=0.5

New PLS Cox Park´s PLS Cox

−20

−10 0 10 20 30

Difference in deviance from null model

Deviance

Null model

New PLS Cox Park´s PLS Cox

−4

−3.5

−3

−2.5

−2

−1.5

−1

−0.5 0

log10 p−value

Log rank test

p=0.5

New PLS Cox Park´s PLS Cox

−20

−10 0 10 20 30

Difference in deviance from null model

Deviance

Null model

ØÕX\]>d^TVU ß bLæb:

s^v beZVlY0bef

s

j(TX\[^]kbed^TL[aU påSÚÕÖ¨b0_fgU Z`abW_p+X\Z`_Z`aUgbeTX\]>X\[4j

v

fgU Z`abtWb(i3S*j(TgU Z³j

v { °

²>à>à>²

±}jiZVU T

s

U T8ibeTfxX\[^].ú

à

TBj([aW^bef l

s^v

X\ZVlX\[tZVbZTBj(X\[^X\[^]

j([aWkZVU0lVZHlVU ZVlzbe[Z`aUWaj(ZBjlVU ZVlub(i>j([3ãZBU0U T

°

ZVb

sks j([aU

v

±uj([aW¨ÖRQeT

v

X<U

°

mbeZZVbef

s

j([aU

v

±${Ú3U$iZ

s

j([aU

v

l`abApRlZzo>j

v

daU0liTVbef

v

be]hTBj([^rZVU0lZuibeTuZTVU [aW_j(fgbe[^]hibed^T

ld^m^]>TVbed

s

lNm4jelVU0WÈbe[

s

TVbe]>[ab>lZX<YcX\[aW^U$~j([aW¨TX\]>`tZ

s

j([aU

v

l`ab:pRlNWXßÊ~U TVU [aY0U0lX\[

W^U tXj([aY0UziTVbefõZ`aUL[td

v\v fgbW^U

v

{æ³beZ`rY TX\ZVU TXjcj(TVUW^U0lVY TX\mÌU0WhX\[ÖU0Y ZX<be[ ç {ß {

Ø*X\]>d^TVU ß lV`ab:pRlZ`aUrTVU0ld

v

ZVlcX\[ZVU Tfglb(izmÌb0

s^v

beZVlcbA;U TZ`aUZ"pbnY TX\ZVU TXj{

Ë³`aU÷Zùej

v

daU0l+iTVbef

v

be]xTBj([^ZVU0lZVlRj(TVULl`abAp+[rX\[qZ`aU

v

U$iZ

s

j([aU

v

lAaj([aWqW^U tXj([aY0U

iTVbef [d

v\v fgbtW^U

v

X\[ÈZàUTX\]>`Z:wp+X\Z`nZàUc>j([3ãZ!BU0U T.Waj(ZBjq]>X\;U [X\[ÈZàUd

s^s U T

s

j([aU

v

lhj([aWZ`aUÖRQeT

v

X<UWaj(ZBj_X\[Z`aU

v

b:pU T:{ÍØabeTZ`aU>j([3ãZBU0U TWaj(ZBj¨pUlVU0U

Z`4j(ZZàU TVU+X<l[abeZfdaYB`WXßÊ~U TVU [aY0URmÌU Z"pU0U [cZàURZp}bfgU ZàbtW^lX\[gZVU Tfglb(i~ZàUZ

ej

v

daU0lÕiTVbef

v

be]uTBj([^ZVU0lZVlÕi'beTÕZTVU [aW~>U$^Y0U

s

ZwZ`4j(Z*bed^TwfgU Z`abW.l`ab:pRlwlVbefgU p+`4j(Z

v

U0lVl>j(TXj(m^X

v

X\Z"y;{zØabeTuZàUWÛ Xj([aY0UNp}UNlVU0UZ`4j(Zzbed^TufgU ZàbtWk`4jelHl

v

X\]>`Z

vy v bAp}U T

fgU0WXj([_j([aW>j(TXj(m^X

v

X\Z"y;{zØabeTzZ`aUxÖRQeT

v

X<UNWaj(ZBjcZ`aU.WXßÊÌU TVU [aY0U0lLj(TVU[abeZLlVbcY

v

U:j(T:

m^d^Zbed^TfgU Z`abW_`4jell

v

X\]>`Z

v

y_lfcj

v\v

U TfgU0WXj([nY TX\ZVU TXjq>j

v

daU0l:{c[ÈY0be[aY

v

dalX<be[3

bed^TufgU Z`abW¬]>X\;U0lj(Z

v

U:jelZLjelz];btbW

s

TVU0WX<Y ZX<be[aljelzZ`aUfgU Z`abW¬b(i}Swj(T¯Û ÜHÝeÞè{

°

²>à>à>²

±i'beT+Z`aU0lVULWaj(ZBjxlVU ZVl:{

(14)

ËbxX

v\v

dalZTBj(ZVU`ab:pì[abe[o];U [abefxX<Y>j(TXj(m

v

U0lRY:j([qmÌUzX\[aY

v

daW^U0WqZVbe];U Z`aU TRp+X\Z`q];U [aU

U$

s

TVU0lVlVX<be[Waj(ZBjxX\[rbed^TuSÚÕÖrb:rfgbtW^U

v

j([aWr`ab:pÍX\Zfcj0yhmUzdalBU0WqZVbgU0lZX\fcj(ZVU

ld^TtX\>j

v³s TVbem4j(m^X

v

X\ZX<U0lgpUhdalVUZ`aUqWaj(ZBj¬lVU Zxb(izÖRQeT

v

X<UnÛ ÜÝeÞ<í

°

²>à>à>ô

±NW^U0lBY TX\mU0W

j(mbA;U>{

Ë³`aU é [abe[o];U [abefxX<Yej(TXj(m

v

U0l³X\[hZ`aUzWaj(ZBjNlVU ZRj(TVUzj(];U>

v

yf

s

`h[abtW^UzlZBj(Zdal:

U0lZTVbe];U [qTVU0Y0U

s

ZVbeTRlZBj(Zdal:Zd^fgbeT+Z`^X<YBt[aU0lVlAtfgU ZBjelVZBjelX<l+X\[aWX<Y:j(ZVbeTj([aW]>TBjeW^ULb(i

WX<lVU:jelVU>{q¨w^Y0U

s

ZHi'beTLj(];U>3j

v\v

b(iZ`aU0lBU>j(TXj(m

v

U0lj(TVUY:j(ZVU ];beTX<Y:j

v

>j(TXj(m

v

U0l:{zØabeT

U:jeYV`cb(iZ`aU³ej(TXj(m

v

U0l*Îj

v

lVbj(];U>;p+`^X<YV`gpU+WX<YV`abeZVbefxX\:URX\[tZVbLb:;U T}j([aWNd^[aW^U T}ú>ú

y;U:j(TVlÎ.p}UuY TVU:j(ZVUHWd^fxfyg>j(TXj(m

v

U0l}X\[aWX<Y:j(ZX\[^].p+`aU Z`aU T+j([X\[aWX\X<Wd4j

v

mU

v

be[^];l

ZVbnj_Y:j(ZVU ];beTybeTc[abeZ:{ìÖtX\[aY0UkZ`aUq[td^fmÌU Thb(iLX\[aWX\X<Wd4j

v

lcmÌU

v

be[^]>X\[^]ÈZVbnU:jeYV`

Y:j(ZVU ];beTyÈY0bed

v

W¨mÌUctd^X\ZVUclfcj

v\v

*pUxi'bed^[aW¨X\Z[aU0Y0U0lBlBj(Ty_ZVbWX<YB`ZVbefxX\:Uqj

v\v Z`aU

Y0b:>j(TXj(ZVU0luU$^Y0U

s

ZRiTVbef

v

yf

s

`[abW^UlZBj(Zdalzj([aWrZd^fgbeTHZ`^X<YV[aU0lVl:Qp+`^X<YV`p}U TVU

fgU T];ULX\[ZVb ô ]>TVbed

s

l:{

"[j.Y

v

jelBlX<Y:j

v

lVU ZZX\[^]xp+`aU TVU

s

TVU0WX<Y ZX<be[alHj(TVUzZVb.mÌULW^be[aUuiTVbefõY

v

X\[^X<Y:j

v

ej(TXßo

j(m

v

U0lbe[

v

y;*be[aUgp}bed

v

WÈ[4j(Zd^TBj

v\v

y¨lZBj(TZbed^Zmty [aWX\[^]jqld^malBU Zb(i³lVX\]>[^X Y:j([Z

Y0b:>j(TXj(ZVU0lxmylVbefgUej(TXj(m

v

UqlVU

v

U0Y ZX<be[

s

TVbY0U0Wd^TVU>{¨ð¨UhW^bZ`^X<l.mynm4jeYVpj(TVW

lVU

v

U0Y ZX<be[34X{U>{4my TVlZuU f

s^v

b:yX\[^]beTVWX\[4j(Tyqfd

v

ZX\ej(TXj(ZVUxb0rTVU ]>TVU0lVlVX<be[kbe[j

v\v

Z`aU+Y

v

X\[^X<Y:j

v

Y0b:>j(TXj(ZVU0l:;Z`aU [cTVU fgb:X\[^]Z`aU

v

U:jelZlX\]>[^X Y:j([tZY0b:>j(TXj(ZVU>tj([aW

s

TVb(o

Y0U0U0WX\[^]kZ`aUlBj(fgUgp³j0y_d^[ZX

v

jrY0bAej(TXj(ZVUlVU Zp+X\Z`be[

v

y¨lX\]>[^X

Y:j([Z.Y0b:>j(TXj(ZVU0l

TVU fcj(X\[al

v

U$iZ:{gË³`^X<l

v

U:jeW^lZVbrjqld^malVU Zb(i³be[

v

lZBj(Zdal

°

àPª

¨ÙÄ[aU ]j(ZX\;U>

ßª

¨Ù

s

b>lX\ZX\;UA±xj([aW®]>TBjeW^U

°

àPª

`^X\]>`]>TBjeW^U>

ßª

v

b:p

]>TBjeW^UA±$wp+X\Z`nY0bU$ÉcY X<U [Z.U0lZX\fcj(ZVU0lä¢«A@<

°h¬

ºëä¢«;?;±j([aW

4

ä¢«>;

°h¬

ºh ä¢<;ä±$

TVU0l

s

U0Y ZX\;U

v

y;{

ðÜ_[ab:p pj([ZZVb¯X\[;U0lZX\]j(ZVU¨p+àU ZàU TX\[aY

v

daWX\[^]âZ`aU¬];U [abefxX<YÈej(TXj(m

v

U0l

j v

be[^]rp+X\Z`Èbed^TY

v

X\[^X<Y:j

v

ej(TXj(m

v

U0l

v

U:jeW^lLZVbqX\f

s

TVb:;U0W

s

TVU0WX<Y ZX<be[al:{cËÕbrW^bqZ`^X<l

p}UqdalVUqjkm^X\ZgWXßÊ~U TVU [ZcU >j

v

d4j(ZX<be[

s

TVbY0U0Wd^TVUhZ`4j([¯ZàUqbe[aUqWÛ0lVY TX\mU0W®X\[¯ZàU

s

TVU tX<bedallVd^malVU0Y ZX<be[3>X\[.p+`^X<YV`xpU>WdaUZVbuZ`aU³TBj(Z`aU Tlfcj

v\v

[d^fmÌU Tb(i

s

j(ZX<U [ZVl:

U f

s^v

b:yY TVb>lVloej

v

X<Waj(ZX<be[kZVbgZ`aUp+`ab

v

UWaj(ZBjglVU Z:4TBj(Z`aU THZ`4j([c1dalVZRZ`aUZTBj(X\[^X\[^]

lVU Z:ZVb [aWZ`aULb

s

ZX\fcj

v

[td^fmÌU Tb(iÕSÚ*Öo"WX\TVU0Y ZX<be[alRi'beT³Z`aUH];U [abefxX<Yz>j(TXj(m

v

U0l:{

ØabeTHfgb>lVZb(iZ`aULi'b

v

W^lHbe[aUbeTRfgbeTVUSÚÕÖo"WX\TVU0Y ZX<be[alupjel

s

X<YV;U0Wbed^ZX\[aWX<Y:j(ZX\[^]

Z`4j(ZX\[aY

v

daWX\[^]®Z`aUk];U [abefxX<Yk>j(TXj(m

v

U0l

v

U:jeW^lcX\f

s

TVbA;U0W

s

TVU0WX<Y ZX<be[al:{÷Ë³`^X<lcX<l

Y0be[ TfgU0WnmtyÈËÕj(m

vU ô p+`^X<YV`¯l`ab:pRlNZ`4j(ZNZ`aU

v

be]eo

v

X\;U

v

X\`abbW~wp+`^X<YV`®`aU TVU>*ibeT

mbeZ`¯Y0b:>j(TXj(ZVUhfgbW^U

v

l:wX<l.ld^fxfgU0W¯b:;U T.Z`aU

v

be]eo

v

X\;U

v

X\`abtbWej

v

daU0lxb(iHZ`aU

ß:à

v

U$iZ8o"bed^Z

s

j(TZVlcX\[Z`aUY TVb>lVloej

v

X<Waj(ZX<be[3+X<lcX\[aY TVU:jelVU0WiTVbef

4

7Ae¢«®¨ZVb

4

DJ>¢=ä

jiZVU TNX\[aY

v

dalX<be[¯b(iRZ`aUc];U [abefxX<Y>j(TXj(m

v

U0l:{ð¨Uj

v

lBb[abeZVUZ`4j(ZZ`aUY0bU$ÉcY X<U [Z

U0lZX\fcj(ZVU0lYB`4j([^];Uj

v

X\ZZ

v

Up+`aU [Z`aU];U [abefxX<YfgU:jelVd^TVU fgU [ZVlj(TVUX\[aY

v

daW^U0W~(p+`^X<YV`

X<l

s

U T`4j

s

l.p+`4j(Zxbe[aUfxX\]>`ZxU$

s

U0Y ZgjelNX\[ibeTfcj(ZX<be[âbe[Z`aUhY

v

X\[^X<Y:j

v

ej(TXj(m

v

U0l

j(TVUrY0be[ZBj(X\[aU0WX\[âZ`aUq];U [aUrU$

s

TVU0lVlX<be[al:}m^d^ZxX\ZgX<lgtd^X\ZVUqX\[tZVU TVU0lZX\[^]ÈZ`4j(ZgZ`aU