(1)Comparison of the effects of low childhood socioeconomic position and low adulthood socioeconomic position on self rated health in four European studies. Martin Hyde, Jakub Hrkal, Maria Melchior, Floor van Oort, Simone Weyers. To cite this version: Martin Hyde, Jakub Hrkal, Maria Melchior, Floor van Oort, Simone Weyers. Comparison of the effects of low childhood socioeconomic position and low adulthood socioeconomic position on self rated health in four European studies.. J Epidemiol Community Health, 2006, 60 (10), pp.882-6. �10.1136/jech.2005.043083�. �inserm-00108382�. HAL Id: inserm-00108382 https://www.hal.inserm.fr/inserm-00108382 Submitted on 4 Feb 2010. HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés..
(2) HAL author manuscript.
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(113) f V @P'FVWGW
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(116) ]@,A*]p0M/AGd?> ; AjF U%W
(117) P, P'H; *MH*d+
(118) l tH0F@d2> @,A*M/@^d+VH%F V@,
(119) Vt; AF]P, W `*z = W*MGx
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(121) W*=jl n
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(124) l EV@,P^d?>7=+H$d xGWAjFH A$>+d EVjW dHg2;k>2VjH =V;%FtNGHH A]@,A z i UP,;*d(d l wiWjM>2@,AH6AjWAj a;AM;TP l
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(126) @,P,P'HF a];A$M;P lGl ` Ha]@'W= MGA
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(137) FCVjH;Pr>2V] U%W
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(140) W ]Hd?>/>2V@=F Wg/>2VH0F@d?>2= @RNM> @RW!A t;$d UWA
(141) d+@'FH =+H%F ;dxGWW=7VH;Pr>2V*VH0F@^d?>2= @NM> @,WA/d"Wg7U V@P F*VWGW
(142) F `*z 7lG;F$MGPr>2VWGWGF `$z ; AjFExWW=VH;Pr>2V @,A H;UV]Wg >2VjHCd+;a]x
(143) P'H$d ; =+H6x=+H$dHA$> HFE@,AC> ;kNGP'H . . HAL author manuscript. inserm-00108382, version 1. A;P1DdH$d. V*=+HH0P,W
(144) @'d?> @,U6=+H =+Hd(d+@,W
(145) A]a]WGFHP^d ]H=+H0UWA
(146) d?>2=2MU> HF0>2W> H$d2>
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(148) FEWAExjWW="d+HP,g2?=+;k> HFEVjH;Pr> V]@,A];F$MPr>2VjW
(149) WGF
(150) q A0>2VH6g2@1=d?>atW
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(152) FHPG a]WGFHP q q q [NW$>2V]U V@,P'FVjW
(153) WGF]; AF];F$MGPr> VWGWGF `*z tH =+H6@AGUPrMFGHFC>2WGH(>2VH =K 0A;P,DG d+Hd ]H=+H0U; = =+@,H%F W*M*>"dH xG; =+;(> H PD g2W="a]HA];A!F tWa]HAjljM d+@,A* H@r> VH =[>2VjH ` > ;(>2@d2> @RU;P*;U LG;GHg2W= ` W
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(155) '*)+& - 0
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(158) U V@'P'FVjW
(159) WGF `$zi` | ~
(160) }G¢~ P,W
(161) ;F$MPr>2VjW
(162) WGF `$zi` G |
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(165) UV@P'FVGWWGF `*z ];$d =+H P,;k> H%FO>WExWW=od+HP,g =+;k> H%FCVH;Pr> V]@,AFH xGHAFHA> PD Wg7;F$M/P¢> `*z =H P,;k> HF0>2Wd+HP,g 2=+;k> HFEVH%;TP¢>2V @,AEY =+;AjUH0 \6w G*+lGCHK=+ a ;A*D \6 w ¢|*"; AjF>2VH y Hk>2VH=8PR;TAjF d \iw 2;kNGP'H6+
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(167) ; AjFO>2VjH y HK>2VH = P';AF
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(169) P';AF] \6 w ¢|+l
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(171) d \6 w ¢|
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(180) FHP q
(181) P,
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(183) F `z0` Z/dV@
(184) V UV@P'FVjW
(185) WF `*zi` , Q o: WGFH P q q
(186) PR W ;F$MPr>2VWWGF `$zi` ZdK V@,
(187) V ;F$MPr> VWGW
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(199) P,
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(203) WF `*zi` ,
(204) Q"o: WGFH P q q
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(206) V ;F$MPr> VWGW
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(208) A@'g?@'U;A$> ;k>/>2Vj"H !$# r
(209) iP,H ZHTP . HAL author manuscript inserm-00108382, version 1. . (%.( '. VH6xGH =d+@d2> H AU%H0Wgd+WGU@,WG HUWAWa]@U0@,AGH $M;P@r> @'H$d ]@¢> V@,A]a ;TA*D z MG=+WxGH; AtUWjMGA>2= @,H$dl
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(211) ]HKZGH =+l >2WOWjMG=LAj W OP,HF*GHl*>2VH=+H6V;kZH NHHTAOAWU= W/d(d?A;k> @,WAG;PGUW
(212) aExG; =+@^d+WA
(213) d Wg/>2VH6=HTPR;k> @RWA/d+V@,xENGHk> tHHA P,
(214) W UV@,P'FVjW
(215) WGF]; AFEP,
(216) W ;F$MPr>2VjW
(217) WGF `*z WAOVH;Pr> V]P,; > H =[@,A]P,@g H* q AC>2VH0;kN dHAUH0Wgd?MUV];Cd?>^MF*Djl tH0;k>> H aOx*> HF>2W H xGP,W=+Hv>2VjH$d+H6x=W
(218) UHd(d+Hdo@,A]g2W*MG=" H G@?d2>2@1AAj;k> @RWAj;TP d+;a]xGPHd NDtV; =+a]W
(219) A@^d+@,A WjMG= =+H$d xGHUk>2@ZH0a]H;*d?MG=+Hd"Wg `*z ; AjFd+HP,g ?=;k> HFEVH;Pr>2V f WA$>2=+;=?DC>W]WjMj=V*D*xGW*>2VHd+H$dl
(220) P,
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(222) F
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(224) U@,;k> H%F O@r>2VExGWGW*=VH%;TP¢>2VC>2V;A]U V@'P'FVjW
(225) WGF]U @=+UkMa3d?> ; AjUH*dK VH$dHg2@,AGF@,A d"; =+H0U%WAGd+@d2> H A$> O@r>2V]W$>2VjH =d?>^MF*@,H*d[>2Vj;k>d V
(226) W ZG;=8@R;k> @RWA]@,AC>2VH0(H > H A$> ; AjF a ; GA@r>^MFH0WgdW
(227) U@,;P/@,AG H $M;P@¢> @'H$d"@,A]VH;Pr> V];U =W ddo@,AGF$M d2>2= @,;P@ u HF]UW*MGA$>2= @HdQK V@d"a ; DENGH%l
(228) @,A xG; =?>ljNHU;kM dH >2VH0F@d?>2=+@N*M> @,WA
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(230) ;AF @¢> V;*d[NHHTA d?MGGH$d2> HFC>2V;k>G>2VHCd xGHU@1g @U0FHK> H = a]@,AG;TA>+d"W*g[@,AG H $M;P'@r> @'H*d"a]; D AW*>/NGH0@,FHA$> @,U;PG@1A H;%UTV A;K> @,WA X TBO
(231) W ]HKZGH =+l@r>7@^d"@1A> H =+H$d2>2@,A*E>2V;k>>2VH ZG;=8@';k>2@'WAE@,AC>2VH0a ; GA@r>^MFH0Wg/>2VjHCd+@
(232) A@'g?@'U;A$> ;$dd+WG U@,;k> @,WA
(233) dd+Vj W tHFEGH AFGH ="F@,g?g H =+HAU%HjdTYW= OWa]HAl
(234) @,A UW*MGA$> = @,H*d OVGH =+H `*z @d";d(d+WGU@';k> H!F E@¢>2V xGWW=[VH%;TP¢>2V] z A*GP;AjFl y Hk>2VH=8PR;TAjF d ; AF] H =+a;A*D+l*>2VH =H ];$d ;6=+H P,;k> @ZGH0VW
(235) atWGH AjH@r>?DtW
(236) g/>2VH . 7.
(237) HAL author manuscript inserm-00108382, version 1. ?d >2=H A**>2V]Wg/>2VH0;$dd+WGU @';k>2@,WA/B]W
(238) tHkZGH =lg2W=a]HAC>2VHCd >2=H A**>2VOWg7;$dd+WGU@;K>2@,WA/d d+VW
(239) ]HFEa]W=+H Z; =+@;% >2@,WA/ q A];FF@r> @,WAl*>2VH6=+H$d2MGPr>+d=+HKZGH;P
(240) @,A$> H=+H$d?> @,A*]AG;k>2@,WA;PF@,g g H =+HAjUH*do@,AC>2VjH6GH AFH=+HFExG;k>^> H = AOWg ;$dd+WGUT@R;k> @RWA/d q A> H =+H$d^>2@,A*GP1D AjHT@¢> VjH =oPR W `jz @,A]UV@P'FVWGW
(241) FCAjW=@,A];%F$M/Pr>2VjW
(242) WGF t;$d";$dd+WGU@,;k> H!F ]@r>2V xGWW=[VH%;TP¢>2V g2W= tWa]HA]@,AC>2VH Y =+HAUVd+;a]xGPHTBt W OHKZGH =[>2V@^d"@^do@,A]P,@,AGH ]@r> V]W$>2VH ==H$d+H;=+U V ;a]WA* ]WGa]HA @,AC>2VjH0 z n d2>^MFjD X (V@^d"UW*MGP,Fl
(243) @,AExG; =2> ljNH0F$MHv>2W0>2VH0g2;Uk>/>2Vj;k>/>2VH OWa HA @,AC>2VH6Y =+HAjUTV d?>^MF*D]; =H0F*=+ ; OA g^=Wa ;A]WGUUkMGxG;k>2@RWAj;TPUWVW=> OV@,Pd2>/>2VW/d+H6@,AC>2VjH0W$>2VH ="U%WjMGA>^=?D d?>^MF*@RHjd ; =+H6GH AjH =+;PxGWx*MP';k>2@,WAd+;a]xGPH*d MH >2W>2VjH6A;k>^MG=H6Wg >2VjHCd?>^MF$Djl*>2VH =+H0;=+Hv> OW]a]Hk>2VWGFWP,WG@,U;PUWA
(244) d+@'FH =+;k> @,WA
(245) d[>2Vj;k>7AHH%F >2WCNH > ; LGH A]@,A$> W];UUW*MGA$> VjH =+H0; =H6@dKd?MH*d[>2Vj;k> ;k=+H0UWa atW
(246) AC>2W ; P,P
(247) P'@g HUW*MG=(d+HCd2>^MF*@,H*d"; AjF W*>2VH= @^dKd?MH$d7>2V;k> ; =+H0UWa atW
(248) AC>2W ; P,PGU =+W/d(dAj;k> @,WAj;Pd2>^MF*@H*d*\6MG=a]H;$d2MG=+H*d"Wg[UV@,P'FVjW
(249) WGF `$z =+H P,@'HF MGxGWAE=+H(>2= W/d xGHUK>2@rZH6=+HU;P,P ]V@'UTV]a]; D]NGH0@,a]x/H =+g2HUK>[X q >7@d=+H;d(d?MG=+@,AGl*>2VH Ajlj>2Vj;k>"d>^MF*@RH$d"UWA F$MUk> HFE@,AC>2VjH mEA@r> H%FOpO@,AGFW
(250) a ;AF]@1A >2VH mOA@r> HF ` > ;k> H$dd V
(251) W >2Vj;k>7a]Ha]W=8@RHjd Wg xG;$d2>odW
(252) U@,W
(253) H%UW
(254) AWGa @'U0U@=+UKM/a3d?> ;AjUH*d[> H AFC>WONH6=+H P,@'; NGPH _ _ I y WAHk>2VjHP,H*d(d+lxG; =?>2@RUT@,xG;A$>+d ]@r>2VC>2VjHa]W/d?>F*@d;F ZG;A> ; GHF]U@=+UkMa3d?> ; AjU$Hdoa ; D]Vj;%ZH0g2;@P'HFC>2WE=+HxGW*=>/>'VjHT@,="g2;k>2VH= ?d"WGUUkMGxG;k>2@RWA jg2W=@,A
(255) d2> ; AUH > H A xGH ="UHA$>7Wg/>2VH Y =+HAGUTV d+;a]x
(256) P'H0F@,F AjW$>[@,AjF@'U;k> H >2VjH@=g2;k>2VH= ^d +WNl
(257) ; AjFd+@1AGU%H >2VH !D tH =+H0a]W=+H P@,LGHP1D > WE=+H xGW*=^>7xWW*=VH%;TP¢>2V] F;k> ;0;kZ;@1P'; NGP'H0WAO=+ H $MH$d2>2>2V*@^d"F;K> ; ];$d x= W*NG;kNGP,D AW$>7a]@dKd+@,A ;k> =+; AjFW
(258) a3\iZH =+;PPRl
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(260) W t; =+F
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(283) W ]HKZGH =g2 H d?>^MF@,H*d"@1g7;A*D UWGP1P'HUK>[=H>2= W. . . 8.
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(395) x=+W d xGHU(>2@RZHCd2>^MFTDtW
(396) g/>2VH0a]W*>2VH =(d Wg/>2VH
(397) }0hs= @r> @d+V h0@ =?>2V f WVjW=^> a]H =+@'U;AEJKW*MG= A;PGW
(398) g/ MNGP@'U BtH;Pr> VE/
(399) ,j
(400) 8} |( KG* * Bt; = xGH = ` l n DAUVEJljB d?M]b n l z ZGH =(dWA ` l*B]@,P,P'H$a H@H=[: :<l*wi; GV$MA;k>2Vj;TAt z H> ; P^ n @1g H UW*MG=(d+HCd WGU@,W
(401) H%UWAjWa]@'U0UWAF@r> @,WA/d ; AF];F$MPr>7x/d DGUVW/d+WGU@,;P
(402) g^MAUk> @,WA@1A q A> H = A;K>2@,WAj;P JKW*MG= Aj;TPGWg z xG@,FHa@RW
(403) P,WD]G* , ?
(404) ?G 2G* n ; ]PRW= l z N=+;V@a ` l ;kZH%D ` a@¢>2V] F*ZGH =(dHCdW
(405) U@,WGHUWAWa]@'U6xGW d+@r>2@RWA];%U =+W/d(d[>2VjH P@,g HUWjMG=d+H6@,AGU =+H;d+H*d"UW= WA;=DOVGH; =2>F*@'d+H;$d+H6=+@^d L UkMGaEMP';k> @ZHTP,D7*g2@1AGF@,A/d"g^=+W
(406) a>2VH hs=+@r>2@^d+V tWa]HA dVH; =?> ; AjFEVH;Pr>2Vd2>^MFjDJKW*MG= A;PGW
(407) g z x@,FGHTa]@,WGP,WDt;TAjF f WGa aEMA@r>2DCB H%;TP¢> V G
(408) ,G r~
(409) } ~ 2 K h0PR;TAGH l*B]; =^> fon l ` a]@r> V] lGC@,P,P@^d f w0l*BtWP,H JKl*Bt ; C>2VjW= AH 0: Ed(d+WGU@,;k> @,WA]Wg U; =F@,W*ZG;*dUkM/P'; ="F@dH$;d+H6=+@^d Lg2;%Uk> W=d E@¢>2Vd+WGU@,W
(410) H%UWAjW*a@'U6xGW/d+@r> @RWA]F$MG=+@,A* U V@'P'FVjW
(411) WGF]; AF F$MG=+@,A* ;F$MPr>2VWGW
(412) FGThs= @¢> @d+V :<HF@'U;P
(413) JWjMG= Aj;P | , ~~* K G( K }j 2 p0MV l*Bt; =+F*DCwil n ; A*GHA*NH = f l*w6@RUTVG;=+F
(414) d[:<l*b;F d ]W=^>2VC: z J: W=^> ; P,@r>2D]@,A;%F$M/Pr>+d ; GHFEG|8EDjH; =d=+HP';k> HF>Wd W
(415) U@,W
(416) H%UWAjW
(417) a]@'U0UWAjF@¢> @'WA
(418) d"@,A]UV@1P'FVWGW
(419) F]; AjF];F$M/P¢>2VWWGF xGW/d> t; =NG@ =?>2V]UWVW=> d?>^MF$DThs=+@r>2@^d+VC:HF@'U;PGJKW*MG= A;PG* , / ~ ~* ~|(
(420) }/ 2 Bt; =?> f n ljBOWP,H JKl ` a]@r>2V] q Ag2PMHTAjUH0Wg dW
(421) U@,WGHUWAWa @'U0U@=UkMa3d?> ; AjUH*do@,A]H%; =+P1Dt;TAjF P';k> H =P,@g H0WAd?>2= WLGH5= @^d L ;a]WA*a HA]@,A]; ` UW$>>2@d+VtUWVjW=2>d^>^MF$D/ ` >2= WLGH G , G G~/ 2 :<;=8atWj> :<l ` V@xGP'H DE:<l*hs=?MGAAH = z l*B]H a]@,A
(422) t;%DOB3wiHTPR;k> @ZH0UWA>2= @N*M> @,WA]Wg7H;=8PD P@,g H ; AjF ;%F$M/Pr>"dW
(423) U@,WGHUWAWa]@U0g2;Uk>2W=(d >2W];F$MGPr> a]W=?NG@,F@r>?D @,AC>2VjHib V@¢> HTVj;PP q q d2>^MF$D/JKW*MG= Aj;TP Wg z xG@,FHa@,W
(424) PRWD];AjF f W
(425) a]aEMA@r>?D BtH;Pr> VOG *,G8 ~
(426) 2/ F;a3doJljbV@r> H :<l* H; =+UH : ` l$ ; = LGH = n n @,g H0UW*MG=(dHa]H%;jd2MG=+H$d"Wgd+WGU@,W
(427) H%UWAjWa]@'U xGW/d @r> @,WA];AFd+HP,g[=+HxGW=^> HFEVH;Pr>2Vt;k> ; GHC Tx= W/d xGHUk>2@ZH0UWVjW=^>"d^>^MF$D/JKW*MG= Aj;TPGWg z xG@, FHa]@,W
(428) P,WD ;TAjF f Wa]aEM/A@r>2D B H;Pr> VEG* ,
(429) } */}( *G/ 2G|* z Pd2> ;FEJ q f V@,PFVWGWGFE;F$ZGH=(d+@r> @,H*d";AFEVH;Pr> VEZG; =+@';k>2@,WA
(430) d ;TatW
(431) A* a @'FFP'H ; GHF]a HTA *;6=+Hk> =+W/d xGHU(>2@ZGH0P@,g H$U%WjMG=(dHCd?>^MF$D z MG= WxGH%; AEJKW*MG= Aj;TPGWg/[MNGP'@U BtH;Pr> VEG
(432) , ( KR +}G 11.
(433) HAL author manuscript inserm-00108382, version 1. 2G~* q FP,H = z n ljhiH A*D;a @,AG@ ` HP,g2?=+;K> HFEVH;Pr> V]; AjF a]W=?>2;P,@r>2D7* =+H ZG@'H Wg/> tH A$>2Dj8d+H ZGHA UWa]atMA@r>2D3d?>^MF*@'H$d$JWjMG= A;PGWg/BtH;Pr> V];AF ` W
(434) U @R;TPh HV; ZG@,W=+~ , }(Kk ~/ 2/} :<WP,P'H = n ljp =+@^d?> HA/d+HA] ` l*BOWP1P,AG; GHP*B ` HP,g =+;k> HFEVGH;Pr>2V];d";6x=+HF@,Uk> W=7Wg7UW= WA;=D VH%; =?> F*@^d+H;*d+H0@,A f WxGHAV; HAl H Aa ; = L $JWjMG= Aj;PGWg z x@,F
(435) Ha]@,W
(436) PRWD ;AF f W
(437) a]aEM/A@r>2D BtH;Pr>2V | ,
(438) ?k ?/}j 2G* :<@,@PMA*xG;P,W ` l MW*= @ q l
(439) \ +; l*;d+; AGHAC:ljmO= xWAHAtB ` H P,g 2=+;k> HFEVH%;TP¢>2Vd?> ;k>^M d ;$d"; VH%;TP¢> V]a H;$d2MG=+H*VH6x=+H%F@'Uk>2@ZH ZG;PMH0W
(440) gd+HP,g ?=+H xGW=>HFEVH;Pr> Vd2> ;k>^M dWA0>2VH M d+H0Wg xV*D/d+@' U@,;Ad+H=ZG@'UH*d";AF]WA]a]W=?> ; P,@r>2D]@,AE>2VH tW= L@1AG ; GH6xGWx*MGP,;k> @,WA/JKW*MG= A;PGWg f P@,AG@U%;TP z xG@, FHa]@,W
(441) P,WD ~ ,
(442) 8kR ~8/}G * :<;=8atWj> : 0l*hsW*NG; LE: q A> Hk= Aj;k>2@,WAG;PGUW
(443) aExG; =;k> W=d7Wg xGW*ZGH =?>^Dt;AF]VH;Pr> V]@1A z MG=+WxGH hs=+@r> @'d+VC:<HF@'U;TPJWjMG= A;P
(444) G , KG K/}G K f ; ZGHP';; =(d z J8:<l*p0MA/d?> z lG HkMG=>+d7J(J+:<l*B]HP,a H =?>/mtl n MGAF*NGH = \ lj: @'HTP'U L cHk> ; P^ :<W=?NG@,F@r>2D]F@g2g H =+HAGUH$dNDtW
(445) UUKMGxG;k> @RWAj;TPGUP';*d(d";a]WGA a HA]@,Ad+H ZGHA z MG=+WxGH; A]U%WjMGA>2= @,H$dk ; A];xx
(446) P'@U%;k> @RWA]Wg/>2VH z = @L d+WA WP,F$>2VW= xGHCd+WGU @,;PUP;*ddd+UVHa H* q A$> H= A;k> @,WA;PGJKW*MG= A;PGW
(447) g z x@,F
(448) Ha]@,W
(449) PRWD
(450) } ,*G~?k G? G ";%DjP,W=[w0l f W*A t; D n l f ;P,FH = ]WGW
(451) F n l n H$dd+Wg f :<H >2VjW
(452) FWP,WD/:<;=8atWj>/:ljhi; AL/dJKl h0P¢M/AjFHTP'Pwil n H$dKd+Wg f l y ; u =+WW]JKlHF*@¢> W=(d0G n W*AFWAl q Y ` B]H%;TP¢>2!V ]H%;TP¢>2V];AF P,@'g H d?>^DjP'Hjd Wg/>2VH0WP,FH =xGWx*MGP,;k> @,WA]@1A z A*GP';TAjF/*VH6G* z A*GP,@d+V n WA
(453) @r>^MF@,AG;P ` >^MF$DtWg 0GH@,A hiWAjHAg2;TA> ` l f MG=H> H P,P@'UH =[:l
(454) WPRFjNH = E:<l*pO;A@ H 3d LG@ y l n HUP'H =++U l
(455) \ u *MP,H = cHk> ;P^ n ;0UWVjW=^> H0 ; u H PGFH$d Gl1CZW
(456) P,WA$> ;@=+H$d* AA H K 0G* ; = @dl q y `*z w :{mEA@r> }}G Bt;T@^d LGHTAj H y H Jo l*Y =+@,U L]JowO H$d L*>2WxUWaExG;A@,W
(457) AC>WO>2VjH0CH= a];A ` W
(458) U@,WG z U WAWa]@'U ; AHP ` >^MF$D/ G ThiH = P1@,Ajl ` \ z :<;%U LGHA*NG;UVEJ+l O; AFGHa VGH%HTA B]l ` >2= WAL/d[p * x=+W
(459) d xGHUk> @ZGH0UWVW=>"d^>^MF$D]@,A*ZGH*d2> @G;K> @,A* >2VH0 H xGP;Aj;k> @RWA]Wgd+WGU@,W
(2) HAL author manuscript.
(3) "!$#% !'& &(% *)+% ( ,+ &-!'$# & ./!,+ & (% *)+% 0 1+ '-( !,2) *+%&- *!,+ 3 . 546.7 8.& '(9 J Epidemiol Community Health 2006;60(10):882-6. HAL author manuscript. :<;=?>2@,ACBEDGFHEI JK;L*M
(4) NEBO= LG;PQ :<;=8@R; :SHTP'UV@,W=X Y7P,WGW=[Z; A]\ W=^> _ ` @,a]WGAH bcH DGH=(d"e. inserm-00108382, version 1. I f H A$>2=H6g2W=[hiH Vj;kZG@,W*MG=+;P/;AF ` WGU @,;P ` U@'HAUH*d"@,AC:SHF@,U@1AGH%ljm fon ljmEp Qq AGd?>2@r>^M> HsWg/BtH;Pr>2V q Ag2W=+a];k> @,WAt;TAjF ` > ;(>2@d2> @,U*d"Wg/>^VjH fvu H$UVCwiH x*MGNGP,@'U X q^y `$z w :{m]|
(5) }~ q Y/wi|l ` ; @,A$> ^:<;kMG=+@,UH%ljY =;TAjUH _3 H xG;=?>2a]HA$>Wg]MGNGP@'U B]H;Pr>2Vjl z =;$d+aEM d-: f lCmOA@RZH=(d+@r>2D:<H%F@'U;P f HTA> H =3w0W$>'> H =+F; atl>2VH y HK2> VH =+P,;AF/d e H xG; =^>2a]HA$>7g2W=[:HF@,U;P ` WGU@,WPRWDjljm]A@ZH =d+@r>?DtW
(6) g C dd+HP'FW= g2lG H =+a];A*D f W= =+H$d xjWAjF@,A;KM>2VW= :<;=?>2@,ACBEDGFH f HA$>2=+H6g2W=[hiH V;kZG@RWjMG=+;P;AF ` W
(7) U @R;TP ` U@'HAGUH$d"@,At:HF@,U@,AGH mOA@RZH=(d+@r>2D f W
(8) P,PHGH n WAjFWA VH bW
(9) P,g8dWACh5M@P'F@1A /}0w0@,F@,AEB]W*M d+H ` >2=HH> n WAFWACb q b~ z "HTP$ * GE~|~]
(10) z a;@,P a;=?>2@,A/rV*DFH ¡MUTP2¢;U* MGL 1.
(11)
(12) "!$#% !'& &(% *)+% ( ,+ &-!'$# & ./!,+ & (% *)+% 0 1+ '-( !,2) *+%&- *!,+ 3 . 546.7 8.& '(9 HAL author manuscript. ++
(13) . &. ` WGU @,WG HUWAWa]@U @1AGH$M;TP'@r> @Hd @1A VGH%;TP¢>2V ; =+H ; xGH =(d+@^d?> HA$> g H%;k>^MG=+H >2V*=WjMGVjWjM> z MG= WxGH*w0Hd+H; =U VH =Kd";AjFtxGWGP1@'U D a ; LGH =Kd"; =+H0@,AGU =+H;d+@1AGP1D HTa]xGP,WDG@,A ;P'@g HUW*MG=(d+H6xGH=(d xGHUK> @ZGH > W H jx
(14) P';@,At> VHd+HC@,AG H $M;P@¢> @'H$d ;AF]F@1=HUk>7xGW
(15) P,@'U%D$BtW
(16) ]HkZH =[>2VH=+HC;=+Hg H tl
(17) @g ;A*DGl/U =W dd+?Aj;k> @RWAj;TPP@g H UW*MG=(d+H0UWaExG; =+@^d+WA/do@,AC>2V@^d";=+H;*. inserm-00108382, version 1. + &
(18) Ed(dW
(19) U@,;K> @,WA
(20) d"NGHk> tHHA3d+WGU@,W
(21) H%UWAjWa]@'U0x/W/d @r> @,WA `*z 7"@1A UV@P'FVWGW
(22) F]; AjF@,A;%F$M/Pr> VWGWGF ; AjF xGWGW=Cd+HP,g2?=+;K> HFVH;Pr> V ;a]W
(23) A a HA ;AF ]Wa HA ;k>0a]@,F P'@1g H ]H =H > H$d?> HF@,A g2WjMG= z MG= WxGH;A y l,| +lY =+;AGUHC y l
(24) +lCH = a];A*D3 y Gl} +l/; AjFt>2VH y Hk>2V d?>^MF*@RHjd g^=+W
(25) a z A*GP';AF H =+P,;AF
(26) d y l} K(. (./!, vY7W= tWa]HAjlCaCM>^M;P,P1Dc;F M d?> HF ; Aj;P1D/dH*dd+VjW tHFd+@GA@g @'U;A>3;d(d+WGU@,;k> @,WA
(27) d3NGHk> tHHA xGWW=d+HP,g2?=+;k> HFEVjH$;Pr>2V ;AF]P,W
(28) `jz @,A NWj>2VtU V@P'FVWGW
(29) F]; AjF ;%F$M/Pr> VWGWGFt@,A z A*GP;AjF;AFC>2VH y Hk>2V H =+P,;AF
(30) dl5WAPD<P,
(31) W UV@'PFVWGWGF `*z c@1A CH=8a ;A*D ;AGF AH@r> VH =]UV@P'FVjW
(32) WGF AW*=t;F$MGPr>2VWGWGF `*z @A Y =+;AjUH*[Y7W=Ea]HAl5aCM>^M;P1P,D<; F M d?> HF ;A;P1DdH$dd+Vj W tHF d+@GA@g @'U;A>O;$d(dW
(33) U@,;k> @,WA
(34) dENHk> ]H%H A xGWGW*= d+HP,g ?=+;k> HFEVjH;Pr> Vt;TAjF P,
(35) W `*z @,A NWj>2V]UV@P'FVjW
(36) WGF];kAjF];F$M/P¢> VjW
(37) WGFE@1AEY =;TAjUH0;AFE>2VH y Hk>2VH =+P';AF
(38) dl WAPRD ]@r> V];F$MPr> `*z @,A z A*GP;AjF ;AjF WAP!D t@r> VtUTV@'P^F*VjW
(39) WGF `*z @,A] H =+a ;A*D/ . " !. . q A a]W/d?> U%WjMGA>2= @,H*dO;F$M/P¢> `jz # t;$dd2>^=+WA*GH=>2Vj; A UTV@'P'FVjW
(40) WGF `*z =+H P,;K> HF >W d+HP,g2 =+;k> H%FtVjH;Pr>2VlGVW
(41) ]HkZH = UTV@,P'FVWGW
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(43) U@';k>2@,WA/d NH > ]HHAUTV@'P'FVjW
(44) WGF-;AF;F$M/P¢>2VWGW
(45) F `*z 7WP1@R U@,H*d3FHd+@1GAH%F> W =+HF$MUH @1Aj H $M;P@r> @'H*d3@,A VGH;Pr>2V AGHHF>W @1AjUW= xGW*=+;(> H ;¡P,@'g HU%WjMG=(dH¡xGH =d xGHUk> @ZGH OV@UV @^dd+HA/d+@r> @ZH >2W F*@,g2g H =HTA>]A;K>2@,WAG;Pi;TAjF GHAFGH =@^dd?MH*dKom]P¢> @,a ;k> HPDl0a]W=+H U=+W dd+?Aj;k> @,WAj;$P d?>^MF*@RHjd ; =+H6=+ H $M@=+H%FO>WCNGHk>'> H =[MGAFH =d?> ; AjF>2VH$dH6x=+WGUH$d(dH*dK % &]#t & ('` W
(46) U @R;TP@1AGH$M;TP'@r> @Hd+l/d+WGUT@RW
(47) HU%WAjWa]@'U6xGW d+@¢> @,WAlVH%;TP¢> Vjl ) & " . *6N d?>2=+;%Uk>$ |+ ]W*=+F
(48) d-,$:;@1A > H *>$ j. z MG= WxGHlP,@1g HUW*MG=(dH. 2.
(49)
(50) "!$#% !'& &(% *)+% ( ,+ &-!'$# & ./!,+ & (% *)+% 0 1+ '-( !,2) *+%&- *!,+ 3 . 546.7 8.& '(9 HAL author manuscript. /+ & . + . inserm-00108382, version 1. H$d xG@r> H<WjZH =+;P,P]@a]x=+W*ZGHa HTA>+d@,A xGWx*MP,;k> @,WAVjH;Pr> Vjl d+WGU@,WG HUWAWa]@U<@1AGH$M;TP'@r> @Hd @A VH%;TP¢> V ; =+H];Ex/H=(d+@^d?> H A>5g2H;k>^MG=+H]Wga]Wd2>5@,AF$M d2>2=8@R;TP'@ u H%F dW
(51) U@,Hk> @,H*d I _K/V*=WjMGVjWjM> z MG= WxGHl xWP1@'UD a ; LGH =(dl NWj>2V ;k>>2VH z m ;TAjF-;K>>2VHE@,AGF@ZG@'F$M ;P7aHa]NGH =0d?> ;K> HCP,H ZHP,l[V; ZGHEa ;@,A$> ;@,AGH$F >2VjH@1=vUW
(52) a] a@¢> a HA$>>W=+HF$MU @,A* W=6=+Ha]W*ZG@,A->2VH*dH@1AGH $M;TP'@r> @^H$d e VjH =+H3@dFH%N;k> H; NWjM> EVjHk>2VH=0@1A> H =+ ZGHA> @,WA
(53) d @,A3UV@P'FVWGW
(54) FEW="@1A ;F$MPr>2VjW
(55) WGF OW*MGP,FtNH aW/d^>"H g2g HUk> @RZHC@,A]=+HF$MU@,A3VH;Pr> V@,AG H $M;P@¢> @'H$d q AjU =+H;$d+@,AGP1D ;U;FHa @U]=+H$dH$;=+U VGH =(di;AF-xGWP,@'U%DGa ; LH =(di; =+H ;FWx$>2@A ;P@,g H$U%WjMG=(dH xGH =d xGHUk>2@ZHt> W MGAFH=(d?> ; AjF Vj W d+WGU @,;P/F@^d+;F*ZG;A> ; GH0U; AE=H$d?MPr>@,AExWW=[VH%;TP¢>2V VH3F@g2g H=+HA$>0P,@'g HU%WjMG=(dHatW
(56) FHP^dEVj;%ZHNGH%HTA UW
(57) aEx=H VjHTA/d+@ZHP1D¡FHjdU =+@NHF ;TAjF F@^d+UkM7d(dH$F HP^d+ H ]VjH =+H ,I QKb V@P^d?>">2VH=+H @^d d?> @1P,PdW
(58) a]HFH N;k> H]W$ZGH = ]V@'UVa]WGFHP[NGH$d2>5FH$dU =+@NHjdsV
(59) W F@^d+;F ZG;A> ; GH]; AF-VjH;TP¢>2V; =+H]UWAAHUk> H%F-;U=+W dds; A@1AGF@Z/@ F$M;P ^dsP@,g H%l >2VH=+H @^dsA
(60) W ;E=
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(62) H%UWAjWa]@'U6xGW/d+@r> @RWA `*z @,AENGW$>2V U V@'PFVWGWGF-; AjF-;%F$MGPr>2VWGW
(63) F3WA;E=+; AGH Wg"VGH;Pr> VW*M*>UWa]H*d I rI X Q I BO W tHkZGH=+l dWa]H]W$>2VjH =0d?>^MF*@,H*d V; ZHg2W*MGAF @1AGFHxGHTAjFHA$>sHg2g HUk>+diWgsUV@,P'FVjW
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(89) . inserm-00108382, version 1. VH z A*GP@^d+Vd+;a]xGPH0@^d"F*=+; OA]g^=+W
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(244) d+@'FH =+;k> @,WA
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(255) d2> ; AUH > H A xGH ="UHA$>7Wg/>2VH Y =+HAGUTV d+;a]x
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(283) W ]HKZGH =g2 H d?>^MF@,H*d"@1g7;A*D UWGP1P'HUK>[=H>2= W. . . 8.
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(320) ; AjFC>2V;k> P,@'g H0UW*MG=(dH0F*@d;F*ZG;A > ; GH0; g2g2HUk>+dAj;k>2@,WA/d";AF atHTAt;TAj!F ]Wa]HA]F@g2g H =HTA> PD . .
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(322) wiHTg2H=+HAUH n @^d2> HAL author manuscript inserm-00108382, version 1. K b '@ P1LG@,A/d+WACwiCl*:<;=8atWj> : E ` WGU @,;PGFHk> H =+a]@,AG;TA>+d"WgVjH;TP¢>2V/ VjHCd+W
(323) P,@'F g2;UK>+dKAF]HF/ H Aa ; = L7$b W= P,FCBtH;Pr> V]\= G; A@ u ;K>2@,WA,G 2 p0MA/d?> z l*hsW/d l n ; VHPa ; z ljhi; =^>2P,H DE:l n @^d(d+;KM q ljwiH G@,FW= z H(> ; P^ =H AF
(324) d"@,Ad+WGU@,WG HUWAWa]@'U@,AG H $M;P@¢> @'H$d"@,A3d+HP,g ;*dd+H*d(dHF VjH;Pr> V]@,A z MG= WxGH; A]U%WjMGA>2= @,H$d q A> H = Aj;k> @RWAj;TP JKW*MG= Aj;TPGWg z xG@,FHa@RW
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(326) , G? G
(327)
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(329) 0=+WH AVjW
(330) g/Y7lGCHkMG=2>+dJ(J+:<l 0AFGH =(d+HA]\cHk> ;P^ ` WGU @,WGHUWAWa]@'U@,AG H $M;P@¢> @'H$d"@,A]a]W= NG@'F@r>?Dt;AF]aW=^> ; P,@r>?Dt@1A H$d?> H= A z MG= WxGH* n ; AUHK> ~ , G ||* |
(331) |
(332) / 2 f ; ZGHP';; =(d z J8:<l*p0MA/d?> z lG HkMG=>+d7J(J+:<l f =8@R;TP'H$d+@Gw0lG0= W$>^ZHF$> n l$B]H P,a H =?> m H> ; P^ @,g2 g H =+HAUH*d"@,Ad+HP'g=H xGW=^> HFEa]W=?NG@'F@¢>?DENDtHF$M U;k> @,WA;P
(333) P HkZGHP
(334) cUWaOx/; =+@dWAtW
(335) g vbH$d2> H = A z MG= WxGH; A]U%WjMGA>2= @,H$d$JWjMG= Aj;PGW
(336) g z xG@,FHa]@,W
(337) P,WD ;TAjF f Wa aEMA@r>2DCB H%;TP¢> V
(338) } , G? ?G~
(339) + UVH*d+WA q AFH xGHAFHA>[@, A $M/@,= D]@,A$> W]@1Aj H $M ;TP,@r> @'H*do@,AEVGH%;TP¢> V
(340) }G n WAFWAlVH ` > ; >2@,WA; = Dt\Cg g2@'U$H |* h6D=+AH z Aj;kNGP@,A]GW
(341) WGFCVjH;Pr>2V]g2W=";P,P^
(342) =+Hg2PH%Uk> @RWA]x= W
(343) UHd(d"g2W=";5A H z m VH;Pr>2V d?>2=+;k> H DCG* h6=2M d(d+HPdl z m ~* :<;%U LGHA*NG;UVEJ+l*BtW tFH A f V;x
(344) a ;AC y H xGH =(d xGHUk>2@ZGH*d"WAdW
(345) U @RW
(346) HU%WAjWa]@'U@,AGH $M;P'@ >2@,H$d"@,A]VH;Pr>2V/ H =(d xGHUk> @RZH$d"@,Athi@,W
(347) P,WD];AFC:HF@'U@,A/H6G ,G| /}?/ +} 0=+; V;a B3h5M/@,P'F@1A ; A]@,A$> H=+ F@dU@x
(348) P'@,AG; = D3d+U@'HAUH0W*g[VjH$;Pr>2V]@,AG H $M;P@¢> @'H$dkT>2VH0H ;aExGP'H Wg[P,@g HUW*MG=(d+H6=H$d+H;=+U V/ ` W
(349) U@,;P ` U@'HTAjUH :HF@'U@,AGH6G* ,
(350) K G
(351) ?G |/ * hiHA ` VP,W
(352) a]W l*p0MGV * cP1@'g H0U%WjMG=(dH0; xx= W
(353) ;UVC>2W UkV=+WA@'U0F@^d+H;$dH0Hx
(354) @,FHa @,W
(355) P,WD*UWA UH x*>^M;P
(356) a]WGFHP^d+lGHTaOx
(357) @,=+@'U;P/UV;P'PHAGH$d";AF]@1A> H =+F@^d+U@xGP,@1AG;=DOxGH =(d x/H%Uk> @ZH$dK q A$> H= A;k> @,WA;P JKW*MG= Aj;TPGWg z xG@,FHa@RW
(358) P,WD]G* , ? /}?G * n DAGUVEJKl ` a]@r> Vt * cP,@g H0UWjMG=d+H0; xx= W
(359) ;%U VC>2W U V*= W*A@'U0F@^dH;*d+H0H xG@'FHTa]@,WGP,WD AA$M ;TP wiH ZG@ H Wg MNGP'@U BtH;Pr> VEG
(360) ,G| G K p0MV l*hiH A ` VP,W
(361) a]W l n DAGUVEJljBt;P1P *ZG@^d?>7JKl*7
(362) W ]HK= f n @,g H0UWjMG=d+H0H x@,FHa @,W
(363) P,WD JKW*MG= Aj;TPGWg z xG@,FHa@RW
(364) P,WD ;AjF f Wa]atMA@r>2DEBtH;Pr> VOG ,
(365) ~( *kr~~
(366) } ~
(367) } K h0PR;TAGH VjH6P1@'g H0U%WjMG=(dHl$>2VHCdW
(368) U@,;P
(369) =+;%F@'HA$> l; AjFEVGH;Pr>2V/ q A :<; =+a]W*> : 0ljb@1P,LG@,A/d+WA wClGHF*@r> W=(dK ` W
(370) U @R;TPGFGHk> H = a @,AG;A$>+d Wg VH;Pr>2V*\ Gg2W=+F *\ Gg2W=+FCmEA@ZGH=kd+@¢>?D 7=+H$d( d , / |*G8}/ WP,P,@r>^> w ljwiW/d+H p0:ljpt;kMg?a ;AEJ ` z Z;PRM;K> @,A*E>2VjH0HkZG@'FHTAjUHg2W=a]WGFHTP'd"Wg7P@,g H0UWjMG=d+H d+WGU@,WGHUWAWa @'U0g2;Uk> W=(d"; AjF]U; =+F*@,W*Z;$dUkM/P'; ="W*M*> U%Wa]H*dk*;Cd DGd?> Ha ;k>2@'U6=+HkZG@' H Th5: f MNGP@'U BtH;Pr>2VEG
(371) ,
(372) G 10.
(373) HAL author manuscript inserm-00108382, version 1. K Bt; = xGH = ` l n DAUVEJljB d?M]b n l z ZGH =(dWA ` l*B]@,P,P'H$a H@H=[: :<l*wi; GV$MA;k>2Vj;TAt z H> ; P^ n @1g H UW*MG=(d+HCd WGU@,W
(374) H%UWAjWa]@'U0UWAF@r> @,WA/d ; AF];F$MPr>7x/d DGUVW/d+WGU@,;P
(375) g^MAUk> @,WA@1A q A> H = A;K>2@,WAj;P JKW*MG= Aj;TPGWg z xG@,FHa@RW
(376) P,WD]G*, ?
(377) ?G n MW l$b;T@¢> H n J VjH@,a]xG;Uk> Wg[UV@P'FVjW
(378) WGFE; AjF];F$MGPr> `*z0` WAExV*D/d+@'U;P'l
(379) a]HA> ;TPRl
(380) ; AjF UWA@r> @RZH ]HP'P,?NGH@,A@,A]P;K> H =P,@g H*$JWjMG= A;P^d"Wg7 H =+W*A> WP,WD ` H =+@,H$d7h0^od DUVW
(381) P,WG@,U;TP ` U@, H AjU$Hd";AF ` W
(382) U @R;TP ` U@HAjUH*dG
(383) ,|2 ` ` |* ` a]@r>2Vt ljBt; =?> f n @,g H% UW*MG=(d+HCdW
(384) U @RW
(385) HU%WAjWa]@'U0;AFtNHV; ZG@,W=+;P
(386) @,AGg?PM HTAjUH$d"WA]U;=+F@RW
(387) ZG;*dUkM/P'; ="F@dH;d+H0a]W=2> ; P,@r>?D*VH0UW
(388) P,P'; NGW=+;k>2@ZGHCd2>^MFjD * a]H =+@'U;AEJWjMG= Aj;PGW
(389) g/MNGP'@'U B]H;Pr> V G* ,j*G8} KG
(390) KG
(391) }G ~* [MG= =+H P,PG l n DAGUVEJ(bljpt; xGP';TAt l z ZH =(dWA ` ljBtH P,LG;P'; z n l*pO;kMV;AHAEJ5HK>;P^ ` WGU @,WG HUWAWa]@'U6xGW d+@r> @,WA];U =W dd[>2VH6P,@g HUW*MG=(dH0; AF]UWA@r> @RZH0gMAUk> @,WA @,A]P';k> H0a @RFFP'H0; GH* JKW*MG= Aj;TP^d"Wg7CH=+WA>2WP,WD ` H =+@,H*d[hi"d DGUVWP,W
(392) @'U;P ` U@,HAjU$Hd";AF ` W
(393) U @R;TP ` U@HAjUH*dG*, ~( K ` ` } W tH = f l*B D*xxGWAHA z l ` a]@r>2Vt ` WGU @,WGHUWAWa]@U0xW/d+@r> @,WA @,A]UV@,P'FVjW
(394) WGF]; AF]H;=8PD ;F$MPr>7P,@g H0;TAjFE=8@'d L Wg7a]W=?> ; P,@r>2D7
(395) x=+W d xGHU(>2@RZHCd2>^MFTDtW
(396) g/>2VH0a]W*>2VH =(d Wg/>2VH
(397) }0hs= @r> @d+V h0@ =?>2V f WVjW=^> a]H =+@'U;AEJKW*MG= A;PGW
(398) g/ MNGP@'U BtH;Pr> VE/
(399) ,j
(400) 8} |( KG* * Bt; = xGH = ` l n DAUVEJljB d?M]b n l z ZGH =(dWA ` l*B]@,P,P'H$a H@H=[: :<l*wi; GV$MA;k>2Vj;TAt z H> ; P^ n @1g H UW*MG=(d+HCd WGU@,W
(401) H%UWAjWa]@'U0UWAF@r> @,WA/d ; AF];F$MPr>7x/d DGUVW/d+WGU@,;P
(402) g^MAUk> @,WA@1A q A> H = A;K>2@,WAj;P JKW*MG= Aj;TPGWg z xG@,FHa@RW
(403) P,WD]G* , ?
(404) ?G 2G* n ; ]PRW= l z N=+;V@a ` l ;kZH%D ` a@¢>2V] F*ZGH =(dHCdW
(405) U@,WGHUWAWa]@'U6xGW d+@r>2@RWA];%U =+W/d(d[>2VjH P@,g HUWjMG=d+H6@,AGU =+H;d+H*d"UW= WA;=DOVGH; =2>F*@'d+H;$d+H6=+@^d L UkMGaEMP';k> @ZHTP,D7*g2@1AGF@,A/d"g^=+W
(406) a>2VH hs=+@r>2@^d+V tWa]HA dVH; =?> ; AjFEVH;Pr>2Vd2>^MFjDJKW*MG= A;PGW
(407) g z x@,FGHTa]@,WGP,WDt;TAjF f WGa aEMA@r>2DCB H%;TP¢> V G
(408) ,G r~
(409) } ~ 2 K h0PR;TAGH l*B]; =^> fon l ` a]@r> V] lGC@,P,P@^d f w0l*BtWP,H JKl*Bt ; C>2VjW= AH 0: Ed(d+WGU@,;k> @,WA]Wg U; =F@,W*ZG;*dUkM/P'; ="F@dH$;d+H6=+@^d Lg2;%Uk> W=d E@¢>2Vd+WGU@,W
(410) H%UWAjW*a@'U6xGW/d+@r> @RWA]F$MG=+@,A* U V@'P'FVjW
(411) WGF]; AF F$MG=+@,A* ;F$MPr>2VWGW
(412) FGThs= @¢> @d+V :<HF@'U;P
(413) JWjMG= Aj;P | , ~~* K G( K }j 2 p0MV l*Bt; =+F*DCwil n ; A*GHA*NH = f l*w6@RUTVG;=+F
(414) d[:<l*b;F d ]W=^>2VC: z J: W=^> ; P,@r>2D]@,A;%F$M/Pr>+d ; GHFEG|8EDjH; =d=+HP';k> HF>Wd W
(415) U@,W
(416) H%UWAjW
(417) a]@'U0UWAjF@¢> @'WA
(418) d"@,A]UV@1P'FVWGW
(419) F]; AjF];F$M/P¢>2VWWGF xGW/d> t; =NG@ =?>2V]UWVW=> d?>^MF$DThs=+@r>2@^d+VC:HF@'U;PGJKW*MG= A;PG* , / ~ ~* ~|(
(420) }/ 2 Bt; =?> f n ljBOWP,H JKl ` a]@r>2V] q Ag2PMHTAjUH0Wg dW
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(422) t;%DOB3wiHTPR;k> @ZH0UWA>2= @N*M> @,WA]Wg7H;=8PD P@,g H ; AjF ;%F$M/Pr>"dW
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(424) PRWD];AjF f W
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(426) 2/ F;a3doJljbV@r> H :<l* H; =+UH : ` l$ ; = LGH = n n @,g H0UW*MG=(dHa]H%;jd2MG=+H$d"Wgd+WGU@,W
(427) H%UWAjWa]@'U xGW/d @r> @,WA];AFd+HP,g[=+HxGW=^> HFEVH;Pr>2Vt;k> ; GHC Tx= W/d xGHUk>2@ZH0UWVjW=^>"d^>^MF$D/JKW*MG= Aj;TPGWg z xG@, FHa]@,W
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(429) } */}( *G/ 2G|* z Pd2> ;FEJ q f V@,PFVWGWGFE;F$ZGH=(d+@r> @,H*d";AFEVH;Pr> VEZG; =+@';k>2@,WA
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(432) , ( KR +}G 11.
(433) HAL author manuscript inserm-00108382, version 1. 2G~* q FP,H = z n ljhiH A*D;a @,AG@ ` HP,g2?=+;K> HFEVH;Pr> V]; AjF a]W=?>2;P,@r>2D7* =+H ZG@'H Wg/> tH A$>2Dj8d+H ZGHA UWa]atMA@r>2D3d?>^MF*@'H$d$JWjMG= A;PGWg/BtH;Pr> V];AF ` W
(434) U @R;TPh HV; ZG@,W=+~ , }(Kk ~/ 2/} :<WP,P'H = n ljp =+@^d?> HA/d+HA] ` l*BOWP1P,AG; GHP*B ` HP,g =+;k> HFEVGH;Pr>2V];d";6x=+HF@,Uk> W=7Wg7UW= WA;=D VH%; =?> F*@^d+H;*d+H0@,A f WxGHAV; HAl H Aa ; = L $JWjMG= Aj;PGWg z x@,F
(435) Ha]@,W
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(438) ?k ?/}j 2G* :<@,@PMA*xG;P,W ` l MW*= @ q l
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(443) aExG; =;k> W=d7Wg xGW*ZGH =?>^Dt;AF]VH;Pr> V]@1A z MG=+WxGH hs=+@r> @'d+VC:<HF@'U;TPJWjMG= A;P
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(445) UUKMGxG;k> @RWAj;TPGUP';*d(d";a]WGA a HA]@,Ad+H ZGHA z MG=+WxGH; A]U%WjMGA>2= @,H$dk ; A];xx
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(447) g z x@,F
(448) Ha]@,W
(449) PRWD
(450) } ,*G~?k G? G ";%DjP,W=[w0l f W*A t; D n l f ;P,FH = ]WGW
(451) F n l n H$dd+Wg f :<H >2VjW
(452) FWP,WD/:<;=8atWj>/:ljhi; AL/dJKl h0P¢M/AjFHTP'Pwil n H$dKd+Wg f l y ; u =+WW]JKlHF*@¢> W=(d0G n W*AFWAl q Y ` B]H%;TP¢>2!V ]H%;TP¢>2V];AF P,@'g H d?>^DjP'Hjd Wg/>2VH0WP,FH =xGWx*MGP,;k> @,WA]@1A z A*GP';TAjF/*VH6G* z A*GP,@d+V n WA
(453) @r>^MF@,AG;P ` >^MF$DtWg 0GH@,A hiWAjHAg2;TA> ` l f MG=H> H P,P@'UH =[:l
(454) WPRFjNH = E:<l*pO;A@ H 3d LG@ y l n HUP'H =++U l
(455) \ u *MP,H = cHk> ;P^ n ;0UWVjW=^> H0 ; u H PGFH$d Gl1CZW
(456) P,WA$> ;@=+H$d* AA H K 0G* ; = @dl q y `*z w :{mEA@r> }}G Bt;T@^d LGHTAj H y H Jo l*Y =+@,U L]JowO H$d L*>2WxUWaExG;A@,W
(457) AC>WO>2VjH0CH= a];A ` W
(458) U@,WG z U WAWa]@'U ; AHP ` >^MF$D/ G ThiH = P1@,Ajl ` \ z :<;%U LGHA*NG;UVEJ+l O; AFGHa VGH%HTA B]l ` >2= WAL/d[p * x=+W
(459) d xGHUk> @ZGH0UWVW=>"d^>^MF$D]@,A*ZGH*d2> @G;K> @,A* >2VH0 H xGP;Aj;k> @RWA]Wgd+WGU@,W
